Dietary interventions for fetal growth restriction – therapeutic potential of dietary nitrate supplementation in pregnancy

Abstract

Fetal growth restriction (FGR) affects around 5% of pregnancies and is associated with significant short- and long-term adverse outcomes. A number of factors can increase the risk of FGR, one of which is poor maternal diet. In terms of pathology, both clinically and in many experimental models of FGR, impaired uteroplacental vascular function is implicated, leading to a reduction in the delivery of oxygen and nutrients to the developing fetus. Whilst mechanisms underpinning impaired uteroplacental vascular function are not fully understood, interventions aimed at enhancing nitric oxide (NO) bioavailability remain a key area of interest in obstetric research. In addition to endogenous NO production from the amino acid L-arginine, via nitric oxide synthase (NOS) enzymes, research in recent years has established that significant NO can be derived from dietary nitrate, via the 'alternative NO pathway'. Dietary nitrate, abundant in green leafy vegetables and beetroot, can increase NO bioactivity, conferring beneficial effects on cardiovascular function and blood flow. Given the beneficial effects of dietary nitrate supplementation to date in non-pregnant humans and animals, current investigations aim to assess the therapeutic potential of this approach in pregnancy to enhance NO bioactivity, improve uteroplacental vascular function and increase fetal growth.

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Oropharyngeal swabs analyzed by ddPCR is a quantitative, rapid, and effective method for minimally invasive oncogenic HPV detection. This assay represents the most sensitive and accurate mode of HPV detection in OPSCC without a tissue biopsy in the available literature.

http://sfaki.blogspot.com/2017/01/hpv-opscc-is-commonly-diagnosed-by-rt.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Tumor uptake of 18F-BPA and 11C-Met : The distribution of 4-borono-2-18F-fluoro-phenylalanine (18F-BPA) and L-[methyl-11C] methionine (11C-Met) in normal organs and tumors and to evaluate the usefulness of 11C-Met/PET in screening potential candidates for boron neutron capture therapy (BNCT).

http://sfaki.blogspot.com/2017/01/relationship-between-uptake-of-18f.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

A novel homozygous truncating mutation of the SFRP4 gene in Pyle's disease

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Diltiazem prevents stress-induced contractile deficits in cardiomyocytes, but does not reverse the cardiomyopathy phenotype in Mybpc3-knock-in mice

Abstract

Left ventricular hypertrophy, diastolic dysfunction and fibrosis are main features of hypertrophic cardiomyopathy (HCM). Guidelines recommend β-adrenoceptor or Ca²⁺ channel antagonists as pharmacological treatment. The Ca²⁺ channel blocker diltiazem recently showed promising beneficial effects in pre-clinical HCM, particularly in patients carrying MYBPC3 mutations. In the present study we evaluated whether diltiazem could ameliorate or reverse the disease phenotype in cells and in vivo in Mybpc3-targeted knock-in (KI) mouse model of HCM. Sarcomere shortening and Ca²⁺ transient were measured in KI and wild-type (WT) cardiomyocytes in basal condition (1-Hz pacing) and under stress conditions (30 nm isoprenaline, 5-Hz pacing) with or without pre-treatment with 1 μm diltiazem. KI cardiomyocytes exhibited lower diastolic sarcomere length (dSL) at baseline, a tendency to a higher positive inotropic response to isoprenaline than WT, and a marked reduction of dSL and a tendency towards arrhythmias under stress conditions. Pre-treatment of cardiomyocytes with 1 μm diltiazem reduced the drop in dSL and arrhythmia frequency in KI, and attenuated the positive inotropic effect of isoprenaline. Furthermore, diltiazem reduced the contraction amplitude at 5 Hz but did not affect diastolic Ca²⁺ load and Ca²⁺ transient amplitude. Six-month diltiazem treatment of KI mice did not reverse cardiac hypertrophy and dysfunction, activation of the fetal gene program or fibrosis. In conclusion, diltiazem blunted the response to isoprenaline in WT and KI and improved diastolic relaxation under stress conditions in KI cardiomyocytes. This beneficial effect of diltiazem in cells did not translate in therapeutic efficacy when applied chronically in KI mice.

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Late gestational intermittent hypoxia induces metabolic and epigenetic changes in male adult offspring mice

Abstract

Pregnancy, particularly late gestation, has been associated with a relatively high prevalence of obstructive sleep apnea (OSA). Intermittent hypoxia (IH), a hallmark of OSA, could impose significant long-term effects on somatic growth, energy homeostasis, and metabolic function in offspring. We hypothesized that IH during late pregnancy (LG-IH) may increase the propensity for metabolic dysregulation and obesity in adult offspring via epigenetic modifications. Time-pregnant female C57BL/6 mice were exposed to LG-IH or room air (LG-RA) during days 13–18 of gestation. At 24 weeks, blood samples were collected from offspring mice for lipid profiles and insulin resistance (HOMA-IR), indirect calorimetry was performed, and visceral white adipose tissues (VWAT) were assessed for inflammatory cells as well as for differentially methylated gene regions (DMR) using MeDIP-Chip. Body weight, food intake, adiposity index, fasting insulin, triglycerides, and cholesterol levels were all significantly higher in LG-IH male but not female offspring. LG-IH also altered metabolic expenditure and locomotor activities in male offspring, and increased number of pro-inflammatory macrophages emerged in VWAT along with 1520 DMRs (P < 0.0001), associated with 693 genes. Pathway analyses showed that genes affected by LG-IH were mainly associated with molecular processes related to metabolic regulation and inflammation. LG-IH induces metabolic dysfunction as reflected by increased body weight and adiposity index in adult male offspring that is paralleled by epigenomic alterations and inflammation in VWAT. Thus, perturbations to fetal environment by OSA during pregnancy can therefore have long-term detrimental effects to the fetus, and lead to persistent metabolic dysfunction in adulthood.

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Tensions flare over Calif. ambulance response to calls

The firefighters union claimed ambulances from AMR are frequently unavailable to cover their response area

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