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C Varga

Publications and source records attributed to C Varga.

At least 19 recordsLinked to original sources

Estrogen-induced region specific decrease in the density of 5-bromo-2-deoxyuridine-labeled cells in the olfactory bulb of adult female rats.

Effects of chronic estrogen treatment on the survival rate of newly integrated interneurons were studied in the olfactory bulb of adult (250-300 g) female rats. Ovariectomized rats received 17-beta estradiol dissolved in sesame oil (i.p., 100 microg/100 g body weight [b.w.]) during six consecutive days, and on day 6 they were also injected with the mitotic marker 5-bromo-2-deoxyuridine (BrdU, i.p., 50 mg/kg b.w.) in every 2 hours during 8 hours. After 21 days of survival animals were killed and the density of BrdU-immunoreactive cells was analyzed in the granule cell and glomerular layer both in the main and accessory olfactory bulb. A significant decrease was found in the density of BrdU-labeled cells in both layers examined in the accessory olfactory bulb of ovariectomized and estradiol-treated rats when compared with those of ovariectomized and vehicle-treated animals. In the main olfactory bulb, in contrast, no difference was observed in the density of BrdU-immunoreactive cells in either of the two layers. Our results suggest that cells destined to the glomerular and granule cell layers react in the same way to chronic estrogen treatment, and the effect of estradiol is region specific, at least, within the olfactory bulb. 17-Beta estradiol reduces the density of newly generated cells in the accessory olfactory bulb, an area involved in the perception of pheromones, thus having a role in regulating sexual behavior, while the rate of integration and survival of newly born cells in the first relay station of the main olfactory pathway, i.e. the main olfactory bulb, remains unchanged.

Analysis of Variance↗

Effects of dopamine and dopamine-active compounds on oxytocin and vasopressin production in rat neurohypophyseal tissue cultures.

The effects of dopamine (DA) or DA-active drugs on the synthesis of neurohypophyseal (NH) hormones were studied in 13-14 day cultures of isolated NH tissue from rats. The following DA-active compounds were used (10(-6) M in each medium): DA, apomorphine (APM), Pro-Lys-Gly (PLG), butaclamol (B), haloperidol (HP), chlorpromazine (CPZ) and sulpiride (SP). The oxytocin (OT) and vasopressin (VP) contents of the condensed media were determined by RIA after a 1 or 2 h incubation. Significantly increased contents of OT and VP were detected in the tissue culture media following DA, APM or PLG administration. This elevation of NH hormone production could be blocked by previous administration of B or the DA receptor antagonists HP, CPZ or SP. The application of B after DA agonists proved ineffective. The results indicate that NH hormone production can be directly influenced by the DA-ergic system. The DA-ergic control of NH hormone secretion in rats can occur independently of the hypothalamus, at the level of the posterior pituitary.

Animals↗

Vasopressin pressor receptor-mediated activation of HPA axis by acute ethanol stress in rats.

The plasma arginine vasopressin (AVP), ACTH, and corticosterone levels and the hypothalamic corticotropin-releasing hormone (CRH) content were measured after oral administration of 1 ml of 75% ethanol to rats, a model known to induce acute gastric erosions and stress. Elevated plasma AVP, ACTH, and corticosterone levels were detected 1 h after ethanol administration. Treatment with the vasopressin pressor (V(1)) receptor antagonist [d(CH(2))(5)Tyr(Me)-AVP] before ethanol administration significantly reduced the ACTH and corticosterone level increases. A higher hypothalamic CRH content was measured at 30 or 60 min after ethanol administration. V(1) receptor antagonist injection, 5 min before ethanol administration, inhibited the rise in hypothalamic CRH content. The protein synthesis blocker cycloheximide prevented the hypothalamic CRH content elevation after stress. The AVP-, CRH-, and AVP + CRH-induced in vitro ACTH release in normal anterior pituitary tissue cultures was also prevented by pretreatment with the V(1) receptor antagonist. The results support the hypothesis that stress-induced AVP may not only act directly on the ACTH producing anterior pituitary cells but also indirectly at the hypothalamic level via the synthesis and release of CRH.

Adrenocorticotropic Hormone↗

Maximizing liver transplantation from non-heart-beating donors.

In order to increase the supply of transplantable organs, an increasing number of organ procurement organizations are adopting policies regarding donations from non-heart-beating donors. Few centers, however, actually recover and transplant these organs. This article reviews a case in which kidneys and livers imported from out of state were successfully recovered from a non-heart-beating donor and transplanted. In addition, the article demonstrates how cooperation and flexibility in transplant personnel can increase the number of organs transplanted from a non-heart-beating donor.

Adolescent↗

On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: II. Tissue specificity studies using comet assay.

Epidemiological data seem to be equivocal on the probable increase in cancer incidence in populations exposed to asbestos-fibre contaminated drinking water. Although animal experiments failed to demonstrate carcinogenicity of oral asbestos exposure, the large surface area of the fibres, however, creates the possibility of cogenotoxic action with adsorbed water-borne organics. In our animal model, rats were gavaged with untreated UICC crocidolite and anthophyllite fibres and fibres that had been allowed to adsorb benzo[a]pyrene molecules from aqueous solutions. Peritoneal macrophages and intestine, parietal peritoneum and omentum samples were obtained from the animals after 24 h. The alkaline single-cell microgel electrophoresis assay (comet assay) was performed on cells isolated from the solid tissues. Tail moment was applied as a basis of evaluation following image analysis. Our results indicate high levels of DNA strand breaks in the cells prepared from the omentum and intestine. We could also demonstrate a significant potentiating effect of the adsorbed carcinogen on the induction of DNA damage in the omentum. The parietal peritoneum and macrophages were not involved in the early genotoxic alterations under study. Our results support the molecular model of asbestos cocarcinogenesis, including both asbestos-induced deletions and mutations caused by a mutagen carried by the same fibres.

Animals↗

Synthesis of oxytocin antagonists containing conformationally constrained amino acids in position 2.

Analogues of oxytocin containing D-Trp, 2-amino-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid (Atc) or 1,2,3,4-tetrahydro-beta-carboline-1-carboxylic acid (Car) with R or S configurations in position 2 were synthetized, and their receptor bindings were tested on isolated guinea-pig uterus, rat liver and rat kidney inner medulla plasma membranes. The peptides were synthetized in the solid phase by using racemates of Car and Atc. The resulting diastereomeric mixtures were separated by means of RP-HPLC. The binding to the oxytocin receptor was somewhat decreased for the Atc isomers and dramatically decreased for both R- and S-Car, while the D-Trp-containing analogue displayed a relatively high receptor affinity. However, the V1 receptor affinities were almost the same as those of the parent peptide for the Car-containing analogues and dramatically decreased for the S-Atc substituted analogue, which has a relatively high OT/V1 receptor selectivity of 44.5.

Animals↗

Vasopressin receptor antagonist OPC-31260 prevents cerebral oedema after subarachnoid haemorrhage.

The effects of the non-peptide vasopressin V2 receptor antagonist, 5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrah ydro-1 H-benzazepine hydrochloride (OPC-31260) on the cerebral oedema induced by subarachnoid haemorrhage were studied in rats. Subarachnoid haemorrhage induced significant water retention after water loading, increased the brain content of water and Na+ and increased plasma vasopressin levels. The water retention and brain water and Na+ accumulation were prevented by OPC-31260 administration, but the plasma vasopressin levels were further enhanced by OPC-31260. These results demonstrate the important role of vasopressin in the development of antidiuresis and disturbances in brain water and electrolyte balance in response to subarachnoid haemorrhage. The subarachnoid haemorrhage-induced cerebral oedema was significantly reduced following oral OPC-31260 administration. The protective mechanism exerted by OPC-31260 stems from its influence on renal tubular function: it blocks the renal vasopressin V2 receptors. These observations might suggest a new, effective approach to the treatment of subarachnoid haemorrhage-induced cerebral oedema in humans.

Animals↗

Dual effect of female sex steroids on drug-induced gastroduodenal ulcers in the rat.

Since the sexual dimorphism of gastroduodenal ulcers is well known and might possibly relate to the actions of sex hormones, we studied the role of the female sex steroids, progesterone and 17beta-estradiol in cysteamine-induced mucosal ulcers in female Wistar rats (200-220 g). Administration of cysteamine (400 mg/kg, s.c.) provoked macroscopic gastroduodenal mucosa injury as assessed planimetrically, an increase in microvascular permeability in the stomach and the duodenum as assessed by extravasation of radiolabelled albumin, and decreased gastroduodenal mucus levels as assessed by the Alcian blue technique. Ovariectomy (2 weeks before cysteamine) decreased plasma 17beta-estradiol level as assessed by radioimmunoassay, gastroduodenal macroscopic injury and albumin extravasation, and increased mucus levels following cysteamine challenge. Administration of progesterone (10-50 mg/kg/week, s.c.) attenuated in a dose-dependent manner cysteamine-induced gastroduodenal mucosa injury and microvascular leakage, while it increased mucus levels in the stomach and the duodenum. In contrast, administration of 17beta-estradiol (1-5 mg/kg/week, s.c.) dose-dependently augmented gastric and duodenal macroscopic mucosa lesions and microvascular injury provoked by cysteamine, and caused a further reduction in gastroduodenal mucus levels observed after cysteamine administration. In different experiments, ovariectomy decreased indomethacin-induced gastroduodenal injury. The injection of 17beta-estradiol (1-5 mg/kg/week) did not affect gastroduodenal damage, while treatment with progesterone (10-50 mg/kg/week) protected against indomethacin-provoked mucosa ulcers. It is concluded that female sex steroids play a role in drug-induced gastroduodenal ulcers by modulating microvascular permeability and mucus secretion.

Animals↗

Detrimental effects of oestradiol on cysteamine-induced gastroduodenal ulceration in the female rat.

The actions of the female sex steroid, oestradiol on cysteamine-induced mucosal ulceration has been evaluated in female Wistar rats. Administration of cysteamine (400 mg x kg(-1), s.c.) provoked macroscopic gastroduodenal mucosal injury (assessed planimetrically) and an increase in microvascular permeability (assessed by the extravasation of radiolabeled albumin) in the stomach and duodenum, determined 24 h later. Ovariectomy (2 weeks before cysteamine) reduced gastroduodenal macroscopic injury, and albumin extravasation following cysteamine challenge. Administration of oestradiol (1-5 mg x kg(-1), as an i.m. depot 1 week before cysteamine) dose-dependently augmented gastric and duodenal macroscopic mucosal lesions and microvascular permeability provoked by cysteamine. These findings indicate that oestradiol can exacerbate gastroduodenal ulceration and microvascular injury.

Animals↗

Endogenous vasopressin increases acute endotoxin shock-provoked gastrointestinal mucosal injury in the rat.

Administration of a low dose of endotoxin (from Escherichia coli, 3 mg kg(-1), i.v.), which does not affect vascular permeability or blood pressure over 1 h, leads to the release of endogenous vasopressin and damage to the mucosal microvasculature. Thus, endogenous vasopressin could be involved in septic shock. In the present study, we investigated the role of endogenous vasopressin in gastrointestinal mucosal injury induced by acute endotoxin shock, which was generated in rats by administering a high dose of E. coli endotoxin (50 mg kg(-1), i.v.). Tissues were removed 15 min after endotoxin. The vasopressin V1 receptor antagonist, d[CH2]5Tyr[Me]arginine-vasopressin (0.2-1 microg kg(-1), i.v.), was injected 10 min before endotoxin. Monastral blue (30 mg kg(-1), i.v.), which stains damaged vasculature, was injected 10 min before autopsy. Endotoxin reduced systemic arterial blood pressure (from 115+/-5 to 42+/-4 mmHg), generated macroscopic and microvascular injury, and elevated plasma vasopressin levels (from 3.4+/-0.2 to 178+/-16 pg ml(-1)). The vasopressin V1 receptor antagonist reduced this macroscopic injury, and in the vasopressin-deficient Brattleboro rat a similar reduction of gastrointestinal mucosal damage was found. Substantial decreases in endotoxin-induced microvascular damage were observed in each tissue, e.g., the gastric Monastral blue staining was reduced by 47+/-3% and 96+/-3% (P < 0.01) after vasopressin V1 receptor antagonist treatment and in Brattleboro rats, respectively. Vasopressin, acting through its V1 receptors, thus appears to be involved in acute endotoxin shock-provoked gastrointestinal injury.

Animals↗

On the mechanism of cogenotoxic action between ingested amphibole asbestos fibres and benzo[a]pyrene: I. Urinary and serum mutagenicity studies with rats.

Recently, there has been concern that ingested asbestos may cause an increase in cancer incidence in populations exposed to fibre-contaminated drinking water. Although animal experiments failed to demonstrate carcinogenicity of the oral asbestos exposure, the high adsorption capacity of the fibres creates the possibility of cocarcinogenic action with adsorbed organics. In a simple in vivo model we demonstrated earlier that UICC crocidolite and anthophyllite asbestos fibres were able to adsorb carcinogen molecules from aqueous solutions. When orally administered, these fibres increased the sister chromatid exchange frequency in bone marrow cells of rats. In the present study we tried to follow the desorption and metabolization processes of carcinogenic benzo[a]pyrene molecules transported by the ingested fibres using the highly sensitive Salmonella/Ames mutagenicity assay. The bacterial test was performed on concentrated serum and urine samples of the treated animals by using the TA98 and 100 strains in the presence and absence of liver microsomal and deconjugating enzymes. All sets of urine and serum samples failed to show mutagenic activity indicating a lack of both desorption in the serum and the ability of the liver to metabolize. Considering our results, the cytogenetic impact demonstrated earlier in the bone marrow can be explained by a local action of accumulated and transported carcinogen molecules.

Animals↗

Identification of oxytocin and vasopressin from neurohypophyseal cell culture.

Our observation that dispersed cultures of neurohypophysis obtained from adult rats are capable of synthesizing and releasing oxytocin and vasopressin is unexpected, because in whole animals these hormones are known only to be stored, not to be produced in the posterior lobe of the pituitary. The hormone content of cell culture medium was elevated from 0 to 129 +/- 14 pg/mg protein for oxytocin and from 0 to 42 +/- 4 pg/mg protein for vasopressin during two weeks as determined by specific radioimmunoassay. By molecular mass and structure determination (tandem mass spectrometry) we have proved that the supernatant of the cell cultures contains not only immunologically but mass spectrometrically identified neurohypophyseal hormones.

Animals↗

Damaging actions of testosterone on cysteamine-induced gastroduodenal ulceration and vascular leakage in the rat.

The sexual dimorphism of gastroduodenal ulceration is suggested on the basis of clinical and experimental observations. This difference probably relates to the actions of endogenous sexual steroids. In the present study, the role of testosterone was evaluated in the generation of gastroduodenal mucosal injury provoked by cysteamine (400 mg/kg, s.c.). We found that macroscopic mucosal damage and microvascular (125)I-human serum albumin leakage (2 microCi/kg, i.v.) developed in the stomach and duodenum of male rats 24 h after the administration of cysteamine. This mucosal injury was prevented by orchidectomy and by the pretreatment with the antiandrogen, cyproterone acetate (12 mg/kg per day for 8 consecutive days). It was also shown that pretreatment with testosterone (4-20 mg/kg per week) dose-dependently aggravated cysteamine-induced gastroduodenal mucosal injury. Our results thus suggest an aggressive role of testosterone in the generation of cysteamine-induced gastroduodenal ulceration.

Androgen Antagonists↗

In vivo studies on genotoxicity and cogenotoxicity of ingested UICC anthophyllite asbestos.

Early cytogenetic action of oral exposure to UICC anthophyllite, an amphibole type of asbestos, was studied in Fischer-344 rats. The animals were gavaged with a suspension of untreated fibres (50 mg/kg) and fibres which had been allowed to adsorb benzo[alpha]pyrene molecules from aqueous solutions of 0.25-2.5 micrograms/ml. HPLC measurements indicated effective adsorption of the benzo[alpha]pyrene molecules on the fibres. The authors consider this system a suitable model for the drinking of water containing asbestos fibres and organic micropollutants. The formation of micronuclei and sister chromatid exchanges was studied in bone marrow samples taken from animals 24 h after oral administration of suspensions. Whereas anthophyllite fibres failed to induce cytogenetic alterations, fibres pretreated with the polycyclic aromatic solutions caused dose-dependent increase in the sister chromatid exchange frequencies. The observed cytogenetic impact can be explained by a local action of carcinogen molecules accumulated and subsequently transported. The results support the hypothesis that epidemiological evidence of carcinogenicity of asbestos in potable water may rather be explained by cogenotoxic action of the asbestos fibres and biologically active organic micropollutants adsorbed on their surface.

Administration, Oral↗

Changes in superoxide anion production and phagocytosis by circulating neutrophils during tumor progression in a rat model.

The functional state of circulating neutrophils was monitored in a rat model of mesoblastic nephroma during tumor progression. Superoxide anion (O2.-) production in response to PMA and phagocytosis of yeast particles (Saccharomyces cerevisiae) were measured every second day after tumor cell implantation. Both phagocytosis and PMA-induced 02.- generation were found to be enhanced in the first period (on Days 6, 8, and 10), while they became significantly reduced in the advanced stage of cancer (on Days 12, 14, 16, and 18). The suppression of PMNL functions was accompanied with tumor progression and an increased number of neutrophils in the peripheral blood. Studies were also carried out on PMNLs isolated from normal rats and the cells were treated with plasma samples obtained from tumor-bearing animals at different stages of nephroma. Incubation of the normal cells with plasmas separated on the 2nd and 8th days of tumor growth influenced neither the 02.- generation nor the phagocytosis. In contrast, plasma preparations obtained on the 14th day significantly inhibited both 02.- production and phagocytosis by normal neutrophils. The alterations in 02'- generation and phagocytosis by PMNLs were observed in close association with tumor growth, thus they could be considered as indicators of tumor progression. However, further studies are required to see whether the granulocyte dysfunctions observed in our animal model could provide additional prognostic information in the case of human malignancies as well as to clarify the origin of inhibitory factor(s) present in the blood of tumorous animals.

Animals↗

Cerebral oedema after subarachnoid haemorrhage. Pathogenetic significance of vasopressin.

The authors report the frequency, characteristic clinical symptoms, laboratory alterations and diagnostic criteria of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after subarachnoid haemorrhage. The data on 290 patients with subarachnoid haemorrhage (SAH) during a period of years at the Division of Neurosurgery, University Medical School, Szeged, are analysed. Twenty-seven (9.3%) patients developed SIADH. Thirteen (4.5%) patients had severe and 14 (4.8%) had mild SIADH. The problems of the treatment are discussed in detail and the different therapeutic methods are listed: NaCl infusion, water withdrawal and administration of Dilantin, diuretics, mineralocorticosteroids, lithium and demeclocycline. The undesirable side-effects observed accompanying various therapeutic regimen are analysed. The introduction of V2 antagonists into clinical practice appears to be a most perspective procedure. For study of the pathogenesis of SIADH following SAH, the possibility of treatment with V2 antagonists on an experimental model of SAH in rat was created. A significant water retention and increases in brain water and sodium content were observed in rats with SAH. Plasma AVP levels were also elevated after SAH. AVP plays an important role in the development of antidiuresis following water loading and disturbance of the brain water and electrolyte balance after SAH. Water retention and the higher brain water and sodium accumulation could be totally prevented by administration of a V2 antagonist. These results demonstrate that cerebral oedema generated by artificial cerebral bleeding in rats is significantly reduced following the administration of a highly specific V2 antagonist, suggesting a new approach to the treatment of SIADH.

Animals↗