Thiazolidinedione Derivatives: In Silico, In Vitro, In Vivo, Antioxidant and Anti-Diabetic Evaluation.

This work aimed to synthesize a new antihyperglycemic thiazolidinedione based on the spectral data. The DFT\B3LYP\6-311G** level of theory was used to investigate the frontier molecular orbitals (FMOs), chemical reactivity and map the molecular electrostatic potentials (MEPs) to explain how the synthesized compounds interacted with the receptor. The molecular docking simulations into the active sites of PPAR-γ and α-amylase were performed. The in vitro potency of these compounds via α-amylase and radical scavenging were evaluated. The data revealed that compounds (4-6) have higher potency than the reference drugs. The anti-diabetic and anti-hyperlipidemic activities for thiazolidine-2,4-dione have been investigated in vivo using the alloxan-induced diabetic rat model along with the 30 days of treatment protocol. The investigated compounds didn't show obvious reduction of blood glucose during pre-treatments compared to diabetic control, while after 30 days of treatments, the blood glucose level was lower than that of the diabetic control. Compounds (4-7) were able to regulate hyperlipidemia levels (cholesterol, triglyceride, high-density lipoproteins and low- and very-low-density lipoproteins) to nearly normal value at the 30th day.

Helicobacter pylori infection, serum pepsinogens as markers of atrophic gastritis, and leukocyte telomere length: a population-based study.

BACKGROUND: Persistent infections that induce prolonged inflammation might negatively affect the leukocyte telomere length (LTL); however, the role in LTL of Helicobacter pylori (H. pylori) infection, which persistently colonizes the stomach, remains unknown. The study objective was to examine associations of sero-prevalence of H. pylori immunoglobulin G (IgG) antibody and serum pepsinogens (PGs), as markers of atrophic gastritis, with LTL. A cross-sectional study was performed among 934 Arab residents of East Jerusalem, aged 27-78 years, randomly selected from Israel's national population registry. Sera were tested for H. pylori IgG and PG levels by ELISA. LTL was measured by southern blots. Multiple linear regression models were fitted to adjust for sociodemographic and lifestyle factors. RESULTS: LTL decreased significantly with age (p < 0.001) and was shorter in men than women (p = 0.032). The mean LTL was longer in H. pylori sero-positive persons than negative ones: mean difference 0.13 kb (95% CI 0.02, 0.24), p = 0.016. Participants with atrophic gastritis (PGI < 30 µg/L or a PGI: PGII < 3.0) had shorter LTL than did those without: mean difference - 0.18 (95% CI - 0.32, - 0.04). The difference was of larger magnitude between persons who had past H. pylori infection (sero-negative to H. pylori IgG antibody) and atrophic gastritis, compared to those who were H. pylori sero-negative and did not have atrophic gastritis: mean difference - 0.32 kb (95% CI - 0.55, - 0.10). This association remained significant after adjustment for age, sex, and religiosity: beta coefficient - 0.21 kb (95% CI - 0.41, - 0.001), p = 0.049. The results were similar after further adjustment for lifestyle factors. In bivariate analysis, mean LTL was longer in physically active persons than non-active ones, and shorter in persons with than without obesity; however, these differences were diminished and were not significant in the multivariable model. CONCLUSIONS: H. pylori IgG sero-positivity per se was not related to reduced LTL. However, persons with past H. pylori infection (i.e., lacking H. pylori IgG serum antibody) and with serological evidence of atrophic gastritis, had a significantly shorter LTL than did those without atrophic gastritis.

DCAF4, a novel gene associated with leucocyte telomere length.

BACKGROUND: Leucocyte telomere length (LTL), which is fashioned by multiple genes, has been linked to a host of human diseases, including sporadic melanoma. A number of genes associated with LTL have already been identified through genome-wide association studies. The main aim of this study was to establish whether DCAF4 (DDB1 and CUL4-associated factor 4) is associated with LTL. In addition, using ingenuity pathway analysis (IPA), we examined whether LTL-associated genes in the general population might partially explain the inherently longer LTL in patients with sporadic melanoma, the risk for which is increased with ultraviolet radiation (UVR). RESULTS: Genome-wide association (GWA) meta-analysis and de novo genotyping of 20 022 individuals revealed a novel association (p=6.4×10(-10)) between LTL and rs2535913, which lies within DCAF4. Notably, eQTL analysis showed that rs2535913 is associated with decline in DCAF4 expressions in both lymphoblastoid cells and sun-exposed skin (p=4.1×10(-3) and 2×10(-3), respectively). Moreover, IPA revealed that LTL-associated genes, derived from GWA meta-analysis (N=9190), are over-represented among genes engaged in melanoma pathways. Meeting increasingly stringent p value thresholds (p<0.05, <0.01, <0.005, <0.001) in the LTL-GWA meta-analysis, these genes were jointly over-represented for melanoma at p values ranging from 1.97×10(-169) to 3.42×10(-24). CONCLUSIONS: We uncovered a new locus associated with LTL in the general population. We also provided preliminary findings that suggest a link of LTL through genetic mechanisms with UVR and melanoma in the general population.

Lifestyle physical activity among urban Palestinians and Israelis: a cross-sectional comparison in the Palestinian-Israeli Jerusalem risk factor study.

BACKGROUND: Urban Palestinians have a high incidence of coronary heart disease, and alarming prevalences of obesity (particularly among women) and diabetes. An active lifestyle can help prevent these conditions. Little is known about the physical activity (PA) behavior of Palestinians. This study aimed to determine the prevalence of insufficient PA and its socio-demographic correlates among urban Palestinians in comparison with Israelis. METHODS: An age-sex stratified random sample of Palestinians and Israelis aged 25-74 years living in east and west Jerusalem was drawn from the Israel National Population Registry: 970 Palestinians and 712 Israelis participated. PA in a typical week was assessed by the Multi-Ethnic Study of Atherosclerosis (MESA) questionnaire. Energy expenditure (EE), calculated in metabolic equivalents (METs), was compared between groups for moderate to vigorous-intensity physical activity (MVPA), using the Wilcoxon rank-sum test, and for domain-specific prevalence rates of meeting public health guidelines and all-domain insufficient PA. Correlates of insufficient PA were assessed by multivariable logistic modeling. RESULTS: Palestinian men had the highest median of MVPA (4740 METs-min*wk-1) compared to Israeli men (2,205 METs-min*wk-1 p < 0.0001), or to Palestinian and Israeli women, who had similar medians (2776 METs-min*wk-1). Two thirds (65%) of the total MVPA reported by Palestinian women were derived from domestic chores compared to 36% in Israeli women and 25% among Palestinian and Israeli men. A high proportion (63%) of Palestinian men met the PA recommendations by occupation/domestic activity, compared to 39% of Palestinian women and 37% of the Israelis. No leisure time PA was reported by 42% and 39% of Palestinian and Israeli men (p = 0.337) and 53% and 28% of Palestinian and Israeli women (p < 0.0001). Palestinian women reported the lowest level of walking. Considering all domains, 26% of Palestinian women were classified as insufficiently active versus 13% of Palestinian men (p < 0.0001) who did not differ from the Israeli sample (14%). Middle-aged and elderly and less educated Palestinian women, and unemployed and pensioned Palestinian men were at particularly high risk of inactivity. Socio-economic indicators only partially explained the ethnic disparity. CONCLUSIONS: Substantial proportions of Palestinian women, and subgroups of Palestinian men, are insufficiently active. Culturally appropriate intervention strategies are warranted, particularly for this vulnerable population.

Different Factors Are Associated With Sex Hormones and Leydig Cell Function in Israelis and Palestinians in Jerusalem.

Total testosterone (TT) is known to influence health and virility in men. Among men from United States and Europe, numerous sociodemographic and lifestyle factors were reported to be associated with TT. However, associations with TT and Leydig cell function in the Middle East are poorly described. A cross-sectional, population-based sample had a structured interview, physical examinations, and blood tests in two hospitals in Jerusalem, Israel. A subsample (25- to 44-year-old men, n = 286: 124 Israelis, 162 Palestinians) had sex hormone measurements. The primary outcomes were TT and free testosterone/luteinizing hormone (FT/LH) ratio, representing Leydig cell function. Associations with sociodemographic and lifestyle factors, body mass index (BMI), and physical activity (PA) were evaluated using multivariable linear regression. Compared with Palestinians, Israelis had similar TT (4.81 vs. 5.09 ng/mL, p = .405) and higher FT/LH (31.2 vs. 25.8 ng/IU, p = .002). In ln-transformed values, marital status had a stronger association in Palestinians (P for interaction = 0.03). Age, BMI, and PA had a stronger association with TT in Israelis with significant interactions with ethnicity. BMI <25 and a higher PA quartile were associated with a higher TT (p < .001). Among Israelis, age (p = .007), married marital status (p = .007), and BMI <25 were significantly associated with FT/LH. No associations of any factors were identified among Palestinians. Associations with several modifiable factors identified in Western samples were replicated in Israelis and to a lesser degree in Palestinians. Different relationships of several factors with TT and FT/LH could result from ethnically diverse genetic, sociodemographic, and behavioral characteristics that warrant further research.

Discovery Potent of Thiazolidinedione Derivatives as Antioxidant, α-Amylase Inhibitor, and Antidiabetic Agent.

This work aimed to synthesize safe antihyperglycemic derivatives bearing thiazolidinedione fragment based on spectral data. The DFT theory discussed the frontier molecular orbitals (FMOs), chemical reactivity of compounds, and molecular electrostatic potential (MEP) to explain interaction between thiazolidinediones and the biological receptor. α-amylase is known as the initiator-hydrolysis of the of polysaccharides; therefore, developing α-amylase inhibitors can open the way for a potential diabetes mellitus drug. The molecular docking simulation was performed into the active site of PPAR-γ and α-amylase. We evaluated in vitro α-amylase's potency and radical scavenging ability. The compound 6 has the highest potency against α-amylase and radical scavenging compared to the reference drug and other members. They have been applied against anti-diabetic and anti-hyperlipidemic activity (in vivo) based on an alloxan-induced diabetic rat model during a 30-day treatment protocol. The most potent anti hyperglycemic members are 6 and 11 with reduction percentage of blood glucose level by 69.55% and 66.95%, respectively; compared with the normal control. Other members exhibited moderate to low anti-diabetic potency. All compounds showed a normal value against the tested biochemical parameters (CH, LDL, and HDL). The ADMET profile showed good oral bioavailability without any observed carcinogenesis effect.

Cutting balloon angioplasty and stent implantation for aorto-ostial lesions: clinical outcome and 1-year follow-up.

BACKGROUND: Percutaneous interventions for aorto-ostial narrowing of native coronary arteries are challenging because of early elastic recoil after the procedure and the high restenosis rate. Cutting balloon angioplasty may reduce this complication. HYPOTHESIS: The purpose of the study was to evaluate the clinical outcomes of cutting balloon angioplasty and stent implantation for aorto-ostial lesions with a 1-year clinical follow-up. METHODS: All patients with aorto-ostial lesions in our laboratory underwent cutting balloon angioplasty and were followed for approximately 1 year. RESULTS: Forty-eight patients underwent balloon angioplasty; 36 of whom had lesions in the ostial right coronary artery, and 12 of whom had lesions in the left main coronary artery (LMCA). Thirty-five patients (73%) had a stent implanted. Procedural success was achieved in all patients. The in-hospital rate of major adverse cardiac events (MACEs) was 2.1% because of the death of 1 patient following urgent bypass surgery. Mean clinical follow-up was 11.6 +/- 7 month. Twelve patients (27%) required repeat coronary angiography, and restenosis was found in 7 patients (16%). Six patients (13.6%) had MACEs. CONCLUSIONS: Cutting balloon angioplasty in combination with bare metal stent (BMS) implantation has a good clinical outcome. This technique should be compared with implantation of drug-eluting stents (DESs) in a controlled study.

Stent thrombosis: a poor man's disease?

BACKGROUND: Stent thrombosis is a rare but devastating complication of coronary stent implantation. The incidence and potential predictors were assessed in a "real world" single center. OBJECTIVES: To examine whether socioeconomic status indeed affects the occurrence of stent thrombosis. METHODS: We searched our database for cases of "definite" stent thrombosis (according to the ARC Dublin definitions). Each case was matched by procedure date, age and gender with three cases of stenting that did not result in stent thrombosis. Demographic and clinical parameters were compared and socioeconomic status was determined according to a standardized polling and market survey database. RESULTS: A total of 3401 patients underwent stent implantation in our hospital during the period 2004-2006. Their mean age was 63 +/- 11 years, and 80% were males. Twenty-nine cases (0.85%) of "definite" sub-acute/late stent thrombosis were recorded. Mortality at 30 days was recorded in 1 patient (3.5%). Thrombosis occurred 2 days to 3 years after stent implantation. All patients presented with acute myocardial infarction. Premature clopidogrel discontinuation was reported in 60%. Patients with stent thrombosis had significantly higher rates of AMI at the time of the initial procedure (76 vs. 32%, P < 0.001) and were cigarette smokers (60 vs. 28%, P < 0.001). Drug-eluting stents were used less in the stent thrombosis group. There was no difference in stent diameter or length between the two groups. Socioeconomic status was significantly lower in the stent thrombosis group, 3.4 +/- 2.4 vs. 5.4 +/- 2.6 (mean +/- SD, scale 1-10, P < 0.01). CONCLUSIONS: The incidence rate of stent thrombosis is at least 0.85% in our population. It appears in patients with significantly lower socioeconomic status and with certain clinical predictors. These results warrant stricter follow-up and support the policy of healthcare providers regarding patients at risk for stent thrombosis.

Prevalence and determinants of serological evidence of atrophic gastritis among Arab and Jewish residents of Jerusalem: a cross-sectional study.

OBJECTIVE: Understanding the correlates of premalignant gastric lesions is essential for gastric cancer prevention. We examined the prevalence and correlates of serological evidence of atrophic gastritis, a premalignant gastric condition, using serum pepsinogens (PGs) in two populations with differing trends in gastric cancer incidence. METHODS: In a cross-sectional study, using ELISA we measured serum PGI and PGII concentrations (Biohit, Finland), Helicobacter pylori serum IgG and cytotoxin-associated gene A (CagA) antigen IgG antibodies in archived sera of 692 Jews and 952 Arabs aged 25-78 years, randomly selected from Israel's population registry in age-sex and population strata. Multivariable logistic regression analyses were performed. RESULTS: Using cut-offs of PGI <30µg/L or PGI:PGII <3.0, the prevalence of atrophic gastritis was higher among Arab than Jewish participants: 8.8% (95% CIs 7.2% to 10.8%) vs 5.9% (95% CI 4.4% to 7.9%), increasing with age in both groups (p<0.001 for trend). Among Jewish participants, infection with H. pylori CagA phenotype was positively related to atrophic gastritis: adjusted OR (aOR) 2.16 (95% CI 0.94 to 4.97), but not to non-CagA infections aOR 1.17 (95% CI 0.53 to 2.55). The opposite was found among Arabs: aOR 0.09 (95% CI 0.03 to 0.24) for CagA positive and aOR 0.15 (95% CI 0.06 to 0.41) for Cag A negative phenotypes (p<0.001 for interaction). Women had a higher atrophic gastritis prevalence than men. Obesity and smoking were not significantly related to atrophic gastritis; physical activity tended to be inversely associated in Arabs (p=0.08 for interaction). CONCLUSIONS: The prevalence of atrophic gastritis was higher among Arabs than Jews and was differently associated with the CagA phenotype.

Sero-prevalence of Helicobacter pylori CagA immunoglobulin G antibody, serum pepsinogens and haemoglobin levels in adults.

Associations observed of Helicobacter pylori infection with haemoglobin levels are inconsistent. We examined associations of H. pylori sero-prevalence and serum pepsinogens (PGs), as non-invasive markers of atrophic gastritis, with haemoglobin levels. A cross-sectional study was undertaken among 654 Jewish and 937 Arab residents of Jerusalem, aged 25-78 years, randomly selected from Israel's national population registry in age-sex and population strata. Sera were tested for H. pylori IgG, cytotoxin-associated gene A (CagA) antigen IgG antibody and PGs levels. Multivariable models were fitted to account for confounders. Participants with atrophic gastritis (PGI < 30 µg/L or a PGI: PGII < 3.0) had lower haemoglobin levels than those without: beta-coefficient -0.34 (95% CI -0.59, -0.09); in men -0.27 (95% CI -0.67, 0.12), and in women -0.43 (95% CI -0.74, -0.12). Lower haemoglobin levels were noted in persons with CagA antibody than in those H. pylori sero-negative or H. pylori-CagA sero-negative: beta-coefficient -0.14 (95% CI -0.29, 0.01). Anaemia was more common among women and men with than without atrophic gastritis: adjusted OR 2.58 (95% CI 1.48, 4.48) and 1.52 (95% CI 0.59, 3.95), respectively. In conclusion, independent of known correlates, atrophic gastritis and apparently CagA sero-positivity, a marker of H. pylori virulent strains, are associated with lower haemoglobin levels.

Body mass index is negatively associated with telomere length: a collaborative cross-sectional meta-analysis of 87 observational studies.

Background: Even before the onset of age-related diseases, obesity might be a contributing factor to the cumulative burden of oxidative stress and chronic inflammation throughout the life course. Obesity may therefore contribute to accelerated shortening of telomeres. Consequently, obese persons are more likely to have shorter telomeres, but the association between body mass index (BMI) and leukocyte telomere length (TL) might differ across the life span and between ethnicities and sexes. Objective: A collaborative cross-sectional meta-analysis of observational studies was conducted to investigate the associations between BMI and TL across the life span. Design: Eighty-seven distinct study samples were included in the meta-analysis capturing data from 146,114 individuals. Study-specific age- and sex-adjusted regression coefficients were combined by using a random-effects model in which absolute [base pairs (bp)] and relative telomere to single-copy gene ratio (T/S ratio) TLs were regressed against BMI. Stratified analysis was performed by 3 age categories ("young": 18-60 y; "middle": 61-75 y; and "old": >75 y), sex, and ethnicity. Results: Each unit increase in BMI corresponded to a -3.99 bp (95% CI: -5.17, -2.81 bp) difference in TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -7.67 bp (95% CI: -10.03, -5.31 bp) difference. Each unit increase in BMI corresponded to a -1.58 × 10(-3) unit T/S ratio (0.16% decrease; 95% CI: -2.14 × 10(-3), -1.01 × 10(-3)) difference in age- and sex-adjusted relative TL in the total pooled sample; among young adults, each unit increase in BMI corresponded to a -2.58 × 10(-3) unit T/S ratio (0.26% decrease; 95% CI: -3.92 × 10(-3), -1.25 × 10(-3)). The associations were predominantly for the white pooled population. No sex differences were observed. Conclusions: A higher BMI is associated with shorter telomeres, especially in younger individuals. The presently observed difference is not negligible. Meta-analyses of longitudinal studies evaluating change in body weight alongside change in TL are warranted.

Comparison of 4 and 6 French catheters for coronary angiography: real-world modeling.

BACKGROUND: Femoral artery vascular complications are the most common adverse events following cardiac catheterization. Smaller diameter introducer sheaths and catheters are likely to lower the puncture site complication rate but may hinder visualization. OBJECTIVES: To evaluate the safety and angiographic quality of 4 French catheters. METHODS: The study was designed to simulate real-life operator-based experience. Diagnostic angiography was performed with either 4F or 6F diagnostic catheters; the size of the catheter used in each patient was predetermined by the day of the month. Patients undergoing 4F and 6F diagnostic angiography were ambulated after 4 and 6 hours, respectively. The following technical parameters were recorded by the operator: ease of introducer sheath insertion, ease of coronary intubation, ease of injection, coronary opacification, collateral flow demonstration, and overall assessment. Adverse events were recorded in all patients and included minor bleeding, major bleeding (necessitating blood transfusion), minor hematoma, major hematoma, pseudo-aneurysm formation and arteriovenous fistula. RESULTS: The study group included 177 patients, of whom 91 were in the 4F arm and 86 in the 6F arm. Demographic and procedural data were similar in both groups. Seventy-seven percent of 6F and 50% of 4F procedures were evaluated as excellent (P < 0.05). This difference was attributed to easier intubation of the coronary ostium and contrast material injection, increased opacification of the coronary arteries, and demonstration of collateral flow with 6F catheters. Complications occurred in 22% of patients treated with 6F catheters and in 10% of those treated with 4F catheters (P = 0.11). Of the 50 patients who switched from 4F to 6F 12% had complications. In patients undergoing diagnostic angiography, the complication rate was 10% vs. 27% (most of them minor) in the 4F and 6F groups, respectively (P < 0.05). CONCLUSIONS: Patients catheterized with 4F have fewer complications compared with 6F diagnostic catheters even when ambulated earlier. Although 4F had a reduced quality compared to 6F angiographies, they were evaluated as satisfactory or excellent in quality 85% of the time. 4F catheters have a potential for reduced hospitalization stay and are a good option for primary catheterization in patients not anticipated to undergo coronary intervention.

Palestinian Arab ethnicity is associated with an adverse metabolic phenotype.

Urban-dwelling Palestinians have been shown to have higher cardiovascular morbidity and mortality and prevalence of diabetes than urban Israelis. Inflammation is implicated in the etiology of these conditions. We hypothesized that increased inflammatory activation, manifested as increased GlycA, a novel biomarker of global inflammation, would be evident in Palestinians. We compared GlycA concentrations between Palestinians and Israelis and assessed the associations of GlycA with anthropometric, health behavioral and clinical variables in a sample of 1674 Palestinians and Israelis aged 25-74, residing in Jerusalem. The main outcome measure was GlycA concentration. GlycA was higher in Palestinians than Israelis (p<0.001). This finding persisted in young Palestinians with normal glucose tolerance. GlycA, total white blood cell count, the triglyceride to HDL-cholesterol ratio and small LDL-cholesterol particles were all significantly higher in Palestinians compared to Israelis across obesity and glucose tolerance categories. Palestinian women had greater GlycA compared to Israeli women and men of both ethnicities. GlycA as well as adverse cardiovascular biomarkers are all higher in Palestinian Arabs than Israeli Jews, even in young healthy adults. This propensity to inflammation may be a driver of the higher risk of cardiovascular disease, insulin resistance and diabetes observed in this population.

Small and medium sized HDL particles are protectively associated with coronary calcification in a cross-sectional population-based sample.

BACKGROUND AND AIMS: Failure of trials to observe benefits by elevating plasma high-density lipoprotein cholesterol (HDL-C) has raised serious doubts about HDL-C's atheroprotective properties. We aimed to identify protective HDL biomarkers by examining the association of nuclear magnetic resonance (NMR) measures of total HDL-particle (HDL-P), large HDL-particle, and small and medium-sized HDL-particle (MS-HDL-P) concentrations and average HDL-particle size with coronary artery calcification (CAC), which reflects the burden of coronary atherosclerosis, and compare with that of HDL-C. METHODS: Using a cross-sectional design, 504 Jerusalem residents (274 Arabs and 230 Jews), recruited by population-based probability sampling, had HDL measured by NMR spectroscopy. CAC was determined by multidetector helical CT-scanning using Agatston scoring. Independent associations between the NMR measures and CAC (comparing scores ≥100 vs. <100) were assessed with multivariable binary logistic models. RESULTS: Comparing tertile 3 vs. tertile 1, we observed protective associations of HDL-P (multivariable-adjusted OR 0.42, 95% CI 0.22-0.79, plinear trend = 0.002) and MS-HDL-P (OR 0.36, 95% CI 0.19-0.69), plinear trend = 0.006 with CAC, which persisted after further adjustment for HDL-C. HDL-C was not significantly associated with CAC (multivariable-adjusted OR 0.59, 95% CI 0.27-1.29 for tertiles 3 vs. 1, plinear trend = 0.49). Large HDL-P and average particle size (which are highly correlated; r = 0.83) were not associated with CAC: large HDL-P (OR 0.77, 95% CI 0.33-1.83, plinear trend = 0.29) and average HDL-P size (OR 0.72, 95% CI 0.35-1.48, plinear trend = 0.58). CONCLUSIONS: MS-HDL-P represents a protective subpopulation of HDL particles. HDL-P and MS-HDL-P were more strongly associated with CAC than HDL-C. Based on the accumulating evidence, incorporation of MS-HDL-P or HDL-P into the routine prediction of CHD risk should be evaluated.

Differences in the triglyceride to HDL-cholesterol ratio between Palestinian and Israeli adults.

AIMS: To evaluate differences in the triglyceride to HDL-cholesterol ratio (TG/HDL), thought to be a proxy measure of insulin resistance, between Palestinian and Israeli adults in view of the greater incidence of coronary heart disease and high prevalence of diabetes in Palestinian Arabs. RESEARCH METHODS: A population-based observational prevalence study of cardiovascular and diabetes risk factors in Jerusalem. Participants (968 Palestinians, 707 Israelis, sampled at ages 25-74 years) underwent fasting and 2 h post-75 g oral challenge plasma glucose determinations. Metabolic risk was assessed using the surrogate index TG/HDL. Sex-specific comparisons were stratified by categories of body mass index and sex-specific waist circumference quartiles, adjusted by regression for age, glucose tolerance status and use of statins. RESULTS: Prevalence of overweight and obesity was substantially larger in Palestinians (p = 0.005). Prevalence of diabetes was 2.4 and 4 fold higher among Palestinian men and women, respectively (p<0.001). Adjusted TG/HDL was higher in Palestinians than Israelis across BMI and waist circumference categories (p<0.001 for both). Higher TG/HDL in Palestinians persisted in analyses restricted to participants with normal glucose tolerance and off statins. Notably, higher TG/HDL among Palestinians prevailed at a young age (25-44 years) and in normal weight individuals of both sexes. CONCLUSIONS: Palestinians have a higher TG/HDL ratio than Israelis. Notably, this is evident also in young, healthy and normal weight participants. These findings indicate the need to study the determinants of this biomarker and other measures of insulin resistance in urban Arab populations and to focus research attention on earlier ages: childhood and prenatal stages of development.

Premature aging of leukocyte DNA methylation is associated with type 2 diabetes prevalence.

BACKGROUND: Type 2 diabetes mellitus (T2D) is highly prevalent in Middle-Eastern and North African Arab populations, but the molecular basis for this susceptibility is unknown. Altered DNA methylation levels were reported in insulin-secreting and responding tissues, but whether methylation in accessible tissues such as peripheral blood is associated with T2D risk remains an open question. Age-related alteration of DNA methylation level was reported in certain methylation sites, but no association with T2D has been shown. Here we report on a population-based study of 929 men and women representing the East Jerusalem Palestinian (EJP) Arab population and compare with the findings among Israeli Ashkenazi Jews. This is the first reported epigenetic study of an Arab population with a characteristic high prevalence of T2D. RESULTS: We found that DNA methylation of a prespecified regulatory site in peripheral blood leukocytes (PBLs) is associated with impaired glucose metabolism and T2D independent of sex, body mass index, and white blood cell composition. This CpG site (Chr16: 53,809,231-2; hg19) is located in a region within an intron of the FTO gene, suspected to serve as a tissue-specific enhancer. The association between PBL hypomethylation and T2D varied by age, revealing differential patterns of methylation aging in healthy and diabetic individuals and between ethnic groups: T2D patients displayed prematurely low methylation levels, and this hypomethylation was greater and occurred earlier in life among Palestinian Arabs than Ashkenazi Jews. CONCLUSIONS: Our study suggests that premature DNA methylation aging is associated with increased risk of T2D. These findings should stimulate the search for more such sites and may pave the way to improved T2D risk prediction within and between human populations.

Leukocyte telomere length and coronary artery calcification in Palestinians.

OBJECTIVE: Shorter leukocyte telomere length (LTL) is associated with higher incidence of coronary heart disease (CHD) and increased mortality. We examined the association of LTL with coronary artery calcification (CAC), which reflects the cumulative burden of coronary atherosclerosis, in an urban Arab sample of Palestinians, a population at high risk of CHD. METHODS: Using a cross-sectional design, a random sample of East Jerusalem residents, comprising 250 men aged 45-77 and women aged 55-76 and free of CHD or past stroke, was drawn from the Israel national population register. LTL was measured by Southern blots. CAC was determined by 16-slice multidetector helical CT scanning using Agatston scoring. We applied multivariable logistic modeling to examine the association between sex-specific tertiles of LTL and CAC (comparing scores >100 vs. <100, and the upper third vs. the lower 2 thirds), controlling for age, sex, education and coronary risk factors. RESULTS: CAC, evident in 65% of men and 52% of women, was strongly associated with age (sex-adjusted Spearman's rho 0.495). The multivariable-adjusted odds ratios for CAC >100 (found in 30% of men and 29% of women) were 2.92 (95% CI 1.28-6.68) and 2.29 (0.99-5.30) for the lower and mid-tertiles of LTL vs. the upper tertile, respectively (Ptrend = 0.008). Findings were similar for CAC scores in the upper tertile (Ptrend = 0.006), and persisted after the exclusion of patients with diabetes or receiving statins. CONCLUSIONS: Shorter LTL was associated with a greater prevalence of asymptomatic coronary atherosclerosis in an urban Arab population-based sample. Mechanisms underlying this association should be sought.

Postpartum multivessel coronary artery dissection treated with coronary artery bypass grafting.

Spontaneous coronary artery dissection is a rare but potentially life-threatening event associated with the peripartum period. We present a case of acute anterolateral ST elevation myocardial infarction in the postpartum period in a young woman. Thrombolytic therapy was successful, but later the patient required emergent coronary artery bypass grafting due to another acute inferolateral myocardial infarction that developed 4 h after cardiac catheterization which showed multivessel spontaneous coronary artery dissection.

Effect of gradual computerized angioplasty on outcomes of patients undergoing coronary stenting.

Mechanical trauma caused by percutaneous coronary intervention is a major factor contributing to subsequent cardiac events, restenosis, and the need for target lesion revascularization (TLR). To minimize this trauma, we developed a Computerized Angioplasty Pressure Sensor and Inflator Device (CAPSID) for gradual inflation. The objective of the present prospective randomized study was to examine whether the use of this novel device reduced TLR, as well as cardiac events, in patients undergoing stenting. Patients undergoing coronary stenting were eligible and randomized to receive CAPSID or standard manual percutaneous coronary intervention. In the CAPSID group, slow, gradual balloon inflation was performed using a personal computer. Patients with acute ST-elevation myocardial infarction or the need for percutaneous coronary intervention for total occlusions, left main disease, and vein grafts were excluded. Clinical follow-up for major adverse cardiac events, including death, acute myocardial infarction, and TLR, was performed at 12 months. A total of 310 patients were enrolled in the study. No significant differences were found in the clinical characteristics between the CAPSID and control groups. At 1 year of follow-up, the CAPSID group had had a significantly lower rate of major adverse cardiac events (8% vs 18%, p <0.01) driven by significantly lower rates of acute myocardial infarction (1% vs 7%, p <0.01) and TLR (5% vs 12%, p <0.05). In conclusion, gradual computerized balloon inflation using CAPSID as a platform for angioplasty and stenting significantly reduced TLR and major adverse cardiac events at 1 year in patients undergoing coronary stenting. The use of this novel device may improve outcomes in patients undergoing coronary stenting.

Computerized gradual balloon inflation: a novel strategy of coronary angioplasty superior to a standard manual approach.

BACKGROUND: Mechanical trauma caused by PCI is a primary reason for restenosis and subsequent target lesion revascularization (TLR). To minimize this trauma, we developed a computerized angioplasty pressure sensor and inflator device (CAPSID) for gradual inflation. The objective of this prospective randomized study was to examine whether use of CAPSID reduces early and late cardiac events in patients undergoing PCI. METHODS: Patients undergoing PCI were eligible and randomized to CAPSID or standard balloon inflation (plain old balloon angioplasty). In the CAPSID group, a slow, gradual balloon inflation was performed by a personal computer. Stenting was used in both groups only for suboptimal results. Patients with total occlusions and vein grafts were excluded. Clinical follow-up for major adverse cardiac events (MACE) was performed at 6 and 12 months, with repeat coronary angiography performed for clinical symptoms or positive stress testing. RESULTS: A total of 234 patients completed the study. At 1-year follow-up, the CAPSID group had a significantly lower rate of MACE (21% vs. 37%, P<.005). In patients who underwent angiography, there was a significantly lower rate of restenosis in the CAPSID group (20.2% vs. 35.5%). The reduction in TLR was even more pronounced in the subgroup undergoing stenting (8% vs. 24%; P<.001). CONCLUSIONS: We conclude that gradual computerized balloon inflation is more effective than standard manual balloon inflation in reducing adverse coronary events. The combination of CAPSID and subsequent stent deployment was especially effective in reducing TLR.