Syndecan-4 proteoliposomes enhance fibroblast growth factor-2 (FGF-2)-induced proliferation, migration, and neovascularization of ischemic muscle

Ischemia of the myocardium and lower limbs is a common consequence of arterial disease and a major source of morbidity and mortality in modernized countries. Inducing neovascularization for the treatment of ischemia is an appealing therapeutic strategy for patients for whom traditional treatment modalities cannot be performed or are ineffective. In the past, the stimulation of blood vessel growth was pursued using direct delivery of growth factors, angiogenic gene therapy, or cellular therapy. Although therapeutic angiogenesis holds great promise for treating patients with ischemia, current methods have not found success in clinical trials. Fibroblast growth factor-2 (FGF-2) was one of the first growth factors to be tested for use in therapeutic angiogenesis. Here, we present a method for improving the biological activity of FGF-2 by codelivering the growth factor with a liposomally embedded coreceptor, syndecan-4. This technique was shown to increase FGF-2 cellular signaling, uptake, and nuclear localization in comparison with FGF-2 alone. Delivery of syndecan-4 proteoliposomes also increased endothelial proliferation, migration, and angiogenic tube formation in response to FGF-2. Using an animal model of limb ischemia, syndecan-4 proteoliposomes markedly improved the neovascularization following femoral artery ligation and recovery of perfusion of the ischemic limb. Taken together, these results support liposomal delivery of syndecan-4 as an effective means to improving the potential of using growth factors to achieve therapeutic neovascularization of ischemic tissue.     

Low HDL predicts differential blood pressure effects from two weight-loss approaches: a secondary analysis of blood pressure from a randomized, clinical weight-loss trial

Examining predictors of blood-pressure (BP) response to weight-loss diets might provide insight into mechanisms and help guide clinical care. We examined whether certain baseline patient characteristics (e.g. diet, medical history and laboratory tests) predicted BP response to two weight-loss diet approaches that differ in macronutrient content. One hundred and forty-six overweight adult outpatients were randomized to either a low-carbohydrate diet (N = 72) or orlistat plus a low-fat diet (N = 74) for 48 weeks. Predictors of BP reduction were evaluated using a structured approach and random effects regression models. Participants were 56% African-American, 72% male and 53 (±10) years-old. Of the variables considered, low baseline high-density lipoprotein (HDL) predicted greater reduction in BP in those patients who received the low-carbohydrate diet (p = 0.03 for systolic BP; p = 0.03 for diastolic BP and p = 0.02 for mean arterial pressure). A low HDL level may identify patients who will have greater BP improvement on a low-carbohydrate diet.     

White paper on antimicrobial stewardship in solid organ transplant recipients

Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.     

A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma

The presence of asbestos bodies (ABs) in lung parenchyma is considered a histopathologic hallmark of past exposure to asbestos fibers, of which there was a population of longer fibers. The mechanisms underlying AB formation are complex, involving inflammatory responses and iron (Fe) metabolism. Thus, the responsiveness to AB formation is variable, with some individuals appearing to be poor AB formers. The aim of this study was to disclose the possible role of genetic variants of genes encoding inflammasome and iron metabolism proteins in the ability to form ABs in a population of 81 individuals from North East Italy, who died after having developed malignant pleural mesothelioma (MPM). This study included 86 genetic variants distributed in 10 genes involved in Fe metabolism and 7 genetic variants in two genes encoding for inflammasome molecules. Genotypes/haplotypes were compared according to the number of lung ABs. Data showed that the NLRP1 rs12150220 missense variant (H155L) was significantly correlated with numbers of ABs in MPM patients. Specifically, a low number of ABs was detected in individuals carrying the NLRP1 rs12150220 A/T genotype. Our findings suggest that the NLRP1 inflammasome might contribute in the development of lung ABs. It is postulated that the NLRP1 missense variant may be considered as one of the possible host genetic factors contributing to individual variability in coating efficiency, which needs to be taken when assessing occupational exposure to asbestos.     

Intérêt de l''exploration de l''auto-immunité biologique en pathologie gynéco-obstétricale

The relationship between autoimmunity and obstetrical pathology is reviewed in the light of data from the literature and of the authors' own experience. The link, already demonstrated, between recurrent spontaneous abortion and the risk factor represented by antibodies directed against phospholipids (circulating anticoagulant antibodies of the lupus type, anticordiolipin antibody) is described, and the pathogenetic theories concerning these antibodies are presented, together with the treatments used for routine prevention of the foetal and maternal risk (corticosteroids, anti-platelet drugs, heparin). The results of screening for antinuclear antibodies in 354 non-pregnant women are reported. Antinuclear antibodies were present in titers of 1/100 in 4.2 percent and 1/50 in 8.7 percent of these women. In the same category of women the frequency of antithyroid antibodies was as high as 12 percent. These data should encourage routine examination for auto-antibodies before and during pregnancy in order to evaluate and prevent the obstetrical risk to which these women are exposed.