Functional characterization of a Ca2+-activated non-selective cation channel in human atrial cardiomyocytes

Cardiac arrhythmias, which occur in a wide variety of conditions where intracellular calcium is increased, have been attributed to the activation of a transient inward current ( I _ti). I _ti is the result of three different [Ca]_i-sensitive currents: the Na⁺–Ca²⁺ exchange current, a Ca²⁺-activated chloride current and a Ca²⁺-activated non-selective cationic current. Using the cell-free configuration of the patch-clamp technique, we have characterized the properties of a Ca²⁺-activated non-selective cation channel (NSC_Ca) in freshly dissociated human atrial cardiomyocytes. In excised inside-out patches, the channel presented a linear I–V relationship with a conductance of 19 ± 0.4 pS. It discriminated poorly among monovalent cations (Na⁺ and K⁺) and was slightly permeable to Ca²⁺ ions. The channel's open probability was increased by depolarization and a rise in internal calcium, for which the K _d for [Ca²⁺]_i was 20.8 μ m . Channel activity was reduced in the presence of 0.5 m m ATP or 10 μ m glibenclamide on the cytoplasmic side to 22.1 ± 16.8 and 28.5 ± 8.6%, respectively, of control. It was also inhibited by 0.1 m m flufenamic acid. The channel shares several properties with TRPM4b and TRPM5, two members of the 'TRP melastatin' subfamily. In conclusion, the NSC_Ca channel is a serious candidate to support the delayed after-depolarizations observed in [Ca²⁺] overload and thus may be implicated in the genesis of arrhythmias.     

Idiopathic aneurysm of the pulmonary artery trunk. Report of a case

Aneurysms of the aorta are frequent and treatment is well known, correlated with a statistical risk of rupture. Pulmonary artery aneurysms are less frequent. They may occur in connection with other conditions (infection, cardiopathy, notably pulmonary artery hypertension, endovascular trauma) or much more exceptionally regarded as idiopathic. Chest x-ray, CT-scan and digitalized pulmonary angiography and echocardiography give the diagnosis and help evaluate extension and localization. We report the case of a 72-year-old woman who developed idiopathic aneurysm of the left pulmonary artery which was discovered fortuitously. Because of the stability of the lesion and the lack of any worsening factor, we decided not to operate this high-risk patient. After 3 years, no complication has been observed and the CT-scan shows no evolution. In case of proximal idiopathic aneurysm of the pulmonary artery, the indication of surgery should be discussed.     

Cardiogenic shock due to myocardial infarction: surgical revascularization with centrifugal left ventricular assistance. Report of 2 cases treated successfully

Cardiogenic shock in the acute phase of myocardial infarction still carries a high mortality. In young patients who cannot be revascularised by angioplasty, when medical therapy is failing, some workers recommend an energetic approach, even cardiac transplantation, often with the bridge of mechanical cardiac assistance. This is not possible everywhere, thus preventing possible myocardial salvage and resulting in fairly high mortality. The authors report two cases in which endoluminal revascularisation was not possible and so complete surgical revascularisation with left ventricular assistance was chosen. The two patients survived and one was successfully transplanted electively. This management may be proposed in young patients with multiple occlusions of large coronary arteries in post-infarction cardiogenic shock when medical management is failing despite intra-aortic balloon pumping.     

A Combination of Constitutive Damage Model and Artificial Neural Networks to Characterize the Mechanical Properties of the Healthy and Atherosclerotic Human Coronary Arteries

It has been indicated that the content and structure of the elastin and collagen of the arterial wall can subject to a significant alteration due to the atherosclerosis. Consequently, a high tissue stiffness, stress, and even damage/rupture are triggered in the arterial wall. Although many studies so far have been conducted to quantify the mechanical properties of the coronary arteries, none of them consider the role of collagen damage of the healthy and atherosclerotic human coronary arterial walls. Recently, a fiber family‐based constitutive equation was proposed to capture the anisotropic mechanical response of the healthy and atherosclerotic human coronary arteries via both the histostructural and uniaxial data. In this study, experimental mechanical measurements along with histological data of the healthy and atherosclerotic arterial walls were employed to determine the constitutive damage parameters and remodeling of the collagen fibers. To do this, the preconditioned arterial tissues were excised from human cadavers within 5‐h postmortem, and the mean angle of their collagen fibers was precisely determined. Thereafter, a group of quasistatic axial and circumferential loadings were applied to the arterial walls, and the constrained nonlinear minimization method was employed to identify the arterial parameters according to the axial and circumferential extension data. The remodeling of the collagen fibers during the tensile test was also predicted via Artificial Neural Networks algorithm. Regardless of loading direction, the results presented a noteworthy load‐bearing capability and stiffness of the atherosclerotic arteries compared to the healthy ones (P < 0.005). Theoretical fiber angles were found to be consistent with the experimental histological data with less than 2 and 5° difference for the healthy and atherosclerotic arterial walls, respectively. The pseudoelastic damage model data were also compared with that of the experimental data, and interestingly, the arterial mechanical behavior for both the primary loading (up to the elastic region) and the discontinuous softening (up to the ultimate stress) was well addressed. The proposed model predicted well the mechanical response of the arterial tissue considering the damage of collagen fibers for both the healthy and atherosclerotic arterial walls.     

The role of improved water quality on inflammatory markers in patients undergoing regular dialysis

Hemodialysis utilizes large quantities of water for the preparation of dialysis fluid. Such water meets national standards and international standards but a considerable disparity exists between such standards with respect to microbiological purity. This study collated and retrospectively analyzed the impact of upgrading water systems from that specified in the US standards to those specified in European standards on clinical measures associated with inflammation in four metropolitan dialysis units for two periods. Two periods were compared, three months prior to and six months post upgrading the water treatment systems. The monthly total erythropoietin dosage and intravenous iron supplementation for each patient were also compared over these periods. Variables with significant pre-post differences were assessed using multivariate models to control for confounding factors. The results indicated significant increases in hemoglobin, ferritin and TSat (all p < 0.0001) and albumin (p = 0.0001) were associated with improvement in water quality. Decreases in CRP and creatinine (both p < 0.0001) were also noted. These findings suggest that the current regulations in the United States set the microbiological limits of water and dialysis fluid inappropriately high, and the limits should be revised downwards, since such an approach is reflected in improvement in markers of inflammation.     

In vitro cytotoxic effect of garlic extract on malignant and nonmalignant cell lines

Cancer is one of the major causes of death in the world and despite many years of research, the treatment of cancer is still a problem. Epidemiological observations and laboratory studies have indicated anticarcinogenic potential of garlic, which has been traditionally used for various human diseases around the world. In this study the cytotoxicity of garlic extract against three malignant cancer cell lines including gastric (AGS), breast (MCF-7) and colon (HT-29) and a nonmalignant cell line (L929) were evaluated by the MTT assay. The results of this study reveal MCF-7 and AGS cells were sensitive to garlic extract. Despite a many reports on inhibitory effects of garlic on cancer cell line, our data showed these effects are tumor specific and dose dependent. Further studies on animal models and humans are needed to clarify the important molecules and their mechanisms.     

Synthesis with improved yield and study on the analgesic effect of 2-hydroxyphencyclidine

Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP) has shown analgesic effects. Some of its derivatives have been synthesized and their biological properties were studied. Since a hydroxyl group has been added to the position 2 of the cyclohexane ring of PCP, this compound would be more hydrophilic than PCP. This compound was synthesized using a different and improved method with a higher yield. Its analgesic effect was studied using the tail-flick test on rats and was compared with that of ketamine (CAS 1867-66-9). The results showed that 2-hydroxyphencyclidine can increase tail-flick latencies as compared to the control group and indicate that the maximum analgesic effect of this compound occurs 2-5 min after its injection while the effect of ketamine is observed 10-25 min after injection.