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Selected AbstractsNoradrenergic Regulation of Hypothalamic Cells that Produce Growth Hormone-Releasing Hormone and Somatostatin and the Effect of Altered Adiposity in SheepJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2005J. Iqbal Abstract The growth hormone (GH) axis is sensitive to alteration in body weight and there is evidence that central noradrenergic systems regulate neurones that produce growth hormone-releasing hormone (GHRH) and somatostatin (SRIF). This study reports semiquantitative estimates of the noradrenergic input to neuroendocrine GHRH and SRIF neurones in the sheep of different body weights. We also studied the effects of altered body weight on expression of dopamine ,-hydroxylase (DBH), the enzyme that produces noradrenalin from dopamine. Ovariectomised ewes were made Lean (39.6 ± 2.6 kg; Mean ± SEM) by dietary restriction, whereas Normally Fed animals (61.2 ± 0.8 kg) were maintained on a regular diet. Brains were perfused for immunohistochemistry and in situ hybridisation. The Mean ± SEM number of GHRH-immunoreactive (-IR) cells was lower in Normally Fed (65 ± 7) than in Lean (115 ± 14) animals, whereas the number of SRIF-IR cells was similar in the two groups (Normally Fed, 196 ± 17; Lean 230 ± 21). Confocal microscopic analysis revealed that the percentage of GHRH-IR cells (Normally Fed 36 ± 1.5% versus Lean 32 ± 4.6%) and percentage of SRIF-IR cells (Normally Fed 30 ± 40.4% versus Lean 32 ± 2.3%) contacted by noradrenergic fibres did not change with body weight. FluoroGold retrograde tracer injections confirmed that noradrenergic projections to the arcuate nucleus are from ventrolateral medulla and noradrenergic projections to periventricular nucleus arise from the ventrolateral medulla, nucleus of solitary tract, locus coeruleus (LC) and the parabrachial nucleus (PBN). DBH expressing cells were identified using immunohistochemistry and in situ hybridisation and the level of expression (silver grains/cell) quantified by image analysis. The number of DBH cells was similar in Normally Fed and Lean animals, but the level of expression/cell was lower (P < 0.02) in the PBN and LC of Lean animals. These results provide an anatomical basis for the noradrenergic regulation of GHRH and SRIF cells and GH secretion. Altered activity or noradrenergic neurones in the PBN and LC that occur with reduced body weight may be relevant to the control of GH axis. [source] Galactosamine-induced hepatotoxic effect and hepatoprotective role of a protein isolated from the herb Cajanus indicus L in vivo,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2007Prasenjit Manna Abstract dd(+)-Galactosamine is a well-known experimental hepatotoxin. The present study was conducted to determine the protective role of a 43-kD protein isolated from the leaves of the herb Cajanus indicus L against dd(+)-galactosamine (GalN) induced liver damage in mice. Both preventive and curative effects of the protein have been investigated in the study. The protein was administered intraperitoneally at a dose of 2 mg/kg body weight for 4 days before and after GalN intoxication at a dose of 800 mg/kg body weight for 3 days. The increased activities of serum marker enzymes, alanine aminotransferase, and alkaline phosphatase because of GalN administration, were significantly reduced by the protein treatment. The protein also normalized the altered activities of antioxidant enzymes superoxide dismutase, catalase, glutathione reductase, and glutathione- S -transferase as well as the levels of cellular metabolites, reduced glutathione, glutathione disulfide, and total thiols. In addition, the enhanced hepatic lipid peroxidation because of GalN intoxication was also effectively inhibited by the protein treatment. Results suggest that GalN caused hepatic damages via oxidative insult and that the protein provided protection through its antioxidant mechanism. © 2007 Wiley Periodicals, Inc. J Biochem Mol Toxicol 21:13,23, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20154 [source] Acupuncture: is it effective for treatment of insulin resistance?DIABETES OBESITY & METABOLISM, Issue 7 2010F. Liang Insulin resistance (IR) is closely associated with obesity, type 2 diabetes mellitus (T2DM), hypertension, polycystic ovary syndrome (PCOS), non-alcohol fatty liver diseases (NAFLD) and metabolic syndrome and is also a risk factor for serious diseases such as cardiovascular diseases. Pharmacological treatments available for IR are limited by drug adverse effects. Because acupuncture has been practiced for thousands of years in China, it has been increasingly used worldwide for IR-related diseases. This review analyses 234 English publications listed on the PubMed database between 1979 and 2009 on the effectiveness of acupuncture as a treatment for IR. These publications provide clinical evidence, although limited, in support of the effectiveness of acupuncture in IR. At this stage, well-designed, evidence-based clinical randomized controlled trial studies are therefore needed to confirm the effects of acupuncture on IR. Numerous experimental studies have demonstrated that acupuncture can correct various metabolic disorders such as hyperglycemia, overweight, hyperphagia, hyperlipidemia, inflammation, altered activity of the sympathetic nervous system and insulin signal defect, all of which contribute to the development of IR. In addition, acupuncture has the potential to improve insulin sensitivity. The evidence has revealed the mechanisms responsible for the beneficial effects of acupuncture, though further investigations are warranted. [source] Fronto-striatal dysfunction and potential compensatory mechanisms in male adolescents with fragile X syndromeHUMAN BRAIN MAPPING, Issue 6 2007Fumiko Hoeft Abstract Response inhibition is an important facet of executive function. Fragile X syndrome (FraX), with a known genetic etiology (fragile X mental retardation-1 (FMR1) mutation) and deficits in response inhibition, may be an ideal condition for elucidating interactions among gene-brain-behavior relationships. Functional magnetic resonance imaging (fMRI) studies have shown evidence of aberrant neural activity when individuals with FraX perform executive function tasks, though the specific nature of this altered activity or possible compensatory processes has yet to be elucidated. To address this question, we examined brain activation patterns using fMRI during a go/nogo task in adolescent males with FraX and in controls. The critical comparison was made between FraX individuals and age, gender, and intelligent quotient (IQ)-matched developmentally delayed controls; in addition to a control group of age and gender-matched typically developing individuals. The FraX group showed reduced activation in the right ventrolateral prefrontal cortex (VLPFC) and right caudate head, and increased contralateral (left) VLPFC activation compared with both control groups. Individuals with FraX, but not controls, showed a significant positive correlation between task performance and activation in the left VLPFC. This potential compensatory activation was predicted by the interaction between FMR1 protein (FMRP) levels and right striatal dysfunction. These results suggest that right fronto-striatal dysfunction is likely an identifiable neuro-phenotypic feature of FraX and that activation of the left VLPFC during successful response inhibition may reflect compensatory processes. We further show that these putative compensatory processes can be predicted by a complex interaction between genetic risk and neural function. Hum Brain Mapp, 2007. © 2007 Wiley-Liss, Inc. [source] Mechanistic insights into oxidosqualene cyclizations through homology modelingJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 6 2003Gasch, Tanja Schulz Abstract 2,3-Oxidosqualene cyclases (OSC) are key enzymes in sterol biosynthesis. They catalyze the stereoselective cyclization and skeletal rearrangement of (3S)-2,3-oxidosqualene to lanosterol in mammals and fungi and to cycloartenol in algae and higher plants. Sequence information and proposed mechanism of 2,3-oxidosqualene cyclases are closely related to those of squalene-hopene cyclases (SHC), which represent functional analogs of OSCs in bacteria. SHCs catalyze the cationic cyclization cascade converting the linear triterpene squalene to fused ring compounds called hopanoids. High stereoselectivity and precision of the skeletal rearrangements has aroused the interest of researchers for nearly half a century, and valuable data on studying mechanistic details in the complex enzyme-catalyzed cyclization cascade has been collected. Today, interest in cyclases is still unbroken, because OSCs became targets for the development of antifungal and hypocholesterolemic drugs. However, due to the large size and membrane-bound nature of OSCs, three-dimensional structural information is still not available, thus preventing a complete understanding of the atomic details of the catalytic mechanism. In this work, we discuss results gained from homology modeling of human OSC based on structural information of SHC from Alicyclobacillus acidocaldarius and propose a structural model of human OSC. The model is in accordance with previously performed experimental studies with mechanism-based suicide inhibitors and mutagenesis experiments with altered activity and product specificity. Structural insight should strongly stimulate structure-based design of antifungal or cholesterol-lowering drugs. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 741,753, 2003 [source] EFFECT OF BUTYRIC ACID SUPPLEMENTATION ON SERUM AND RENAL ANTIOXIDANT ENZYME ACTIVITIES IN STREPTOZOTOCIN-INDUCED DIABETIC RATSJOURNAL OF FOOD BIOCHEMISTRY, Issue 2010A. PUNEETH KUMAR ABSTRACT Reactive oxygen metabolites, which are constant products of normal aerobic cell metabolism, play a key role in worsening the pathophysiological complications of diabetes. The present investigation was aimed at understanding the effect of butyric acid supplementation along with wheatbran and guar gum on serum and renal antioxidant enzyme activities and lipid peroxidation in streptozotocin (STZ)-induced diabetic rats. Activities of superoxide dismutase, catalase, glutathione peroxidase were evaluated in serum and kidney of control and experimental rats. Results clearly showed that the altered activity of the enzymes during diabetes was significantly ameliorated by butyric acid (500 mg/kg body weight/day) supplementation compared with other experimental groups. Further, the increased lipid peroxidation in serum and kidney of diabetic rats was also significantly reduced in butyric acid-supplemented diabetic rats. The study led us to conclude that butyric acid exert antioxidant property, thereby minimizing oxidative stress induced diabetes and its related complications. PRACTICAL APPLICATIONS Butyric acid , a product of dietary fiber fermentation , is a four-carbon fatty acid, which has wide range of application in disease management. This product is involved in various physiological functions of body like cell differentiation, apoptosis, colonic homeostasis, histone acetylation, etc. It is also known to decrease the incidence of bowel cancer and some of its analogues are shown to selectively improve glucose-stimulated insulin release and glucose tolerance in both normal and diabetic rats. This study aims to evaluate the beneficial effects of butyric acid supplementation on oxidative stress-induced diabetic complications in rats. [source] Crystallization and preliminary X-ray analysis of a novel haloalkane dehalogenase DbeA from Bradyrhizobium elkani USDA94ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 4 2009Tatyana Prudnikova A novel enzyme, DbeA, belonging to the haloalkane dehalogenase family (EC 3.8.1.5) was isolated from Bradyrhizobium elkani USDA94. This haloalkane dehalogenase is closely related to the DbjA enzyme from B. japonicum USDA110 (71% sequence identity), but has different biochemical properties. DbeA is generally less active and has a higher specificity towards brominated and iodinated compounds than DbjA. In order to understand the altered activity and specificity of DbeA, its mutant variant DbeA1, which carries the unique fragment of DbjA, was also constructed. Both wild-type DbeA and DbeA1 were crystallized using the sitting-drop vapour-diffusion method. The crystals of DbeA belonged to the primitive orthorhombic space group P212121, while the crystals of DbeA1 belonged to the monoclinic space group C2. Diffraction data were collected to 2.2,Å resolution for both DbeA and DbeA1 crystals. [source] Polymorphisms of ADIPOR1 and ADIPOR2 are associated with phenotypes of type 2 diabetes in KoreansCLINICAL ENDOCRINOLOGY, Issue 1 2009Jin Taek Kim Summary Objective, Adiponectin receptors 1 and 2 (ADIPOR1 and ADIPOR2) are considered as candidate genes for type 2 diabetes because they mediate the metabolic effects of adiponectin on target tissues. We investigated whether common polymorphisms of ADIPOR1 and ADIPOR2 are associated with type 2 diabetes or its related phenotypes in Koreans. Design and patients, By sequencing of the DNA samples from 24 unrelated Korean subjects, we selected seven single nucleotide polymorphisms (SNPs) from ADIPOR1 and four SNPs from ADIPOR2 for genotyping in 757 type 2 diabetic patients and 644 nondiabetic subjects. Results, None of the SNPs were associated with the risk of type 2 diabetes. However, g.,7309A>G (rs75172865) in ADIPOR1 was associated with lower insulin resistance, measured by the homeostasis model assessment of insulin resistance (HOMA-IR). Thereafter, we transfected three different human cell lines with plasmids harbouring g.,7309A>G and found that this variant reduced the promoter activity of ADIPOR1. In ADIPOR2, g.,63442G (novel SNP) and g.33447T (rs1044471) were associated with smaller waist circumference. Conclusions, None of the SNPs in either ADIPOR1 or ADIPOR2 were associated with the risk of type 2 diabetes in Koreans. However, the altered activity of the ADIPOR1 promoter was associated with insulin resistance and SNPs of ADIPOR2 were associated with waist circumference. [source] |