Relaxant effects of pravastatin, atorvastatin and cerivastatin on isolated rat aortic rings

Increasing evidence suggests that statins may have pleiotropic effects on vascular wall independent of their cholesterol lowering properties. In the present study, we investigated the acute vascular effects of pravastatin, atorvastatin and cerivastatin on rat isolated aortic rings. Statins effectively and comparably relaxed the aortic rings precontracted submaximally with noradrenaline, in a concentration-dependent manner, in which a high potency was observed with cerivastatin. Endothelium removal or incubation of the aortic rings with nitric oxide synthase inhibitor L-NOARG (10(-4) M) and/or cyclooxygenase inhibitor indomethacin (10(-5) M) significantly attenuated the acute vasorelaxation induced by either of statin. Additionally, different from the other two statins, a significant reduction was observed in response to cerivastatin in the presence of KATP channel inhibitor, glibenclamide (10(-5) M) and Na+- K+ ATPase inhibitor, ouabain (10(-4) M). Furthermore, pretreatment of the rings with the cholesterol precursor mevalonate (10(-3) M) significantly inhibited the endothelium-mediated relaxant effects of the statins. Our findings suggest that statins could acutely modulate vascular tone importantly by endothelium-dependent and mevalonate-related pathways.     

Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome

Andersen's syndrome is characterized by periodic paralysis, cardiac arrhythmias, and dysmorphic features. We have mapped an Andersen's locus to chromosome 17q23 near the inward rectifying potassium channel gene KCNJ2. A missense mutation in KCNJ2 (encoding D71V) was identified in the linked family. Eight additional mutations were identified in unrelated patients. Expression of two of these mutations in Xenopus oocytes revealed loss of function and a dominant negative effect in Kir2.1 current as assayed by voltage-clamp. We conclude that mutations in Kir2.1 cause Andersen's syndrome. These findings suggest that Kir2.1 plays an important role in developmental signaling in addition to its previously recognized function in controlling cell excitability in skeletal muscle and heart.     

Steering vaccinomics innovations with anticipatory governance and participatory foresight

Vaccinomics is the convergence of vaccinology and population-based omics sciences. The success of knowledge-based innovations such as vaccinomics is not only contingent on access to new biotechnologies. It also requires new ways of governance of science, knowledge production, and management. This article presents a conceptual analysis of the anticipatory and adaptive approaches that are crucial for the responsible design and sustainable transition of vaccinomics to public health practice. Anticipatory governance is a new approach to manage the uncertainties embedded on an innovation trajectory with participatory foresight, in order to devise governance instruments for collective "steering" of science and technology. As a contrast to hitherto narrowly framed "downstream impact assessments" for emerging technologies, anticipatory governance adopts a broader and interventionist approach that recognizes the social construction of technology design and innovation. It includes in its process explicit mechanisms to understand the factors upstream to the innovation trajectory such as deliberation and cocultivation of the aims, motives, funding, design, and direction of science and technology, both by experts and publics. This upstream shift from a consumer "product uptake" focus to "participatory technology design" on the innovation trajectory is an appropriately radical and necessary departure in the field of technology assessment, especially given that considerable public funds are dedicated to innovations. Recent examples of demands by research funding agencies to anticipate the broad impacts of proposed research--at a very upstream stage at the time of research funding application--suggest that anticipatory governance with foresight may be one way how postgenomics scientific practice might transform in the future toward responsible innovation. Moreover, the present context of knowledge production in vaccinomics is such that policy making for vaccines of the 21st century is occurring in the face of uncertainties where the "facts are uncertain, values in dispute, stakes high and decisions urgent and where no single one of these dimensions can be managed in isolation from the rest." This article concludes, however, that uncertainty is not an accident of the scientific method, but its very substance. Anticipatory governance with participatory foresight offers a mechanism to respond to such inherent sociotechnical uncertainties in the emerging field of vaccinomics by making the coproduction of scientific knowledge by technology and the social systems explicit. Ultimately, this serves to integrate scientific and social knowledge thereby steering innovations to coproduce results and outputs that are socially robust and context sensitive.     

Assessment of Atrial Electromechanical Delay by Tissue Doppler Echocardiography in Obese Subjects

Our aim was to evaluate whether atrial electromechanical delay measured by tissue Doppler imaging (TDI), which is an early predictor of atrial fibrillation (AF) development, is prolonged in obese subjects. A total of 40 obese and 40 normal‐weight subjects with normal coronary angiograms were included in this study. P‐wave dispersion (PWD) was calculated on the 12‐lead electrocardiogram (ECG). Systolic and diastolic left ventricular (LV) functions, inter‐ and intra‐atrial electromechanical delay were measured by TDI and conventional echocardiography. Inter‐ and intra‐atrial electromechanical delay were significantly longer in the obese subjects compared with the controls (44.08 ± 10.06 vs. 19.35 ± 5.94 ms and 23.63 ± 6.41 vs. 5.13 ± 2.67 ms, P < 0.0001 for both, respectively). PWD was higher in obese subjects (53.40 ± 5.49 vs. 35.95 ± 5.93 ms, P < 0.0001). Left atrial (LA) diameter, LA volume index and LV diastolic parameters were significantly different between the groups. Interatrial electromechanical delay was correlated with PWD (r = 0.409, P = 0.009), high‐sensitivity C‐reactive protein (hsCRP) levels (r = 0.588, P < 0.0001). Interatrial electromechanical delay was positively correlated with LA diameter, LA volume index, and LV diastolic function parameters consisting of mitral early wave (E) deceleration time (DT) and isovolumetric relaxation time (IVRT; r = 0.323, P = 0.042; r = 0.387, P = 0.014; r = 0.339, P = 0.033; r = 0.325, P = 0.041; respectively) and, negatively correlated with mitral early (E) to late (A) wave ratio (E/A) (r = ?0.380, P = 0.016) and myocardial early‐to‐late diastolic wave ratio (E_m/A_m) (r = ?0.326, P = 0.040). This study showed that atrial electromechanical delay is prolonged in obese subjects. Prolonged atrial electromechanical delay is due to provoked low‐grade inflammation as well as LA enlargement and early LV diastolic dysfunction in obese subjects.     

Analysis of the DOK1 gene in breast cancer

Molecular Biology Reports - Breast cancer, which is the most common type of cancer among women, is a heterogenous disease. It results from progressive accumulation of genetic and epigenetic...     

Changes in chemical compositions of substrates before and after <Emphasis Type="Italic">Ganoderma lucidum</Emphasis> cultivation

After the commercial cultivation of Ganoderma lucidum, that is becoming increasingly popular because of its valuable medicinal effects, a large amount of Ganoderma spent substrate (GSS) remains as a residual material. It is important to identify differences in the chemical compositions among GSS to indicate their suitability. This study was carried out to characterize and evaluate the substrates and GSS for the some chemical contents such as; pH, EC, organic carbon (C), total nitrogen (N), macro and micro elements and C:N ratios. The substrates were prepared by the mixtures of hornbeam and oak sawdust supplemented with wheat bran in a ratio of 20% (20WB) and tea manufacture waste in different ratios (10, 15, 20 and 25%). Organic C, C:N and pH values decreased in GSS, while N, P, K, Mg, Fe, Mn and Zn contents increased. EC and pH values of GSS varied between 1.13 and 2.33 dS m⁻¹, and 5.14 and 5.69, respectively. GSS was found rich in all investigated mineral nutrients. The highest increases in all nutrient contents were generally determined in hornbeam sawdust with 20TW spent substrate. Initial mineral composition of the wastes influenced the mineral composition of the substrates and spent substrates.     

Neural stem cells: historical perspective and future prospects

How a single fertilized cell generates diverse neuronal populations has been a fundamental biological problem since the 19(th) century. Classical histological methods revealed that postmitotic neurons are produced in a precise temporal and spatial order from germinal cells lining the cerebral ventricles. In the 20(th) century, DNA labeling and histo- and immunohistochemistry helped to distinguish the subtypes of dividing cells and delineate their locations in the ventricular and subventricular zones. Recently, genetic and cell biological methods have provided insights into sequential gene expression and molecular and cellular interactions that generate heterogeneous populations of NSCs leading to specific neuronal classes. This precisely regulated developmental process does not tolerate significant in?vivo deviation, making replacement of adult neurons by NSCs during pathology a colossal challenge. In contrast, utilizing the trophic factors emanating from the NSC or their derivatives to slow down deterioration or prevent death of degenerating neurons may be a more feasible strategy.