PubMed Health⌕ Search

Biomedical subjects

C Varga

Publications and source records attributed to C Varga.

At least 37 records · Page 2Linked to original sources

Effects of testosterone on the rat renal medullary vasopressin receptor concentration and the antidiuretic response.

The renal concentrating ability declines with age in humans and animals. Studies suggest that the concentrating defect is due to a decrease in renal vasopressin sensitivity. With ageing, expression of the renal vasopressin V2 receptor in rat is impaired; the normal receptor expression is restored by testosterone treatment. The effect of testosterone on the renal sensitivity to vasopressin was investigated in young rats. Male rats after orchidectomy and chronic antiandrogen cyproterone acetate treatment, and female rats after chronic testosterone phenylpropionate treatment, were used. The plasma arginine-vasopressin (AVP) and testosterone concentrations, and the antidiuretic responses to AVP and the V2 agonist deamino-[8-D-arginine]-vasopressin (dDAVP) after volume loading were measured, and the renal [3H]AVP binding density was determined. The plasma AVP level decreased slightly, but not significantly, in male rats after orchidectomy and cyproterone acetate treatment, but did not alter in female rats after testosterone treatment. The AVP and dDAVP sensitivities decreased in male rats after orchidectomy and cyproterone acetate administration, and increased in female rats treated with testosterone, as compared with the animals with a normal gonadal function. [3H]AVP binding to the renal inner medullary membranes was decreased following orchidectomy or antiandrogen treatment in male rats, and increased in testosterone-treated female rats. The results suggest that testosterone may play a physiological role in maintenance of the V2 vasopressin receptor expression and hence in the normal urinary concentrating ability in rat.

Androgen Antagonists↗

Urinary and serum mutagenicity studies with rats bearing experimental tumours.

Urine and serum samples of rats bearing three different experimental tumours (hepatocellular carcinoma, myelomonocytic leukemia and mesoblastic nephroma) were investigated for mutagenicity with the Ames Salmonella test. Enhancement of mutagenic activity in TA98 and TA100 was observed only in the case of urine samples obtained from animals bearing nephromas. Mutagenicity increased with increasing time after implantation of tumours. There was no coincidence between urinary and serum mutagenicity under the experimental conditions employed. Further studies are needed to determine the origins, and chemical and genotoxic characteristics of urinary mutagens. In addition, the question as to whether any mutagenic substances can be detected in fractions of plasma/serum should also be experimentally addressed.

9,10-Dimethyl-1,2-benzanthracene↗

Genotoxicity studies on urine and bone marrow samples of rats bearing transplanted nephroma.

It was demonstrated earlier that urine of rats bearing transplanted mesoblastic nephroma had high mutagenic activity in Salmonella typhimurium, which could not be detected in serum samples of the same animals. In this paper, cytogenetic alterations are discussed and the lack of enhanced micronucleus formation in bone marrow of tumorous rats is described. The cytogenetic effect of the hydrophobic (XAD-4) urinary fraction, which has been found to be mutagenic in the TA98 Salmonella strain, was examined in CBA mice. Sister chromatid exchange (SCE) analyses were performed on bone marrow cells of animals treated with single injections of concentrated urine samples. Significant and continuous increases could be detected in the SCE frequencies caused by the urinary concentrates with development of the tumour. Pseudouridine, a suggested urinary tumour marker nucleoside, was also studied for mutagenicity in the Ames Salmonella test. Both derivatives (alpha and beta), however, failed to induce mutations in the TA98/TA100 strains, either with or without metabolic activation. In conclusion, urinary mutagen(s) produced during the renal tumour growth have a spectrum of genotoxicity involving at least two endpoints, but the high pseudouridine excretion may not be responsible for these effects.

Animals↗

Aggressive role of vasopressin in development of different gastric lesions in rats.

The effects of endogenous or exogenous vasopressin in models of gastric mucosal injury with a different pathophysiology (ethanol, indomethacin, reserpine, cold-restraint stress and haemorrhagic shock-induced lesions) were investigated in rats. [Mca1,TyrMe2,Arg8]vasopressin, a vasopressin pressor (V1) receptor antagonist, was found to reduce dose dependently the extent of the lesions in all models, and to protect the deeper layer of the mucosa (assessed by histology). Endogenous vasopressin deficiency, as in Brattleboro homozygous rats, had a similar effect. [Lys8]Vasopressin injected exogenously aggravated all types of lesions in normal rats. Circulating vasopressin levels were increased by ethanol, reserpine, cold-restraint stress and haemorrhagic shock, but not by indomethacin, whereas the intramucosal vasopressin content was found to be elevated in all models. Additionally, specific binding sites for vasopressin were shown on the blood vessels of the gastric mucosa (assessed by autoradiography). It is concluded that vasopressin plays a significant aggressive role in the generation of these types of lesions.

Animals↗

The separation of the granulocytes from different rat strains. A comparative study.

Different Percoll density gradients were used to purify granulocytes from Long-Evans, Fischer, Sprague-Dawley, and Fischer/Long-Evans hybrid rats. Three different discontinuous gradient types were developed which permitted the separation of polymorphonuclear leukocytes (PMNLs) from the peripheral blood of the different rat strains. Our purification techniques were compared to each other in terms of purity and yield. Purities of 97.7 +/- 0.6%, 97.0 +/- 1.1%, 96.4 +/- 1.2% and 96.7 +/- 1.1% were achieved for the granulocyte fractions of LE, F344, SD and FL/F1 rats, respectively. The superoxide production of the isolated cells was also investigated and it was established that the granulocytes could be activated by phorbol-12-myristate-13-acetate (PMA).

Animals↗

Difference between male and female rats in vasopressor response to arginine vasopressin.

A study was carried out how the sexual difference influences the increase in blood pressure (BP) induced by arginine vasopressin (AVP), and how the binding characteristics of 3H-labelled AVP on membranes prepared from the vascular bed were affected. After the administration of various doses of AVP, a significantly higher BP increase was observed in male rats than in females. The vasopressor effect of AVP was reduced in males following orchidectomy or administration of the antiandrogen cyproterone acetate. The vasopressin (VP) antagonist d(CH2)5Tyr(Me)AVP diminished the BP response to AVP in both sexes. The plasma AVP level was found to be much higher in males than in females, but it was decreased to the level of females after orchidectomy. The density of AVP-binding sites in the aorta membrane preparation was smaller in females, and in orchidectomized or cyproterone acetate-treated male rats than in the control males. The results demonstrate that testosterone upregulates the number of AVP-binding sites, leading to an increase in the pressor response to AVP in the rat vascular bed.

Animals↗

Biological activities of some new arginine vasopressin analogues containing unusual amino acids.

Solid-phase synthesis methods were applied to prepare some arginine vasopressin (AVP) analogues containing L- or D-pipecolic acids or alpha-L-homoproline in position 7, D-Cys in position 6, D-Val in position 4, O-alkylated D- or L-Tyr in position 2 and Pmp [1-(beta-mercapto-beta, beta-cyclopentamethylidenepropionic acid)] in position 1. Antidiuretic, vasopressor, antidiuretic antagonist and vasopressor antagonist activities were measured by biological methods. Antidiuretic effects were observed for all analogues. Pip7-AVPPmp1D-Tyr(Et)2D-Val4AVP and Mpa1dGly-NH-CH3(9) AVP had higher antidiuretic activities than that of AVP. None of the analogues exhibited an antidiuretic antagonist effect. With the exception of Pip7-AVP, none of the analogues had a vasopressor effect. Small vasopressor antagonist effects were found for DPip7AVP and Mpa1, DPip7AVP. The pharmacological significance of these new AVP analogues and the relationship between the chemical structure and biological activity are discussed.

Amino Acids↗

Influence of sex hormones on ethanol-induced gastric haemorrhagic erosions in rats.

The role of sex hormones in the pathogenesis of ethanol-induced gastric erosions was investigated following the recent observation that ethanol generates more severe gastric damage in male rats. Female and male Wistar rats aged 110 +/- 6 days were used. Intact female, ovariectomized female, intact male, orchidectomized male and cyproterone acetate-pretreated (this compound a testosterone antagonist) male rats were investigated. 1 ml of 75% ethanol was used to induce gastric lesions. The extent of the erosions was determined planimetrically 60 min after ethanol administration. The plasma testosterone and 17-beta-oestradiol levels were checked by radioimmunoassay (RIA) in gonadectomized rats. Ethanol generates more severe lesions in male rats. Orchidectomy and cyproterone acetate treatment each reduced the extent of ethanol-induced gastric erosions in male rats. Ovariectomy had no effect in this model. The plasma testosterone and 17-beta-oestradiol levels were significantly reduced after gonadectomy. It is concluded that endogenous testosterone plays an aggressive role in the pathogenesis of ethanol-induced gastric erosions in rats.

Animals↗

Comparative studies on genotoxic and carcinogenic effects of different cytostatic protocols. I. In vivo cytogenetic analyses in CBA mice.

In vivo rodent cytogenetics may provide an important basis for an animal model for the assessment of the carcinogenic potential of antitumor drugs in man. In this paper, genotoxic alterations (i.e. sister chromatid exchanges and micronuclei) caused by different cytostatic protocols in CBA/Ca mice are described. The strongest sister chromatid exchange inducing effects were shown by the ABVD (doxorubicin-dacarbazine-bleomycinvinblastine) group and combinations containing cyclophosphamide. Compounds which affect the mitotic spindle induced only micronuclei, but not sister chromatid exchanges.

Animals↗

Prevalence of gallstones in liver cirrhosis: a sonographic survey.

A sonographic prospective study of the prevalence of gallstones was performed in 140 patients with liver cirrhosis and in 140 controls. Gallstones were found more often in cirrhotic patients (29.2%) than in controls (13.6%) (p less than 0.01). Their prevalence increased with age. The ratio of women to men in cirrhotics was the same as in the general population, with a higher prevalence in women. The prevalence of gallstones increased in decompensated liver disease. There was a significantly higher prevalence of both hypersplenism and hemolysis in cirrhosis. No difference was found in gallstone prevalence in relation to cirrhosis etiology. This prospective study confirms, by means of sonography, the high prevalence of cholelithiasis in liver cirrhosis, and extends the previous data about the lithogenic risk factors in this disease.

Adult↗

Vasopressin deficiency decreases the frequency of gastroduodenal ulceration in humans.

Vasopressin is a stress hormone released from the posterior pituitary. In humans suffering from central diabetes insipidus, this release of vasopressin is diminished. It was shown previously that the congenitally vasopressin-deficient Brattleboro homozygous rat is less sensitive to various ulcerogenic stimuli. In this study, we investigated the incidence of gastroduodenal ulceration in vasopressin deficient patients. Data on patients aged 20-70, hospitalized in Hungary between 1992 and 1995 were compared with those on the total population in this age group (6,681,020 in 1994). Subjects with central diabetes insipidus were selected separately (815 cases). Gastroduodenal ulceration was compared in subjects with an intact vasopressin release and vasopressin-deficient patients. The frequencies of gastroduodenal ulceration were also examined separately in male and female subjects. In the total population, the frequency of gastroduodenal ulceration was lower in vasopressin-deficient cases (2.22% versus 0.61%; P < 0.005). Among normal-vasopressin subjects, males have a higher risk of gastroduodenal ulceration than females (3.04% versus 1.46%, respectively; P < 0.001). Among vasopressin-deficient subjects, a similar male:female ratio was observed, but it was not significant (P = 0.36). In comparison to the normal-vasopressin population, the incidence of gastroduodenal ulceration was reduced among vasopressin-deficient males and females by 77% (P < 0.01) and by 82% (P < 0.05), respectively. In conclusion, endogenous vasopressin has a significant harmful action towards the human gastroduodenal mucosa. Peptide and non-peptide vasopressin receptor antagonists might have a potential therapeutic benefit in the treatment (as an adjuvant) and prevention of gastroduodenal ulceration.

Adult↗

Further prove on oxidative stress in alloxan diabetic rat tissues.

After intravenous administration of alloxan monohydrate (AL) diabetes developed in rats. Forty-eight hours after the injection the animals were sacrificed, their blood was collected in heparin containing tubes and the tissues were dissected and frozen (-70 degrees C) until their homogenization for pro- and antioxidant testing. Our results can be summarised as follows: (i) In the blood hemolysate the lipid peroxidation slightly elevated and the activity of antioxidant enzymes and reduced glutathione decreased. (ii) Similar phenomena could be observed in the different examined organ homogenates. The organs tested for pro- and antioxidant system were as follows: the liver, heart, skeletal muscle, kidney and pancreas. In our present work we attempt to confirm the data in support of the oxidative predominance over antioxidants in oxidative stress of AL diabetic rats.

Animals↗