Human sperm pattern of movement during chemotactic ＇e-orientation towards a progesterone source

Human spermatozoa may chemotactically find out the egg by following an increasing gradient of attractant molecules. Although human spermatozoa have been observed to show several of the physiological characteristics of chemotaxis, the chemotactic pattern of movement has not been easy to describe. However, it is apparent that chemotactic cells may be identified while returning to the attractant source. This study characterizes the pattern of movement of human spermatozoa during chemotactic re-orientation towards a progesterone source, which is a physiological attractant candidate. By means of videomicroscopy and image analysis, a chemotactic pattern of movement was identified as the spermatozoon returned towards the source of a chemotactic concentration of progesterone (10 pmol l⁻¹). First, as a continuation of its original path, the spermatozoon swims away from the progesterone source with linear movement and then turns back with a transitional movement that can be characterized by an increased velocity and decreased linearity. This sperm behaviour may help the spermatozoon to re-orient itself towards a progesterone source and may be used to identify the few cells that are undergoing chemotaxis at a given time.     

Changes with ageing in several leukocyte functions of male and female rats

The impairment of the immune system with aging, or immunosenescence, appears to contribute to the increased morbidity and mortality of aged subjects. T cell functions and Natural Killer activity seem to be the immune responses most affected by ageing. Since the immune system works more efficiently in females than in males, we have studied the changes of several immune functions with age in rats of both sexes. In addition, we have investigated if ovariectomy, a model of menopause in rats, produces a loss of this gender-related advantage. In the present work, the changes with age (2, 6, 12, 14, 18, 22 and 24 months old) in lymphocyte chemotaxis, T lymphoproliferative response to the mitogen ConA, IL-2 release and Natural Killer activity of cells from axillary nodes and spleen of male and female rats as well as of females ovariectomized at 12 months of age have been studied. An age-related decrease was found in all investigated functions, with a slightly different evolution depending on the immune organ and gender considered. In general, the data obtained show that a certain degree of immunosenescence takes place with age in rats, with males being less immunocompetent than intact age-matched females, but showing an immune response similar to that of ovariectomized animals.     

Impact of a Standardized Titration Protocol with Carvedilol in Heart Failure: Safety,Tolerability, and Efficacy—A Report from the GESICA Registry

Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA) studied whether a standardized protocol for the initiation and titration of the β-blocker carvedilol in a multicenter, open-label program would optimize β-blocker use in heart failure (HF) patients. The program included: (1) the carvedilol initiation and titration period, and (2) long-term follow-up at 6 and 12 months. Of 1299 patients in the registry, 504 were excluded due to current therapy; of the remaining 795 eligible patients, 293 were excluded due to contraindications. Of the included patients with follow-up data (n = 316), 93.3% tolerated carvedilol initiation and 47.7% of the patients reached the target dose of 50 mg/day for a mean dose of 39 mg/day. Rates were comparable in the elderly (n = 83), of which 53% achieved a target dose for a mean dose of 43.08 mg/day. This protocol improved therapy rates and achieved target doses quickly (average of 4 visits). Concomitant medications did not have to be adjusted and there were low withdrawal rates (10%) and hospital admissions (7.2%) for HF. Patients were able to maintain carvedilol therapy at 6 and 12 months. These results indicate that a standardized titration protocol, as used in GESICA, for the initiation and titration of β-blockers is well tolerated and may improve β-blocker use in carefully selected heart failure patients.The study authors are members of the GESICA Steering Committee and Subcommittees     

Beta-blockers alprenolol and carvedilol stimulate beta-arrestin-mediated EGFR transactivation

Recent evidence suggests that binding of agonist to its cognate receptor initiates not only classical G protein-mediated signaling, but also beta-arrestin-dependent signaling. One such beta-arrestin-mediated pathway uses the beta(1)-adrenergic receptor (beta(1)AR) to transactivate the EGFR. To determine whether beta-adrenergic ligands that do not activate G protein signaling (i.e., beta-blockers) can stabilize the beta(1)AR in a signaling conformation, we screened 20 beta-blockers for their ability to stimulate beta-arrestin-mediated EGFR transactivation. Here we show that only alprenolol (Alp) and carvedilol (Car) induce beta(1)AR-mediated transactivation of the EGFR and downstream ERK activation. By using mutants of the beta(1)AR lacking G protein-coupled receptor kinase phosphorylation sites and siRNA directed against beta-arrestin, we show that Alp- and Car-stimulated EGFR transactivation requires beta(1)AR phosphorylation at consensus G protein-coupled receptor kinase sites and beta-arrestin recruitment to the ligand-occupied receptor. Moreover, pharmacological inhibition of Src and EGFR blocked Alp- and Car-stimulated EGFR transactivation. Our findings demonstrate that Alp and Car are ligands that not only act as classical receptor antagonists, but can also stimulate signaling pathways in a G protein-independent, beta-arrestin-dependent fashion.     

Increased risk of tuberculosis in patients with rheumatoid arthritis

OBJECTIVE: To quantify the risk of tuberculosis (TB) in an unselected sample of patients with rheumatoid arthritis (RA) compared to the risk in the general population. METHODS: The incidence of TB in the general population of Spain was obtained from the National Network of Epidemiological Surveillance reports. The incidence of TB was ascertained from a cohort of 788 patients with RA selected randomly from the registries of 34 participating centers throughout Spain. A patient was considered a TB case only if information about disease symptoms, microorganism identification, and TB treatment were confirmed in the clinical records. The relative risk of TB in RA was calculated by dividing the standardized mean incidence of TB from 1990 to 2000 in the RA cohort by the mean incidence of TB in Spain during the same years. RESULTS: The mean incidence of TB in the general population of Spain from 1990 to 2000 was 23 cases per 100,000. Seven cases of TB were identified in the RA cohort, yielding a mean annual incidence (1990-2000) of 134/100,000 patients. The incidence risk ratio of pulmonary TB in patients with RA compared to the general population is 3.68 (95% CI 2.36-5.92). CONCLUSION: We found a 4-fold increased risk of TB infection in patients diagnosed with RA. These results might help to interpret the magnitude of the problem attributable to the introduction of new therapies in RA.     

Peritoneal and intestinal tuberculosis: an ancestral disease that poses new challenges in the technological era. Case report and review of the literature

Tuberculosis is a public health problem. The most common presentation is pulmonary disease. The diagnosis of any extrapulmonary forms are quite difficult. Clinical manifestations of gastrointestinal tuberculosis are non-specific and compatible with pathologies such as inflammatory bowel disease, advanced ovarian cancer, deep mycosis, yersinia infection and amebomas. Abdominal form is located at 6th place of the extrapulmonary forms, after lymphatic, genitourinary, osteoarticular, miliary and meningeal infections. Eventually, 25 to 75% of patients with abdominal tuberculosis will require surgery. These procedures should be limitated with the purpose to preserve small bowel. Resection should be limitated for complicated cases. The surgical indications include: Intestinal occlusion (15-60%), perforation (1-15%), abscesses and fistulas (2-30%) and hemorrhage (2%). CONCLUSIONS: In most of the cases, the diagnosis of peritoneal or intestinal tuberculosis is made during a laparoscopy or laparotomy even during surgery performed by different purposes. Excessive manipulation of the intraabdominal organs may produced unexpected bowel lesions, increasing morbidity and mortality. Medical treatment is highly effective in the resolution of moderate complications such as bowel obstruction. Resectional procedures should be reserved for complications like perforation, bleeding or stenosis non-suitable for stricturoplasty.     

The MPO Study: just a European HEMO Study or something very different?

Although results from observational and epidemiological studies suggested a survival benefit associated with high-flux hemodialysis, conclusive evidence from prospective randomized clinical trials has been lacking. Both the HEMO Study in the USA and the Membrane Permeability Outcome Study (MPO Study) in Europe are randomized studies investigating the effect of high- and low-flux hemodialysis on patient outcomes, even though there were some significant differences in the design of the two studies. An earlier randomized clinical trial could not show differences on patient survival between patient groups being treated with membranes of different material and permeability, but this trial was not designed specifically to examine this particular endpoint. Based on these previous experiences, the MPO Study addressed a hemodialysis patient population which was considered to be more susceptible to the intervention with high-flux dialysis. To identify these patients with an elevated risk, low serum albumin levels were chosen as an indicator; low serum albumin is associated with malnutrition, inflammation, atherosclerosis, and with increased risk of morbidity and mortality. Together with low serum albumin, patients had to be new to dialysis to be selected for the MPO Study. These particular considerations on patient selection, together with additional methodological refinements in the study design allow the conclusion that the MPO Study is valid on its own rather than being a European version of the HEMO Study.     

Glucose-6-phosphate dehydrogenase (G-6-PD) mutations in Mexico: four new G-6-PD variants

Screening for mutations at the G-6-PD gene by PCR-SSCP combined with restriction enzyme analysis and DNA sequencing was performed in nine G-6-PD deficient individuals with negative results for the presence of the most frequent G-6-PD mutations previously observed in Mexican population. The variants G-6-PD Valladolid(406T), G-6-PD Durham(713G), and G-6-PD Viangchan(871A) and four new G-6-PD mutant alleles were identified. The new mutations are located at cDNA nt 376 A --> T (126 Asn --> Tyr), nt 770 G --> T (257 Arg --> Leu), nt 1094 G --> A (365 Arg --> His), and nt 1285 A --> G (429 Lys --> Glu) and they were named G-6-PD San Luis Potosi, G-6-PD Zacatecas, G-6-PD Veracruz, and G-6-PD Yucatán, respectively. To date, a total of 18 different G-6-PD variants have been observed in Mexico and several of them are common in Africa, South Europe, and Southeast Asia.     

The Genetics of Hypogammaglobulinemia

Etiologies for human hypogammaglobulinemias are diverse and include genetic and nongenetic causes. Although recent reviews focus on the complex genetics of common variable immunodeficiency, in this review, we survey different causes of hypogammaglobulinemias and discuss possible mechanisms.     

Coronary endarterectomy and bypass grafting without cardiopulmonary bypass

We prospectively analyzed patients who underwent simultaneous off-pump coronary artery bypass grafting and endarterectomy between March 1, 1997 and February 28, 2002. The incidence of perioperative myocardial infarction, need for inotropic support, morbidity, long-time functional class, and mortality were evaluated.Nine endarterectomies were performed in eight patients, more frequently in the right coronary artery. Dopamine was used in four patients. One perioperative myocardial infarction (12.5%) occurred. No deaths occurred and all patients are now functional class I. Tests for ischemia have been negative in all patients.Coronary endarterectomy is an alternative procedure that has little morbidity and enables complete myocardial revascularization without cardiopulmonary bypass.