Maternal nutrient restriction and the fetal left ventricle: Decreased angiotensin receptor expression

BACKGROUND: Adequate maternal nutrition during gestation is requisite for fetal nutrition and development. While a large group of epidemiological studies indicate poor fetal nutrition increases heart disease risk and mortality in later life, little work has focused on the effects of impaired maternal nutrition on fetal heart development. We have previously shown that 50% global nutrient restriction from 28–78 days of gestation (early to mid-pregnancy; term = 147 days) in sheep at mid-gestation retards fetal growth while protecting growth of heart and results in hypertensive male offspring at nine months of age. In the present study, we evaluate LV gene transcription using RNA protection assay and real-time reverse transcriptase polymerase chain reaction, and protein expression using western blot, of VEGF and AT1 and AT2 receptors for AngII at mid-gestation in fetuses from pregnant ewes fed either 100% (C) or 50% (NR) diet during early to mid-gestation. RESULTS: No difference between the NR (n = 6) and C (n = 6) groups was found in gene transcription of the AngII receptors. Immunoreactive AT1 (1918.4 +/- 154.2 vs. 3881.2 +/- 494.9; P < 0.01) and AT2 (1729.9 +/- 293.6 vs. 3043.3 +/- 373.2; P < 0.02) was decreased in the LV of NR fetuses compared to C fetuses. The LV of fetuses exposed to NR had greater transcription of mRNA for VEGF (5.42 ± 0.85 vs. 3.05 ± 0.19; P < 0.03) than respective C LV, while no change was observed in immunoreactive VEGF. CONCLUSION: The present study demonstrates that VEGF, AT1 and AT2 message and protein are not tightly coupled, pointing to post-transcriptional control points in the mid gestation NR fetus. The present data also suggest that the role of VEGF and the renin-angiotensin system receptors during conditions inducing protected cardiac growth is distinct from the role these proteins may play in normal fetal cardiac growth. The present findings may help explain epidemiological studies that indicate fetuses with low birth weight carry an increased risk of mortality from coronary and cardiovascular disease, particularly if these individuals have reduced cardiovascular reserve due to an epigenetic decrease in vascularization

The pharmacokinetics of antibiotics in cystic fibrosis

Introduction Dosing of antibiotics in people with cystic fibrosis (CF) is challenging, due to altered pharmacokinetics, difficulty of lung tissue penetration, and increasing presence of antimicrobial resistance. Areas covered The purpose of this work is to critically review original data as well as previous reviews and guidelines on pharmacokinetics of systemic and inhaled antibiotics in CF, with the aim to propose strategies for optimization of antibacterial therapy in both children and adults with CF. Expert opinion For systemic antibiotics, absorption is comparable in CF patients and non-CF controls. The volume of distribution (Vd) of most antibiotics is similar between people with CF with normal body composition and healthy individuals. However, there are a few exceptions, like cefotiam and tobramycin. Many antibiotic class-dependent changes in drug metabolism and excretion are reported, with an increased total body clearance for ss-lactam antibiotics, aminoglycosides, fluoroquinolones, and trimethoprim. We, therefore, recommend following class-specific guidelines for CF, mostly resulting in higher dosages per kg bodyweight in CF compared to non-CF controls. Higher local antibiotic concentrations in the airways can be obtained by inhalation therapy, with which eradication of bacteria may be achieved while minimizing systemic exposure and risk of toxicity

Chemical-looping combustion - a thermodynamic study

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A systematic review exploring characteristics of youth with severe and enduring mental health problems (SEMHP)

A small group of youth and emerging adults deals with severe and enduring mental health problems (SEMHP). Current mental health care struggles to recognize and treat this group timely and adequately, leaving these youth between the cracks of the system. A first step to improve care for this group is to gain a deeper understanding of the characteristics of youth with SEMHP. Therefore, this study aimed at reviewing current literature about this target group and what is known so far about their characteristics. We included 39 studies with a focus on youth aged 12-25 years with SEMHP. After critical appraisal, a content analysis and in-depth thematic analysis were conducted. According to the included studies, youth with SEMHP were characterized by severe distress and recurrent comorbid mental health problems, with pervasive suicidality. Further, underlying trauma, family conflicts, peer rejection, deep feelings of hopelessness, and psychosocial malfunctioning characterized SEMHP. It was described that for youth with SEMHP a pervasive pattern of dysfunction in multiple domains is present leading to a detrimental impact. Subsequently, this pattern exerts a reciprocal influence on the mental health problems, causing a vicious circle further worsening SEMHP. Our findings emphasize the need for a holistic approach and to look beyond the traditional classification system in order to meet the needs of these youth with wide-ranging comorbid mental health problems.New methods for child psychiatric diagnosis and treatment outcome evaluatio