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Biomedical subjects

S Kacew

Publications and source records attributed to S Kacew.

At least 55 records · Page 3Linked to original sources
PubMed1985

Adverse tissue reactions to drugs: a five-year surveillance study.

Over a 5-year duration a total number of 57 881 tissue specimens from hospitalized patients were evaluated clinicopathologically for evidence of adverse tissue reactions to drugs. The incidence of alleged adverse tissue reactions was 3.7% of which 1.5% were definitely shown to be caused by a specific pharmacological agent. Regardless of the category of the adverse tissue reaction, the frequency of drug-related responses occurred most often in females, especially between the ages of 41 and 60 years. The target tissue affected adversely most often was endometrium where hyperplasia was the predominant response noted. An oestrogenic preparation was found most frequently to be implicated in the observed adverse tissue reaction. Evaluation of adverse drug reactions with the use of morphologic technique provides a rigorous and reliable mechanism to monitor deleterious effects in hospitalized patients.

Adolescent↗
PubMed1985

Renal and hepatic concentrations of platinum: relationship to cisplatin time, dose, and nephrotoxicity.

Autopsy tissues were obtained from 30 patients who had received cisplatin antemortem; the tissues were assayed for platinum by flameless atomic absorption spectrometry. Patients with antemortem evidence of renal toxicity had higher renal cortical platinum concentrations than did patients without evidence of kidney damage. In addition, patients with nephrotoxicity were more likely than patients without toxicity to have renal cortical platinum concentrations that were higher than renal medullary platinum concentrations. Overall, the two variables most closely associated with an increase in serum creatinine with treatment were renal cortical platinum concentration (P less than .02) and cumulative dose of cisplatin (P less than .05). These two variables were important independently of one another. Renal cortex platinum concentrations correlated inversely with time from last treatment until death, whereas hepatic platinum concentrations did not. In contrast, hepatic platinum concentrations correlated with dose of cisplatin while renal platinum concentrations did not. Our results suggest the following: (1) cisplatin-induced renal toxicity is tissue-platinum-concentration dependent and cisplatin-dose dependent; and (2) cisplatin may be handled differently at the molecular level in liver and kidney.

Adult↗
PubMed1985

Newborn response to cationic amphiphilic drugs.

Administration of various cationic amphiphilic drugs in utero results in induction of a phospholipid storage disorder in many tissues, particularly in lungs. In addition to the phospholipidosis in utero, drug exposure results in toxicity to the offspring; newborn rats die within 48 h of birth. Although drug-induced pulmonary pathological changes appear to be involved in the observed mortality, this relationship remains unclear. In contrast to mammals, administration of cationic amphiphilic drugs to the chick embryo seems not to induce phospholipid storage in the tissues examined. Treatment of newborn rats directly with these drugs also induces phospholipidosis in several tissues including lung and kidney; however, mortality does not occur. Concurrent administration of phenobarbital and chlorphentermine reduces or prevents amphiphilic drug-induced phospholipid storage in newborn rat lung and kidney. Modification of chlorphentermine actions by phenobarbital may be caused by alterations in amphiphilic drug excretion, metabolism, and catabolic phospholipase activity. Evidence thus indicates that regardless of age, animals appear susceptible to the effects of cationic amphiphilic drugs; however, species and tissues examined, as well as specific drug administration, play an important role in the observed qualitative and quantitative responses.

Animals↗
PubMed1985

Gentamicin or chlorphentermine induction of phospholipidosis in the developing organism: role of tissue and species in manifestation of toxicity.

Daily, s.c. injection of gentamicin (100 mg/kg) for 2 days produced a significant increase in total phospholipid content of newborn rat kidney. Separation of individual phospholipid components revealed a significant rise in renal phosphatidylserine, phosphatidylinositol and phosphatidylcholine, whereas no marked change was noted in sphingomyelin, phosphatidylethanolamine or phosphatidylglycerol. Gentamicin did not significantly alter individual phospholipid classes and total phospholipid content in newborn rat liver and lung. Daily, oral chlorphentermine (60 mg/kg) administration also elevated total renal phospholipid levels and all individual phospholipid classes except sphingomyelin. In addition, a significant rise in all phospholipid components and total phospholipid content was noted in lungs of chlorphentermine-treated newborns. In the case of rat kidney, both gentamicin and chlorphentermine produced the greatest percentage of increase in phosphatidylinositol, whereas in lung phosphatidylcholine exhibited the highest percentage of elevation in response to chlorphentermine. In newborn rat liver, chlorphentermine did not induce alterations in individual and total phospholipid content. Gentamicin or chlorphentermine (1 mg/egg) failed to induce a phospholipidosis in chick embryo kidney and liver. Evidence suggests that drug-induced phospholipidosis is both species- and tissue-dependent and that this metabolic phenomenon is associated with inhibition of lysosomal phospholipases.

Animals↗
PubMed1984

A teratological evaluation and analysis of fetal tissue levels following administration of tetrachlorobenzene isomers to the rat.

Three tetrachlorobenzene (TCB) congeners (1,2,3,4- 1,2,3,5-, and 1,2,4,5-) were administered daily by gavage to pregnant Sprague-Dawley rats at levels of 50, 100, or 200 mg/kg from day 6 through day 15 of gestation. Mothers were sacrificed on day 21 of gestation and the pups removed by cesarian section for teratological evaluation. Administration of 1,2,3,4- and 1,2,3,5-TCB failed to alter maternal body weight, organ weights, hematological, or the biochemical parameters studied. The highest dose level of 1,2,4,5-tetrachlorobenzene caused maternal death in nine of ten animals. In addition it induced mixed function oxidases and increased serum cholesterol values at 50 and 100 mg/kg. There was a decrease in the number of fetuses at the highest dose levels of 1,2,3,4- and 1,2,3,5-TCB and at the lowest dose level of the 1,2,4,5- congener. None of the congeners produced any anomalies. There were no treatment-related histopathological changes in either the mothers or fetuses. Residues of all three congeners were found in maternal and fetal tissues but generally the amounts of the 1,2,4,5- isomer were about 100 times higher than the other two.

Abnormalities, Drug-Induced↗
PubMed1984

Monitoring of adverse drug reactions by means of autopsy tissue examination.

Morphologic examination of autopsy tissue specimens was undertaken to establish the incidence of adverse drug reactions in a population of hospitalised patients. By removal of subjective bias recording of adverse reactions, the incidence of toxic tissue manifestations was 33%. In those reactions classified as definitely linked to a specific causative agent males between the ages of 41 and 60 displayed the highest frequency of adverse effects. In the probable and possible categories the incidence of toxic manifestations was equal amongst both sexes and highest in patients over 40 y. Regardless of the type of adverse reaction the most common causative agent identified was alcohol and hepatic tissue was primarily altered morphologically. Unlike the conventional mechanism used to monitor adverse drug reactions, autopsy tissue examination provides a system of measurement of toxic manifestations to both prescription as well as non-prescription compounds.

Adult↗
PubMed1984

Role of age in amphiphilic drug-induced pulmonary morphological and metabolic responses.

The morphological and metabolic responsiveness of pulmonary tissue to amphiphilic agents is dependent on age. Daily oral administration of chlorphentermine (60 mg/kg) for 1 wk produced an accumulation of phospholipid-rich hypertrophic macrophages in pulmonary alveoli accompanied by an increase in relative lung weight and elevation in levels of phosphatidylcholine (PC), sphingomyelin (S), phosphatidylserine (PS) plus phosphatidylinositol (PI), phosphatidylethanolamine (PE) plus phosphatidylglycerol (PG), and total phospholipid (TPL) in newborn rats. Chlorcyclizine treatment (60 mg . kg-1 . day-1) for 1 wk also resulted in an accumulation of hypertrophic macrophages and an increase in both TPL and PC levels in newborn lung. However, unlike chlorphentermine, the chlorcyclizine-stimulated increase in pulmonary cells was associated with no marked change in relative lung weight and levels of S, PG plus PE, and PS plus PI. Phenobarbital (30 mg/kg) reduced the chlorphentermine-induced (60 mg/kg) effect on neonatal relative lung weight, accumulation of hypertrophic macrophages, and phospholipid levels. Withdrawal from drug treatment for 2 wk in newborns previously given chlorphentermine for 7 days resulted in a disappearance of pulmonary hypertrophic macrophages and a return of TPL levels to control values. Our data support the view that age plays a role in the observed amphiphilic drug-induced morphological and metabolic responses in rat lung.

Aging↗
PubMed1983

Chlorphentermine-induced alterations in pulmonary phospholipid content in rats.

Daily, intraperitoneal administration of the anorectic drug chlorphentermine (30 mg/kg) for 5 days to rats significantly increased phosphatidylcholine and total phospholipid content after 1 week and reached a maximal level 4 weeks after treatment in whole lung tissue (unlavaged lungs) and in sessile tissue in which alveolar lipids and macrophages were removed by pulmonary lavage (lavaged lungs). In lavaged lung, a significant rise in the content of sphingomyelin, phosphatidylserine plus phosphatidylinositol component, and phosphatidylethanolamine plus phosphatidylglycerol fraction occurred after 2 weeks, remained at this increased level for 4 weeks, and was followed by a return to control amounts after 5 weeks. In unlavaged lung, the chlorphentermine-induced elevation in sphingomyelin content seen after 1 week persisted at this same significant level even 5 weeks after treatment. Regardless of experimental duration, pulmonary glycogen levels were not altered markedly by chlorphentermine in unlavaged or lavaged tissue. Phenobarbital (30 mg/kg) did not markedly alter pulmonary glycogen and phospholipid component levels. Simultaneous phenobarbital and anorectic drug administration prevented the chlorphentermine-induced rise in total phospholipid, sphingomyelin, and phosphatidylcholine in unlavaged lung without a change in glycogen. A 7-day withdrawal from chlorphentermine treatment in rats previously injected with drug for 2 weeks resulted in a return to control in the levels of sphingomyelin, phosphatidylcholine, and total phospholipid in unlavaged lung. Extension of withdrawal from treatment for 2 weeks produced a significant decrease in all phospholipid components below control values, suggesting that a possible imbalance in synthetic and catabolic activity may persist after drug removal. The concentration of lung glycogen was not altered significantly by chlorphentermine treatment or withdrawal from drug administration. Our results indicate that the chlorphentermine-induced rise in phospholipid components was time-dependent in lavaged and unlavaged lungs, and the increase in phosphatidylcholine occurred independently of a change in glycogen. In addition, the present study shows that the chlorphentermine-induced changes in phospholipid levels are reversible and almost completely prevented by phenobarbital.

Animals↗
PubMed1983

Induction of feather malformations in chick embryos by cadmium: protection by zinc.

Various doses of cadmium chloride were injected to chick embryos between the seventh and 14th day of incubation. Doses over 15 micrograms/egg produced high mortality and, when injected between the tenth and 11th day, widespread curling of the feathers in the surviving embryos. A different type of malformation, consisting of hemorrhagic atrophy of the distal part of the feathers, was observed in the embryos injected with similar doses during the 12th day. No feather malformations were observed in embryos injected before the ninth or after the 12th day of incubation. The simultaneous injection of an equimolar amount of zinc sulfate prevented the feather malformations.

Abnormalities, Drug-Induced↗
PubMed1982

Effects of parenteral vanadium administration on pulmonary metabolism of rats.

Daily, intraperitoneal administration of either vanadium pentoxide (VP) or sodium vanadate (NaV) at a dose of 1 mg/kg for 14 days produced no marked change in pulmonary protein, glycogen and phospholipid (PL) levels of adult male rats. Increasing the VP dose to 4 mg/kg decreased lung PL content, while an equivalent NaV dose elevated tissue glycogen. Treatment with either dosage of NaV elevated the activities of pulmonary 6-phosphogluconate dehydrogenase (6PGDH), pyruvate kinase (PK) and glutathione peroxidase (GP), and the higher dose increased lactate dehydrogenase (LDH) and glutathione reductase (GR). The 1 mg/kg VP produced a significant rise in glucose-6-phosphate dehydrogenase (G6PDH) and 6PGDH. while the higher VP dose in general failed to alter enzymic activity. Our data suggest that similar to intratracheal instillation, parenteral administration of vanadium exerts an effect on lung metabolism of rats.

Animals↗
PubMed1981

The effect of phenobarbital on chlorphentermine-induced lipidosis-like alterations in renal tissue of adult and newborn rats.

Daily oral administration of 20 or 60 mg/kg chlorphentermine for 1 week produced a dose-related increase in the number of myeloid bodies in renal tissue of both adult and newborn rats. In adults myeloid bodies were present throughout the kidney while in neonates these bodies were found predominantly in the medullary region. Simultaneous administration of phenobarbital and either chlorphentermine dose resulted in a reduction in the number of myeloid bodies in kidneys of adults and newborns. Our data show that phenobarbital prevented the chlorphentermine-induced lipidosis in renal tissue and that newborns appear less sensitive than adults to the histopathologic action of anorectic on kidney.

Animals↗
PubMed1981

Modification by hyperoxia of chlorphentermine- or phentermine- induced effects on newborn rat lung morphology and metabolism.

Treatment of newborns with 20 mg/kg/day chlorphentermine orally for 1 week increased incorporation of thymidine into lung DNA without an associated change in tissue morphology or cyclic AMP levels. An increase in chlorphentermine dose to 60 mg/kg resulted in an accumulation of alveolar hypertrophic macrophages and a rise in incorporation of thymidine into lung DNA; however, cyclic AMP levels were decreased. In contrast, 20 or 60 mg/kg/day for 1 week phentermine-induced depression in the incorporation of thymidine into pulmonary DNA was accompanied by a decrease in cyclic AMP but no apparent alteration in tissue morphology. Hyperoxia did not modify the phentermine-induced changes in cyclic AMP levels and pulmonary ultrastructure. In contrast, hyperoxia altered the responsiveness of newborns to 20 mg/kg chlorphentermine as evidenced by the presence of foam cells. Data suggest that the chlorphentermine-induced increase in DNA synthesis in newborn lung seems independent of changes in cyclic AMP and tha modification of drug-induced alterations by hyperoxia may be related to the chemical structure of a compound.

Animals↗
PubMed1980

Ultrastructural and biochemical alterations in the livers from chick embryos maintained in shell-less culture.

Ultrastructural and biochemical studies were conducted on the livers from chick embryos maintained in shell-less culture up to stage 39 (Hamburger-Hamilton) and from control embryos developed in ovo up to the same stage. The ultrastructural characteristics of hepatic cells from the cultured embryos were similar to those found in the controls except that they contained many large lipid droplets and were almost devoid of lipoprotein granules normally associated with the Golgi complex and the smooth endoplasmic reticulum. These changes suggest the existence of alterations in the lipid metabolism. The livers from cultured embryos showed also a decreased incorporation of tritiated leucine into proteins, which indicates a reduced rate of protein synthesis. These results are consistent with previous reports showing that cultured embryos possess hypoproteinemia. Lactic dehydrogenase activity was similar and pyruvic kinase higher in the livers from cultured with respect to control embryos. This appears to indicate that both aerobic and anaerobic glycolysis were not depressed and that the changes observed in the rate of protein synthesis should not be attributed to hypoxia. "Fat-storing cells" similar to those described in mammals were found both in control and cultured embryos. They had not been previously described in the livers from chick embryos.

Animals↗