ABSTRACT
Nonsteroidal antiinflammatory drugs and analgesic drugs, such as N‐acetyl‐p‐aminophenol (APAP; acetaminophen, paracetamol), are widely used by pregnant women. Accumulating evidence has ...indicated that these molecules can favor genital malformations in newborn boys and reproductive disorders in adults. However, the consequences on postnatal testis development and adult reproductive health after exposure during early embryo‐genesis are still unknown. Using the mouse model, we show that in utero exposure to therapeutic doses of the widely used APAP‐ibuprofen combination during the sex determination period leads to early differentiation and decreased proliferation of male embryonic germ cells, and early 5‐mefhylcytosine and extracellular matrix protein deposition in 13.5 d postcoitum exposed testes. Consequently, in postnatal testes, Sertoli‐cell maturation is delayed, the Leydig‐cell compartment is hyperplasia and the spermatogonia A pool is decreased. This results in a reduced production of testosterone and in epididymal sperm parameter defects. We observed a reduced sperm count (19%) in utero–exposed (FO) adult males and also a reduced sperm motility (40%) in their offspring (Fl) when both parents were exposed, which leads to subfertility among the 6 mo old Fl animals. Our study suggests that the use of these drugs during the critical period of sex determination affects the germ‐line development and leads to adverse effects that could be passed to the offspring.—Rossitto, M., Marchive, C., Pruvost, A., Sellem, E., Ghettas, A., Badiou, S., Sutra, T., Poulat, F., Philibert, P., Boizet‐Bonhoure, B. Intergenerational effects on mouse sperm quality after in utero exposure to acetaminophen and ibuprofen. FASEB J. 33, 339–357 (2019). www.fasebj.org
Point of care testing makes it possible to obtain results in an extremely short time. Recently, radiometer has expanded the panel of tests available on its ABL90 FLEX PLUS blood gas analyzer (ABL90) ...by adding urea and creatinine. The aim of this study was to verify the performance of these new parameters. This included assessment of imprecision, linearity, accuracy by comparison with central laboratory standard assays and interferences. In addition, clinical utility in a dialysis center was evaluated. Within-lab coefficients of variation were close to 2%. The mean and limits of agreement (mean ± 1.96 SD) of the difference between ABL90 and Roche enzymatic assays on cobas 8000 were 0.5 (from −1.4 to 2.3) mmol/L and −0.9 (from −19.5 to 17.8) µmol/L for urea and creatinine, respectively. The ABL90 enzymatic urea and creatinine assays met the acceptance criteria based on biological variation for imprecision and showed good agreement with central laboratory. The two assays were unaffected by hematocrit variation between 20 and 70%, hemolysis and icterus interferences. It should be noted that the relationship between lab methods and ABL90 was conserved even for high pre-dialysis values allowing easy access to dialysis adequacy parameters (Kt/V) and muscle mass evaluation (creatinine index). Rapid measurement of creatinine and urea using whole blood specimens on ABL90 appears as a fast and convenient method. Analytical performances were in accordance with our expectations without any significant interferences by hemolysis or icterus.
Palm olein (PO) and olive oil (OO) are widely consumed in the world. PO is considered harmful to health, whereas OO is considered healthy. The aim of the study was to compare the effects of ...consumption of these oils on antioxidant status and inflammation in rats. This was an experimental study in male wistar rats fed a diet containing 30% of each oil. Rats had free access to food and water. After being fed for 12 weeks, animals were sacrificed and liver and aortic blood were collected. Plasma was used for the determination of interleukin-6 (IL-6) and oxidative stress parameters (Superoxide dismutase -SOD; Gluthation peroxidase - GPx; Thiobarbituric acid reactive substances - TBARS; Thiol groups and isoprostane). The inflammation and oxidative stress status as well as the expression of several genes/proteins were also analyzed in liver homogenate. No significant differences were observed between PO and OO in plasma and liver levels of the studied inflammation and oxidative stress parameters. This study showed that the consumption of PO induces an antioxidant status superimposable to that of OO. Key words : Palm olein - Olive oil - Oxidative stress - Inflammation - High fat diet.
Enrichment of durum wheat pasta with legume flour enhances their protein and essential amino acid content, especially lysine content. However, despite its nutritional potential, the addition of a ...legume alters the rheological properties of pasta. High temperature drying of pasta reduces this negative effect by strengthening its protein network. The aim of our study was to determine if these changes in the pasta structure alter its in vitro carbohydrate digestibility, in vivo glycemic, insulin and satiety responses. We also investigated if high temperature drying of pasta can reduce the well-known digestive discomfort associated with the consumption of legume grains. Fifteen healthy volunteers consumed three test meals: durum wheat pasta dried at a low temperature (control), and pasta enriched with 35% faba bean dried at a low and at a very high temperature. When enriched with 35% legume flour, pasta maintained its nutritionally valuable low glycemic and insulin index, despite its weaker protein network. Drying 35% faba bean pasta at a high temperature strengthened its protein network, and decreased its in vitro carbohydrate digestion with no further decrease in its in vivo glycemic or insulin index. Drying pasta at a very high temperature reduced digestive discomfort and enhanced self-reported satiety, and was not associated with a modification of energy intake in the following meal.
Many patients are maintained at the lower end of the tacrolimus (TAC) reference range (3-7 ng/mL), requiring the use of analytical methods displaying a very low limit of quantification for their ...follow-up. Therefore, the new Dimension TAC, based on affinity chrome-mediated immunoassay technology, was evaluated on the Dimension EXL Integrated Chemistry System (Siemens Healthcare Diagnostics Inc). The aims of this study were (1) to evaluate the analytical performances with special emphasis on sensibility at low levels of TAC, (2) to compare the results with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method.
Analytical performance (imprecision, linearity, limit of detection, and limit of quantification) was evaluated. Comparison to UPLC/MS/MS was performed on 106 whole blood samples from 88 transplant recipients using regression analysis and Bland-Altman plot analysis.
Repeatability and within-laboratory coefficients of variation were <6% at mean TAC control levels of 3.7, 11.7, and 19.2 ng/mL. Linearity was confirmed between 1.0 and 22 ng/mL. Passing-Bablok regression analysis of Siemens TAC assay in comparison with UPLC/MS/MS values displayed a slope of 1.09 and an intercept of -0.42. Using Bland-Altman analysis, the mean bias was 0.27 ng/mL with 1.96 SD limits of -2.14 and 2.67 ng/mL.
The new Dimension TAC immunoassay on the EXL analyzer demonstrated reliable and reproducible performances allowing routine monitoring in transplant patients, even at TAC concentrations at the lower end of the therapeutic range.
A new particle-enhanced turbidimetric immunoassay, Quantitative Microsphere System (QMS) everolimus, was evaluated using an Indiko analyzer (Thermo Fisher Scientific).
Analytical performances ...(imprecision, linearity, limit of detection, and limit of quantification) of this new immunoassay were evaluated. The method was compared with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC/MS/MS) method and with the previously available Innofluor Certican immunoassay on 120 whole-blood samples from 74 transplant recipients. Passing-Bablok regression and Bland-Altman plot were used for method comparisons.
Within- and between-day coefficients of variation were <10% at mean levels of 4.3, 8.2, and 15.9 ng/mL, respectively. This assay could be used at everolimus concentrations between 1.7 and 20 ng/mL. We obtained a Passing-Bablok regression of y = 0.99 × -0.15 (r = 0.95) when comparing with the UPLC/MS/MS method and of y = 0.81 × -0.09 (r = 0.94) when comparing with Innofluor assay. The mean and limits of agreement (mean ± 1.96 SD) of the difference between QMS everolimus and UPLC/MS/MS were -0.13 (from -2.0 to 1.74) ng/mL and were -1.19 (from -3.39 to 1.01) ng/mL between QMS everolimus and Innofluor.
The QMS everolimus method on Indiko analyzer demonstrated reliable and reproducible performances allowing routine monitoring in transplant patients.
Recent studies showed that hydrogen peroxide (H2O2) enhanced bone markers expression in vascular smooth muscle cells (VSMCs) implicated in osteoblastic differentiation. This study aimed at ...investigating the role of NAD(P)H oxidase in vascular calcification processes. A7r5 rat VSMCs were incubated with -glycerophosphate (10 mm) or uremic serum to induce a diffuse mineralization. H2O2 production by VSMCs was determinated by chemiluminescence. NAD(P)H oxidase sub-unit (p22phox), Cbfa-1, ERK phosphorylation and bone alkaline phosphatase (ALP) expressions were measured by Western blotting. VSMCs exhibited higher production of H2O2 and early expression of p22phox with -glycerophosphate or uremic serum within 24 h of treatment. -glycerophosphate-induced oxidative stress was associated with Cbfa-1 expression followed by ALP expression and activity, meanwhile the VSMCs expressing ALP diffusely calcified their extracellular matrix. Interestingly, diphenyleneiodonium partly prevented the osteoblastic differentiation. Results from this model strongly suggest a major implication of vascular NAD(P)H oxidase in vascular calcification supported by VSMCs osteoblastic differentiation.
We previously showed that grape extracts enriched in different polyphenolic families were similarly able to prevent reactive oxygen species (ROS) production, although having differential effects on ...various features of metabolic syndrome when administered at a dose of 21 mg/kg to the fructose (60%)-fed rat (a model of metabolic syndrome). In the present work, we analyzed on the same model the effect of pure polyphenolic molecules (catechin, resveratrol, delphinidin, and gallic acid) administered at a dose of 2.1 mg/kg. Delphinidin and gallic acid prevented insulin resistance, while gallic acid prevented the elevation of blood pressure. All molecules prevented cardiac ROS overproduction and NADPH overexpression. We also showed that fructose feeding was associated with cardiac fibrosis (accumulation of collagen I) and expression of osteopontin, a factor induced by ROS and a collagen I expression inducer. Collagen I and osteopontin expressions were prevented by the administration of all polyphenolic molecules. The potential use of polyphenols in the prevention of cardiac fibrosis should be further explored.
The effects of fruit and vegetable extract (Oxxynea) on plasma cholesterol, early atherosclerosis, cardiac production of superoxide anion, and NAD(P)H oxidase expression were studied in an animal ...model of atherosclerosis. Thirty six hamsters were divided into two groups of 18 and fed an atherogenic diet for 12 weeks. They received by gavage either water or Oxxynea in water at a human dose equivalent of 10 fruits and vegetables per day. Oxxynea lowered plasma cholesterol and non-HDL cholesterol, but not HDL-cholesterol, and increased plasma antioxidant capacity. It also strongly reduced the area of aortic fatty streak deposition by 77%, cardiac production of superoxide anion by 45%, and p22phox subunit of NAD(P)H oxidase expression by 59%. These findings support the view that chronic consumption of antioxidants supplied by fruits and vegetables has potential beneficial effects with respect to the development of atherosclerosis. The underlying mechanism is related mainly to inhibiting pro-oxidant factors and improving the serum lipid profile. Keywords: Atherosclerosis; hamsters; fruits and vegetables; antioxidant compounds; NADPH oxidase
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