Molecular hepatoprotective effects of lipoic acid against carbon tetrachloride-induced liver fibrosis in rats: Hepatoprotection at molecular level.

BACKGROUND: Liver fibrosis is a noteworthy well-being issue that can prompt the progression of liver cirrhosis and hepatocellular carcinoma. Prominently, many antioxidants have been shown to have defensive impacts against liver fibrosis. AIM: Subsequently, in the present study, the viability of alpha-lipoic acid (α-LA) in ensuring against carbon tetrachloride (CCl4)-actuated liver fibrosis and the mechanism(s) involved in this defensive impact were considered in rats. RESULTS: The present results uncovered that in the CCl4-treated group, the expression of antioxidant enzymes and matrix metalloproteinase-13 (MMP-13) messenger RNA (mRNA) was downregulated ( p < 0.05), and the levels of lipid peroxide and nitric oxide were increased ( p < 0.05) in the treated rat livers along with increased collagen deposition compared to that of the control group. Also, the gene expression levels of the proinflammatory factors interleukin-6 and tumor necrosis factor-alpha, nuclear factor-kappa B (NF-κB) p65, transforming growth factor-alpha, and inducible nitric oxide synthase (iNOS) were upregulated significantly ( p < 0.05) in the CCl4 group. These negative impacts were all restrained by α-LA. CONCLUSIONS: These outcomes show that α-LA might be compelling at forestalling collagen deposition and hepatic oxidative stress as well as downregulating the expression of hepatic proinflammatory cytokines, iNOS, and NF-κB and upregulating MMP-13 expression.

Effect of Genetic Polymorphisms in GH/Hpa II and MSTN / Dra I Loci on Body Weight in Friesian Bull Calves.

OBJECTIVE: The GH and MSTN gene polymorphisms and their association with body weight were declared in a population of 100 Friesian bull calves. MATERIALS AND METHODS: For DNA extraction, collection of blood samples was carried out from the studied animals. The PCR for GH and MSTN genes yielded fragments of 329 and 1346 bp, respectively. RESULTS: The PCR-HpaII digestion of 329 bp of GH gene revealed three genotypes: AA genotype possess undigested fragment (329 bp), AB genotype has three fragments (329, 224 and 105 bp) and BB genotype has two fragments (224 and 105 bp). The GH genotypes incidence and alleles frequency were calculated. For the 100 Friesian bull calves, genotypic frequencies for the AA, AB and BB genotypes were 0.1, 0.78 and 0.12, respectively and the allele frequencies for A and B allele frequencies were 0.49 and 0.51. Statistical analysis revealed that there was a significant effect of GH genotypes on body weight. The AB genotype possessed higher body weight than the other 2 genotypes. Regarding MSTN gene, PCR-DraI digestion of 1346 bp fragment was monomorphic; where it yielded four fragments (505, 427, 321 and 93 bp) in all animals under study. CONCLUSION: The outcome of this study is that it highlights the effectiveness of GH/HpaII locus as candidate marker for body weight in cattle rather than MSTN/DraI.

Chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract against chromium-induced testicular toxicity in rats.

This study was conducted to determine the mechanism underlying the chemotherapeutic efficacy of an ethanolic Moringa oleifera leaf extract (MOLEE) against chromium-induced impairments of rat testes using biochemical methods. Twenty male Wistar rats were divided into four groups of five animals each. Group I (control), group II injected potassium dichromate (8 mg kg(-1) ) i.p., group III gastrogavaged MOLEE (500 mg kg(-1) ) p.o. and group IV received (potassium dichromate plus MOLEE) by the same doses for 60 days. After the blood samples were collected, the animals were sacrificed to determine the testicular antioxidant status and sperm parameters. The chromium-treated group exhibited a significant decrease in testicular antioxidant enzymatic activities, local immunity and sperm parameters as well as an increase in inflammatory markers when compared with the control and MOLEE-treated group. However, concurrent administration of chromium and MOLEE significantly ameliorated the chromium effects on the sperm parameters, local immunity, inflammatory markers and antioxidant enzymatic activities compared with rats exposed to chromium alone. This study concludes that chronic exposure to chromium produces clear testicular toxicity, which can either be prevented or at least decreased by concomitant administration of MOLEE. Interestingly, the metal ion chelation could attribute partly the antioxidant activities of MOLEE.

Poor sleep in PCOS; is melatonin the culprit?

STUDY QUESTION: Are daily cycles in urinary melatonin and oxidative stress marker levels (8-hydroxydeoxyguanosine) altered in PCOS, and is this associated with changes in sleep quality? SUMMARY ANSWER: There is an association between elevated nighttime melatonin and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, and poor sleep quality in our PCOS study group. WHAT IS KNOWN ALREADY: Women with PCOS are known to have poorer sleep. However, there have been few studies examining the possible association between melatonin levels and sleep quality in women with polycystic ovarian syndrome (PCOS). STUDY DESIGN, SIZE, DURATION: This is a case-control study of PCOS (n = 26) and non-PCOS control (n = 26) subjects recruited from a tertiary gynaecological centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: The participants were requested to complete sleep questionnaires for a month. In a subgroup from these cohorts (PCOS, n = 15; controls, n = 18), urine samples were also collected at various time points over a 24-h period. In addition, their sleep patterns and lighting environment were monitored for 3 consecutive days and nights using a wrist-mounted Actiwatch device. MAIN RESULTS AND THE ROLE OF CHANCE: PCOS women had significantly elevated night-time urinary levels of the melatonin metabolite 6-sulfatoxymelatonin (aMT6s) and of 8-OHdG (both at P < 0.05), as well as significantly reduced sleep quality (P < 0.05), compared with the controls. LIMITATIONS, REASONS FOR CAUTION: Due to the small sample size of the study, further studies will be required to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Our preliminary work provides a possible new insight into the interactions between melatonin, increased oxidative stress and sleep in women with PCOS. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Faculty of Medicine, University of Southampton.

Intralipid therapy for recurrent implantation failure: new hope or false dawn?

Recurrent embryo implantation failure (RIF) is a disorder with potentially devastating physiological and psychological manifestations for those affected. Although its prevalence is not uncommon, many of the mechanisms involved still require elucidation. Both organ-specific and systemic autoimmunity are associated with an increased prevalence of recurrent miscarriage and reproductive failure, rendering the role of the maternal immunological system in fertility a key concept. It is believed by some that central to this theme is the maternal cytokine profile, with particularly T-helper (Th) cells. Immune modulating therapies have therefore been mooted as potential therapeutic strategies. Recent reports of high pregnancy rates achievable in women with RIF have added fuel to the debate regarding the effectiveness of intralipid in modulating the immune system. We would like to assess if there is sufficient current evidence of acceptable quality to permit an assumption that intralipid therapy is an effective treatment for women undergoing repeated assisted reproduction cycles. We have concluded that appropriately controlled, large-scale, confirmatory studies are necessary to prove the efficacy of intralipid before it can be recommended for routine use.

Variation in stability of housekeeping genes in endometrium of healthy and polycystic ovarian syndrome women.

BACKGROUND: The use of housekeeping genes (HKG) as internal controls for real-time qPCR studies of gene expression is based on the assumption of their inherent stability. However, it is unclear whether this stability is maintained in disease states. In order to test this, the present study investigated the expression of specific HKG in the endometrium of healthy and polycystic ovarian syndrome (PCOS) women. METHODS: Endometrial tissue samples were taken from women with PCOS (n= 9) and controls (n= 10). The stability of nine candidate reference genes in the endometrial tissues were evaluated; four encode mitochondrial proteins [ATP5B, succinate dehydrogenase complex subunit A (SDHA), cytochrome c-1, glyceraldehyde-3-phosphatedehydrogenase], two encode ribosomal protein genes (18s ribosomal RNA, ribosomal protein L13A), one for cell structure (SDHA), one for cell signalling (beta actin, ACTB) and one involved in DNA repair (topoisomerase I, TOP1). The expression stability of these HKGs was calculated using geNORM qbasePLUS software, with stability defined by M-values, where higher M-value indicating less stability. In addition, changes in their cycle threshold values were analysed to determine direction of change between groups, and a Mann-Whitney U-test was used to determine statistical differences in expression. RESULTS: The most stable HKGs observed across both PCOS endometrium were found to be YWHAZ, CYC1 and ACTB. Further TOP1 demonstrated higher gene expression in the endometrium from PCOS women compared with those from healthy women. CONCLUSIONS: Of the nine HKGs examined, only YWHAZ, CYC1 and ACTB were stable in both control and PCOS endometrium: these should therefore be used as internal controls for quantitative reverse transcription-polymerase chain reaction analysis. Published discrepancies between endometrial gene expression studies may therefore be due in part to in the inappropriate HKG selection, and future gene expression studies should be based on HKG of known stability in both the disease and healthy states to avoid erroneous interpretation of results.

Adhesion reduction agents in gynaecological procedures: can NHS aff ord it? An economic cost efficiency analysis.

We examined the total costs to the National Health Service (NHS, UK) paid to treat adhesion complications and determine the theoretical savings and cost-effectiveness incurred if anti-adhesion agents were adopted. Using Healthcare Resource Groups (HRG) codes, we calculated the costs incurred through Payment by Results (PbR) and then calculated the financial savings that could be realised through the use of anti-adhesion agents. There were 62,186 adhesion-related consultant episodes between 2004 and 2008 encountered within the NHS. If an anti-adhesion agent cost £110 per usage, and can reduce adhesions in 25% of patients undergoing surgery, assuming that 25% of patients were readmitted in the first year after the primary surgery, the financial cost to the health service is, at best, savings of more than £700,000 and at worst, cost neutral to the NHS.