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T Kadar

Publications and source records attributed to T Kadar.

At least 19 recordsLinked to original sources
PubMed1992

NG-nitro-L-arginine enhances neuronal death following transient forebrain ischemia in gerbils.

Experiments were performed with Mongolian gerbils to study the effect of the specific nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (L-NNA) on ischemic brain damage induced by 5 min bilateral carotid occlusion. A single i.p. injection of L-NNA did not result in any neuronal loss in the central nervous system. In animals undergoing ischemia, a selective destruction of hippocampal CA1 cells was observed whereas pretreatment with 50 mg/kg L-NNA 4 h before administration of ischemia produced significantly more extensive cell damage in the hippocampus and other brain regions. These findings demonstrate that in this model inhibition of nitric oxide generation augments ischemia-induced neuronal cell injury in the brain.

Animals↗
PubMed1992

Long-term study of brain lesions following soman, in comparison to DFP and metrazol poisoning.

The long-term histopathological effects of acute lethal (95 micrograms kg-1) and sublethal (56 micrograms kg-1) doses of soman were studied in rats and were compared to lesions caused by equipotent doses of either another cholinesterase (ChE) inhibitor, DFP (1.8 mg kg-1), or a non-organophosphorus convulsant, metrazol (100 mg kg-1). Severe toxic signs were noted following one LD50 dose administration of all the compounds, yet only soman induced brain lesions. Moreover, even when administered at a sublethal dose (0.5 LD50), soman induced some histological changes without any clinical signs of intoxication. Soman-induced brain lesions were assessed quantitatively using a computerized image analyser. The analysis was carried out for up to 3 months following administration, and a dynamic pattern of pathology was shown. The cortical thickness and area of CA1 and CA3 cells declined significantly as early as 1 week post-exposure. No pathological findings were detected following DFP and metrazol administration. It is therefore suggested that brain lesions are not common for all ChE inhibitors and that convulsions per se are not the only factor leading to brain damage following the administration of soman. The degenerative process (found also with the sublethal dose of soman) might be due to a secondary effect, unrelated to soman's clinical toxicity, but leading to long-term brain injuries.

Animals↗
PubMed1991

Nimodipine improves spatial working memory and elevates hippocampal acetylcholine in young rats.

The calcium channel blocker nimodipine has been reported to improve cognitive performance in aged and brain-damaged animals. In the present study, the effects of nimodipine and placebo on spatial working memory and hippocampal acetylcholine were studied in young Fischer-344 rats. Nimodipine or placebo was administered via subcutaneously implanted, sustained-release pellets. Each active pellet contained 20 mg of nimodipine and released the drug over approximately 21 days. Two days after the drug or placebo pellets were implanted, training in the 8-arm radial maze started and continued for 12 days. Rats were required to learn a win-shift surgery. Nimodipine-treated animals learned the maze more rapidly than a placebo-treated group as indicated by the number of correct choices out of the first eight arms visited (p less than 0.001). Treated rats also made twice as many choices per unit time during the first week of training (p = 0.005). To assess hippocampal acetylcholine release, in vivo microdialysis was performed while animals were awake and unrestrained, 19-21 days after pellet implantation. A probe with a 3 mm semipermeable tip was placed in the hippocampus (CA1 and dentate gyrus), and individual microliters dialysate samples were collected at 2 microliters/min and immediately analyzed by high performance liquid chromatography with electrochemical detection. Significantly higher extracellular ACh levels were found in nimodipine-treated rats (71.4 +/- 3.6 nM; n = 4) compared to controls (52.5 +/- 2.5 nM; n = 5) (p = 0.003) and in another group of rats of the same age that received identical drug treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

Immediate dressing of the burn wound--will it change its natural history?

Thirty deep dermal burns were inflicted on six domestic pigs. On the treated animals, the epidermis was removed and immediately replaced with Omiderm, Xeroform or Mettalin dressings. Burns in which the blister was left intact or not dressed after epidermis removal, served as controls. Macroscopic and microscopic assessment of the healing process was then carried out. Surprisingly, the no-epidermis controls healed somewhat faster than did the untreated controls (those with blister intact). On day 7, 83 per cent of the treated lesions showed initiation of epidermal regeneration, compared with 58 per cent in the no-treatment and no-epidermis controls. All dressing materials were found equal in this model, and differences between control and treatment groups were not significant after 12 days.

Animals↗
PubMed1991

Bimodal effect of neuropeptide Y on feeding, and its antagonism by receptor blocking agents in rats.

Satiated rats received intracerebroventricular (icv.) injections of several doses of neuropeptide Y (NPY) and the food intake was measured in the following 4 h. The peptide exerted a dose-dependent biphasic effect; the 100 dose significantly suppressed the food intake, but doses of 1 microgram and 5 micrograms stimulated feeding. After the injection of 2 microliters NPY-antiserum (icv., 1:50 dilution), the cumulative food intake decreased significantly in the first 24 h. From the drugs tested the alpha-1-antagonist prazosine (4 micrograms icv.) and the opiate antagonist naloxone (NX, 0.5 micrograms, icv.) selectively inhibited the feeding-stimulatory effect a high icv. dose of NPY. The alpha-2-antagonist yohimbine (4 micrograms icv.) and the non-selective beta-antagonist propranolol (5 micrograms icv.) did not influence either effect of NPY on feeding. The results suggest the involvement of alpha-1-adrenergic and opiate receptors in the food intake-stimulatory effect of a large icv. dose of NPY. The food intake-inhibitory effect of a low icv. peptide dose was not selectively antagonized by the receptor blocking agents used.

Animals↗
PubMed1991

Neuropeptide Y and catecholamine-mediated neuronal transmission in mechanisms of feeding-behaviour induction.

Intracerebroventricular administration of various doses of neuropeptide Y (NPY) to rats had different effects on their feeding behaviour: the lowest dose (100 ng) decreased food intake, but higher doses (5 micrograms) markedly increased the intake. Prazosin, a selective blocker of alpha 1-adrenergic receptors, suppressed the effect induced by 5 micrograms (but not 100 ng) NPY. No such effect was observed with injections of yohimbine or propranolol. The opiate receptor antagonist, naloxone, blocked the feeding behaviour induced by 5 micrograms NPY without having any other effects on the responses induced by 100 ng NPY. The data obtained testify to heterogeneity within the NPY receptors of the central nervous system. It is concluded that the effects of high doses of NPY on feeding behaviour are mediated, at least in part, by alpha 1-adrenergic receptors.

Animals↗
PubMed1990

Selective hippocampal lesion following omega-conotoxin administration in rats.

Histopathological evaluation of rat brains 3 days following unilateral i.c.v. injections of omega-conotoxin GVIA (omega-ctx), 0.032 and 0.1 nmol/kg, was performed. An isolated unilateral lesion confined to the injected hemisphere was found in the hippocampal CA3 neurons. Morphometric analysis of these cells revealed a significant reduction in cell area in both dose groups compared to i.c.v. injected vehicle, and to the contralateral hemisphere. These data indicate a specific degenerative process and suggest that CA3 cells possess omega-ctx-sensitive Ca2+ channels which are essential to their viability.

Animals↗
PubMed1990

Age-related structural changes in the rat hippocampus: correlation with working memory deficiency.

Age-related histopathological changes in the hippocampal formation were correlated with cognitive performance, evaluated in rats at the 8-arm radial maze. Experiments were conducted using young (3 months), mature (12 months), middle-aged (17 months) and aged (24 months) Wistar rats. Significant memory impairments were already observed at the age of 12 months in all the measured parameters (correct choices, percent errors and total time). No further decline was observed between 12 and 17 months of age, while at 24 months additional decline was monitored mainly in the percent errors parameter. Morphometric analysis revealed a decrease in the area of cells within the hippocampus and the number of cells in the CA3 subfield. This pattern of morphological changes with age corresponded well with the cognitive impairments, with high correlation especially to lesions at the CA3 subfield. It had also been confirmed in this study that lipofuscin appeared to be a good histochemical marker for CNS cell degeneration. It is concluded that 12-month-old Wistar rats may serve as the animal model of choice for the study of specific age-related behavioral deficits and that the hippocampal CA3 region might play a major role in the age-dependent cognitive decline.

Aging↗
PubMed1990

Effects of CBDP and MEPQ on the toxicity and distribution of [3H]-soman in mice.

Soman poisoning presents a problem in terms of its detailed pathophysiology and its detoxification mechanism(s). The present study was designed to evaluate the role of carboxylesterases (CaE) and cholinesterase (ChE) in the distribution and detoxification of soman in vivo. Mice were injected (i.v.) with 0.06-1.0 LD50 of [3H]-soman, 60 min following pretreatment with either 2-O-cresyl-4H-1:2:3 benzodioxa-phosphorine-2-oxide (CBDP), which blocks CaE or 7-(methylethoxyphosphinyloxy)-1-methyl quinolinium iodide (MEPQ), which selectively inhibits intravascular ChE. One hour after [3']-soman administration animals were sacrificed and whole body autoradiography was performed. High concentrations of [3H]-soman were found in lung and kidney in control mice, and low concentrations were found in central nervous system. Pretreatment with CBDP caused a 93% decrease in radioactive labelling in the lung, and a minor decrease in overall labelling, whereas pretreatment with MEPQ did not change the distribution pattern of [3H]-soman. It is concluded that lung is a major target organ for soman detoxification and that it exerts this effect by means of enzymatic reaction with soman through the abundant amounts of CaE which are present in the lung. Intravascular ChE has little (if any) effect on the distribution and detoxification of soman in vivo.

Animals↗
PubMed1990

The effects of somatostatin and somatostatin antiserum on the retention of passive avoidance behavior after neofrontal decortication in rats.

Rats were tested for passive avoidance behavior in a one-trial step-through learning paradigm. After the learning trial, the animals underwent neofrontal decortication or sham operation. On the 8th day after operation, the lesioned or sham-operated rats received intracerebroventricular (ICV) injections of somatostatin (SST; 4 micrograms/2 microliters) or somatostatin antiserum (SST-AB; 2 microliters) 1 hr before the retention test. Decortication alone decreased the latency in comparison to that in the sham-operated group, and ICV treatment did not influence this impairment. After treatment with SST-AB the latency decreased, indicating that endogenous SST may play a role in the maintenance of normal memory processes.

Animals↗
PubMed1990

Age-related changes in the cholinergic components within the central nervous system. II. Working memory impairment and its relation to hippocampal muscarinic receptors.

Cognitive performance in aging Wistar rats was monitored using the radial arm maze and the latter was correlated with the density of muscarinic receptors in the CNS, using quantitative in vitro receptor autoradiography. Significant working memory deficits were observed in 12, 17 and 24-month-old rats as compared to 3-month-old animals. In addition, the number of the muscarinic receptors declined significantly with age (from 27 to 42% depending on the brain region sampled) utilising [3H]QNB and [3H]PZ receptor binding assays. The above trend became evident already at the age of 12 months. The present findings support the association of central cholinergic activity with memory processes.

Age Factors↗
PubMed1989

Age-related changes in the cholinergic components within the central nervous system of CW1 female mice. I. Structural analysis.

Histomorphometric analysis of age-related structural changes in the brain was performed in CW1 female mice, 3, 9, 24 and 32 months of age. Cholinergic regions, such as the hippocampus, NBM and the medial habenula (MH) were investigated in more detail focusing on morphological parameters. The thickness of the frontoparietal cortex (FPC), and the surface area of the dorsal hippocampus and the MH were found to decrease significantly from 9 to 24 months of age. Except for the unique appearance of pseudo-cysts within the FPC, the structural changes culminated by 24 months. Cells' degeneration, in the CA3 hippocampal subfield, was noted already by 9 months of age whereas in other regions the cells' surface area decreased only between 9 and 24 months. Lipofuscin accumulation was most pronounced in the large neurons of the cortex, hippocampus and NBM at 24 months of age.

Aging↗
PubMed1988

Prolactin and luteinizing hormone-releasing hormone receptors in human benign prostatic hyperplasia and prostate cancer.

Using a sensitive micromethod for the determination of prolactin (PRL) binding sites based on 125I-human PRL ligand, PRL receptor levels in specimens of benign prostatic hyperplasia (BPH) and human prostate cancer were estimated by the one-point assay system. Ten of 19 BPH specimens (53%), showed significant PRL binding, four being in the 9-12 fmol/mg range. All ten of these cases had an histological diagnosis of nodular glandular hyperplasia. Of ten adenocarcinomas examined, four samples (40%) exhibited positive PRL binding, the highest receptor levels being 10.2 fmol/mg protein. To characterize the receptors from BPH membranes, samples were then separately pooled according to the results obtained in one-point assays. In the PRL-negative pool no displacement could be detected. In the PRL-positive pool, the Scatchard analysis revealed one class of receptors with an average affinity Kd = 1.1 X 10(-9) M and capacity Bmax = 287 fmol/mg protein. In the prostate cancer specimens, luteinizing hormone-releasing hormone receptors with a high affinity and a low capacity were also found. The results indicate the presence of prolactin receptors in prostate cancer and in BPH. The clinical implications of such findings are not clear, but it is possible that a certain proportion of BPH and prostate cancers might be in part PRL dependent. Further studies are necessary to ascertain this hypothesis in an attempt to improve the treatment of BPH and prostate cancer.

Gonadotropin-Releasing Hormone↗
PubMed1988

Receptors for prolactin, somatostatin, and luteinizing hormone-releasing hormone in experimental prostate cancer after treatment with analogs of luteinizing hormone-releasing hormone and somatostatin.

Membrane receptors for luteinizing hormone-releasing hormone (LH-RH), somatostatin, and prolactin (PRL) were investigated in the Dunning R-3327H rat prostate adenocarcinoma specimens after in vivo treatment with microcapsules of the agonist [D-Trp6]LH-RH and the somatostatin analog RC-160. The LH-RH receptors showed a low-binding affinity (Kd = 54 nM) and high capacity (Bmax = 12.0 pmol/mg). Treatment with the [D-Trp6]LH-RH decreased the binding affinity (Kd = 0.52 microM). Specific somatostatin receptors, with Kd = 1.3 nM and Bmax = 543 fmol/mg, were also found. Treatment with [D-Trp6]LH-RH lowered Bmax to 44 fmol/mg, and administration of RC-160 reduced Kd to 30 nM. After the combined treatment with the two analogs, Kd and Bmax were decreased. Specific PRL receptors (Kd = 0.72 nM; Bmax = 161 fmol/mg) were also detected. Treatment with either analog reduced Bmax by 50%, but a much greater reduction of PRL binding capacity was revealed after in vitro dissociation of the bound endogenous PRL by MgCl2. The dramatic fall in the total number of PRL receptors after combination treatment with both analogs could be partially responsible for the decrease in the weight and volume of prostate tumors. The findings support the concept that analogs of LH-RH and somatostatin can inhibit tumors directly through their own respective receptors. One of several mechanisms of the antineoplastic activity of these analogs could be the elimination of tumor growth-promoting effect of PRL by the reduction of the total number of PRL receptors.

Adenocarcinoma↗
PubMed1988

Characterization of prolactin receptors and their distribution among American and Israeli women with breast cancer: implications for prediction of hormonal dependency and treatment.

A micro-method is reported for the determination and characterization of prolactin (PRL) receptors in human breast cancer specimens using either intact biopsy tissue or the pellet fraction remaining from biopsies previously processed for steroid hormone receptors. Labeled human PRL is used as the ligand. The specific PRL-binding of 307 human breast cancer specimens was evaluated by this micro-method. A significant level of specific PRL-binding (3-25 fmol per mg membrane protein) was detected in 41% of US breast cancer patients and 42% of Israeli patients. Scatchard analyses, performed on pooled membrane fractions with the highest specific PRL-binding revealed one class of receptors having a dissociation constant, Kd = 4.1 x 10(-9), and specific binding capacity, Bmax = 1.3 pmol per mg protein. These preparations were exposed to 3 M MgCl2, which dissociates the endogenous-bound PRL from the hormone-receptor complex and allows the characterization of the "total" PRL receptors. Two classes of receptors were then revealed. One class of receptors showed high affinity (Kd1 = 8.1 x 10(-10) M) and low capacity (Bmax1 = 335 fmol per mg protein), while the other possessed lower affinity (Kd2 = 8.2 x 10(-8) M), but a higher capacity (Bmax2 = 34.4 pmol per mg protein). Since PRL facilitates the growth of human breast cancer cell lines, these results indicate that a high proportion of human breast cancers may be PRL dependent. Routine determination of PRL receptors in biopsies of human breast cancer may permit the selection of a better treatment, since it is possible that the reduction in PRL levels could inhibit those tumors which are prolactin dependent.

Breast Neoplasms↗
PubMed1988

Lack of relationship between the levels of prolactin receptors and steroid receptors in women with breast cancer.

The levels of prolactin receptors (PRL-R), based on a new micro-method, estrogen receptors (ER) and progesterone receptors (PG-R), were determined in 159 breast cancer specimens. Sixty-seven of 159 tumors (42%) had PRL-R levels of 20 fmol/mg protein or higher, and were regarded as PRL-R positive. In 60 of the 159 samples (38%), no PRL-R could be detected, and the remaining 32 samples (20%) were considered borderline. While a positive correlation was found between the presence of ER and PGR, no correlation was detected between PRL-R and any steroid receptors (r = -0.024 for ER vs PRL-R, 0.052 for PGR vs PRL-R and 0.002 for ER + PGR vs PRL-R). Furthermore, PRL-R in levels of 20 fmol/mg protein or higher were found in 35% of samples in which no steroid receptors were detected as well as in 38% and in 27% of samples which exhibited positive ER or PGR respectively (greater than or equal to 20 fmol/mg protein). On the other hand, in 47% of the samples possessing both ER and PGR, the PRL receptors could not be found. These results clearly demonstrate that in the human breast cancer, the presence of PRL-R is independent of the status of either ER or PGR. It is suggested that the measurement of PRL-R could serve as a chemical marker to guide a possible therapeutic use of PRL-suppressing drugs in women with breast cancer.

Adult↗
PubMed1986

Micromethod for the determination of free and total prolactin receptors: measurement of receptor levels in normal and malignant mammary and prostate tissues.

A sensitive micromethod for the determination of free and total prolactin receptors in normal or malignant tissues has been developed. Positive and negative quality controls are incorporated in the procedure. Either whole tissue or the pellet fraction remaining from tissue that had undergone processing for estrogen receptors can be used. Crude microsomal and plasma membrane fractions obtained by homogenization and differential centrifugation are incubated with labeled prolactin in the presence or absence of increasing amounts of unlabeled hormone. The labeled ligand is prepared by a stoichiometric iodination procedure in which one atom of iodine-125 is incorporated into one molecule of the hormone, resulting in an intact labeled prolactin with a high specific activity of 170-186 muCi/micrograms (1 Ci = 37 GBq). Human prolactin labeled by this procedure has much greater specific binding capacity to various rat tissues than does iodinated rat prolactin. This technique permits an accurate measurement of prolactin receptors in as little as 50 micrograms of membrane protein. Highest levels of free and total prolactin receptors were found in the liver of 60-day-old female rats that served as a positive control. Liver of immature 21-day-old male rats, devoid of prolactin receptors, was used as a negative control. The amount of detectable free receptors was dependent on the level of circulating plasma prolactin. In 3-day postpartum lactating rats with high prolactin levels in plasma, all prolactin receptors in the mammary glands were found to be occupied, and no free receptors could be detected. When these receptors were desaturated from the endogenous prolactin by exposure to 3 M MgCl2, one class of receptors in a high quantity (1.75 nmol/mg of protein) and with a moderate affinity (Kd = 6.41 X 10(-9) M) was detected. A similar type of receptor was found in the mammary glands of rats at midpregnancy and of cycling adult female rats. In malignant rat mammary tissue, however, fewer receptors (27 pmol/mg of protein) but with a very high affinity (Kd = 6.8 X 10(-14) M) were detected. Normal ventral and dorsolateral rat prostate contained two classes of prolactin receptors (Kd = 3.46 X 10(-10) M and 1.93 X 10(-8) M). In the cancerous rat prostate, however, only one of these two classes of receptors was detected, and the number was smaller.

Animals↗