Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Dose-Response Relationship, Radiation: The relationship between the dose of administered radiation and the response of the organism or tissue to the radiation.Oxytropis: A plant genus of the family FABACEAE. Members contain SWAINSONINE.Livestock: Domesticated farm animals raised for home use or profit but excluding POULTRY. Typically livestock includes CATTLE; SHEEP; HORSES; SWINE; GOATS; and others.Methicillin-Resistant Staphylococcus aureus: A strain of Staphylococcus aureus that is non-susceptible to the action of METHICILLIN. The mechanism of resistance usually involves modification of normal or the presence of acquired PENICILLIN BINDING PROTEINS.Staphylococcal Infections: Infections with bacteria of the genus STAPHYLOCOCCUS.Carrier State: The condition of harboring an infective organism without manifesting symptoms of infection. The organism must be readily transmissible to another susceptible host.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Methicillin Resistance: Non-susceptibility of a microbe to the action of METHICILLIN, a semi-synthetic penicillin derivative.Neuroleptic Malignant Syndrome: A potentially fatal syndrome associated primarily with the use of neuroleptic agents (see ANTIPSYCHOTIC AGENTS) which are in turn associated with dopaminergic receptor blockade (see RECEPTORS, DOPAMINE) in the BASAL GANGLIA and HYPOTHALAMUS, and sympathetic dysregulation. Clinical features include diffuse MUSCLE RIGIDITY; TREMOR; high FEVER; diaphoresis; labile blood pressure; cognitive dysfunction; and autonomic disturbances. Serum CPK level elevation and a leukocytosis may also be present. (From Adams et al., Principles of Neurology, 6th ed, p1199; Psychiatr Serv 1998 Sep;49(9):1163-72)Psychomotor Agitation: A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions.Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus.Dantrolene: Skeletal muscle relaxant that acts by interfering with excitation-contraction coupling in the muscle fiber. It is used in spasticity and other neuromuscular abnormalities. Although the mechanism of action is probably not central, dantrolene is usually grouped with the central muscle relaxants.Haloperidol: A phenyl-piperidinyl-butyrophenone that is used primarily to treat SCHIZOPHRENIA and other PSYCHOSES. It is also used in schizoaffective disorder, DELUSIONAL DISORDERS, ballism, and TOURETTE SYNDROME (a drug of choice) and occasionally as adjunctive therapy in INTELLECTUAL DISABILITY and the chorea of HUNTINGTON DISEASE. It is a potent antiemetic and is used in the treatment of intractable HICCUPS. (From AMA Drug Evaluations Annual, 1994, p279)Mutism: The inability to generate oral-verbal expression, despite normal comprehension of speech. This may be associated with BRAIN DISEASES or MENTAL DISORDERS. Organic mutism may be associated with damage to the FRONTAL LOBE; BRAIN STEM; THALAMUS; and CEREBELLUM. Selective mutism is a psychological condition that usually affects children characterized by continuous refusal to speak in social situations by a child who is able and willing to speak to selected persons. Kussmal aphasia refers to mutism in psychosis. (From Fortschr Neurol Psychiatr 1994; 62(9):337-44)Loxapine: An antipsychotic agent used in SCHIZOPHRENIA.Adrenocorticotropic Hormone: An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).Adrenal Insufficiency: Conditions in which the production of adrenal CORTICOSTEROIDS falls below the requirement of the body. Adrenal insufficiency can be caused by defects in the ADRENAL GLANDS, the PITUITARY GLAND, or the HYPOTHALAMUS.Corticotropin-Releasing Hormone: A peptide of about 41 amino acids that stimulates the release of ADRENOCORTICOTROPIC HORMONE. CRH is synthesized by neurons in the PARAVENTRICULAR NUCLEUS of the HYPOTHALAMUS. After being released into the pituitary portal circulation, CRH stimulates the release of ACTH from the PITUITARY GLAND. CRH can also be synthesized in other tissues, such as PLACENTA; ADRENAL MEDULLA; and TESTIS.Pituitary-Adrenal System: The interactions between the anterior pituitary and adrenal glands, in which corticotropin (ACTH) stimulates the adrenal cortex and adrenal cortical hormones suppress the production of corticotropin by the anterior pituitary.Hypothalamo-Hypophyseal System: A collection of NEURONS, tracts of NERVE FIBERS, endocrine tissue, and blood vessels in the HYPOTHALAMUS and the PITUITARY GLAND. This hypothalamo-hypophyseal portal circulation provides the mechanism for hypothalamic neuroendocrine (HYPOTHALAMIC HORMONES) regulation of pituitary function and the release of various PITUITARY HORMONES into the systemic circulation to maintain HOMEOSTASIS.Hydrocortisone: The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.Glycosylation End Products, Advanced: Products derived from the nonenzymatic reaction of GLUCOSE and PROTEINS in vivo that exhibit a yellow-brown pigmentation and an ability to participate in protein-protein cross-linking. These substances are involved in biological processes relating to protein turnover and it is believed that their excessive accumulation contributes to the chronic complications of DIABETES MELLITUS.Cell Transdifferentiation: A naturally occurring phenomenon where terminally differentiated cells dedifferentiate to the point where they can switch CELL LINEAGES. The cells then differentiate into other cell types.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.Pyruvaldehyde: An organic compound used often as a reagent in organic synthesis, as a flavoring agent, and in tanning. It has been demonstrated as an intermediate in the metabolism of acetone and its derivatives in isolated cell preparations, in various culture media, and in vivo in certain animals.Epithelial Cells: Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.GlyoxalOrganophosphonates: Carbon-containing phosphonic acid compounds. Included under this heading are compounds that have carbon bound to either OXYGEN atom or the PHOSPHOROUS atom of the (P=O)O2 structure.HIV Infections: Includes the spectrum of human immunodeficiency virus infections that range from asymptomatic seropositivity, thru AIDS-related complex (ARC), to acquired immunodeficiency syndrome (AIDS).Adenine: A purine base and a fundamental unit of ADENINE NUCLEOTIDES.Prodrugs: A compound that, on administration, must undergo chemical conversion by metabolic processes before becoming the pharmacologically active drug for which it is a prodrug.Anti-HIV Agents: Agents used to treat AIDS and/or stop the spread of the HIV infection. These do not include drugs used to treat symptoms or opportunistic infections associated with AIDS.CD4 Lymphocyte Count: The number of CD4-POSITIVE T-LYMPHOCYTES per unit volume of BLOOD. Determination requires the use of a fluorescence-activated flow cytometer.Antiretroviral Therapy, Highly Active: Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.Diabetes Mellitus, Experimental: Diabetes mellitus induced experimentally by administration of various diabetogenic agents or by PANCREATECTOMY.Diabetic Retinopathy: Disease of the RETINA as a complication of DIABETES MELLITUS. It is characterized by the progressive microvascular complications, such as ANEURYSM, interretinal EDEMA, and intraocular PATHOLOGIC NEOVASCULARIZATION.Receptors, GABA: Cell-surface proteins that bind GAMMA-AMINOBUTYRIC ACID with high affinity and trigger changes that influence the behavior of cells. GABA-A receptors control chloride channels formed by the receptor complex itself. They are blocked by bicuculline and usually have modulatory sites sensitive to benzodiazepines and barbiturates. GABA-B receptors act through G-proteins on several effector systems, are insensitive to bicuculline, and have a high affinity for L-baclofen.Streptozocin: An antibiotic that is produced by Stretomyces achromogenes. It is used as an antineoplastic agent and to induce diabetes in experimental animals.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Retinal Neurons: Nerve cells of the RETINA in the pathway of transmitting light signals to the CENTRAL NERVOUS SYSTEM. They include the outer layer of PHOTORECEPTOR CELLS, the intermediate layer of RETINAL BIPOLAR CELLS and AMACRINE CELLS, and the internal layer of RETINAL GANGLION CELLS.Hyperglycemia: Abnormally high BLOOD GLUCOSE level.Megestrol Acetate: Megestrol acetate is a progestogen with actions and uses similar to those of the progestogens in general. It also has anti-androgenic properties. It is given by mouth in the palliative treatment or as an adjunct to other therapy in endometrial carcinoma and in breast cancer. Megestrol acetate has been approved to treat anorexia and cachexia. (From Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)Megestrol: 17-Hydroxy-6-methylpregna-3,6-diene-3,20-dione. A progestational hormone used most commonly as the acetate ester. As the acetate, it is more potent than progesterone both as a progestagen and as an ovulation inhibitor. It has also been used in the palliative treatment of breast cancer.Appetite Stimulants: Agents that are used to stimulate appetite. These drugs are frequently used to treat anorexia associated with cancer and AIDS.Cachexia: General ill health, malnutrition, and weight loss, usually associated with chronic disease.Anorexia: The lack or loss of APPETITE accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder ANOREXIA NERVOSA.Skin Tests: Epicutaneous or intradermal application of a sensitizer for demonstration of either delayed or immediate hypersensitivity. Used in diagnosis of hypersensitivity or as a test for cellular immunity.Anorexia Nervosa: An eating disorder that is characterized by the lack or loss of APPETITE, known as ANOREXIA. Other features include excess fear of becoming OVERWEIGHT; BODY IMAGE disturbance; significant WEIGHT LOSS; refusal to maintain minimal normal weight; and AMENORRHEA. This disorder occurs most frequently in adolescent females. (APA, Thesaurus of Psychological Index Terms, 1994)

Decreased liver and lung drug-metabolizing activity in mice treated with Corynebacterium parvum. (1/73494)

Injections of killed suspensions of Corynebacterium parvum (i.p.) in young male mice were followed by time- and dose-dependent decreases in the drug-metabolizing activity of liver microsomes and lung homogenates. In vitro assays with model substrates [aminopyrine, aniline, p-nitroanisole, and benzo(a)pyrene] were used to quantitate drug-metabolizing activity. It is likely that such decreases in mixed function oxidases activity will act to significantly alter the pharmacokinetics of concurrently or subsequently administered drugs. The results provide a possible mechanism to explain several previously reported immunochemotherapeutic interactions.  (+info)

The incorporation of 5-iodo-2'-deoxyuridine into the DNA of HeLa cells and the induction of alkaline phosphatase activity. (2/73494)

Inhibition of DNA synthesis during the period of exposure of HeLa cells to 5-iodo-2'-deoxyuridine (IUdR) inhibited the induction of alkaline phosphatase activity. This finding, taken together with previous findings that IUdR did not induce alkaline phosphatase activity in the presence of 2-fold molar excess thymidinemonstrated that IUdR incorporation into DNA is correlated with the increase in alkaline phosphatase activity. With the exception of an interim period described in the text, induction of alkaline phosphatase activity was linearly related to medium concentrations of IUdR of up to at least 3 muM. However, the extent of IUdR substitution in DNA did not appear to be related to the degree of enzyme induction. Alkaline phosphatase activity continued to increase at medium concentrations of IUdR from 1 to 3 muM, while little further substitution of DNA occurred.  (+info)

The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. (3/73494)

We have established or characterized six lines of human breast cancer maintained in long-term tissue culture for at least 1 year and have examined these lines for estrogen responsiveness. One of these cell lines, MCF-7, shows marked stimulation of macromolecular synthesis and cell division with physiological concentrations of estradiol. Antiestrogens are strongly inhibitory, and at concentrations greater than 3 X 10(-7) M they kill cells. Antiestrogen effects are prevented by simultaneous treatment with estradiol or reversed by addition of estradiol to cells incubated in antiestrogen. Responsive cell lines contain high-affinity specific estradiol receptors. Antiestrogens compete with estradiol for these receptors but have a lower apparent affinity for the receptor than estrogens. Stimulation of cells by estrogens is biphasic, with inhibition and cell death at concentrations of 17beta-estradiol or diethylstilbestrol exceeding 10(-7) M. Killing by high concentrations of estrogen is probably a nonspecific effect in that we observe this response with 17alpha-estradiol at equivalent concentrations and in the otherwise unresponsive cells that contain no estrogen receptor sites.  (+info)

The effects of glucocorticoids and progesterone on hormone-responsive human breast cancer in long-term tissue culture. (4/73494)

Glucocorticoids, at physiological concentration, inhibit cell division and thymidine incorporation in three lines of human breast cancer maintained in long-term tissue culture. At steroid concentrations sufficient to inhibit thymidine incorporation 50%, little or no effect is seen on protein synthesis 48 hr after hormone addition. All three of these lines are shown to have glucocorticoid receptors demonstrable by competitive protein binding assays. Receptors are extensively characterized in one line by sucrose density gradient analysis and binding specificity studies. Good correlation between receptor-binding specificity and biological activity is found except for progesterone, which binds to glucocorticoid receptor but is noninhibitory. Cross-competition and quantification studies demonstrate a separate receptor for progesterone. This receptor has limited binding specificities restricted largely to progestational agents, whereas the glucocorticoid receptor bound both glucocorticoids and progesterone. Two other human breast cancer lines neither contain glucocorticoid receptor nor are inhibited by glucocorticoids. It is concluded that in some cases glucocorticoids can directly limit growth in human breast cancer in vitro without requiring alterations in other trophic hormones.  (+info)

Tissue pharmacokinetics, inhibition of DNA synthesis and tumor cell kill after high-dose methotrexate in murine tumor models. (5/73494)

In Sarcoma 180 and L1210 ascites tumor models, the initial rate of methotrexate accumulation in tumor cells in the peritoneal cavity and in small intestine (intracellularly) after s.c. doses up to 800 mg/kg, showed saturation kinetics. These results and the fact that initial uptake in these tissues within this dosage range was inhibited to the expected relative extent by the simultaneous administration of leucovorin suggest that carrier mediation and not passive diffusion is the major route of drug entry at these extremely high doses. Maximum accumulation of intracellular drug occurred within 2 hr and reached much higher levels in small intestine than in tumor cells at the higher dosages. At a 3-mg/kg dose of methotrexate s.c., intracellular exchangeable drug levels persisted more than four times longer in L1210 cells than in small intestine, but differences in persistence (L1210 cell versus gut) diminished markedly with increasing dosage. At 96 mg/kg, the difference in persistence was less than 2-fold. In small intestine and L1210 cells, theduration of inhibition of DNA synthesis at different dosages correlated with the extent to which exchangeable drug was retained. Toxic deaths occurred when inhibition in small intestine lasted longer than 25 to 30 hr. Recovery of synthesis in small intestine and L1210 cells occurred synchronously and only below dosages of 400 mg/kg. Within 24 hr after dosages of greater than 24 mg/kg, the rate of tumor cell loss increased to a point characterized by a single exponential (t1/2=8.5 hr). The total cell loss, but not the rate of cell loss, was dose dependent.  (+info)

Quantification of baroreceptor influence on arterial pressure changes seen in primary angiotension-induced hypertension in dogs. (6/73494)

We studied the role of the sino-aortic baroreceptors in the gradual development of hypertension induced by prolonged administration of small amounts of angiotensin II (A II) in intact dogs and dogs with denervated sino-aortic baroreceptors. Short-term 1-hour infusions of A II(1.0-100 ng/kg per min) showed that conscious denervated dogs had twice the pressor sensitivity of intact dogs. Long-term infusions of A II at 5.0 ng/kg per min (2-3 weeks) with continuous 24-hour recordings of arterial pressure showed that intact dogs required 28 hours to reach the same level of pressure attained by denervated dogs during the 1st hour of infusion. At the 28th hour the pressure in both groups was 70% of the maximum value attained by the 7th day of infusion. Both intact and denervated dogs reached nearly the same plateau level of pressure, the magnitude being directly related both the the A II infusion rate and the daily sodium intake. Cardiac output in intact dogs initially decreased after the onset of A II infusion, but by the 5th day of infusion it was 38% above control, whereas blood volume was unchanged. Heart rate returned to normal after a reduction during the 1st day of infusion in intact dogs. Plasma renin activity could not be detected after 24 hours of A II infusion in either intact or denervated dogs. The data indicate that about 35% of the hypertensive effect of A II results from its acute pressor action, and an additional 35% of the gradual increase in arterial pressure is in large measure a result of baroreceptor resetting. We conclude that the final 30% increase in pressure seems to result from increased cardiac output, the cause of which may be decreased vascular compliance. since the blood volume remains unaltered.  (+info)

Acute and chronic dose-response relationships for angiotensin, aldosterone, and arterial pressure at varying levels of sodium intake. (7/73494)

We examined the acute and chronic dose-response relationships between intravenously infused angiotensin II (A II) and the resulting changes in arterial pressure and plasma aldosterone concentration at varying levels of sodium intake. Sequential analysis of plasma aldosterone at each A II infusion rate resulted in an acute dose-related increase in plasma aldosterone which was markedly attenuated after the first 24 hours of infusion, the final level being directly related to the dose of A II and inversely related to sodium intake. A II infused at 5,15, and 23 ng/kg per min was associated with an initial increase (2nd to 8th hour) in plasma aldosterone to 2,6, and 9 times control values, respectively, in dogs receiving 40 mEq Na+/day. But, after the 1st day, aldosterone averaged only 1, 1.7, and 3 times control values for the next 2 weeks at the same rates of A II infusion. Dogs receiving 120 mEq Na+/day during A II infusion exhibited only a transient increase in plasma aldosterone during the 1st day. Sustained hypertension developed over a period of a week at all doses of A II at normal and high sodium intake, but did not occur at any dose of A II in sodium-depleted dogs. Increasing sodium intake from 40 to 120 mEq/day resulted in higher levels of hypertension, 125% compared to 140% of ocntrol values for dogs infused with A II, 5.0 ng/kg per min. We conclude that primary angiotensin-induced hypertension need not be associated with increased levels of plasma aldosterone, which appears to remain elevated only with amounts of A II greater than those required to sustain a significant degree of hypertension.  (+info)

Stimulation of renin release from rabbit renal cortex by arachidonic acid and prostaglandin endoperoxides. (8/73494)

The mechanism by which renal prostaglandins stimulate renin secretion in vivo is unknown. In this in vitro study we measured the effects of activation of the prostaglandin (PG) system on renin release from slices of rabbit renal cortex. The PG precursor arachidonic acid (C20:4), a natural PG endoperoxide (PGG2), two stable synthetic PG endoperoxide analogues (EPA I and II), PGE2, PGF2alpha, and two different PG synthesis inhibitors [indomethacin and 5,8,11,14-eicosatetraynoic acid (ETA)] were used to evaluate the possibility of a direct action of the cortical PG system on renin secretion. Renin release increased significantly with time after addition of C20:4, PGG2, EPA I, and EPA II to the incubation medium. Stimulation of renin release was se-related for C20:4 in concentrations of 0.6 to 4.5 X 10(-6) M, for EPA I in concentrations of 0.7 to 2.8 X 10(-6) M, and for EPA II in concentrations of 1.4 to 14.0 X 10(-6) M. Indomethacin (10(-4) M) and ETA (10(-4) M) significantly decreased basal renin release as well as the renin release stimulated by C20:4 and EPA I. PGE2(10(-12) to 10(-6) M) had no effect on renin release, whereas PGF2alpha (10(-12) to 10(-6) M) decreased renin release in a dose-dependent manner. These data raise the possibility of a direct action of the renal cortical PG system on renin secretion. The results further indicate that stimulation of renin release by C20:4 may depend more specifically on the action of PG endoperoxides than on the primary prostaglandins.  (+info)

  • Part D: Randomized GSK2118436 HPMC Cohorts Primary: To determine the single and stady-state PK of GSK2118436 HPMC capsules alone and in combination with GSK1120212 dosed orally. (mdanderson.org)
  • Typically, different doses are recommended for children 6 years and under, children aged 6 to 12 years, and persons 12 years and older, but outside of those ranges the guidance is slim. (wikipedia.org)
  • To evaluate differences in steroid concentrations induced by different doses and routes of administration of progesterone. (diva-portal.org)
  • Different doses of progesterone, given vaginally or orally, were added sequentially during the last 14 days of each treatment cycle. (diva-portal.org)
  • Exactly how to quantify the dose of exercise, and how different doses influence cardiovascular, musculoskeletal, or metabolic outcomes, are among the most important current issues in exercise science (5, 6) . (annals.org)
  • Currently metabolic networks (e.g. folate metabolism) are being used to develop a deeper understanding of the functional relationships between genetic variation and trait variation, and of the mechanisms by which genetic and environmental variables interact to produce phenotypes. (duke.edu)
  • Together with sex it explains 11% of the between-subject variability in apparent oral clearance, but predictions could potentially be improved if additional alleles causing reduced drug metabolism were identified. (kb.se)
  • The effect of supraphysiological doses of anabolic androgenic steroids on collagen metabolism. (exrx.net)
  • An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. (springer.com)
  • Thus, HCC therapy is hampered by the fact that the liver is central for xenobiotic metabolism resulting in rapid modifications and efflux of drugs. (aacrjournals.org)
  • 8 This is of particular concern because a substantial number of children with hypertension have underlying systemic diseases that might influence metabolism, dosing, efficacy, and safety. (ahajournals.org)
  • To evaluate the efficacy and tolerability of ESL when used as an add-on treatment for people with drug-resistant focal epilepsy. (cochrane.org)
  • Dose regression analysis showed evidence that ESL reduced seizure frequency with an increase in efficacy with increasing doses of ESL. (cochrane.org)
  • To maximise therapeutic efficacy, sufficient antibody doses should be administered to ensure the saturation of antigen targets by therapeutic antibodies in all patients. (springer.com)
  • The efficacy of this class of drugs has been demonstrated in the treatment of a number of acid-related gastrointestinal diseases, in particular, gastroesophageal reflux and ulcer disease. (ahajournals.org)
  • We aimed to establish a human model of EMT to examine drug efficacy and specificity in HCC progression. (aacrjournals.org)
  • Most remarkably, combined treatment with doxorubicin and sorafenib caused increased susceptibility of both HCC cell types resulting in enhanced drug efficacy. (aacrjournals.org)
  • Taken together, this EMT model of human HCC allows the identification of molecular mechanisms and the assessment of therapeutic drug efficacy during liver cancer progression in preclinical studies. (aacrjournals.org)
  • We evaluated the efficacy, safety, and dose-response relationship of fosinopril in children aged 6 to 16 years with hypertension or high-normal blood pressure with an associated medical condition requiring treatment. (ahajournals.org)
  • 9,10 This study was designed to evaluate the efficacy, safety, and dose-response relationship of fosinopril in hypertensive children. (ahajournals.org)
  • Providing public access to clinical information on the safety and efficacy of drugs and on the safety and effectiveness of medical devices can enable independent re-analyses of data, foster new research questions, and benefit Canadians by helping them make informed decisions about their health. (canada.ca)
  • In drugs where multiple doses of treatment are needed in a day, the physician must take into account information regarding the total amount of the drug which is safe to use in one day, and how that should be broken up into intervals for the most effective treatment for the patient. (wikipedia.org)
  • Dose-response relationships between antimicrobial use (log 2 DDDA/Y) and livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) predicted probabilities in pigs (A) and humans (B), the Netherlands, 2011-2013. (cdc.gov)
  • However, the new data also showed that some DIPG cells develop resistance to the drug, which means it will likely need to be combined with other drugs to achieve the best results in humans. (stanford.edu)
  • The drugs were chosen because they were thought to have possible effects against brain tumors and were already used in humans or were being developed for human use. (stanford.edu)
  • To examine selectivity of tolerated doses of an inhibitor of the inducible COX-2 in humans, we examined the effects of celecoxib on indices of COX-1-dependent platelet thromboxane (Tx) A 2 and on systemic biosynthesis of prostacyclin in vivo . (pnas.org)
  • Over-the-counter medications are typically accompanied by a set of instructions directing the patient to take a certain small dose, followed by another small dose if their symptoms don't subside. (wikipedia.org)
  • Dosing should be titrated based on individual patient plasma ammonia levels and clinical symptoms. (rxlist.com)
  • Metronidazole, an antibiotic used to treat aerobic and protozoal infections, has been known at high doses to produce neurologic symptoms associated with toxic leukoencephalopathy. (wikipedia.org)
  • Patients with severe symptoms or lack of response to first-line therapies should be referred to a psychiatrist. (aafp.org)
  • To be considered for this review, studies were required to be prospective, controlled trials of self-administered drug treatments aimed at the relief of symptoms of individual episodes of headache in patients with migraine. (nih.gov)
  • Nonsteroidal anti-inflammatory drugs (NSAIDs), both nonselective and cyclooxygenase-2-specific inhibitors, are commonly used medications for the relief of acute and chronic pain associated with a wide range of medical conditions. (nih.gov)
  • The recommended initial dose for acute hyperammonemia is 100 mg/kg/day to 250 mg/kg/day. (rxlist.com)
  • Acute renal failure has been associated with non-steroidal anti-inflammatory drugs in healthy children. (greenmedinfo.com)
  • High doses of intravenous methotrexate, a necessary component of chemotherapy for acute lymphoblastic leukemia, is known to cause asymptomatic leukoencephalopathy in children. (wikipedia.org)
  • Adverse drug events (ADEs) impose a major clinical and cost burden on acute hospital services. (bioportfolio.com)
  • A substantial body of high-quality evidence exists describing the effectiveness of various drugs for the treatment of acute migraine. (nih.gov)
  • Synthesis and dissemination of this information may help correct the underuse or misuse of acute drug treatment strategies for migraine headache. (nih.gov)
  • The objective of this Technical Review is to provide a comprehensive review and analysis of published reports of randomized controlled trials (RCTs) and other prospective, comparative clinical trials of self-administered drug treatments for the acute, episodic treatment of migraine headaches. (nih.gov)
  • Studies of parenteral treatments ordinarily administered in a clinical setting will be covered in a companion report (Parenteral drug treatments for acute migraine headache). (nih.gov)
  • ICCDDPTD 2020 has teamed up with the Special Journal Issue on Clinical Drug Development Process and Trial Design . (waset.org)
  • Help us be a 2020 "Top Rated Nonprofit", and spread accurate info about psychoactive drugs, health, culture, & policies. (erowid.org)
  • Medication underdosing occurs commonly when physicians write prescriptions for a dosage that is correct for a certain time, but fails to increase the dosage as the patient needs (i.e. weight based dosing in children, or increasing dosages of chemotherapy drugs if a patient's condition worsens). (wikipedia.org)
  • Various chemotherapy drugs have shown increased risk of cancer patients developing leukoencephalopathy. (wikipedia.org)
  • There have been over 200 clinical trials of chemotherapy drugs for DIPG, and none have shown any survival benefit," said Michelle Monje , MD, PhD, assistant professor of neurology at Stanford and a senior author of the paper. (stanford.edu)
  • In the new study, the research team screened 16 DIPG cell lines derived from patients' tumors against 83 possible chemotherapy drugs, exposing cells to small samples of each drug. (stanford.edu)
  • In conclusion, it is important that cardiologists, who are not among those physicians frequently prescribing NSAIDs, have a particular responsibility to have up-to-date, thoughtfully synthesized information about the CV risks of these drugs, especially when administered to patients receiving low-dose aspirin for cardioprotection. (nih.gov)
  • To evaluate the risk of developing upper gastrointestinal (UGI) bleeding from nonsteroidal anti-inflammatory drugs (NSAIDs), a retrospective (historical) cohort study was performed, using a computerized data base including 1980 billing data from all Medicaid patients in the states of Michigan and Minnesota. (rti.org)
  • Objective To evaluate whether prenatal use of non-steroidal anti-inflammatory drugs (NSAIDs) is associated with increased risk of miscarriage. (bmj.com)
  • Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs in the developed world 1 - 3 and are often used by pregnant women. (bmj.com)
  • Inhibition of prostaglandin synthesis is thought to account for both the therapeutic and adverse effects associated with the administration of conventional nonsteroidal antiinflammatory drugs (NSAIDs) ( 23 , 24 ). (pnas.org)
  • In a dose-escalation study, patients add weekly PEG-Intron to their antiretroviral therapy for up to 6 weeks. (clinicaltrials.gov)
  • An integrated nano-scale approach to MEDICINE which involves concurrent diagnosis, drug delivery, therapy, and monitoring of therapeutic response. (bioportfolio.com)
  • In a US Medicaid population, PPIs accounted for 5.6% of the net pharmacy expenditures and ranked first in expenditures among all drug therapy classes during the 12 months before the implementation of the PPI prior-authorization policy. (ahajournals.org)
  • Augmenting SSRI therapy with an atypical antipsychotic is effective in some patients with OCD who have inadequate response to SSRI therapy. (aafp.org)
  • Because therapy with pramipexole dihydrochloride tablets is initiated at a low dose and gradually titrated upward according to clinical tolerability to obtain the optimum therapeutic effect, adjustment of the initial dose based on gender, weight, or age is not necessary. (nih.gov)
  • Of special interest is the possibility that acid-suppressive drugs could increase susceptibility to respiratory infections because these drugs increase gastric pH, thus allowing bacterial colonization. (cmaj.ca)
  • 6 , 7 Several previous studies have shown that treatment with acid-suppressive drugs might be associated with an increased risk of respiratory tract infections 8 and community-acquired pneumonia in adults 6 , 7 and children. (cmaj.ca)
  • Some drugs produce their effects by interaction with membrane lipids . (britannica.com)
  • ED 50 values provide a useful way of comparing the potencies of drugs that produce physiologically similar effects at different concentrations. (britannica.com)
  • When a drug is used therapeutically, it is important to understand the margin of safety that exists between the dose needed for the desired effect and the dose that produces unwanted and possibly dangerous side effects. (britannica.com)
  • In general, the narrower this margin, the more likely it is that the drug will produce unwanted effects. (britannica.com)
  • The Food and Drug Administration (FDA) lists hostility, anxiety, depression, and suicidal thoughts as possible side effects of this medication. (everydayhealth.com)
  • Given these potential adverse effects, clinicians should use caution in prescribing acid-suppressive drugs for patients at risk. (cmaj.ca)
  • Dose-response curves may illustrate the relationship of these metabolic effects. (wikipedia.org)
  • Drugs and Addiction Drugs have many effects on the body and mind. (majortests.com)
  • However, toxic leukoencephalopathy induced by drug abuse or environmental toxins have had more damaging side effects. (wikipedia.org)
  • Outcomes investigated included 50% or greater reduction in seizure frequency, seizure freedom, treatment withdrawal, adverse effects , and drug interactions. (cochrane.org)
  • Debonnel G, Saint-Andre E, Hebert C, de Montigny C, Lavoie N, Blier P. Differential physiological effects of a low dose and high doses of venlafaxine in major depression. (springer.com)
  • Drugs, Society and Human Behavior provides the latest information on drug use and its effects on society as well as on the individual. (mheducation.com)
  • Schild regression analysis, named for Heinz Otto Schild, is a useful tool for studying the effects of agonists and antagonists on the cellular response caused by the receptor or on ligand-receptor binding. (wikipedia.org)
  • ActRI mRNA levels were increased in a dose-dependent manner by activin-A with the maximal effect observed at the dose of 10 ng/ml.Time course studies revealed that activin-A had maximal effects on ActRI mRNA levels at 6 hours after treatment.In addition, inhibin-A inhibited basal, as well as activin-A-induced ActRI mRNA levels. (nih.gov)
  • The effects of activin-A on ActRI mRNA levels was blocked by follistatin, an activin binding protein, in a dose-dependent manner. (nih.gov)
  • At the doses of 50 and 100 ng/ml, follistatin-288 completely blocked the effects of activin-A on the ActRI mRNA levels (Fig. 5). (nih.gov)
  • Selective publication: studies showing significant effects of drug were published as stand alone publications more often than studies with non-significant results. (bmj.com)
  • For multivariate analysis multiple logistic regression was performed for constipation with the number of drugs, use of drugs with known constipation side effects, and each drug class (Anatomical Therapeutic Chemical Classification System (ATC) level 4) as independent variables. (mdpi.com)
  • 0.001) and the usage of drugs with known constipation adverse effects (odds ratio 2.21, p = 0.009). (mdpi.com)
  • These findings suggest that constipation is associated with the number of drugs used, particularly those with constipation adverse-effects, in the elderly of GWS. (mdpi.com)
  • Effects of low-dose recombinant human insulin-like growth factor-I on insulin sensitivity, growth hormone and glucagon levels in young adults with insulin-dependent diabetes mellitus. (tripdatabase.com)
  • The aim of the present study was to evaluate the long-term (30 months) metabolic effects of recombinant human GH (rhGH) given in a mean dose of 6.7 microg/kg x day (= 1.6 IU/day), in 11 patients with adult GH deficiency. (tripdatabase.com)
  • A logistic growth function accounting for natural paw growth and an indirect response model for paw edema and drug effects (inhibition of k in ) was applied. (aspetjournals.org)
  • Additional information is available on global doses from nuclear bomb tests and doses from nuclear fuel processing and medical uses can be found in United Nations Scientific Committee on the Effects of Atomic Radiations. (cdc.gov)
  • To evaluate the anti-HIV activity of PMPA prodrug, as demonstrated by increases in CD4 cell counts and decreases in HIV RNA, when administered orally as a single dose and daily for 4 weeks to HIV-infected patients with CD4 cell counts of 200 or more cells/mm3. (clinicaltrials.gov)
  • ANTHIM is supplied as 600 mg/6 mL in single-dose vials for intravenous infusion. (rxlist.com)
  • The recommended dosage of ANTHIM in adult patients is a single dose of 16 mg/kg administered intravenously over 90 minutes (1 hour and 30 minutes) [see Administration ]. (rxlist.com)
  • The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. (drugs.com)
  • Serious adverse cardiovascular (CV) events have been reported with NSAID use, but unfortunately, definitive evidence regarding the precise CV risk associated with these drugs, as a class and individually, is lacking. (nih.gov)
  • Our study supports the need for caution when using intramuscularly administered, abruptly increasing, high-dose neuroleptics, particularly in mentally retarded or agitated patients, regardless of environmental temperature. (wiley.com)
  • If the dose is tolerated, patients are added and if safety criteria are met, patients are enrolled in the next higher dose level. (clinicaltrials.gov)
  • Patients initially receive the next lower PEG-Intron dose to the optimal dose identified in Cohort I [AS PER AMENDMENT 07/23/01: or 1 microg/kg if the optimal dose proves to be 1 microg/kg]. (clinicaltrials.gov)
  • If this dose is safely tolerated, additional patients are added. (clinicaltrials.gov)
  • If this dose level meets safety criteria, patients are enrolled to receive the optimal dose level. (clinicaltrials.gov)
  • This study will test the relationship for single doses of oCRH in normal volunteers and patients with disorders of the HPA axis. (clinicaltrials.gov)
  • This study seeks to explore these clinical applications by determining the dose-response relationship for single doses of ovine CRH (oCRH) in normal volunteers and in patients with disorders of the hypothalamic-pituitary-adrenal axis. (clinicaltrials.gov)
  • To evaluate and compare the safety, tolerability, and effectiveness of long-term biweekly administration of 1 of 2 doses of aerosol pentamidine when used as a prophylactic agent in patients who have had multiple episodes of AIDS associated Pneumocystis carinii pneumonia (PCP). (clinicaltrials.gov)
  • Patients will be randomized to either Balanced Dose or Low Dose RTV treatment arms. (nih.gov)
  • Patients in the Balanced Dose Arm will receive RTV and IDV in approximately equal doses. (nih.gov)
  • Patients will have intensive pharmacokinetic analysis at Week 4 (or 2 weeks after a stable dose of study drugs has been reached) and Week 16. (nih.gov)
  • to determine the ED90 (minimum effective dose in 90% of patients) of sugammadex for the reversal of rocuronium-induced moderate neuromuscular blockade (NMB) in patients with grade III obesity undergoing bariatric surgery. (scielo.br)
  • Measures of weight correction to indicate the best scheme of drug administration in obese patients have been proposed 4 - 6 . (scielo.br)
  • Results in patients with grade III obesity submitted to laparoscopic bariatric surgery under NMB indicated an optimal dose of 2mg/kg of sugammadex based on 140% of the IBW for patients with moderate neuromuscular blockade 14 . (scielo.br)
  • However, a prospective observational study found that 23.4% of patients required a second dose of sugammadex to reverse moderate NMB over a two-minute time interval when a dose of 2mg/kg was used in comparison with the time of reversion between non-obese subjects 15 . (scielo.br)
  • The aim of this study was to determine the minimum effective dose of sugammadex in 90% of obese patients (ED 90) required to complete the reversal of rocuronium-induced moderate neuromuscular blockage using the up-and-down design of biased coin (BCD) in patients with grade III obesity submitted to bariatric surgery. (scielo.br)
  • Dose optimisation of tacrolimus with therapeutic drug monitoring and CYP3A5 polymorphism in myasthenia gravis patients. (bioportfolio.com)
  • However, patients have to take immunosuppressive drugs to. (bioportfolio.com)
  • Based on limited data in 22 patients receiving maintenance treatment with Carbaglu® in a retrospective case series, maintenance doses were usually less than 100 mg/kg/day. (rxlist.com)
  • ANTHIM is indicated in adult and pediatric patients for the treatment of inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs. (rxlist.com)
  • The recommended dose for pediatric patients is based on weight as shown in Table 1 below. (rxlist.com)
  • Patients with OCD require higher SSRI dosages than for other indications, and the treatment response time is typically longer. (aafp.org)
  • Adverse drug events and medication problems in hospital at home patients. (bioportfolio.com)
  • Prospective validation of clinical criteria to identify emergency department patients at high risk for adverse drug events. (bioportfolio.com)
  • But serum RBP declined by about 75% in the early enrollers receiving 300 mg a day of the drug, and these patients had the smallest mean increase in lesion size. (medpagetoday.com)
  • Dose-response relationships of inhaled insulin delivered via the Aerodose insulin inhaler and subcutaneously injected insulin in patients with type 2 diabetes. (tripdatabase.com)
  • Prostaglandins (PGs) are autacoidal lipid mediators of importance in physiological responses, inflammation and thrombosis ( 1 ). (pnas.org)
  • Background Observational studies and randomized controlled trials have yielded inconsistent findings about the association between the use of acid-suppressive drugs and the risk of pneumonia. (cmaj.ca)
  • The aim of this study was to summarize the association between the use of acid-suppressive drugs and the risk of pneumonia in observational studies and randomized controlled trials. (cmaj.ca)
  • A drug of this type is the antifungal agent amphotericin B , which binds to a specific molecule ( ergosterol ) found in fungal cells. (britannica.com)
  • Responses of the GABA(C) receptor, the predominant GABA receptor on rat rod bipolar cells, exhibited a greater sensitivity to GABA, larger maximum current responses, slower response kinetics, and a smaller single channel conductance among diabetic cells relative to those recorded from normal controls. (nih.gov)
  • Compared with the properties of homomeric rho1 and heteromeric rho1rho2 receptors formed in a heterologous expression system, these results suggested that there was a greater contribution from the rho1 subunit in the GABA(C) receptor-mediated response of diabetic cells. (nih.gov)
  • A dose- and time-dependent induction of autophagy was observed in tumour cells following cisplatin treatment, as demonstrated by up-regulation of autophagy-inducing protein beclin-1 and subsequent appearance of acridine orange-stained acidic autophagic vesicles. (nih.gov)
  • Taken together, these data suggest that cisplatin-triggered activation of AMPK and subsequent suppression of mTOR activity can induce an autophagic response that protects tumour cells from cisplatin-mediated apoptotic death. (nih.gov)
  • The team tracked six of the drugs' dose-response relationship on DIPG cells and selected panobinostat for further study. (stanford.edu)
  • Volunteers received doses of 100, 400, or 800 mg of celecoxib or 800 mg of a nonselective inhibitor, ibuprofen. (pnas.org)
  • drug monitoring (TDM) is essential for tacrolimus to optimize dosage and prevent adverse reactions. (bioportfolio.com)
  • Several studies have investigated sex as a risk factor for the occurrence of adverse drug reactions (ADRs) and found that women are more likely to experience ADRs than men. (springer.com)
  • Martin RM, Biswas PN, Freemantle SN, Pearce GL, Mann RD. Age and sex distribution of suspected adverse drug reactions to newly marketed drugs in general practice in England: analysis of 48 cohort studies. (springer.com)
  • Sex-related differences in hospital admissions attributed to adverse drug reactions in the Netherlands. (springer.com)
  • Drici MD, Clement N. Is gender a risk factor for adverse drug reactions? (springer.com)
  • Vilhelmsson A, Svensson T, Meeuwisse A, Carlsten A. What can we learn from consumer reports on psychiatric adverse drug reactions with antidepressant medication? (springer.com)
  • No differences between men and women in adverse drug reactions related to psychotropic drugs: a survey from France, Italy and Spain. (springer.com)
  • A method for estimating the probability of adverse drug reactions. (springer.com)
  • Medication reconciliation (MR) at hospital admission, transfer, and discharge has been designated as a required hospital practice to reduce adverse drug events. (bioportfolio.com)
  • However, the incidence of adverse drug events in these programs is unknown. (bioportfolio.com)
  • This study describes adverse drug events an. (bioportfolio.com)
  • Adverse drug events cause or contribute to one in nine emergency department presentations in North America, and are often misdiagnosed. (bioportfolio.com)
  • Bivariate associations between constipation and number of drug use and number of drug use with constipation adverse effect were compared. (mdpi.com)
  • The Low Dose RTV Arm will receive a dosing ratio of RTV:IDV of approximately 1:3. (nih.gov)
  • The dose of cannabis depends on the individual, the condition being treated, and the ratio of cannabidiol (CBD) to tetrahydrocannabinol (THC) in the cannabis. (wikipedia.org)
  • The children enrolled in this study will have high HIV viral loads despite taking anti-HIV drugs. (nih.gov)
  • For bacterial or viral agents, dose typically refers to the amount of the pathogen required to infect a host. (wikipedia.org)
  • Contraindications to high-dose megestrol acetate (poorly controlled hypertension or heart failure or deep vein thrombosis). (clinicaltrials.gov)
  • The majority of drugs with high lipid solubility have a high distribution volume 3 . (scielo.br)
  • Inderal (propranolol hydrochloride) and other drugs in the beta-blocker class, used to treat high blood pressure. (everydayhealth.com)
  • Also, high quality research contributions describing original and unpublished results of conceptual, constructive, empirical, experimental, or theoretical work in all areas of Clinical Drug Development Process and Trial Design are cordially invited for presentation at the conference. (waset.org)
  • To examine the dose-response relationship between match-play high-speed running (HSR), very high-speed running (VHSR), and sprint (SPR) distances versus subsequent ratings of fatigue and soreness. (humankinetics.com)
  • The primary objective of the dose-response phase was to determine whether low (0.1 mg/kg), medium (0.3 mg/kg), or high (0.6 mg/kg) doses of fosinopril based on established adult dosing affect trough seated systolic blood pressure. (ahajournals.org)
  • In a nontolerant person the estimated lethal dose of heroin may range from 200 to 500 mg, but addicts have tolerated doses as high as 1800 mg without even being sick. (erowid.org)
  • The number of affecting variables is very high, and some of them are inversely related with caffeine content (brewing time and brew volume), while others exhibit a direct relationship (grinding level, dose, and tamping). (intechopen.com)
  • A 'dose' of any chemical or biological agent (active ingredient) has several factors which are critical to its effectiveness. (wikipedia.org)
  • Prespecified subgroup analyses by renal recovery, baseline chronic kidney disease, preadmission drug regimen, and HbA 1c were performed. (diabetesjournals.org)
  • The purpose of this study is to find a combination of RTV and IDV that is safe, well tolerated, and produces drug levels in the blood of children that are comparable to effective drug levels in the blood of adults. (nih.gov)
  • Because children appear to be more sensitive to lower doses of fosinopril than adults, starting doses for children should be ≤0.1 mg/kg. (ahajournals.org)
  • These observations have led to the hypothesis that COX-2 expression mediates the enhanced prostanoid release, which characterizes the inflammatory response ( 21 ). (pnas.org)
  • Despite these risks, substance use is common: 60 million Americans smoke, 14 million are alcohol-dependent, and 14 million use illicit drugs (including marijuana) (1). (cdc.gov)
  • Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs. (hudson.org)