The objectives of this retrospective study were to use in-line milk progesterone (mP4) data to investigate relationships of (1) commencement of luteal activity (CLA), and (2) luteal phase (LP) length and frequency preceding first postpartum AI, with parity and AI outcomes in Canadian Holstein cows. Starting 21 ± 1 days postpartum (DPP), levels of mP4 were assessed every 2.2 ± 2.0 d through an automated in-line milk analysis system (Herd Navigator™, DeLaval International, Tumba, Sweden) until ∼55 d after first or second AI in 748 Holstein cows from two herds. The CLA was defined as the DPP of the first of at least two consecutive samples with mP4 ≥5 ng/mL, and the period with elevated mP4 (≥5 ng/mL) was defined as the LP. Cows were categorized by CLA [earlier (≤) or later (>) than 28, 35, 42, 49, 56, and 63 DPP], and by the pattern of LP frequency preceding first AI as having or not: (1) one or more normal LP (LP length ≥7 and ≤19 d); (2) one or more abnormal LP (LP length <7 or >19 d, or interluteal period ≥12 d); and (3) two or more LP (either normal or abnormal). Outcomes of first or second AI were determined by the interval between AI and cessation of the ensuing LP as: non-pregnant (mP4-decline ≤30 d), presumed-pregnant (no mP4-decline until 55 d), or presumed-pregnancy loss (mP4-decline between 31 and ≤55 d). The odds of pregnancy per AI (P/AI) at 55 d and pregnancy loss were evaluated using generalized linear mixed models. Primiparous cows had lower odds of having CLA ≤28 DPP [Odds ratio (OR) = 0.58, P = 0.002] and one or more abnormal LP (OR = 0.73, P = 0.04) than multiparous cows. In multiparous cows, CLA ≤28 DPP decreased pregnancy loss (OR = 0.48, P = 0.05) and CLA ≤56 DPP increased P/AI (OR = 4.69, P < 0.01) compared to a later CLA. Primiparous and multiparous cows that had one or more normal LP before first AI had increased P/AI (OR = 3.85 and 3.45, respectively, P < 0.01) and reduced pregnancy loss (OR = 0.26 and 0.27, respectively, P < 0.01) than cows without a normal LP. Primiparous cows that had one or more abnormal LP had decreased P/AI (OR = 0.62, P = 0.04) and increased pregnancy loss (OR = 1.64, P = 0.04) compared to those without an abnormal LP. In summary, AI outcomes were improved in multiparous cows that had early CLA and in cows of both parity groups that had at least one normal LP before first AI. However, primiparous cows that had at least one abnormal LP had reduced AI outcomes. Relationships between early postpartum luteal activity and AI outcomes were inconsistent between primiparous and multiparous cows.
Cisplatin is commonly prescribed for the treatment of various solid tumors but its use is limited due to certain side effects and renal injury is a true example. Oxidative stress and inflammation may contribute to the cisplatin induced nephrotoxicity. Accordingly, we evaluated the effect of oral vanillin intake (100 mg/kg body weight) daily for 4 weeks to combat this hazard. The present results have demonstrated significant attenuation of oxidative stress and renal injury where reduced glutathione (GSH) showed significant increase along with malondialdehyde (MDA) decrease. Fibrotic markers like fibroblast growth factor-23 (FGF-23), transforming growth factor-β1 (TGF-β1), inflammatory mediators such as nuclear factor-κB (NF-κB) and tumor necrosis factor-α (TNF-α) showed also significant decrease in vanillin treated rats as compared with the control group.Renal function showed also significant improvement where urea and creatinine demonstrated significant decrease and the histopathological study presented a good support to the biochemical markers results. Our conclusion that vanillin is a potent antioxidant, anti-inflammatory and anti-fibrotic agent. Additionally, it is a good modulator candidate for the renal injury induced by cisplatin intake.
Recientes estudios han demostrado que algunos tipos de pesticidas estan relacionados con el desarrollo de enfermedades neurodegenerativas como el Parkinson y el Alzheimer, por lo que se postula la posibilidad de que tambien lo esten con la Esclerosis Lateral Amiotrofica (ELA). Para determinar la existencia de esta relacion se llevo a cabo una revision bibliografica de los estudios epidemiologicos publicados hasta la fecha que evaluaran el riesgo de desarrollar ELA tras la exposicion a pesticidas. Posteriormente, se aplico un meta-analisis sobre los datos numericos publicados en ellos para obtener un valor combinado de Odds Ratio (OR) que permitiera evaluar el riesgo de manera estadistica. Siete estudios epidemiologicos fueron incluidos en el analisis tras aplicar los criterios de inclusion. Se obtuvo un valor de OR de 1,42 (con intervalo de confianza del 95% de 1,09-1,86) con un p-valor altamente significativo (p=0,001). A partir de los resultados obtenidos se puede concluir que parece existir una relacion de causalidad entre la exposicion a pesticidas y el desarrollo de ELA, aunque esta podria estar relacionada tambien con otros factores.
While urine has been an easily accessible and feasible matrix for human biomonitoring, analytical measurements in internal tissues and organs can provide more accurate exposure assessments to understand disease etiology. This is especially important for the endocrine active compound, bisphenol A (BPA), where studies investigating internal doses at sensitive periods of human development are currently lacking. Herein, BPA concentrations, BPA-specific metabolizing enzyme gene expression, and global DNA methylation were characterized across three matched tissues from elective pregnancy terminations of 2nd trimester human fetuses: the placenta, liver, and kidney (N = 12 each; N = 36 total). Compared to liver (free: 0.54–50.5 ng g−1), BPA concentrations were lower in matched placenta (<0.05–25.4 ng g−1) and kidney (0.08–11.1 ng g−1) specimens. BPA-specific metabolism gene expression of GUSB, UGT2B15, STS, and SULT1A1 differed across each tissue type; however, conjugation and deconjugation expression patterns were similar across the fetus. Average LINE1 and CCGG global methylation were 58.3% and 59.2% in placenta, 79.5% and 66.4% in fetal liver, and 77.9% and 77.0% in fetal kidney, with significant tissue-specific DNA methylation differences in both LINE1 (p-value <0.001) and CCGG content (p-value <0.001). Total BPA concentrations were positively associated with global methylation for the placenta only using the LINE1 assay (p-value: 0.002), suggesting organ-specific biological effects after fetal exposure. Utilizing sensitive human clinical specimens, results are informative for BPA toxicokinetics and toxicodynamics assessment in the developing human fetus.
Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels of neutrophil gelatinase-associated lipocalin (NGAL), liver–fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87 ml/min per 1.73 m2 and urinary albumin excretion 1141 mg/24 h. Patients with the highest compared with the lowest quartile of urinary NGAL at baseline had higher urinary KIM-1 levels and a significant decrease in their GFR each year. Using linear regression analysis, we found that elevated urinary NGAL and KIM-1 concentrations were associated with a faster decline in GFR, but not after adjustment for known promoters of progression. Urinary LFABP was not related to decline in GFR. Losartan treatment (100 mg/day) reduced urinary KIM-1 by 43% over a 12-month period. Thus, urine biomarker measurements in patients with type 1 diabetic nephropathy did not provide additional prognostic information to that of known progression promoters.