Tobacco smoking strongly modifies the association of prothrombin G20210A with undetermined stroke: consecutive survivors and population-based controls.

OBJECTIVE: Due to contradictory results of previous studies evaluating the association between ischemic stroke (IS) and thrombophilic polymorphisms, their routine screening in IS patients, particularly those older than 60 years, is not recommended. We evaluated the differences in the distribution of rs6025 and rs1799963 polymorphisms according to IS subtypes and their interaction with smoking. METHODS: We conducted a case-control study of 423 hospital-based consecutive survivors of their first-ever IS and 614 population-based controls. Survivors (18-81 years) with IS documented by brain imagining were examined at a median of 16 months after the index event. The stroke subtype was categorized using the Causative Classification of Stroke System. Controls (50-75 years) were free of a history of stroke/TIA, coronary heart disease, and venous thromboembolism. RESULTS: Age- and gender-adjusted prevalence of individuals carrying at least one copy of the rs1799963A minor allele was 5.3% among stroke survivors (by subtypes: 3.1% in large artery atherosclerosis, 2.0% in cardio-aortic embolism, 2.4% in small artery occlusion, and 10.3% in undetermined stroke) vs. 2.4% among controls. In multinomial multivariate adjusted analysis, rs1799963 was exclusively associated with undetermined stroke (OR: 3.67; 95% CI: 1.52-8.85; p = 0.004). There was strong evidence of rs1799963 × smoking synergistic interaction (OR: 5.14; 95% CI: 1.65-16.01; p = 0.005). There was no association of rs6025 with IS in general, or with any subtype. CONCLUSIONS: In our consecutive IS survivors, carriage of the rs1799963A allele is associated with undetermined stroke. This effect appears to be confined to smokers.

A randomised controlled trial of roller versus centrifugal cardiopulmonary bypass pumps in patients undergoing pulmonary endarterectomy.

OBJECTIVES: There is some controversy as to whether there is a benefit from the use of a centrifugal pump compared with a roller pump during cardiopulmonary bypass to facilitate cardiac surgery. We compared the two pumps, with the primary aim of determining any difference in the effects on inflammation after pulmonary endarterectomy surgery which required prolonged cardiopulmonary bypass and deep hypothermic circulatory arrest. METHODS: Between September 2010 and July 2013, 58 elective patients undergoing pulmonary endarterectomy were included in this prospective, randomised, controlled study; 30 patients were randomly allocated to the control group, which used a roller pump, and 28 patients to the treatment group, which used a centrifugal pump. Interleukin-6, procalcitonin, C-reactive protein, thromboelastographic parameters, P-selectin, international normalised ratio, activated prothrombin time, free haemoglobin, haematocrit, red blood cell count, white blood cell count, platelet count and protein S100ß were recorded during and after the procedure. We also recorded the length of intensive care unit stay, blood loss and transfusion, neurological outcomes and respiratory and renal failure. RESULTS: There was a significant difference in the primary outcome measure: Interleukin-6 was significantly higher in the roller pump group (587 ± 38 ng · l(-1) vs. 327 ± 37 ng · l(-1); p<0.001) 24 hours after surgery, which we interpreted as an increased inflammatory response. This was confirmed by a significant rise in the procalcitonin level in the roller pump group 48 hours following surgery (0.79 (0.08-25.25) ng · ml(-1) vs. 0.36 (0.02-5.83) ng · ml(-1); p<0.05). There were, however, no significant differences in clinical outcome data. CONCLUSIONS: We have shown that the use of a centrifugal pump during prolonged cardiopulmonary bypass and deep hypothermic circulatory arrest is associated with a reduced inflammatory response compared to the standard roller pump. Larger multi-centre trials in this area of practice are required.

[Importance of the endocannabinoid system in the regulation of energy homeostasis]. / Význam endokanabinoidního systému v regulaci energetické rovnováhy.

The endocannabinoid system is an endogenous signaling system that plays a role in the regulation of energy homeostasis and lipid and glucose metabolism-all of which can influence cardiometabolic risk. The endocannabinoid system appears to be a promising novel mechanistic pathway that modulates important aspects afcardiovascular and metabolic function. The endocannabinoid system is normally a silent physiologic system that becomes transiently activated, that is, only when needed. Evidence suggests that the endocannabinoid system is tonically overactive in human obesity and in animal models of genetic and diet-induced obesity. However, there is evidence in studies that the ECS is tonically overactivated in obesity, although it remains unclear whether overactivation of the ECS precedes or is consequent to expression of the obese phenotype. Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce smoking, body weight and improve and improves the profile of several metabolic risk factors in high-risk patients.

Biochemical markers of endothelial dysfunction in patients with endocrine and essential hypertension.

The aim of our study was to evaluate potential differences in the concentration of biochemical markers of endothelial dysfunction between essential hypertension, endocrine hypertension (pheochromocytoma, primary hyperaldosteronism) and control healthy group and to assess a potential relationship between these markers of endothelial dysfunction and vasopressor substances overproduced in endocrine hypertension. We have investigated 21 patients with moderate essential hypertension, 29 patients with primary hyperaldosteronism, 24 subjects with pheochromocytoma and 26 healthy volunteers. Following parameters of endothelial dysfunction were measured, von Willebrand factor (vWf), plasminogen activator (t-PA) and E-selectin (E-sel). Clinical blood pressure was measured according to the European Society of Hypertension recommendations. We found significantly higher levels of the von Willebrand factor in patients with essential hypertension in comparison with a control group (114+/-20 IU/dl vs 90+/-47 IU/dl; P=0.04) and patients with primary hyperaldosteronism (114+/-20 IU/dl vs 99+/-11 IU/dl; P=0.01). Patients with endocrine hypertension revealed increased levels of vWF compared to the control group, but these differences did not reach statistical significance. Levels of t-PA were increased in patients with pheochromocytoma in comparison with the control group (4.6+/-1.9 ng/ml vs 3.4+/-0.9 ng/ml; P=0.01) and with primary hyperaldosteronism (4.6+/-1.9 ng/ml vs 3.4+/-1.1 ng/ml; P<0.01). In case of E-selectin we found lower levels in patients with pheochromocytoma in comparison with other groups, but they differed significantly only with primary hyperaldosteronism (40.2+/-15.0 ng/ml vs 51.3+/-23.0 ng/ml; P=0.05). Our study did not reveal any convincing evidence of differences in the levels of biochemical markers of endothelial dysfunction between essential and endocrine hypertension. No correlation between the biochemical markers of endothelial dysfunction and vasopressor substances activated in endocrine hypertension was found.

[Endocannabinoids--the new option in the treatment of metabolic syndrome and in smoking cessation]. / Endokanabinoidy--nová moznost v lécbe metabolického syndromu a odvykáiní kourení.

Development of the metabolic syndrome results from the interaction of genetic and environmental factors. Metabolic syndrome together with smoking represents risk factors for the development of cardiovascular complications. They may result from the hyperstimulation of the endocannabinoid system. The CB1 receptor has been assumed to play an important role in the endocannabionoid system. It is abundantly expressed in the brain, and in other parts of human body such as in the fat tissue. Rimonabant is a selective blocker of cannabinoid-1 (CB1) receptors and participates in the regulation of impaired endocannabinoid system. In the overweight humans, it stimulates sustained reduction of the body weight, girth size and it improves lipid and glucose metabolism. Rimonabant also reduces nicotine self-administration and may be effective not only as an aid for smoking cessation but also in the prevention of body weight increase related to the smoking cessation as it was documented in Rio-Lipids and Stratus-us studies.

Apoptosis and growth factors in parathyroid adenomas.

Detection of apoptotic cells and of immunoreactivity to transforming growth factor alpha (TGF-alpha) and to its ligand, epidermal growth factor receptor (EGFR), was studied in 20 cases of parathyroid adenoma. The DNA nick-end labelling method revealed that 85% of these adenomas contained apoptotic cells. Detection rates of TGF-alpha and EGFR were very high, but neither TGF-alpha nor EGFR was correlated to apoptosis. As TGF-alpha exerts its effect via EGFR, the concomitant demonstration of the two factors occurring in both the adenomatous tissue and the surrounding rim of normal tissue may reflect a significant mutual association. The markers were located mainly within the cytoplasm, indicating their important role in growth regulation, cell differentiation and cell function. The synchronous expression of TGF-alpha and EGFR in both parathyroid adenomas and normal glandular parenchyma suggests that these functions may be mediated by an autocrine mechanism.

Detection of apoptotic cells and expression of Ki-67 antigen, Bcl-2, p53 oncoproteins in human parathyroid adenoma.

Presence of apoptotic cells and immunoreactivity to Ki-67, bcl-2 and p53 were studied in 20 cases of parathyroid adenoma. To determine apoptosis, the DNA nick end labeling method was used. 85% of the parathyroid adenomas were found to harbor apoptotic cells. All of the 20 adenomas contained Ki-67 immunoreactive cells. Proliferative activity was not more confined to nodular than to diffuse areas, but there was a highly significant difference in Ki-67 immunoreactivity between adenomatous tissue and the residual rim of normal tissue outside the adenoma. No Ki-67 immunoreactive cells were found in two normal parathyroid glands used as controls. All but one of the adenomas (95%) demonstrated immunoreactivity to bcl-2, but expression of p53 was detected in only a few adenomas (15%). There was a significant relationship between the adenoma weights and both Ki-67 and bcl-2. This study suggests that parathyroid adenomas contain cell populations with proliferative activity (clonal proliferation), but the weak immunoreactive expression of p53 combined with the relatively strong expression of bcl-2 might contribute to a slow glandular growth.