Modulation of eosinophil generation and migration by Mangifera indica L. extract (Vimang)

The effects of Vimang, an aqueous extract of the stem bark of Mangifera indica L. (Anacardiaceae), on cell migration in an experimental model of asthma was investigated. In vivo treatment of Toxocara canis-infected BALB/c mice for 18 days with 50 mg/kg Vimang reduced eosinophil migration into the bronchoalveolar space and peritoneal cavity. Also, eosinophil generation in bone marrow and blood eosinophilia were inhibited in infected mice treated with Vimang. This reduction was associated with inhibition of IL-5 production in serum and eotaxin in lung homogenates. In all these cases the effects of Vimang were more selective than those observed with dexamethasone. Moreover, Vimang treatment is not toxic for the animals, as demonstrated by the normal body weight increase during infection. These data confirm the potent anti-inflammatory effect of Vimang and support its potential use as an alternative therapeutic drug to the treatment of eosinophilic disorders including those caused by nematodes and allergic diseases.     

Effect of bosentan treatment on surrogate markers in pulmonary arterial hypertension

OBJECTIVE: The aim of this study was to evaluate the effect of the oral dual ET(A)/ET(B) receptor antagonist bosentan on different surrogate markers in patients with pulmonary arterial hypertension (PAH). DESIGN AND SETTING: Prospective, open label, uncontrolled study in a University Hospital in Brazil. POPULATION: Fifteen PAH patients (11 females) with mean age of 40 +/- 11 years (5 in WHO functional class II, 10 in class III). METHODS: All patients were investigated at baseline and after 16 weeks of bosentan treatment. We used the following surrogate markers for patients' evaluation: 6-min walk test, quality of life questionnaire (Short Form SF-36) and N-terminal proBNP (B type natriuretic peptide) fraction levels in blood. RESULTS: Between the evaluation at baseline and week 16, the 6-min walk test distance changed from 396 +/- 135 to 434 +/- 137 m (p < 0.05). Each of the eight domains of the SF-36 was significantly improved. Mean NT-proBNP levels were decreased from a mean of 1670 pg/mL to 1010 pg/mL (p = 0.01). CONCLUSION: The study suggests that bosentan treatment results in the improvement of different kinds of surrogate markers independently of their specificity to reflect functional capacity, quality of life and myocardial stress. It is concluded that the combined use of these different markers may be an alternative endpoint for future short duration clinical trials.     

Postmenopausal hormone therapy: new questions and the case for new clinical trials

Observational studies suggest that postmenopausal hormone therapy (HT) prevents coronary heart disease, whereas randomized clinical trials have not confirmed a cardioprotective effect. Although observational studies may have overestimated the coronary benefit conferred by postmenopausal hormone use, there are other plausible explanations for the apparent discrepancy between previous results and the less favorable findings from clinical trials such as the large Women's Health Initiative. There is now a critical mass of data to support the hypothesis that age or time since menopause may importantly influence the benefit-risk ratio associated with HT, especially with respect to cardiovascular outcomes, and that the method of administration, dose, and formulation of exogenous hormones may also be relevant. Although the weight of the evidence indicates that older women and those with subclinical or overt coronary heart disease should not take HT, estrogen remains the most effective treatment currently available for vasomotor symptoms, and its effects on the development of coronary disease in newly postmenopausal women remain unclear. Moreover, effects of HT on quality of life and cognitive function in recently postmenopausal women merit further study. These unresolved clinical issues provide the rationale for the design of the Kronos Early Estrogen Prevention Study, a 5-year randomized trial that will evaluate the effectiveness of low-dose oral estrogen and transdermal estradiol in preventing progression of atherosclerosis in recently postmenopausal women.     

Reconstruction of a mandibular critical-sized defect using iliac graft in rats

OBJECTIVE: To evaluate, histologically and by optical densitometry of radiographs, the healing of a critical-sized defect in the rat mandible filled with iliac graft. MATERIALS: The study was conducted on 25 adult Wistar rats. With the rats under general anesthesia, a bicortical critical-sized osseous defect was created in the right mandibular ramus and filled with autogenous iliac crest graft. The animals were divided into 5 groups, with 5 rats in each. They were sacrificed after 1, 7, and 14 days, and 1 and 3 months. The mandibles were removed, fixed in formalin, and radiographed. The right hemi-mandibles were decalcified, and sections were cut and stained with hematoxylin and eosin. RESULTS: Initially, an acute inflammatory process was noted along the graft that was tightly fitted to the defect. Subsequently, intense bone neoformation from external corticals and in the inner spaces of the graft was observed, while medullar spaces were occupied by granulation tissue and osteoblasts. There was remodelation of the receptor site, with a decrease in the graft volume and medullary space, as well as cancellous bone replaced by compact bone. Later, the receptor site was similar to the normal mandible, and only devitalized remnants of corticals of the graft were found. Optical densitometry of radiographs revealed statistically significant differences between experimental and control sites. CONCLUSIONS: This experimental model is valuable in the study of bone healing. The study showed that autogenous iliac graft promoted healing of the critical-sized defect of the mandible with complete bony remodeling.