Lack of an association between connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 and lymphotoxin-alpha genes and acute coronary syndrome in Czech Caucasians

BACKGROUND:

The majority of acute coronary syndrome (ACS) cases cannot be explained by the analysis of commonly recognized risk factors; thus, the analysis of possible genetic predispositions is of interest. The genes for connexin-37, stromelysin-1, plasminogen activator-inhibitor type 1 (PAI-1) and lymphotoxin-alpha are among many presently known candidate genes that are associated with risk factors for ACS.

OBJECTIVE:

To identify the potential impact of the functional variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha on ACS in a Caucasian Czech population.

METHODS:

A total of 1399 consecutive patients (1016 men and 383 women) with ACS from five coronary care units located in Prague (Czech Republic) were analyzed; a representative sample of 2559 healthy individuals (1191 men and 1368 women) were also genotyped and served as controls.

RESULTS:

The gene variants analyzed were not significantly associated with the prevalence of ACS or the classical risk factors of ACS development such as high plasma lipid levels, hypertension, diabetes, high body mass index or smoking.

CONCLUSION:

In a Caucasian Czech population sample, genetic variants of connexin-37, stromelysin-1, PAI-1 and lymphotoxin-alpha were not significantly associated with a predisposition toward ACS.     

Right-left discrimination is related to the right hemisphere

We aimed to determine the functional localisation of right-left discrimination (RLD) by functional MRI (fMRI). In this study, 16 male volunteers were examined. There were three task sessions: one active and two baseline tasks. During the baseline tasks participants were instructed to show numbers with their fingers. The first baseline task was performed with the right hand, the second one with the left hand. During the active (RLD) task participants were also instructed to show numbers. The difference between baseline and active tasks was that during the active task the hand with which the participant should perform the instruction was assigned randomly. Thus, participants were unaware which hand should be used before the instruction command. During RLD, activations occurred in the right-sided frontal, precuneus, postcentral, angular, lingual, and superior temporal gyri. Activations also appeared in the left-sided temporal gyri and precuneus. Of the activations, 76.7% appeared in the right hemisphere, 23.3% in the left hemisphere. Conclusively, we found that RLD is mainly related to the right hemisphere, and requires activation of the parieto-temporo-occipital junction and the visual system including cuneus, precuneus, and gyrus lingualis.     

Diabetes mellitus attenuates the repolarization reserve in mammalian heart

OBJECTIVE: In diabetes mellitus several cardiac electrophysiological parameters are known to be affected. In rodent experimental diabetes models changes in these parameters were reported, but no such data are available in other mammalian species including the dog. The present study was designed to analyse the effects of experimental type 1 diabetes on ventricular repolarization and its underlying transmembrane ionic currents and channel proteins in canine hearts. METHODS AND RESULTS: Diabetes was induced by a single injection of alloxan, a subgroup of dogs received insulin substitution. After the development of diabetes (8 weeks) electrophysiological studies were performed using conventional microelectrodes, whole cell voltage clamp, and ECG. Expression of ion channel proteins was evaluated by Western blotting. The QTc interval and the ventricular action potential duration in diabetic dogs were moderately prolonged. This was accompanied by significant reduction in the density of the transient outward K+ current (I(to)) and the slow delayed rectifier K+ current (I(Ks)), to 54.6% and 69.3% of control, respectively. No differences were observed in the density of the inward rectifier K+ current (I(K1)), rapid delayed rectifier K+ current (I(Kr)), and L-type Ca2+ current (I(Ca)). Western blot analysis revealed a reduced expression of Kv4.3 and MinK (to 25+/-21% and 48+/-15% of control, respectively) in diabetic dogs, while other channel proteins were unchanged (HERG, MiRP1, alpha(1c)) or increased (Kv1.4, KChIP2, KvLQT1). Insulin substitution fully prevented the diabetes-induced changes in I(Ks), KvLQT1 and MinK, however, the changes in I(to), Kv4.3, and Kv1.4 were only partially diminished by insulin. CONCLUSION: It is concluded that type 1 diabetes mellitus, although only moderately, lengthens ventricular repolarization, attenuates the repolarization reserve by decreasing I(to) and I(Ks) currents, and thereby may markedly enhance the risk of sudden cardiac death.     

Fourier transform infrared spectroscopic imaging of cardiac tissue to detect collagen deposition after myocardial infarction

Myocardial infarction often leads to an increase in deposition of fibrillar collagen. Detection and characterization of this cardiac fibrosis is of great interest to investigators and clinicians. Motivated by the significant limitations of conventional staining techniques to visualize collagen deposition in cardiac tissue sections, we have developed a Fourier transform infrared imaging spectroscopy (FT-IRIS) methodology for collagen assessment. The infrared absorbance band centered at 1338 cm(-1), which arises from collagen amino acid side chain vibrations, was used to map collagen deposition across heart tissue sections of a rat model of myocardial infarction, and was compared to conventional staining techniques. Comparison of the size of the collagen scar in heart tissue sections as measured with this methodology and that of trichrome staining showed a strong correlation (R=0.93). A Pearson correlation model between local intensity values in FT-IRIS and immuno-histochemical staining of collagen type I also showed a strong correlation (R=0.86). We demonstrate that FT-IRIS methodology can be utilized to visualize cardiac collagen deposition. In addition, given that vibrational spectroscopic data on proteins reflect molecular features, it also has the potential to provide additional information about the molecular structure of cardiac extracellular matrix proteins and their alterations.     

The contribution of vascular smooth muscle, elastin and collagen on the passive mechanics of porcine carotid arteries

The main components responsible for the mechanical behavior of the arterial wall are collagen, elastin, and smooth muscle cells (SMCs) in the medial layer. We determined the structural and mechanical changes in porcine carotid arteries after administration of Triton? X-100, elastase, and collagenase using the inflation-deflation test. The arteries were intraluminarly pressurized from 0 to 200 mmHg, and the outer diameter of the artery was measured. The pressure-strain elastic modulus was determined based on the pressure/diameter ratio. The intima-media thickness, wall thickness, thickness of the tunica adventitia layer, and the area fractions of SMCs, elastin, and collagen within the arterial wall (A(A)(SMC/elastin/collagen, wall)) were measured using stereological methods. The relative changes in the relevant components of the treated samples were as follows: the decrease in A(A)(SMC, wall) after administration of Triton? X-100 was 11% ± 7%, the decrease in A(A)(elastin, wall) after administration of elastase was 40% ± 22%, and the decrease in A(A)(collagen, wall) after the application of collagenase was 51% ± 22%. The Triton? X-100 treatment led to a decrease in the SMC content that was associated with enlargement of the arterial wall (outer diameter) for pressures up to 120 mmHg, and with mechanical stiffening of the arterial wall at higher pressures. Elastase led to a decrease in the elastin content that was associated with enlargement of the arterial wall, but not with stiffening or softening. Collagenase led to a decrease in collagen content that was associated with a change in the stiffness of the arterial wall, although the exact contribution of mechanical loading and the duration of treatment (enlargement) could not be quantified.     

Inhibition of soluble epoxide hydrolase by cis-4-[4-(3-adamantan-1-ylureido)cyclohexyl-oxy]benzoic acid exhibits antihypertensive and cardioprotective actions in transgenic rats with angiotensin II-dependent hypertension

The present study was undertaken to evaluate the effects of chronic treatment with c-AUCB {cis-4-[4-(3-adamantan-1-ylureido)cyclohexyl-oxy]benzoic acid}, a novel inhibitor of sEH (soluble epoxide hydrolase), which is responsible for the conversion of biologically active EETs (epoxyeicosatrienoic acids) into biologically inactive DHETEs (dihydroxyeicosatrienoic acids), on BP (blood pressure) and myocardial infarct size in male heterozygous TGR (Ren-2 renin transgenic rats) with established hypertension. Normotensive HanSD (Hannover Sprague-Dawley) rats served as controls. Myocardial ischaemia was induced by coronary artery occlusion. Systolic BP was measured in conscious animals by tail plethysmography. c-AUCB was administrated in drinking water. Renal and myocardial concentrations of EETs and DHETEs served as markers of internal production of epoxygenase metabolites. Chronic treatment with c-AUCB, which resulted in significant increases in the availability of biologically active epoxygenase metabolites in TGR (assessed as the ratio of EETs to DHETEs), was accompanied by a significant reduction in BP and a significantly reduced infarct size in TGR as compared with untreated TGR. The cardioprotective action of c-AUCB treatment was completely prevented by acute administration of a selective EETs antagonist [14,15-epoxyeicosa-5(Z)-enoic acid], supporting the notion that the improved cardiac ischaemic tolerance conferred by sEH inhibition is mediated by EETs actions at the cellular level. These findings indicate that chronic inhibition of sEH exhibits antihypertensive and cardioprotective actions in this transgenic model of angiotensin II-dependent hypertension.     

Short-coherence off-axis holographic phase microscopy of live cell dynamics

We demonstrate a single-shot holographic phase microscope that combines short-coherence laser pulses with an off-axis geometry. By introducing a controlled pulse front tilt, ultrashort pulses are made to interfere over a large field-of-view without loss of fringe contrast. With this microscope, quantitative phase images of live cells can be recorded in a full-field geometry without moving parts. We perform phase imaging of HEK293 cells, to study the dynamics of cell volume regulation in response to an osmotic shock.OCIS codes: (110.0110) Imaging systems, (090.1995) Digital holography, (170.1650) Coherence imaging, (320.7160) Ultrafast technology, (170.1530) Cell analysis     

Long-term survival of solid embryonic cerebellar grafts in Lurcher mice

The periaqueductal gray (PAG) is important for the organization of organismal response to different types of stress and painful stimuli. Its dorsolateral (dlPAG) column is distinctly characterized by the presence of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), which in many brain regions, is an indication of constitutive nitric oxide (NO) synthase (NOS)-containing neurons. Different stress paradigms activate the dlPAG NOS machinery presumably by a presynaptic influence of NO on dlPAG neurons to modulate the nuclear dynamics to elicit an appropriate response. Since presynaptic components of synapses reside in axonal varicosities, this study assessed the number of varicosities and inter-varicosity spacing of NADPH-d neurons in the dlPAG of free-behaving (control) and acutely restrained male rats. The study tested the hypothesis that stress-induced increase in endogenous NO synthesis involved changes in synaptic density and inter-varicosity spacing and therefore, a non-synaptic component of NO involvement in the dlPAG response to stress. Compared with control, the number of NADPH-d-positive cells, the staining intensity and the number of varicosities per microgram tissue were significantly higher in restrained animals. Also, the inter-varicosity spacing was significantly higher in control than restrained rats, presumably due to the increase in varicosities induced by restraint. Since neural connectivity and synaptogenesis depend on mean varicosity spacing and pattern of varicosity, respectively, the present observations suggest a mechanism whereby restraint stress induces increased activity via synaptic and non-synaptic NO-mediated neurotransmission within the dlPAG.