Biomedical subjects

T Zima

Publications and source records attributed to T Zima.

At least 109 records · Page 6Linked to original sources

PubMed1994

[The effect of chronic administration of ethanol on experimental adriamycin nephropathy].

BACKGROUND: Alcoholic liver disease may be in humans frequently complicated by mesangial proliferation and sclerosis. The influence of chronic ethanol administration on experimental nephrotic syndrome has not been, however, studied yet. METHODS AND RESULTS: Experimental nephrotic syndrome was induced in rats by the i.v. administration of adriamycin in ethanol fed rats and in rats given common laboratory chow. Chronic administration of ethanol was in nephrotic rats accompanied by the exaggerated lipolysis (free fatty acids were in control nephrotic rats lower than in nephrotic ethylic rats 6 weeks after adriamycin administration: 914.8 + 96.8 mumol/l vs. 1186.3 + 178.7 mumol/l, p < 0.01) and increased proteocatabolism; the development of nephrotic syndrome was ameliorated, or at least delayed, however, in ethylic rats (control nephrotic rats had higher proteinuria than nephrotic ethylic rats 3 weeks after adriamycin administration: 5.79 + 3.15 vs. 0.55 + 0.34 g protein/mmol creatinine, p < 0.01). In autopsy, diffuse global glomerulosclerosis was found in control nephrotic rats with only mild focal and segmental changes in nephrotic ethylic rats. CONCLUSIONS: Chronic ethanol administration ameliorated and/or delays the development of nephrotic syndrome in adriamycin nephropathy in rats. Mechanism of this effect of chronic ethanol feeding remains to be elucidated. Metabolic, immunosuppressive and renal haemodynamic effects of ethanol should be taken into consideration.

Animals↗

PubMed1994

[Plasma volume in polycystic kidney disease].

Hypertension is a common and serious complication of autosomal dominant polycystic kidney disease (ADPKD), occurring early in the course of the disease. Disorders of tubular transport of sodium and increased plasma and blood volume (PV and BV), as a consequence, are thought to be involved in the pathogenesis of hypertension in ADPKD. In order to evaluate PV and BV in early stage of ADPKD, PV and BV were measured with radioactive serum albumin dilution technique. Three groups of subjects with normal glomerular filtration rate were studied: ADPKD hypertensive (ADPKD H, n = 10, age: 36.2 +/- 8.7 y), ADPKD normotensive (ADPKD N, n = 15, age: 33.4 +/- 7.4 y), and healthy volunteers (C, m = 8, age: 32.6 +/- 6.8 y). PV and BV expressed per kilogram of body weight did not differ among the 3 groups. When PV and BV were expressed per meter square of body surface area, diminished BV in the group ADPKD H in comparison to ADPKD N and group c (p < 0.05) was found, other parameters did not differ between the 3 groups. In conclusion--our results do not support the hypothesis of a significantly increased PV and BV of patients with ADPKD prior to the onset of hypertension.

Adult↗

PubMed1994

[Lithium clearance in polycystic kidney disease].

Disorders of tubular transport of sodium are thought to be involved in pathogenesis of cyst formation and development of hypertension in autosomal dominant polycystic kidney disease (ADPKD). Recently lithium has been proposed as a quantitative marker of proximal tubular reabsorption of sodium and lithium clearance as a method to analyze tubular sodium handling. To evaluate tubular sodium handling in early stage of ADPKD, lithium clearance (600 mg of Lithium carbonicum p.o.) was performed in a control group of pts. with ADPKD and normal glomerular filtration rate (n = 28), age 19.9 +/- 8.8 years) and in a control group of healthy volunteers (n = 43), age 30.3 +/- 9.0 years). Both groups did not differ in plasma or urine concentrations of electrolytes; plasma creatinine levels were slightly higher in ADPKD group than in controls (83.4 +/0 18.0 mumol/l vs. 93.4 +/- 24.2 mumol/l, p < 0.05). We did not demonstrate any statistically significant difference between the group of ADPKD and control group in lithium clearance and in fraction excretion of lithium (23.6 +/- 14.5 vs. 19.5 +/- 8.7 ml/min, resp. 15.3 +/- 8.8 vs 13.8 +/- 7.8%). Nor proximal tubular resorption of sodium, neither distal tubular resorption of sodium did differ between the group of ADPKD and control group (86.18 +/- 2.2 vs 84.7 +/- 1.80% resp. 94.7 +/- 2.6 vs. 94.5 +/- 3.6%). When comparing parameters of sodium handling between pts. with ADPKD and hypertension (6/28) and pts. with ADPKD without hypertension no difference was found. In conclusion, we could not demonstrate any statistically significant difference in tubular handling of sodium, when based on lithium clearance between the groups of ADPKD with normal glomerular filtration rate and control group.

Adolescent↗

PubMed1994

[Experimental models of polycystic kidney disease].

An overview of actually accepted hypothesis of etiology and pathogenesis as well as overview of experimentally induced models of autosomal dominant polycystic kidney disease (ADPKD) is presented. Though chemically induced renal cysts in rats and other small laboratory animals fed by antioxidants (diphenylamine and s.o.) represent the commonest experimental model, strains of animals with inherited cystic kidney disease were inbred too. Experimental works on tissue cultures derived from patients with ADPKD, which are aimed especially on study of epithelial changes (epithelial hyperplasia and s.o.), deserved special attention. On conclusion, advantages of the different models and next steps necessary to accomplish for understanding etiology and pathogenesis of ADPKD are indicated.

Animals↗

PubMed1994

Nephrotoxic effects of platinum cytostatics--preventative effects of nifedipine and cimetidine.

The study focuses on the observation of nephrotoxic effects of cis-platinum (cis-dichloro-diaminoplatinum, CDDP) and carboplatinum (cis-diamino-cyclobutancarboxyplatinum, CBDCP) and these to affect them by applying Ca-channel blocker (nifedipine) and a selective antagonist of tubular secretion of organic cations (cimetidine). The urine levels of tubular enzymes alkaline phospatase (AP), gamma-glutamyl-transferase (GMT) and N-acetyl-beta-D-glucosaminidase were selected for the evaluation or tubular toxicity. The clearance of endogenous creatinine was observed as well. The experiments were carried out on male rats of outbred Wistar strain within 7 days after the cytostatics had been applied. A significant increase of urine levels of all enzymes studied was observed in animals, which were given CBDCP only. A maximum change was observed in the urine excretion of NAG. Nifedipine application decreased the change significantly, cimetidine had no effect. The effect of combined nifedipine and cimetidine application did not vary from the effect of application of nifedipine itself. In animals given CDDP only, a significant increase of urine levels of all studied enzymes was proved, the maximum change was observed in NAG excretion. This change significantly decreased by nifedipine application. The same effect was reached by cimetidine application. Preventive effects of nifedipine and cimetidine potentiated mutually each other. In conclusion we consider nifedipine as a convenient prevention of CDDP and CBDCP nephrotoxic effects while cimetidine can be used as a prevention of CDDP nephrotoxic effect only.

Animals↗

PubMed1994

Xanthine oxidoreductase. Biochemical, biological and pathogenic functions.

Primary biochemical role of xanthine oxidoreductase (XOR, EC 1.1.1.204 and EC 1.1.3.22.) is the hydroxylation of hypoxathine and xanthine to form uric acid. This enzyme may produce very reactive oxygen forms which can be pathogenic. Although it is one of the longest known and most continuously studied enzymes, its biological function remains unclear. The review of these aspects is discussed in relation to the authors' experimental results.

Animals↗

PubMed1993

[The preventive effect of calcium-channel blockers (nifedipine, verapamil) on the tubular toxicity of radiographic contrast media (Verografin, Hexabrix)].

The authors investigated the nephrotoxic effect of the high-osmolar X-ray contrast medium (diatrizoate) and low-osmolar contrast medium (ioxaglate) and attempted to influence it by Ca channel blockers (nifedipine and verapamil). The criterium of tubular toxicity was the monitoring of urine wastes of tubular enzymes--alkaline phosphatase (ALP), gamma glutamyl transferase (GMT) and N-acetyl-beta-D-glucosaminidase (NAG). As criterium of glomerular functions he authors assessed the endogenous creatinine clearance. The experiments were made on outbred male rats Wistar strain for a total of 7 days following administration of the contrast medium. In animals to whom contrast medium only was administered a significant increase of urine waste of the investigated enzymes was observed. Maximum changes were recorded in the excretion of brushborder enzymes. Diatrizoate caused a significantly higher increase of enzymuria than ioxaglate. Administration of Ca channel blockers significantly reduced this rise of enzymuria, but the authors were unable to eliminate this rise completely. There were no statistically significant differences between the action of nifedipine and verapamil.

Acetylglucosaminidase↗

PubMed1993

[Rhabdomyolysis and acute renal failure].

Rhabdomyolysis is damage of the skeletal muscles due to different causes which leads to the release of the contents of muscle cells into the blood stream and conversely to the penetration of water and other substances into muscles via the damaged membrane. This initiates many processes which damage the organism: hypovolaemia, hypocalcaemia, hyperkalaemia, hyperuricaemia, disseminated intravascular coagulation, renal failure. Renal failure in particular is a frequent and very serious complication. However, when correct treatment is provided, it is usually reversible. The diagnosis and differential diagnosis is not difficult if the possible presence of rhabdomyolysis is considered. Therapy involves in particular supplementation of the vascular volume and forced diuresis.

Acute Kidney Injury↗

PubMed1993

[Acute kidney failure associated with rhabdomyolysis].

The authors describe three cases of rhabdomyolysis and acute renal failure. In all patients rhabdomyolysis developed in conjunction with ingestion of alcohol, in two moreover in combination with compression of an extremity by body weight during prolonged immobility. One patient was hospitalized on the day when rhabdomyolysis developed, the second one more than 24 hours after and the third one only several days after development of the condition. In none of them the diagnosis was established before the development of renal failure. All were subjected repeatedly to haemodialysis. One patient died from a complication--embolism of the brain--the remaining two patients recovered without sequelae. In the discussion the authors deal with reasons of late diagnosis of the disease.

Acute Kidney Injury↗

PubMed1993

Diagnosis and treatment of carpal tunnel syndrome.

Secondary amyloidosis is a complication typical for patients on long-term hemodialysis. The first clinical signs are usually shoulder joint pain and carpal tunnel syndrome (CTS). We have questioned 74 patients who were on regular hemodialysis (HD) treatment and divided them into 3 groups according to the length of HD. Group 1--on HD for 1-4 years: There were 35 patients in this group, 15 of them (i.e., 43%) had shoulder joint pain and/or CTS. None of these patients had symptoms that would require surgical treatment. Group II--on HD for 5-9 years: There were 22 patients in this group, 15 of them (i.e., 68%) had shoulder joint pain and/or CTS. Three patients from this group had severe night pain and were therefore indicated for surgical treatment for CTS, each of them on 1 hand only. In 2 cases amyloid was present in the histological examination. Group III--on HD for over 10 years: There were 17 patients in this group, 13 of them (i.e., 76%) had shoulder joint pain and/or CTS. Five patients from this group were operated on both hands for severe night pain due to carpal tunnel syndrome. Only 1 patient had positive amyloid on both hands in the histological examination. All the 8 patients (i.e., 13 hands) were examined by EMG before the operation, showing reduction of motor conduction on n. medianus by 30.7 +/- 15.1%. After the operation the EMG control was done in 4 patients (7 hands), showing no improvement in 2 cases and in 5 cases the conduction on the n. medianus was found to be in the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Amyloid Neuropathies↗

PubMed1993

[Ethanol metabolism and pathobiochemistry of organ damage--1992. I. Metabolism of ethanol by alcohol dehydrogenase, cytochrome P450IIE1 and catalase].

Three metabolic pathways of ethanol in human body have been described thus far: 1) alcohol dehydrogenase (ADH), 2) microsomal oxidizing ethanol system (MEOS), 3), catalase. The main role in alcohol metabolism is being payed by cytosolic enzyme, alcohol dehydrogenase, which catalyses metabolism of ethanol to acetaldehyde. It occurs in many dimeric isoenzyme forms which are divided into three classes, according to substrate specifics and other chemical-physical properties. ADH is regulated by development and sex, its activity has been described in many tissues (liver, stomach, kidneys, ovaria, uterus, testes, retina, iris). In 1991 Yoshida found a new gene of alcohol dehydrogenase-ADH 6. 4-hydroxyalkenals, cytotoxic products of lipid peroxidation, are also substrates of ADH. Acetaldehyde is further metabolised by aldehyde dehydrogenase (AIDH) to acetate. AIDH occurs in the form of several isoenzymes in cytosole, mitochondria and microsomes of almost all tissues. Acetaldehyde thus binds to nucleic acids, phospholipids and especially to proteins, it may change their structure and function. In activates collagen synthesis and stimulates lipid peroxidation. Human body may be impaired by immune reaction caused by acetaldehyde binding proteins. Acetaldehyde has the function of a hapten. In 1968 Lieber and DeCarli described microsomal ethanol oxidizing system (MEOS). MEOS is one of cytochrome P450 isoenzymes, now called P450IIE1. Having a gene on chromosome 10, composed of 492 amino acids, this isoenzyme is present in cytoplasmatic reticulum. It is inducible and in case of chronic alcoholism, it accelerates elimination of ethanol from the human body. Inducted P450IIE1 is also present in Kupffer cells which participate in fibrogenesis of liver tissue and produce interleukin 1.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Dehydrogenase↗

PubMed1993

[Ethanol metabolism and pathobiochemistry of organ damage--1992. II. Relation between ethanol metabolism and free radicals, and the metabolism of saccharides and amino acids. Ethanol as a carcinogen. Drug interactions with ethanol].

Ethanol metabolism induces formation of free radicals which are responsible for lipid peroxidation of biological membranes with subsequent aldehyde formation (malondialdehyde,4-hydroxy-nonenal). These aldehydes are competitive or mixed inhibitors of aldehyde dehydrogenase, and they cause an increase in hepatocellular toxicity of aldehydes. The activity of antioxidative systems in human body after chronic as well as acute ethanol intake is being reduced. Interference of ethanol metabolism and gluconeogenesis is caused by inhibition of intake substrates or by decrease NADH/NAD+, ratio in hepatocyte. The blood level of glucose decreases, lactate level increases as well as the ration of lactate, pyruvate and NADH/NAD+ which inhibit cytosole pyruvate carboxykinase. An acute ethanol administration reduces the concentration of most amino acids in plasma by ethanol oxidation impacts on increase of NADH/NAD+ ratio or by mechanism mediated by beta-adrenergic receptors. Chronic alcoholics develop tolerance to decreased plasmatic levels of amino acids. Accumulation of proteins in liver may be explained by larger amount of proteins binding to fatty acids, and also by diminished degradation of proteins with decreasing autophagosome and autolysosome formations. Alcohol is one of carcinogenic factors. Ethanol, acetaldehyde and originating free radicals impaired the DNA repairing enzyme. Binding itself to DNA, acetaldehyde changes DNA properties. Ethanol may also function as a co-carcinogen due to its ability to increase disolution and absorption of carcinogens. Chronic alcoholism induces cytochrome P450 which takes part in the activation and metabolism of carcinogens. Mutual interaction of drugs metabolism and ethanol is connected mainly with cytochrome P450-MEOS. Acute ethanol intake inhibits MEOS, as MEOS gives preference to ethanol as a substrate, however, chronic alcoholism induces MEOS.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

PubMed1993

[Ethanol metabolism and pathobiochemistry of organ damage--1992. III. Mechanisms of damage to the gastrointestinal tract and the liver by ethanol].

Alternations of stomach mucose caused by ethanol are in direct correlation with its concentration. ADH in stomach mucose is an efficient barrier against ethanol system toxicity. It stimulates higher secretion of HC1, dilutes protective barrier of mucose and phospholipids in membranes. Inflammatory reaction also participates in the damage of stomach mucose, with a share of products of arachidonic metabolism and free radicals. After ethanol administration the pancreas blood circulation diminishes and resistance in microcirculation increases. This can cause necroses in periphery of lobules. Activated phospholipase C may result in hypersecretion of Ca2+ dependent proteinkinases. Ischemic changes participate in alcohol impairment of pancreas and increase its vulnerability to enzyme attract and free radical reactions. Ethanol excesses may result in diarrhoea, dyspepsia, malnutrition and cause morphologic alternations of intestinal mucose (erosion, hemorrhagia). Absorption of nutrients and vitamins is affected by inhibition of active transport or by decrease of enzyme activity. Ethanol increases mucose permeability, alteres intestinal motility and damages absorption of water and electrolytes. In chronic alcoholics lower villi and changes in bacterial flora are described. The following mechanism of ethanol caused liver injury are observed: acetaldehyde toxicity, change in NAD+/NADH ratio connected with acidosis, cytoskeletal impairment, inhibition of protein synthesis and their secretion, relative perivenular hypoxia, activation of fibrogenesis, increased formation of free radicals with lipid peroxidation and immunological reaction. In hepatocyte there are morphological changes (megamitochondria, etc.) and functional changes (inhibition of glycolysis, inhibition of Krebs cycle and beta oxidation of fatty acids). Ethanol intake activates leukocytes, trombocytes, endothelial and Kupffer cells and their mediators, which result in increase of collagen and proteoglycans synthesis furthermore in fibrotic changes in liver.

Alcoholism↗

PubMed1993

[Ethanol metabolism and pathobiochemistry of organ damage--1992. IV. Ethanol in relation to the cardiovascular system. Hematologic, immunologic, endocrine disorders and muscle and bone damage caused by ethanol. Fetal alcohol syndrome].

Peripheral vasodilatation with increased cardiac output, tachycardia and increased blood pressure are described after alcohol administration. An increased HDL-cholesterol is found in moderate drinkers (both HDL-2 and HDL-3 fractions), with diminishing risk of coronary heart diseases. Acute ethanol intake causes an increased the level of triglycerides without changes in HDL-cholesterol level. This may be put into correlation with higher incidence of cardiovascular diseases in so-called "week-end" drinkers. Alcohol abuse may result in central diabetes insipidus. An increased elimination of lactate diminishes tubular secretion of uric acid with subsequent secondary hyperuricemia. Ethanol reduced the number of lymphocytes, reduces phagocytosis by macrophages and diminishes the activity of NK-cells. Bone marrow cellulity diminishes with the subsequent reduction in erythropoiesis, trombopoiesis and leukopoiesis. Alcohol may cause sideropenic and megaloblastic anemia. There are two forms of alcohol muscle injury: the acute one, with myonecrosis and inflammatory reaction, and chronic one, with muscle weakness and atrophy. Alcohol is one of etiologic factors of osteoporosis. An acute intoxication result in transitory hypoparatthyreoidism, while chronic ethanol intake make grow the PTH level and decreases the level of D vitamin metabolises. Stimulation of cortisol secretion, decrease of testosterone level and a reversible decrease of T3 and T4 levels have been described following ethanol administration. Hypothalamic-pituitary-adrenal axis suffers alteration in alcoholics, and secondary amenorrhea is observed in female alcoholics. Ethanol behaves as an agonist on GABA receptor. Fetal alcohol syndrome together with Down's syndrome and spina bifida are the most frequent reasons of mental retardation in developed countries. Toxicity of ethanol affects the whole pregnancy period.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcoholism↗

PubMed1993

Plasma xanthine oxidase level and alcohol administration.

The acute administration of ethanol by gastric catheter significantly increases the plasma xanthine oxidase activity in both rats and hamsters without changing other enzyme activities--alanine aminotransferase and aspartate aminotransferase. The plasma xanthine oxidase level seems to be a sensitive marker of liver damage. Its higher activity due to the acute ethanol intoxication may have an impact on ethanol organ damage.

Alanine Transaminase↗

PubMed1993

Lipid peroxidation on dialysis membranes.

The aim of this study was to compare the changes of lipid peroxidation during haemodialysis (HD), using various types of dialyser membranes. A significantly higher concentration of total and free TBARS (thiobarbituric acid reacting substance) was found in blood and in plasma of HD patients, compared with the control group of blood donors. During the HD session the TBARS levels grow significantly, compared to the initial levels on both membranes (Alpha 500, Pro500), and are significantly higher after 15 min of HD on Alpha 500 membrane. The levels of TBARS appear to be significantly higher in patients on regular HD treatment, which may be due to a more intensive lipid peroxidation. There were significant acute changes in lipid peroxidation during one HD session. The changes in lipid peroxidation differ with the use of various HD membranes.

Adult↗

PubMed1992

Protective effects of verapamil on cis-platinum and carboplatinum nephrotoxicity in dehydrated and normohydrated rats.

The aim of the study was to compare the nephrotoxic effects of cis-platinum (CDDP) and carboplatinum (CBDCA) and the protective potential of verapamil in rats. CDDP (3 mg/kg) and CBDCA (60 mg/kg) were administered intraperitoneally in a single dose on day 1. Verapamil (0.1 mg/kg) was administered 30 min before i.p. injection. Rats were assayed daily for urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), alkaline phosphatase (AP) and gamma-glutamyl-transferase (GMT), on day 3 they were assayed for creatinine clearance. CBDCA appears to be less nephrotoxic than CDDP. Verapamil shows protective effects against the nephrotoxicity of platinum derivatives in both groups of rats.

Acetylglucosaminidase↗

PubMed1992

[The effect of bleeding on blood alcohol levels in an experimental model].

There are factors changing kinetics of alcohol turnover in comparison to widely accepted norm comprise e.g. effect of stomach contents on resorption of ethanol, activity of ethanol metabolizing enzyme systems, and hydration of organism (blood volume). One of possible factors--effect of bleeding on alcohol blood level--was studied in rats. Blood alcohol levels were significantly higher in a group of rats where bleeding is one hour after ethanol administration than in a group with bleeding before ethanol administration, and than in controls devoid of bleeding. That's question, this results may be applicable to man.

Animals↗