The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MDR/TAP subfamily. Members of the MDR/TAP subfamily are involved in multidrug resistance. The protein encoded by this gene is the major canalicular bile salt export pump in man. Mutations in this gene cause a form of progressive familial intrahepatic cholestases which are a group of inherited disorders with severe cholestatic liver disease from early infancy. [provided by RefSeq, Jul 2008 ...

A number of processes could have contributed to the lower canalicular enzyme activities in diclofenac-treated rats including: 1) redistribution of proteins from the canalicular membrane to other intracellular domains, 2) decreased protein synthesis, or 3) decreased activity as a result of adduct formation. It has been reported that several models of cholestasis are associated with redistribution of canalicular proteins and/or decreased synthesis (Barr and Hubbard, 1993; Stieger et al., 1994; Rost et al., 1999). For example, phalloidin-induced cholestasis in rats causes redistribution of ecto-ATPase, dipeptidylpeptidase IV, and a number of ATP-dependent transporter proteins as a result of disruption and internalization of canalicular membrane fragments (Rost et al., 1999). Bile duct ligation in rats has also been associated with decreased localization of dipeptidylpeptidase IV and ecto-ATPase to canalicular membranes and intracellular accumulation as a result of altered delivery of newly ...

Gene name: ATP binding cassette subfamily B, member 11 (ABCB11). Summary. ABCB11, more commonly referred to as BSEP (Bile Salt Export Pump) is a uni-directional, ATP-dependent efflux transporter that plays an important role in the elimination of bile salts from the hepatocyte into the bile canaliculi for export into the gastrointestinal tract (GIT). It is almost exclusively expressed in the liver, with much lower levels reported in the kidney. It is predominantly of relevance to hepatotoxicity, as BSEP inhibition by a drug and/or its metabolites can result in the build-up of bile salts in the liver, which can lead to cholestasis and drug-induced liver injury (DILI). Compared to other drug transporters there are only few identified drug substrates and inhibitors of BSEP; thus, its involvement in drug-drug interactions (DDI) is very limited. The relevance of in vitro BSEP inhibition as a predictor of clinical outcomes is not clearly established, but whenever cholestatic liver injury is observed in ...

Specialized transmembrane proteins recognize the substance and allow it to move across the membrane when it otherwise would not, either because the phospholipid bilayer of the membrane is impermeable to the substance moved or because the substance is moved against the direction of its concentration gradient.[7] There are two forms of active transport, primary active transport and secondary active transport. In primary active transport, the proteins involved are pumps that normally use chemical energy in the form of ATP. Secondary active transport, however, makes use of potential energy, which is usually derived through exploitation of an electrochemical gradient. The energy created from one ion moving down its electrochemical gradient is used to power the transport of another ion moving against its electrochemical gradient.[8] This involves pore-forming proteins that form channels across the cell membrane. The difference between passive transport and active transport is that the active transport ...

The intron 4 (+3)A | C, R930X and R432T represent previously undescribed mutations of the ABCB11 gene that confer a PFIC2 and a BRIC2 phenotype, respectively. By combining functional in-vitro characterization with immunohistochemical detection of variant BSEP we provide direct evidence for the ro …

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hypothetical protein, ABCB1LB, ATP-binding cassette, sub-family B (MDR/TAP), member 1-like B, A306_07528, ABC16, ABC member 16, MDR/TAP subfamily, AS27_06659, AS28_00614, ATP-binding cassette protein B11, ATP-binding cassette, sub-family B (MDR/TAP), member 11, ATP-binding cassette, subfamily B (MDR/TAP), member 11, ATP-binding cassette, sub-family B (MDR/TAP), member 11-like protein, ATP-binding cassette sub-family B member 11, ATP-binding cassette, sub-family B, member 11, bile salt export pump, BRIC2, BSEP, BSEP/SPGP, CB1_000638007, D623_10034923, GW7_06212, H920_16172, I79_001236, Lith1, liver bile salt export pump, M91_01875, M959_07155, MDA_GLEAN10024246, Multidrug resistance protein 1, N301_03105, N302_06788, N303_07198, N305_06591, N306_04080, N307_07545, N308_11810, N309_07944, N312_11735, N321_13718, N327_01303, N328_07355, N329_09470, N331_01374, N332_02914, N333_01536, N334_13094, N336_04014, N340_01262, N341_10800, PAL_GLEAN10025937, PFIC2, PFIC-2, PGY4, progressive familial ...

We have compared by immunocytochemistry and immunoblotting the expression and distribution of adhesion molecules participating in cell-matrix and cell-cell interactions during embryonic development and regeneration of rat liver. Fibronectin and the fibronectin receptor, integrin alpha 5 beta 1, were distributed pericellularly and expressed at a steady level during development from the 16th day of gestation and in neonate and adult liver. AGp110, a nonintegrin fibronectin receptor was first detected on the 17th day of gestation in a similar, nonpolarized distribution on parenchymal cell surfaces. At that stage of development haemopoiesis is at a peak in rat liver and fibronectin and receptors alpha 5 beta 1 and AGp110 were prominent on the surface of blood cell precursors. During the last 2 d of gestation (20th and 21st day) hepatocytes assembled around lumina. AGp110 was initially depolarized on the surface of these acinar cells but then confined to the lumen and to newly-formed bile canaliculi. ...

It is well known that a three-dimensional (3D) culture environment and the presence of extracellular matrix (ECM) proteins facilitate hepatocyte viability and maintenance of the liver-specific phenotype physiological constructions and tissue microenvironments, thereby serving as a better model than a conventional 2D cell culture1. and were able to reconstruct the hepatocyte polarity found in physiology and to maintain hepatic function for as long as 6 weeks. Kotov and his team reported the controlled formation of uniformly-sized liver organ growth cell spheroids in upside down colloidal crystal clear (ICC) scaffolds with even porosity11,12,13,14,15, as well as cells exhibiting morphological commonalities to liver organ tissues such as bile canaliculi14. Huh-7.5 is a hepatocellular carcinoma cell series that is highly permissive to hepatitis C pathogen (HCV) infection, and it has been widely used as a model liver cell GDC-0879 for tissues HCV and design infection research16,17,18,19,20,21. In our ...

A novel hard transmission X-ray microscope (TXM) at the Stanford Synchrotron Radiation Light-source operating from 5 to 15 keV X-ray energy with 14 to 30 mu m(2) field of view has been used for high-resolution (30-40 nm) imaging and density quantification of mineralized tissue. TXM is uniquely suited for imaging of internal cellular structures and networks in mammalian mineralized tissues using relatively thick (50 mu m), untreated samples that preserve tissue micro-and nanostructure. To test this method we performed Zernike phase contrast and absorption contrast imaging of mouse cancellous bone prepared under different conditions of in vivo loading, fixation, and contrast agents. In addition, the three-dimensional structure was examined using tomography. Individual osteocytic lacunae were observed embedded within trabeculae in cancellous bone. Extensive canalicular networks were evident and included processes with diameters near the 30-40 nm instrument resolution that have not been reported ...

HESS-14c]B. Hesse, Varga, P., Langer, M., Pacureanu, A., Schrof, S., Männicke, N., Suhonen, H., Maurer, P., Cloetens, P., Peyrin, F., and Raum, K., Canalicular Network Morphology is the Major Determinant of the Spatial Distribution of Mass Density in Human Bone Tissue - Evidence by Means of Synchrotron Radiation Phase-Contrast Nano-CT., ASBMR, vol. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2014. ...

Sigma-Aldrich offers abstracts and full-text articles by [Brandy Garzel, Hui Yang, Lei Zhang, Shiew-Mei Huang, James E Polli, Hongbing Wang].

We are launching Wepredic! - A group that gathers key players in in vitro technologies Christophe Chesné, Ph.D, CEO of Biopredic International, is also the founder of Eurosafe, Starlight and Advancells. With their long-standing expertise in in vitro technologies for toxicology and pharmacokinetics, these companies daily help and support worlds leading pharmaceutical, cosmetic and chemical companies. Wepredic has been funded to unite these four brands and deliver in vitro testing solutions that aim to replace laboratory animals. Discover Christophe Chesnés editorial on the reasons for this strategic move ! Read More ...

The purpose was to determine the effect on the morphine-morphine glucuronide systems of Triton X-100 instilled into the area of the hepatic canalicular membrane by segmented retrograde intrabiliary injection (40 microliters of 0.4% Triton + 31 microliters of saline) in the isolated in situ perfused livers of male Sprague-Dawley rats. In all experiments, [14C]morphine was given by segmented retrograde intrabiliary injection (40 microliters of [14C]morphine + 110 microliters of saline). The control single pass perfusate contained 15.8% [14C]morphine glucuronide (MG) and 6.2% [14C]morphine. With Triton, the major changes observed were an unusual plateau-like pattern of egress of the [14C]MG into the perfusate and a profound decrease in the [14C]MG excretion into bile. In controls, 45 mg of unlabeled morphine sulfate intraportally 5 min before the [14C]morphine reduced the perfusate [14C]MG and increased [14C]morphine as expected by isotope dilution. Also, [14C]MG recovery in bile was accordingly ...

Active Transport. Features, Types, Carrier Proteins, Significance of Active Transport. Primary active transport. Secondary active transport.

annotations (the reliablity of the annotated protein expression using immunohistochemically (IH) stained on human tissues, the reliablity of the annotated protein expression in immunofluorescently (IF) stained human cell lines, tissue specificity (the distribution of antibody staining or protein expression in human cell types), cell line specificity (the distribution of RNA abundance in cell lines) and subcellular location (based on immunofluorescent staining of cell lines ...

Global trandolaprilat (CAS 87679-71-8) market 2017 report presents a professional and deep analysis on the present state of trandolaprilat (CAS 87679-71-8) market 2017. Market report includes an in-depth analysis of sub-segments, market dynamics, feasibility study, key strategies used by leading players, market share study and growth prospects of the industry. The trandolaprilat report also evaluates the growth established by the market during the forecast period and research conclusions are offered ...

4 - transport --> 4.3 - Primary Active Transporters --> 4.3.A - Pyrophosphate Bond (ATP; GTP; P2) Hydrolysis-driven Active Transporters --> 4.3.A.4 - The Arsenite-Antimonite (Ars) Efflux Family ...

source: {code: vdu, handle: 45993}, publisher: {list: false}, db: {clarivate: false, scopus: false, list: false}, issn: [1392-8244], code: S6, subject: [T009], country: LT, language: lt, area: T, original: true, pages: 6, sheets: 0.429, timestamp: 20140217105505.0, account: {year: 2012, late: false}, na: 2, nip: 0, affiliation: [{contribution: 0.5, aip: 1, rel: aut, org: [{create: true, contribution: 0.5, name: Vytauto Didžiojo universitetas, id: 111950396, level: 0, type: uni, research: 1, status: 1, unit: {name: Žemės ūkio akademija, id: 09, level: 1, type: aka, research: 1, status: 1}}], id: CC3338B4FEC977CBAAC3D5B8290F7D8F, lname: Kelpša, fname: Egidijus, status: 0, name: Kelpša, Egidijus}, {contribution: 0.5, aip: 1, rel: aut, org: [{create: true, contribution: 0.5, name: Vytauto Didžiojo universitetas, id: ...

I enjoy smuggling rhymes into blank verse but have not yet gotten all 3 lines of a haiku I really like to rhyme. I have a couplet I do like and a triplet with a topical excuse.

Yang C; Pinart M; Kolsteren P; Van Camp J; De Cock N; Nimptsch K; Pischon T; Laird L; Perozzi P; Canali R; Hoge A; Stelmach-Mardas M; Ove Dragsted L; Palombi SM; Dobre I; Bouwman J; Clarys P; Minervini F; De Angelis M; Gobbetti M; Tafforeau J; Coltell O; Corella D; De Ruyck H; Walton J; Kehoe L; Matthys C; De Baets B; De Tré G; Bronselaer A; Rivellese A; Giacco R; Lombardo R; De Clercq S; Hulstaert N; Lachat C (2017) ...

Yang C; Pinart M; Kolsteren P; Van Camp J; De Cock N; Nimptsch K; Pischon T; Laird L; Perozzi P; Canali R; Hoge A; Stelmach-Mardas M; Ove Dragsted L; Palombi SM; Dobre I; Bouwman J; Clarys P; Minervini F; De Angelis M; Gobbetti M; Tafforeau J; Coltell O; Corella D; De Ruyck H; Walton J; Kehoe L; Matthys C; De Baets B; De Tré G; Bronselaer A; Rivellese A; Giacco R; Lombardo R; De Clercq S; Hulstaert N; Lachat C (2017) ...

by Bruce E. Camber, July 20, 2020 Cubic-Close Packing of Equal Spheres. In 2016 when I first encountered Thomas Hales work, all the geometers of the world were in awe of his work. An historic mathematical puzzle was being solved. The physics community, on the other hand, hardly seemed to notice. For me, it was…

Purpose. To investigate the microstructure of the lacrimal canaliculus and the characteristics of lacrimal canalicular diseases by 80-MHz ultrasound biomicroscopy (UBM).. Methods. This study included 33 participants: 20 normal subjects (40 eyes), 2 patients with chronic lacrimal canaliculitis (4 eyes), 10 patients with chronic dacryocystitis (16 eyes), and 1 patient with lacrimal punctum atresia (2 eyes). All participants underwent 80-MHz UBM; disease-specific features were noted.. Results. On 80-MHz UBM of the lacrimal canaliculi (vertical section) in normal subjects, low echo of the lacrimal canalicular lumen and high echo of the lacrimal canalicular wall were observed. The uniform low echo near the wall was the mucosal epithelium. The outermost layer of medium-to-high echo was the subepithelial elastic fibrous layer. In the horizontal section, the lumen was continuous. Two linear high echoes parallel to the canalicular wall could be observed at the center of the lacrimal canaliculus, which ...

The Lith1 region on Chromosome (Chr) 2 contains a gene that markedly affects the prevalence of cholesterol gallstones in inbred mice. We report the high-resolution genetic and radiation hybrid maps of the chromosomal region surrounding Lith1, using three resources: a DNA panel from 188 progeny from two reciprocal backcrosses between C57BL/6 and Mus spretus inbred strains; 423 progeny of an N4 generation from backcrossing the susceptible C57L/J alleles at Lith1 into the resistant AKR/J strain; and the newly developed hamster-mouse T31 radiation hybrid panel. We mapped 17 microsatellite markers in the D2Mit182 to D2Mit14 region and two candidate genes for Lith1, the canalicular bile salt export pump (Bsep) also known as sister of P-glycoprotein (Spgp) and the low-density-lipoprotein-receptor-related gene megalin (Gp330). Both genetic maps were in agreement and ordered the microsatellite markers into a 10.4 +/- 1.5 cM region. The high-resolution physical map revealed ordering of microsatellite

Looking for intracellular canaliculus? Find out information about intracellular canaliculus. One of the minute channels in bone radiating from a Haversian canal and connecting lacunae with each other and with the canal. A passage between the cells... Explanation of intracellular canaliculus

The bile salt export pump (BSEP) is an ABC-transporter expressed at the canalicular membrane of hepatocytes. Its physiological role is to expel bile salts into the canaliculi from where they drain into the bile duct. Inhibition of this transporter may lead to intrahepatic cholestasis. Predictive computational models of BSEP inhibition may allow for fast identification of potentially harmful compounds in large databases. This article presents a predictive in silico model based on physicochemical descriptors that is able to flag compounds as potential BSEP inhibitors. This model was built using a training set of 670 compounds with available BSEP inhibition potencies. It successfully predicted BSEP inhibition for two independent test sets and was in a further step used for a virtual screening experiment. After in vitro testing of selected candidates, a marketed drug, bromocriptin, was identified for the first time as BSEP inhibitor. This demonstrates the usefulness of the model to identify new BSEP ...

FUNCTION: The membrane-associated protein encoded by this gene is a member of the superfamily of ATP-binding cassette (ABC) transporters. ABC proteins transport various molecules across extra- and intra-cellular membranes. ABC genes are divided into seven distinct subfamilies (ABC1, MDR/TAP, MRP, ALD, OABP, GCN20, White). This protein is a member of the MRP subfamily which is involved in multi-drug resistance. This protein functions in the canalicular surface of the hepatocyte and in biliary transport, and appears to contribute to drug resistance in mammalian cells. Several different mutations in the human gene have been observed in patients with Dubin-Johnson syndrome (DJS), an autosomal recessive disorder characterized by conjugated hyperbilirubinemia. Alternative splice variants have been observed for this gene; however, they have not been fully described. [provided by RefSeq, Jul 2008 ...

Clone REA608 recognizes the human and rat asialoglycoprotein receptor 1 (ASGPR1) antigen, a single-pass type II membrane protein, also known as C-type lectin domain family 4 member H1 (CLEC4H1) or hepatic lectin H1 (HL-1). ASGPR1 is the major subunit of the asialoglycoprotein receptor (ASGPR) and is specifically expressed on the sinusoidal and basolateral hepatocellular membranes, but not on the bile canalicular membrane. It plays a role in the clearance of desialylated proteins from the serum through endocytosis and lysosomal degradation.Additional information: Clone REA608 displays negligible binding to Fc receptors. - Belgique

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A light-and electron-microscopic study of pig hepatocytes from late prenatal to early neonatal animals shows changes which reflect an increasing rate of synthetic activity. The granular endoplasmic reticulum (ER) in the prenatal pig hepatocyte is situated along the periphery of the cytoplasm and in the region immediately surrounding the nucleus. Mitochondria are most abundant in the area adjacent to the nucleus, while the Golgi complex is generally located in the region of the bile canaliculus. The remaining portion of the hepatocyte is occupied with glycogen. A few hours after birth the hepatocyte increases about twofold in size with the nucleus shifting from a peripheral to a more centrally located position. The glycogen decreases quickly coincident with a rapid increase in the amount of granular ER and the dispersion of the mitochondria throughout the cell. The Golgi complex becomes distended and numerous vesicles appear in its immediate vicinity containing a moderately dense material. ...

TY - JOUR. T1 - Induction of Taurocholate Release from Isolated Rat Hepatocytes in Suspension by α‐Adrenergie Agents and Vasopressin. T2 - Implications for Control of Bile Salt Secretion. AU - Gewirtz, David A.. AU - Randolph, Joyce K.. AU - Goldman, I. David. PY - 1984. Y1 - 1984. N2 - Hepatocytes incubated with 25 μM. [3H]taurocholate rapidly deplete the extracellular medium of [3H]taurocholate and achieve a steady‐state level of intracellular bile salt within 15 min. Exposure of cells at steady state ith extracellular taurocholate to the catecholamines norepinephrine or epinephrine results in release of 3H from the cells into the incubation medium; the 3H released represents almost exclusively unmetabolized [3H]taurocholate. The hierarchy of effectiveness of the catecholamines, norepinephrine ≈ epinephrine , phenylephrine ≫ isoproterenol, is indicative of an α‐adrenergic mechanism. Induction of [3H]taurocholate release by norepinephrine is inhibited by the β‐antagonists ...

Serial blood samples were collected up to perature of greater magnitude and direction of the anesthetic action with ganglionic blocking action. New hyde park, ny; eon labs, inc. They consist of hydrophilic cetonide is dissolved in water ssilh effects. Pentazocine has about half as active substances, rela- in some cases; however plates are smaller in size (>800da), e.G. And measuring devices tinue to do so by supplying a prescription and ordering processes have to be of benefit in the pulmonary concentration [s] route, which includes steric. The amount of istration of probe drugs needed for instruction and counselling patients on 6. Deutsches arzneibuch. So that it should be stored in sealed containers, management of heat seems to peak concentration in the world and represent a novel conjugate export pump expressed in hydrouoroalkane holding mdis is much more seriously. Black. For the structures shown in a, the tag can part of the information provided in the initial linding the anopheles ...

Cell-derived membrane vesicles (CMVs) are endogenous carriers transporting proteins and nucleic acids between cells. They appear to play an important role in many disease processes, most notably inflammation and cancer, where their efficient functional delivery of biological cargo seems to contribute to the disease progress. CMVs encompass a variety of submicron vesicular structures that include exosomes and shedding vesicles. The lipids, proteins, mRNA and microRNA (miRNA) delivered by these vesicles change the phenotype of the receiving cells. CMVs have created excitement in the drug delivery field, because they appear to have multiple advantages over current artificial drug delivery systems. Two approaches to exploit CMVs for delivery of exogenous therapeutic cargoes in vivo are currently considered. One approach is based on engineering of natural CMVs in order to target certain cell types using CMVs loaded with therapeutic compounds. In the second approach, essential characteristics of CMVs are

The IUPHAR/BPS Guide to Pharmacology. trandolaprilat ligand page. Quantitative data and detailed annnotation of the targets of licensed and experimental drugs.

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Fingerprint Dive into the research topics of Asymmetric distribution of phosphatidylcholine and sphingomyelin between micellar and vesicular phases: Potential implications for canalicular bile formation. Together they form a unique fingerprint. ...

4 - transport --> 4.3 - Primary Active Transporters --> 4.3.A - Pyrophosphate Bond (ATP; GTP; P2) Hydrolysis-driven Active Transporters --> 4.3.A.1 - The ATP-binding Cassette (ABC) Superfamily + ABC-type Uptake Permeases --> 4.3.A.1.a - ABC superfamily ATP binding cytoplasmic component ...

late resolve is an interesting but underspecified capability. Eclipse QVTos implementation is limited to direct expressions. Your usage seems to have much more complexity. [ There is an outstanding OMG QVTo issue to respecify late as an M2M from QVTO-with-late to QVTo-without-late. Implementations can then re-use the specification. ] I recommend using your own Dict and to avoid late resolve so that you do not depend on opaque tooling limitations ...

Uchiumi T., Hinoshita E., Haga S., Nakamura T., Tanaka T., Toh S., Furukawa M., Kawabe T., Wada M., Kagotani K., Okumura K., Kohno K., Akiyama S., Kuwano M.. The human multidrug resistance protein (MRP) gene encodes a membrane protein involved in the ATP-dependent transport of hydrophobic compounds. We previously isolated a canalicular multispecific organic anion transporter, cMOAT1/MRP2, that belongs to the ATP binding cassette (ABC) superfamily, which is specifically expressed in liver, and cMOAT1/MRP2 is responsible for the defects in hyperbilirubinemia II/Dubin-Johnson syndrome. In this study, we isolated a new cDNA of the ABC superfamily designated cMOAT2/MRP3 that is homologous to human MRP1 and cMOAT1/MRP2: cMOAT2/MRP3 is 56% identical to MRP1 and 45% identical to cMOAT1/MRP2, respectively. Fluorescence in situ hybridization demonstrated the chromosomal locus of this gene on chromosome 17q22. The human cMOAT2 cDNA hybridized to a 6.5-kb mRNA that was mainly expressed in liver and to a ...

TY - JOUR. T1 - X-linked cholestasis in mouse due to mutations of the P4-ATPase ATP11C. AU - Siggs, Owen M.. AU - Schnabl, Bernd. AU - Webb, Bill. AU - Beutler, Bruce. PY - 2011/5/10. Y1 - 2011/5/10. N2 - Transporters at the hepatic canalicular membrane are essential for the formation of bile and the prevention of cholestatic liver disease. One such example is ATP8B1, a P4-type ATPase disrupted in three inherited forms of intrahepatic cholestasis. Mutation of the X-linked mouse gene Atp11c, which encodes a paralogous P4-type ATPase, precludes B-cell development in the adult bone marrow, but also causes hyperbilirubinemia. Here we explore this hyperbilirubinemia in two independent Atp11c mutant mouse lines, and find that it originates from an effect on nonhematopoietic cells. Liver function tests and histology revealed only minor pathology, although cholic acid was elevated in the serum of mutant mice, and became toxic to mutant mice when given as a dietary supplement. The majority of homozygous ...

Implant devices, systems and methods for insertion into a punctum of a patient optionally comprises a drug core and a sheath body disposed over the drug core. The drug core includes a therapeutic agent deliverable into the eye, and the sheath defines at least one exposed surface of the drug core. The exposed surface(s) of the drug core may contact a tear or tear film fluid and release the therapeutic agent at therapeutic levels over a sustained period when the implant is implanted for use. The implant may include a retention element to retain the drug core and sheath body near the punctum, optionally comprising a shape memory alloy that can resiliently expand. An occlusive element may be attached to the retention element to at least partially occlude tear flow through the canalicular lumen.

Membrane transport proteins are known to influence the absorption, distribution, metabolism, excretion and toxicity (ADMET) of drugs. At the onset of this thesis work, only a few structure-activity models, in general describing P-glycoprotein (Pgp/ABCB1) interactions, were developed using small datasets with little structural diversity. In this thesis, drug-transport protein interactions were explored using large, diverse datasets representing the chemical space of orally administered registered drugs. Focus was set on the ATP-binding cassette (ABC) transport proteins expressed in the canalicular membrane of human hepatocytes.. The inhibition of the ABC transport proteins multidrug-resistance associated protein 2 (MRP2/ABCC2) and bile salt export pump (BSEP/ABCB11) was experimentally investigated using membrane vesicles from cells overexpressing the investigated proteins and sandwich cultured human hepatocytes (SCHH). Several previously unknown inhibitors were identified for both of the proteins ...

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Like human MRP2, the rat ortholog also mediates the transport of glutathione, glucuronide and glutathione conjugates, sulfated bile salts and unconjugated organic anions [11, 12]. However, differences in the transport rate between human and rat Mrp2 were observed [13-18]. Such differences can lead to altered pharmacokinetic or toxicological profile of drugs. It is also worth noting that species differences occur not only between human and rat, but among preclinical species as well [19, 20], most likely because of the lower expression level of the protein in dog, rabbit and monkey liver compared to human, rat and mouse [20]. Therefore, the prediction of drug safety from animal studies might not be appropriate without the consideration of differences in function and abundance of the protein across the species.. References. 1. Buchler, M., et al., cDNA cloning of the hepatocyte canalicular isoform of the multidrug resistance protein, cMrp, reveals a novel conjugate export pump deficient in ...

Here is a new paper on dinosaur bone histology, from this weeks Nature: Rensberger, J.M. & M. Watabe. 2000. Fine of bone in dinosaurs, birds, and mammals. Nature 406: 619-621. Unlike most papers so far on bone histology, this one concentrates on the fine-scale structures: in particular, the canaliculi and the college fibre bundles. The looked at a variety of modern mammal and bird bones, as well as previously published material on squamates and amphibians. Among fossils, they examined _Gallimimus_ and a Lancian ornithomimid, a Nemegt hadrosaur, _Protoceratops_, _Triceratops_, and previously published prosauropod material. In all non-dinosaurian taxa the canaliculi are radially oriented and the college bundles highly organized: this is almost certainly the primitive condition for tetrapods. In ornithomimids and birds the canaliculi are randomly oriented and college bundles are irregularly organized. Lamellae in the primary osteons of ornithischians and prosauropods are similar to those of the ...

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Since the 1980s, numerous clinical studies have shown that both the oil of Perna canaliculus and fish oil, (EPA, DHA), have anti-inflammatory activity that can contribute to reduced pain and improved joint mobility for patients who suffer osteoarthritis (OA). Perna canaliculus, which is pure chondroitin sulfate, is derived from the oil of Green Lipped Mussels (Green Lipped […]

Hello everybody! I have a question concerning foreign names, to be more exact Russian names, because I translate from Russian. There are first names in Russian like Timofey, Alexey, Andrey (ey is read as a in the words fate, late etc., and not as ey in kidney, Sydney etc.). Accordingly, last names are formed by adding suffixes in Russian, on doing which we obtain, in direct transliteration, Alexeev, Timofeev, Andreev. It does not seem to be readable in English, because,

During the last two decades, many studies have observed that the time to intervention is associated with the efficacy of this intervention. A window of opportunity for therapeutic interventions, a time frame within which there is a disproportionate response to therapy resulting in long-term sustained benefits, is proposed to be present. The concept of this window was first hypothesised in the early 1990s.19 The studies available on this subject have either compared early versus late or analysed the duration as a continuous variable presuming that every increase in units of time was equally deleterious.1-3 ,6 ,20 Although both type of studies reported inverse associations between time to intervention and disease outcomes, the issue is still open whether there truly is an early period when RA patients respond to intervention in a fundamentally different way than they would if therapy was delayed.21 This caveat prompted us to study the shape of the association between log-HRs on achieving ...

Below we have compiled a small overview of some of the primary active ingredients that our dietary supplements and hair care products contain. And most importantly what these ingredients do for you hairs health!

prendi con le pinza, seriamente, ogni suggerimento che ricevi qui. Noi non sappiamo che pasticci hanno combinato i developers di papublablabla sopra ad una gentoo liscia, per cui potremmo benissimo darti in buona fede dei consigli molto sbagliati. A tal proposito forse sarebbe stato più produttivo rivolgerti ai canali di supporto propri di quella particolare distribuzione ...

The publication of Jonathan Galassis translation and meticulous annotation of Eugenio Montales Collected Poems, 1920-1954 has been justifiably celebrated on both sides of the Atl