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Journal Article 2002; 23(Suppl 4): 67-77 PubMed PMID: 12496737 Citation  Keywords:  Animals, Cognition:drug effects, Embryonic Development:drug effects, Gonadal Steroid Hormones:pharmacology, Humans, Models, Biological, Periodicity, Seasons, Sex Characteristics,.   

: The major sex differences in cognitive skills are summarized, and the role of sex hormones in early organization and possible maintenance of these differences is discussed. Using animal models and human hormonal anomalies, a good case can be made that prenatal androgens strongly influence adult cognitive pattern, though the relation between baseline androgens and spatial ability, for example, need not be linear. Moreover, men and women remain sensitive to variation in hormonal state, as evidenced in the fluctuations in cognitive and motor performance across natural diurnal, menstrual and circannual rhythms. Evidence from administration of exogenous hormones in humans is more equivocal, though this field ultimately should yield useful information....

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Journal Article 2002; 23(5-6): 437-439 PubMed PMID: 12500166 Citation  Keywords:  Animals, Diabetes Mellitus, Experimental:chemically induced, Disease Models, Animal, Insulin:pharmacology, Insulin-Like Growth Factor I:analysis, Male, Rats, Rats, Sprague-Dawley, Sulfonylurea Compounds:pharmacology,.   

OBJECTIVE: Diabetes Mellitus is associated with decreased insulin-like growth factor-I (IGF-I) levels and also, poor growth in diabetes is related with low circulating levels of IGF-I. Insulin acts via an increase of IGF-I synthesis on growth. We studied the effects of insulin and sulphonylureas on serum IGF-I levels and aimed to evaluate the restoration of IGF-I in different therapeutic strategies.

DESIGN AND SETTING: Thirty male rats were used in the study and diabetes was induced by a single intraperitoneal injection of streptozotocin (35 mg/kg body weight). After confirmation of hyperglycemia, rats were divided into three groups. The first group was treated with insulin, and second group with glimepiride, third group was not treated (control group). IGF-I levels were measured at basal, after streptozotocin and at the end of the treatment period.

RESULTS: Serum IGF-I levels were found to decrease from 577.2 ng/ml to 253.0 ng/ml after streptozotocin (p<0.005). After 1 month, IGF-1 levels were found 524.0 ng/ml in insulin group, 449.3 ng/ml in sulphonylurea group, and 313.1 ng/ml in control group. The increase in IGF-I was statistically significant in insulin group (p<0.005), and in sulphonylurea group (p<0.05), but it was not significant in control group (p>0.05).

CONCLUSIONS: Serum IGF-I levels decrease in diabetes and insulin treatment restores IGF-I depletion significantly. And although less effective, treatment with glimepiride restores IGF-I levels significantly....

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Journal Article 2002; 23(5-6): 432-436 PubMed PMID: 12500165 Citation  Keywords:  Adrenergic alpha-2 Receptor Antagonists, Adrenergic alpha-Antagonists, Adrenergic beta-Antagonists:pharmacology, Animals, Calcium Channel Blockers:pharmacology, Diabetes Mellitus, Experimental:chemically induced, Disease Models, Animal, Dose-Response Rela.   

OBJECTIVE: Ghrelin is a newly discovered peptide, which was first demonstrated in the epithelium of rat stomach. The purpose of the study was to examine the effect of ghrelin on glucagon secretion from pancreatic tissue fragments of normal and diabetic rats.

METHODS: Diabetes was induced by streptozotocin (60 mg Kg body weight 1) given intraperitoneally. Four weeks after the onset of diabetes, pancreatic fragments of normal and diabetic rats were incubated with different concentrations (10 12 10 6 M) of ghrelin. Glucagon release was measured using radioimmunoassay technique.

RESULTS: Ghrelin failed to stimulate or inhibit glucagon secretion from normal rat pancreas. However, it induced significant increases in glucagon secretion from pancreatic tissue fragments of diabetic rats. Either atropine (muscarinic cholinergic receptor antagonist) or propranolol (beta-adrenergic receptor antagonist) or yohimbine (alpha2-adrenergic receptor antagonist) or diltiazem (calcium channel antagonist) did not affect ghrelin-glucagon interaction. Moreover, a combination of atropine, propranolol and yohimbine had no significant effect on the interaction of ghrelin with glucagon.

CONCLUSION: The ghrelin-induced glucagon secretion in diabetic rats is not controlled via cholinergic or adrenergic pathways. In conclusion, it appears that the main target of ghrelin in the rat endocrine pancreas is not glucagon-producing cells but rather insulin secreting cells which are more involve in weight gain and body growth....

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Journal Article 2002; 23(5-6): 411-416 PubMed PMID: 12500162 Citation  Keywords:  Animals, Cell Division:drug effects, Cell Membrane:chemistry, Cerebral Cortex:chemistry, Concanavalin A:pharmacology, Crosses, Genetic, Enzyme Activation:drug effects, Interleukin-1:metabolism, Lymphocyte Activation:drug effects, Male, Mice, Mice, Inbred .   

OBJECTIVES: The aim of this research consisted in studying the effects of tetrapeptide Epitalon on both thymocyte proliferation and interleukin-1beta (IL-1beta) signal transduction via sphingomyelin pathway in the cerebral cortex membranes of mice exposed to stresses exerting diverse effects upon humoral immune response.

DESIGN AND SETTING: The experiments were performed on male (CBAxC(57)BL(6))F1 mice aged 8 10 weeks. Two models of experimental stress were used: immune-stimulatory rotation stress and immune-suppressive combined stress (cooling followed by immobilization). The concomitant effect of Epitalon was determined according to its influence on thymocyte proliferation stimulated by concanavalin A at a sub-optimal dose and recombinant IL-1beta. The activity of membrane neutral sphingomyelinase (nSMase), the key enzyme of the sphingomyelin signal transduction pathway, was assayed according to modified Rao and Spence's method (1976).

RESULTS: The investigation demonstrated that Epitalon increased thymocyte proliferative activity, both enhanced under rotation stress and suppressed under combined one. It also increased IL-1beta concomitant effect. These findings corresponded to Epitalon effect on diverse stress-induced changes in nSMase activity in cerebral cortex fraction P2. Epitalon activated nSMase in the cerebral cortex membranes of intact mice and increased IL-1beta stimulatory effect on the enzyme activity.

CONCLUSIONS: The obtained results provided a conclusive evidence of Epitalon stress-protective effect at the level of IL-1beta signal transduction via sphingomyelin pathway in the nerve tissue, as well as at the level of target thymocyte proliferation....

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Journal Article 2002; 23(4): 335-340 PubMed PMID: 12195237 Citation  Keywords:  Animals, Anticonvulsants:pharmacology, Cell Division:drug effects, DNA:biosynthesis, Drug Interactions, Hepatocytes:drug effects, Male, Melatonin:pharmacology, Mutagens:pharmacology, Necrosis, Nitroparaffins:pharmacology, Propane:analogs & derivatives, Ra.   

OBJECTIVES: 2-Nitropropane (2-NP) is mutagenic in a number of short-term mutagenicity assays in vitro and in vivo, and is a potent hepatocarcinogen in rats. Many studies have determined that differences in the metabolism and disposition of the chemicals that produce mutagenicity were not responsible for their observed carcinogenic differences, but that carcinogenicity correlated with the ability of the respective isomer to induce cell proliferation in the target organ.

METHODS: Three groups of male rats (control, 2-NP-treated [4 mmol/kg] and 2-NP + melatonin [10 mg/kg]) were used in the current study. Cell proliferation was quantitated by incorporation of 3H-thymidine, detected by autoradiography, into newly synthesized DNA. Histopatholgical study was carried out to investigate the morphological changes.

RESULTS: Twenty four hours after 2-NP administration, there was an increase in the labelling index (LI) and grain count per labelled nucleus (GC/N) in the hepatocytes of 2-NP-injected rats versus those of control animals. The increase was 69.5% in LI and 29.4% in GC/N. Melatonin treatment, 30 minutes preceding 2-NP, reduced the increase in LI (44.4%) and GC/N (20.7%) when compared with 2-NP-treated rats. Histopathology revealed multiple focal areas of necrosis in the liver following 2-NP injection. In the lung, there was a mucinous degeneration of the bronchial epithelium. Melatonin treatment restored the histopathological changes in both the liver and lung and they are more or less normal.

CONCLUSION: Overall, these results seem to indicate that the stimulatory effect of 2-NP on the cellular proliferation and the rate of DNA synthesis in the liver may be one of mechanisms by which the carcinogen induces its carcinogenic action. Also, melatonin treatment strongly protects the studied organs against the toxic effect of 2-NP....

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Journal Article 2002; 23(4): 325-328 PubMed PMID: 12195235 Citation  Keywords:  Animals, Antineoplastic Agents:pharmacology, Astrocytes:cytology, Cerebral Cortex:cytology, DNA-Binding Proteins:metabolism, Gene Expression:drug effects, Glioma, Growth Inhibitors:pharmacology, Interferon-gamma:pharmacology, Interleukin-6:pharmacology, L.   

OBJECTIVES: The purpose of this study was to compare the effects of neurotrophic cytokines on the JAK/STAT transcription factors and the immediate early gene, c-fos, in C6 glioma cells and in primary astrocyte cultures.

METHODS: In this study we compared the effects of interleukin 6, leukemia inhibitory factor and interferon gamma on C6 glioma cells and on primary astrocyte cultures using electrophoretic mobility shift assay and quantitative solution hybridization/Northern Blot analysis.

RESULTS: We show that interleukin 6, leukemia inhibitory factor and interferon gamma treatment induce the nuclear STAT3 and STAT1 proteins to bind to the sis inducible element of c-fos in both C6 glioma cells and primary cortical astrocytes. Furthermore, quantitative solution hybridization and Northern blot analysis show the differential regulation of c-fos mRNA levels by interleukin-6 (8.1 and 4.0 folds) and leukemia inhibitory factor (5.4 and 3.2 folds) in C6 and astrocyte cultures (respectively). However, interferon gamma increases in c-fos mRNA levels (2.9 fold in both C6 and astrocyte cultures) were not significant in a one way ANOVA.

CONCLUSION: This study suggests that two initial cytokine signaling pathways are present and functional in C6 glioma cells and in primary astrocyte cultures....

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Journal Article 2002; 23(4): 321-324 PubMed PMID: 12195234 Citation  Keywords:  Adjuvants, Immunologic:pharmacology, Animals, Carcinogenicity Tests, Dehydroepiandrosterone:pharmacology, Estradiol:pharmacology, Female, Galanin:genetics, Gene Expression:drug effects, Pituitary Gland, Anterior:drug effects, Prolactin:blood, RNA, Messeng.   

OBJECTIVES: The effects of dehydroepiandrosterone (DHEA) on galanin (GAL) and prolactin (PRL) mRNA expression in the anterior pituitary of Fischer 344 rats were studied, taking in consideration that: (1) DHEA is an androgen with estrogenic activity on pituitary lactotrophs; (2) estrogens induce prolactinomas in Fischer 344 rats; and (3) GAL has been considered the main mediator of estrogen-induced lactotroph proliferation.

DESIGN: Female rats were ovariectomized and used as controls or treated during 2 weeks with DHEA (500 mg/kg/day or 5 mg/kg/day or 50 mg/kg/day) or estradiol (E2, 50 microg/kg/day), as a positive control for pituitary growth and GAL induction. GAL and PRL mRNA expression were studied by in situ hybridization.

RESULTS: Both DHEA and E2 induced PRL mRNA synthesis. However, DHEA neither produced pituitary enlargement nor GAL induction, in contrast to E2.

CONCLUSIONS: Our results shows that GAL is not involved in the estrogenic activity of DHEA on pituitary lactotrophs, and suggest that DHEA effects are exerted directly on the PRL gene or through another mechanism(s) not related to GAL....

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Comparative Study 2002; 23(3): 249-254 PubMed PMID: 12080287 Citation  Keywords:  Animals, Body Temperature, Brain Ischemia:pathology, Infarction, Middle Cerebral Artery:drug therapy, Male, Neuropeptides:pharmacology, Neuroprotective Agents:pharmacology, Pituitary Adenylate Cyclase-Activating Polypeptide, Rats, Rats, Wistar, Vasoactive.   

OBJECTIVES: Pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) belong to the same peptide family, and both neuropeptides have been shown to exert in vitro and in vivo neurotrophic and neuroprotective effects. The aim of the present study was to investigate and compare the protective effects of PACAP and VIP in permanent focal cerebral ischemia in rats. The effect on the progression of the cerebral infarct was also studied.

METHOD: Male rats were injected 450 pmol PACAP or VIP dissolved in physiological saline intracerebroventricularly, preceding the occlusion of the middle cerebral artery. Control animals received vehicle treatment. Permanent focal ischemia was induced by the intraluminal filament occlusion of the middle cerebral artery. Animals were sacrificed 12 or 24 hours after the onset of ischemia, and infarcted brain areas were determined by staining bran sections with triphenyl-tetrazolium chloride.

RESULTS: Twelve hours after ischemia, the infarcted brain volume resulted to be 14.8% in the control group, 15.3% in the VIP-treated group and 5.8% in the PACAP-treated animals. Twenty-four hours after middle cerebral artery occlusion, the infarcted brain volumes were 21.5%, 20.7% and 14.3% in the control, VIP and PACAP-treated animals, respectively.

CONCLUSION: Our results provide further evidence for the neuroprotective effects of PACAP38 as given in form of a preischemic bolus. It slows down the progression of the evolution of the infarct and reduces the final infarct size. In contrast, a related peptide, VIP, does not have neuroprotective effects under the same experimental conditions....

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