Severe alcoholic hepatitis (SAH) is associated with iron accumulation in hepatocytes/macrophages. This possibly correlates with inflammation and stress but the exact mechanism still remains obscure. To understand the role of iron and the mechanisms of systemic iron-overload, a transcriptomic study of liver and Peripheral Blood -Mononuclear-Cells (PBMCs) was undertaken in SAH patients, with and without hepatic iron-overload. Our results show that iron-overload in hepatocytes/macrophages is due to an increased expression of iron-loading receptors and CD163 signaling cascade. Increase in labile iron pool induces expression of iron-loading, oxidative-stress and inflammatory genes along with expression of CD163 and ADAM17. Increased liver iron correlated with circulatory iron, TNF-α, macrophage activation (sCD163) and peroxide-stress in CD163+macrophages in patients who were iron-overloaded and died. Circulatory TNF-α and sCD163 levels were associated with poor outcome. Temporal iron/Fenton stress induced in healthy monocyte-derived-macrophage (MDM)/Tohoku-Hospital-Pediatrics-1(THP1) cells showed higher expression of iron-regulatory, inflammatory and oxidative-stress genes. These genes could be suppressed by iron-chelation. These results suggest that iron mediates inflammation through ADAM17 induction, resulting in macrophage activation and increased shedding of TNF-α and sCD163. These events could be inhibited with iron chelation or with ADAM17-blockade, postulating a therapeutic strategy for SAH patients with iron overload.
u-Alb modifications are reflective of serum albumin modifications. Further baseline u-Alb levels could be exploited to predict steroid response and mortality in SAH patients.
Background: Anoestrus is still one of the most prevalent reproductive disorders in dairy cows despite technological advances in animal husbandry. Evaluation of blood biochemical profile is of diagnostic value to determine disease or health status of animal. The current study was aimed to evaluate the effect of different therapeutic regimen on blood biochemical profile, oestrus induction response and conception rate of anoestrus cows.Methods: Thirty two postpartum anoestrus cows randomly allocated to four groups as G0 (negative control), GI, GII, GIII, GIV and 8 normal cyclic as GV (positive control). Dewormer and mineral mixture administered to GI, GII, GIII, GIV while group GII, GIII and GIV additionally received janova, sepia and Ovsynch protocol respectively.Result: Different therapeutic protocols have variable effects on blood biochemical parameters. Overall oestrus induction response in G0, GI, GII, GIII, GIV and GV is 0.00, 50, 62.5, 75, 87.5 and 100.00 per cent respectively with corresponding conception rate of 0.00, 75, 80, 66.66, 57.13 and 75.00 per cent. On the basis of findings it can be concluded that aforesaid therapeutic regimens have definite bearings on fertility and can be used to manage postpartum anoestrus in cows.
This study tested the hypothesis that premature condensation of chromatin in goat oocytes following superovulation with 1200 i.u. pregnant mare serum gonadotrophin (PMSG) is mediated by the high luteinizing hormone (LH) activity inherent in this gonadotrophin. Goats were treated with either a standard (3.95 mL) or high (7.90 mL) dose of a highly purified follicle-stimulating hormone (FSH) preparation (Ovagen), and different doses of human chorionic gonadotrophin (hCG) were added to increase the level of LH bioactivity during superovulation. The meiotic status of oocytes obtained at sponge withdrawal was compared between different treatments and correlated with profiles of LH bioactivity in peripheral plasma. Injection of 100 i.u. hCG (which gave a plasma LH profile comparable to 1200 i.u. PMSG) or 200 i.u. hCG resulted in significantly more oocytes showing premature condensation of chromatin without germinal vesicle breakdown than with 25 i.u. hCG or treatment with FSH alone. Nevertheless, nuclear maturation was also prematurely activated in a significant number of oocytes with a high dose of FSH alone, even though LH bioactivity was not detected in plasma. It is concluded that high LH bioactivity during superovulation of goats with gonadotrophins activates the initial stages of nuclear maturation in oocytes. However, highly purified FSH preparations in high doses can also induce this apparent abnormality in the timing of oocyte maturation through mechanisms unrelated to any LH contamination.
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