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Biomedical subjects

A Somogyi

Publications and source records attributed to A Somogyi.

195 records · Page 11Linked to original sources
PubMedDate not supplied

Survey of animal drugs with carcinogenic properties.

Residues of animal drugs with carcinogenic potential cannot always be avoided in food. The risk/benefit evaluation of carcinogenic drugs used in food-producing animals is a scientifically unresolved problem. Nonetheless, a pragmatic solution taking into account such drugs' putative mechanisms of action, their relative potency, and their significance in the prevention and therapy of disease must and can be achieved. While it is unlikely that a new animal drug possessing overt carcinogenic properties would pass the approval process practiced in most countries today, a number of carcinogenic drugs for use in food-producing animals are currently on the market. Their re-evaluation from the viewpoint of human food safety is necessary, particularly if they are genotoxic (for example nitrofurans, nitroimidazoles, quinoxaline-di-N-oxides). The carcinogenicity of hormonally active animal drugs, none of which has genotoxic potential, is believed to be related to their hormonal action. Thus, the establishment of a threshold level for these drugs and their residues appears possible. It is difficult to evaluate certain other nongenotoxic animal drugs which are carcinogenic at very high dose levels and in one species only. No carcinogenic substance, regardless of its hypothetical mechanism of action, should be used in food-producing animals for which a very significant therapeutic benefit has not been demonstrated.

Animals↗
PubMedDate not supplied

Renal transport of drugs: specificity and molecular mechanisms.

1. The kidney is principally an excretory organ for drugs and their metabolites and has developed high capacity transport systems to rapidly eliminate the large quantities of foreign compounds delivered to it. 2. There are specific and selective transporters for organic cations and organic anions at the contraluminal and luminal membranes of epithelial cells lining the proximal tubule. 3. For organic anions, the transporter (termed PAH-transporter) is located at the contraluminal cell membrane and uptake is a tertiary active transport process. Important physico-chemical properties for interaction with this transporter are hydrophobicity, ionic charge strength and electron-attracting side groups. 4. For organic cations, there is evidence for one common transport system at the contraluminal membrane and substrate requirements are the degree of hydrophobicity, ionic charge strength and hydrogen bond formation. At the luminal membrane, an electroneutral H+/organic cation exchanger in which the degree of substrate hydrophobicity is critical for interaction and a choline transport system have been described. 5. P-Glycoprotein present in renal brush border membranes transports organic cationic drugs but is dissimilar to the luminal electroneutral H+/organic cation exchanger. 6. Clinically, several drugs have been implicated in causing interactions via these transport systems. For organic anions, probenecid blocks the tubular secretion of other organic anions and this has been used to prolong the duration of action of penicillin-like compounds. For organic cations, cimetidine and trimethoprim are potent inhibitors of the secretion of a number of organic cations, particularly procainamide, which can result in significant clinical toxicity. 7. An understanding of the mechanisms of renal tubular secretion of drugs and their metabolites will allow for the prediction of drug interactions involving renal excretory mechanisms.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Pharmacokinetics and bioavailability of cimetidine in gastric and duodenal ulcer patients.

The pharmacokinetics and bioavailability of cimetidine after 200 mg given intravenously and orally was studied in 6 gastric and 6 duodenal ulcer patients aged between 28 and 64 years. There were no differences in any of the pharmacokinetic parameters between the two ulcer groups, but there was considerable variation which was mainly age-related. Bioavailability was not complete, but was about 60% based on the plasma concentration data. The volume of distribution at steady-state was about 80% of body weight, and the plasma clearance value of 495 ml/min was mainly due to renal clearance (293 ml/min). The elimination half-life was approximately 2 hours. These pharmacokinetic parameters together with the percentage of dose excreted unchanged in urine following intravenous administration were all highly age correlated; all decreasing with age except the elimination half-life which increased with age. Of clinical importance is the finding that the time for which the plasma concentration exceeded 0.5 microgram/ml following oral administration was also highly age-dependent, increasing by more than 2-fold in the elderly (53 to 64y) compared with the younger (28 to 45y) patients.

Adult↗
PubMedDate not supplied

Clinical pharmacokinetics of cimetidine.

Cimetidine is the first histamine H2-receptor antagonist with wide clinical application. It is a weak base and a highly water-soluble compound which can be measured in biological fluids by a number of high-pressure liquid chromatographic methods. Following intravenous administration, the plasma concentration profile follows multicompartmental characteristics. The total systemic clearance is high (500 to 600 ml/min) and is mainly determined by renal clearance. The volume of distribution (Vd beta or Vdss) is of the order of 1 L/kg and this about equals bodyweight. Elimination half-life is approximately 2 hours. Following oral administration of cimetidine, 2 plasma concentration peaks are frequently observed, probably due to discontinuous absorption in the intestine. The absolute bioavailability in healthy subjects is about 60%. In patients with peptic ulcer disease, bioavailability is around 70%, but the variation is much greater than in healthy subjects. Absorption and clearance of cimetidine are linear after 200 and 800mg doses. Mean steady-state plasma concentrations on a standard 1000mg daily dose are 1.0 microgram/ml (range 0.64-1.64 micrograms/ml) and are reproducible after treatment periods of up to 2 years. When taken with food, the extent of absorption is unaltered, but a delay occurs and only 1 peak in the plasma concentration curve is apparent. Partial gastrectomy (Billroth I, II) causes an increase in systemic availability of cimetidine by an unclear mechanism. Distribution of cimetidine leads to extensive uptake into kidney, lung and muscle tissues. It distributes into the cerebrospinal fluid (CSF) at a ratio of 0.1 to 0.2 compared with plasma. The mean saliva to plasma ratio is 0.2 (range 0.1-0.55). Plasma protein binding is 20%, and there is no relevant effect of changes in binding on the pharmacokinetics of cimetidine. Uptake of cimetidine into red blood cells leads to concentrations equal to those in plasma. Between 50 and 80% of the dose administered intravenously is recovered in urine as unchanged cimetidine. This fraction is less after oral doses, but is independent of the amount of the dose. In ulcer patients, 40% is recovered unchanged in urine after oral administration. Biliary excretion of cimetidine accounts for only 2% of the dose.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMedDate not supplied

[Effect of hyperlipemia on mitogen-induced blastogenesis in lymphocytes isolated from the rat spleen].

Lipoproteins suppress several immune functions (mitogen-induced lymphoblast transformation, macrophage functions). Low density lipoprotein (LDL) is responsible for most of these effects. Diet may cause an elevation in LDL level. Therefore, we investigated the effect of cholesterol-rich diet upon the mitogen response of rats. The cholesterol and LDL-cholesterol level of rats was elevated after 8 days of diet. The blastogenic response of spleen cells separated by Ficoll-Paque gradient decreased. The response to phytomitogens 1, and 10 micrograms/ml phytohaemagglutinin (PHA) and 10 micrograms/ml concanavalin A (Con A) was measured by thymidine incorporation after 3 days of culture. The decrease of blastogenic response was more pronounced at the higher doses (10 micrograms/ml PHA, and 10 micrograms/ml Con A). For the lymphocyte cultures that did not contain autologous (rat) serum, we suggest that suppressed response was caused by an alteration of either in the membrane or in the metabolism of cells participating in the mitogen response. The decreased amount of LDL receptors and a derangement in intracellular cholesterol biosynthesis are supposed. The clinical implications of the immunosuppressive effect of dietary cholesterol is discussed.

Animals↗
PubMedDate not supplied

Trace analysis of chloramphenicol residues in eggs, milk, and meat: comparison of gas chromatography and radioimmunoassay.

A radioimmunological assay (RIA) to detect chloramphenicol (CAP) residues in eggs, milk, and meat is described. For tissues and other edible products of chloramphenicol-treated animals (chickens, cows, and pigs), the limit of detection is about 200 ng/kg. Residue levels above 1 microgram/kg can easily be quantitated. When highly specific antisera produced in sheep were used, cross-reactivity was insignificant except for metabolites deviating from the parent compound in the acyl side chain only. Thiamphenicol fails to bind to the antisera; hence, it does not interfere with the assay. In the procedure described, the role of cleanup is merely to remove lipids. Thus, skim milk can be analyzed following appropriate dilution without cleanup. The results obtained by RIA were confirmed by gas chromatography with electron capture detection. The new RIA allows rapid, sensitive, and specific screening of large numbers of samples.

Animals↗
PubMedDate not supplied

Coronary artery bypass surgery on the beating heart.

Authors report their experiences with coronary artery bypass surgery without cardiopulmonary bypass. Between January 1993 and June 1995, 151 patients were operated upon by the same surgeon for ischaemic heart disease (IHD); 7 were of them without extracorporeal circulation (ECC). Patients were selected for the procedure on the following criteria: (1) symptomatic patient with proximally occluded, anteriorly located, major subepicardial artery(ies) unsuitable for, or after failed, PTCA; (2) presence of associated disease (like hypertension, diabetes mellitus, chronic obstructive pulmonary disease) enhancing a possible deleterious effect of cardiopulmonary bypass; (3) favourable response to beta-blocking agent pretreatment without side effects. Seven patients' perioperative data (white cell count, platelet count, whole plasma protein level, chest drainage, CK-MB release--incidence of perioperative myocardial mess loss--and days spent in the intensive care unit /ICU/) are compared to the corresponding data of patients with comparable pathology operated on with ECC. No blood transfusion was required, nor perioperative myocardial necrosis occurred. The patients operated on without ECC spent only 24 hours in the ICU, and the clinical check-up after 1-24 months revealed conditions free from angina pectoris. The patient's quality of life improved.

Aged↗
PubMedDate not supplied

Drug-related Churg-Strauss syndrome?

Churg-Strauss syndrome (CSS) is a rare disease belonging to the group of necrotizing vasculitides affecting medium and small vessels, classified together with Wegener granulomatosis and microscopic polyarteritis. The literature is reviewed concerning vasculitides associated with drug use, focusing on CSS. A representative case of CSS is reported, in whom the possibility could not be excluded that oestrogen replacement therapy contributed to the onset of CSS. The case of a 56-year-old female patient is presented who had a history of allergic rhinitis and steroid-dependent asthma for years. To prevent postmenopausal complaints and further loss of bone density, she received oestrogen replacement therapy. After three months of hormone therapy, signs of CSS appeared. Oestrogen administration (1 mg norethisterone acetate, 1 mg oestriol and 2 mg oestradiol daily) was stopped. The diagnosis was confirmed by the clinical appearance, laboratory tests and tissue biopsies. The patient received corticosteroids and cyclophosphamide treatment and subsequently the eosinophil count returned to normal within two weeks and her condition improved significantly.

Churg-Strauss Syndrome↗