Biophysical, histopathological and pharmacological characterization of crotamine isoforms F22 and F32.

Two major crotamine isoforms (F22 and F32) were obtained after three chromatographic steps and were assayed in mouse phrenic nerve-diaphragm preparations. F32 and F22 (0.5 microg/ml, n=4) produced a facilitatory effect, which increased isometric twitch-tension by 300 and 230%, respectively, after a 120 min incubation. At a concentration of 0.1 microg/ml, both isoforms increased the twitch-tension by about 160%. However, when the isoforms were co-incubated (final concentration, 0.5 microg/ml) for 30 min prior to testing, they did not cause the facilitation seen with > or =0.1 microg/ml of each isoform alone. Histologically, F32 and F22 at 0.5 and 1 microg/ml were quantitatively alike in inducing tissue myonecrosis. However, a mixture of the two isoforms (final concentration, 0.5 microg/ml) significantly attenuated the damage seen with either toxin alone. Mass spectrometry analysis showed that the isoforms had the same molecular mass (4.8 kDa) and that they existed as monomers with a highly stable structure. These results indicate that F22 and F32 acted on muscle cells of the mouse phrenic-nerve diaphragm preparation through similar mechanisms. Since the isoforms did not produce the expected summation in the increase in muscle twitch-tension, it is possible that they may have different affinities for the sodium channel subunits.     

Pharmacological and structural characterization of a novel phospholipase A2 from Micrurus dumerilii carinicauda venom.

We have isolated a new phospholipase A2 (MiDCA1) from the venom of the coral snake Micrurus dumerilii carinicauda. This toxin, which had a molecular mass of 15,552Da, shared high sequence homology with the PLA2 toxins MICNI A and B from Micrurus nigrocinctus venom (77.7% and 73.1%, respectively). In chick biventer cervicis preparations, MiDCA1 produced concentration- and time-dependent neuromuscular blockade that reached 100% after 120 min (2.4 microM, n = 6); contractures to exogenously applied carbachol (8 microM) and KCl (13 mM) were still seen after complete blockade. In mouse phrenic-nerve diaphragm preparations, MiDCA1 (2.4 microM; n = 6) caused triphasic changes followed by partial neuromuscular blockade. Intracellular recordings of end-plate potentials (EPPs) and miniature end-plate potentials (MEPPs) from mouse diaphragm preparations showed that MiDCA1 increased the quantal content by 386+/-12% after 10 min (n = 14; p<0.05) and caused a triphasic change in the frequency of MEPPs. MiDCA1 also decreased the resting membrane potential, an effect that was prevented by tetrodotoxin and/or low extracellular calcium, but not by d-tubocurarine. The toxin increased the amplitude of mouse sciatic-nerve compound action potentials by 30+/-9% (0.6 microM; p<0.05). Potassium currents elicited in freshly dissociated dorsal root ganglia neurones were blocked by 31+/-1% (n = 4; p<0.05) in the presence of 2.4 microM MiDCA1. These results show that MiDCA1 is a new presynaptic phospholipase A2 that produces neuromuscular blockade in vertebrate nerve-muscle preparations. The triphasic effects seen in mammalian preparations and the facilitatory response were probably caused mainly by the activation of sodium channels, complemented by the blockade of nerve terminal potassium channels. The inability of d-turocurarine to prevent the depolarization by MiDCA1 indicated that cholinergic nicotinic receptors were not involved in this phenomenon.     

Relationships between leisure-time physical activity, obesity and disability in elderly men

BACKGROUND AND AIMS: Relationships have already been shown between leisure-time physical activity, obesity and body composition in young adults. However, this association needs to be confirmed in the elderly. The aim of this study was to investigate the relationship between leisure-time physical activity, obesity, preservation of muscle mass and disability in elderly men. METHODS: Cross-sectional analysis of a sample of 85 community-dwelling men, 68 to 79 years of age. Body mass index (BMI) was used to quantify obesity. Body composition was evaluated using Dual Energy X-ray Absorptiometry. Disability was measured using a modified version of the Activities of Daily Living scale. Leisure-time physical activity was evaluated by a validated self-administered questionnaire. RESULTS: A negative relation between obesity and weekly walking was observed. Walking less than 30 minutes per day was associated with a 2.7 greater probability of being obese (95% CI 1.1-6.7). High-intensity exercise, such as brisk walking or gardening, was inversely correlated with body fat (R = -0.296, p < 0.01) and directly correlated with appendicular skeletal mass (R = 0.238, p < 0.05). The prevalence of disability was the highest (58%) among overweight elderly subjects at the lowest tertile of exercise. Multiple logistic regression selected BMI as a positive predictor and high-intensity exercise as a negative predictor of disability. CONCLUSIONS: Our study shows that, in elderly men, leisure-time physical activity is inversely associated with body fat, BMI, and reported disability, but positively associated with appendicular fat-free mass. The highest prevalence of reported disability was observed in sedentary subjects with BMI higher than 25 kg/m2.     

Expressed emotion and family burden in relatives of patients in first-episode psychosis

BACKGROUND

Evidence suggests that expressed emotion (EE) and family burden (FB) are phenomena that interact, but there is a lack of studies that analyze this association in patients in first-episode psychosis.

Pediatric scaphoid fracture: diagnostic performance of various radiographic views

Emergency Radiology - The purpose of this study was to systematically investigate the performance of different radiographic views in the identification of scaphoid fractures in children. This...