Reopening of L-type calcium channels in human ventricular myocytes during applied epicardial action potentials

AIMS: Present study was performed to compare the dynamics of human L-type calcium current (ICa,L) flowing during rectangular voltage pulses, voltage ramps, and action potentials (APs) recorded from epicardiac and endocardiac canine ventricular cells. METHODS: ICa,L was recorded in single myocytes isolated from undiseased human hearts using the whole cell voltage clamp technique. RESULTS: The decay of ICa,L was monotonic when using rectangular pulses or endocardial APs as voltage commands, whereas the current became double-peaked (displaying a second rise and fall) during epicardial (EPI) APs or voltage ramps used to mimic EPI APs. These ICa,L profiles were associated with single-hooked and double-hooked phase-plane trajectories, respectively. No sustained current was observed during the AP commands. Kinetics of deactivation and recovery from inactivation of human ICa,L were determined using twin-pulse voltage protocols and voltage ramps, and the results were similar to those obtained previously in canine cells under identical experimental conditions. CONCLUSIONS: ICa,L can inactivate partially before and deactivate during the phase-1 repolarization of the epicardiac AP, and reopening of these channels seems to be associated with formation of the dome.     

Antibody response after RSV infection in children younger than 1 year of age living in a rural area of Mozambique

Serological responses have been studied in respiratory syncytial virus (RSV) infected children < 1 year of age attending the outpatient department of the Manhiça District Hospital (Mozambique). Molecular characterization of viral RNA in nasopharyngeal aspirates from the infected children indicated a high level of genetic uniformity among the infecting viruses, all of which belonged to a single genotype of RSV group A. A representative virus strain, Moz00, was isolated from one of the infants and was used, together with the group A strain A2 and the group B strain 8/60, as antigens in the quantification of infant antibody responses. In this study, 97.5% (39/40) and 96.4% (27/28) of infected children produced an antibody response against Moz00 detected by the membrane fluorescent antibody test (MFAT) and the neutralization test (NT), respectively. Seroconversion rates decreased when the A2 and 8/60 strains were used as antigen in MFAT (95.4% and 88.2%, respectively) or NT (81.8% and 54.5%, respectively), indicating that antibody responses had both group‐ and strain‐specific components. Antibodies in convalescent sera of infected children were compared with maternally derived antibodies detected in a group of children also < 1 year of age, but with no evidence of RSV infection. The convalescent sera exhibited reduced neutralizing capacity when the 8/60 strain was used as antigen (P = 0.028), suggesting that the infant antibody response lacks neutralizing capacity against strains of the heterologous virus group. Restricted cross‐reactivity and neutralizing capacity of antibodies generated by young children might be expected to induce only moderate protection in subsequent epidemics against genetically distant strains. J. Med. Virol. 69:579–587, 2003. © 2003 Wiley‐Liss, Inc.     

Clinical significance of serum hepatitis C virus (HCV) RNA as marker of HCV infection.

We have evaluated the clinical significance of hepatitis C virus (HCV) RNA determination by analyzing a group of 221 hospitalized patients with abnormal liver function tests. Serum HCV RNA was detected by "nested" PCR amplification followed by nonisotopic hybridization. Of the 200 (90.5%) patients with anti-HCV-positive enzyme-linked immunosorbent assay results, 152 (76%) were RIBA reactive, 47 (23.5%) had indeterminate results, and 1 (0.5%) was nonreactive. Of the 180 (90%) patients positive for anti-HCV and HCV RNA, 138 (76.7%) were RIBA reactive and 42 (23.3%) were RIBA indeterminate. The pattern of RIBA reactivity did not correlate with the presence of HCV RNA. Elevated alanine aminotransferase levels were associated neither with the presence of viremia nor with the RIBA pattern. Histological findings consistent with non-A non-B hepatitis correlated with the presence of HCV RNA but not with the RIBA pattern. HCV RNA was detected in 11 of 21 (52.4%) anti-HCV-negative patients. These 11 patients were either immunosuppressed or in the prodromic phase of acute hepatitis C. Circulating HCV RNA can therefore be described as being predictive of virus-induced liver damage in anti-HCV-positive patients and may be useful in the diagnosis of HCV infection in anti-HCV-negative immunosuppressed patients or in those with early acute infection.     

A novel frame shift mutation in the HMG box of the SRY gene in a patient with complete 46,XY pure gonadal dysgenesis.

Pure gonadal dysgenesis or Swyer syndrome is a sex-reversal disorder resulting from embryonic testicular regression sequences especially during the first few weeks of fetal life and is induced by mutations in the SRY gene. In the present report, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis. Molecular analysis using sequential PCR to detect Y chromosomal microdeletions showed the presence of SRY, ZFY and AZFa, b and c regions. Automated sequencing of the SRY region revealed a new mutation (deletion of A (adenine) in codon 82 at position +244), leading to a frame shift mutation within the helix I of the HMG-box domain. This mutation generates a truncated protein and is very likely to produce an impairment of SRY DNA binding activity. The present findings further support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.     

Contributions to the kinetics of the acetylcholine-receptor function

Summary 1. Action-concentration curves have been plotted for the stimulation of the cat's superior cervical ganglion by acetylcholine. The free and the innervated receptors of the postsynaptic membrane, described by the authors, have been studied separately from this point of view.2. In the case of both the free and the innervated receptors, the action-concentration curves were similar in shape to the enzyme-substrate curve of cholinesterase. Analyzing these curves by the method of Lineweaver and Burk, in the case of free receptors, the dissociation constants of acetylcholine turned out to be: with stimulating RS complexes: 5.4·10^–6–2.1·10^–5M, with inhibitory RS ₂ complexes: 3.2·10^–5 – 5.2·10^–5 M. The pertaining values for innervated receptors were 3.45 · 10^–5 and 2.22 · 10^–4 M, respectively.3. The parallelisms and divergences between the cholinesterase and acetylcholine-receptor functions are discussed.With 4 Figures in the Text     

Effect of Hypolaetin-8-Glucoside on Human Platelet Aggregation induced by ADP

Hypolaetin-8-glucoside, a flavonoid isolated from SIDERITIS MUGRONENSIS possessing anti-inflammatory activity inhibited dose-dependently the human PRP aggregation induced by ADP with a IC (50) = 2.4 x 10 (-4) M. This action does not seem to be related to cyclo-oxygenase, as this flavonoid is not an inhibitor and even is able to act as a cofactor for this enzyme.     

Surgical management of aortic coarctation associated with ruptured cerebral artery aneurysm

We report two patients with coarctation of the aorta who were admitted to the hospital with ruptured cerebral artery aneurysms. In both patients, we surgically treated the coarctation and later repaired the intracranial lesion. One patient, a 34-year-old woman, is alive and well after 3 years; whereas, the other, a 19-year-old man, did not survive. We discuss the sequence for surgery, which continues to be subjected to debate.     

Physicians' attitudes toward breast self-examination: a pilot study

Recent case control studies suggest that breast self-examination (BSE) is efficacious in the early clinical diagnosis of breast cancer. Population studies also indicate that adoption of this behavior depends largely on physicians. This pilot study was designed to determine whether physicians' attitudes on this subject could be obtained through a mail questionnaire. The results show that a self-administered mail questionnaire can be used successfully in physician studies. Although questionnaire length does affect response rates (78% one page, 69% four page, and 57% eight page), it does not affect either respondent characteristics or question response.     

Influence of the BDNF Val66Met polymorphism on weight loss after bariatric surgery: a 24-month follow-up

BackgroundBariatric surgery is currently the most effective long-term treatment for severe obesity. However, interindividual variation in surgery outcome has been observed, and research suggests a moderating effect of several factors including baseline co-morbidities (e.g., type 2 diabetes [T2D] and genetic factors). No data are currently available on the interaction between T2D and variants in brain derived neurotrophic factor (BDNF) and its effect on weight loss after surgery.ObjectivesTo examine the role of the BDNF Val66Met polymorphism (rs6265) and the influence of T2D and their interaction on weight loss after bariatric surgery in a cohort of patients with severe obesity.SettingUniversity hospital in Spain.MethodsThe present study evaluated a cohort of 158 patients with obesity submitted to bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for 24 months (loss to follow-up: 0%). During the postoperative period, percentage of excess body mass index loss (%EBMIL), percentage of excess weight loss (%EWL), and total weight loss (%TWL) were evaluated.ResultsLongitudinal analyses showed a suggestive effect of BDNF genotype on the %EWL (P = .056) and indicated that individuals carrying the methionine (Met) allele may experience a better outcome after bariatric surgery than those with the valine/valine (Val/Val) genotype. We found a negative effect of a T2D diagnosis at baseline on %EBMIL (P = .004). Additionally, we found an interaction between BDNF genotype and T2D on %EWL and %EBMIL (P = .027 and P = .0004, respectively), whereby individuals with the Met allele without T2D displayed a greater %EWL and greater %EBMIL at 12 months and 24 months than their counterparts with T2D or patients with the Val/Val genotype with or without T2D.ConclusionOur data showed an association between the Met variant and greater weight loss after bariatric surgery in patients without T2D. The presence of T2D seems to counteract this positive effect.