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Journal Article 2010; 31(1): 67-72 PubMed PMID: 20150874 Citation  Keywords:  Animals, Animals, Genetically Modified, Cell Proliferation:drug effects, Chick Embryo:metabolism, Down-Regulation:drug effects, Embryonic Development:drug effects, Ganglia, Spinal:drug effects, Gene Expression Regulation, Developmental:drug effects, Gene .   

OBJECTIVE: Protein Isl-1 RNA interference and over expression in early chicken embryo dorsal root ganglia (DRG) were used to investigate the function of Isl-1 in DRG cell proliferation.

METHODS: Isl-1 targeted shRNA expression vector and Isl-1 over-expression vector were transfected into chicken embryo DRG by in ovo electroporation. Then, the DRG proliferation rate was detected by BrdU immunohistochemistry.

RESULTS: The rate of DRG cell proliferation increased after Isl-1 knock-down and decreased after Isl-1 over-expression.

CONCLUSIONS: In this study, we found that Isl-1 negatively modulates DRG cell proliferation....

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Journal Article 2010; 31(1): 117-121 PubMed PMID: 20150873 Citation  Keywords:  Adult, Autistic Disorder:urine, Brief Psychiatric Rating Scale, Bufotenin:analysis, Case-Control Studies, Chromatography, High Pressure Liquid, Female, Humans, Male, Mass Spectrometry, Research Design, Schizophrenia:urine, Up-Regulation, Young Adult,.   

OBJECTIVE: Previous studies have suggested that the endogeneous psychotomimetic molecule bufotenine (N-N-dimethyl-5-idroxytryptamine) may play a role in the pathogenesis of severe mental disorders. The potential association of bufotenine with the clinical features of autism and schizophrenia is not entirely understood. In this study, we measured urinary levels of bufotenine in subjects with autistic spectrum disorder (ASD), schizophrenia and healthy comparison subjects free of psychiatric symptoms. We also sought to assess whether urine concentrations of this molecule may be associated with the clinical characteristics of psychiatric patients.

DESIGN: Urine bufotenine levels were measured using a high-performance liquid chromatography-mass spectrometry (HPLC-MS) assay in young adults with severe ASD (n=15), patients with schizophrenia (n=15), and healthy control subjects (n=18). The Vineland Adaptive Behavior Scale was used to measure adaptive behaviors in ASD individuals. The Brief Psychiatric Rating Scale (BPRS) was used for patients with schizophrenia.

RESULTS: Urine bufotenine levels were significantly higher in ASD subjects (3.30 +/- 0.49 microg/L, p<0.05) and patients with schizophrenia (4.39 +/- 0.43 microg/L, p<0.001) compared with controls (1.53 +/- 0.30 microg/L). Among patients with ASD, there was a significant positive correlation between urine bufotenine and hyperactivity scores on the Vineland Adaptive Behavior Scale (r=0.479, p<0.05). No other associations were detected.

CONCLUSIONS: Our results indicate that elevated urine levels of the endogeneous psychotomimetic molecule bufotenine may play a role in ASD and schizophrenia, and can be correlated with hyperactivity scores in autism....

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Evaluation Studies 2010; 31(1): 113-116 PubMed PMID: 20150872 Citation  Keywords:  Adult, Aged, Biomarkers, Tumor:blood, Carcinoma:blood, Carcinoma, Non-Small-Cell Lung:blood, Humans, Lung Neoplasms:blood, Male, Middle Aged, Neoplasm Staging:methods, Neopterin:blood, Predictive Value of Tests, Prognosis, Prostatic Neoplasms:blood, alpha.   

OBJECTIVE: Increased serum levels of alpha-1 antitrypsin (alpha1-AT) and neopterin were observed in many diseases including different types of cancer. The aim of this work is to determine alpha1-AT and neopterin serum levels in newly diagnosed untreated non-small cell lung and prostate cancer patients and to test their relation to cancer staging.

METHODS: Radial Immunodiffusion and ELISA methods were used to determine alpha1-AT and neopterin serum levels, consequently.

RESULTS: alpha1-AT and neopterin mean serum levels were found to be elevated in non-small-cell lung and prostate cancer patients. In non-small cell lung cancer patients alpha1-AT was 454.5+/-129.2 mg/dL (p<0.0005) and neopterin was 7.9+/-4.2 ng/mL (p<0.0005). In prostate cancer patients alpha1-AT was 462.7+/-116.9 mg/dL (p<0.0005) and neopterin was 8.1+/-3.1 ng/mL (p<0.0005). These elevated levels were significantly correlated with the stage of cancer. The mean serum level of alpha1-AT in stages I, II, III, and IV among non-small cell lung cancer patients were 305.1, 453.6, 490.3 and 616.0 mg/dL respectively, and the mean serum levels for neopterin were 4.0, 7.0, 8.1 and 14.9 ng/mL, correspondingly. The mean serum level of alpha1-AT in stages A, B, C, and D among prostate cancer patients were 342.9, 418.5, 467.8 and 593.5 mg/dL respectively and the mean serum levels for neopterin were 4.9, 6.6, 8.7 and 11.6 ng/mL, correspondingly.

CONCLUSIONS: Based on the above mentioned findings alpha1-AT and neopterin serum levels should be considered in the follow up as well as in the prognosis of cancer patients....

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Journal Article 2010; 31(1): 11-18 PubMed PMID: 20150871 Citation  Keywords:  Cannabinoid Receptor Modulators:biosynthesis, Catechol O-Methyltransferase:genetics, Cytochrome P-450 CYP2D6:genetics, Enzymes:genetics, Genetic Predisposition to Disease, Health, Humans, Mental Disorders:genetics, Metabolic Networks and Pathways:genetics.   

: Endogenous morphine has been detected in human tissues from the vascular, immune and nervous systems. The genes/enzymes (CYP2D6, COMT and PNMT) that are involved in the biosynthesis of morphine have variations that affect their functionality. Some of these variations are the result of single nucleotide polymorphisms of DNA sequences. This review highlights some of the functional differences in the critical enzymes required for the biosynthesis of morphine that may affect human health. These variations have been shown to change the way animals react to stressors, perceive pain and behave. The presence of morphine signaling in almost all organ systems suggests that it is most likely playing a role in maintaining the health and promoting the normal functioning of these physiological systems....

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Journal Article 2010; 31(1): 87-91 PubMed PMID: 20150870 Citation  Keywords:  Animals, Antidiuretic Agents:administration & dosage, Ascorbic Acid:administration & dosage, Central Nervous System:drug effects, Consciousness, Dose-Response Relationship, Drug, Drug Evaluation, Preclinical, Injections, Intraventricular, Male, Natriuresi.   

OBJECTIVE: Ascorbic acid represents one of the most important antioxidants and neuromodulators, and plays an important role in the cerebral system. In the present study, we investigated the central effect of ascorbic acid on fluid regulation and electrolyte homeostasis.

METHODS: Male Wistar rats were implanted with stainless steel cannulas into the lateral ventricle, and sodiun excretion and urinary volume were measured after intracerebroventricular (i.c.v.) injection of ascorbic acid (200 or 600 nmol/rat). In another set of experiments, vasopressin and oxytocin plasma levels were evaluated 10, 20 and 30 minutes after ascorbic acid i.c.v. injection.

RESULTS: The administration of ascorbic acid to conscious rats resulted in a significant decrease in urinary volume and an increase in the renal excretion of sodium, with a concomitant increase in the plasma levels of vasopressin and oxytocin.

CONCLUSIONS: These results suggest that ascorbic acid may play a significant role in the central regulation of fluid and electrolyte homeostasis....

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Journal Article 2010; 31(1): 63-66 PubMed PMID: 20150869 Citation  Keywords:  Case-Control Studies, Cystinyl Aminopeptidase:blood, Down-Regulation, Enzyme Activation, Female, Gestational Age, Humans, Pre-Eclampsia:blood, Pregnancy, Premature Birth:blood, Severity of Illness Index, Term Birth:blood,.   

OBJECTIVE: Placental Leucine Aminopeptiadse (P-LAP) also known as oxytocinase, is secreted by syncytiotrophoblast and increases gradually during pregnancy until delivery. It is a regulator of uterine contractions, of vascular resistance and of volume of the retroplacental blood pool. Recently, it was shown that it could also regulate metalloproteinase 9 activity and thus, invasiveness of trophoblastic cells. Since development of preeclampsia could be initiated by decreased cytotrophoblastic invasion of spiral arterioles and a reduced uteroplacental perfusion, we speculate that circulating P-LAP activity could be decreased during preeclampsia.

MATERIALS AND METHODS: Case-control study was evaluated in 84 women. P-LAP activity was measured in n=51 healthy pregnant women at term, and compared with n=16 normotensive women delivering preterm and n=17 women diagnosed with pre-eclampsia. P-LAP activity was determined by colorimetry in plasma samples using L-Leucine-p-nitroanilide as substrate.

RESULTS: P-LAP activity was significantly lower in sera of preeclamptic women (0.91+/-0.122 mDO/min) as compared to normotensive controls (1.41+/-0.103 mDO/min; p=0.003) irrespective of time of delivery.

CONCLUSIONS: These findings confirm the probable involvement of P-LAP in trophoblast invasion and development of preeclampsia....

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Journal Article 2010; 31(1): 155-160 PubMed PMID: 20150868 Citation  Keywords:  Aged, Aged, 80 and over, Biomarkers:analysis, Body Mass Index, Bone Density, Bone Remodeling:physiology, Bone and Bones:metabolism, Calcium:analysis, Female, Humans, Leptin:blood, Male, Middle Aged, Osteoporosis:blood,.   

OBJECTIVE: Clinical data have suggested that obesity protects against osteoporosis. Leptin, mainly secreted by white adipose tissue, might be involved by mediating an effect on bone metabolism. This study was conducted to investigate a possible relationship of leptin and bone turn-over in postmenopausal women with osteoporosis.

METHODS: We measured bone mineral density (BMD), serum leptin levels and markers of bone metabolism, including osteocalcin and cross-laps in 44 patients with osteoporosis. The main group consisted of 32 postmenopausal women.

RESULTS: Mean serum leptin was 13.1 microg/L and showed no statistically significant difference to the levels measured in a collective of normal persons adjusted for age and BMI. When related to serum cross-laps as markers of bone resorption, a positive correlation (p<0.05) was observed, whereas no correlation with osteocalcin could be seen.

CONCLUSIONS: A dual control of bone formation by leptin is assumed: This involves local mechanisms acting on osteoblasts and a central inhibitory effect on bone metabolism via a hypothalamic relay. Our data indicate that the net effect of circulating leptin may cause bone loss and is significantly related to high-turnover serum bone markers, at least in postmenopausal women with osteoporosis....

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Journal Article 2010; 31(1): 4-10 PubMed PMID: 20150867 Citation  Keywords:  Alcoholism:genetics, Child, Developmental Disabilities:genetics, Feeding and Eating Disorders:genetics, Genetic Predisposition to Disease, Humans, Mental Disorders:genetics, Mood Disorders:genetics, Mutant Proteins:physiology, Polymorphism, Genetic:physio.   

: Both serotonin and the serotonin transporter, which transports the neurotransmitter serotonin from synaptic spaces into presynaptic neurons, play an important role in the pathophysiology of several psychiatric disorders. Mutations associated with the serotonin transporter gene may result in changes in serotonin transporter function. The serotonin transporter gene promoter variant, consisting of a long (L) and a short (S) variant, is one of the major factors which contribute to the etiology of many psychiatric disorders. In this regard, many studies have been published on association of this variant with various psychiatric disorders. This repeat length variant in the promoter region of this gene has been shown to affect the rate of serotonin uptake and may play a role in post-traumatic stress disorder and depression-susceptibility in people experiencing emotional trauma. Associations between a functional variant in the serotonin transporter anxiety-related personality traits were found, as well as the risk of developing depression, alcoholism or suicidal behavior. Understanding of possible associations of these variants and psychiatric disorders would bring progress in principles and treatment of many disorders....

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