Early influences on cardiovascular and renal development

The hypothesis that a developmental component plays a role in subsequent disease initially arose from epidemiological studies relating birth size to both risk factors for cardiovascular disease and actual cardiovascular disease prevalence in later life. The findings that small size at birth is associated with an increased risk of cardiovascular disease have led to concerns about the effect size and the causality of the associations. However, recent studies have overcome most methodological flaws and suggested small effect sizes for these associations for the individual, but an potential important effect size on a population level. Various mechanisms underlying these associations have been hypothesized, including fetal undernutrition, genetic susceptibility and postnatal accelerated growth. The specific adverse exposures in fetal and early postnatal life leading to cardiovascular disease in adult life are not yet fully understood. Current studies suggest that both environmental and genetic factors in various periods of life may underlie the complex associations of fetal growth retardation and low birth weight with cardiovascular disease in later life. To estimate the population effect size and to identify the underlying mechanisms, well-designed epidemiological studies are needed. This review is focused on specific adverse fetal exposures, cardiovascular adaptations and perspectives for new studies. Copyrigh

Quantitative, high-resolution epigenetic profiling of CpG loci identifies associations with cord blood plasma homocysteine and birth weight in humans

Supplementation with folic acid during pregnancy is known to reduce the risk of neural tube defects and low birth weight. It is thought that folate and other one-carbon intermediates might secure these clinical effects via DNA methylation. We examined the effects of folate on the human methylome using quantitative interrogation of 27,578 CpG loci associated with 14,496 genes at single-nucleotide resolution across 12 fetal cord blood samples. Consistent with previous studies, the majority of CpG dinucleotides located within CpG islands exhibited hypomethylation while those outside CpG islands showed mid-high methylation. However, for the first time in human samples, unbiased analysis of methylation across samples revealed a significant correlation of methylation patterns with plasma homocysteine, LINE-1 methylation and birth weight centile. Additionally, CpG methylation significantly correlated with either birth weight or LINE-1 methylation were predominantly located in CpG islands. These data indicate that levels of folate-associated intermediates in cord blood reflect their influence and consequences for the fetal epigenome and potentially on pregnancy outcome. In these cases, their influence might be exerted during late gestation or reflect those present during the peri-conceptual period

Dental Mold: A Novel Formulation to Treat Common Dental Disorders

Oral administration of antibiotics to treat dental problems mostly yields slow actions due to slow onset and hepatic “first-pass.” Again, commonly used dental paints are generally washed out by saliva within few hours of application. To overcome the challenges, polymeric molds to be placed on an affected tooth (during carries and gum problems) were prepared and evaluated in vitro for sustained drug release for prolonged local action. Here, amoxicillin trihydrate and lidocaine hydrochloride were used as model drugs. Dental molds were prepared using corn zein, carbopol 934 P, gum karaya powder, and poloxamer 407 by mixing and solvent evaporation technique. Different physicochemical evaluation studies such as tooth adhesion test, surface pH, swelling index, and drug-distribution pattern were carried out. Percentage swelling varied from 56% to 93%. Average tooth adhesion strength and mean initial surface pH of the formulations were 50 g and 6.5, respectively. As assessed by scanning electron microscopy, drug distribution was uniform throughout the matrix. Cumulative percentage release of lidocaine hydrochloride and amoxicillin trihydrate in simulated saliva were 98% and 50%, respectively. In vitro drug-release studies revealed the sustained-release patterns of the drugs in simulated saliva at least for 24 h. The stability study shows that the drugs were stable in the formulations following the conditions as per ICH guideline. The formulation is a novel approach to deliver the drug(s) for a prolonged period for local action upon its application on an affected tooth