A macrolide compound obtained from Streptomyces hygroscopicus that acts by selectively blocking the transcriptional activation of cytokines thereby inhibiting cytokine production. It is bioactive only when bound to IMMUNOPHILINS. Sirolimus is a potent immunosuppressant and possesses both antifungal and antineoplastic properties.
Agents that suppress immune function by one of several mechanisms of action. Classical cytotoxic immunosuppressants act by inhibiting DNA synthesis. Others may act through activation of T-CELLS or by inhibiting the activation of HELPER CELLS. While immunosuppression has been brought about in the past primarily to prevent rejection of transplanted organs, new applications involving mediation of the effects of INTERLEUKINS and other CYTOKINES are emerging.
A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro.
The transference of a kidney from one human or animal to another.
A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. (From Martindale, The Extra Pharmacopoeia, 30th ed).
An antibiotic substance derived from Penicillium stoloniferum, and related species. It blocks de novo biosynthesis of purine nucleotides by inhibition of the enzyme inosine monophosphate dehydrogenase. Mycophenolic acid is important because of its selective effects on the immune system. It prevents the proliferation of T-cells, lymphocytes, and the formation of antibodies from B-cells. It also may inhibit recruitment of leukocytes to inflammatory sites. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1301)
A CALCIUM and CALMODULIN-dependent serine/threonine protein phosphatase that is composed of the calcineurin A catalytic subunit and the calcineurin B regulatory subunit. Calcineurin has been shown to dephosphorylate a number of phosphoproteins including HISTONES; MYOSIN LIGHT CHAIN; and the regulatory subunits of CAMP-DEPENDENT PROTEIN KINASES. It is involved in the regulation of signal transduction and is the target of an important class of immunophilin-immunosuppressive drug complexes.
An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient.
The practice of replacing one prescribed drug with another that is expected to have the same clinical or psychological effect.
A disease characterized by the progressive invasion of SMOOTH MUSCLE CELLS into the LYMPHATIC VESSELS, and the BLOOD VESSELS. The majority of the cases occur in the LUNGS of women of child-bearing age, eventually blocking the flow of air, blood, and lymph. The common symptom is shortness of breath (DYSPNEA).
A benign tumor containing vascular, adipose, and muscle elements. It occurs most often in the kidney with smooth muscle elements (angiolipoleiomyoma) in association with tuberous sclerosis. (Dorland, 27th ed)
A serine threonine kinase that controls a wide range of growth-related cellular processes. The protein is referred to as the target of RAPAMYCIN due to the discovery that SIROLIMUS (commonly known as rapamycin) forms an inhibitory complex with TACROLIMUS BINDING PROTEIN 1A that blocks the action of its enzymatic activity.
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
A tumorlike condition characterized by SMOOTH MUSCLE and ENDOTHELIUM proliferation of LYMPHATIC VESSELS and LYMPH NODES in the MEDIASTINUM and retroperitoneum, also in the lung. It may be manifested by chylous PLEURAL EFFUSION and ASCITES.
The administration of substances into the eye with a hypodermic syringe.
Recurrent narrowing or constriction of a coronary artery following surgical procedures performed to alleviate a prior obstruction.
Therapy with two or more separate preparations given for a combined effect.
Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.
An opaque, milky-white fluid consisting mainly of emulsified fats that passes through the lacteals of the small intestines into the lymphatic system.
The transference of a part of or an entire liver from one human or animal to another.
Hydrocarbons with more than one double bond. They are a reduced form of POLYYNES.
Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.
Stents that are covered with materials that are embedded with chemicals that are gradually released into the surrounding milieu.
Creatinine is a waste product that's generated from muscle metabolism, typically filtered through the kidneys and released in urine, with increased levels in blood indicating impaired kidney function.
Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.
Agents that affect the rate or intensity of cardiac contraction, blood vessel diameter, or blood volume.
Elements of limited time intervals, contributing to particular results or situations.
The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically.
The transference of pancreatic islets within an individual, between individuals of the same species, or between individuals of different species.
Small containers or pellets of a solid drug implanted in the body to achieve sustained release of the drug.
The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.
Transference of a tissue or organ from either an alive or deceased donor, within an individual, between individuals of the same species, or between individuals of different species.
Fluoroimmunoassay where detection of the hapten-antibody reaction is based on measurement of the increased polarization of fluorescence-labeled hapten when it is combined with antibody. The assay is very useful for the measurement of small haptenic antigens such as drugs at low concentrations.
Chemical substances, produced by microorganisms, inhibiting or preventing the proliferation of neoplasms.
Devices that provide support for tubular structures that are being anastomosed or for body cavities during skin grafting.
Deliberate prevention or diminution of the host's immune response. It may be nonspecific as in the administration of immunosuppressive agents (drugs or radiation) or by lymphocyte depletion or may be specific as in desensitization or the simultaneous administration of antigen and immunosuppressive drugs.
Diseases that result in THROMBOSIS in MICROVASCULATURE. The two most prominent diseases are PURPURA, THROMBOTIC THROMBOCYTOPENIC; and HEMOLYTIC-UREMIC SYNDROME. Multiple etiological factors include VASCULAR ENDOTHELIAL CELL damage due to SHIGA TOXIN; FACTOR H deficiency; and aberrant VON WILLEBRAND FACTOR formation.
Agents that interact with TUBULIN to inhibit or promote polymerization of MICROTUBULES.
A dicarboxylic acid ketone that is an important metabolic intermediate of the CITRIC ACID CYCLE. It can be converted to ASPARTIC ACID by ASPARTATE TRANSAMINASE.
Biocompatible materials usually used in dental and bone implants that enhance biologic fixation, thereby increasing the bond strength between the coated material and bone, and minimize possible biological effects that may result from the implant itself.
A plant species of the genus CITRUS, family RUTACEAE that produces the familiar grapefruit. There is evidence that grapefruit inhibits CYTOCHROME P-450 CYP3A4, resulting in delayed metabolism and higher blood levels of a variety of drugs.
Kidney disorders with autosomal dominant inheritance and characterized by multiple CYSTS in both KIDNEYS with progressive deterioration of renal function.
An immunosuppressive agent used in combination with cyclophosphamide and hydroxychloroquine in the treatment of rheumatoid arthritis. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), this substance has been listed as a known carcinogen. (Merck Index, 11th ed)
Compounds used extensively as acetylation, oxidation and dehydrating agents and in the modification of proteins and enzymes.
The transference of a heart from one human or animal to another.
Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.
The action of a drug that may affect the activity, metabolism, or toxicity of another drug.
Providers of tissues for transplant to non-related individuals.
Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.
Serum containing GAMMA-GLOBULINS which are antibodies for lymphocyte ANTIGENS. It is used both as a test for HISTOCOMPATIBILITY and therapeutically in TRANSPLANTATION.
Autosomal dominant neurocutaneous syndrome classically characterized by MENTAL RETARDATION; EPILEPSY; and skin lesions (e.g., adenoma sebaceum and hypomelanotic macules). There is, however, considerable heterogeneity in the neurologic manifestations. It is also associated with cortical tuber and HAMARTOMAS formation throughout the body, especially the heart, kidneys, and eyes. Mutations in two loci TSC1 and TSC2 that encode hamartin and tuberin, respectively, are associated with the disease.
A loss of mucous substance of the mouth showing local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue. It is the result of a variety of causes, e.g., denture irritation, aphthous stomatitis (STOMATITIS, APHTHOUS); NOMA; necrotizing gingivitis (GINGIVITIS, NECROTIZING ULCERATIVE); TOOTHBRUSHING; and various irritants. (From Jablonski, Dictionary of Dentistry, 1992, p842)
Conditions in which the KIDNEYS perform below the normal level in the ability to remove wastes, concentrate URINE, and maintain ELECTROLYTE BALANCE; BLOOD PRESSURE; and CALCIUM metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of PROTEINURIA) and reduction in GLOMERULAR FILTRATION RATE.
Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.
A family of mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. These cells do not have a normal anatomic homolog. (From Fletcher CDM, et. al., World Health Organization Classification of Tumors: Pathology and Genetics of Tumors of Soft Tissue and Bone, 2002).
A family of ribosomal protein S6 kinases that are considered the major physiological kinases for RIBOSOMAL PROTEIN S6. Unlike RIBOSOMAL PROTEIN S6 KINASES, 90KDa the proteins in this family are sensitive to the inhibitory effects of RAPAMYCIN and contain a single kinase domain. They are referred to as 70kDa proteins, however ALTERNATIVE SPLICING of mRNAs for proteins in this class also results in 85kDa variants being formed.
A cyclodecane isolated from the bark of the Pacific yew tree, TAXUS BREVIFOLIA. It stabilizes MICROTUBULES in their polymerized form leading to cell death.
Abnormal passage in any organ of the biliary tract or between biliary organs and other organs.
Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body.
A detailed review and evaluation of selected clinical records by qualified professional personnel to improve the quality of patient care and outcomes. The clinical audit was formally introduced in 1993 into the United Kingdom's National Health Service.
Adrenal cortex hormones are steroid hormones produced by the outer portion of the adrenal gland, consisting of glucocorticoids, mineralocorticoids, and androgens, which play crucial roles in various physiological processes such as metabolism regulation, stress response, electrolyte balance, and sexual development and function.
Broad spectrum antifungal agent used for long periods at high doses, especially in immunosuppressed patients.
Abnormally infrequent menstruation.
Preparative treatment of transplant recipient with various conditioning regimens including radiation, immune sera, chemotherapy, and/or immunosuppressive agents, prior to transplantation. Transplantation conditioning is very common before bone marrow transplantation.
Drugs used for their effects on the respiratory system.
An order of zygomycetous fungi, usually saprophytic, causing damage to food in storage, but which may cause respiratory infection or MUCORMYCOSIS in persons suffering from other debilitating diseases.
Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.
A group of polycyclic compounds closely related biochemically to TERPENES. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (STEROLS), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. (From Hawley's Condensed Chemical Dictionary, 11th ed)
Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.
Implants constructed of materials designed to be absorbed by the body without producing an immune response. They are usually composed of plastics and are frequently used in orthopedics and orthodontics.
A cytochrome P-450 suptype that has specificity for a broad variety of lipophilic compounds, including STEROIDS; FATTY ACIDS; and XENOBIOTICS. This enzyme has clinical significance due to its ability to metabolize a diverse array of clinically important drugs such as CYCLOSPORINE; VERAPAMIL; and MIDAZOLAM. This enzyme also catalyzes the N-demethylation of ERYTHROMYCIN.
Non-cadaveric providers of organs for transplant to related or non-related recipients.
Organic salts and esters of benzenesulfonic acid.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Strategy for the analysis of RANDOMIZED CONTROLLED TRIALS AS TOPIC that compares patients in the groups to which they were originally randomly assigned.
Obstruction of flow in biological or prosthetic vascular grafts.
Radiography of the vascular system of the heart muscle after injection of a contrast medium.
The presence of proteins in the urine, an indicator of KIDNEY DISEASES.

High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. (1/4814)

BACKGROUND: Fully adapting a forward genetic approach to mammalian systems requires efficient methods to alter systematically gene products without prior knowledge of gene sequences, while allowing for the subsequent characterization of these alterations. Ideally, these methods would also allow function to be altered in a temporally controlled manner. RESULTS: We report the development of a miniaturized cell-based assay format that enables a genetic-like approach to understanding cellular pathways in mammalian systems using small molecules, rather than mutations, as the source of gene-product alterations. This whole-cell immunodetection assay can sensitively detect changes in specific cellular macromolecules in high-density arrays of mammalian cells. Furthermore, it is compatible with screening large numbers of small molecules in nanoliter to microliter culture volumes. We refer to this assay format as a 'cytoblot', and demonstrate the use of cytoblotting to monitor biosynthetic processes such as DNA synthesis, and post-translational processes such as acetylation and phosphorylation. Finally, we demonstrate the applicability of these assays to natural-product screening through the identification of marine sponge extracts exhibiting genotype-specific inhibition of 5-bromodeoxyuridine incorporation and suppression of the anti-proliferative effect of rapamycin. CONCLUSIONS: We show that cytoblots can be used for high-throughput screening of small molecules in cell-based assays. Together with small-molecule libraries, the cytoblot assay can be used to perform chemical genetic screens analogous to those used in classical genetics and thus should be applicable to understanding a wide variety of cellular processes, especially those involving post-transitional modifications.  (+info)

Rapamycin causes poorly reversible inhibition of mTOR and induces p53-independent apoptosis in human rhabdomyosarcoma cells. (2/4814)

The mammalian target of rapamycin (mTOR) has been shown to link growth factor signaling and posttranscriptional control of translation of proteins that are frequently involved in cell cycle progression. However, the role of this pathway in cell survival has not been demonstrated. Here, we report that rapamycin, a specific inhibitor of mTOR kinase, induces G1 cell cycle arrest and apoptosis in two rhabdomyosarcoma cell lines (Rh1 and Rh30) under conditions of autocrine cell growth. To examine the kinetics of rapamycin action, we next determined the rapamycin sensitivity of rhabdomyosarcoma cells exposed briefly (1 h) or continuously (6 days). Results demonstrate that Rh1 and Rh30 cells were equally sensitive to rapamycin-induced growth arrest and apoptosis under either condition. Apoptosis was detected between 24 and 144 h of exposure to rapamycin. Both cell lines have mutant p53; hence, rapamycin-induced apoptosis appears to be a p53-independent process. To determine whether induction of apoptosis by rapamycin was specifically due to inhibition of mTOR signaling, we engineered Rh1 and Rh30 clones to stably express a mutant form of mTOR that was resistant to rapamycin (Ser2035-->Ile; designated mTOR-rr). Rh1 and Rh30 mTOR-rr clones were highly resistant (>3000-fold) to both growth inhibition and apoptosis induced by rapamycin. These results are the first to indicate that rapamycin-induced apoptosis is mediated by inhibition of mTOR. Exogenous insulin-like growth factor (IGF)-I protected both Rh1 and Rh30 from apoptosis, without reactivating ribosomal p70 S6 kinase (p70S6K) downstream of mTOR. However, in rapamycin-treated cultures, the response to IGF-I differed between the cell lines: Rh1 cells proliferated normally, whereas Rh30 cells remained arrested in G1 phase but viable. Rapamycin is known to inhibit synthesis of specific proteins but did not inhibit synthesis or alter the levels of mTOR. To examine the rate at which the mTOR pathway recovered, the ability of IGF-I to stimulate p70S6K activity was followed in cells treated for 1 h with rapamycin and then allowed to recover in medium containing > or =100-fold excess of FK506 (to prevent rapamycin from rebinding to its cytosolic receptor FKBP-12). Our results indicate that, in Rh1 cells, rapamycin dissociates relatively slowly from FKBP-12, with a t1/2 of approximately 17.5 h. in the presence of FK506, whereas there was no recovery of p70S6K activity in the absence of this competitor. This was of interest because rapamycin was relatively unstable under conditions of cell culture having a biological t1/2 of approximately 9.9 h. These results help to explain why cells are sensitive following short exposures to rapamycin and may be useful in guiding the use of rapamycin analogues that are entering clinical trials as novel antitumor agents.  (+info)

Hmo1p, a high mobility group 1/2 homolog, genetically and physically interacts with the yeast FKBP12 prolyl isomerase. (3/4814)

The immunosuppressive drugs FK506 and rapamycin bind to the cellular protein FKBP12, and the resulting FKBP12-drug complexes inhibit signal transduction. FKBP12 is a ubiquitous, highly conserved, abundant enzyme that catalyzes a rate-limiting step in protein folding: peptidyl-prolyl cis-trans isomerization. However, FKBP12 is dispensible for viability in both yeast and mice, and therefore does not play an essential role in protein folding. The functions of FKBP12 may involve interactions with a number of partner proteins, and a few proteins that interact with FKBP12 in the absence of FK506 or rapamycin have been identified, including the ryanodine receptor, aspartokinase, and the type II TGF-beta receptor; however, none of these are conserved from yeast to humans. To identify other targets and functions of FKBP12, we have screened for mutations that are synthetically lethal with an FKBP12 mutation in yeast. We find that mutations in HMO1, which encodes a high mobility group 1/2 homolog, are synthetically lethal with mutations in the yeast FPR1 gene encoding FKBP12. Deltahmo1 and Deltafpr1 mutants share two phenotypes: an increased rate of plasmid loss and slow growth. In addition, Hmo1p and FKBP12 physically interact in FKBP12 affinity chromatography experiments, and two-hybrid experiments suggest that FKBP12 regulates Hmo1p-Hmo1p or Hmo1p-DNA interactions. Because HMG1/2 proteins are conserved from yeast to humans, our findings suggest that FKBP12-HMG1/2 interactions could represent the first conserved function of FKBP12 other than mediating FK506 and rapamycin actions.  (+info)

Interaction of asparagine and EGF in the regulation of ornithine decarboxylase in IEC-6 cells. (4/4814)

Our laboratory has shown that asparagine (ASN) stimulates both ornithine decarboxylase (ODC) activity and gene expression in an intestinal epithelial cell line (IEC-6). The effect of ASN is specific, and other A- and N-system amino acids are almost as effective as ASN when added alone. In the present study, epidermal growth factor (EGF) was unable to increase ODC activity in cells maintained in a salt-glucose solution (Earle's balanced salt solution). However, the addition of ASN (10 mM) in the presence of EGF (30 ng/ml) increased the activity of ODC 0.5- to 4-fold over that stimulated by ASN alone. EGF also showed induction of ODC with glutamine and alpha-aminoisobutyric acid, but ODC induction was maximum with ASN and EGF. Thus the mechanism of the interaction between ASN and EGF is important for understanding the regulation of ODC under physiological conditions. Therefore, we examined the expression of the ODC gene and those for several protooncogenes under the same conditions. Increased expression of the genes for c-Jun and c-Fos but not for ODC occurred with EGF alone. The addition of ASN did not further increase the expression of the protooncogenes, but the combination of EGF and ASN further increased the expression of ODC over that of ASN alone. Western analysis showed no significant difference in the level of ODC protein in Earle's balanced salt solution, ASN, EGF, or EGF plus ASN. Addition of cycloheximide during ASN and ASN plus EGF treatment completely inhibited ODC activity without affecting the level of ODC protein. These results indicated that 1) the increased expression of protooncogenes in response to EGF is independent of increases in ODC activity and 2) potentiation between EGF and ASN on ODC activity may not be due to increased gene transcription but to posttranslational regulation and the requirement of ongoing protein synthesis involving a specific factor dependent on ASN.  (+info)

Cyclosporin A treatment alters characteristics of Ca2+-release channel in cardiac sarcoplasmic reticulum. (5/4814)

Chronic treatment with cyclosporin A (CsA) has been reported (H. S. Banijamali, M. H. ter Keurs, L. C. Paul, and H. E. ter Keurs. Cardiovasc. Res. 27: 1845-1854, 1993; I. Kingma, E. Harmsen, H. E. ter Keurs, H. Benediktsson, and L. C. Paul. Int. J. Cardiol. 31: 15-22, 1991) to induce reversible alterations of contractile properties in rat hearts. To define the molecular mechanisms underlying the physiological alterations, the Ca2+-release channel (CRC) and Ca2+-ATPase from sarcoplasmic reticulum in rats were examined. Ryanodine binding to whole homogenates of rat hearts shows time- and dose-dependent alterations in CRC properties by CsA. On 3 wk of treatment with 15 mg CsA. kg body wt-1. day-1, 1) maximal ryanodine binding (Bmax) decreased, 2) the dissociation constant of ryanodine (Kd) increased, 3) caffeine sensitivity of CRC increased, and 4) ruthenium red sensitivity of CRC decreased. On the other hand, Bmax and Kd of ryanodine binding in rat skeletal muscles were not changed. Ryanodine-sensitive oxalate-supported Ca2+ uptake in whole homogenates was lower in CsA-treated rat hearts than in control hearts, whereas total Ca2+ uptake in the presence of 500 M ryanodine was not changed. Functional experiments with rapamycin and Western blot analysis suggest that the CsA-induced alteration of ryanodine binding is due at least in part to an upregulation of calcineurin. The heart muscle-specific alterations of CRC could be responsible for the previously reported contractile changes of CsA-treated rat hearts.  (+info)

Inhibition of cell cycle progression by rapamycin induces T cell clonal anergy even in the presence of costimulation. (6/4814)

Costimulation (signal 2) has been proposed to inhibit the induction of T cell clonal anergy by either directly antagonizing negative signals arising from TCR engagement (signal 1) or by synergizing with signal 1 to produce IL-2, which in turn leads to proliferation and dilution of negative regulatory factors. To better define the cellular events that lead to the induction of anergy, we used the immunosuppressive agent rapamycin, which blocks T cell proliferation in late G1 phase but does not affect costimulation-dependent IL-2 production. Our data demonstrate that full T cell activation (signal 1 plus 2) in the presence of rapamycin results in profound T cell anergy, despite the fact that these cells produce copious amounts of IL-2. Similar to conventional anergy (induction by signal 1 alone), the rapamycin-induced anergic cells show a decrease in mitogen-activated protein kinase activation, and these cells can be rescued by culture in IL-2. Interestingly, the rapamycin-induced anergic cells display a more profound block in IL-3 and IFN-gamma production upon rechallenge. Finally, in contrast to rapamycin, full T cell activation in the presence of hydroxyurea (which inhibits the cell cycle in early S phase) did not result in anergy. These data suggest that it is neither the direct effect of costimulation nor the subsequent T cell proliferation that prevents anergy induction, but rather the biochemical events that occur upon progression through the cell cycle from G1 into S phase.  (+info)

p70(S6K) controls selective mRNA translation during oocyte maturation and early embryogenesis in Xenopus laevis. (7/4814)

In mammalian cells, p70(S6K) plays a key role in translational control of cell proliferation in response to growth factors. Because of the reliance on translational control in early vertebrate development, we cloned a Xenopus homolog of p70(S6K) and investigated the activity profile of p70(S6K) during Xenopus oocyte maturation and early embryogenesis. p70(S6K) activity is high in resting oocytes and decreases to background levels upon stimulation of maturation with progesterone. During embryonic development, three peaks of activity were observed: immediately after fertilization, shortly before the midblastula transition, and during gastrulation. Rapamycin, an inhibitor of p70(S6K) activation, caused oocytes to undergo germinal vesicle breakdown earlier than control oocytes, and sensitivity to progesterone was increased. Injection of a rapamycin-insensitive, constitutively active mutant of p70(S6K) reversed the effects of rapamycin. However, increases in S6 phosphorylation were not significantly affected by rapamycin during maturation. mos mRNA, which does not contain a 5'-terminal oligopyrimidine tract (5'-TOP), was translated earlier, and a larger amount of Mos protein was produced in rapamycin-treated oocytes. In fertilized eggs rapamycin treatment increased the translation of the Cdc25A phosphatase, which lacks a 5'-TOP. Translation assays in vivo using both DNA and RNA reporter constructs with the 5'-TOP from elongation factor 2 showed decreased translational activity with rapamycin, whereas constructs without a 5'-TOP or with an internal ribosome entry site were translated more efficiently upon rapamycin treatment. These results suggest that changes in p70(S6K) activity during oocyte maturation and early embryogenesis selectively alter the translational capacity available for mRNAs lacking a 5'-TOP region.  (+info)

Growth hormone-dependent differentiation of 3T3-F442A preadipocytes requires Janus kinase/signal transducer and activator of transcription but not mitogen-activated protein kinase or p70 S6 kinase signaling. (8/4814)

The signals mediating growth hormone (GH)-dependent differentiation of 3T3-F442A preadipocytes under serum-free conditions have been studied. GH priming of cells was required before the induction of terminal differentiation by a combination of epidermal growth factor, tri-iodothyronine, and insulin. Cellular depletion of Janus kinase-2 (JAK-2) using antisense oligodeoxynucleotides (ODNs) prevented GH-stimulated JAK-2 and signal transducer and activator of transcription (STAT)-5 tyrosine phosphorylation and severely attenuated the ability of GH to promote differentiation. Although p42(MAPK)/p44(MAPK) mitogen-activated protein kinases were activated during GH priming, treatment of cells with PD 098059, which prevented activation of these kinases, did not block GH priming. However, antisense ODN-mediated depletion of mitogen-activated protein kinases from the cells showed that their expression was necessary for terminal differentiation. Similarly, although p70(s6k) was activated during GH priming, pretreatment of cells with rapamycin, which prevented the activation of p70(s6k), had no effect on GH priming. However, rapamycin did partially block epidermal growth factor, tri-iodothyronine, and insulin-stimulated terminal differentiation. By contrast, cellular depletion of STAT-5 with antisense ODNs completely abolished the ability of GH to promote differentiation. These results indicate that JAK-2, acting specifically via STAT-5, is necessary for GH-dependent differentiation of 3T3-F442A preadipocytes. Activation of p42(MAPK)/p44(MAPK) and p70(s6k) is not essential for the promotion of differentiation by GH, although these signals are required for GH-independent terminal differentiation.  (+info)

Sirolimus is a medication that belongs to a class of drugs called immunosuppressants. It is also known as rapamycin. Sirolimus works by inhibiting the mammalian target of rapamycin (mTOR), which is a protein that plays a key role in cell growth and division.

Sirolimus is primarily used to prevent rejection of transplanted organs, such as kidneys, livers, and hearts. It works by suppressing the activity of the immune system, which can help to reduce the risk of the body rejecting the transplanted organ. Sirolimus is often used in combination with other immunosuppressive drugs, such as corticosteroids and calcineurin inhibitors.

Sirolimus is also being studied for its potential therapeutic benefits in a variety of other conditions, including cancer, tuberous sclerosis complex, and lymphangioleiomyomatosis. However, more research is needed to fully understand the safety and efficacy of sirolimus in these contexts.

It's important to note that sirolimus can have significant side effects, including increased risk of infections, mouth sores, high blood pressure, and kidney damage. Therefore, it should only be used under the close supervision of a healthcare provider.

Immunosuppressive agents are medications that decrease the activity of the immune system. They are often used to prevent the rejection of transplanted organs and to treat autoimmune diseases, where the immune system mistakenly attacks the body's own tissues. These drugs work by interfering with the immune system's normal responses, which helps to reduce inflammation and damage to tissues. However, because they suppress the immune system, people who take immunosuppressive agents are at increased risk for infections and other complications. Examples of immunosuppressive agents include corticosteroids, azathioprine, cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus.

Tacrolimus is an immunosuppressant drug that is primarily used to prevent the rejection of transplanted organs. It works by inhibiting the activity of T-cells, which are a type of white blood cell that plays a central role in the body's immune response. By suppressing the activity of these cells, tacrolimus helps to reduce the risk of an immune response being mounted against the transplanted organ.

Tacrolimus is often used in combination with other immunosuppressive drugs, such as corticosteroids and mycophenolate mofetil, to provide a comprehensive approach to preventing organ rejection. It is available in various forms, including capsules, oral solution, and intravenous injection.

The drug was first approved for use in the United States in 1994 and has since become a widely used immunosuppressant in transplant medicine. Tacrolimus is also being studied as a potential treatment for a variety of other conditions, including autoimmune diseases and cancer.

Kidney transplantation is a surgical procedure where a healthy kidney from a deceased or living donor is implanted into a patient with end-stage renal disease (ESRD) or permanent kidney failure. The new kidney takes over the functions of filtering waste and excess fluids from the blood, producing urine, and maintaining the body's electrolyte balance.

The transplanted kidney is typically placed in the lower abdomen, with its blood vessels connected to the recipient's iliac artery and vein. The ureter of the new kidney is then attached to the recipient's bladder to ensure proper urine flow. Following the surgery, the patient will require lifelong immunosuppressive therapy to prevent rejection of the transplanted organ by their immune system.

Cyclosporine is a medication that belongs to a class of drugs called immunosuppressants. It is primarily used to prevent the rejection of transplanted organs, such as kidneys, livers, and hearts. Cyclosporine works by suppressing the activity of the immune system, which helps to reduce the risk of the body attacking the transplanted organ.

In addition to its use in organ transplantation, cyclosporine may also be used to treat certain autoimmune diseases, such as rheumatoid arthritis and psoriasis. It does this by suppressing the overactive immune response that contributes to these conditions.

Cyclosporine is available in capsule, oral solution, and injectable forms. Common side effects of the medication include kidney problems, high blood pressure, tremors, headache, and nausea. Long-term use of cyclosporine can also increase the risk of certain types of cancer and infections.

It is important to note that cyclosporine should only be used under the close supervision of a healthcare provider, as it requires regular monitoring of blood levels and kidney function.

Mycophenolic Acid (MPA) is an immunosuppressive drug that is primarily used to prevent rejection in organ transplantation. It works by inhibiting the enzyme inosine monophosphate dehydrogenase, which is a key enzyme for the de novo synthesis of guanosine nucleotides, an essential component for the proliferation of T and B lymphocytes. By doing this, MPA reduces the activity of the immune system, thereby preventing it from attacking the transplanted organ.

Mycophenolic Acid is available in two forms: as the sodium salt (Mycophenolate Sodium) and as the morpholinoethyl ester (Mycophenolate Mofetil), which is rapidly hydrolyzed to Mycophenolic Acid after oral administration. Common side effects of MPA include gastrointestinal symptoms such as diarrhea, nausea, and vomiting, as well as an increased risk of infections due to its immunosuppressive effects.

Calcineurin is a calcium-calmodulin-activated serine/threonine protein phosphatase that plays a crucial role in signal transduction pathways involved in immune response and neuronal development. It consists of two subunits: the catalytic A subunit (calcineurin A) and the regulatory B subunit (calcineurin B). Calcineurin is responsible for dephosphorylating various substrates, including transcription factors, which leads to changes in their activity and ultimately affects gene expression. In the immune system, calcineurin plays a critical role in T-cell activation by dephosphorylating the nuclear factor of activated T-cells (NFAT), allowing it to translocate into the nucleus and induce the expression of cytokines and other genes involved in the immune response. Inhibitors of calcineurin, such as cyclosporine A and tacrolimus, are commonly used as immunosuppressive drugs to prevent organ rejection after transplantation.

Graft rejection is an immune response that occurs when transplanted tissue or organ (the graft) is recognized as foreign by the recipient's immune system, leading to the activation of immune cells to attack and destroy the graft. This results in the failure of the transplant and the need for additional medical intervention or another transplant. There are three types of graft rejection: hyperacute, acute, and chronic. Hyperacute rejection occurs immediately or soon after transplantation due to pre-existing antibodies against the graft. Acute rejection typically occurs within weeks to months post-transplant and is characterized by the infiltration of T-cells into the graft. Chronic rejection, which can occur months to years after transplantation, is a slow and progressive process characterized by fibrosis and tissue damage due to ongoing immune responses against the graft.

Drug substitution, also known as medication substitution, refers to the practice of replacing a prescribed medication with a different one that is therapeutically equivalent or similar. This may be done for various reasons such as:

* Cost: The substitute drug may be less expensive than the original medication.
* Availability: The substitute drug may be more readily available than the original medication.
* Adverse effects: The substitute drug may have fewer or less severe side effects than the original medication.
* Drug interactions: The substitute drug may have fewer or no interactions with other medications that the patient is taking.
* Efficacy: The substitute drug may be equally or more effective than the original medication.

It's important to note that any changes to a patient's medication regimen should be made in consultation with their healthcare provider, as substituting medications can have potential risks and benefits. Additionally, some states have laws and regulations that govern when and how drug substitution can be done.

Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease that primarily affects women of childbearing age. It is characterized by the abnormal growth of smooth muscle cells in the airways, blood vessels, and lymphatic system of the lungs. These cells can form cysts and lesions that can obstruct the airways and cause lung function to decline over time.

LAM can also affect other organs, such as the kidneys, where it can cause angiomyolipomas (benign tumors composed of blood vessels, muscle cells, and fat). In some cases, LAM may be associated with tuberous sclerosis complex (TSC), a genetic disorder that causes benign tumors to grow in various organs of the body.

The exact cause of LAM is not fully understood, but it is believed to be related to mutations in the TSC1 or TSC2 genes, which regulate cell growth and division. There is currently no cure for LAM, but treatments such as lung transplantation and medications that suppress the growth of smooth muscle cells may help manage symptoms and slow disease progression.

Angiomyolipoma is a type of benign tumor that occurs most commonly in the kidney. It is composed of blood vessels (angio-), smooth muscle cells (myo-), and fat cells (lipo-). Angiomyolipomas are usually associated with the genetic disorder tuberous sclerosis complex, but they can also occur spontaneously or as a result of other genetic conditions.

These tumors can vary in size and may cause symptoms such as pain, blood in the urine, or a palpable mass in the abdomen if they grow large enough. In some cases, angiomyolipomas may also be at risk for rupture and bleeding, particularly if they are larger than 4 cm in size.

Treatment options for angiomyolipomas include surveillance with imaging tests, medication to reduce the risk of bleeding, or surgical removal of the tumor. The choice of treatment depends on factors such as the size and location of the tumor, the presence of symptoms, and the patient's overall health.

TOR (Target Of Rapamycin) Serine-Threonine Kinases are a family of conserved protein kinases that play crucial roles in the regulation of cell growth, proliferation, and metabolism in response to various environmental cues such as nutrients, growth factors, and energy status. They are named after their ability to phosphorylate serine and threonine residues on target proteins.

Mammalian cells express two distinct TOR kinases, mTORC1 and mTORC2, which have different protein compositions and functions. mTORC1 is rapamycin-sensitive and regulates cell growth, proliferation, and metabolism by phosphorylating downstream targets such as p70S6 kinase and 4E-BP1, thereby controlling protein synthesis, autophagy, and lysosome biogenesis. mTORC2 is rapamycin-insensitive and regulates cell survival, cytoskeleton organization, and metabolism by phosphorylating AGC kinases such as AKT and PKCα.

Dysregulation of TOR Serine-Threonine Kinases has been implicated in various human diseases, including cancer, diabetes, and neurological disorders. Therefore, targeting TOR kinases has emerged as a promising therapeutic strategy for the treatment of these diseases.

Graft survival, in medical terms, refers to the success of a transplanted tissue or organ in continuing to function and integrate with the recipient's body over time. It is the opposite of graft rejection, which occurs when the recipient's immune system recognizes the transplanted tissue as foreign and attacks it, leading to its failure.

Graft survival depends on various factors, including the compatibility between the donor and recipient, the type and location of the graft, the use of immunosuppressive drugs to prevent rejection, and the overall health of the recipient. A successful graft survival implies that the transplanted tissue or organ has been accepted by the recipient's body and is functioning properly, providing the necessary physiological support for the recipient's survival and improved quality of life.

Lymphangiomyoma is a rare, benign tumor that typically arises in the soft tissues of the body. It is composed of smooth muscle cells and lymphatic vessels. These tumors most commonly occur in the cervix, mediastinum, and retroperitoneum. They can cause various symptoms depending on their location, such as abdominal pain or distention, difficulty breathing, or abnormal vaginal bleeding.

Lymphangiomyomas are thought to arise from aberrant smooth muscle proliferation around lymphatic vessels. While they are generally considered benign, they can still cause problems due to their mass effect and potential for local invasion. Treatment typically involves surgical excision of the tumor.

It is important to note that while I strive to provide accurate information, my responses should not be used as a substitute for professional medical advice or treatment.

Intraocular injections are a type of medical procedure where medication is administered directly into the eye. This technique is often used to deliver drugs that treat various eye conditions, such as age-related macular degeneration, diabetic retinopathy, and endophthalmitis. The most common type of intraocular injection is an intravitreal injection, which involves injecting medication into the vitreous cavity, the space inside the eye filled with a clear gel-like substance called the vitreous humor. This procedure is typically performed by an ophthalmologist in a clinical setting and may be repeated at regular intervals depending on the condition being treated.

Coronary restenosis is the re-narrowing or re-occlusion of a coronary artery after a previous successful procedure to open or widen the artery, such as angioplasty or stenting. This narrowing is usually caused by the excessive growth of scar tissue or smooth muscle cells in the artery lining, which can occur spontaneously or as a response to the initial procedure. Restenosis can lead to recurrent symptoms of coronary artery disease, such as chest pain or shortness of breath, and may require additional medical intervention.

Combination drug therapy is a treatment approach that involves the use of multiple medications with different mechanisms of action to achieve better therapeutic outcomes. This approach is often used in the management of complex medical conditions such as cancer, HIV/AIDS, and cardiovascular diseases. The goal of combination drug therapy is to improve efficacy, reduce the risk of drug resistance, decrease the likelihood of adverse effects, and enhance the overall quality of life for patients.

In combining drugs, healthcare providers aim to target various pathways involved in the disease process, which may help to:

1. Increase the effectiveness of treatment by attacking the disease from multiple angles.
2. Decrease the dosage of individual medications, reducing the risk and severity of side effects.
3. Slow down or prevent the development of drug resistance, a common problem in chronic diseases like HIV/AIDS and cancer.
4. Improve patient compliance by simplifying dosing schedules and reducing pill burden.

Examples of combination drug therapy include:

1. Antiretroviral therapy (ART) for HIV treatment, which typically involves three or more drugs from different classes to suppress viral replication and prevent the development of drug resistance.
2. Chemotherapy regimens for cancer treatment, where multiple cytotoxic agents are used to target various stages of the cell cycle and reduce the likelihood of tumor cells developing resistance.
3. Cardiovascular disease management, which may involve combining medications such as angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, diuretics, and statins to control blood pressure, heart rate, fluid balance, and cholesterol levels.
4. Treatment of tuberculosis, which often involves a combination of several antibiotics to target different aspects of the bacterial life cycle and prevent the development of drug-resistant strains.

When prescribing combination drug therapy, healthcare providers must carefully consider factors such as potential drug interactions, dosing schedules, adverse effects, and contraindications to ensure safe and effective treatment. Regular monitoring of patients is essential to assess treatment response, manage side effects, and adjust the treatment plan as needed.

Treatment outcome is a term used to describe the result or effect of medical treatment on a patient's health status. It can be measured in various ways, such as through symptoms improvement, disease remission, reduced disability, improved quality of life, or survival rates. The treatment outcome helps healthcare providers evaluate the effectiveness of a particular treatment plan and make informed decisions about future care. It is also used in clinical research to compare the efficacy of different treatments and improve patient care.

Chyle is a milky, slightly opaque fluid that is present in the lymphatic system. It is formed in the small intestine during the digestion of food, particularly fats. Chyle consists of emulsified fat droplets (chylomicrons), proteins, electrolytes, and lymphocytes suspended in a watery solution. It is transported through the lacteals in the villi of the small intestine into the cisterna chyli and then to the thoracic duct, where it empties into the left subclavian vein. From there, it mixes with blood and circulates throughout the body. Chyle formation plays a crucial role in fat absorption and transportation in the human body.

Liver transplantation is a surgical procedure in which a diseased or failing liver is replaced with a healthy one from a deceased donor or, less commonly, a portion of a liver from a living donor. The goal of the procedure is to restore normal liver function and improve the patient's overall health and quality of life.

Liver transplantation may be recommended for individuals with end-stage liver disease, acute liver failure, certain genetic liver disorders, or liver cancers that cannot be treated effectively with other therapies. The procedure involves complex surgery to remove the diseased liver and implant the new one, followed by a period of recovery and close medical monitoring to ensure proper function and minimize the risk of complications.

The success of liver transplantation has improved significantly in recent years due to advances in surgical techniques, immunosuppressive medications, and post-transplant care. However, it remains a major operation with significant risks and challenges, including the need for lifelong immunosuppression to prevent rejection of the new liver, as well as potential complications such as infection, bleeding, and organ failure.

Polyenes are a group of antibiotics that contain a long, unsaturated hydrocarbon chain with alternating double and single bonds. They are characterized by their ability to bind to ergosterol, a steroid found in fungal cell membranes, forming pores that increase the permeability of the membrane and lead to fungal cell death.

The most well-known polyene antibiotic is amphotericin B, which is used to treat serious systemic fungal infections such as candidiasis, aspergillosis, and cryptococcosis. Other polyenes include nystatin and natamycin, which are primarily used to treat topical fungal infections of the skin or mucous membranes.

While polyenes are effective antifungal agents, they can also cause significant side effects, particularly when used systemically. These may include kidney damage, infusion reactions, and electrolyte imbalances. Therefore, their use is typically reserved for severe fungal infections that are unresponsive to other treatments.

Homologous transplantation is a type of transplant surgery where organs or tissues are transferred between two genetically non-identical individuals of the same species. The term "homologous" refers to the similarity in structure and function of the donated organ or tissue to the recipient's own organ or tissue.

For example, a heart transplant from one human to another is an example of homologous transplantation because both organs are hearts and perform the same function. Similarly, a liver transplant, kidney transplant, lung transplant, and other types of organ transplants between individuals of the same species are also considered homologous transplantations.

Homologous transplantation is in contrast to heterologous or xenogeneic transplantation, where organs or tissues are transferred from one species to another, such as a pig heart transplanted into a human. Homologous transplantation is more commonly performed than heterologous transplantation due to the increased risk of rejection and other complications associated with xenogeneic transplants.

Drug-eluting stents (DES) are medical devices used in the treatment of coronary artery disease. They are small, flexible tubes that are coated with a medication that is slowly released (eluted) over time to prevent the formation of scar tissue and reduce the risk of renarrowing (restenosis) of the artery after it has been treated with angioplasty and stenting.

The stent is typically placed in a narrowed or blocked coronary artery during a percutaneous coronary intervention (PCI) procedure, such as angioplasty, to open up the blood vessel and improve blood flow to the heart muscle. The medication on the DES helps to prevent the growth of smooth muscle cells and the formation of scar tissue in the artery, which can cause restenosis and require additional treatments.

The most commonly used medications on DES are sirolimus, paclitaxel, zotarolimus, and everolimus. These drugs work by inhibiting the growth of smooth muscle cells and reducing inflammation in the artery. While DES have been shown to reduce the risk of restenosis compared to bare-metal stents, they also carry a small increased risk of late stent thrombosis (blood clots forming in the stent), which can lead to serious complications such as heart attack or stroke. Therefore, patients who receive DES are typically prescribed long-term antiplatelet therapy to reduce this risk.

Creatinine is a waste product that's produced by your muscles and removed from your body by your kidneys. Creatinine is a breakdown product of creatine, a compound found in meat and fish, as well as in the muscles of vertebrates, including humans.

In healthy individuals, the kidneys filter out most of the creatinine and eliminate it through urine. However, when the kidneys are not functioning properly, creatinine levels in the blood can rise. Therefore, measuring the amount of creatinine in the blood or urine is a common way to test how well the kidneys are working. High creatinine levels in the blood may indicate kidney damage or kidney disease.

A kidney, in medical terms, is one of two bean-shaped organs located in the lower back region of the body. They are essential for maintaining homeostasis within the body by performing several crucial functions such as:

1. Regulation of water and electrolyte balance: Kidneys help regulate the amount of water and various electrolytes like sodium, potassium, and calcium in the bloodstream to maintain a stable internal environment.

2. Excretion of waste products: They filter waste products from the blood, including urea (a byproduct of protein metabolism), creatinine (a breakdown product of muscle tissue), and other harmful substances that result from normal cellular functions or external sources like medications and toxins.

3. Endocrine function: Kidneys produce several hormones with important roles in the body, such as erythropoietin (stimulates red blood cell production), renin (regulates blood pressure), and calcitriol (activated form of vitamin D that helps regulate calcium homeostasis).

4. pH balance regulation: Kidneys maintain the proper acid-base balance in the body by excreting either hydrogen ions or bicarbonate ions, depending on whether the blood is too acidic or too alkaline.

5. Blood pressure control: The kidneys play a significant role in regulating blood pressure through the renin-angiotensin-aldosterone system (RAAS), which constricts blood vessels and promotes sodium and water retention to increase blood volume and, consequently, blood pressure.

Anatomically, each kidney is approximately 10-12 cm long, 5-7 cm wide, and 3 cm thick, with a weight of about 120-170 grams. They are surrounded by a protective layer of fat and connected to the urinary system through the renal pelvis, ureters, bladder, and urethra.

Cardiovascular agents are a class of medications that are used to treat various conditions related to the cardiovascular system, which includes the heart and blood vessels. These agents can be further divided into several subcategories based on their specific mechanisms of action and therapeutic effects. Here are some examples:

1. Antiarrhythmics: These drugs are used to treat abnormal heart rhythms or arrhythmias. They work by stabilizing the electrical activity of the heart and preventing irregular impulses from spreading through the heart muscle.
2. Antihypertensives: These medications are used to lower high blood pressure, also known as hypertension. There are several classes of antihypertensive drugs, including diuretics, beta-blockers, calcium channel blockers, and angiotensin-converting enzyme (ACE) inhibitors.
3. Anticoagulants: These drugs are used to prevent blood clots from forming or growing larger. They work by interfering with the coagulation cascade, which is a series of chemical reactions that lead to the formation of a blood clot.
4. Antiplatelet agents: These medications are used to prevent platelets in the blood from sticking together and forming clots. They work by inhibiting the aggregation of platelets, which are small cells in the blood that help form clots.
5. Lipid-lowering agents: These drugs are used to lower cholesterol and other fats in the blood. They work by reducing the production or absorption of cholesterol in the body or increasing the removal of cholesterol from the bloodstream. Examples include statins, bile acid sequestrants, and PCSK9 inhibitors.
6. Vasodilators: These medications are used to widen blood vessels and improve blood flow. They work by relaxing the smooth muscle in the walls of blood vessels, causing them to dilate or widen. Examples include nitrates, calcium channel blockers, and ACE inhibitors.
7. Inotropes: These drugs are used to increase the force of heart contractions. They work by increasing the sensitivity of heart muscle cells to calcium ions, which are necessary for muscle contraction.

These are just a few examples of cardiovascular medications that are used to treat various conditions related to the heart and blood vessels. It is important to note that these medications can have side effects and should be taken under the guidance of a healthcare provider.

In the field of medicine, "time factors" refer to the duration of symptoms or time elapsed since the onset of a medical condition, which can have significant implications for diagnosis and treatment. Understanding time factors is crucial in determining the progression of a disease, evaluating the effectiveness of treatments, and making critical decisions regarding patient care.

For example, in stroke management, "time is brain," meaning that rapid intervention within a specific time frame (usually within 4.5 hours) is essential to administering tissue plasminogen activator (tPA), a clot-busting drug that can minimize brain damage and improve patient outcomes. Similarly, in trauma care, the "golden hour" concept emphasizes the importance of providing definitive care within the first 60 minutes after injury to increase survival rates and reduce morbidity.

Time factors also play a role in monitoring the progression of chronic conditions like diabetes or heart disease, where regular follow-ups and assessments help determine appropriate treatment adjustments and prevent complications. In infectious diseases, time factors are crucial for initiating antibiotic therapy and identifying potential outbreaks to control their spread.

Overall, "time factors" encompass the significance of recognizing and acting promptly in various medical scenarios to optimize patient outcomes and provide effective care.

Drug monitoring, also known as therapeutic drug monitoring (TDM), is a medical practice that involves testing blood or other bodily fluids to determine the concentration of a particular medication. This information is used to ensure that the patient is receiving an appropriate dosage and to help guide adjustments in medication therapy. It can be especially important for medications with a narrow therapeutic index, meaning that there is a small range between the effective dose and a toxic dose.

The goal of drug monitoring is to optimize medication effectiveness while minimizing potential side effects. This may involve measuring the concentration of a drug at various times after dosing to determine how quickly it is being metabolized or eliminated from the body, as well as to assess compliance with the prescribed treatment regimen.

Drug monitoring can be performed using a variety of methods, including immunoassays, chromatography, and mass spectrometry. The specific method used will depend on the drug being monitored and the level of sensitivity required. Results from drug monitoring tests are typically interpreted in conjunction with other clinical information, such as the patient's age, weight, renal function, liver function, and overall health status.

Islets of Langerhans transplantation is a surgical procedure that involves the transplantation of isolated islets from a deceased donor's pancreas into another person with type 1 diabetes. The islets of Langerhans are clusters of cells within the pancreas that produce hormones, including insulin, which regulates blood sugar levels.

In type 1 diabetes, the body's immune system mistakenly attacks and destroys these insulin-producing cells, leading to high blood sugar levels. Islet transplantation aims to replace the damaged islets with healthy ones from a donor, allowing the recipient's body to produce and regulate its own insulin again.

The procedure involves extracting the islets from the donor pancreas and infusing them into the recipient's liver through a small incision in the abdomen. Once inside the liver, the islets can sense glucose levels in the bloodstream and release insulin as needed to maintain normal blood sugar levels.

Islet transplantation has shown promising results in improving blood sugar control and reducing the risk of severe hypoglycemia (low blood sugar) in people with type 1 diabetes. However, it requires long-term immunosuppressive therapy to prevent rejection of the transplanted islets, which can have side effects and increase the risk of infections.

A drug implant is a medical device that is specially designed to provide controlled release of a medication into the body over an extended period of time. Drug implants can be placed under the skin or in various body cavities, depending on the specific medical condition being treated. They are often used when other methods of administering medication, such as oral pills or injections, are not effective or practical.

Drug implants come in various forms, including rods, pellets, and small capsules. The medication is contained within the device and is released slowly over time, either through diffusion or erosion of the implant material. This allows for a steady concentration of the drug to be maintained in the body, which can help to improve treatment outcomes and reduce side effects.

Some common examples of drug implants include:

1. Hormonal implants: These are small rods that are inserted under the skin of the upper arm and release hormones such as progestin or estrogen over a period of several years. They are often used for birth control or to treat conditions such as endometriosis or uterine fibroids.
2. Intraocular implants: These are small devices that are placed in the eye during surgery to release medication directly into the eye. They are often used to treat conditions such as age-related macular degeneration or diabetic retinopathy.
3. Bone cement implants: These are specially formulated cements that contain antibiotics and are used to fill bone defects or joint spaces during surgery. The antibiotics are released slowly over time, helping to prevent infection.
4. Implantable pumps: These are small devices that are placed under the skin and deliver medication directly into a specific body cavity, such as the spinal cord or the peritoneal cavity. They are often used to treat chronic pain or cancer.

Overall, drug implants offer several advantages over other methods of administering medication, including improved compliance, reduced side effects, and more consistent drug levels in the body. However, they may also have some disadvantages, such as the need for surgical placement and the potential for infection or other complications. As with any medical treatment, it is important to discuss the risks and benefits of drug implants with a healthcare provider.

Glomerular filtration rate (GFR) is a test used to check how well the kidneys are working. Specifically, it estimates how much blood passes through the glomeruli each minute. The glomeruli are the tiny fibers in the kidneys that filter waste from the blood. A lower GFR number means that the kidneys aren't working properly and may indicate kidney disease.

The GFR is typically calculated using a formula that takes into account the patient's serum creatinine level, age, sex, and race. The most commonly used formula is the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation. A normal GFR is usually above 90 mL/min/1.73m2, but this can vary depending on the individual's age and other factors.

Transplantation is a medical procedure where an organ or tissue is removed from one person (the donor) and placed into another person (the recipient) for the purpose of replacing the recipient's damaged or failing organ or tissue with a functioning one. The goal of transplantation is to restore normal function, improve quality of life, and extend lifespan in individuals with organ failure or severe tissue damage. Common types of transplants include kidney, liver, heart, lung, pancreas, small intestine, and bone marrow transplantations. The success of a transplant depends on various factors, including the compatibility between the donor and recipient, the health of both individuals, and the effectiveness of immunosuppressive therapy to prevent rejection of the transplanted organ or tissue.

A Fluorescence Polarization Immunoassay (FPIA) is a type of biochemical test used for the detection and quantitation of various analytes, such as drugs, hormones, or proteins, in a sample. It is based on the principle of fluorescence polarization, which measures the rotation of molecules in solution.

In an FPIA, the sample is mixed with a fluorescent tracer that binds specifically to the analyte of interest. When the mixture is excited with plane-polarized light, the fluorescent tracer emits light that retains its polarization if it remains bound to the large complex (analyte+tracer). However, if the tracer is not bound to the analyte and is free to rotate in solution, the emitted light becomes depolarized.

The degree of polarization of the emitted light is then measured and used to determine the amount of analyte present in the sample. Higher concentrations of analyte result in a higher degree of polarization, as more tracer molecules are bound and less likely to rotate.

FPIAs offer several advantages over other types of immunoassays, including simplicity, speed, and sensitivity. They are commonly used in clinical laboratories for the detection of drugs of abuse, therapeutic drugs, and hormones.

Antibiotics are a type of medication used to treat infections caused by bacteria. They work by either killing the bacteria or inhibiting their growth.

Antineoplastics, also known as chemotherapeutic agents, are a class of drugs used to treat cancer. These medications target and destroy rapidly dividing cells, such as cancer cells, although they can also affect other quickly dividing cells in the body, such as those in the hair follicles or digestive tract, which can lead to side effects.

Antibiotics and antineoplastics are two different classes of drugs with distinct mechanisms of action and uses. It is important to use them appropriately and under the guidance of a healthcare professional.

A stent is a small mesh tube that's used to treat narrow or weak arteries. Arteries are blood vessels that carry blood away from your heart to other parts of your body. A stent is placed in an artery as part of a procedure called angioplasty. Angioplasty restores blood flow through narrowed or blocked arteries by inflating a tiny balloon inside the blocked artery to widen it.

The stent is then inserted into the widened artery to keep it open. The stent is usually made of metal, but some are coated with medication that is slowly and continuously released to help prevent the formation of scar tissue in the artery. This can reduce the chance of the artery narrowing again.

Stents are also used in other parts of the body, such as the neck (carotid artery) and kidneys (renal artery), to help maintain blood flow and prevent blockages. They can also be used in the urinary system to treat conditions like ureteropelvic junction obstruction or narrowing of the urethra.

Immunosuppression is a state in which the immune system's ability to mount an immune response is reduced, compromised or inhibited. This can be caused by certain medications (such as those used to prevent rejection of transplanted organs), diseases (like HIV/AIDS), or genetic disorders. As a result, the body becomes more susceptible to infections and cancer development. It's important to note that immunosuppression should not be confused with immunity, which refers to the body's ability to resist and fight off infections and diseases.

Thrombotic microangiopathies (TMAs) are a group of disorders characterized by the formation of blood clots in small blood vessels, causing damage to the end organs. This process leads to a constellation of clinical symptoms including thrombocytopenia (low platelet count), microangiopathic hemolytic anemia (breakdown of red blood cells leading to anemia), and organ dysfunction such as renal failure, neurological impairment, or cardiac involvement.

TMAs can be primary or secondary. Primary TMAs are caused by genetic mutations affecting the complement system, coagulation cascade, or other regulatory proteins involved in vascular homeostasis. Examples of primary TMAs include atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), and complement-mediated TMA.

Secondary TMAs are caused by various underlying conditions or exposures, such as infections, autoimmune diseases, malignancies, drugs, pregnancy-related complications, or other systemic disorders. The pathogenesis of secondary TMAs is often multifactorial and may involve endothelial injury, complement activation, and platelet aggregation.

The diagnosis of TMAs requires a combination of clinical, laboratory, and sometimes histopathological findings. Treatment depends on the underlying cause and may include supportive care, plasma exchange, immunosuppressive therapy, or targeted therapies such as complement inhibitors.

Tubulin modulators are a class of drugs that target and alter the function or structure of tubulin, which is a key component of microtubules in cells. These drugs can either stabilize or destabilize microtubules by interacting with tubulin, leading to various effects on cell division and other processes that rely on microtubule dynamics.

There are two main types of tubulin modulators:

1. Microtubule stabilizers: These drugs promote the assembly and stability of microtubules by binding to tubulin, preventing its disassembly. Examples include taxanes (e.g., paclitaxel) and vinca alkaloids (e.g., vinblastine). They are primarily used as anticancer agents because they interfere with the division of cancer cells.
2. Microtubule destabilizers: These drugs inhibit the formation and stability of microtubules by binding to tubulin, promoting its disassembly. Examples include colchicine, vinca alkaloids (e.g., vinorelbine), and combretastatins. They can also be used as anticancer agents because they disrupt the mitotic spindle during cell division, leading to cancer cell death.

Tubulin modulators have various other effects on cells beyond their impact on microtubules, such as interfering with intracellular transport and signaling pathways. These diverse actions contribute to their therapeutic potential in treating diseases like cancer, but they can also lead to side effects that limit their clinical use.

Oxaloacetic acid is a chemical compound that plays a significant role in the Krebs cycle, also known as the citric acid cycle. It is a key metabolic intermediate in both glucose and fatty acid catabolism. Oxaloacetic acid is a four-carbon carboxylic acid that has two carboxyl groups and one ketone group.

In the Krebs cycle, oxaloacetic acid reacts with acetyl-CoA (an activated form of acetic acid) to form citric acid, releasing CoA and initiating the cycle. Throughout the cycle, oxaloacetic acid is continuously regenerated from malate, another intermediate in the cycle.

Additionally, oxaloacetic acid plays a role in amino acid metabolism as it can accept an amino group (NH3) to form aspartic acid, which is an essential component of several biochemical processes, including protein synthesis and the urea cycle.

Biocompatible coated materials refer to surfaces or substances that are treated or engineered with a layer or film designed to interact safely and effectively with living tissues or biological systems, without causing harm or adverse reactions. The coating material is typically composed of biomaterials that can withstand the conditions of the specific application while promoting a positive response from the body.

The purpose of these coatings may vary depending on the medical device or application. For example, they might be used to enhance the lubricity and wear resistance of implantable devices, reduce the risk of infection, promote integration with surrounding tissues, control drug release, or prevent the formation of biofilms.

Biocompatible coated materials must undergo rigorous testing and evaluation to ensure their safety and efficacy in various clinical settings. This includes assessing potential cytotoxicity, genotoxicity, sensitization, hemocompatibility, carcinogenicity, and other factors that could impact the body's response to the material.

Examples of biocompatible coating materials include:

1. Hydrogels: Cross-linked networks of hydrophilic polymers that can be used for drug delivery, tissue engineering, or as lubricious coatings on medical devices.
2. Self-assembling monolayers (SAMs): Organosilane or thiol-based molecules that form a stable, well-ordered film on surfaces, which can be further functionalized to promote specific biological interactions.
3. Poly(ethylene glycol) (PEG): A biocompatible polymer often used as a coating material due to its ability to reduce protein adsorption and cell attachment, making it useful for preventing biofouling or thrombosis on medical devices.
4. Bioactive glass: A type of biomaterial composed of silica-based glasses that can stimulate bone growth and healing when used as a coating material in orthopedic or dental applications.
5. Drug-eluting coatings: Biocompatible polymers impregnated with therapeutic agents, designed to release the drug over time to promote healing, prevent infection, or inhibit restenosis in various medical devices.

'Citrus paradisi' is the scientific name for a citrus fruit also known as the grapefruit. Grapefruits are a hybrid of pomelo and orange, believed to have originated in Barbados in the 18th century. They are known for their tangy, slightly bitter taste and juicy pulp.

Grapefruits are popular for their nutritional benefits as they are high in vitamin C, fiber, and antioxidants like lycopene and flavonoids. Some studies suggest that consuming grapefruit may help with weight loss, reduce the risk of certain cancers, and improve heart health. However, it's important to note that grapefruits can interact with certain medications, so it's always best to consult with a healthcare provider before adding them to your diet if you are taking medication.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a genetic disorder characterized by the growth of multiple cysts in the kidneys. These cysts are fluid-filled sacs that can vary in size and can multiply, leading to enlarged kidneys. The increased size and number of cysts can eventually result in reduced kidney function, high blood pressure, and potentially kidney failure.

ADPKD is an autosomal dominant disorder, meaning it only requires one copy of the altered gene (from either the mother or father) to have the disease. Each child of an affected individual has a 50% chance of inheriting the mutated gene. The two genes most commonly associated with ADPKD are PKD1 and PKD2, located on chromosomes 16 and 4, respectively.

Symptoms can vary widely among individuals with ADPKD, but they often include high blood pressure, back or side pain, headaches, increased abdominal size due to enlarged kidneys, blood in the urine, and kidney failure. Other complications may include cysts in the liver, pancreas, and/or brain (berries aneurysms).

Early diagnosis and management of ADPKD can help slow down disease progression and improve quality of life. Treatment typically includes controlling high blood pressure, managing pain, monitoring kidney function, and addressing complications as they arise. In some cases, dialysis or a kidney transplant may be necessary if kidney failure occurs.

Azathioprine is an immunosuppressive medication that is used to prevent the rejection of transplanted organs and to treat autoimmune diseases such as rheumatoid arthritis, lupus, and inflammatory bowel disease. It works by suppressing the activity of the immune system, which helps to reduce inflammation and prevent the body from attacking its own tissues.

Azathioprine is a prodrug that is converted into its active form, 6-mercaptopurine, in the body. This medication can have significant side effects, including decreased white blood cell count, increased risk of infection, and liver damage. It may also increase the risk of certain types of cancer, particularly skin cancer and lymphoma.

Healthcare professionals must carefully monitor patients taking azathioprine for these potential side effects. They may need to adjust the dosage or stop the medication altogether if serious side effects occur. Patients should also take steps to reduce their risk of infection and skin cancer, such as practicing good hygiene, avoiding sun exposure, and using sunscreen.

Acetic anhydride is a chemical compound with the formula (CH3CO)2O. It is a colorless liquid that is used as a reagent in organic synthesis, particularly in the production of cellulose acetate and other acetate esters. Acetic anhydride is also an important intermediate in the synthesis of certain pharmaceuticals and dyes.

In medical terminology, acetic anhydride is not typically used as a diagnostic or therapeutic agent. However, it can be used in laboratory settings to synthesize compounds that may have medical applications. For example, acetic anhydride has been used to produce certain antiviral drugs and antibiotics.

It is important to note that acetic anhydride can be harmful or fatal if swallowed, inhaled, or absorbed through the skin. It can cause burns and eye damage, and may be harmful to the respiratory system if inhaled. Therefore, it should be handled with care and used only in well-ventilated areas with appropriate personal protective equipment.

Heart transplantation is a surgical procedure where a diseased, damaged, or failing heart is removed and replaced with a healthy donor heart. This procedure is usually considered as a last resort for patients with end-stage heart failure or severe coronary artery disease who have not responded to other treatments. The donor heart typically comes from a brain-dead individual whose family has agreed to donate their loved one's organs for transplantation. Heart transplantation is a complex and highly specialized procedure that requires a multidisciplinary team of healthcare professionals, including cardiologists, cardiac surgeons, anesthesiologists, perfusionists, nurses, and other support staff. The success rates for heart transplantation have improved significantly over the past few decades, with many patients experiencing improved quality of life and increased survival rates. However, recipients of heart transplants require lifelong immunosuppressive therapy to prevent rejection of the donor heart, which can increase the risk of infections and other complications.

Follow-up studies are a type of longitudinal research that involve repeated observations or measurements of the same variables over a period of time, in order to understand their long-term effects or outcomes. In medical context, follow-up studies are often used to evaluate the safety and efficacy of medical treatments, interventions, or procedures.

In a typical follow-up study, a group of individuals (called a cohort) who have received a particular treatment or intervention are identified and then followed over time through periodic assessments or data collection. The data collected may include information on clinical outcomes, adverse events, changes in symptoms or functional status, and other relevant measures.

The results of follow-up studies can provide important insights into the long-term benefits and risks of medical interventions, as well as help to identify factors that may influence treatment effectiveness or patient outcomes. However, it is important to note that follow-up studies can be subject to various biases and limitations, such as loss to follow-up, recall bias, and changes in clinical practice over time, which must be carefully considered when interpreting the results.

A drug interaction is the effect of combining two or more drugs, or a drug and another substance (such as food or alcohol), which can alter the effectiveness or side effects of one or both of the substances. These interactions can be categorized as follows:

1. Pharmacodynamic interactions: These occur when two or more drugs act on the same target organ or receptor, leading to an additive, synergistic, or antagonistic effect. For example, taking a sedative and an antihistamine together can result in increased drowsiness due to their combined depressant effects on the central nervous system.
2. Pharmacokinetic interactions: These occur when one drug affects the absorption, distribution, metabolism, or excretion of another drug. For example, taking certain antibiotics with grapefruit juice can increase the concentration of the antibiotic in the bloodstream, leading to potential toxicity.
3. Food-drug interactions: Some drugs may interact with specific foods, affecting their absorption, metabolism, or excretion. An example is the interaction between warfarin (a blood thinner) and green leafy vegetables, which can increase the risk of bleeding due to enhanced vitamin K absorption from the vegetables.
4. Drug-herb interactions: Some herbal supplements may interact with medications, leading to altered drug levels or increased side effects. For instance, St. John's Wort can decrease the effectiveness of certain antidepressants and oral contraceptives by inducing their metabolism.
5. Drug-alcohol interactions: Alcohol can interact with various medications, causing additive sedative effects, impaired judgment, or increased risk of liver damage. For example, combining alcohol with benzodiazepines or opioids can lead to dangerous levels of sedation and respiratory depression.

It is essential for healthcare providers and patients to be aware of potential drug interactions to minimize adverse effects and optimize treatment outcomes.

"Unrelated donors" in the context of medicine, specifically in transplantation medicine, refer to individuals who are not genetically related to the recipient and are searched for in national or international registries. They are identified as having a similar human leukocyte antigen (HLA) type to the recipient, making them suitable to donate stem cells for bone marrow transplantation or solid organs such as kidneys, liver, heart, lungs, and pancreas.

The process of finding an unrelated donor is coordinated by transplant centers and registries, such as the National Marrow Donor Program (NMDP) in the United States or World Marrow Donor Association (WMDA) globally. The success of finding a suitable unrelated donor depends on various factors, including the recipient's HLA type, age, ethnicity, and medical urgency.

It is important to note that unrelated donors undergo rigorous screening processes to ensure their health and suitability for donation, as well as to minimize any potential risks to both the donor and the recipient.

Retrospective studies, also known as retrospective research or looking back studies, are a type of observational study that examines data from the past to draw conclusions about possible causal relationships between risk factors and outcomes. In these studies, researchers analyze existing records, medical charts, or previously collected data to test a hypothesis or answer a specific research question.

Retrospective studies can be useful for generating hypotheses and identifying trends, but they have limitations compared to prospective studies, which follow participants forward in time from exposure to outcome. Retrospective studies are subject to biases such as recall bias, selection bias, and information bias, which can affect the validity of the results. Therefore, retrospective studies should be interpreted with caution and used primarily to generate hypotheses for further testing in prospective studies.

Antilymphocyte serum (ALS) is a type of immune serum that contains antibodies against human lymphocytes. It is produced by immunizing animals, such as horses or rabbits, with human lymphocytes to stimulate an immune response and the production of anti-lymphocyte antibodies. The resulting serum is then collected and can be used as a therapeutic agent to suppress the activity of the immune system in certain medical conditions.

ALS is primarily used in the treatment of transplant rejection, particularly in organ transplantation, where it helps to prevent the recipient's immune system from attacking and rejecting the transplanted organ. It can also be used in the management of autoimmune diseases, such as rheumatoid arthritis and lupus, to suppress the overactive immune response that contributes to these conditions.

It is important to note that the use of ALS carries a risk of side effects, including allergic reactions, fever, and decreased white blood cell counts. Close monitoring and appropriate management of these potential adverse events are essential during treatment with ALS.

Tuberous Sclerosis Complex (TSC) is a rare genetic disorder that causes non-cancerous (benign) tumors to grow in many parts of the body. These tumors can affect the brain, skin, heart, kidneys, eyes, and lungs. The signs and symptoms of TSC can vary widely, depending on where the tumors develop and how severely a person is affected.

The condition is caused by mutations in either the TSC1 or TSC2 gene, which regulate a protein that helps control cell growth and division. When these genes are mutated, the protein is not produced correctly, leading to excessive cell growth and the development of tumors.

TSC is typically diagnosed based on clinical symptoms, medical imaging, and genetic testing. Treatment for TSC often involves a multidisciplinary approach, with specialists in neurology, dermatology, cardiology, nephrology, pulmonology, and ophthalmology working together to manage the various symptoms of the condition. Medications, surgery, and other therapies may be used to help control seizures, developmental delays, skin abnormalities, and other complications of TSC.

An oral ulcer is a defect or break in the continuity of the epithelium, the tissue that lines the inner surface of the mouth, leading to an inflamed, painful, and sometimes bleeding lesion. They can be classified as primary (e.g., aphthous ulcers, traumatic ulcers) or secondary (e.g., those caused by infections, underlying systemic conditions, or reactions to medications). Oral ulcers may cause discomfort, impacting speech and food consumption, and their presence might indicate an underlying medical issue that requires further evaluation.

Renal insufficiency, also known as kidney failure, is a medical condition in which the kidneys are unable to properly filter waste products and excess fluids from the blood. This results in a buildup of these substances in the body, which can cause a variety of symptoms such as weakness, shortness of breath, and fluid retention. Renal insufficiency can be acute, meaning it comes on suddenly, or chronic, meaning it develops over time. It is typically diagnosed through blood tests, urine tests, and imaging studies. Treatment may include medications to control symptoms, dietary changes, and in severe cases, dialysis or a kidney transplant.

Kidney function tests (KFTs) are a group of diagnostic tests that evaluate how well your kidneys are functioning by measuring the levels of various substances in the blood and urine. The tests typically assess the glomerular filtration rate (GFR), which is an indicator of how efficiently the kidneys filter waste from the blood, as well as the levels of electrolytes, waste products, and proteins in the body.

Some common KFTs include:

1. Serum creatinine: A waste product that's produced by normal muscle breakdown and is excreted by the kidneys. Elevated levels may indicate reduced kidney function.
2. Blood urea nitrogen (BUN): Another waste product that's produced when protein is broken down and excreted by the kidneys. Increased BUN levels can suggest impaired kidney function.
3. Estimated glomerular filtration rate (eGFR): A calculation based on serum creatinine, age, sex, and race that estimates the GFR and provides a more precise assessment of kidney function than creatinine alone.
4. Urinalysis: An examination of a urine sample to detect abnormalities such as protein, blood, or bacteria that may indicate kidney disease.
5. Electrolyte levels: Measurement of sodium, potassium, chloride, and bicarbonate in the blood to ensure they're properly balanced, which is essential for normal kidney function.

KFTs are often ordered as part of a routine check-up or when kidney disease is suspected based on symptoms or other diagnostic tests. Regular monitoring of kidney function can help detect and manage kidney disease early, potentially preventing or slowing down its progression.

Perivascular Epithelioid Cell Neoplasms (PEComas) are a rare group of mesenchymal tumors that demonstrate unique clinical and pathological features. These neoplasms are characterized by the proliferation of perivascular epithelioid cells (PECs), which are distinctive cells with an epithelioid appearance and a close association with blood vessel walls.

PEComas can occur in various organs, such as the kidney, liver, lung, pancreas, and gastrointestinal tract, but they most commonly involve the uterus. The World Health Organization (WHO) recognizes three main types of PEComas: epithelioid angiomyolipoma, clear cell "sugar" tumor, and lymphangioleiomyomatosis (LAM).

PEComas exhibit a wide range of clinical behaviors, from benign to malignant. Malignant PEComas typically display features such as infiltrative growth, high cellularity, nuclear atypia, increased mitotic activity, and necrosis. The pathogenesis of PEComas is not well understood, but recent studies suggest that they may be related to the TSC1 or TSC2 gene mutations, which are also associated with tuberous sclerosis complex (TSC), a genetic disorder characterized by benign tumors in multiple organs.

Diagnosis of PEComas is based on histopathological examination and immunohistochemical staining. The typical immunophenotype of PECs includes positivity for both melanocytic markers (such as HMB-45 and Melan-A) and smooth muscle markers (such as actin and desmin).

Treatment options for PEComas depend on the tumor's location, size, and clinical behavior. Surgical resection is the primary treatment modality for localized, symptomatic, or malignant PEComas. In some cases, systemic therapy with mammalian target of rapamycin (mTOR) inhibitors may be considered, particularly in metastatic or recurrent tumors.

Ribosomal Protein S6 Kinases, 70-kDa (p70S6K or RPS6KB1) are serine/threonine protein kinases that play a crucial role in the regulation of cell growth and metabolism. They are so named because they phosphorylate the 40S ribosomal protein S6, which is a component of the small ribosomal subunit. This phosphorylation event is believed to contribute to the control of protein synthesis rates in response to various cellular signals, including growth factors and nutrients.

p70S6K is activated by the PI3K/AKT/mTOR signaling pathway, which is a critical regulator of cell growth, proliferation, and survival. The activation of p70S6K involves a series of phosphorylation events, primarily by mTORC1 (mammalian target of rapamycin complex 1). Once activated, p70S6K promotes several processes related to cell growth, such as:

1. Translation initiation and elongation: Phosphorylation of ribosomal protein S6 and other translation factors enhances the translation of specific mRNAs involved in cell cycle progression, ribosome biogenesis, and metabolic enzymes.
2. Nucleolar formation and rRNA transcription: p70S6K promotes nucleolar formation and increases rRNA transcription by phosphorylating upstream binding factor (UBF), a critical transcriptional regulator of rDNA.
3. mRNA stability: Phosphorylation of certain RNA-binding proteins, such as 4E-BP1, by p70S6K can lead to increased mRNA stability and translation efficiency.

Abnormal regulation of p70S6K has been implicated in various diseases, including cancer, diabetes, and cardiovascular disorders. Therefore, understanding the function and regulation of p70S6K is essential for developing novel therapeutic strategies targeting these conditions.

Paclitaxel is a chemotherapeutic agent derived from the bark of the Pacific yew tree (Taxus brevifolia). It is an antimicrotubule agent that promotes the assembly and stabilization of microtubules, thereby interfering with the normal dynamic reorganization of the microtubule network that is essential for cell division.

Paclitaxel is used in the treatment of various types of cancer including ovarian, breast, lung, and pancreatic cancers. It works by inhibiting the disassembly of microtubules, which prevents the separation of chromosomes during mitosis, leading to cell cycle arrest and apoptosis (programmed cell death).

Common side effects of paclitaxel include neutropenia (low white blood cell count), anemia (low red blood cell count), alopecia (hair loss), peripheral neuropathy (nerve damage causing numbness or tingling in the hands and feet), myalgias (muscle pain), arthralgias (joint pain), and hypersensitivity reactions.

A biliary fistula is an abnormal connection or passage between the biliary system (which includes the gallbladder, bile ducts, and liver) and another organ or structure, usually in the abdominal cavity. This connection allows bile, which is a digestive fluid produced by the liver, to leak out of its normal pathway and into other areas of the body.

Biliary fistulas can occur as a result of trauma, surgery, infection, or inflammation in the biliary system. Symptoms may include abdominal pain, fever, jaundice (yellowing of the skin and eyes), nausea, vomiting, and clay-colored stools. Treatment typically involves addressing the underlying cause of the fistula, such as draining an infection or repairing damaged tissue, and diverting bile flow away from the site of the leak. In some cases, surgery may be necessary to repair the fistula.

A biopsy is a medical procedure in which a small sample of tissue is taken from the body to be examined under a microscope for the presence of disease. This can help doctors diagnose and monitor various medical conditions, such as cancer, infections, or autoimmune disorders. The type of biopsy performed will depend on the location and nature of the suspected condition. Some common types of biopsies include:

1. Incisional biopsy: In this procedure, a surgeon removes a piece of tissue from an abnormal area using a scalpel or other surgical instrument. This type of biopsy is often used when the lesion is too large to be removed entirely during the initial biopsy.

2. Excisional biopsy: An excisional biopsy involves removing the entire abnormal area, along with a margin of healthy tissue surrounding it. This technique is typically employed for smaller lesions or when cancer is suspected.

3. Needle biopsy: A needle biopsy uses a thin, hollow needle to extract cells or fluid from the body. There are two main types of needle biopsies: fine-needle aspiration (FNA) and core needle biopsy. FNA extracts loose cells, while a core needle biopsy removes a small piece of tissue.

4. Punch biopsy: In a punch biopsy, a round, sharp tool is used to remove a small cylindrical sample of skin tissue. This type of biopsy is often used for evaluating rashes or other skin abnormalities.

5. Shave biopsy: During a shave biopsy, a thin slice of tissue is removed from the surface of the skin using a sharp razor-like instrument. This technique is typically used for superficial lesions or growths on the skin.

After the biopsy sample has been collected, it is sent to a laboratory where a pathologist will examine the tissue under a microscope and provide a diagnosis based on their findings. The results of the biopsy can help guide further treatment decisions and determine the best course of action for managing the patient's condition.

A clinical audit is a quality improvement process that involves systematically evaluating and improving the care delivered to patients. It is based on comparing current practice against evidence-based standards or guidelines, identifying gaps between current and desired practice, and implementing changes to close those gaps. Clinical audits can focus on various aspects of healthcare delivery, including clinical outcomes, patient safety, patient experience, and clinical processes. The aim of a clinical audit is to ensure that patients receive high-quality care that meets best practice standards, leading to improved health outcomes and patient satisfaction.

The adrenal cortex hormones are a group of steroid hormones produced and released by the outer portion (cortex) of the adrenal glands, which are located on top of each kidney. These hormones play crucial roles in regulating various physiological processes, including:

1. Glucose metabolism: Cortisol helps control blood sugar levels by increasing glucose production in the liver and reducing its uptake in peripheral tissues.
2. Protein and fat metabolism: Cortisol promotes protein breakdown and fatty acid mobilization, providing essential building blocks for energy production during stressful situations.
3. Immune response regulation: Cortisol suppresses immune function to prevent overactivation and potential damage to the body during stress.
4. Cardiovascular function: Aldosterone regulates electrolyte balance and blood pressure by promoting sodium reabsorption and potassium excretion in the kidneys.
5. Sex hormone production: The adrenal cortex produces small amounts of sex hormones, such as androgens and estrogens, which contribute to sexual development and function.
6. Growth and development: Cortisol plays a role in normal growth and development by influencing the activity of growth-promoting hormones like insulin-like growth factor 1 (IGF-1).

The main adrenal cortex hormones include:

1. Glucocorticoids: Cortisol is the primary glucocorticoid, responsible for regulating metabolism and stress response.
2. Mineralocorticoids: Aldosterone is the primary mineralocorticoid, involved in electrolyte balance and blood pressure regulation.
3. Androgens: Dehydroepiandrosterone (DHEA) and its sulfate derivative (DHEAS) are the most abundant adrenal androgens, contributing to sexual development and function.
4. Estrogens: Small amounts of estrogens are produced by the adrenal cortex, mainly in women.

Disorders related to impaired adrenal cortex hormone production or regulation can lead to various clinical manifestations, such as Addison's disease (adrenal insufficiency), Cushing's syndrome (hypercortisolism), and congenital adrenal hyperplasia (CAH).

Ketoconazole is an antifungal medication that is primarily used to treat various fungal infections, including those caused by dermatophytes, Candida, and pityrosporum. It works by inhibiting the synthesis of ergosterol, a crucial component of fungal cell membranes, which leads to increased permeability and ultimately results in fungal cell death.

Ketoconazole is available as an oral tablet for systemic use and as a topical cream or shampoo for localized applications. The oral formulation is used to treat severe or invasive fungal infections, while the topical preparations are primarily indicated for skin and scalp infections, such as athlete's foot, ringworm, jock itch, candidiasis, and seborrheic dermatitis.

Common side effects of oral ketoconazole include nausea, vomiting, headache, and altered liver function tests. Rare but serious adverse reactions may include hepatotoxicity, adrenal insufficiency, and interactions with other medications that can affect the metabolism and elimination of drugs. Topical ketoconazole is generally well-tolerated, with local irritation being the most common side effect.

It's important to note that due to its potential for serious liver toxicity and drug-drug interactions, oral ketoconazole has been largely replaced by other antifungal agents, such as fluconazole and itraconazole, which have more favorable safety profiles. Topical ketoconazole remains a valuable option for treating localized fungal infections due to its effectiveness and lower risk of systemic side effects.

Oligomenorrhea is a medical term used to describe infrequent menstrual periods, where the cycle length is more than 35 days but less than 68 days. It's considered a menstrual disorder and can affect people of reproductive age. The causes of oligomenorrhea are varied, including hormonal imbalances, polycystic ovary syndrome (PCOS), thyroid disorders, excessive exercise, significant weight loss or gain, and stress. In some cases, it may not cause any other symptoms, but in others, it can be associated with infertility, hirsutism (excessive hair growth), acne, or obesity. Treatment depends on the underlying cause and may include lifestyle modifications, hormonal medications, or surgery in rare cases.

Transplantation conditioning, also known as preparative regimen or immunoablative therapy, refers to the use of various treatments prior to transplantation of cells, tissues or organs. The main goal of transplantation conditioning is to suppress the recipient's immune system, allowing for successful engraftment and minimizing the risk of rejection of the donor tissue.

There are two primary types of transplantation conditioning: myeloablative and non-myeloablative.

1. Myeloablative conditioning is a more intensive regimen that involves the use of high-dose chemotherapy, radiation therapy or both. This approach eliminates not only immune cells but also stem cells in the bone marrow, requiring the recipient to receive a hematopoietic cell transplant (HCT) from the donor to reconstitute their blood and immune system.
2. Non-myeloablative conditioning is a less intensive regimen that primarily targets immune cells while sparing the stem cells in the bone marrow. This approach allows for mixed chimerism, where both recipient and donor immune cells coexist, reducing the risk of severe complications associated with myeloablative conditioning.

The choice between these two types of transplantation conditioning depends on various factors, including the type of transplant, patient's age, overall health, and comorbidities. Both approaches carry risks and benefits, and the decision should be made carefully by a multidisciplinary team of healthcare professionals in consultation with the patient.

Respiratory system agents are substances that affect the respiratory system, which includes the nose, throat (pharynx), voice box (larynx), windpipe (trachea), bronchi, and lungs. These agents can be classified into different categories based on their effects:

1. Respiratory Stimulants: Agents that increase respiratory rate or depth by acting on the respiratory center in the brainstem.
2. Respiratory Depressants: Agents that decrease respiratory rate or depth, often as a side effect of their sedative or analgesic effects. Examples include opioids, benzodiazepines, and barbiturates.
3. Bronchodilators: Agents that widen the airways (bronchioles) in the lungs by relaxing the smooth muscle around them. They are used to treat asthma, chronic obstructive pulmonary disease (COPD), and other respiratory conditions. Examples include albuterol, ipratropium, and theophylline.
4. Anti-inflammatory Agents: Agents that reduce inflammation in the airways, which can help relieve symptoms of asthma, COPD, and other respiratory conditions. Examples include corticosteroids, leukotriene modifiers, and mast cell stabilizers.
5. Antitussives: Agents that suppress coughing, often by numbing the throat or acting on the cough center in the brainstem. Examples include dextromethorphan and codeine.
6. Expectorants: Agents that help thin and loosen mucus in the airways, making it easier to cough up and clear. Examples include guaifenesin and iodinated glycerol.
7. Decongestants: Agents that narrow blood vessels in the nose and throat, which can help relieve nasal congestion and sinus pressure. Examples include pseudoephedrine and phenylephrine.
8. Antimicrobial Agents: Agents that kill or inhibit the growth of microorganisms such as bacteria, viruses, and fungi that can cause respiratory infections. Examples include antibiotics, antiviral drugs, and antifungal agents.

Mucorales is a order of fungi that includes several genera of mold-like fungi, such as Mucor, Rhizopus, and Absidia. These fungi are commonly found in soil, decaying vegetation, and animal manure. Some species can cause mucormycosis, a serious and often life-threatening invasive fungal infection that primarily affects people with weakened immune systems, such as those with uncontrolled diabetes, cancer, or organ transplants. The infection typically begins in the respiratory tract, but it can spread to other parts of the body, including the sinuses, brain, and lungs. Mucormycosis is difficult to diagnose and treat, and it has a high mortality rate.

Prospective studies, also known as longitudinal studies, are a type of cohort study in which data is collected forward in time, following a group of individuals who share a common characteristic or exposure over a period of time. The researchers clearly define the study population and exposure of interest at the beginning of the study and follow up with the participants to determine the outcomes that develop over time. This type of study design allows for the investigation of causal relationships between exposures and outcomes, as well as the identification of risk factors and the estimation of disease incidence rates. Prospective studies are particularly useful in epidemiology and medical research when studying diseases with long latency periods or rare outcomes.

Steroids, also known as corticosteroids, are a type of hormone that the adrenal gland produces in your body. They have many functions, such as controlling the balance of salt and water in your body and helping to reduce inflammation. Steroids can also be synthetically produced and used as medications to treat a variety of conditions, including allergies, asthma, skin conditions, and autoimmune disorders.

Steroid medications are available in various forms, such as oral pills, injections, creams, and inhalers. They work by mimicking the effects of natural hormones produced by your body, reducing inflammation and suppressing the immune system's response to prevent or reduce symptoms. However, long-term use of steroids can have significant side effects, including weight gain, high blood pressure, osteoporosis, and increased risk of infections.

It is important to note that anabolic steroids are a different class of drugs that are sometimes abused for their muscle-building properties. These steroids are synthetic versions of the male hormone testosterone and can have serious health consequences when taken in large doses or without medical supervision.

Postoperative complications refer to any unfavorable condition or event that occurs during the recovery period after a surgical procedure. These complications can vary in severity and may include, but are not limited to:

1. Infection: This can occur at the site of the incision or inside the body, such as pneumonia or urinary tract infection.
2. Bleeding: Excessive bleeding (hemorrhage) can lead to a drop in blood pressure and may require further surgical intervention.
3. Blood clots: These can form in the deep veins of the legs (deep vein thrombosis) and can potentially travel to the lungs (pulmonary embolism).
4. Wound dehiscence: This is when the surgical wound opens up, which can lead to infection and further complications.
5. Pulmonary issues: These include atelectasis (collapsed lung), pneumonia, or respiratory failure.
6. Cardiovascular problems: These include abnormal heart rhythms (arrhythmias), heart attack, or stroke.
7. Renal failure: This can occur due to various reasons such as dehydration, blood loss, or the use of certain medications.
8. Pain management issues: Inadequate pain control can lead to increased stress, anxiety, and decreased mobility.
9. Nausea and vomiting: These can be caused by anesthesia, opioid pain medication, or other factors.
10. Delirium: This is a state of confusion and disorientation that can occur in the elderly or those with certain medical conditions.

Prompt identification and management of these complications are crucial to ensure the best possible outcome for the patient.

Absorbable implants are medical devices that are designed to be placed inside the body during a surgical procedure, where they provide support, stabilization, or other functions, and then gradually break down and are absorbed by the body over time. These implants are typically made from materials such as polymers, proteins, or ceramics that have been engineered to degrade at a controlled rate, allowing them to be resorbed and eliminated from the body without the need for a second surgical procedure to remove them.

Absorbable implants are often used in orthopedic, dental, and plastic surgery applications, where they can help promote healing and support tissue regeneration. For example, absorbable screws or pins may be used to stabilize fractured bones during the healing process, after which they will gradually dissolve and be absorbed by the body. Similarly, absorbable membranes may be used in dental surgery to help guide the growth of new bone and gum tissue around an implant, and then be resorbed over time.

It's important to note that while absorbable implants offer several advantages over non-absorbable materials, such as reduced risk of infection and improved patient comfort, they may also have some limitations. For example, the mechanical properties of absorbable materials may not be as strong as those of non-absorbable materials, which could affect their performance in certain applications. Additionally, the degradation products of absorbable implants may cause local inflammation or other adverse reactions in some patients. As with any medical device, the use of absorbable implants should be carefully considered and discussed with a qualified healthcare professional.

Cytochrome P-450 CYP3A is a subfamily of the cytochrome P-450 enzyme superfamily, which are primarily involved in drug metabolism in the human body. These enzymes are found predominantly in the liver, but also in other tissues such as the small intestine, kidneys, and brain.

CYP3A enzymes are responsible for metabolizing a wide variety of drugs, including many statins, benzodiazepines, antidepressants, and opioids. They can also metabolize endogenous compounds such as steroids and bile acids. The activity of CYP3A enzymes can be influenced by various factors, including genetic polymorphisms, age, sex, pregnancy, and the presence of other drugs or diseases.

The name "cytochrome P-450" refers to the fact that these enzymes contain a heme group that absorbs light at a wavelength of 450 nanometers when it is complexed with carbon monoxide. The term "CYP3A" denotes the specific subfamily of cytochrome P-450 enzymes that share a high degree of sequence similarity and function.

A living donor is a person who voluntarily donates an organ or part of an organ to another person while they are still alive. This can include donations such as a kidney, liver lobe, lung, or portion of the pancreas or intestines. The donor and recipient typically undergo medical evaluation and compatibility testing to ensure the best possible outcome for the transplantation procedure. Living donation is regulated by laws and ethical guidelines to ensure that donors are fully informed and making a voluntary decision.

Benzenesulfonates are organic compounds that contain a benzene ring substituted with a sulfonate group. In chemistry, a sulfonate group is a functional group consisting of a sulfur atom connected to three oxygen atoms (-SO3). Benzenesulfonates are often used as detergents, emulsifiers, and phase transfer catalysts in various chemical reactions. They can also be found in some pharmaceuticals and dyes.

A dose-response relationship in the context of drugs refers to the changes in the effects or symptoms that occur as the dose of a drug is increased or decreased. Generally, as the dose of a drug is increased, the severity or intensity of its effects also increases. Conversely, as the dose is decreased, the effects of the drug become less severe or may disappear altogether.

The dose-response relationship is an important concept in pharmacology and toxicology because it helps to establish the safe and effective dosage range for a drug. By understanding how changes in the dose of a drug affect its therapeutic and adverse effects, healthcare providers can optimize treatment plans for their patients while minimizing the risk of harm.

The dose-response relationship is typically depicted as a curve that shows the relationship between the dose of a drug and its effect. The shape of the curve may vary depending on the drug and the specific effect being measured. Some drugs may have a steep dose-response curve, meaning that small changes in the dose can result in large differences in the effect. Other drugs may have a more gradual dose-response curve, where larger changes in the dose are needed to produce significant effects.

In addition to helping establish safe and effective dosages, the dose-response relationship is also used to evaluate the potential therapeutic benefits and risks of new drugs during clinical trials. By systematically testing different doses of a drug in controlled studies, researchers can identify the optimal dosage range for the drug and assess its safety and efficacy.

Intention-to-treat (ITT) analysis is a principle used in the design and interpretation of clinical trials, where all participants who are randomly assigned to a treatment group, regardless of whether they receive or complete the intended intervention, are included in the final analysis. The primary aim of ITT analysis is to mirror real-world scenarios as closely as possible by preserving the original randomization scheme and accounting for potential confounding factors, such as dropouts, protocol deviations, or crossovers between treatment groups.

In an ITT analysis, participants are analyzed in their originally assigned groups, even if they do not receive the intended intervention or switch to another group during the study. This approach helps maintain the balance of prognostic factors across treatment groups and reduces bias that may arise from selective exclusion of non-compliant or non-adherent individuals.

The ITT principle is particularly important in superiority trials, where the primary goal is to demonstrate a significant difference between two interventions. By including all participants in the analysis, researchers can minimize potential biases and maintain statistical power, ensuring that the results are more generalizable to the broader target population. However, it is essential to recognize that ITT analyses may underestimate treatment effects compared to per-protocol or as-treated analyses, which only include participants who adhere to their assigned intervention.

In summary, an intention-to-treat analysis is a medical research principle in clinical trials where all randomly assigned participants are analyzed in their original groups, regardless of whether they receive or complete the intended intervention. This approach helps maintain statistical power and reduce bias, providing results that are more generalizable to real-world scenarios.

Graft occlusion in the context of vascular surgery refers to the complete or partial blockage of a blood vessel that has been surgically replaced or repaired with a graft. The graft can be made from either synthetic materials or autologous tissue (taken from another part of the patient's body).

Graft occlusion can occur due to various reasons, including:

1. Thrombosis: Formation of a blood clot within the graft, which can obstruct blood flow.
2. Intimal hyperplasia: Overgrowth of the inner lining (intima) of the graft or the adjacent native vessel, causing narrowing of the lumen and reducing blood flow.
3. Atherosclerosis: Deposition of cholesterol and other substances in the walls of the graft, leading to hardening and narrowing of the vessel.
4. Infection: Bacterial or fungal infection of the graft can cause inflammation, weakening, and ultimately occlusion of the graft.
5. Mechanical factors: Kinking, twisting, or compression of the graft can lead to obstruction of blood flow.

Graft occlusion is a significant complication following vascular surgery, as it can result in reduced perfusion to downstream tissues and organs, leading to ischemia (lack of oxygen supply) and potential tissue damage or loss.

Coronary angiography is a medical procedure that uses X-ray imaging to visualize the coronary arteries, which supply blood to the heart muscle. During the procedure, a thin, flexible catheter is inserted into an artery in the arm or groin and threaded through the blood vessels to the heart. A contrast dye is then injected through the catheter, and X-ray images are taken as the dye flows through the coronary arteries. These images can help doctors diagnose and treat various heart conditions, such as blockages or narrowing of the arteries, that can lead to chest pain or heart attacks. It is also known as coronary arteriography or cardiac catheterization.

Proteinuria is a medical term that refers to the presence of excess proteins, particularly albumin, in the urine. Under normal circumstances, only small amounts of proteins should be found in the urine because the majority of proteins are too large to pass through the glomeruli, which are the filtering units of the kidneys.

However, when the glomeruli become damaged or diseased, they may allow larger molecules such as proteins to leak into the urine. Persistent proteinuria is often a sign of kidney disease and can indicate damage to the glomeruli. It is usually detected through a routine urinalysis and may be confirmed with further testing.

The severity of proteinuria can vary, and it can be a symptom of various underlying conditions such as diabetes, hypertension, glomerulonephritis, and other kidney diseases. Treatment for proteinuria depends on the underlying cause and may include medications to control blood pressure, manage diabetes, or reduce protein loss in the urine.

... seems to lower the cancer risk in some transplant patients. Sirolimus was shown to inhibit the progression of dermal ... Sirolimus blocks this pathway. The safety and efficacy of sirolimus treatment of LAM were investigated in clinical trials that ... Sirolimus is used to treat vascular malformations. Treatment with sirolimus can decrease pain and the fullness of vascular ... Sirolimus is a relatively new medical therapy for the treatment of vascular malformations in recent years, sirolimus has ...
... produces sirolimus. List of Streptomyces species LPSN bacterio.net UniProt Deutsche Sammlung von ...
In 2003, the U.S. Food and Drug Administration approved sirolimus-eluting coronary stents, which are used in patients with ... "CYPHER Sirolimus-eluting Coronary Stent - P020026". Food and Drug Administration. Retrieved 25 September 2012. "Torisel". ... Ridaforolimus (AP23573, MK-8669), or deforolimus, is another rapamycin analogue that is not a prodrug for sirolimus. Like ... The bacterial natural product rapamycin or sirolimus, a cytostatic agent, has been used in combination therapy with ...
"CYPHER™ Sirolimus-eluting Coronary Stent - P020026". FDA.gov. U.S. Food and Drug Administration. Retrieved 1 Aug 2016. "J&J to ... Sirolimus: Anti-proliferative effects "Learn about CYPHER Stent, the latest advance in stent technology". Cordis Corporation. ... An anti-rejection-type medication, sirolimus, helps to limit the overgrowth of normal cells while the artery heals which ...
Sirolimus is used to treat lymphangioma . Treatment with sirolimus can decrease pain and the fullness of venous malformations, ... Sirolimus is a relatively new medical therapy for the treatment of vascular malformations, in recent years, sirolimus has ... Sirolimus (rapamycin, trade name Rapamune) is a macrolide compound. It has immunosuppressant and antiproliferative functions in ... "Sirolimus in the treatment of vascular anomalies." https://www.jvascsurg.org/article/S0741-5214(19)32236-0/fulltext, Journal of ...
H. Mawardi; M. Pavlakis; D.S. Mandelbrot; S.B. Woo (2010). "Sirolimus oral ulcer with Cedecea davisae superinfection". Transpl ... Mawardi, H., Pavlakis, M., Mandelbrot, D., Woo, S. B. (2010). Sirolimus oral ulcer with Cedecea davisae superinfection. Transpl ...
Sirolimus and mycophenolate have less evidence for their use in the treatment of chronic hives but reports have shown them to ... Morgan M (2009). "Treatment of refractory chronic urticaria with sirolimus". Arch Dermatol. 145 (6): 637-9. doi:10.1001/ ... Immunosuppressants used for CU include cyclosporine, tacrolimus, sirolimus, and mycophenolate. Calcineurin inhibitors, such as ... At this point, anti-inflammatory medications (dapsone, sulfasalazine), immunosuppressants (cyclosporin, sirolimus) or other ...
The Combo Dual Therapy Stent is a coronary stent that combines Genous with an antiproliferative, biodegradable sirolimus drug ... Sirolimus-Eluting Stent Found 'Safe,' and 'Effective.'" Cardiology News. "Dual-Therapy Stenting: The Next Step in the Evolution ...
It is a derivative and prodrug of sirolimus. Temsirolimus is a specific inhibitor of mTOR and interferes with the synthesis of ... Though temsirolimus shows activity on its own, it is also known to be converted to sirolimus (rapamycin) in vivo; therefore, ...
... favourable response to sirolimus". BMJ Case Reports. 15 (3): e244915. doi:10.1136/bcr-2021-244915. ISSN 1757-790X. PMC 8948400 ...
Medications including sirolimus and everolimus can slow disease progression. A repeat heart transplantation may be required. ... On detection of CAV, medications including mTOR inhibitors sirolimus and everolimus have been shown to slow disease progression ...
It is a semi-synthetic derivative of sirolimus (rapamycin). It was designed for use in stents with phosphorylcholine as a ...
"Sirolimus in Treating Patients With Angiomyolipoma of the Kidney". ClinicalTrials.gov (NIH). 21 November 2006. Retrieved 10 ... 2002 Treatment with rapamycin (sirolimus) was found to shrink tumours in the Eker rat (TSC2) and mouse (TSC1) models of ... "Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus Trial (The MILES Trial)". ClinicalTrials.gov (NIH). 6 ...
Some recipients may instead take ciclosporin, sirolimus, or azathioprine. The risk of early rejection of the transplanted ... These food products are known to interact with the transplant medications, specifically tacrolimus, cyclosporin and sirolimus; ...
Poon, Michael; Badimon, Juan Jose; Fuster, Valentin (2002-02-16). "Overcoming restenosis with sirolimus: from alphabet soup to ... Poon, Michael; Badimon, Juan Jose; Fuster, Valentin (2002). "Viewpoint Overcoming restenosis with sirolimus: From alphabet soup ...
"Concept Medical Receives 3rd IDE Approval From USFDA For Its Sirolimus Coated Balloon". BW Defence. 2 May 2023. "कॉन्सेप्ट ... "Concept Medical receives 3rd IDE approval from USFDA for its MagicTouch-Sirolimus Coated Balloon". Express Healthcare. 2023-05- ... "Concept Medical receives 3rd IDE approval from US FDA for MagicTouch-Sirolimus-coated balloon - ET HealthWorld". ETHealthworld. ... "Concept Medical raises Rs 440 cr for sirolimus coated balloon". Financial Express. 2018-10-12. Sriram, M. (2018-12-11). " ...
Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune ... Hypothetically, Sirolimus may have lower risk of secondary cancers as opposed to other immune suppressants and requires ... 2009). "Treatment with sirolimus results in complete responses in patients with autoimmune lymphoproliferative syndrome". ... It may cause hypogammaglobulinemia (transient) requiring IVIgG replacement.[citation needed] Sirolimus (rapamycin, rapamune) ...
Sirolimus has been effective in improving the quality of life in some people with FAVA. "Fibro-Adipose Vascular Anomaly (FAVA ... Erickson J, McAuliffe W, Blennerhassett L, Halbert A (November 2017). "Fibroadipose vascular anomaly treated with sirolimus: ...
"Cordis' CYPHER TM Sirolimus-eluting Stent Receives CE Mark Approval" (PDF). Cordis Corporation. April 15, 2002. Archived from ... Spaulding C, Daemen J, Boersma E, Cutlip DE, Serruys PW (2007). "A pooled analysis of data comparing sirolimus-eluting stents ... Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo ... 2002). "A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization". N Engl J ...
Sirolimus (Rapamycin), ascomycin, and tacrolimus were isolated from Streptomyces. Pimecrolimus is a derivative of ascomycin. ...
Everolimus is an analog of sirolimus and also is an mTOR inhibitor. Zotarolimus is a semi-synthetic derivative of sirolimus ... Sirolimus (rapamycin, trade name Rapamune) is a macrolide lactone, produced by the actinomycete bacterium Streptomyces ... Therefore, sirolimus acts synergistically with ciclosporin and, in combination with other immunosuppressants, has few side ... In a similar manner, Sirolimus prevents B cell differentiation into plasma cells, reducing production of IgM, IgG, and IgA ...
"PKCι & mTOR Inhibition With Auranofin+Sirolimus for Squamous Cell Lung Cancer". Retrieved 2023-02-13. "Georgia State ... The Mayo clinic is running a clinical trial to research the effects of auranofin and sirolimus on squamous, ras mutated lung ...
The first two drug-eluting stents to be utilized were the paclitaxel-eluting stent and the sirolimus-eluting stent, both of ... Most current FDA-approved drug-eluting stents use sirolimus (also known as rapamycin), everolimus and zotarolimus. Biolimus A9- ... Claessen BE, Henriques JP, Dangas GD (2010). "Clinical studies with sirolimus, zotarolimus, everolimus, and biolimus A9 drug- ...
Sirolimus, a compound that inhibits mTOR signalling, is being studied to treat plexiform neurofibromas. The combination of ... Clinical trial number NCT00652990 for "Sirolimus to Treat Plexiform Neurofibromas in Patients With Neurofibromatosis Type I" at ... erlotinib with sirolimus was studied to treat low-grade gliomas. Early research has shown potential for using the c-kit ... ClinicalTrials.gov Clinical trial number NCT00634270 for "A Phase II Study of the mTOR Inhibitor Sirolimus in Neurofibromatosis ...
Impact of Avoiding Loading Dose of Sirolimus on Wound Complication After Kidney Transplant. A Single Center Experience, Ayran, ... Safety and Efficacy of Sirolimus, Low Dose Tacrolimus and Early Steroid Withdrawal in Patients with Cadaveric Renal Allographs ... M., Jabri, M., El-Ghoroury, M., Oh, H., Provenzano, R., Impact of Avoiding Loading Dose of Sirolimus on Wound Complication ... A Comparative Study, Nagrecha, N., El-Ghoroury, M., Provenzano, R., Safety and Efficacy of Sirolimus, Low Dose Tacrolimus and ...
... thymoglobulin and sirolimus. Newer, so-called "biologic drugs" or monoclonal antibodies, are also used in these conditions and ...
The sirolimus drug reduces the risk of stent restenosis through inhibiting the formation of neointima while the anti-CD34 ... Antiproliferative drugs like sirolimus and paclitaxel were used in the first-generation drug-eluting stents to inhibit the ... The COMBO stent is a pro-healing stent with sirolimus drug elution and anti-CD3 monoclonal antibodies that has enhanced degree ... The COMBO stent's enhanced endothelization is due to the sirolimus drug that reduces the risk of stent restenosis and the ...
It also may have a similar role to sirolimus in kidney and other transplants. Although, sirolimus had generated fears over use ... It is the 40-O-(2-hydroxyethyl) derivative of sirolimus and works similarly to sirolimus as an inhibitor of mammalian target of ... Everolimus treatment of mice results in reduced metabolic side effects compared to sirolimus. Use During Pregnancy and ...
For example, the mTOR inhibitor, Sirolimus, can be used to treat diffuse neonatal hemangiomatosis. It is important to note that ...
... topical application of sirolimus, i.e. rapamycin, (1% solution). Some of the latter methods have been used in order to preserve ... Topical Sirolimus Electrofulguration and Excision". Skin Appendage Disorders. 7 (1): 66-70. doi:10.1159/000511743. PMC 7879313 ...
Sirolimus seems to lower the cancer risk in some transplant patients. Sirolimus was shown to inhibit the progression of dermal ... Sirolimus blocks this pathway. The safety and efficacy of sirolimus treatment of LAM were investigated in clinical trials that ... Sirolimus is used to treat vascular malformations. Treatment with sirolimus can decrease pain and the fullness of vascular ... Sirolimus is a relatively new medical therapy for the treatment of vascular malformations in recent years, sirolimus has ...
... is a cyclic ketone (CHEBI:3992) sirolimus (CHEBI:9168) is a ether (CHEBI:25698) sirolimus (CHEBI:9168) ... sirolimus (CHEBI:9168) is a antibiotic antifungal drug (CHEBI:87113) sirolimus (CHEBI:9168) is a cyclic acetal (CHEBI:59770) ... sirolimus (CHEBI:9168) is a organic heterotricyclic compound (CHEBI:26979) sirolimus (CHEBI:9168) is a secondary alcohol (CHEBI ... sirolimus (CHEBI:9168) has role antibacterial drug (CHEBI:36047) sirolimus (CHEBI:9168) has role anticoronaviral agent (CHEBI: ...
Sirolimus: learn about side effects, dosage, special precautions, and more on MedlinePlus ... while taking sirolimus, and for 12 weeks after stopping sirolimus. If you become pregnant while taking sirolimus, call your ... Before taking sirolimus,. *tell your doctor and pharmacist if you are allergic to sirolimus, any other medications, or any of ... Sirolimus is used in combination with other medications to prevent rejection of kidney transplants. Sirolimus is in a class of ...
... or pancreas transplants who were treated with sirolimus and low-dose tacrolimus experienced a low rate of rejection and ... A series of 32 recipients of liver, kidney, or pancreas transplants who were treated with sirolimus and low-dose tacrolimus ... Vivian C. McAlister, Zu-hua Gao, Kevork Peltekian, Javier Domingues, et al.. "Sirolimus-tacrolimus combination ...
Sirolimus coated tablets 0.5, 1 and 2 mg, oral solution 1 mg/ml product-specific bioequivalence guidance (PDF/78.3 KB) Adopted ... Draft sirolimus product-specific bioequivalence guidance (PDF/82.69 KB) Draft: consultation closed. First published: 15/11/2013 ... Overview of comments received on draft sirolimus product-specific bioequivalence guidance (PDF/116.5 KB) First published: 07/ ... This document provides product-specific guidance on the demonstration of the bioequivalence of sirolimus. ...
About HYFTOR™ (sirolimus topical gel) 0.2% HYFTOR is the first and only clear topical medication approved by the FDA to treat ... Increased levels of cholesterol and triglycerides (fat or lipids) in the blood have happened in people who have taken sirolimus ... Do not use HYFTOR if you are allergic to sirolimus or any of the other ingredients in HYFTOR. ... HYFTOR™ (sirolimus topical gel) 0.2% is indicated for the treatment of facial angiofibroma associated with tuberous sclerosis ...
The use of sirolimus in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo ... Reddy s Sirolimus tablets in 1 mg and 2 mg are available in bottle counts of 100. ... In this and another study in de novo liver transplant patients, the use of sirolimus in combination with cyclosporine or ... Reddy s Laboratories (NYSE: RDY) announced today that it has launched Sirolimus Tablets 1 mg and 2 mg, a therapeutic equivalent ...
Noninfectious uveitis dosing for sirolimus intravitreal frequency-based adverse effects, comprehensive interactions, ... encoded search term (sirolimus intravitreal ((sirolimus intravitreal))) and sirolimus intravitreal ((sirolimus intravitreal)) ... Intravitreal sirolimus inhibits the protein kinase that plays a critical role in inflammation ...
Results: The limit of quantification for the commercial assay was 0.5 ng/mL for everolimus, sirolimus, and tacrolimus and 5 ng/ ... Evaluation of a novel commercial assay for the determination of cyclosporine A, tacrolimus, sirolimus, and everolimus by liquid ... sirolimus, and tacrolimus in patient whole blood samples. ...
The ultra-thin strut sirolimus-eluting coronary stent: SUPRAFLEX. Publication. Publication. Future Cardiology , Volume 17 - ... of the sirolimus elution within 7 days. SUPRAFLEX has been assessed in large scale randomized controlled trials. This review ... The ultra-thin strut sirolimus-eluting coronary stent: SUPRAFLEX. Future Cardiology, 17(2), 227-238. doi:10.2217/fca-2019-0083 ...
Introducci n: La sobrevida de los receptores de trasplante renal ha mejorado a trav s de los a os, sirolimus (SRL) ha probado ... Monoterapia con sirolimus en trasplante renal. Presentaci n de caso y revisi n de la literatura. Trabajo libre R30. XV Congreso ... El uso de sirolimus en pacientes receptores de trasplante renal reduce el n mero de efectos adversos. Trabajo libre 22. XIII ... M todos: Se realiz una b squeda sistem tica bajo los t rminos: sirolimus , rapamycin , kidney transplantation , mTOR y M xico ...
Sirolimus is classified as a Type IV allosteric kinase inhibitor [10]. Ligand Activity Visualisation Charts. These are box plot ... Comment: Sirolimus is a macrolide produced by the bacteria Streptomyces hygroscopicus. It has potent immunosuppressive and ... Synonyms: AY-22989 , Fyarro® (sirolimus albumin-bound particles) , Rapamune® , rapamycin , WY-090217 ...
Long-term vascular healing in response to sirolimus- and paclitaxel-eluting stents: An optical coherence tomography study. ... Long-term vascular healing in response to sirolimus- and paclitaxel-eluting stents: An optical coherence tomography study. JACC ... and coronary evaginations as markers of healing 5 years after implantation of sirolimus-eluting stents (SES) and paclitaxel- ...
XTOSI (Xtreme Touch Sirolimus coated PTA balloon) is a single arm trial for Sirolimus Coated Balloon (MagicTouch PTA) ... Sirolimus Coated Balloon in BTK Treatment makes a bold presence at VEITH 2022 - Lights up NY Times Square, NASDAQ. PRNewswire ... Sirolimus Coated Balloon for PAD continues its march, knocking on the doors of the US and lighting up the iconic New York Times ... It is the worlds first trial of Sirolimus Coated Balloon for BTK disease and has the longest follow up data. While the primary ...
Patients who have undergone kidney transplants are less likely to develop skin cancer when given sirolimus for ... Sirolimus reduces post-transplant skin cancer risk. August 8, 2012. Bill Gillette ... Serious adverse events were seen in 60 patients on sirolimus and in 14 of those on a calcineurin inhibitor. The occurrence of ... The time it took the cutaneous tumors to develop also was longer in the sirolimus group (15 months versus seven months), ...
... for Sirolimus. Available for instant download from Affygility Solutions. ... Sirolimus, also known as rapamycin is an immunosuppressant indicated for prevention of organ rejection in patient receiving a ... To order an OEL/ADE monograph for Sirolimus, just click the ADD TO CART button. ...
The first-step of decreasing the dose of sirolimus was associated with a decrease in plasma level of sirolimus from 14.7 to 6 ... Sirolimus-associated lymphoedema: eight new cases and a proposed mechanism. Br J Dermatol 2009; 160: 1322-1326.. 4. Naouri M, ... Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012; 367: 329-339.. 12. Bretagnol A, ... Sirolimus was then replaced with cyclosporine and the dose of mycophenolate mofetil was unchanged. Oedema and erythema of the ...
Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia. May 27, 2020. ... Sirolimus, Idarubicin, and Cytarabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia Lithium Carbonate and ...
Sirolimus Is Associated With Veno-Occlusive Disease of the Liver After Myeloablative Allogeneic Stem Cell Transplantation. Go ... Sirolimus is an effective agent used in graft-versus-host disease (GVHD) prophylaxis after allogeneic transplantation. It also ... When used with cyclophosphamide/total body irradiation (Cy/TBI) conditioning, sirolimus is associated with an increased ... and retrospectively reviewed the records of 488 patients to determine the association between sirolimus and VOD. ...
RAPAMUNE® (RAAP-a-mune) (sirolimus) Tablets. RAPAMUNE® (RAAP-a-mune) (sirolimus) Oral Solution. ... sirolimus). Oral Solution. Be sure that you read and understand the following instructions for the correct way to dilute and ... sirolimus). Oral Solution. Be sure that you read and understand the following instructions for the correct way to dilute and ... sirolimus). Oral Solution. Be sure that you read and understand the following instructions for the correct way to dilute and ...
Four patients take only 1 mg sirolimus daily with levels of 3-4 ng/mL. One patient showed clinical signs of rejection at month ... Early and limited use of tacrolimus to avoid rejection in an alemtuzumab and sirolimus regimen for kidney transplantation: ... "Early and limited use of tacrolimus to avoid rejection in an alemtuzumab and sirolimus regimen for kidney transplantation: ... Early and limited use of tacrolimus to avoid rejection in an alemtuzumab and sirolimus regimen for kidney transplantation: ...
As more experience with sirolimus has been gained, it began to be used ... Sirolimus is one such medication that can be considered an off-label second line treatment option (as well as for prophylaxis) ... Sirolimus Use in Graft Versus Host Disease C. Andrew Kistler, MD, PharmD ... Sirolimus is an oral mammalian target of rapamycin (mTOR) inhibitor that is approved by the US Food and Drug Administration ( ...
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... 提供 Sirolimus 相关产品,包含各种抑制剂、激动剂和化合物库, ... 雷帕霉素;西罗莫司 Rapamycin (Sirolimus) 是一种有效且特异性的 mTOR 抑制剂,作用于 HEK293 细胞,抑制 mTOR,IC50 为 0.1 nM。Rapamycin 与 FKBP12 结合且抑制 mTORC1。 ... 雷帕霉素;西罗莫司 Rapamycin (Sirolimus) 是一种有效且特异性的 mTOR 抑制剂,作用于 HEK293 细胞,抑制 mTOR,IC50 为 0.1
Phase II trials pinpointed sirolimus effectiveness as a drug therapy. Efficacy and safety of sirolimus thus need to be ... Evolution of malformations before (left) and after sirolimus treatment (right). Evolution after 3 months of sirolimus treatment ... 107 completed 12 or more months of sirolimus, including 61 who were treated for the whole 2-year period. Sirolimus resulted in ... Within 1 month of sirolimus treatment, daily bleeding ceased; surgical resection became possible after 4 months of sirolimus ...
Sirolimus [INN] [USAN] [Wiki] (1R,9S,12S,15R,16E,. 18R,19R,21R,23S,24E. ,26E,28E,30S,32S,35. R)-1,18-Dihydroxy-1. 2-{(1R)-2-[( ...
sirolimus Topic. Replies. Views. Activity. Grapefruit vs pomelo while taking rapamycin? Supplements sirolimus , anti-aging , ... Where to buy Highest Quality Sirolimus? (at US Pharmacies) rapamycin , rapamune , sirolimus ...
Sirolimus. This T-cell proliferation inhibitor was approved in 1999 for immunosuppression in solid organ transplant recipients. ... early sirolimus exposure during pregnancy does not appear to be associated with structural defects in offspring. [55] ...
A randomized trial comparing a novel sirolimus-eluting bioresorbable scaffold with everolimus-eluting metallic stents in ... angiographic analysis in patients with de novo native coronary artery lesions treated with novel poly-l-lactide based sirolimus ...
The Biochemistry Laboratory at Colchester underwent an Assessment from UKAS for ISO 15189 Accreditation in December 2022. This was a process that started in April 2019 and the Department have worked hard to pass this Assessment and have now been granted accreditation, the 1st Pathology Laboratory at Colchester to achieve this accolade. What does ISO […]. Read more ...

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