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.

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.

Crude polysaccharides (MPS) from soybean residue fermented with Morchella esculenta were extracted and purified by DEAE Sephadex A-50 chromatography and Sephadex G-100 size-exclusion chromatography in sequence. Three main fractions MP-1, MP-3 and MP-4 were obtained during the purification steps. The recovery rates based on MPS used were 26.2%, 29.1% and 18.7% for MP-1, MP-3 and MP-4 respectively. The monosaccharide composition, ultraviolet spectrum, infrared spectrum and NMR of the three fractions were analyzed. Furthermore, the influence of polysaccharides fractions upon activation of macrophage cells (RAW 264.7), antitumor activities of the human hepatocellular cell line (HepG-2) and human cervical carcinoma cells (Hela) in vitro were evaluated. The results indicated that the proliferation of MP-3 on RAW 264.7 was 313.57% at 25 μg/mL, which is high while MP-1 had a higher growth inhibition effect on HepG-2 cells of 68.01% at concentration of 50 μg/mL. The fractions of MP-1, MP-3 and MP-4 induced apoptosis in HepG-2 cells and Hela cells by arresting cell cycle progression at the G0/G1 phase. These findings suggest that the purified polysaccharides fractions may be a potent candidate for human hepatocellular and cervical carcinoma treatment and prevention in functional foods and pharmacological fields.

El impacto económico del cáncer de próstata es cada vez mayor, teniendo en cuenta el incremento de su incidencia y la mayor supervivencia de los pacientes. Los ensayos clínicos son esenciales para la evaluación de la eficacia y seguridad de los nuevos tratamientos, pero también pueden suponer un beneficio económico al evitar el coste derivado del fármaco. Nuestro objetivo es determinar el coste evitado en medicamentos en investigación en los ensayos clínicos en cáncer de próstata realizados en un período de 18 años en un centro de tercer nivel.Se realizó un estudio observacional de prevalencia, con recogida de datos retrospectiva de los ensayos clínicos realizados en los que se utilizaron medicamentos comercializados actualmente. Se calculó el coste evitado durante el periodo de estudio (1996-2013).De los 18 ensayos clínicos realizados sobre cáncer de próstata se incluyeron en el presente trabajo 5 que cumplieron criterios de selección, todos ellos fase iii, multicéntricos e internacionales y con fármacos actualmente comercializados. Incluyeron 136 pacientes. Se obtuvo un coste evitado global de 696.002 €, un coste medio evitado por ensayo clínico de 139.200 € y un coste medio evitado por paciente de 5.118 €.El coste evitado en medicamentos en investigación es un beneficio tangible de los ensayos clínicos, cuya realización supone una fuente de ingresos para el hospital, no solo por los generados directamente por cada ensayo. Los ensayos clínicos suponen un contexto excepcional para el avance en investigación clínica, así como un ahorro real para nuestro sistema sanitario.Economic impact of prostate cancer is increasing in relation to its increased incidence and increased patient survival. Clinical trials are essential to evaluate the efficacy and safety of new treatments but may also result in economic benefits by avoiding the cost of the drug. Our objective is to determine the avoided cost in investigational drugs in clinical trials of prostate cancer conducted in a period of 18 years in a tertiary center.We carried out an observational of prevalence study with retrospective collected data of clinical trials involving currently marketed drugs and cost avoidance during the study period (1996-2013) was calculated.We include in this review five clinical trials on prostate cancer that met selection criteria of 18 performed. All of them were phase III, multicenter, international and with current marketed drugs. 136 patients were included. Total cost avoidance of 696,002€ and an average cost avoidance by clinical trial of 139,200€ were obtained. Average cost avoidance per patient was 5,118€.Cost avoidance in investigational drugs is a tangible benefit of clinical trials, whose realization is a source of economic benefits for the hospital, not only by directly generated by each trial. Clinical trials are an exceptional framework for progress in clinical research and real savings for the health system

Introduction and Aims: Clinical studies have demonstrated the risk of chronic kidney disease after the occurrence of an acute kidney injury (AKI).Experimental works indicate that AKI result in incomplete repair, persistent tubulointerstitial inflammation and fibrosis.Cysteine-rich protein 61 (Cyr61), a secreted matrix-associated protein, has been found to be up-regulated in the kidney ischemia reperfusion injury (IRI) animal model.The present study aimed to investigate the role of Cyr61 in the kidney after IRI.Methods: Using mouse unilateral IRI model, we analyzed gene and protein expression of Cyr61.We further investigated the effect of blockade of Cyr61 in unilateral IRI mice by treating polyclonal anti-Cyr61 antibody or non-specific IgG.In addition, we used proximal tubular epithelial (NRK-52E) cells for cell culture studies.Results: After IRI, kidney Cyr61 expression increased significantly in both mRNA and protein level.Immunofluorescence staining indicated Cyr61 was predominantly expressed in renal proximal tubular epithelial cells.This was supported by in vitro studies showing hypoxia condition stimulate Cyr61 expression in NRK-52E cells.Daily treatment with anti-Cyr61 antibody produced a decrease in the renal type 1 collagen, PAI-1, MCP-1, and IL-1 gene expression, as well as α-SMA protein production at day 14 after IRI.The degree of collagen fibril accumulation, evaluated by picrosirius red staining, and macrophage infiltration were both attenuated by the Cyr61 blockade on day 7 and 14.Concurrently, renal VEGF-A gene expression was enhanced and vessel density was more preserved at day 14 in the treatment group.Conclusions: Renal Cyr61 expression by tubular epithelial cells is enhanced after IRI.Our findings suggest that Cyr61 contributes to the renal inflammation, vascular rarefaction, and fibrosis after ischemic AKI.