Cathelicidins and innate defense against invasive bacterial infection

Cathelicidins are small cationic peptides that possess broad-spectrum antimicrobial activity. These gene-encoded 'natural antibiotics' are produced by several mammalian species on epithelial surfaces and within the granules of phagocytic cells. Since their discovery over a decade ago, cathelicidins have been speculated to function within the innate immune system, contributing to a first line of host defense against an array of microorganisms. Consequently, cathelicidins have captured the interest of basic investigators in the diverse fields of cell biology, immunology, protein chemistry and microbiology. A burgeoning body of experimental research now appears to confirm and extend the biological significance of these fascinating molecules. This article reviews the latest advances in the knowledge of cathelicidin antimicrobial peptides, with particular emphasis on their role in defense against invasive bacterial infection and associations with human disease conditions.     

Different modalities of classification and prognostic significance of ventricular arrhythmias after acute myocardial infarct. Prospective study

In our study we compared the prognostic significance of clinical variables, laboratory results and different classification models of ventricular ectopic beats recorded by means of a pre-discharge 24 hour ambulatory electrocardiographic monitoring, in 210 survivors of acute myocardial infarction. In addition a full multivariate analysis of the factors affecting survival time was carried out using Cox's proportional hazards (multiple) regression model. Multivariate stepwise discriminant analysis identified hypertension, congestive heart failure assessed by Killip class, and the grading system for ventricular arrhythmias as the most important prognostic variables. When Moss grading system for ventricular arrhythmias was used, the relative risk was a superior as heavy Moss grading system (Moss 2 vs Moss 1 and Moss 3-4 vs Moss 1, relative risk = 1.2 and 3.6 total death, respectively). Furthermore, the hazard ratio of Moss grading system was higher utilizing as comparison patients without ventricular ectopic beats (relative risk = 1.7 for Moss 2 and 5.3 for Moss 3-4) than patients with ventricular ectopic beats less than one/hour (relative risk = 1.2 for Moss 2 and 3.7 for Moss 3-4). Thus, in survivors of acute myocardial infarction, a rational and useful ventricular ectopic beats categorization includes both frequency and the presence or absence of malignant characteristics.     

Clinical experience with the Carpentier-Edwards porcine bioprosthesis: short-term results (from 2 to 4.5 years)

All patients undergoing a heart valve replacement with a glutaraldehyde Carpentier-Edwards xenograft from April 1978 through December 1980 were reviewed. This analysis included 189 patients: 117 having a mitral valve replacement (MVR), 45 having an aortic valve replacement (AVR), and 27 having mitral and aortic valve replacements (MAVR). Out of 174 patients discharged from the hospital, one was lost to follow-up and is excluded from the analysis. There were 11 late deaths, which represent an incidence of 1.89% per patient-year for the MVR (6/106), 0.83% per patient-year for the AVR (1/41), and 5.83% per patient-year for the MAVR (4/26). There were 6 instances of infective endocarditis (4 MVR, 2 MAVR), which represent a linearized incidence o 1.26% and 2.91% per patient-year for the MVR and MAVR respectively. All were successfully treated with medication. There were 10 thromboembolic events in 7 patients (6 MVR had 9 events and 1 AVR had 1 event). This represents a linearized incidence of 2.84% and 0.83% per patient-year for MVR and AVR, respectively. Primary tissue failure was observed in 3 patients (2 MVR, 1 MAVR), who required reoperation for explantation of the mitral valves. This represents an overall linearized incidence of mitral failures of 0.78% per patient-year. The probability of being free from primary tissue failure is 95.9 +/- 4.9% for all mitral prostheses at 4.5 years of follow-up. These current results indicate that the Carpentier-Edwards porcine xenograft valve can be considered as a valid alternative for heart valve replacement.     

Hepatocellular carcinoma,hepatitis C virus infection and miRNA involvement: Perspectives for new therapeutic approaches

Chronic hepatitis C virus (HCV) infection is the principal etiology of cirrhosis and, ultimately, hepatocellular carcinoma (HCC). At present, approximately 71 million people are chronically infected with HCV, and 10%–20% of these are expected to develop severe liver complications throughout their lifetime. Scientific evidence has clearly shown the causal association between miRNAs, HCV infection and HCC. Although it is not completely clear whether miRNA dysregulation in HCC is the cause or the consequence of its development, variations in miRNA patterns have been described in different liver diseases, including HCC. Many studies have analyzed the importance of circulating miRNAs and their effect on cell proliferation and apoptosis. In this Review, we aim to summarize current knowledge on the association between miRNA, HCV and HCC from a diagnostic point of view, and also the potential implications for therapeutic approaches.     

Acute and long-term changes in central and pituitary mechanisms regulating pulsatile luteinizing hormone secretion after ovariectomy in the rat

These experiments examined the time course of changes in the characteristics of pulsatile luteinizing hormone (LH) secretion that occur after ovariectomy (OVX) in the rat, and compared the response of the brain and pituitary to the absence of ovarian steroid negative feedback. The literature indicates that the brain could respond to OVX by altering the frequency and/or amplitude of the pulsatile luteinizing hormone releasing hormone (LH-RH) release which triggers pulsatile LH secretion, while the pituitary could respond by altering basal LH output and/or its response to LH-RH. In vivo experiments examined changes in mean blood LH levels, LH pulse amplitudes and pulse frequencies in control rats on diestrus 1 (D1) and at 7 h, 14 h, 1, 2 or 8 days, or 3 weeks following OVX. In addition, anterior pituitaries from rats on D1 or rats ovariectomized for 1, 2 or 8 days, or 3 weeks, were incubated in vitro with or without LH-RH to examine changes in both basal and LH-RH-induced LH release. Mean blood LH levels increased within 17-24 h following OVX. This acute, rapid elevation was due to increases in both LH pulse frequency and pulse amplitude. Blood LH levels continued to increase over a 3-week period. However, the long-term increase seen at 8 days or 3 weeks was not only due to increases in LH pulse frequency and amplitude, but also to dramatic increases in basal LH secretion. The frequency of pulsatile LH release was maximal within 8 days, with no further increases occurring over the next 2 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)     

The relationship between anemia, fecal stercobilinogen, erythrocyte survival, and globin synthesis in heterozygotes for beta-thalassemia.

Erythrocyte survival, fecal stercobilinogen, and the alpha/beta-chain synthesis ratio in recticulocytes and bone marrow (six cases only) were determined and related to the hemoglobin levels in ten heterozygous carriers of beta-thalassemia with different degrees of anemia. Erythrocyte survival values were low, though not related to the degree of anemia, whereas stercobilinogen values and changes in the peripheral blood alpha/beta-chain ratios were so correlated. In the case of bone marrow, on the other hand, the ratio between alpha-chain and beta-chain synthesis was virtually 1, irrespective of the degree of anemia. It is suggested that the severity of anemia in heterozygous carriers is independent of peripheral hemolysis and entirely attributable to destruction of erythroblasts within the marrow.