Antidiabetic and renoprotective effects of the chloroform extract of Terminalia chebula Retz. seeds in streptozotocin-induced diabetic rats

BACKGROUND: Terminalia chebula (Combretaceae) has been widely used in Ayurveda for the treatment of diabetes. In the present investigation, the chloroform extract of T. chebula seed powder was investigated for its antidiabetic activity in streptozotocin-induced diabetic rats using short term and long term study protocols. The efficacy of the extract was also evaluated for protection of renal functions in diabetic rats. METHODS: The blood glucose lowering activity of the chloroform extract was determined in streptozotocin-induced (75 mg/kg, i.p.; dissolved in 0.1 M acetate buffer; pH 4.5) diabetic rats, after oral administration at the doses of 100, 200 and 300 mg/kg in short term study. Blood samples were collected from the eye retro-orbital plexus of rats before and also at 0.5, 1, 2, 4, 6, 8 and 12 h after drug administration and the samples were analyzed for blood glucose by using glucose-oxidase/peroxidase method using a visible spectrophotometer. In long term study, the extract (300 mg/kg) was administered to streptozotocin-induced diabetic rats, daily for 8 weeks. Blood glucose was measured at weekly intervals for 4 weeks. Urine samples were collected before the induction of diabetes and at the end of 8 weeks of treatments and analyzed for urinary protein, albumin and creatinine levels. The data was compared statistically using one-way ANOVA with post-hoc Dunnet's t-test. RESULTS: The chloroform extract of T. chebula seeds produced dose-dependent reduction in blood glucose of diabetic rats and comparable with that of standard drug, glibenclamide in short term study. It also produced significant reduction in blood glucose in long term study. Significant renoprotective activity is observed in T. chebula treated rats. The results indicate a prolonged action in reduction of blood glucose by T. chebula and is probably mediated through enhanced secretion of insulin from the β-cells of Langerhans or through extra pancreatic mechanism. The probable mechanism of potent renoprotective actions of T. chebula has to be evaluated. CONCLUSION: The present studies clearly indicated a significant antidiabetic and renoprotective effects with the chloroform extract of T. chebula and lend support for its traditional usage. Further investigations on identification of the active principles and their mode of action are needed to unravel the molecular mechanisms involved in the observed effects

Human Papillomaviruses and genital co-infections in gynaecological outpatients

<p>Abstract</p> <p>Background</p> <p>High grade HPV infections and persistence are the strongest risk factors for cervical cancer. Nevertheless other genital microorganisms may be involved in the progression of HPV associated lesions.</p> <p>Methods</p> <p>Cervical samples were collected to search for human Papillomavirus (HPV), bacteria and yeast infections in gynaecologic outpatients. HPV typing was carried out by PCR and sequencing on cervical brush specimens. <it>Chlamydia trachomatis </it>was identified by strand displacement amplification (SDA) and the other microorganisms were detected by conventional methods.</p> <p>Results</p> <p>In this cross-sectional study on 857 enrolled outpatients, statistical analyses revealed a significant association of HPV with <it>C. trachomatis </it>and <it>Ureaplasma urealyticum (</it>at high density) detection, whereas no correlation was found between HPV infection and bacterial vaginosis, <it>Streptococcus agalactiae</it>, yeasts, <it>Trichomonas vaginalis </it>and <it>U. urealyticum</it>. <it>Mycoplasma hominis </it>was isolated only in a few cases both in HPV positive and negative women and no patient was infected with <it>Neisseria gonorrhoeae</it>.</p> <p>Conclusion</p> <p>Although bacterial vaginosis was not significantly associated with HPV, it was more common among the HPV positive women. A significant association between HPV and <it>C. trachomatis </it>was found and interestingly also with <it>U. urealyticum </it>but only at a high colonization rate. These data suggest that it may be important to screen for the simultaneous presence of different microorganisms which may have synergistic pathological effects.</p

Aging diminishes the resistance of AO rats to EAE: putative role of enhanced generation of GM-CSF Expressing CD4+T cells in aged rats

Background: Aging influences immune response and susceptibility to EAE in a strain specific manner. The study was designed to examine influence of aging on EAE induction in Albino Oxford (AO) rats. Results: Differently from 3-month-old (young) rats, which were resistant to EAE induction, the majority of aged (24-26-month-old) rats developed mild chronic form of EAE. On 16th day post-immunization, when in aged rats the neurological deficit reached plateau, more mononuclear cells, including CD4+ T lymphocytes was retrieved from spinal cord of aged than young rats. The frequencies of IL-17+ and GM-CSF+ cells within spinal cord infiltrating CD4+ lymphocytes were greater in aged rats. To their increased frequency contributed the expansion of GM-CSF + IL-17 + IFN-gamma+ cells, which are highly pathogenic in mice. The expression of the cytokines (IL-1 beta and IL-23/p19) driving GM-CSF + IL-17 + IFN-gamma + cell differentiation in mice was also augmented in aged rat spinal cord mononuclear cells. Additionally, in aged rat spinal cord the expansion of GM-CSF + IL-17-IFN-gamma- CD4+ T lymphocytes was found. Consistently, the expression of mRNAs for IL-3, the cytokine exhibiting the same expression pattern as GM-CSF, and IL-7, the cytokine driving differentiation of GM-CSF + IL-17-IFN-gamma- CD4 + lymphocytes in mice, was upregulated in aged rat spinal cord mononuclear cells, and the tissue, respectively. This was in accordance with the enhanced generation of the brain antigen-specific GM-CSF+ CD4+ lymphocytes in aged rat draining lymph nodes, as suggested by (i) the higher frequency of GM-CSF+ cells (reflecting the expansion of IL-17-IFN-gamma- cells) within their CD4+ lymphocytes and (ii) the upregulated GM-CSF and IL-3 mRNA expression in fresh CD4+ lymphocytes and MBP-stimulated draining lymph node cells and IL-7 mRNA in lymph node tissue from aged rats. In agreement with the upregulated GM-CSF expression in aged rats, strikingly more CD11b + CD45(int) (activated microglia) and CD45(hi) (mainly proinflammatory dendritic cells and macrophages) cells was retrieved from aged than young rat spinal cord. Besides, expression of mRNA for SOCS1, a negative regulator of proinflammatory cytokine expression in innate immunity cells, was downregulated in aged rat spinal cord mononuclear cells. Conclusions: The study revealed that aging may overcome genetic resistance to EAE, and indicated the cellular and molecular mechanisms contributing to this phenomenon in AO rats

Fine mapping of a QTL affecting levels of skatole on pig chromosome 7

Abstract Background Previous studies in the Norwegian pig breeds Landrace and Duroc have revealed a QTL for levels of skatole located in the region 74.7–80.5 Mb on SSC7. Skatole is one of the main components causing boar taint, which gives an undesirable smell and taste to the pig meat when heated. Surgical castration of boars is a common practice to reduce the risk of boar taint, however, a selection for boars genetically predisposed for low levels of taint would help eliminating the need for castration and be advantageous for both economic and welfare reasons. In order to identify the causal mutation(s) for the QTL and/or identify genetic markers for selection purposes we performed a fine mapping of the SSC7 skatole QTL region. Results A dense set of markers on SSC7 was obtained by whole genome re-sequencing of 24 Norwegian Landrace and 23 Duroc boars. Subsets of 126 and 157 SNPs were used for association analyses in Landrace and Duroc, respectively. Significant single markers associated with skatole spanned a large 4.4 Mb region from 75.9–80.3 Mb in Landrace, with the highest test scores found in a region between the genes NOVA1 and TGM1 (p < 0.001). The same QTL was obtained in Duroc and, although less significant, with associated SNPs spanning a 1.2 Mb region from 78.9–80.1 Mb (p < 0.01). The highest test scores in Duroc were found in genes of the granzyme family (GZMB and GZMH-like) and STXBP6. Haplotypes associated with levels of skatole were identified in Landrace but not in Duroc, and a haplotype block was found to explain 2.3% of the phenotypic variation for skatole. The SNPs in this region were not associated with levels of sex steroids. Conclusions Fine mapping of a QTL for skatole on SSC7 confirmed associations of this region with skatole levels in pigs. The QTL region was narrowed down to 4.4 Mb in Landrace and haplotypes explaining 2.3% of the phenotypic variance for skatole levels were identified. Results confirmed that sex steroids are not affected by this QTL region, making these markers attractive for selection against boar taint

Academic advancement of authors receiving tutoring from a medical journal

BACKGROUND: Although publishing in scientific journals has an educational component, the educational role of journals in medicine has not been evaluated. - - - - - PURPOSE: To assess whether tutoring authors in a medical scientific journal could be related to their long-term scientific publications and academic advancement. - - - - - METHODS: The study included 47 journal authors who were individually tutored in scientific writing and data presentation by the editors of the Croatian Medical Journal during the 1991-1995 war years and 47 colleagues the authors identified as their academic peers at the time of tutoring. We assessed their published articles in scientific journals, citations to these articles, and academic advancement, defined as the level of postgraduate education and advancement in the academic rank. - - - - - RESULTS: By 2003, tutored authors published more articles in MEDLINE-indexed journals than their academic peers (median = 4, interquartile range = 1-9 vs. 1 [0-5], respectively; p = .0265), and received more citations to these articles (4 [0-16] vs. 1 [0-6], p = .0275). They also made a significantly greater academic advancement, assessed as a score of their academic rank and research degree (2 [0-4] vs. 1 [0-2], p = .0369). - - - - - CONCLUSIONS: Editorial tutoring of journal authors can positively influence their long-term academic advancement. Journals may have an important teaching role in local academic communities

An immunomodulatory peptide related to frenatin 2 from skin secretions of the Tyrrhenian painted frog Discoglossus sardus (Alytidae)

Norepinephrine-stimulated skin secretions of the Tyrrhenian painted frog Discoglossus sardus Tschudi, 1837 (Alytidae) did not contain any peptide with antimicrobial or hemolytic activity. However, peptidomic analysis of the secretions revealed the presence of an abundant peptide with structural similarity to frenatin 2, previously isolated from the Australian frog Litoria infrafrenata (Hylidae). The primary structure of the peptide, termed frenatin 2D, was established as DLLGTLGNLPLPFI.NH2 by automated Edman degradation and mass spectrometry with electron-transfer dissociation (ETD)-based fragmentation and confirmed by chemical synthesis. The structure of a second frenatin 2-related peptide, termed frenatin 2.1D, that was present in much lower abundance was established as GTLGNLPAPFPG. Frenatin 2D (20 μg/ml) significantly stimulated production of the proinflammatory cytokines TNF-α (P<0.05) and IL-1β (P<0.01) by mouse peritoneal macrophages but the peptide did not potentiate the stimulation produced by lipopolysaccharide (LPS). The peptide increased IL-12 production in both unstimulated (P<0.01) and LPS-stimulated (P<0.05) cells but stimulatory effects on IL-6 production were not significant. The biological role of frenatin 2D is unknown but it is speculated that the peptide acts on skin macrophages to produce a cytokine-mediated stimulation of the adaptive immune system in response to invasion by microorganisms