Cysteine Glutathionylation Acts as a Redox Switch in Endothelial Cells

Oxidative post-translational modifications (oxPTM) of receptors, enzymes, ion channels and transcription factors play an important role in cell signaling. oxPTMs are a key way in which oxidative stress can influence cell behavior during diverse pathological settings such as cardiovascular diseases (CVD), cancer, neurodegeneration and inflammatory response. In addition, changes in oxPTM are likely to be ways in which low level reactive oxygen and nitrogen species (RONS) may contribute to redox signaling, exerting changes in physiological responses including angiogenesis, cardiac remodeling and embryogenesis. Among oxPTM, S-glutathionylation of reactive cysteines emerges as an important regulator of vascular homeostasis by modulating endothelial cell (EC) responses to their local redox environment. This review summarizes the latest findings of S-glutathionylated proteins in major EC pathways, and the functional consequences on vascular pathophysiology. This review highlights the diversity of molecules affected by S-glutathionylation, and the complex consequences on EC function, thereby demonstrating an intricate dual role of RONS-induced S-glutathionylation in maintaining vascular homeostasis and participating in various pathological processes

Prevalence of depressive symptoms among non insulin treated Greek type 2 diabetic subjects

<p>Abstract</p> <p>Background</p> <p>Depression is common among diabetic subjects. We conducted the present study to estimate the prevalence of depression in subjects with type 2 diabetes (T2D) in Greece.</p> <p>Methods</p> <p>The study sample consisted of 320 T2D subjects without overt macrovascular disease attending the diabetes outpatient clinic of our hospital, from June 2007 to December 2007. Depressive symptoms were measured using the 21-item Beck Depression Inventory, modified for use in diabetic subjects.</p> <p>Results</p> <p>Of the study subjects 107 (33.4%) reported elevated depressive symptoms. More women than men with diabetes reported symptoms of depression (48.4% vs. 12.7%, <it>P </it>< 0.001). In the female study group, depressive symptoms were correlated with HbA_1c(<it>P </it>= 0.04), and duration of diabetes (<it>P </it>= 0.004). In the male study group, univariate linear regression analysis showed no significant relationships between depressive symptoms and the testing variables.</p> <p>Conclusion</p> <p>The prevalence of depression in Greek T2D subjects is high. Diabetic female subjects showed increased levels of depressive symptoms compared with male subjects. Independent risk factors of depressive symptoms in diabetic female subjects were diabetes duration and glycemic control.</p

Metabolic syndrome is not associated with reduction in aortic distensibility in subjects with type 2 diabetes mellitus

<p>Abstract</p> <p>Background</p> <p>Aortic distensibility (AD) is a marker of the elastic properties of the aorta. Reduction of AD occurs early in subjects with type 2 diabetes mellitus (T2DM) and it is associated with subclinical generalized atherosclerosis. Metabolic syndrome (MetS) is common in subjects with T2DM and predicts cardiovascular morbidity and mortality. This study examined the potential relationship between MetS and AD in a cohort of subjects with T2DM.</p> <p>Methods and results</p> <p>A total of 210 subjects with T2DM were studied. MetS was diagnosed using the NCEP/ATP-III criteria. AD was assessed non-invasively by ultrasonography. The prevalence of MetS was 64.8%. AD was not significantly different between subjects with and without MetS (1.80 ± 0.54 vs. 1.84 ± 0.53 10^-6dyn^-1cm², p = 0.55). Univariate linear regression analysis showed that AD was associated positively with male sex (p = 0.02) as well as glomerular filtration rate (p < 0.001), and negatively with age (p = 0.04), history of hypertension (p = 0.001), as well as duration of diabetes (p < 0.001). After multivariate adjustment, AD was associated independently and significantly only with age (p = 0.02), duration of diabetes p < 0.001), and history of hypertension (p = 0.004); no significant relationship was found with MetS status, the sum of the components of the MetS or the individual components-besides hypertension-of the MetS.</p> <p>Conclusion</p> <p>In subjects with T2DM, MetS status <it>per se </it>is not associated with reduction of AD. In addition, it was shown that besides ageing, duration of glycemia was a strong predictor of AD. From the components of the MetS only hypertension was associated with reduction of the elastic properties of the aorta.</p

Prevalence of target organ damage in hypertensive subjects attending primary care: C.V.P.C. study (epidemiological cardio-vascular study in primary care)

<p>Abstract</p> <p>Background</p> <p>Except for the established risk factors, presence of target organ damage has an important role in the treatment of hypertensive subjects. The aim of the present study was to estimate the prevalence of target organ damage in primary care subjects.</p> <p>Methods</p> <p>This multi-centre, cross-sectional survey of 115 primary care physicians recruited 1095 consecutive subjects with hypertension: 611 men (55.8%); and 484 women (44.2%). A detailed history for the presence of cardiovascular disease and a thorough clinical examination was performed to each subject.</p> <p>Results</p> <p>Of the total study population, 44.5% (n = 487) had target organ damage (33.0% had left ventricular hypertrophy, 21.8% increased carotid intima media thickness, 11.0% elevated plasma creatinine levels and 14.6% microalbuminuria). Target organ damage was more prevalent in males than in females (P = 0.05). In addition, males had more often increased carotid intima media thickness than females (P = 0.009). On the contrary, females had more often microalbuminuria (P = 0.06) than males. No differences were observed between the two genders regarding left ventricular hypertrophy (P = 0.35) and elevated plasma creatinine levels (P = 0.21). Logistic regression analysis showed associations between target organ damage and dyslipidemia (P < 0.001), presence of metabolic syndrome (P = 0.005), diabetes (P < 0.001) and coronary artery disease (P < 0.001).</p> <p>Conclusion</p> <p>A significant proportion of hypertensive subjects in primary care had documented associated target organ damage, with left ventricular hypertrophy being the most prevalent target organ damage.</p

Prevalence of asymptomatic bacteriuria in type 2 diabetic subjects with and without microalbuminuria

<p>Abstract</p> <p>Background</p> <p>Diabetic subjects, especially women, show high prevalence of asymptomatic bacteriuria (ASB). The aim of the present study was to evaluate the prevalence of ASB in subjects with type 2 diabetes mellitus (T2D) with and without microalbuminuria (MA).</p> <p>Findings</p> <p>A hundred diabetic subjects with MA (53 males/47 females, mean age ± standard deviation: 65.5 ± 11.1 years) and 100 diabetic subjects without MA (52 males/48 females, mean age ± standard deviation: 65.4 ± 11.3 years), consecutively attending the outpatient diabetes clinic of our hospital were recruited in the study. Subjects with overt diabetic nephropathy or nephropathy from other causes were excluded. In addition, subjects with symptoms of urinary track infection or use of antimicrobial drugs in the last 14 days were excluded by the study.</p> <p>Diabetic subjects with MA showed increased prevalence of ASB compared to diabetic subjects without MA (21% versus 8%, P < 0.001, respectively). <it>Escherichia coli </it>was the most prevalent pathogen isolated in diabetic subjects with and without MA (12% versus 3.0%, P = 0.01, respectively) followed by <it>Proteus mirabilis </it>(6% versus 5%, P = 0.75, respectively) and <it>Klebsiella </it>spp (5% versus 1%, P = 0.09, respectively). Univariate logistic analysis showed that ASB was associated with the presence of coronary artery disease [odds ratio (OR): 0.29, 95% Confidence Intervals (95% CI): 0.09-0.95, P = 0.04] and gender (OR: 0.09, 95% CI: 0.02-0.35, P < 0.001) in the diabetic study group with MA.</p> <p>Conclusions</p> <p>ASB is more prevalent among T2D subjects with MA. Screening for ASB is warranted in diabetic patients especially if pyuria is detected in urine analysis since ASB has been found to be a risk factor for developing symptomatic urinary tract infection.</p

Predicting successful prosthetic rehabilitation in major lower-limb amputation patients: a 15-year retrospective cohort study

Objective: To determine and compare specific factors that could be associated and predictive with successful prosthetic rehabilitation in major lower-limb amputations. Methods: A 15-year long (2000-2014) retrospective observational cohort study was conducted. Two different criteria were used to define successful prosthetic rehabilitation: (1) the ability to walk at least 45 m, regardless of assistive devices; and (2) walking >45 m without other ambulatory aids than one cane (if required). Age, gender, comorbidities, cause and level of amputation, stump characteristics, ulcers in the preserved limb, and time between surgery and physical therapy were examined as predictors of successful prosthetic rehabilitation. Results: A total of 169 patients (61.60±15.9 years) were included. Regarding walking ability with or without walking aids, the presence of ulcers in the preserved limb was individually associated with failed prosthetic rehabilitation (p < 0.001), while being male (OR = 0.21; 95%CI = 0.06-0.80) and transtibial level of amputation (OR = 6.73; 95%CI = 1.92-23.64) were identified as independent predictors of failure and success, respectively. Regarding the criterion of successful rehabilitation, a shorter time until rehabilitation was individually associated with improved walking ability (p < 0.013), while failure could be predicted by comorbidities (OR = 0.48; 95%CI = 0.29---0.78) and age groups of 65---75 years old (OR = 0.19; 95%CI = 0.05-0.78) and over 75 years old (OR = 0.19; 95%CI = 0.04-0.91). Conclusions: Regarding walking ability with or without walking aids, male gender and transtibiallevel of amputation are independently associated with failure and success respectively, whereasolder age and comorbidities can predict failed prosthetic rehabilitation when assistive walking devices are considered. Future prospective cohort studies are needed to confirm these findings

Association of depression with newly diagnosed type 2 diabetes among adults aged between 25 to 60 years in Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>The combination of depression with type 2 diabetes is a public health problem. If diabetes is managed in its initial phase, the morbidity and mortality due to this combination may be prevented at an early stage. Therefore, we aimed to determine the association of depression with newly diagnosed type 2 diabetes among adults aged between 25 to 60 years in Karachi, Pakistan.</p> <p>Methods</p> <p>From July 2006 to September 2007, a matched case control study (n = 592) was conducted in Civil Hospital, Karachi. Incident cases of type 2 diabetes (n = 296) diagnosed within one month were recruited from diabetic Out Patient Department (OPD) of Civil Hospital, Karachi. They were matched on age and sex with controls (n = 296), who were attendants sitting in the medical out patient department of the same hospital, recruited on the basis of absence of classical symptoms of polyuria and polydispia along with random blood glucose level of <200 mg/dl measured by a glucometer. Depression was identified by the Siddiqui Shah Depression Scale. Conditional logistic regression was applied to examine the association of depression and other independent variables with newly diagnosed type 2 diabetes at 95% C.I. and P < 0.05.</p> <p>Results</p> <p>The study comprised of 592 subjects with 432(73%) males and 160(27%) females. Depression was significantly associated with newly diagnosed type 2 diabetes having mild level (mOR: 3.86; 95%CI: 2.22,6.71) and moderate to severe level (mOR: 3.41; 95%CI: 2.07,5.61). History of (h/o) gestational diabetes (mOR: 2.83; 95%CI: 1.05,7.64), family h/o diabetes (mOR: 1.59; 95%CI: 1.04,2.43), nuclear family (mOR: 1.75; 95%CI: 1.14,2.69), BMI (mOR: 1.62; 95%CI: 1.01,2.60 for obese and mOR: 2.12; 95%CI: 1.19,3.79 for overweight vs healthy to underweight) were also significantly associated with outcome, adjusting for age, sex, marital status, h/o smoking and h/o high BP.</p> <p>Conclusions</p> <p>Diabetics should be screened simultaneously for depression and concomitant preventive strategies for gestational diabetes, nuclear family and high BMI should also be used to prevent mortality/morbidity among patients between 25 to 60 years of age.</p