Pregnenolone and its sulphate modulate GABAA-receptor-mediated contractile responses in the guinea-pig isolated ileum

Pregnenolone and its sulphate had concentration-dependent dual actions on gamma-aminobutyric acid (GABAA)-receptor-mediated ileal contractile responses, enhancing at 0.001-1 microM but inhibiting at 10 microM. There was a sinistral shift of the GABA dose-response curve in the presence of 0.01 microM pregnenolone, with a significant potentiation over the lower concentration range of GABA (3-30 microM), whilst 10 microM pregnenolone depressed the curve by 50% without a significant change in the EC50, in a manner resembling non-competitive inhibition with picrotoxin. Pregnenolone and its sulphate evidently have modulatory actions at ileal GABAA-receptor complexes in keeping with those seen using neurochemical studies in the central nervous system.     

Clinical and serum lipid findings in a large family with autosomal dominant retinitis pigmentosa

Retinitis pigmentosa, of unknown cause, has recently been associated with decreased amounts of the polyunsaturated fatty acid, docosahexaenoic acid, in the plasma of affected as compared with unaffected relatives. It has been suggested that this finding may serve as a marker for the disease and might indicate alterations in photoreceptor cell metabolism. The authors studied 54 members of a family with dominantly inherited retinitis pigmentosa in five generations. In addition to the typical clinical findings of retinitis pigmentosa, eight persons also had a bull's eye maculopathy, and four persons had uni- or bilateral optic nerve drusen. When the authors determined the plasma fatty acid and lipid contents, they saw the expected age-related effect on cholesterol and triglycerides, but an unexpected, significant reduction in fatty acids in the unaffected controls as compared with persons with retinitis pigmentosa. The authors' results emphasize the heterogeneity of phenotypic expression of retinitis pigmentosa within a single family.     

Threshold Amsler grid testing in maculopathies

The Amsler grid is a suprathreshold target and thus may fail to detect relative scotomas. If the grid is viewed through two cross-polarizing filters creating low luminance conditions (threshold Amsler grid testing) the test is far more sensitive. Ten patients with disorders of the macula with normal standard white Amsler grid testing were studied with three other Amsler grid tests. Of the 15 involved eyes, 12 had visual field defects present with threshold Amsler grid testing. Tangent screen examination showed defects in 10 of these 12 eyes. The two red grids used were not as sensitive as the threshold grid. Three eyes had metamorphopsia with the white grid which became the site of a visual field defect with threshold testing. Threshold Amsler grid testing is a rapid and sensitive technique for the evaluation of the central 10 degrees of visual field in patients with maculopathies.     

Endometriosis and angiogenesis

Endometriosis is a common gynecological condition, responsible for significant morbidity and social-economic impact. Although the condition has been recognized for many years, the underlying pathophysiology is poorly understood. In turn, this results in inadequate treatment and high recurrence rates. Various theories try to explain the presence of endometrial tissue outside the uterine cavity. However, none of them can explain all disease locations and appearances, and it is unclear how these fragments establish into endometriotic lesions. New vessel formation has long been recognized as a feature of endometriosis, often clearly visible at laparoscopy. Recent work has focused on identifying the role of vascularization in the pathogenesis of endometriosis, by allowing lesions to establish and grow. In this review the authors outline the basic mechanisms of angiogenesis and vasculogenesis in the human eutopic endometrium, and consider how this data can be applied to endometriotic implants. Furthermore, the authors discuss molecular mechanisms of angiogenesis and vasculogenesis, and how this may be used to therapeutic advantage in the treatment of endometriosis.     

Intravaginally applied metronidazole is as effective as orally applied in the treatment of bacterial vaginosis, but exhibits significantly less side effects

Objective

Metronidazole is the drug of choice for the treatment of bacterial vaginosis (BV). However, so far the oral administration has not been clinically compared to the intravaginal application regarding efficacy, side effects and patient satisfaction in a scientific sound fashion.

Study design

Therefore, this randomized, double-blind, placebo-controlled clinical trial was designed to demonstrate non-inferiority of short-term intravaginal (i.vag.) application of metronidazole (2× 1000 mg pessaries 24 h apart) vs. a single oral dose (p.o.) of metronidazole (1 × 2000 mg tablets) in 263 patients with BV (double-dummy design). The follow-up period was 12 weeks. In addition, the number and the type of adverse events induced by the two regimens were compared, assuming better tolerability of the intravaginal application.

Results

Following the diagnosis of BV a total of 129 women (mean age 36.2 years) was orally treated with a single dose of 2 g metronidazole whereas a total of 134 patients (mean age 35.5 years) was treated intravaginally with 1 g metronidazole each day on two consecutive days and included in the per-protocol analysis. Non-inferiority of i.vag. application compared to p.o. administration was statistically significant regarding efficacy: Following intravaginal application the cure rate, assessed on day 8 after starting of the treatment, was 92.5% as compared to 89.9% after oral administration. Nausea was the most common adverse event reported in 10.2% i.vag. vs. 30.4% p.o. of all cases (p < 0.001), abdominal pain in 16.8% i.vag. vs. 31.9% p.o. (p < 0.01), a “metallic taste” in 8.8% i.vag. vs. 17.9% p.o. (p < 0.05). Women treated i.vag. were highly satisfied with the treatment and more content as compared to the women treated p.o. with metronidazole (p < 0.05, intent-to-treat analysis).

Conclusion

In this clinical trial the intravaginal application was as effective as the oral administration of metronidazole in treating BV. However, significantly less adverse events were reported after short-term intravaginal as compared to oral application (p = 0.023) and probably led to a better patient compliance.