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Comparative Study 2004; 25(5): 351-355 PubMed PMID: 15580169 Citation  Keywords:  Administration, Oral, Animals, Anticonvulsants:administration & dosage, Aspartate Aminotransferases:blood, Body Weight:drug effects, Drug Administration Schedule, Female, Fertility:drug effects, Fructose:administration & dosage, Male, Organ Size, Prostate.   

PURPOSE: A case control study was conducted to assess the effects of long-term ingestion of Topiramate on fertility, body and reproductive organ weight and level of sex hormones in Sprague-Dawley male rats.

METHODS: Ten adult male rats were exposed to Topiramate diets at a concentration of 100 mg /kg for 60 days. Another ten control male rats received vehicle (distilled water). After 24 hours of the last dose, animals were autopsied under light anesthesia. Several parameters including, body and reproductive organ weight, sperm count and motility, serum testosterone, FSH, levels of cholesterol, triglyceride, SGOT and SGPT were all measured. Assessment of pregnancies in females mixed with tested males was also measured. The results of histological, histometrical and biochemical profiles were compared to that of the control group, and the significance of these results was measured using student's ''t'' and Chi- square tests.

RESULTS: Long-term ingestion of Topiramate for 60 days caused a significant decrease in spermatogenesis in seminiferous tubules of the testes. Sperm motility and density were also significantly reduced in cauda epididymides and testes of the treated group. The body weights and weight of reproductive organs (testes, epididymides, ventral prostate and seminal vesicle) were decreased considerably. Hormonal assay also showed significant decrease in testosterone levels. Testicular cell population dynamics also demonstrated a decrease in the number of both primary and secondary spermatocytes and spermatids in the treatment group. The number of female rats impregnated by male rats on long-term Topiramate diet had decreased. The number of implantations and the number of viable fetuses were also notably decreased in female rats impregnated by male rats ingested Topiramate. Histometry of reproductive organs confirmed these results.

CONCLUSION: these results confirm that the long-term Topiramate ingestion produces adverse effects on fertility and reproductive system in adult male rat....

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Journal Article 2004; 25(3): 219-222 PubMed PMID: 15349089 Citation  Keywords:  Animals, Estradiol:pharmacology, Female, Hypothalamus:enzymology, Rats, Rats, Wistar, Sexual Maturation:physiology, Synaptic Transmission:drug effects,.   

OBJECTIVES: To determine the hypothalamic activity of nitric oxide synthase (NOS, the enzyme involved in the synthesis of nitric oxide NO) during sexual maturation in prepubertal (15 days old) and peripubertal female rats (30 days old) as well as the effect of estradiol administration on this neurotransmitter system.

METHODS: Hypothalamic samples containing the anterior preoptic and medial basal areas (APOA-MBH) were homogenized with HEPES 20 mM, pH = 7.4 and NOS activity was determined in APO-MBH after 10 minutes of incubation by the conversion of 14C arginine to 14C citrulline.

RESULTS: The hypothalamic concentration of NOS is significantly higher in peripubertal than in prepubertal rats. Treatment with EB increased significantly the activity of the enzyme in both groups compared with control and the increases was similar at both ages.

CONCLUSIONS: These results clearly demonstrated that the hypothalamic NOS activity increases in peripubertal rats as compared with prepubertal animals. Estradiol has a similar stimulatory effect on hypothalamic NOS activity at both ages of sexual maturation, indicating that the increase in NOS during sexual maturation is connected with the peripubertal increase of estradiol rather than an increase in the sensitivity of the enzyme to the ovarian hormone....

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Comparative Study 2004; 25(1-2): 78-82 PubMed PMID: 15159688 Citation  Keywords:  Adenosine Triphosphatases:genetics, Animals, Cation Transport Proteins:genetics, Copper:deficiency, Disease Models, Animal, Female, Male, Median Eminence:diagnostic imaging, Menkes Kinky Hair Syndrome:genetics, Mice, Mice, Mutant Strains, Mutation, Recomb.   

OBJECTIVES: The mosaic mutation (Atp7a(mo-ms)) linked to X-chromosome is caused by changes in the Atp7a gene encoding CPx-type protein responsible for the ATP-dependent copper transport across cell membranes. Mosaic mutant males represent an animal model for Menkes disease in humans. Starting from the eighth day of life the mosaic males exhibit a progressive decrease in body weight with poor viability and progressive paresis of the hind limbs. In order to examine whether hypothalamic somatostatin metabolism may be different in normal and copper deficient mice, somatostatin accumulation at the level of median eminence in 14 days old normal and mosaic mutant males was compared.

METHODS: An electron microscopic immunocytochemical study on ultrathin brain slices was performed according to post-embedding immunogold procedure.

RESULTS: In non-mutant animals somatostatin has been detected in many synapses within median eminence. Gold particles moderately decorated synaptic vesicles and mitochondria. In mosaic mutant animals somatostatin expression within the median eminence was very low and only a few gold particles represented somatostatin. Particles were sporadically associated with synaptic vesicles, mitochondria or cytoskeleton elements. Moreover, pre- and post- synaptic parts of synapses were very often swollen.

CONCLUSION: Our data demonstrating that copper deficiency leads to the pathological changes within the median eminence ultrastructure and severe impairment of somatostatin expression suggest that this trace metal is an important element necessary for normal neurohormonal brain development....

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Journal Article 2003; 24(5): 329-333 PubMed PMID: 14647006 Citation  Keywords:  Aged, Aging:physiology, Cells, Cultured, Euchromatin:drug effects, Heterochromatin:drug effects, Hot Temperature, Humans, Lymphocytes:cytology, Oligopeptides:pharmacology, Protein Denaturation, Ribosomal Proteins:genetics, Transcriptional Activation:drug .   

UNLABELLED: OBJECTIVES and design. We have studied the effect of synthetic peptide Epitalon on the activity of ribosomal genes, denaturation parameters of total heterochromatin, polymorphism of structural C-heterochromatin and the variability of facultative heterochromatin in cultured lymphocytes of persons aged 76-80 years.

RESULTS: The obtained data demonstrate that Epitalon induces the activation of ribosomal genes, decondensation of pericentromeric structural heterochromatin and the release of genes repressed due to the age-related condensation of euchromatic chromosome regions.

CONCLUSIONS: Epitalon has shown its ability to activate chromatin by modifying heterochromatin and heterochromatinized chromosome regions in the cells of older persons....

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Journal Article 2003; 24(3-4): 269-273 PubMed PMID: 14523369 Citation  Keywords:  Adenocarcinoma:pathology, Animals, Cell Nucleus:ultrastructure, Circadian Rhythm:physiology, Colonic Neoplasms:pathology, Male, Mice, Mice, Inbred Strains, Neoplasm Transplantation, Organelles:ultrastructure, Pineal Gland:cytology,.   

OBJECTIVES: Relationship between the pineal gland and neoplastic disease has been repeatedly shown in many both experimental and clinical studies. However, morphological studies of the pineal gland in animals with experimentally-induced tumors are rare. Therefore, we decided to investigate the ultrastructure of pinealocytes in mice with implanted Colon 38 adenocarcinoma.

MATERIAL AND METHODS: Male adult B6D2F1 mice were used in this study. The animals were divided into two groups. Eight mice were subcutaneously implanted with Colon 38 cell suspension, whereas the other eight intact animals served as controls. Three weeks after tumor implantation four animals from each group were sacrificed by spinal cord dislocation at 12:00 h or 24:00 h. The pineal glands were removed and processed for electron microscopic studies. The cross-sectional areas of the pinealocyte and its nucleus, and relative volume of mitochondria, Golgi apparatus, lysosomes, granular endoplasmic reticulum, and lipid droplets, as well as the number of dense-core vesicles were estimated using a digital analyzer connected on-line to IBM-PC computer. Statistical analysis of the data was performed using Student's t-test and Snedecor F test.

RESULTS: In the pineal glands of the tumor-bearing animals killed during the daytime diminished size of pinealocytes and their nuclei, decreased relative volume of granular endoplasmic reticulum, lysosomes, and lipid droplets as well as decreased number of dense-core vesicles were observed. On the contrary, the relative volumes of mitochondria and Golgi apparatus were increased in these animals. In the tumor-bearing animals killed at night, however, increased cross-sectional areas of pinealocytes, and decreased number of dense-core vesicles were observed.

CONCLUSIONS: The results of our study suggest that the presence of the malignant tumor influences the morphology of pineal cells in mice. Considering the fact that different patterns of ultrastructural changes were demonstrated in pinealocytes in different tumor types in various species, it seems that the character of the ultrastructural changes observed in tumor-bearing animals depends on the animal species and tumor type....

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Journal Article 2003; 24(1-2): 68-72 PubMed PMID: 12743536 Citation  Keywords:  Animals, Bivalvia:metabolism, Cold Temperature:adverse effects, Down-Regulation, Ganglia, Invertebrate:metabolism, Nitric Oxide:biosynthesis, RNA:analysis, Receptors, Opioid, mu:biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Stress, Physio.   

OBJECTIVES: Subjecting the marine bivalve Mytilus edulis to an immediate temperature change has been shown to rapidly alter the animals' ganglionic monoamine levels, as well as its ciliary activity. Recently, we extended this observation to include the organism's ganglionic mu opiate receptor and morphine levels. In the past, we demonstrated that M. edulis ganglionic mu receptors exposed to morphine was coupled to the immediate release nitric oxide (NO). In this study, we measured morphine-induced NO release in M. edulis subjected to acute cold stress.

METHODS: NO release was monitored with an NO-selective microprobe. Temporal changes in mu opiate receptor expression were also examined over 24 hours.

RESULTS: In this study, we demonstrate that after 12h cold exposure (4 degrees C from 24 degrees C), the estimated relative mu opiate receptor (MOR) gene expression in M. edulis pedal ganglia, measured by real-time PCR, did not differ significantly from the control group (1.23+/-0.25, p>0.05). However, the measured M. edulis pedal ganglia MOR expression demonstrated that ganglia significantly (0.77+/-0.05, p<0.001) down regulated their mu opiate receptor mRNA expression after 24h exposure to the cold water. The mean value for control animal (24 degrees C, n=14) morphine-stimulated NO release was 36.7 +/- 9.8 nM. Morphine additions to cold-treated tissues (4 degrees C, n=7) produced an average of 6.7 +/- 4.9 nM NO, which was a statistically significant difference between 25 degrees C and 4 degrees C animals (p=0.025).

CONCLUSION: The study further demonstrates that mu opiate receptor expression is coupled to NO release....

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Editorial 2002; 23(5-6): 379-384 PubMed PMID: 12500156 Citation  Keywords:  Authoritarianism, Conflict (Psychology), Humans, Jews:psychology, Memory:physiology, Neurotransmitter Agents:physiology, Personality:physiology, Psychoanalytic Theory, Temperament:physiology,.   

: Research on personality as a useful construct to understand people's behavior in conflict situations was traced over more than fifty years, and an attempt was made to add neurobiological parameters to psycho-socio-cultural approaches. As a starting point, scientists in exile have been called to mind who had been expelled from Nazi Germany for their Jewish origins. Among them were Adorno and Frenkel-Brunswik whose extensive studies on the authoritarian personality structure were quoted. In their work, personality was defined as a more or less enduring organisation of forces within the individual helping to determine responses in various situations, which is responsible for consistency in behavior. As a next step, Cloninger's psychobiology of personality traits was presented. In his personality concept, four temperamental traits (novelty seeking, harm avoidance, reward dependency and persistence) and three character dimensions are included. Temperamental traits are heritable, developmentally stable, emotionally based, uninfluenced by social learning, and linked to specific brain biological features. The temperaments have a certain neuroendocrinological feature which can be determined. Character dimensions develop in a stagelike process from infancy to adulthood and are influenced by temperament, social learning, genetic factors, and random life events. Personality is still considered a useful theoretical approach to conflict management research and practice. A neurobiological point of view seems to be a useful supplementation in addition to traditional psycho-socio-cultural approaches. Measuring biological compounds can supply the conflict manager with an additional tool of knowledge enhancing the ability to understand and anticipate conflict behavior....

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Journal Article 2002; 23(Suppl 1): 55-60 PubMed PMID: 12019353 Citation  Keywords:  Animals, Blotting, Southern, Blotting, Western, Cell Membrane:metabolism, Cell Nucleus:metabolism, Colonic Neoplasms:genetics, Gene Expression Regulation, Neoplastic:genetics, Male, Mice, Neoplasm Transplantation, Nuclear Receptor Subfamily 1, Group F, Me.   

OBJECTIVES: There are some data suggesting that melatonin exerts oncostatic action through membrane as well as nuclear receptors. In previous studies we demonstrated the antiproliferative and proapoptotic action of melatonin on transplantable murine Colon 38 adenocarcinoma cells. Therefore, the aim of the present study was to determine whether the membrane melatonin receptors MT(1) and MT(2) as well as the nuclear receptor RZR/ROR alpha are expressed in Colon 38 cells.

MATERIAL AND METHODS: Adult male B6D2F1 mice were used in this experiment. The induction of tumor was conducted by subcutaneous injection of 0.2 mL of a 33% suspension of Colon 38 cancer cells into axillary region. Expression of mRNA encoding MT(1) and MT(2) melatonin membrane receptors was studied by RT-PCR analysis, and expression of ROR alpha(1) nuclear receptor protein was studied by Western blot analysis.

RESULTS: The expression of mRNA encoding both MT(1) and MT(2) melatonin receptors was demonstrated in Colon 38 cancer cells. Moreover, immunodetection revealed the expression of MT(1) and ROR alpha(1) proteins in these cells.

CONCLUSIONS: Our studies on Colon 38 adenocarcinoma cells support the concept that both membrane and nuclear receptors are involved in the oncostatic action of melatonin....

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