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Journal Article 2013; 34(4): 294-301 PubMed PMID: 23803865 Citation  Keywords:  Animals, Animals, Genetically Modified, Antioxidants:pharmacology, Corpus Luteum:drug effects, Embryo Implantation:drug effects, Embryo Transfer:veterinary, Embryo, Mammalian:drug effects, Female, Genetic Engineering:veterinary, Melatonin:pharmacology, Pr.   

OBJECTIVE: In this study, the effects of melatonin on superovulation and the transfer of transgenic embryos were investigated in Small-Tailed Han sheep.

DESIGN: Different doses of melatonin (0, 40 or 80 mg/animal) were subcutaneously implanted into both multiparous (4-5 years old) donors and recipients before superovulation and estrus synchronization. The one-year-old young ewes without melatonin treatment served to evaluate the reproductive efficiency of the adult multiparous ewes. Ewes with superovulation were used as embryo donors. The estrus were induced in embryo recipients after embryo transpimplanted.

RESULTS: The results showed that the number of corpora lutea of the ewes received subcutaneous 40 or 80 mg melatonin implant (13.4±1.05/ewe, 15.1±1.62/ewe) were significantly higher than that of in control group (8.8±0.37/ewe) (p<0.05). Similarily the number of recovered embryos from the ewes received subcutaneous 40 or 80 mg melatonin implant (10.3±0.84/ewe, 10.9±1.21/ewe) was significantly higher than the control group (6.2±0.60/ewe) (p<0.05). The transimplantd embryos from 40 or 80 mg melatonin treated donors dramatically improved the pregnancy and birth rates compared to control ewes. In addition, both 40 mg and 80 mg melatonin implatation lead to more lambs born per embryo.

CONCLUSIONS: These observations provide valuable information for the application of melatonin in increasing superovulation and transgenic embryo transplantation efficiency in sheep....

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Case Reports 2013; 34(3): 173-176 PubMed PMID: 23685414 Citation  Keywords:  Amino Acid Substitution:genetics, Chromosomes, Human, X, Female, Humans, Insulin Receptor Substrate Proteins:genetics, Middle Aged, Schizophrenia, Paranoid:genetics, Signal Transduction:genetics,.   

: This report deals with a female patient with schizophrenia who was found to have a mutation in the insulin receptor substrate-4 gene that is located on chromosome Xq22.3. Since this mutation is expected to change amino acid coding from histidine to tyrosine and cause an altered insulin receptor substrate-4 protein, and the insulin receptor substrate-4 protein may be involved in neuronal growth and function in the brain, it is possible that it is this insulin receptor substrate-4 gene mutation that underlies this patient's schizophrenia development....

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Journal Article 2013; 34(1): 62-70 PubMed PMID: 23524626 Citation  Keywords:  Animals, Axonal Transport:physiology, Horseradish Peroxidase:pharmacokinetics, Lactic Acid:pharmacology, Microscopy, Electron, Transmission, Myelin Sheath:physiology, Nerve Regeneration:drug effects, Polyesters, Polymers:pharmacology, Rats, Rats, Sprague-.   

OBJECTIVES: To evaluate the poly(dextrogyr-levogyr) lactide acid-triiodothyronine (PDLLA-T3) seeded with Schwann cells conduit for repairing sciatic nerve defect.

MATERIALS & METHODS: The rats were divided into three groups: autologous nerve transplantation (Group A), PDLLA-T3 + Schwann cells (Group B) and PDLLA + Schwann cells (Group C).

RESULTS: Myelin sheath thickness was significantly greater in Group A compared with Group B and Group C. The regenerated nerves had nearly normal structure in Group A, and in Groups B and C nerve tissues filled in the anastomotic site and angiogenesis was noted. The mean number of myelinated nerve fibers and neurons in Group B was greater than in Group C.

CONCLUSIONS: PDLLA-T3 is superior to PDLLA alone for repairing nerve defects....

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Comparative Study 2013; 34(1): 18-26 PubMed PMID: 23524620 Citation  Keywords:  Adolescent, Adult, Age Factors, Aging:blood, Alanine Transaminase:blood, Aspartate Aminotransferases:blood, Biomarkers:blood, Female, Human Growth Hormone:blood, Humans, Insulin-Like Growth Factor I:metabolism, Male, Middle Aged, Opioid-Related Disorders:.   

OBJECTIVE: To compare IGF1 levels in opiate dependent and general patients both absolutely and by age.

DESIGN: A naturalistic observational study was undertaken of opiate dependent and general medical patients.

SETTING: Primary care.

PATIENTS: 74 opiate substance use dependent (SUD) patients were compared with 262 non-SUD (NSUD) patients.

RESULTS: (1) Comparative IGF1 levels; (2) age and sex corrected IGF1 levels; (3) IGF1 levels corrected for age, sex, and hepatic and immune biomarkers.

MAIN FINDINGS: The SUD patients were younger (32.60+0.89 vs. 42.49+0.96 years, mean+S.E.M., p<0.0001) and had more males (72.9% and 39.3%, p<0.0001) than the NSUD patients. Restriction of the age range to 15-45 years (70 vs. 153 patients) made the difference in ages non-significant (31.27+0.71 vs. 32.32+0.61 years, p=0.47) but IGF1 remained elevated in SUD (26.56+1.21 vs. 22.65+0.57nmol/L, p=0.0039). When multiple regression was used to correct for the age and sex disparities, the age: addiction interaction remained significantly elevated (p=0.0003). In an additive model opiate dependence showed a 23.8% elevation in IGF1. When the interactive model was further adjusted by the inclusion of ALT and CRP as indices of hepatic inflammation and immune activation respectively, addictive status remained significant both alone (p=0.0134) and in 2-, 3- and 4-way interactions with age, male sex, and ALT (all p<0.0255).

CONCLUSION: These data demonstrate that serum IGF1 is elevated in opiate dependence both absolutely and after adjustment for age, sex, and markers of immune and hepatic activation....

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Journal Article 2012; 33(6): 631-635 PubMed PMID: 23160224 Citation  Keywords:  Animals, Catecholamines:biosynthesis, Chronic Disease, Dopamine beta-Hydroxylase:metabolism, Functional Laterality:physiology, Hippocampus:enzymology, Male, Norepinephrine Plasma Membrane Transport Proteins:metabolism, Rats, Rats, Wistar, Social Isolation.   

OBJECTIVES: Right-left asymmetry of human brain function has been known for a century. Brain asymmetry and lateralization has been observed at the neurochemical level. At the neurochemical level, it is important to further correlate changes in monoaminergic activity with the synthesis and reuptake of these monoamines. The aim of the present study was to analyze the effect of social isolation on catecholamine stores as well as on the regulation of catecholamine synthesis and uptake in the right and left hippocampus.

METHODS: We examined changes in protein levels of dopamine-β-hydroxylase (DBH), norepinephrine transporter (NET) and vesicular monoamine transporter 2 (VMAT 2) in the right and left hippocampus of socially isolated adult male rats during 12 weeks by Western blot analysis.

RESULTS: Chronic isolation stress reduced norepinephrine content in the right hippocampus. No changes were observed in protein levels of DBH and NET in the right hippocampus, whereas expression of this norepinephrine synthetizing enzyme and transporter were elevated in the left hippocampus. On the other hand, chronic isolation stress caused reduction of VMAT2 protein in the right hippocampus.

CONCLUSION: Our results reveale not only the lateralization of stress regulatory system but they also show that long-term isolation stress produces right-left asymmetry of the hippocampus norepinephrine, different regulation of the catecholamines synthesis and reuptake....

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Journal Article 2012; 33(6): 608-613 PubMed PMID: 23160221 Citation  Keywords:  Cell Line, Transformed, Cell Proliferation:drug effects, Estradiol:metabolism, Follicle Stimulating Hormone, beta Subunit:genetics, Gene Expression Regulation:drug effects, Gonadotropin-Releasing Hormone:metabolism, Humans, Luciferases:genetics, Luteinizi.   

OBJECTIVES: Sex steroid hormones play roles in the regulation of pituitary hormone synthesis and secretion. Here we investigated the role of estradiol (E2) and progesterone (P4) on pituitary gonadotropin luteinizing hormone (LH)β- and follicle stimulating hormone (FSH)β-transcriptional activity in a single colony of gonadotroph LβT2 cells.

METHODS: Pituitary gonadotroph cell line, LβT2 cells were used in this study. Cells were transfected with LHβ- or FSHβ-subunit promoter region-linked luciferase vector, and stimulated with gonadotropin-releasing hormone (GnRH) in the presence or absence of sex steroids. Transcriptional activity for LHβ- and FSHβ-subunit were determined by luciferase assay. Effects of sex steroids on cell proliferation was also determined by measurement of 5-bromoe-2'-deoxyuridine (BrdU) incorporation.

RESULTS: The basal promoter activity of the LHβ subunit was not modulated by 10 nM E2, but gonadotropin releasing hormone (GnRH)-induced LHβ promoter activity was significantly increased by the same concentration of E2. Similarly, although the basal FSHβ promoter was not modulated by 10 nM E2, GnRH-induced FSHβ promoters were significantly potentiated in the presence of E2. One micromole E2 modulated neither basal nor GnRH-induced LHβ and FSHβ promoters. On the other hand, basal LHβ promoter activity was enhanced by 1 µM P4, but the stimulatory response of GnRH on LHβ promoters was significantly inhibited in the presence of 1 µM P4. Similar to LHβ promoters, the basal activity of the FSHβ promoter was increased by 1 µM P4; however, the response to GnRH was not modulated in the presence of P4. Ten micromoles P4 modified neither basal nor GnRH-induced promoter activity for LHβ and FSHβ. E2 had no antagonistic effect on P4-induced basal promoter activities of LHβ or FSHβ. A cell proliferation assay showed that neither E2 nor P4 modulated the growth of LβT2 cells, even in the presence or absence of GnRH.

CONCLUSION: These observations suggest that both E2 and P4 uniquely modulate basal and GnRH-stimulated gonadotropin promoters without affecting cell growth....

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Journal Article 2012; 33(5): 559-564 PubMed PMID: 23090276 Citation  Keywords:  Adolescent, Asthma:blood, Biomarkers:blood, Body Mass Index, Child, Female, Humans, Hypersensitivity:blood, Male, Nicotinamide Phosphoribosyltransferase:blood, Obesity:blood, Severity of Illness Index,.   

OBJECTIVES: Very little is known about the role of adipokines in atopic asthma in children. Studies about the potential role of novel proinflammatory adiopcytokine - visfatin are lacking.

DESIGN AND SETTING: In this cross-sectional study serum visfatin (VISF) levels were measured in 89 asthmatic out-patients (61 boys and 28 girls aged 7.0-17.0 years) and in 33 healthy children.

MATERIAL AND METHODS: Among examined asthmatics 59 (19 girls and 40 boys) had normal weight and 30 (9 girls and 21 boys) were obese. Serum VISF was evaluated using standard ELISA tests and the results were analysed in relation to body weight, asthma severity, and gender were analysed.

RESULTS: The mean serum levels of visfatin were significantly (p<0.001) lower both in obese (2.13±0.07npg/ml) and non-obese asthmatic children (2.05±0.06 npg/ml) than in healthy children (2.57±0.07 pg/ml) regardless of gender. After stratifying by gender, there was a significant decrease (p<0.001) in visfatin levels in obese asthmatic girls (2.30±0.08 ng/ml) and asthmatic girls with normal weight girls (2.21±0,09 ng/ml) compared with girls from control group (2.69 ±0.06 ng/ml). In obese asthmatic boys and non-obese asthmatic boys also significantly lower (p<0.01) mean values of visfatin (2.03±0.06 ng/ml and 1.9±0.06 pg/ml respectively) were observed than in control boys (2.391±0.09 ng/ml). No relationships between examined adipokine levels and asthma severity, spirometric parameters, degree of allergic sensitization, BMI, were observed.

CONCLUSION: Visfatin is not potential biomarker in atopic asthma in children and further studies evaluating the possible role of this proinflammatory adipokine in childhood atopic asthma pathogenesis are needed....

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Journal Article 2012; 33(5): 546-551 PubMed PMID: 23090274 Citation  Keywords:  Animals, Biological Transport:genetics, Bipolar Disorder:genetics, COS Cells, Cercopithecus aethiops, Humans, In Vitro Techniques, Isomerism, Polymorphism, Single Nucleotide, Protein Structure, Tertiary, Schizophrenia:genetics, Serotonin:metabolism, Trans.   

OBJECTIVES: Although single nucleotide polymorphisms of the human vesicular monoamine transporter 1 (hVMAT1) gene SLC18A1 have been associated with neuropsychiatric disorders, there is limited information on the function of naturally occurring hVMAT1 variant proteins. This study evaluated transport activity of full length hVMAT1 isoform-a (NP_003044.1) with a threonine (Thr) or isoleucine (Ile) at amino acid 136 and hVMAT1 isoform-b (NP_00135796.1) with a 136-Thr and deletion of 32 amino acids in the central region of the protein. Genetic studies have previously linked the 136-Thr to bipolar disorder.

METHODS: Expression vectors with hVMAT1 DNA coding for isoform variants were transfected into COS-1 cells. Expression of immunoreactive proteins was assessed by Western blotting, and function was assayed by ATP-dependent transport of radiolabeled serotonin and concentration-dependent inhibition by reserpine.

RESULTS: Immunoreactive isoform-a proteins were observed as a major doublet (68-71 Kd) and a minor 39 Kd protein. The major isoform-b protein was 47 Kd with minor 57 and 115 Kd proteins. Isoform-b had no detectable transport activity, despite a large amount of immunoreactive protein. Transport activity of isoform-a with 136-Thr was 20-50% lower than with 136-Ile in time course studies (2.5-5 min) and in additional 5 min assays repeated with 5-6 transfections per variant. Kinetic analyses indicated a lower transport Vmax of isoform-a with 136-Thr but no significant differences in the transport Km or reserpine IC50.

CONCLUSIONS: Deletion of amino acids 307-338 in hVMAT1 isoform-b abolishes transport activity, and a 136-Thr partially reduces activity of isoform-a....

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