The Impact of Coexistence of Smoking and Diabetes on the Coronary Artery Severity and Outcomes following Percutaneous Coronary Intervention: Results from the 1ST Jordanian PCI Registry.

INTRODUCTION: Diabetes mellitus (DM) and smoking are highly prevalent among Middle Eastern patients admitted with acute coronary syndrome (ACS) or who undergo percutaneous coronary intervention (PCI). METHODS: This study used the analysis of the data from the first Jordanian PCI registry (JoPCR1) to determine the impact of coexistence of smoking and diabetes mellitus on the coronary artery severity and outcome following percutaneous coronary intervention in Middle Eastern patients. RESULTS: Of 2426 patients enrolled, 1300 (53.6%) and 1055 (43.5%) were diabetics and smokers, respectively. The patients' age was 59.0 ± 10.1 and ranged between 24 and 95 years. Males comprised 79.4% of all patients. The patients were divided into four groups: nondiabetic-nonsmokers (22.2%), diabetic-nonsmokers (34.3%), nondiabetic-smokers (24.2%), and diabetic-smokers (19.2%). Compared with the other three groups, patients in the diabetic-nonsmoker group were older, more likely to be females, and having a higher prevalence of hypertension, dyslipidemia, chronic renal disease, and history of CVD and revascularization. Consequently, the diabetic-nonsmoker patients (but not the diabetic-smokers) had a higher prevalence of multivessel CAD and PCI than the other three groups, highlighting the importance of other risk factors (age, gender, metabolic syndrome, and comorbidities) and not only smoking in predisposing for CAD. Furthermore, those patients had a higher incidence of ACS as an indication for PCI than the stable coronary disease (73% vs 27%) and the highest CRUSADE bleeding risk score (63.9%) among other groups. The in-hospital events including in-stent thrombosis and emergency CABG events did not significantly differ among groups (p = 0.5 and 0.22). Heart failure and major bleeding events occurred significantly higher among diabetic-nonsmokers compared to other groups. In-hospital deaths occurred significantly more among diabetic-nonsmokers. Moreover, the one-month and one-year follow-up outcome events (the mortality rate, in-stent thrombosis, readmission for ACS, coronary revascularization, and major bleedings) occurred more frequently in the diabetic-nonsmoker group. However, the difference was statistically significant only for major bleeding incidences. CONCLUSIONS: In this analysis of a completed prospective Middle Eastern PCI registry, the majority of the diabetic-nonsmoker (and not the diabetic-smokers) patients (73%) presented with ACS. This group was the highest at risk for in-hospital PCI complications as well as the worst in outcomes after one year of follow-up. Those patients were more likely to be older, female, and have the worst cardiovascular baseline features, highlighting the importance of other risk factors (age, gender, metabolic syndrome, and comorbidities) and not only smoking in predisposing for CAD. Thus, more sufficient education about controlling CVD risk factors should be implemented in the Middle Eastern region.

Recall of physiology knowledge among medical interns: an exploratory study in Riyadh, Saudi Arabia.

The aim of the study was to explore the factors associated with the recall of basic medical physiology knowledge among medical interns and to determine the level of retained basic science knowledge. Two hundred and four interns, 114 women and 90 men, working in two major tertiary medical care centers, King Fahad Medical City (KFMC; 29 students) and King Khalid University Hospital (KKUH; 117 students), in Riyadh city, participated in the study. An anonymous knowledge test with 10 validated multiple-choice questions was developed specifically for this purpose. One hundred and forty-six interns (117 working at KKUH and 29 at KFMC) had graduated from medical schools adopting a conventional instructional system, whereas 58 (3 from KKUH and 55 from KFMC had graduated from schools adopting an integrated system (hybrid problem-based learning). Fifty-two students (26%) gained a score ≥60%, whereas 152 students (74%) obtained <60% of the score. Higher scores were associated with younger age ( P < 0.01), traditional curriculum ( P < 0.001), interns from KKUH ( P < 0.001), and candidates for postgraduate studies ( P < 0.02). There was no significant association between recall of physiology knowledge and all other variables studied, including sex. Multivariate analyses show that age and traditional curriculum are the only significant predictors of knowledge retention. Almost three-fourths of the interns scored <60%, and higher scores were significantly associated with younger interns, traditional curriculum, working in KKUH, and interns preparing for graduate studies. However, the difference between the two curricula disappears when the influence of hospital training is considered.

Does sildenafil improve ventilatory function in asthmatic subjects?

Can sildenafil be used to treat asthma? http://ow.ly/13Y830bgExG.

MicroRNAs 33, 122, and 208: a potential novel targets in the treatment of obesity, diabetes, and heart-related diseases

Despite decades of research, obesity and diabetes remain major health problems in the USA and worldwide. Among the many complications associated with diabetes is an increased risk of cardiovascular diseases, including myocardial infarction and heart failure. Recently, microRNAs have emerged as important players in heart disease and energy regulation. However, little work has investigated the role of microRNAs in cardiac energy regulation. Both human and animal studies have reported a significant increase in circulating free fatty acids and triacylglycerol, increased cardiac reliance on fatty acid oxidation, and subsequent decrease in glucose oxidation which all contributes to insulin resistance and lipotoxicity seen in obesity and diabetes. Importantly, MED13 was initially identified as a negative regulator of lipid accumulation in Drosophilia. Various metabolic genes were downregulated in MED13 transgenic heart, including sterol regulatory element-binding protein. Moreover, miR-33 and miR-122 have recently revealed as key regulators of lipid metabolism. In this review, we will focus on the role of microRNAs in regulation of cardiac and total body energy metabolism. We will also discuss the pharmacological and non-pharmacological interventions that target microRNAs for the treatment of obesity and diabetes (AU)

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MicroRNAs 33, 122, and 208: a potential novel targets in the treatment of obesity, diabetes, and heart-related diseases.

Despite decades of research, obesity and diabetes remain major health problems in the USA and worldwide. Among the many complications associated with diabetes is an increased risk of cardiovascular diseases, including myocardial infarction and heart failure. Recently, microRNAs have emerged as important players in heart disease and energy regulation. However, little work has investigated the role of microRNAs in cardiac energy regulation. Both human and animal studies have reported a significant increase in circulating free fatty acids and triacylglycerol, increased cardiac reliance on fatty acid oxidation, and subsequent decrease in glucose oxidation which all contributes to insulin resistance and lipotoxicity seen in obesity and diabetes. Importantly, MED13 was initially identified as a negative regulator of lipid accumulation in Drosophilia. Various metabolic genes were downregulated in MED13 transgenic heart, including sterol regulatory element-binding protein. Moreover, miR-33 and miR-122 have recently revealed as key regulators of lipid metabolism. In this review, we will focus on the role of microRNAs in regulation of cardiac and total body energy metabolism. We will also discuss the pharmacological and non-pharmacological interventions that target microRNAs for the treatment of obesity and diabetes.

The ability of phosphodiesterase-5 inhibitors sildenafil and ordonafil to reverse L-NAME induced cardiac hypertrophy in the rabbit: possible role of calcineurin and p38.

Phosphodiesterase 5 inhibitors (PDE-5Is) can suppress and (or) reverse pressure overload induced myocardial hypertrophy. This study investigated the suppressive effect of 2 PDE-5Is (sildenafil and ordonafil) on N-nitro-l-arginine methyl ester (L-NAME)-induced cardiac hypertrophy in rabbit heart, and examined their possible mechanism of action. L-NAME increased left ventricular thickness to 6.1± 0.18 mm from 4.6 ± 0.13 mm (p < 0.05), which regressed after treatment with either sildenafil or ordonafil to 5.1 ± 0.1 mm and 4.8 ± 0.2 mm, respectively (p < 0.05). Phenylephrine increased neonatal rat ventricular myocyte cell surface area to 131% ± 3% of the control value, which was associated with significant increment in ERK1/2 to 143% ± 5% of the control value (p < 0.05). Ordonafil and sildenafil decreased cell surface area to 95% ± 3% and 90% ± 1% of the control value, respectively. Both drugs decreased ERK1/2 to 88% ± 4% of the control value. Calcineurin activity was significantly decreased after 1 h of treatment with 0.1 mg·L(-1) ordonafil (1.15 ± 0.05, p < 0.05). For sildenafil (0.1 mg·L(-1)), calcineurin activity significantly decreased only after 24 h of incubation (22%). Also p38 activation was attenuated by ordonafil and sildenafil (0.1 mg·L(-1)). It is suggested that both drugs have the ability to reverse L-NAME-induced cardiac hypertrophy and suppress phenylphrine-induced myocyte hypertrophy, and that these effects may be mediated through the attenuation of calcineurin and its downstream signaling pathways (p38) in neonatal rat ventricular myocytes.

Vascular function and handgrip strength in rheumatoid arthritis patients.

OBJECTIVE: To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. METHODS: Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. RESULTS: The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r = 0.5; P = 0.0001), and inversely related to RVR (r = -0.3; P = 0.009) and RHVR (r = -0.3; P = 0.007). CONCLUSION: The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals.

Effects of glyburide (glibenclamide) on myocardial function in Langendorff perfused rabbit heart and on myocardial contractility and slow calcium current in guinea-pig single myocytes.

Glyburide, also known as glibenclamide, was shown to have positive inotropic effect in human and animal hearts. The objectives of the present study was to investigate the effects of glyburide on developed left ventricular pressure (DLVP), coronary flow (CF), and heart rate (HR), in isolated rabbit heart as well as its effects on myocardial contractility and L-type calcium current, iCa, in guinea pig myocytes. Rabbit hearts were mounted on Langendorff apparatus and perfused with an oxygenated Krebs for 30 min until reaching steady state to be followed by 20 min of experimental perfusion divided into 5 min of control perfusion and 15 min of perfusion with Glyburide (10 microM). Ventricular myocytes were isolated by enzymatic dispersion technique and superfused in an oxygenated Tyrode solution. Cells were voltage-clamped at holding potential -40 mV to inactivate Na+ current and a step depolarizations, 200 msec duration, to 0 mV was applied to elicit iCa. The contractions of the myocytes were measured by optical methods. Glyburide significantly increased DLVP by 30% and CF by 36% but had no effect on HR. Glyburide increased cell contractility by 7 +/- 6, 18 +/- 7, 28 +/- 9 and 54 +/- 15% for 0.1, 1, 10 and 100 microM respectively, p < 0.001. Meanwhile it depressed iCa by 9 +/- 6 and 19 +/- 8% for 1 and 10 microM respectively. In conclusion, glyburide increased contractility of guinea pig single myocytes and of isolated rabbit heart, as indicated by increased developed left ventricular pressure while it depressed iCa. It is hypothesized that an elevation in intracellular calcium, which caused increased myocardial contractility, could be attributed to an increase in intracellular Na+ that could increase intracellular calcium via Na+/Ca2+ exchange.