Alcohol exposure in utero perturbs retinoid homeostasis in adult rats

Background

Maternal alcohol exposure and adult alcohol intake have been shown to perturb the metabolism of various micro- and macro-nutrients, including vitamin A and its derivatives (retinoids). Therefore, it has been hypothesized that the well-known detrimental consequences of alcohol consumption may be due to deregulations of the metabolism of such nutrients rather than to a direct effect of alcohol. Alcohol exposure in utero also has long-term harmful consequences on the health of the offspring with mechanisms that have not been fully clarified. Disruption of tissue retinoid homeostasis has been linked not only to abnormal embryonic development, but also to various adult pathological conditions, including cancer, metabolic disorders and abnormal lung function. We hypothesized that prenatal alcohol exposure may permanently perturb tissue retinoid metabolism, predisposing the offspring to adult chronic diseases.

Methods

Serum and tissues (liver, lung and prostate from males; liver and lung from females) were collected from 60-75 day-old sprague dawley rats born from dams that were: (I) fed a liquid diet containing 6.7% alcohol between gestational day 7 and 21; or (II) pair-fed with isocaloric liquid diet during the same gestational window; or (III) fed ad libitum with regular rat chow diet throughout pregnancy. Serum and tissue retinoid levels were analyzed by reverse-phase high-performance liquid chromatography (HPLC). Serum retinol-binding protein (RBP) levels were measured by western blot analysis, and liver, lung and prostate mRNA levels of lecithin-retinol acyltransferase (LRAT) were measured by qPCR.

Results

Retinyl ester levels were significantly reduced in the lung of both males and females, as well as in the liver and ventral prostate of males born from alcohol-fed dams. Tissue LRAT mRNA levels remained unchanged upon maternal alcohol treatment.

Conclusions

Prenatal alcohol exposure in rats affects retinoid metabolism in adult life, in a tissue- and sex-dependent manner. We propose that the alcohol-induced perturbations of vitamin A metabolism may predispose to detrimental consequnces on adult health.     

Healing of Fresh Extraction Sockets Filled with Bioactive Glass Particles: Histological Findings in Humans

Purpose: The aim of the present study was to histologically evaluate fresh human sockets filled with bioactive glass after 6 months of healing. Materials and Methods: In 13 patients, 32 single extraction sites in the anterior area underwent socket ridge preservation procedure (RPP) with a bioactive glass (BioRestore?, Inion Oy, Tampere, Finland). At implant installation, 22 bone cores were trephined out and processed for histomorphometric and immunohistochemical analysis. Results: Newly formed immature bone around residual particles of bioactive glass was found in all 22 biopsies. The histomorphometry of the amount of bone, provisional matrix, and residual graft returned a mean ± SD value of 54 ± 31%, 37.9 ± 25.6%, and 8.1 ± 7.8, respectively, 6 months after RPP. Conclusion: The use of this grafting material in fresh extraction sockets appears to delay the healing processes of the alveolar bone; therefore, its indication as a material for RPP when implant placement is considered within 6 months after extraction should be revised.     

Receptor for advanced glycation endproducts (RAGE) and vascular inflammation: Insights into the pathogenesis of macrovascular complications in diabetes

The incidence and severity of atherosclerosis is increased in patients with diabetes. Indeed, accelerated macrovascular disease in diabetic patients has emerged as a leading cause of morbidity and mortality in the United States and worldwide. Multiple investigations have suggested that there are numerous potential contributory factors that underlie these observations. Our laboratory has focused on the contribution of receptor for advanced glycation endproducts (RAGE) and its proinflammatory ligands, advanced glycation endproducts (AGEs) and S100/calgranulins in vascular perturbation, manifested as enhanced atherogenesis or accelerated restenosis after angioplasty. In rodent models of diabetic complications, blockade of RAGE suppressed vascular hyperpermeability, accelerated atherosclerotic lesion area and complexity in diabetic apolipoprotein E-deficient mice, and prevented exaggerated neointimal formation in hyperglycemic fatty Zucker rats subjected to injury of the carotid artery. In this review, we summarize these findings and provide an overview of distinct mechanisms that contribute to the development of accelerated diabetic macrovascular disease. Insights into therapeutic strategies to prevent or interrupt these processes are presented.