Resveratrol Decreases TXNIP mRNA and Protein Nuclear Expressions With an Arterial Function Improvement in Old Mice

Aging leads to a high prevalence of glucose intolerance and cardiovascular diseases, with oxidative stress playing a potential role. Resveratrol has shown promising effects on glucose tolerance and tends to improve endothelial function in elderly patients. Thioredoxin-interacting protein (TXNIP) was recently proposed as a potential link connecting glucose metabolism to oxidative stress. Here, we investigated the resveratrol-induced improvement of arterial aging phenotype in old mice and the expression of aortic TXNIP. Using an in vivo model of old mice with or without 3-month resveratrol treatment, we investigated the effects of resveratrol on age-related impairments from a cardiovascular Doppler analysis, to a molecular level, by studying inflammation and oxidative stress factors. We found a dual effect of resveratrol, with a decrease of age-related glucose intolerance and oxidative stress imbalance leading to reduced matrix remodeling that forestalls arterial aging phenotype in terms of intima-media thickness and arterial distensibility. These results provide the first evidence that aortic TXNIP mRNA and protein nuclear expressions are increased in the arterial aging and decreased by resveratrol treatment. In conclusion, we demonstrated that resveratrol helped to restore several aging impaired processes in old mice, with a decrease of aortic TXNIP mRNA and protein nuclear expression

High-protein-low-carbohydrate diet: deleterious metabolic and cardiovascular effects depend on age

High-protein-low-carbohydrate (HP-LC) diets have become widespread. Yet their deleterious consequences, especially on glucose metabolism and arteries, have already been underlined. Our previous study (2) has already shown glucose intolerance with major arterial dysfunction in very old mice subjected to an HP-LC diet. The hypothesis of this work was that this diet had an age-dependent deleterious metabolic and cardiovascular outcome. Two groups of mice, young and adult (3 and 6 mo old), were subjected for 12 wk to a standard or to an HP-LC diet. Glucose and lipid metabolism was studied. The cardiovascular system was explored from the functional stage with Doppler-echography to the molecular stage (arterial reactivity, mRNA, immunohistochemistry). Young mice did not exhibit any significant metabolic modification, whereas adult mice presented marked glucose intolerance associated with an increase in resistin and triglyceride levels. These metabolic disturbances were responsible for cardiovascular damages only in adult mice, with decreased aortic distensibility and left ventricle dysfunction. These seemed to be the consequence of arterial dysfunctions. Mesenteric arteries were the worst affected with a major oxidative stress, whereas aorta function seemed to be maintained with an appreciable role of cyclooxygenase-2 to preserve endothelial function. This study highlights for the first time the age-dependent deleterious effects of an HP-LC diet on metabolism, with glucose intolerance and lipid disorders and vascular (especially microvessels) and cardiac functions. This work shows that HP-LC lead to equivalent cardiovascular alterations, as observed in very old age, and underlines the danger of such diet

Status and significance of testing for hepatitis B surface antigen and surface antibody

Following Blumberg's discovery of hepatitis B surface antigen (HBsAg), many attempts have been made to develop several in vitro diagnostic techniques for the detection of this antigen and its homologous antibody. The two-dimensional micro-Ouchterlony immunodiffusion has been the first technique used, rapidly replaced by procedures of increasing sensitivity characterized as second-generation and the currently available third-phase tests which include radioimmunoassay (RIA), reverse passive haemagglutination (RPHA), reverse passive latex agglutination (RPLA) and enzyme immunoassay (EIA). Among these, RIA appears to be the most sensitive and specific, whereas EIA, RPHA and RPLA have the advantage of long shelf-life of stable reagents, no need for sophisticated and expensive equipment and no hazard associated with the handling of radioactive isotopes. Moreover, the sensitivity of EIA should increase by objective reading with a colorimeter. The most sensitive method for the detection of surface antibody (anti-HBs) is again RIA, whereas passive haemagglutination (PHA) had the advantage of providing titres. Finally EIA, based on inhibition of a known amount of HBsAg, has at least the same sensitivity as PHA, but has the advantage that reagents are more stable and that it permits screening for both HBsAg and anti-HBs with the same reagents at the same time. The application of these highly sensitive techniques for the detection of HBsAg and anti-HBs has resulted in a consistent reduction in the incidence of post-transfusion hepatitis type B and in a better understanding of the aetiology, epidemiology and natural history of this infection

Growth of sucrose crystals and tapering effect studied by Holographic interferometry

Effects of dopant raffinose on the growth of sucrose crystals are studied by means of holographic interferometry. By the distibution of hologram fringes the selective doping effect is measured on (100), (110) and (1-10) forms. An interpretation is put forward for the tapering effect in the wedge shaped crystals

Biomarker-Assisted Dose Selection for Safety and Efficacy in Early Development of PNU-100480 for Tuberculosis▿

Tuberculosis is a serious global health threat for which new treatments are urgently needed. This study examined the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of the oxazolidinone PNU-100480 in healthy volunteers, using biomarkers for safety and efficacy. Subjects were randomly assigned to PNU-100480 or placebo (4:1) at schedules of 100, 300, or 600 mg twice daily or 1,200 mg daily for 14 days or a schedule of 600 mg twice daily for 28 days to which pyrazinamide was added on days 27 and 28. A sixth cohort was given linezolid at 300 mg daily for 4 days. Signs, symptoms, and routine safety tests were monitored. Bactericidal activity against Mycobacterium tuberculosis was measured in ex vivo whole-blood culture. Plasma drug and metabolite concentrations were compared to the levels required for inhibition of M. tuberculosis growth and 50% inhibition of mitochondrial protein synthesis. All doses were safe and well tolerated. There were no hematologic or other safety signals during 28 days of dosing at 600 mg twice daily. Plasma concentrations of PNU-100480 and metabolites at this dose remained below those required for 50% inhibition of mitochondrial protein synthesis. Cumulative whole-blood bactericidal activity of PNU-100480 at this dose (−0.316 ± 0.04 log) was superior to the activities of all other doses tested (P < 0.001) and was significantly augmented by pyrazinamide (−0.420 ± 0.06 log) (P = 0.002). In conclusion, PNU-100480 was safe and well tolerated at all tested doses. Further studies in patients with tuberculosis are warranted. Biomarkers can accelerate early development of new tuberculosis treatments