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Journal Article 2005; 26(1): 43-49 PubMed PMID: 15726019 Citation  Keywords:  Adrenergic alpha-Agonists:pharmacology, Adrenergic alpha-Antagonists:administration & dosage, Animals, Atmosphere Exposure Chambers, Atmospheric Pressure, Hypoxia:drug therapy, Injections, Intraventricular, Male, Median Eminence:drug effects, Norepinephri.   

OBJECTIVE: We have previously found that chronic hypoxia inhibited thyrotropin-releasing hormone (TRH) mRNA expression in rat paraventricular nucleus (PVN). This study presented the effects of hypoxia on TRH secretion in rat hypothalamus, and the norepinephrine (NE) involvement in the modulation of TRH secretion during acute hypoxia exposure.

SETTING AND DESIGN: Hypoxia was simulated at altitudes of 5 km (10.8% O2) or 7 km (8.2% O2) in a ventilated hypobaric chamber, and control group was set at local altitude of 2.3 km (15.8% O2). The duration of hypoxia exposure was designed acutely and chronically for 0.5, 2, 24 h, 5, 10, and 30 d, respectively. TRH levels were measured by specific radioimmunoassay.

RESULTS: The results showed that hypoxia of 5 km or 7 km significantly enhanced TRH levels of the ME and PVN, and reduced serum T3 levels in most hypoxia-exposed groups. Intraventricular injection (icv) of NE (4 nmol/L) induced a decrease in TRH levels in the median eminence (ME) and PVN, and an increased serum T3 levels following hypoxia of 7 km exposure for 2 h, compared with icv saline control, indicating TRH release increased. The stimulating effect of NE on the TRH secretion was abolished by icv antagonist of adrenergic alpha2-receptor, yohimbine (40 nmol/L).

CONCLUSIONS: We conclude that acute and chronic hypoxia exposure produces an inhibition of hypothalamic TRH secretion from the ME and PVN. Central adrenergic system may play a stimulating role through alpha2-receptor in the acute hypoxia-modulating TRH release from rat hypothalamus....

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Clinical Trial 2005; 26(1): 39-42 PubMed PMID: 15726018 Citation  Keywords:  Aging:physiology, Child, Preschool, Chorionic Gonadotropin:administration & dosage, Cryptorchidism:drug therapy, Humans, Infant, Injections, Intramuscular, Male, Scrotum:pathology,.   

OBJECTIVES: To evaluate the efficacy of hCG therapy on retractile testis in various testicular locations and age groups.

SETTING AND DESIGN: This study comprised 123 boys whose diagnosis were retractile testis with scrotal base, high scrotal and superficial inguinal localizations with an average age of 4,2 (1-8) years.

METHODS: 123 boys with retractile testes were given a total dose of 9000 hCG and its effect on scrotal base, high scrotal and superficial inguinal located testes were evaluated after 2 weeks and 6 months of completing hCG course. The patients were evaluated in four age groups such as less than 2 years of age, between 2-4, 4-6 years and more than 6 years of age and the response rates were also noted in these age groups.

RESULTS: In unilateral cases, the response in base, high scrotal and superficial inguinal levels were found as 100%, 83,3%, 72,7% respectively where as these rates were found as 100%, 92,6%, 76,3% respectively in bilateral cases after 2 weeks of hCG therapy. The response rates in less than 2 year old group, 2-4, 4-6 and more than 6 years group were found as 0%, 80%, 78,7%, 100% respectively in unilateral cases and 33,3%, 90%, 86,9% and 83,3% respectively in bilateral cases. After 6 months, reascend was observed in 12,4% in unilateral group and 6,7% in bilateral group.

MAIN FINDINGS: 72,7-100% of retractile testes respond to hCG administration with the highest response in the age of more than six year group.

CONCLUSION: High response rates observed in retractile testes after hCG therapy in more than 2 years old age group indicate that hCG must be given as a primary treatment in retractile testes and orchiopexy for the failures. Also patients must be followed up closely for reascend cases....

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Clinical Trial 2004; 25(6): 438-442 PubMed PMID: 15665807 Citation  Keywords:  Adult, Estradiol:blood, Follicle Stimulating Hormone:blood, Humans, Hypothalamo-Hypophyseal System:drug effects, Klinefelter Syndrome:blood, Luteinizing Hormone:blood, Male, Naloxone:administration & dosage, Narcotic Antagonists:administration & dosage, P.   

UNLABELLED: AIM TO THE STUDY: The investigation of the influence of anti-opioid drug on hypophyseal and gonadal hormones secretion in case of Klinefelter syndrome.

MATERIAL AND METHODS: The naloxone test (0,4 mg iv) was performed in 14 patients with Klinefelter syndrome aged from 19 to 32 and in 12 age matched control subjects with azoospermia and normal spermatogenesis in testicular histology. The plasma levels of FSH, LH, prolactin, testosterone and estradiol were established before and after 30, 60, 60 and 120 minutes respectively, following the drug administration.

RESULTS: Basal FSH, prolactin and estradiol levels were significantly higher whereas basal testosterone was significantly lower in patients with Klinefelter syndrome than in the control group. After the naloxone administration the mean plasma prolactin level decreased significantly (p=0.01) in Klinefelter subjects. The respective diminution in control group was not significant. The levels of FSH and LH as well as testosterone and estradiol did not change during the naloxone test in both Klinefelter and control subjects.

CONCLUSIONS: The naloxone administration in Klinefelter syndrome caused the decrease in plasma prolactin levels but did not affect the plasma level of another hypophyseal and gonadal hormones. The opioid controlled gonadotropin secretion is altered in case of Klinefelter syndrome....

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Clinical Trial 2004; 25(6): 419-422 PubMed PMID: 15665803 Citation  Keywords:  Adult, Anti-Anxiety Agents:administration & dosage, Antidepressive Agents:administration & dosage, Antipsychotic Agents:administration & dosage, Depression:drug therapy, Drug Therapy, Combination, Female, Humans, Hyperprolactinemia:blood, Male, Middle Age.   

OBJECTIVES: Amisulpride in antipsychotic doses can induce hyperprolactinemia. The aim of this study was to prove whether the same is true for low doses of amisulpride.

METHODOLOGY: Plasma prolactin levels were measured in 5 males and 5 females with depressive symptoms who were treated with 50 mg of amisulpride per day as an augmentation to antidepressants (n=5), benzodiazepine anxiolytics (n=8) or in monotherapy (n=1). Six of these patients were assessed prior to onset of amisulpride treatment and after 10 days of amisulpride use. Four patients had been using amisulpride for more than a month.

RESULTS: There was a significant increase of prolactin levels from mean 16+/-6 ng/ml to 113+/-65 ng/ml (median 14.5 ng/ml to median 92 ng/ml; Wilcoxon matched pair test, p=0.027). All patients had hyperprolactinemia (30-200 ng/ml). The prolactinemia was significantly higher in females (mean 160+/-50 ng/ml; median 198 ng/ml) than in males (mean 48+/-12 ng/ml; median 48 ng/ml; Mann-Whitney U test, p=0.041).

CONCLUSION: Even low doses of amisulpride used as an augmentation to antidepressant treatment, benzodiazepines or in monotherapy seem to be associated with hyperprolactinemia. The co-medication of antidepressants and benzodiazepines can potentially increase intensity of prolactinemia....

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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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Comparative Study 2004; 25(5): 323-330 PubMed PMID: 15580165 Citation  Keywords:  Alkaloids:administration & dosage, Animals, Benzylisoquinolines:administration & dosage, Bivalvia:metabolism, Cell Line, Dose-Response Relationship, Drug, Ganglia, Invertebrate:metabolism, Humans, Monocytes:drug effects, Morphine:metabolism, Nitric Oxide:.   

OBJECTIVES: Given the presence of morphine, its metabolites and precursors in mammalian and invertebrate tissues, it became important to determine if exposing tissues to an opiate alkaloid precursor, reticuline, would result in increasing endogenous morphine levels.

METHOD: Endogenous morphine levels were determined by high pressure liquid chromatography coupled to electrochemical detection and radioimmunoassay following incubation of Mytilus edulis pedal ganglia with reticuline. Nitric oxide (NO) release was determined in real-time via an amperometric probe. Mu opiate receptor affinity for opiate alkaloid precursors was determined by a receptor displacement assay.

RESULTS: Morphine is present in the pedal ganglia of Mytilus edulis (1.43 +/- 0.41 ng/mg +/- SEM ganglionic wet weight). Ganglia incubated with 50 ng of reticuline, a morphine precursor in plants, for 1 hour exhibited a statistical increase in their endogenous morphine levels (6.7 +/- 0.7 ng/mg tissue wet weight; P<0.01). This phenomenon is concentration dependent. The increase in ganglionic morphine levels occurs gradually over the 60 min incubation period, beginning 10 minutes post reticuline addition. We show that reticuline (10(-6) M) does not stimulate ganglionic NO release in a manner resembling that of morphine (10(-6) M), which releases NO seconds after its exposure to the ganglia and lasts for 5 minutes. With reticuline, there is a 3 minute delay, which is followed by an extended release period. Furthermore, in binding displacement experiments both reticuline and salutaridine (another morphine precursor) exhibit no binding affinity for the pedal ganglia mu opiate receptor subtype. This finding is further substantiated using the positive control of human monocytes where the mu3 opiate receptor subtype has been cloned.

CONCLUSION: Taken together, we surmise that the morphine's precursors are being converted to morphine. The experiments strongly indicate that pedal ganglia can synthesize morphine from reticuline....

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Comparative Study 2004; 25(1-2): 70-74 PubMed PMID: 15159686 Citation  Keywords:  Animal Feed, Animals, Antioxidants:physiology, Brain:metabolism, Dose-Response Relationship, Drug, Iodides:administration & dosage, Liver:metabolism, Lung:metabolism, Male, Melatonin:physiology, Oxidative Stress:physiology, Rats, Rats, Wistar, Schiff Base.   

OBJECTIVES: Administration of iodides to animals, living in iodine-deficient areas, can induce necrosis and fibrosis of the thyroid gland. It is believed that structural and functional changes of the thyroid may be related to oxidative processes. Increased lipid peroxidation levels were reported in murine thyroid glands after high doses of iodine. Melatonin (MEL) is believed to exert its effects via electron donation to directly detoxify free radicals, such as, e.g., the highly toxic hydroxyl radical. In numerous reports related to the antioxidative action of MEL, the authors have considered the protective ability of this hormone against peroxidation of lipids. The goal of the study was to evaluate oxidative processes and the protective role of MEL in three organs of the rat (the liver, the brain, and the lungs) during treatment with different doses of iodide.

MATERIAL AND METHODS: Schiff's bases (SB) concentrations (a parameter of oxidative stress) were measured in liver, lung and brain homogenates of male Wistar rats. The animals received iodides in their diet in the following concentrations, for 2 weeks: Group 1--Controls (standard normal-iodine diet, containing approx. 0.7 mg of kalium iodide per kg; KI/kg); Group 2--diet containing 0,25 mg KI/kg; Group 3--diet with 4,0 mg KI/kg; Group 4--diet with 8,0 mg KI/kg. Group 5--standard normal-iodine diet and MEL alone in a dose of 1 mg/kg BW i.p. at 3.00 pm, every day for two weeks. Subsequent three groups (6-8) received KI in their diet in doses as above, respectively, together with MEL.

RESULTS: We noted increased levels of SB in the lungs and in the liver, when compared to those observed in controls. We also found decreased SB concentrations in liver and lung homogenates after an administration of MEL but--unexpectedly--the level of SB increased in the group with the highest dose of iodine in diet in lung homogenates. Increased levels of Schiff's bases suggest that iodine is involved in oxidative processes not only in the thyroid but also in other tissues, and MEL protects against the iodine-induced oxidative stress.

CONCLUSION: Our results confirm the differences in lipid peroxidation among the examined organs. These alterations can possibly be related to different sensitivity rates of examined tissues to oxidative damage....

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Clinical Trial 2003; 24(5): 334-338 PubMed PMID: 14647007 Citation  Keywords:  Adenoma:drug therapy, Adult, Antineoplastic Agents:administration & dosage, Apoptosis:drug effects, Female, Humans, Male, Middle Aged, Peptides, Cyclic:administration & dosage, Pituitary Neoplasms:drug therapy, Somatostatin:administration & dosage,.   

OBJECTIVES: Apoptosis of endocrine cells represents one of factors significantly affected the control of hormones secretion. Present study aimed to examine whether treatment of somatotropinoma types tumours with somatostatine analogue (lanreotide) results in apoptosis.

MATERIAL AND METHODS: The studies were performed on 35 patients with somatotropinoma type tumours on whom adenomectomy was performed by transsphenoidal approach. The operative material was examined by cellular morphology, based on light and electron microscopy and chromosomal ladder formation assay.

RESULTS: The number of apoptotic cells showed features typical for the process as condensation and fragmentation of chromatin, vacuolisation, damage of the inner structure of mitochondria and oligonucleosomal fragmentation of DNA was found in the study material. The results of the studies demonstrated the occurrence of lanreotide induced apoptosis in somatotropinoma type tumours. The grade of apoptotic cells in macroadenomas type adenomas, treated with lanreotide, ranged from 4.0% to 17.1% (mean 8.7+/-2.6%). Patients in whom hypophysectomy was not preceded by lanreotide treatment demonstrated low level of apoptotic cells (no more than 3.5%).

CONCLUSIONS: The studies showed that treatment with somatostatine analogue-lanreotide induced apoptosis of tumour cell suggesting that the induction of apoptotic cell death may be involved in the anticancer activity of somatostatine analogue....

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