Patterns in metabolite profile are associated with risk of more aggressive prostate cancer: A prospective study of 3,057 matched case–control sets from EPIC

Metabolomics may reveal novel insights into the etiology of prostate cancer, for which few risk factors are established. We investigated the association between patterns in baseline plasma metabolite profile and subsequent prostate cancer risk, using data from 3,057 matched case–control sets from the European Prospective Investigation into Cancer and Nutrition (EPIC). We measured 119 metabolite concentrations in plasma samples, collected on average 9.4 years before diagnosis, by mass spectrometry (AbsoluteIDQ p180 Kit, Biocrates Life Sciences AG). Metabolite patterns were identified using treelet transform, a statistical method for identification of groups of correlated metabolites. Associations of metabolite patterns with prostate cancer risk (OR_1SD) were estimated by conditional logistic regression. Supplementary analyses were conducted for metabolite patterns derived using principal component analysis and for individual metabolites. Men with metabolite profiles characterized by higher concentrations of either phosphatidylcholines or hydroxysphingomyelins (OR_1SD = 0.77, 95% confidence interval 0.66–0.89), acylcarnitines C18:1 and C18:2, glutamate, ornithine and taurine (OR_1SD = 0.72, 0.57–0.90), or lysophosphatidylcholines (OR_1SD = 0.81, 0.69–0.95) had lower risk of advanced stage prostate cancer at diagnosis, with no evidence of heterogeneity by follow-up time. Similar associations were observed for the two former patterns with aggressive disease risk (the more aggressive subset of advanced stage), while the latter pattern was inversely related to risk of prostate cancer death (OR_1SD = 0.77, 0.61–0.96). No associations were observed for prostate cancer overall or less aggressive tumor subtypes. In conclusion, metabolite patterns may be related to lower risk of more aggressive prostate tumors and prostate cancer death, and might be relevant to etiology of advanced stage prostate cancer.     

FTIR spectroscopic investigation and modeling of solute/polymer interactions in the hydrated state

Attenuated total reflectance infrared spectroscopy was used to investigate possible interactions during transport of oxprenolol x HCl, bovine serum albumin, alpha-chymotrypsin, and fibrinogen through poly(acrylic acid) and its random copolymeric gels. Carbonyl and carboxylate ion peak shifts were used to identify drug/gel binding due to electrostatic and hydrogen bond interactions between the polymer carrier and the drugs tested. These findings were used to interpret the decrease in calculated diffusion coefficients of drugs diffusing through these gels and the associated hindering of drug transport. A model was developed to analyze this transport process as a function of the binding heat of the drug with the polymer.     

Big Events in Greece and HIV Infection Among People Who Inject Drugs

Big Events are processes like macroeconomic transitions that have lowered social well-being in various settings in the past. Greece has been hit by the global crisis and experienced an HIV outbreak among people who inject drugs. Since the crisis began (2008), Greece has seen population displacement, inter-communal violence, cuts in governmental expenditures, and social movements. These may have affected normative regulation, networks, and behaviors. However, most pathways to risk remain unknown or unmeasured. We use what is known and unknown about the Greek HIV outbreak to suggest modifications in Big Events models and the need for additional research.     

Inflammatory mediators are induced by dietary glycotoxins,a major risk factor for diabetic angiopathy

Diet is a major environmental source of proinflammatory AGEs (heat-generated advanced glycation end products); its impact in humans remains unclear. We explored the effects of two equivalent diets, one regular (high AGE, H-AGE) and the other with 5-fold lower AGE (L-AGE) content on inflammatory mediators of 24 diabetic subjects: 11 in a 2-week crossover and 13 in a 6-week study. After 2 weeks on H-AGE, serum AGEs increased by 64.5% (P = 0.02) and on L-AGE decreased by 30% (P = 0.02). The mononuclear cell tumor necrosis factor-alphabeta-actin mRNA ratio was 1.4 +/- 0.5 on H-AGE and 0.9 +/- 0.5 on L-AGE (P = 0.05), whereas serum vascular adhesion molecule-1 was 1,108 +/- 429 and 698 +/- 347 ngml (P = 0.01) on L- and H-AGE, respectively. After 6 weeks, peripheral blood mononuclear cell tumor necrosis factor-alpha rose by 86.3% (P = 0.006) and declined by 20% (P, not significant) on H- or L-AGE diet, respectively; C-reactive protein increased by 35% on H-AGE and decreased by 20% on L-AGE (P = 0.014), and vascular adhesion molecule-1 declined by 20% on L-AGE (P < 0.01) and increased by 4% on H-AGE. Serum AGEs were increased by 28.2% on H-AGE (P = 0.06) and reduced by 40% on L-AGE (P = 0.02), whereas AGE low density lipoprotein was increased by 32% on H-AGE and reduced by 33% on L-AGE diet (P < 0.05). Thus in diabetes, environmental (dietary) AGEs promote inflammatory mediators, leading to tissue injury. Restriction of dietary AGEs suppresses these effects.     

Securing sustainable funding for viral hepatitis elimination plans

The majority of people infected with chronic hepatitis C virus (HCV) in the European Union (EU) remain undiagnosed and untreated. During recent years, immigration to EU has further increased HCV prevalence. It has been estimated that, out of the 4.2 million adults affected by HCV infection in the 31 EU/ European Economic Area (EEA) countries, as many as 580 000 are migrants. Additionally, HCV is highly prevalent and under addressed in Eastern Europe. In 2013, the introduction of highly effective treatments for HCV with direct‐acting antivirals created an unprecedented opportunity to cure almost all patients, reduce HCV transmission and eliminate the disease. However, in many settings, HCV elimination poses a serious challenge for countries’ health spending. On 6 June 2018, the Hepatitis B and C Public Policy Association held the 2nd EU HCV Policy summit. It was emphasized that key stakeholders should work collaboratively since only a few countries in the EU are on track to achieve HCV elimination by 2030. In particular, more effort is needed for universal screening. The micro‐elimination approach in specific populations is less complex and less costly than country‐wide elimination programmes and is an important first step in many settings. Preliminary data suggest that implementation of the World Health Organization (WHO) Global Health Sector Strategy on Viral Hepatitis can be cost saving. However, innovative financing mechanisms are needed to raise funds upfront for scaling up screening, treatment and harm reduction interventions that can lead to HCV elimination by 2030, the stated goal of the WHO.     

Advanced glycoxidation. A new risk factor for cardiovascular disease?

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. A large body of evidence both in vitro and in vivo suggests an important role for advanced glycoxidation end products (AGE) in the development or progression of CVD. AGE are a heterogenous group of molecules formed within the body during aging and, at an accelerated rate, in diabetes. AGE result from the nonenzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. Diet is considered an important exogenous source of highly reactive AGE. Recent studies have suggested a relationship between AGE and features of CVD. These findings together with the cardioprotective effects of anti-AGE agents demonstrate the causal relationship of AGE to the development and progression of CVD. Prospective outcome and controlled studies are needed to further support this relationship.     

Today’s Mediterranean Diet in Greece: Findings from the National Health and Nutrition Survey—HYDRIA (2013–2014)

Background: This study aimed to investigate the food and macronutrient intake of the population in Greece and evaluate its adherence to the Greek traditional Mediterranean diet. Methods: Adults over 18 years old (n = 4011) were included from the 2013–2014 National Health and Nutrition survey—HYDRIA. Dietary intake was collected using two 24-h recall interviews and a nonquantitative food frequency questionnaire. Macronutrient intakes were calculated using an updated version of the Greek FCT. Results: Only 28.3% of the adult population had high adherence to the Greek traditional Mediterranean diet, with a higher percentage (39.7%) observed for participants over 65 years compared to those under 65 years (25.5%). Differences in adherence to the MD were observed among the four geographical regions in Greece. Younger adults had a higher intake of meat, cereals, alcoholic and nonalcoholic beverages, and sugar products than older individuals who consumed more vegetables, fruits, legumes, dairy, fish, and lipids (mainly from olive oil). Adults do not meet the international dietary recommendations for the intake of several foods and macronutrients. Conclusions: The adult Greek population, especially younger people, has headed away from the Greek traditional Mediterranean diet. These observations indicate potential detrimental consequences in terms of morbidity and mortality.     

Immunohistochemical HLA-DR antigen expression with lymphocyte subsets and proliferative activity in pterygium

The immunohistochemical expression of HLA-DR antigen, CD8, CD4, CD68, S1OO, PCNA and Ki-67 was performed in order to investigate the role of immune mechanisms in pterygium, in correlation with proliferative activity. A series of 98 surgically-excised pterygia, 18 pingueculae and 20 normal conjunctivae, was studied by the avidin-biotin method, on formalin-fixed, paraffin-embedded tissue. HLA-DR antigen was abundantly expressed in pterygium epithelial cells, whereas almost no expression was found in pinguecula and normal conjunctiva. A high value of Ki-67 and PCNA expression coexisted in the same areas with HLA-DR antigen expression in pterygium and a statistically significant positive correlation resulted between them (p = 0.002). Aberrant infiltration of inflammatory cells (CD4, CD8, CD68, S100) was detected in pterygium, while lower densities were found in pinguecula and conjunctiva. The data suggest that immunopathological mechanisms may contribute in the pathogenesis of pterygium. In addition, the aberrant HLA-DR antigen expression seems to be correlated with the growth fraction of the lesion.     

The concurrence of microalbuminuria and retinopathy with cardiovascular risk factors; reliable predictors of asymptomatic coronary artery disease in type 2 diabetes

People with diabetes mellitus type 2 (DM2) have a greater risk for premature morbidity and mortality due to cardiovascular disease than the general population: cardiovascular disease accounts for 75% of deaths in this population group. We examined whether or not the association of clinical cardiovascular risk factors (RF) with both microalbuminuria (MA) and diabetic retinopathy (DR) constitutes reliable evidence for the existence of asymptomatic coronary artery disease (CAD), as assessed by positive myocardial thallium scintiscan using the SPECT method (Tl-scan) in patients with DM2. The study included 76 individuals with DM2 (54 men and 22 women, aged 46-70 years), with a negative history for infarction and negative clinical or ECG findings of CAD. In all patients, 3 overnight (11 pm - 7 am) urine collections were made for evaluation of MA. Fundoscopy after dilatation and a Tl-scan (reference method) were also carried out. In addition, blood pressure and waist/hip ratio were measured and smoking habits were recorded. In the 35 patients with a positive Tl-scan (46%) a higher (p<0.001) incidence of MA, DR, hypertension, smoking and higher waist/hip ratio were detected. Of the 16 patients with concurrent presence of MA and DR, 15 had a positive Tl-scan (94%), whereas the Tl-scan was negative in 30/36 (83%) patients with absence of both MA and DR. One or no cardiovascular RF in the absence of MA and DR increased the prediction of a negative Tl-scan to 100% (NPV: 1.00). Based only on history, fundoscopy and MA testing, and without resorting to expensive and laborious testing procedures, it is possible to safely distinguish patients with type 2 diabetes, who require no further investigations for asymptomatic CAD.     

Advanced glycoxidation end products in commonly consumed foods

OBJECTIVE: Advanced glycoxidation end products (AGEs), the derivatives of glucose-protein or glucose-lipid interactions, are implicated in the complications of diabetes and aging. The objective of this article was to determine the AGE content of commonly consumed foods and to evaluate the effects of various methods of food preparation on AGE production. DESIGN: Two-hundred fifty foods were tested for their content in a common AGE marker (epsilon)N-carboxymethyllysine (CML), using an enzyme-linked immunosorbent assay based on an anti-CML monoclonal antibody. Lipid and protein AGEs were represented in units of AGEs per gram of food. RESULTS: Foods of the fat group showed the highest amount of AGE content with a mean of 100+/-19 kU/g. High values were also observed for the meat and meat-substitute group, 43+/-7 kU/g. The carbohydrate group contained the lowest values of AGEs, 3.4+/-1.8 kU/g. The amount of AGEs present in all food categories was related to cooking temperature, length of cooking time, and presence of moisture. Broiling (225 degrees C) and frying (177 degrees C) resulted in the highest levels of AGEs, followed by roasting (177 degrees C) and boiling (100 degrees C). CONCLUSIONS: The results indicate that diet can be a significant environmental source of AGEs, which may constitute a chronic risk factor for cardiovascular and kidney damage.