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.     

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.     

[68Ga]NODAGA-RGD for imaging ��v��3 integrin expression

Purpose

A molecular target involved in the angiogenic process is the ??_v??₃ integrin. It has been demonstrated in preclinical as well as in clinical studies that radiolabelled RGD peptides and positron emission tomography (PET) allow noninvasive monitoring of ??_v??₃ expression. Here we introduce a ⁶⁸Ga-labelled NOTA-conjugated RGD peptide ([⁶⁸Ga]NODAGA-RGD) and compare its imaging properties with [⁶⁸Ga]DOTA-RGD using small animal PET.

Methods

Synthesis of c(RGDfK(NODAGA)) was based on solid phase peptide synthesis protocols using the Fmoc strategy. The ⁶⁸Ga labelling protocol was optimized concerning temperature, peptide concentration and reaction time. For in vitro characterization, partition coefficient, protein binding properties, serum stability, ??_v??₃ binding affinity and cell uptake were determined. To characterize the in vivo properties, biodistribution studies and microPET imaging were carried out. For both in vitro and in vivo evaluation, ??_v??₃-positive human melanoma M21 and ??_v??₃-negative M21-L cells were used.

Results

[⁶⁸Ga]NODAGA-RGD can be produced within 5?min at room temperature with high radiochemical yield and purity (> 96%). In vitro evaluation showed high ??_v??₃ binding affinity (IC₅₀?=?4.7?±?1.6?nM) and receptor-specific uptake. The radiotracer was stable in phosphate-buffered saline, pH 7.4, FeCl₃ solution, and human serum. Protein-bound activity after 180?min incubation was found to be 12-fold lower than for [⁶⁸Ga]DOTA-RGD. Biodistribution data 60?min post-injection confirmed receptor-specific tumour accumulation. The activity concentration of [⁶⁸Ga]NODAGA-RGD was lower than [⁶⁸Ga]DOTA-RGD in all organs and tissues investigated, leading to an improved tumour to blood ratio ([⁶⁸Ga]NODAGA-RGD: 11, [⁶⁸Ga]DOTA-RGD: 4). MicroPET imaging confirmed the improved imaging properties of [⁶⁸Ga]NODAGA-RGD compared to [⁶⁸Ga]DOTA-RGD.

Conclusion

The introduced [⁶⁸Ga]NODAGA-RGD combines easy accessibility with high stability and good imaging properties making it an interesting alternative to the ¹⁸F-labelled RGD peptides currently used for imaging ??_v??₃ expression.     

Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco smoke in the modulation of lymphocyte bulky DNA adducts and chromosomal aberrations

CYP1A1 plays an important role in the metabolic activation of polycyclic aromatic hydrocarbons (PAH), carcinogenic components of air pollution. The influence of CYP1A1 genotype (*2A, *2B and *4) on the levels of lymphocyte bulky DNA adducts and the frequency of cells with aberrant chromosomes was assessed in 194 non-smoking subjects in whom recent exposure to environmental tobacco smoke (ETS) and airborne particulate-associated PAH were measured during two consecutive seasons (winter and summer). While CYP1A1*4 had no consistent effect on either biomarker of genetic damage, the levels of both biomarkers responded in a parallel fashion to changes in exposure/CYP1A1*2A genotype combinations during both seasons. Specifically, the levels of both biomarkers were increased in carriers of at least one CYP1A1*2A allele, as compared with CYP1A1*1 homozygotes, in subjects with ETS exposures >0.8 h/day during the previous 4 days and mean personal exposure to benzo[a]pyrene <0.9 ng/m3 during the previous 24 h (all P < 0.05). Outside these exposure limits the differential effect in CYP1A1*2A variants was lost. Although the numbers of subjects with the CYP1A1*2B polymorphism was small, the same trend appeared to be followed in this case. These effects are interpreted as resulting from differential induction of CYP1A1 expression in CYP1A1*2A and CYP1A1*2A/*2B carriers by components of ETS-polluted air at levels of exposure readily suffered by large segments of the general population and suggest that subjects with these genotypes may have increased susceptibility to the genotoxic effects of ETS.