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Comparative Study 2008; 29(6): 917-923 PubMed PMID: 19112412 Citation  Keywords:  Animals, Behavior, Animal:drug effects, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Interactions, Exploratory Behavior:drug effects, Male, Motor Activity:drug effects, Neuropeptides:administration & dosage, Neuroprotective Agents:.   

OBJECTIVES: On the animal model of trimethyltin (TMT) induced behavioral deficits the effect of chronic treatment with spirocyclic dipeptide cyclo/alanyl-l-amino-l-cyclopentane-carbonyl (alaptide, AL) was evaluated in adult male rats.

METHODS: Changes in the spontaneous behavioral repertoire were investigated in the open-field test on Day 21 (Session 1) and Day 28 (Session 2) after a single oral TMT administration.

RESULTS: In Experiment 1, rats given the highest TMT dose (7.5 mg/kg) exhibited significantly increased total number of behavioral patterns, the floor sniffing being the most frequent pattern. While the medium TMT dose (5 mg/kg) had a similar effect only in Session 1, the lowest TMT dose (2.5 mg/kg) was entirely ineffective. In Experiment 2, an explicit beneficial influence of both AL doses (5 and 10 mg/kg) given for 10 days before and 10 days after TMT (7.5 mg/kg) on the spontaneous behavior repertoire was observed in both Session 1 and Session 2. The total number of patterns and the time spent in individual patterns of AL+TMT treated animals did not differ from the controls and those given AL alone.

CONCLUSION: We conclude that sufficiently long AL treatment interfered with deleterious effects of TMT and forestalled changes in the structure and timing of spontaneous behavioral patterns. Thus, AL can be designated as a substance having "neuroprotective" effects....

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Letter 2008; 29(1): 59-62 PubMed PMID: 18283267 Citation  Keywords:  Acromegaly:blood, Dose-Response Relationship, Drug, Drug Administration Schedule, Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:metabolism, Octreotide:therapeutic use, Peptides, Cyclic:therapeutic use, Poland, Somatostatin:analogs & derivativ.   

: Consensus statement of the Polish Society for Endocrinology, regarding presurgical somatostatin analogs in acromegaly has been presented. It is suggested to administer depot somatostatin analog (Octreotide LAR at the dose 20 mg and then 30 mg or equivalent doses of Lanreotide Autogel 90/120 mg every 4 weeks) in order to normalize or suppress to a maximal extent GH and IGF-1 concentrations. The period of therapy in case of microadenoma would be at least 3 months (targets: biochemical improvement, reduced risk of disease's complications, perioperative risk reduction, inhibition of tumor growth). The period of therapy in case of macroadenoma would be at least 6 months, until maximal possible reduction of GH and IGF-1 concentrations (targets: tumor shrinkage, biochemical improvement, reduced risk of disease's complications, perioperative risk reduction). Using an uniform approach in a group, as numerous as possible, of treated patients would allow objective evaluation of long-term efficacy of the treatment....

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Clinical Trial 2007; 28(6): 727-733 PubMed PMID: 18063933 Citation  Keywords:  Acromegaly:drug therapy, Adult, Antineoplastic Agents:administration & dosage, Blood Glucose:metabolism, Delayed-Action Preparations, Drug Administration Schedule, Female, Follow-Up Studies, Homeostasis:drug effects, Human Growth Hormone:blood, Humans, In.   

OBJECTIVE: To evaluate the short-term effects of Lanreotide Autogel on insulin sensitivity markers among acromegalic patients with pituitary tumors.

DESIGN: Prospective clinical trial with six months of follow-up.

SETTING: A tertiary endocrinology clinic.

MATERIALS AND METHODS: Naïve patients (patient No. 1 and patient No. 3) and patients who experienced prior somatostatin analogue treatment (patient No. 2, patient No. 4, and patient No. 5) were included. Before and after 6 months of Lanreotide Autogel therapy, insulin sensitivity in each subject was determined using homeostasis model assessment of insulin resistance and beta-cell function formula. Euglycemic hyperinsulinemic clamp test was also performed to evaluate whole insulin sensitivity and was indicated as an 'M' index.

RESULTS: All patients experienced reduction in their HOMA-beta. We noted major HOMA-beta decreases accompanied by pronounced increases in M indices for patients Nos. 1, 2 and 3 (1.03 vs. 8.22, 2.98 vs. 4.70, and 5.09 vs. 13.09, respectively). The increases in M indices of these patients were with marked decreases in GH levels (34.20 vs. 15.30 microg/l, 4.25 vs. 0.74 and 5.0 vs. 0.66 ng/mL, respectively). Minor decline in HOMA-beta and worsened M index and almost stable GH were observed in patients Nos. 4 and 5. Except for patient No. 3, all participants showed declining HOMA-IR.

CONCLUSIONS: Short-term Lanreotide Autogel treatment has been observed to improve M indices of acromegalic patients whose GH levels exhibited marked reduction. This amelioration seemed to be related to decreases in GH levels rather than to a direct drug effect....

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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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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 2001; 22(4): 255-262 PubMed PMID: 11524633 Citation  Keywords:  Animals, Circadian Rhythm:drug effects, Drug Administration Schedule, Growth Hormone:blood, Insulin-Like Growth Factor I:metabolism, Male, Melatonin:administration & dosage, Oscillometry, Osmolar Concentration, Pineal Gland:physiology, Rats, Rats, Wistar,.   

BACKGROUND: A relationship between circadian GH-IGF-I axis activity and pineal gland function in rats is not sufficiently elucidated, particularly in the aspect of melatonin (MEL) participation with relation to a possible mechanism of these dependencies.

OBJECTIVE: Influence of pinealectomy and long-term MEL administration on circadian GH-IGF-I axis function in male rats was evaluated. An attempt was also made to determine whether the effect of exogenous MEL is dependent on the pineal gland presence.

METHODS: Studies were performed in 192 sexually mature male Wistar rats, which were subjected to pinealectomy or sham operation. In half of the animals from each group MEL (Sigma, USA) in dose of 50 microg/ 100g b.m. was administrated intraperitoneally (daily between 5 and 6 pm during a 4-week period). Blood for RIA assays of MEL, GH and IGF-I concentrations was collected every 3 hours during a day-beginning at 8 am (rats killed by decapitation).

RESULTS: Significant influence of pinealectomy and exogenous MEL on a daily profile of endogenous MEL in rats was confirmed. Distinct, dependent on the time of the day anomalies in circadian oscillations of GH and IGF-I showing positive correlation with changes in endogenous MEL concentrations were also shown. GH rhythm was suppressed in a group of rats with removed pineal gland; after pinealectomy distinct decrease and after MEL use - distinct increase of GH and IGF-I concentrations during the day were observed. It had influenced mean daily concentrations and values of amplitude of circadian GH and IGF-I oscillations in all studied groups of animals. In rats with preserved pineal gland the effect of exogenous MEL action was more intensified.

CONCLUSIONS: Pineal gland can influence circadian function of GH-IGF-I axis, and in mechanism of this dependence, changes in endogenous MEL concentrations seem to play an important role. Administration of MEL in rats after pinealectomy only partly prevents changes of GH-IGF-I axis function caused by gland removal, which can indicate participation of other pineal gland substances in generating disturbances. Influence of exogenous MEL on GH-IGF-I axis function during the day is dependent on the presence of pineal gland, which can be connected with indirect and/or direct influence of administrated hormone on this gland....

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Comparative Study 2001; 22(4): 229-237 PubMed PMID: 11524628 Citation  Keywords:  1,2-Dimethylhydrazine:administration & dosage, Animals, Biogenic Monoamines:metabolism, Carcinogens:administration & dosage, Circadian Rhythm:drug effects, Dopamine:metabolism, Drug Administration Schedule, Female, Hydroxyindoleacetic Acid:metabolism, Inj.   

OBJECTIVES: Our data on the contents of norepinephrine (NE), dopamine (DA) and the metabolite of serotonin 5-hydroxyindoleacetic acid (5-HIAA) measured in the suprachiasmatic nuclei (SCN), preoptic area (PA) and median eminence (ME) of hypothalamus of rats after single subcutaneous injection of 1,2-dimethylhydrazine (DMH) as well as the effect of this carcinogen on formation of reactive oxygen species (ROS) in the PA are presented in this paper.

RESULTS: Diurnal changes of DA in all studied brain structures and of NE in the PA have been observed in the control group. Their morning levels were higher than evening ones. Rhythms of 5-HIAA in the SCN and diurnal changes of ROS formation have been shown to have contrary changes in control. Both the morning (11 a.m.) and evening (11 p.m.) subcutaneous administration of DMH at the dose of 21 mg/kg of body weight resulted in changes of all rhythms observed in control. In some cases a phase shift was found, in others the rhythms of neurotransmitters and ROS formation disappeared entirely.

CONCLUSION: The data obtained confirm the idea of dopaminergic and serotoninergic systems taking part in mechanisms of a response of the hypothalamic nuclei to non-photic stimuli. It is suggested that the effect of DMH on the content and diurnal rhythms of neurotransmitters in the hypothalamic structures under study is due to its affecting activities of the enzymes of biogenic amines synthesis, synaptic transmission, melatonin synthesis and secretion rhythms. The change in ROS formation that is caused by administration of DMH is likely to be due to a disturbance of diurnal rhythms of neurotransmitters that are one of the sources of formation of free radicals in the brain....

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Journal Article 2001; 22(1): 53-73 PubMed PMID: 11393163 Citation  Keywords:  Adrenal Glands:physiology, Animals, Biological Clocks, Blood Pressure:physiology, Chronobiology Disorders:physiopathology, Chronobiology Phenomena, Chronotherapy, Circadian Rhythm:physiology, Drug Administration Schedule, Genomics, Homeostasis, Humans, Pi.   

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