Characterization of a Factor H Mutation That Perturbs the Alternative Pathway of Complement in a Family with Membranoproliferative GN

Complement C3 activation is a characteristic finding in membranoproliferative GN (MPGN). This activation can be caused by immune complex deposition or an acquired or inherited defect in complement regulation. Deficiency of complement factor H has long been associated with MPGN. More recently, heterozygous genetic variants have been reported in sporadic cases of MPGN, although their functional significance has not been assessed. We describe a family with MPGN and acquired partial lipodystrophy. Although C3 nephritic factor was shown in family members with acquired partial lipodystrophy, it did not segregate with the renal phenotype. Genetic analysis revealed a novel heterozygous mutation in complement factor H (R83S) in addition to known risk polymorphisms carried by individuals with MPGN. Patients with MPGN had normal levels of factor H, and structural analysis of the mutant revealed only subtle alterations. However, functional analysis revealed profoundly reduced C3b binding, cofactor activity, and decay accelerating activity leading to loss of regulation of the alternative pathway. In summary, this family showed a confluence of common and rare functionally significant genetic risk factors causing disease. Data from our analysis of these factors highlight the role of the alternative pathway of complement in MPGN.     

Acute esophageal necrosis

Acute esophageal necrosis (AEN) or “black esophagus” is a rare condition presented by patients with critical state of health and characterized by a darkened esophagus, usually the distal third, in upper digestive endoscopy. The main clinical manifestation is upper gastrointestinal bleeding and there may be abdominal pain, dysphagia, nausea, vomiting, fever and syncope associated. The diagnosis depends on clinical suspicion and performing endoscopy, the biopsy not being required. In this article we present a case of a patient who had lots of comorbidities and developed AEN during a post-operative period, and discuss the importance of AEN in an increasingly ageing population.     

Physiological responses during linear periodized training in rats

This study was undertaken to characterize the effects of the linear periodized training in rats on aerobic and anaerobic performance, glycogen concentration in soleus, gastrocnemius and liver, hormones concentrations (testosterone and corticosterone), enzymes and metabolites (creatine kinase, lactate dehydrogenase, creatinine, uric acid and urea) as well as antioxidant system (catalase, superoxide dismutase and sulfhydryl groups) after basic, specific and taper periods. Seventy male Wistar rats were randomly separated in two groups: control/sedentary (CT, n = 40) and linear periodized training (LPT, n = 30). The LPT was carried out during a period of 12 weeks (w) with frequency of 6 days/week. The training period was subdivided in three mesocycles: basic (6 weeks), specific (4.5 weeks) and taper (1.5 weeks). The real volume of the training obtained in LPT reduced 7% in relation to the estimated volume. The anaerobic index in LPT after basic and taper was higher than CT in respective period but unchanged intra-group during mesocycles. The aerobic performance in LPT was higher than CT after basic, specific and taper. The creatine kinase and catalase reduced after the taper period in relation to CT and baseline. The glycogen stores in soleus increased after basic in relation to CT. The liver glycogen concentration increased after taper in relation to basic and specific period as well in comparison to CT. In conclusion, the stress biomarkers reduced in taper period in order to increase the aerobic and anaerobic performance in relation to CT.     

Tissue Doppler imaging and long axis left ventricular function: hypertrophic cardiomyopathy versus athlete's heart.

BACKGROUND: The different diagnosis between hypertrophic cardiomyopathy and athlete's heart has important clinical implications. The assessment of long axis left ventricular function with tissue Doppler imaging in hypertrophic cardiomyopathy (showing systolic and diastolic dysfunction with heterogeneity and asynchrony), may be useful in the differentiation of these situations. AIM: To study, with tissue Doppler imaging, long axis left ventricular function in a population of athletes (rowers) and to compare it with a population of non-obstructive hypertrophic cardiomyopathy patients. METHODS: In 24 patients with non-obstructive hypertrophic cardiomyopathy and in 20 competitive rowers with similar age, blood pressure and heart rate, we analyzed mitral annulus motion with pulsed tissue Doppler imaging in the 4 sides of the annulus (septal, lateral, inferior, anterior), in apical views. In each wave (systolic, rapid filling and atrial contraction) we measured velocities, time intervals and velocity-time integrals, and calculated heterogeneity and asynchrony indices. Data were compared between the groups, between the different sides in each group ("parallel analysis") and with conventional indices of global function. RESULTS: Hypertrophic cardiomyopathy patients showed: systolic function: lower velocities and integrals, shorter ejection time and shorter systolic time. These abnormalities occurred even in annular sites contiguous to walls without hypertrophy. DIASTOLIC FUNCTION: Much lower rapid filling velocities and integrals, lower atrial contraction velocities and integrals, lower e/a, longer isovolumic relaxation time and time to peak rapid filling wave. These abnormalities occurred even in annular sites adjacent to walls without hypertrophy. In the athletes group, the e/a ratio was never < 1, in any annular site. In hypertrophic cardiomyopathy patients this ratio was < 1 in 27% of the sites. CONCLUSIONS: 1--Systolic and diastolic long axis left ventricular function is different in hypertrophic cardiomyopathy and in athletes, in all mitral annulus sides. 2--The presence of these abnormalities in annular sites contiguous to walls without hypertrophy suggests that this technique may be useful in the differential diagnosis between these groups, particularly in the "gray zone" of Maron.