Cardiovascular risk factors and subclinical atherosclerosis among Nunavik Inuit

ObjectiveTo evaluate subclinical atherosclerosis in Nunavik Inuit and its correlation to traditional cardiovascular disease risk factor.MethodThe intima–media thickness (IMT) of 12 segments of the carotid arteries (IMT_{12_seg}) free of plaque were assessed in randomly selected 40 years old and older Inuit from. Clinical assessment was performed which included fasting plasma glucose, fasting insulin, systemic blood pressure, body mass index, smoking, circulating blood lipids and oral glucose tolerance test. In addition, documented presence of ischemic heart disease (IHD), stroke, diabetes mellitus, hypertension and dyslipidemia were determined from medical files.ResultsThe average age of the 287 participants was 51.2 ± 0.6 years (56.8% women). Mean IMT_{12_seg} was 0.80 ± 0.17 mm (range: 0.55–1.47 mm). Compared with disease free Inuit, individuals with history of stroke showed greater carotid internal IMT (0.68 ± 0.01 mm vs. 0.96 ± 0.15 mm respectively; p < 0.005) but no difference was observed for IHD. Hypertensive and dyslipidemic Inuit had higher IMT_{12_seg} compared to risk factor free individuals but no difference was observed in diabetics. None of the clinical assessments were associated with IMT_{12_seg}. In a multivariate backward elimination model, only age, gender, and medically documented history of hypertension were found to be predictors of IMT_{12_seg} (adjusted r-square of 0.54; p < 0.0001).ConclusionCompared with disease free Nunavik Inuit, subclinical signs of atherosclerosis determined by IMT was higher in individual diagnosed with stroke. Independent predictors of IMT_{12_seg} in our group were age, gender and history of hypertension. No other traditional risk factors imparted IMT.     

Effect of ivabradine on pulmonary hypertension in chronic obstructive pulmonary disease

In order to assess effect of If-channel blocker ivabradine on severity of pulmonary hypertension in chronic obstructive pulmonary disease (COPD) we studied 60 patients with III-IV stage COPD. We divided these patients into 2 groups with similar clinical characteristics and therapy. Patients of one of these groups received ivabradine (10 mg/day) for 2 weeks, patients of another served as controls. The use of ivabradine was associated with statistically significant lowering of pulmonary hypertension, heart rate, and increase of exercise tolerance without negative effects on myocardial contractility, electrophysiological parameters, or data of spirometry.     

Left main coronary artery stenosis and progression of coronary artery atherosclerosis after angioplasty and stenting in patients directed to coronary artery bypass surgery

Recent investigations demonstrated appearance of left main coronary artery stenosis after PTCA. We performed a retrospective study of specific characteristics of development of coronary lesions after percutaneous coronary interventions (PCI) in patients subjected to coronary artery bypass grafting (CABG) because of angina recurrence after PCI. Data of 150 patients operated because of angina recurrence after PCI were analyzed. The recurrence of angina in 93% of cases was associated with development of significant stenoses in previously intact segments of coronary arteries, but not with restenosis or occlusion of the stented segment. The recurrence of symptoms occurred in 1 year after coronary stenting in 54% of patients. In 19 patients rapid development of a novel left main coronary artery stenosis was observed. Some characteristics of this group (the use of Back-up, XB, AL-catheters, repetitive PCI, manipulations in more than 2 coronary segments, stenting of bifurcations with 2 stents, use of kissing-balloons, small diameter of left coronary artery, and concomitant diabetes) significantly differed from those of the main group. In all patients CABG was successful.     

Analysis of serum cytokine levels in children with chronic cough associated with Toxocara canis infection

Toxocara infection is associated with an increased prevalence of airway symptoms and may be a possible aetiologic agent of chronic cough. The occurrence of toxocariasis in Hungary is mild and/or sporadic. The purpose of this study was to investigate the levels of serum cytokines (IL‐1, IL‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐13, IFN‐gamma and TNF‐alpha) and total IgE, the blood eosinophil count, the results of skin prick and non‐specific bronchus provocation tests in Toxocara‐seropositive children with chronic cough relative to those in healthy controls. The patients exhibited moderate eosinophilia, significantly elevated levels of serum total IgE, IL‐6, IL‐10, IL‐13 and IFN‐gamma, and higher skin reactivity to common allergens, whereas the bronchial hyperreactivity was similar in the two groups. The protective proinflammatory cytokines (IL‐6, IFN‐gamma and IL‐13) in association with the anti‐inflammatory cytokine (IL‐10) were simultaneously increased in Toxocara‐infected children with chronic cough. During infections, the activation and suppression of immune processes occur simultaneously and cytokines of Th1/Th2 and regulatory T cells contribute to the regulation of the immune response evoked by helminth infections (depending on the parasite load, the timing and duration of the infection and the status of the host immune system).     

Dehydroepiandrosterone (DHEA) improves pulmonary hypertension in chronic obstructive pulmonary disease (COPD): a pilot study

ObjectivesIt was previously shown that dehydroepiandrosterone (DHEA) reverses chronic hypoxia-induced pulmonary hypertension (PH) in rats, but whether DHEA can improve the clinical and hemodynamic status of patients with PH associated to chronic obstructive pulmonary disease (PH-COPD) has not been studied whereas it is a very severe poorly treated disease.Patients and methodsEight patients with PH-COPD were treated with DHEA (200 mg daily orally) for 3 months. The primary end-point was the change in the 6-minute walk test (6-MWT) distance. Secondary end-points included pulmonary hemodynamics, lung function tests and tolerance of treatment.ResultsThe 6-MWT increased in all cases, from 333 m (median [IQR]) (257; 378) to 390 m (362; 440) (P < 0.05). Mean pulmonary artery pressure decreased from 26 mmHg (25; 27) to 21.5 mmHg (20; 25) (P < 0.05) and pulmonary vascular resistance from 4.2 UI (3.5; 4.4) to 2.6 UI (2.5; 3.8) (P < 0.05). The carbon monoxide diffusing capacity of the lung (DLCO % predicted) increased significantly from 27.4% (20.1; 29.3) to 36.4% (14.6; 39.6) (P < 0.05). DHEA treatment did not change respiratory parameters of gas exchange and the 200 mg per day of DHEA used was perfectly tolerated with no side effect reported.ConclusionDHEA treatment significantly improves 6-MWT distance, pulmonary hemodynamics and DLCO of patients with PH-COPD, without worsening gas exchange, as do other pharmacological treatments of PH (trial registration NCT00581087).     

Pioglitazone Acutely Reduces Energy Metabolism and Insulin Secretion in Rats

Our objective was to determine if the insulin-sensitizing drug pioglitazone acutely reduces insulin secretion and causes metabolic deceleration in vivo independently of change in insulin sensitivity. We assessed glucose homeostasis by hyperinsulinemic-euglycemic and hyperglycemic clamp studies and energy expenditure by indirect calorimetry and biotelemetry in male Wistar and obese hyperinsulinemic Zucker diabetic fatty (ZDF) rats 45 min after a single oral dose of pioglitazone (30 mg/kg). In vivo insulin secretion during clamped hyperglycemia was reduced in both Wistar and ZDF rats after pioglitazone administration. Insulin clearance was slightly increased in Wistar but not in ZDF rats. Insulin sensitivity in Wistar rats assessed by the hyperinsulinemic-euglycemic clamp was minimally affected by pioglitazone at this early time point. Pioglitazone also reduced energy expenditure in Wistar rats without altering respiratory exchange ratio or core body temperature. Glucose-induced insulin secretion (GIIS) and oxygen consumption were reduced by pioglitazone in isolated islets and INS832/13 cells. In conclusion, pioglitazone acutely induces whole-body metabolic slowing down and reduces GIIS, the latter being largely independent of the insulin-sensitizing action of the drug. The results suggest that pioglitazone has direct metabolic deceleration effects on the β-cell that may contribute to its capacity to lower insulinemia and antidiabetic action.Major drugs developed to treat type 2 diabetes aim at either increasing insulin secretion or reducing insulin resistance (1–4). Two classes of insulin-sensitizing agents are currently used, the biguanides (metformin) and the thiazolidinediones (TZDs), of which the only one still recommended for use in some countries is pioglitazone (5). TZDs are peroxisome proliferator–activated receptor-γ (PPARγ) agonists. They stimulate adipocyte differentiation, relieving other tissues from fat excess, thereby reducing their resistance to insulin (6,7). The beneficial effects of TZDs are not limited to increased insulin sensitivity and also include preservation of β-cell function (8). It is thought that the beneficial effect of TZDs on β-cell function in vivo is indirect and occurs via a relief of the need for insulin hypersecretion because of their insulin sensitizing action. We should, however, consider the possibility that the classical antidiabetic insulin sensitizers, pioglitazone and metformin, might also have beneficial effects on glucose homeostasis via direct reduction of insulin hypersecretion independently of insulin resistance.We previously demonstrated in vitro that pioglitazone acutely slows down glucose and lipid metabolism in the β cell and inhibits glucose-induced insulin secretion (GIIS) primarily at submaximal and much less at maximal glucose concentrations (right shift in the glucose dose response) via a PPARγ-independent mechanism (9). These acute effects of pioglitazone are likely attributable to complex I inhibition of the electron transport chain (10) and involve reduced glucose oxidation, decreased ATP levels, and increased AMPK activation (9). Interestingly, metformin causes similar effects (J.L. and M.P., unpublished data). Hence, we proposed the novel concept of “metabolic deceleration” as a mode of action of some antidiabetic drugs and suggested that the action of pioglitazone to reduce glucose metabolism and insulin secretion in the β-cell may partly explain its beneficial effects (9). The concept that metabolic deceleration protects the β-cell from both oxidative and endoplasmic reticulum stress has recently been reviewed (11,12).In the current study we performed in vivo experiments in normal Wistar and obese Zucker diabetic fatty (ZDF) rats to better understand how acute treatment with pioglitazone alters glucose homeostasis, with particular focus on how it reduces hyperinsulinemia. The following questions were asked: 1) Can we confirm in vivo our previous in vitro findings in isolated rat islet and β-cell line that pioglitazone acutely reduces insulin secretion? 2) Is this acute effect of pioglitazone on insulin secretion independent of its effects on insulin sensitivity? and 3) Does pioglitazone acutely slow down whole-body energy metabolism?