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Biomedical subjects

L Korányi

Publications and source records attributed to L Korányi.

At least 19 recordsLinked to original sources

Exposure to a novel stimulus reduces anxiety level in adult and aging rats.

Male Wistar rats aged 3, 15 and 24 months were isolated and housed individually for 72 h prior to being subjected to inanimate objects (two objects per rat, each 1.5 cm in diameter and 4 cm in length, made of surgical gauze). Following the exposure to the objects, rats were subsequently tested in an elevated plus-maze. The inanimate objects induced locomotor activity, chewing and transportation of the object. This changed to social interaction and play-like behavioral activity in rats of all ages that were kept in small groups with a latency of 1 to 2 min. One hour after the start of exposure, the animals were tested in the elevated plus-maze to measure anxiety behavior. It was found that all age groups spent significantly more time in the open arm of the elevated plus-maze than the corresponding controls. Latencies to first entry into open arms were also significantly lowered. The number of entries to the open or to the dark arm, however, did not show statistical difference, indicating that the novel object-induced activity failed to exert influence on gross motor activity in the elevated plus-maze. In conclusion, the stimulation elicited by the exposure to novel stimulus (inanimate objects) resulted in a significant reduction of anxiety level both in adult and in aging rats.

Aging↗

Inhibitory effect of postpartum lesions or cuts in median raphe nucleus on maternal behavior in female rats.

In order to clarify the role of the median (MRN) and dorsal (DRN) raphe nuclei in regulating maternal care (retrieving and licking behavior), radiofrequency lesions or microknife cuts were made in postpartum rats on the day after delivery. Animals were housed individually without pups after the operation. One week after the surgery, maternal behavioral test was carried out daily for 3 days using pups of 2-6 days age. The results demonstrated that rats with MRN lesions or ventral horizontal cuts of the MRN showed extremely low incidence of the maternal behavior, as compared to those in control and sham-operated groups. DRN-lesions or dorsal cuts of the MRN had no effect. In locomotor activities measured by the infrared sensor system, there was no difference between the groups. This suggest that the MRN but not DRN plays a critical role in regulating retrieving and licking behaviors and ventral outputs are involved in this function in postpartum rats.

Animals↗

Ultrastructural localization of Hsp-72 examined with a new polyclonal antibody raised against the truncated variable domain of the heat shock protein.

In spite of the intensive search for the determination of the continuously widening physiological and pathological roles of different stress proteins, their ultrastructural localization at the electron microscopic (EM) level has hardly been examined. As it becomes increasingly evident that the function and physiological effectiveness of stress proteins are highly dependent on their spatial location and their associations with diverse regulator proteins, the demand for morphological studies which can identify their detailed distribution within the cells is evident. The reason for the practical lack of studies carried out at the EM level, lies in the shortage of reagents with suitable specificity and avidity necessary for this type of examination. To create such a reagent, a polyclonal antibody was raised using a recombinant truncated form of the inducible Hsp-72 protein. The antibody was extensively characterized, using different immunochemical methods to determine and verify its specificity, and then it was tried in ultrastructural examinations. Using the new antibody, it was possible to analyze the intracellular distribution of Hsp-72 with the immunogold technique. The localization of Hsp-72 was demonstrated directly at the ultrastructural level in the cytoplasm (especially at the cisterns of the RER), in the nucleus (mainly around the heterochromatic regions) and at both sides of the nuclear envelope close to the membrane pores. Apart from these localizations, Hsp-72 was found in several membrane bordered intracellular structures, which mainly belong to the endosomal-lysosomal system. We provide the first morphological verification of the appearance of Hsp-72 on the surface of the cells. Also novel is the indication, that the stress protein may recycle from the cell surface using a common route which includes coated pits and the endosomal system.

3T3 Cells↗

Bimoclomol (BRLP-42) ameliorates peripheral neuropathy in streptozotocin-induced diabetic rats.

A reduction in nerve conduction velocity and an increase in resistance to ischemic conduction failure are early signs of neural dysfunction in both diabetic patients and animal models of diabetes. The effect of Bimoclomol (BRLP-42), a drug under clinical development for the treatment of diabetic complications, on experimental peripheral neuropathy was examined in rats made diabetic by injection of streptozotocin. Daily oral doses of Bimoclomol (10 or 20 mg/kg) or control dose of gamma-linolenic acid (260 mg/kg), an agent with known neuropathy-improving effects, were administered for 3 months. Treatments began 1 day after diabetes induction to assess the prophylactic efficacy of Bimoclomol. Neuropathy was evaluated electrophysiologically by measuring motor and sensory nerve conduction velocities and resistance to ischemic conduction failure of sciatic nerve in vivo. Bimoclomol significantly reduced nerve conduction slowing and retarded the typical elevated ischaemic resistance due to streptozotocin-induced neuropathy, suggesting that the drug might be a useful treatment for diabetic peripheral neuropathies.

Animals↗

Bimoclomol: a nontoxic, hydroxylamine derivative with stress protein-inducing activity and cytoprotective effects.

Preservation of the chemical architecture of a cell or of an organism under changing and perhaps stressful conditions is termed homeostasis. An integral feature of homeostasis is the rapid expression of genes whose products are specifically dedicated to protect cellular functions against stress. One of the best known mechanisms protecting cells from various stresses is the heat-shock response which results in the induction of the synthesis of heat-shock proteins (HSPs or stress proteins). A large body of information supports that stress proteins--many of them molecular chaperones--are crucial for the maintenance of cell integrity during normal growth as well as during pathophysiological conditions, and thus can be considered "homeostatic proteins." Recently emphasis is being placed on the potential use of these proteins in preventing and/or treating diseases. Therefore, it would be of great therapeutic benefit to discover compounds that are clinically safe yet able to induce the accumulation of HSPs in patients with chronic disorders such as diabetes mellitus, heart disease or kidney failure. Here we show that a novel cytoprotective hydroxylamine derivative, [2-hydroxy-3-(1-piperidinyl) propoxy]-3-pyridinecarboximidoil-chloride maleate, Bimoclomol, facilitates the formation of chaperone molecules in eukaryotic cells by inducing or amplifying expression of heat-shock genes. The cytoprotective effects observed under several experimental conditions, including a murine model of ischemia and wound healing in the diabetic rat, are likely mediated by the coordinate expression of all major HSPs. This nontoxic drug, which is under Phase II clinical trials, has enormous potential therapeutic applications.

Animals↗

[The effect of prolonged acenocoumarol therapy on bone density].

The effect of chronic cumarin treatment on bone mineral content was investigated. Bone mineral density was determined by double photon densitometry (Lunar DPXL). The density data (mean +/- SE) of 45 cardiac patients (age: 57.0 = +/- 6.3 y, body mass index: 26.7 +/- 3.8 kp/m2, cardiac stadium score, according to New York Heart Association: 2-3), had been treated by acenocumarol at least for 2 years (duration of treatment: 75.0 +/- 52 months), were compared to the values of 45 age, body mass index, cardiac status matched patients not treated by anticoagulant. The density values of L2-L4 lumbar regions were lower in the treated group (1.041 +/- 0.17 vs. controlls: 1.13 +/- 0.15 g/cm2, p < 0.05), while no differences in ultradistal ulnar and radial regions were detected. No correlation between bone mineral density and the length, or the dose of the cumarin treatment were observed. This observation suggests the importance of the regular bone densitometry control of cumarin treated patient.

Acenocoumarol↗

[Effect of menopause on carbohydrate metabolism].

Endocrine alterations in menopause produce disadvantageous changes in the carbohydrate and lipid metabolism. The character and tendency of these alterations are very similar to those found in type II diabetes mellitus. The abdominal visceral fat content as well as the blood level of cholesterol, triglyceride, glucose and insulin increase in postmenopause. These changes can be advantageously influenced by hormone replacement therapy.

Adult↗

Progeny of mothers drinking corticosterone during lactation has lower stress-induced corticosterone secretion and better cognitive performance.

In order to test the hypothesis that maternal corticosterone influences hypothalamus-pituitary-adrenal (HPA) system activity in the adult rat and behaviors related to it, we induced a moderate increase in maternal plasma level of corticosterone by adding the hormone to the drinking water of the dams (200 micrograms/ml) from the day after delivery to weaning. Our previous experiments have shown that this procedure produces plasma levels of the hormone in the range of those following a mild psychic stress (from 4.3 +/- 0.5 to 9.5 +/- 1.8 micrograms/100 ml in the dams, and from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100 ml in the pups at 10 days of lactation). Adrenal weights were slightly and temporarily decreased by treatment in both mothers and offspring. Only the male progeny was investigated in this study. Corticosterone-nursed rats had significantly less corticosterone and ACTH in basal conditions and after a 2 min restraint stress at 3 months of age, and showed better performances at weaning and at 1, 2 and 3 months of life in the Morris water maze. Our results demonstrate that a moderate increase in maternal corticosterone during lactation influences the activity of HPA axis and improves spatial learning ability of the adult offspring.

Adrenal Glands↗

Neuroendocrine and neurochemical consequences of long-term sleep deprivation in rats: similarities to some features of depression.

The paradigm of long-term sleep deprivation was used as a model of chronic inescapable stress in rats. Several basic metabolic parameters (body weight changes, food and water intake, rectal temperature, serum glucose and creatinine), adrenal and thyroid secretion, norepinephrine and dopamine content and turnover in discrete brain regions, and open field behaviour were examined in the course of the exposure to experimental stress. Sleep deprivation over 7-9 days caused complete physical exhaustion of the animals. It was accompanied by hypothermia and hyperphagia. Adrenal activity was characterized by significant hypercorticism, but also by a relative decrease of the responsiveness to ACTH. A gradual decrease in the thyroid secretion was observed. Sleep deprivation elicited a depletion of norepinephrine in the hypothalamus and decreased its turnover, whereas hippocampal norepinephrine content decreased without considerable turnover alterations. Striatal dopamine content and turnover remained unaffected. Behavioural depression and altered open field activity were also observed in exhausted animals. Long-term sleep deprivation, therefore, seems to reproduce some of the biological correlates of the depressive illness, and may be useful in studying the development of coping failure as a result of chronic stress exposure.

Adrenal Glands↗

Preservation of ejaculation in stage I non-seminomatous testicular tumours.

The loss of ejaculation is the most serious postoperative complication of patients having stage I non-seminomatous testicular tumours. In order to preserve the capability for ejaculation even after retroperitoneal lymphadenectomy (RPA) the preservation of paravertebral sympathetic ganglia but that of the sympathetic nerves in the territory of aortic bifurcation and common iliac arteries to be ulcessary.

Aorta↗

Changes of enzyme activity in T-cells during induced maternal behaviour in rats.

Continuous exposure to foster pups elicits specific behavioural patterns in adult naive female or male rats. The first exposure induces active avoidance of young. By day 2 or 3 adults show neutral behaviour. Next day complete maternal behaviour begins to develop; e.g. retrieving of pups, nursing and crouching. The avoidance reaction activates stress mechanisms, and the developed maternal behaviour is associated with moderate prolactin release. The question is raised whether pup-induced catecholamine and prolactin release is able to alter enzyme activity in T-cells. Using Arg-Pro-; Leu-Pro; and Pro-Pro-4-nitroanilide as substrates the activity of a marker enzyme dipeptidyl peptidase IV, DP IV, EC. 3.4.14.5., was measured in T-cell suspension prepared from the thymi of adrenalectomized female and male Wistar rats. We found that changes of DP IV activity during the pup-induced avoidance phase could be prevented by propranolol pretreatment indicating the role of catecholamines in this phenomenon. Prolactin released during artificial maternal behaviour in female rats resulted in an elevation of DP IV activity which failed to develop, if they were given daily injections of bromocriptine or apomorphine. It is concluded that pup-exposure is the most physiological way to influence hormonal mechanisms and immune functions, which are highly responsive to sensory stimuli.

Animals↗

[Combined therapy of malignant testicular tumors].

The 5-year survival of patients with malignant testicular tumors rose during the past 25 years from 10-25% depending on stage to 55-100% after radical castration performed from high inguinal opening, retroperitoneal lymphadenectomy, ultra-tension irradiation and adjuvant chemotherapy. It is stressed that patients diagnosed at stage T1-2, N0-2, M0 may even recover perfectly upon complex therapy. Three to five-year long or even longer survival may be reached with 50% of the patients at the stage T1-3, N1-3, M1. Patients at stage T4, N3-4, M1 die because of the recurrence of the tumor and/or the complication of the adjuvant treatment within 1-3 years and even the interdisciplinary work which is very effective in other stages fails to change this at the present time.

Combined Modality Therapy↗

Changes of dipeptidyl peptidase (DP IV) activity in the T lymphocytes of rats following administration of ACTH, dexamethasone and opiates.

The aim of the work was to study the effect of glucocorticoids, opiates and stressful stimuli on dipeptidyl peptidase IV (DP IV, EC 3.4.14.5) activity of T lymphocytes prepared from the thymus of intact and adrenalectomized rats. Four week old male rats of Wistar strain were used. The in vivo administration of ACTH, dexamethasone and morphine treatment resulted in an increase of DP IV activity in the cell suspension. In adrenalectomized rats ACTH treatment failed to modify the enzyme activity, however, pain or emotional stress resulted in an elevated DP IV activity. Morphine and D-Met2-Pro5-enkephalinamide resulted in a dose dependent activation of DP IV in T cells, an effect which could be modified by naloxone pretreatment. Our findings show that DP IV mechanisms in T cells are highly sensitive to exogenous and endogenous steroids, opiates and biologically active substances released in response to stress in rats.

Adrenocorticotropic Hormone↗

Exocrine pancreatic secretion: effect of subarachnoidal application of cholecystokinin octapeptide in rats.

Administration of cholecystokinin octapeptide (CCK-8) intravenously, or in the subarachnoidal surface of the olfactory lobe in rats, caused an increase in pancreatic protein and amylase secretion. It was observed that for subarachnoidal administration of CCK-8 both protein and amylase outputs were higher than that seen after i.v. injection. This result is consistent with the presence of central CCK receptors which when activated can enhance pancreatic exocrine secretion. The blockade of the effect of CCK by administration of CCK-8-specific antisera proves the specificity of the subarachnoidal CCK-8 stimulation.

Amylases↗

Neural transection between preoptic area and septum inhibits maternal behavior in female and male rats.

Artificially-induced maternal behavior was examined in inexperienced female and male rats following neural transection between the preoptic area and the septum. Anterior roof deafferentation (ARD) of the preoptic area (POA) was performed with an L-shaped microknife. Virgin female and male rats with or without ARD were exposed to the continuous presence of normal pups to induce maternal behavior 3 weeks after surgery. ARD resulted in a significant delay of the onset of maternal behavior in females and a lack of complete development of maternal behavior in males, compared with corresponding sham-operated and intact controls. The results indicate that neural substrates dorsal to the POA play an important role in modulating the expression of maternal behavior in the rat.

Animals↗

Comparative analysis of enzyme activity in human colostrum, milk, and serum.

Changes of enzyme activity in the colostrum, milk, and serum samples of 14 mothers were followed. For the enzyme assay, the colostrum and the milk samples were diluted, 1:10 and 1:5, respectively. The activity of the following enzymes were measured: lactate dehydrogenase (LDH); gammaglutamyl transpeptidase (GGT); aspartate aminotransferase (ASAT); alanine aminotransferase (ALAT); cholinesterase; alkaline, and acid phosphatase. Milk, LDH, ASAT, and ALAT activities did not change during the first four days of lactation, yet were significantly higher than the corresponding activities of serum. The activity of GGT and alkaline and acid phosphatase in milk showed a marked decrease by day 4 postpartum; however, the GGT stayed much higher than that of serum, while the activity of the other two enzymes decreased to the level of the serum. By contrast, as compared to the colostrum, the cholinesterase activity in the breast milk showed a significant increase.

Colostrum↗

Alteration of insulin-binding receptors in non-insulin dependent diabetes of the young.

The behaviour of insulin binding receptors is rather unelucidated in non-insulin-dependent diabetes mellitus of the young. Authors in continuing their previous work studied the behaviour of insulin binding receptors of erythrocytes and monocytes in 9 MODY patients. They observed that specific insulin binding of circulating blood cells was significantly decreased in all cases as compared to the controls despite of a good state of metabolism (in the case of erythrocytes 4.63 +/- 1.1% vs. 6.03 +/- 1.7%, p less than 0.05, in the case of monocytes 2.3 +/- 1.2% vs. 3.6 +/- 1.4%, p less than 0.05). The lower value of insulin binding resulted from the decrease of receptor concentrations (in the case of erythrocytes 2.36 +/- 0.78 pmol/l vs. 3.81 +/- 1.14 pmol/l, p less than 0.05).

Adult↗

Somatostatin-induced inhibition of lipolysis: in vitro studies.

Incubation of epididymal fat tissue slices with somatostatin (SS) led to the inhibition of epinephrine-induced release of free fatty acids (FFA) and glycerol in a dose-dependent manner. The SS administration did not suppress the lipolysis evoked by dibutyryl cAMP. The experimental findings indicate that SS exerts an inhibition of catecholamines-induced lipolysis at the level of adipocytes although the mechanism of action requires further investigations.

Animals↗