Association of the 894G>T polymorphism in the endothelial nitric oxide synthase gene with risk of acute myocardial infarction

Background: This study was designed to investigate the association of the 894G>T polymorphism in the eNOS gene with risk of acute myocardial infarction (AMI), extent of coronary artery disease (CAD) on coronary angiography, and in-hospital mortality after AMI. Methods: We studied 1602 consecutive patients who were enrolled in the GEMIG study. The control group was comprised by 727 individuals, who were randomly selected from the general adult population. Results: The prevalence of the Asp298 variant of eNOS was not found to be significantly and independently associated with risk of AMI (RR = 1.08, 95%CI = 0.77–1.51, P = 0.663), extent of CAD on angiography (OR = 1.18, 95%CI = 0.63–2.23, P = 0.605) and in-hospital mortality (RR = 1.08, 95%CI = 0.29–4.04, P = 0.908). Conclusion: In contrast to previous reports, homozygosity for the Asp298 variant of the 894G>T polymorphism in the eNOS gene was not found to be associated with risk of AMI, extent of CAD and in-hospital mortality after AM

Gene Expression Profiling in Gastric Mucosa from Helicobacter pylori-Infected and Uninfected Patients Undergoing Chronic Superficial Gastritis

Helicobacter pylori infection reprograms host gene expression and influences various cellular processes, which have been investigated by cDNA microarray using in vitro culture cells and in vivo gastric biopsies from patients of the Chronic Abdominal Complaint. To further explore the effects of H. pylori infection on host gene expression, we have collected the gastric antral mucosa samples from 6 untreated patients with gastroscopic and pathologic confirmation of chronic superficial gastritis. Among them three patients were infected by H. pylori and the other three patients were not. These samples were analyzed by a microarray chip which contains 14,112 cloned cDNAs, and microarray data were analyzed via BRB ArrayTools software and Ingenuity Pathways Analysis (IPA) website. The results showed 34 genes of 38 differentially expressed genes regulated by H. pylori infection had been annotated. The annotated genes were involved in protein metabolism, inflammatory and immunological reaction, signal transduction, gene transcription, trace element metabolism, and so on. The 82% of these genes (28/34) were categorized in three molecular interaction networks involved in gene expression, cancer progress, antigen presentation and inflammatory response. The expression data of the array hybridization was confirmed by quantitative real-time PCR assays. Taken together, these data indicated that H. pylori infection could alter cellular gene expression processes, escape host defense mechanism, increase inflammatory and immune responses, activate NF-κB and Wnt/β-catenin signaling pathway, disturb metal ion homeostasis, and induce carcinogenesis. All of these might help to explain H. pylori pathogenic mechanism and the gastroduodenal pathogenesis induced by H. pylori infection

Hadamard and Dragomir-Agarwal inequalities, higher-order convexity and the Euler formula

We obtain bounds relating to Euler's formula for the case of a function with higher--order convexity properties. These are used to derive estimates of the error involved in the use of the trapezoidal formula for integrating such a function

The Growth of Hearing Loss in Neonatal Chicks Exposed to Intense Pure Tones.

One-day-old chicks were exposed to an intense pure tone (0.9 kHz, 120 dB SPL) and assigned to one of eight groups based on continuous exposure durations from 1 to 200 h. As each animal was removed from the exposure, it was anesthetized and an electrode was placed in the nucleus magnocellularis. Sound-evoked potentials were used to measure absolute thresholds and frequency selectivity. Thresholds were measured at 10 frequencies between 0.1 and 4.5 kHz while frequency selectivity was assessed by a simultaneous masking tuning-curve procedure at five probe-tone frequencies between 0.3 and 2.5 kHz. Threshold shift was greatest at 1.3 kHz and reached a maximum loss of approximately 57 dB between 48 and 200 h of exposure. The shape of the threshold-shift curve as a function of exposure duration (for frequencies between 0.9 and 2.5 KHz) suggested the presence of an early and late effect. The loss in tuning sharpness was evaluated by comparing the values of Q10 dB for control and exposed tuning curves and expressing the difference between them as a percent change. Probe-tone tuning curves above 0.9 kHz became less selective as exposure duration increased. A maximum decrease in tuning of about 54 percent was reached by 48 h and this remained constant to 200 h. The low-frequency tuning curves (below 0.9 kHz) did not show any systematic loss in selectivity. The changes in sensitivity and selectivity are discussed in relation to the patterns of cochlear injury that occurred on the basilar papilla as exposure duration lengthened

Mapping of the discontinuous H-kininogen binding site of plasma prekallikrein. Evidence for a critical role of apple domain-2

Plasma prekallikrein, a zymogen of the contact phase system, circulates in plasma as heterodimeric complex with H-kininogen. The binding is mediated by the prekallikrein heavy chain consisting of four apple domains, A1 to A4, to which H-kininogen binds with high specificity and affinity (K(D) = 1.2 x 10(-8) M). Previous work had demonstrated that a discontinuous kininogen-binding site is formed by a proximal part located in A1, a distal part exposed by A4, and other yet unidentified portion(s) of the kallikrein heavy chain. To detect relevant binding segment(s) we recombinantly expressed single apple domains and found a rank order of binding affinity for kininogen of A2 > A4 approximately A1 > A3. Removal of single apple domains in prekallikrein deletion mutants reduced kininogen binding by 21 (A1), 64 (A2), and 24% (A4), respectively, whereas deletion of A3 was without effect. Transposition of homologous A2 domain from prekallikrein to factor XI conferred high-affinity kininogen binding from the former to the latter. The principal role of A2 for H-kininogen docking to the prekallikrein heavy chain was further substantiated by the finding that cleavage of a single peptide bond in A2 drastically diminished the H-kininogen binding affinity. Furthermore, the epitope of monoclonal antibody PKH6 which blocks kallikrein-kininogen complex formation with an IC(50) of 8 nM mapped to the center portion of domain A2. Our data indicate that domain A2 and two flanking sequence segments of A1 and A4 form a discontinuous binding platform for H-kininogen on the prekallikrein heavy chain. Domain-specific antibodies directed to these critical sites efficiently interfered with contact phase-induced bradykinin release from H-kininoge

Threshold shift, hair cell loss, and hair bundle stiffness following exposure to 120 and 125 dB pure tones in the neonatal chick.

One-day old chicks were exposed to one of two pure tone stimuli (0.9 kHz at 120 or 125 dB SPL) for 48 h. Three major results arose from a variety of tests that assessed the structural and functional consequences of the exposure on the peripheral auditory system at either 0 days or 12 to 15 days recovery. First, brainstem response data showed that the 120 and 125 dB groups had maximum evoked potential threshold shifts of 57 and 71 dB immediately after removal from the sound. Fifteen days post-exposure, the thresholds in the 120 dB group returned to near-normal levels, while in the 125 dB group, recovery was within 19 dB of control thresholds. Second, scanning electron microscopic measurements of hair cell density within the lesion showed that at 0 days recovery, the 120 and 125 dB groups had a 30% and 59% short hair cell loss, respectively, but by 15 days no differences could be identified between the exposed and control animals, regardless of exposure level. Finally, at 0 days of recovery, micromechanical stimulation data did not reveal any significant difference in stiffness between the control and surviving hair cells in the lesion area. Although the more intense exposure induced greater structural and functional damage in the chick cochlea, the birds retained or even enhanced their ability to replace lost hair cells and had partial hearing recovery by 15 days post-exposure

Angiotensin-converting enzyme inhibitor induced angioedema of the head and neck.

Angiotensin-converting enzyme (ACE) inhibitors are now in widespread use for the treatment of essential and renovascular hypertension. Consequently, angioedema, an uncommon complication of ACE inhibitor therapy is being encountered with increasing frequency. Since ACE inhibitor angioedema predominantly involves the face, lips, oral cavity, and occasionally the larynx the otolaryngologist is often consulted to evaluate affected patients. Treatment ranges from simple cessation of the drug to emergent airway intervention. The pertinent pharmacologic properties of ACE inhibitors and the pathophysiology of angioedema are discussed. The authors\u27 experience with the evaluation and treatment of ACE inhibitor induced angioedema is presented