Antibacterial Activity of Polymers: Discussions on the Nature of Amphiphilic Balance

© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim The purpose of this Viewpoint is to discuss the molecular design principles that guide development of synthetic antimicrobial polymers, especially those intended to mimic the structure of host defense peptides (HDPs). In particular, we focus on the principle of “amphiphilic balance” as it relates to some recently developed polyphosphoniums with somewhat atypical structure. We find that the fundamental concept of amphiphilic balance is still applicable to these new polymers, but that the method to achieve such balance is somewhat unique. We then briefly outline the future challenges and opportunities in this field

Association Between Plasma Monocyte Chemoattractant Protein-1 Concentration and Cardiovascular Disease Mortality in Middle-Aged Diabetic and Nondiabetic Individuals

OBJECTIVE Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine involved into the pathogenesis of atherosclerosis and has prognostic value in the acute and chronic phases in patients with acute coronary syndromes. RESEARCH DESIGN AND METHODS MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 \ub1 12 years, BMI 30.1 \ub1 6.6 kg/m2, 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990\u20131991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files. RESULTS At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality. CONCLUSIONS In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target

Prevalence, Metabolic Features, and Prognosis of Metabolically Healthy Obese Italian Individuals: The Cremona Study

OBJECTIVE: Some obese individuals have normal insulin sensitivity. It is controversial whether this phenotype is associated with increased all-cause mortality risk. RESEARCH DESIGN AND METHODS: Fifteen-year all-cause mortality data were obtained through the Regional Health Registry for 2,011 of 2,074 Caucasian middle-aged individuals of the Cremona Study, a population study on the prevalence of diabetes in Italy. Individuals were divided in four categories according to BMI (nonobese: <30 kg/m\ub2; obese: 6530 kg/m\ub2) and estimated insulin resistance (insulin sensitive: homeostasis model assessment of insulin resistance <2.5; insulin resistant 652.5). RESULTS: Obese insulin-sensitive subjects represented 11% (95% CI 8.1-14.5) of the obese population. This phenotype had similar BMI but lower waist circumference, blood pressure, fasting glucose, triglycerides, and fibrinogen and higher HDL cholesterol than obese insulin-resistant subjects. In the 15-year follow-up, 495 deaths (cardiovascular disease [CVD]: n = 221; cancer: n = 180) occurred. All-cause mortality adjusted for age and sex was higher in the obese insulin-resistant subjects (hazard ratio 1.40 [95% CI 1.08-1.81], P = 0.01) but not in the obese insulin-sensitive subjects (0.99 [0.46-2.11], P = 0.97) when compared with nonobese insulin-sensitive subjects. Also, mortality for CVD and cancer was higher in the obese insulin-resistant subjects but not in the obese insulin-sensitive subjects when compared with nonobese insulin-sensitive subjects. CONCLUSIONS: In contrast to obese insulin-resistant subjects, metabolically healthy obese individuals are less common than previously thought and do not show increased all-cause, cancer, and CVD mortality risks in a 15-year follow-up study

APOE genotype influences insulin resistance, apolipoprotein CII and CIII according to plasma fatty acid profile in the Metabolic Syndrome

Metabolic markers associated with the Metabolic Syndrome (MetS) may be affected by interactions between the APOE genotype and plasma fatty acids (FA). In this study, we explored FA-gene interactions between the missense APOE polymorphisms and FA status on metabolic markers in MetS. Plasma FA, blood pressure, insulin sensitivity and lipid concentrations were determined at baseline and following a 12-week randomized, controlled, parallel, dietary FA intervention in 442 adults with MetS (LIPGENE study). FA-APOE gene interactions at baseline and following change in plasma FA were assessed using adjusted general linear models. At baseline E4 carriers had higher plasma concentrations of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apo B) compared with E2 carriers; and higher TC, LDL-C and apo B compared with E3/E3. Whilst elevated plasma n-3 polyunsaturated FA (PUFA) was associated with a beneficially lower concentration of apo CIII in E2 carriers, a high proportion of plasma C16:0 was associated with insulin resistance in E4 carriers. Following FA intervention, a reduction in plasma long-chain n-3 PUFA was associated with a reduction in apo CII concentration in E2 carriers. Our novel data suggest that individuals with MetS may benefit from personalized dietary interventions based on APOE genotype

Why does NAFLD predict type 2 diabetes?

Based on the "lipotoxic" hypothesis, the free fatty acid flux from the excessive amount of adipose tissue toward the peripheral tissues would induce the development of insulin resistance especially when the triglyceride storage or the concentration of intermediate fat metabolites (diacylglycerides, ceramides) within the cytoplasm of these cells become excessive. Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis and advanced fibrosis. NAFLD is associated with general and intra-abdominal obesity and with a reduced ability of insulin to stimulate metabolic pathways in the liver itself and in other tissues. There are animal models and models in human diseases sustaining the hypothesis that a primary hepatic disease may determine the development of type 2 diabetes (T2DM). Epidemiologic data generated on surrogate markers of NAFLD (transaminases and \u3b3-glutamyltransferase), semiquantitative assessment of fatty liver (ultrasound), and surrogate algorithms of NAFLD also support a causative effect of NAFLD on the risk to develop T2DM. In spite of the presence of these indirect associations, a clear-cut link between NAFLD and abnormal \u3b2-cell function is yet to be reported. Therefore, more data are warranted to prove what is considered a likely causative relationship between NAFLD and T2DM

Functional characterization of 4 polymorphisms in promoter region of hepatic lipase gene.

Hepatic lipase (HL) is a lipolytic enzyme involved in the metabolism of plasma lipoproteins, especially high density lipoproteins. Association studies have provided strong evidence for relations of common mutations in the promoter region of the HL gene to postheparin plasma HL activity and the plasma high density lipoprotein cholesterol concentration, but the functional relevance of these polymorphisms has not been evaluated to date. We analyzed the physiological significance of 4 common polymorphisms (-250G/A, -514C/T, -710T/C, and -763A/G, all in strong linkage disequilibrium) in the promoter of the HL gene by use of electrophoretic mobility shift assays and transient transfection studies in HepG2 cells. No consistent evidence was found for a significant contribution of any of these polymorphisms to the basal rate of transcription of the HL gene. These data suggest that the 4 polymorphisms in the promoter region of the HL gene are in linkage disequilibrium with &gt;/=1 as-yet-unknown functional polymorphisms in the HL gene locus with a significant effect on HL metabolism and/or enzymatic activity

Free leptin index and thyroid function in male highly trained athletes

Objective: Exercise training may cause changes in thyroid function. This thyroid response may be due to exercise-induced modulation of energy metabolism but also of the adipocytes endocrine function. In particular, the role of leptin and of circulating soluble leptin receptor (sOB-R) was unexplored. The aim of this study was to assess the relationships between thyroid function, whole body energy metabolism, and adipokines \u2013 mainly leptin and its receptor, sOB-R. Methods: We measured serum TSH, free tri-iodothyronine (FT3), free thyroxine, leptin, and sOB-R and assessed energy homeostasis by means of indirect calorimetry, in 27 highly trained athletes and 27 sedentary, healthy men. Results: TSH\u2013FT3 ratio was lower in athletes (P<0.03), either in sustained power or anaerobic power-sprint athletes (n=13) or marathon runners (n=14). Whole body respiratory quotient was lower in athletes. Fasting serum sOB-R was higher and leptin lower in athletes than controls. Also serum adiponectin, resistin, and retinol binding protein-4 concentrations were different in athletes than in controls. The ratio between leptin and sOB-R, the free leptin index (FLI), was lower in athletes than in controls (0.025\ub10.014 vs 0.085\ub10.049; P<0.001). In multivariate analysis, FLI retained independent association with TSH\u2013FT3 ratio. Conclusion: Male, elite athletes had lower TSH\u2013FT3 ratio and FLI than controls while FLI was independently associated with TSH\u2013FT3 ratio supporting the hypothesis that the level of biologically active leptin is involved in the adaptive response of thyroid function in professional athletes