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Journal Article 2011; 32(2): 170-175 PubMed PMID: 21552201 Citation  Keywords:  Animals, Cell Proliferation:drug effects, Dopamine:metabolism, Dose-Response Relationship, Drug, Ethanol:pharmacology, Female, Glutamic Acid:metabolism, Hypothalamus:drug effects, Models, Animal, Neurotransmitter Agents:metabolism, Norepinephrine:metaboli.   

OBJECTIVES: Alcohol induces hyperprolactinemia in both alcoholic men and women, but the mechanism is not fully established. The aim is to investigate the mechanism involved in elevation of serum prolactin level after chronic alcohol administration.

METHODS: In this study, healthy female SD rats were given alcohol for 8 weeks and checked for serum prolactin level by radioimmunoassay. Interior pituitary cell proliferation was determined by immunohistochemistry score of Ki-67, and hypothalamic neurotransmitters were detected by Coulomb HPLC electrochemical array.

RESULTS: We demonstrated that serum prolactin level and wet pituitary weight of alcohol-fed rats were significantly increased. Interior pituitary cell proliferation was significantly enhanced; hypothalamic dopamine, 5-HT and GABA levels were reduced while glutamate level was increased by chronic alcohol administration; hypothalamic noradrenalin level remained unchanged.

CONCLUSION: Our study suggested that chronic alcohol administration resulted in elevated serum prolactin level in normal SD rats probably through enhancing pituitary gland cell proliferation combined with altered hypothalamic neurotransmitters that regulate prolactin level....

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Comparative Study 2011; 32(2): 164-169 PubMed PMID: 21552200 Citation  Keywords:  Acetaminophen:therapeutic use, Acetic Acid:adverse effects, Analgesics, Non-Narcotic:therapeutic use, Analgesics, Opioid:therapeutic use, Animals, Celecoxib, Codeine:therapeutic use, Cyclooxygenase 2 Inhibitors:therapeutic use, Data Interpretation, Statis.   

OBJECTIVES: There is good evidence that opioids can potentiate analgesic activity of some older non-opioid analgesics (such as paracetamol or ibuprofen) but it is not known whether this also holds true for newer non-opioid analgesics that selectively inhibit cyclooxygenase 2 (coxibs). This study was undertaken to determine the nature of the interaction between codeine and celecoxib or etoricoxib in peritoneal irritation-induced visceral pain in mice. For comparison, interactions of codeine with paracetamol and ibuprofen were also tested using the same method.

MATERIAL AND METHODS: A small volume of a weak acetic acid (0.6%) was injected into the peritoneal cavity and the number of writhes (contractions of abdominal muscles) was counted. All drugs were given orally. Their interaction was characterized using isobolographic analysis.

RESULTS: Codeine, etoricoxib, celecoxib, ibuprofen and paracetamol all independently produced dose-dependent suppression of writhing. The isobolographic analysis carried out using equipotent dose ratios showed that the interactions between codeine and etoricoxib or celecoxib were sub-additive or additive, respectively. This was in contrast to combinations of codeine with ibuprofen or paracetamol, which were supra-additive. Interaction indexes γ, determined as a ratio between experimental and theoretical ED50 values of the mixture, were as follows: 2.7 for codeine + etoricoxib, 0.62 for codeine + celecoxib, 0.43 for codeine + ibuprofen and 0.33 for codeine + paracetamol.

CONCLUSIONS: These and other results suggest that opioids do not seem to potentiate analgesic effects of selective COX-2 inhibitors, in contrast to nonselective COX inhibitors or paracetamol....

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Journal Article 2011; 32(2): 193-198 PubMed PMID: 21552199 Citation  Keywords:  Animals, Behavior, Animal:physiology, Corticotropin-Releasing Hormone:metabolism, Cyclic AMP Response Element-Binding Protein:metabolism, Down-Regulation:physiology, Extracellular Signal-Regulated MAP Kinases:physiology, Hippocampus:metabolism, Male, Mice.   

BACKGROUND: Stress results in hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, characterized by increased central CRF activity, elevated circulating glucocorticoid levels, impaired glucocorticoid-mediated negative feedback and abnormal hippocampal functions, possibly contributing to the development of behavioral pathologies, such as depression. The hippocampus is critically involved in the control of the HPA axis as well as in explicit memory, contextual aspects of fear, organization of the behavioral response to environmental novelty and in habituation. We have previously shown that mice that over-express CRF in the brain exhibit impaired novelty detection and altered psychophysiological and behavioral habituation, functions linked to dopamine receptor-dependent hippocampal plasticity.

OBJECTIVE AND METHODS: Therefore, the aim of the present study was to measure D1 and D2 dopamine receptor expression and related signaling, such as CREB and ERK protein levels and phosphorylation, in the hippocampus and other brain regions of mice with post-natal CRF over-expression (CRF-OE mice).

RESULTS: We found a region-specific down-regulation of both D1 and D2 protein expression, without altered CRF receptor protein expression, in the hippocampus in CRF-OE mice. This was accompanied by an impaired phosphorylation of hippocampal CREB, but not ERK1 and ERK2, in the same animals.

CONCLUSIONS: These results suggest that post-natal onset CRF over-expression results in an impairment of dopamine signaling in the hippocampus, which may underlie cognitive and motivational aspects of stress-related, CRF-driven mood disorders....

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Journal Article 2011; 32(2): 187-192 PubMed PMID: 21552198 Citation  Keywords:  Aging:metabolism, Animals, Animals, Newborn, Atrial Natriuretic Factor:metabolism, Cells, Cultured, Cochlea:cytology, Ear, Inner:physiology, Models, Animal, Rats, Rats, Sprague-Dawley, Receptors, Atrial Natriuretic Factor:metabolism, Stria Vascularis:cyto.   

OBJECTIVE: Atrial natriuretic peptide (ANP) regulates the homeostasis of body fluid and blood pressure as a neuropeptide in the central nervous system. To assess the possible physiological role in the inner ear, we investigated the expression of ANP in primary culture of marginal cells, and then we detected the expression of ANP and its receptor (NPR-A) in cochlear tissues derived from neonatal and adult rats of various ages.

METHODS: Marginal cells were isolated from cochlear stria vascularis of the neonatal rats. The cultured cells were subsequently characterized by morphology, immunocytochemistry, and scanning electron microscope (SEM) analysis. In order to examine the expression of ANP in marginal cells as well as in the developing rats' cochleae, immunocytochemistry and reverse-transcription polymerase chain reaction (RT-PCR) were applied respectively.

RESULTS: The present study demonstrated typical characteristics of marginal cells, including cobblestone, polygonal monolayer, pleomorphic growth pattern and the expression of cell type-specific marker, and SEM analysis. Subsequently, immunoreactive product of ANP were found in cultured marginal cells. The mRNAs encoding ANP and NPR-A receptor was expressed in rats' cochleae from postembryonic stage to early postnatal period. During the maturation stage, ANP expression was gradually down-regulated, while the expression of NPR-A receptor was relatively stable.

CONCLUSION: ANP might be synthesized and secreted by marginal cells of stria vascularis, and could play an important role in modulating the microenvironment of the inner ear. In addition, ANP might contribute to development and growth process of cochlea....

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Journal Article 2011; 32(2): 176-186 PubMed PMID: 21552197 Citation  Keywords:  Adult, Animals, Brain:drug effects, Cells, Cultured, Clozapine:pharmacology, Dopamine:pharmacology, Dopamine Antagonists:pharmacology, Dose-Response Relationship, Drug, Female, Haloperidol:pharmacology, Humans, Interferon-gamma:metabolism, Interleukin-10:.   

OBJECTIVES: Dopamine (DA) administration in sepsis is used to modulate the hypotensive condition and to normalize the blood vessels perfusion. However, whether this administration of DA has an effect on the release of cytokines in vivo deserves investigation.

METHODS AND RESULTS: Pre-exposure of DA (1 µg/ml) to whole blood enhanced IL-10 (30%) production level following LPS stimulation. This IL-10 enhancement became statistically significant (p<0.001) upon the addition of D2-DA receptor (DAR) antagonists, Clozapine or Haloperidol. Furthermore, systemic administration of DA (0.5-50 mg/kg) in mice suppressed significantly LPS-induced TNF-α levels in blood, liver, spleen, brain, and lungs; IL-10 levels in blood, brain and liver; and IFN-γ levels in blood, liver, brain, and lungs. On the other hand, DA enhanced significantly LPS-induced IL-10 production in the lungs and spleen, and IFN-γ levels in the spleen. Administration of Clozapine (54 mg/kg) or Haloperidol (62 mg/kg) with LPS (1 µg) and DA (5 mg/kg) reversed DA suppressive effects on LPS-induced cytokines in blood, IFN-γ in brain and lungs, and enhanced significantly LPS-induced IL-10 production in blood, spleen, liver, and lungs.

CONCLUSIONS: These results indicate that DA modulatory effect on LPS-induced blood cytokines-producing cells is mediated mainly by D2-DAR (D2/ D3/D4) through enhancing immune cells migration and extravasation into tissues. Furthermore, DA selectivity on cytokines modulation is tissue specific, mediated by the type of DAR expressed and on the immune cells lodged in each tissue....

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Journal Article 2011; 32(2): 212-219 PubMed PMID: 21552195 Citation  Keywords:  Animals, Gastric Mucosa:cytology, Gastrointestinal Tract:cytology, Male, Models, Animal, Neuropeptide Y:metabolism, Obesity:metabolism, Pancreatic Polypeptide:metabolism, Receptors, Cell Surface:metabolism, Receptors, Neuropeptide Y:metabolism, Shrews,.   

OBJECTIVES: To investigate the immunolocalization of the pancreatic polypeptide (PP)-fold peptide family, important regulatory factors for food intake, in the gastrointestinal tract of Suncus murinus, and to discuss the relation with the obesity-resistance, visceral fat accumulation-resistance phenomenon in Suncus murinus.

METHODS: The gastrointestinal tract of adult Suncus murinus, except for the stomach and pylorus, was divided into five sections (S1, corresponding to the duodenum, S2, S3 and S4, corresponding to the jejunum and ileum, and S5, corresponding to the colon and rectum in other mammals), to investigate the PP family and their receptor-producing cells by means of immunohistochemistry.

RESULTS: NPY, PYY, Y1 and Y4-immunoreactive cells were distributed widely throughout the gastrointestinal tract, moreover, the PP family and their receptor-immunoreactive cells were predominantly distributed at the end of the gastrointestinal tract, the rectum.

CONCLUSION: In this study, we investigated the distribution of the PP family and their receptor-producing cells in the gastrointestinal tract of Suncus murinus in detail for the first time. It was presumed that the wide distribution of Y4 in the gastrointestinal tract may be related to (associated with) the phenomenon of natural obesity-resistance, visceral fat accumulation-resistance in aging Suncus murinus....

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Clinical Trial 2011; 32(2): 141-147 PubMed PMID: 21552193 Citation  Keywords:  Adult, Antibodies:blood, Antipsychotic Agents:therapeutic use, Biomarkers:blood, Case-Control Studies, Dehydroepiandrosterone:analogs & derivatives, Female, Homocysteine:blood, Humans, Hydrocortisone:blood, Immunologic Factors:blood, Iodide Peroxidase:imm.   

OBJECTIVE: Serum levels of neuro- and immunomodulatory adrenal steroids together with selected hormonal, lipid and other relevant biochemical parameters were investigated to examine the differences between first-episode schizophrenia patients and age-matched healthy subjects, and the effect of treatment with atypical antipsychotics.

METHODS: The patient´s group consisted of 22 drug-naive patients (13 men and 9 women), diagnosed with schizophrenia according to ICD-10 criteria, before and after six-months treatment with atypical antipsychotics of olanzapine or non-olanzapine type. Biochemical markers included steroids cortisol, dehydroepiandrosterone, its sulfate, 7-hydroxylated metabolites of dehydroepiandrosterone, prolactin, thyrotropin, free thyroxine, autoantibodies against thyroid peroxidase and thyroglobulin, glucose levels, four major lipid parameters, homocysteine and three other aminothiols. Steroids, prolactin and thyroid parameters were determined by radioimmunoassays, the other markers by standard biochemical methods.

RESULTS: Significantly lower dehydroepiandrosterone sulfate and of 7α-hydroxy- dehydroepiandrosterone levels than in controls were found in male patients. In the female group, the only difference in steroid spectra was significantly higher cortisolemia in the patients. The patients had also higher titres of autoantibodies against thyroid peroxidase. Compared to controls, the patients displayed worse lipid spectra, and higher homocysteinemia. Medication did not lead to significant changes in the parameters, with the exception of expected increase in prolactin levels in non-olanzapine treated subgroups.

CONCLUSION: Lower levels of 7α-hydroxydehydroepiandrosterone, abundant especially in brain, determined for the first time in schizophrenia patients, are in agreement with recent opinion of their neuroprotective and immunoprotective role. High levels of autoantibodies against thyroid peroxidase in the patients support the autoimmunity hypothesis of schizophrenia....

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Journal Article 2011; 32(2): 121-126 PubMed PMID: 21552191 Citation  Keywords:  Humans, Schizophrenia:therapy, Transcranial Magnetic Stimulation, Treatment Outcome,.   

: One of the fundamental prerequisites of the successful schizophrenia treatment is represented by an adequately significant impact on the negative symptoms of schizophrenia. Since the present pharmacotherapy has probably reached its limit in this area, there is a logical effort to utilize other, non-pharmacological methods. One of the most promising supplements that has been for a long time verified in the clinical practice is rTMS. Most of the studies have arrived at the conclusion that rTMS is an efficient method in the treatment of negative symptoms of schizophrenia. A valuable contribution to the assessment of the rTMS application in the treatment of negative symptoms is represented by meta-analyses. The meta-analyses indicate that the effect is mild to moderate (d=0.43 to 0.68). To sum it up, there will be higher probability of the rTMS effect on negative symptoms if 10 Hz stimulating frequency and a longer stimulation period in the extent at least three, ideally four to six weeks is used....

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