Differential protein expression in the midgut of Culex quinquefasciatus mosquitoes induced by the insecticide temephos.

Mosquitoes are vectors for pathogens of malaria, lymphatic filariasis, dengue, chikungunya, yellow fever and Japanese encephalitis. Culex quinquefasciatus Say, 1823 (Diptera: Culicidae) is a known vector of lymphatic filariasis. Its control in Brazil has been managed using the organophosphate temephos. Studies examining the proteins of Cx. quinquefasciatus that are differentially expressed in response to temephos further understanding of the modes of action of the insecticide and may potentially identify resistance factors in the mosquito. In the present study, a comparative proteomic analysis, using 2-dimensional electrophoresis coupled with matrix-assisted laser desorption/ionization (MALDI) time of flight (TOF)/TOF mass spectrometry, and bioinformatics analyses were performed to identify midgut proteins in Cx. quinquefasciatus larvae that were differentially expressed in response to exposure to temephos relative to those in untreated controls. A total of 91 protein spots were differentially expressed; 40 were upregulated and 51 were downregulated by temephos. A total of 22 proteins, predominantly upregulated, were identified as known to play a role in the immune response, whereas the downregulated proteins were involved in energy and protein catabolism. This is the first proteome study of the midgut of Cx. quinquefasciatus and it provides insights into the molecular mechanisms of insecticide-induced responses in the mosquito.

Comparison of the effects on pupil size and accommodation of three regimens of topical dapiprazole.

BACKGROUND: Patients who have their pupils dilated for an eye examination traditionally have to wait several hours before their pupils return to normal size and their blurred vision (caused by paralysis of accommodation) resolves. Earlier studies with dapiprazole have demonstrated an accelerated reversal of dilatation. METHODS: Three regimens of dapiprazole were studied to determine the effects on pupil diameter and accommodation after mydriasis produced by 2.5% phenylephrine and 0.5% tropicamide. Test regimens included one drop and 1 + 1 drop regimens, compared with a 2 + 2 drop reference regimen. Dapiprazole was administered in one eye and placebo in the other. Mean change from baseline was analysed for pupil diameter and accommodation at various time points after drug administration. Also, for the same variables, 90% confidence intervals for the areas under the curve (AUC) were computed. RESULTS: Both test regimens were equivalent to the reference regimen on the basis of mean change from baseline for pupil diameter and accommodation at individual time points, and for the mean AUC. Most signs and symptoms (injection, stinging, burning, lid oedema, and ptosis) were less frequent in the test regimen treated eyes. There was no significant interaction between regimen and eye colour. CONCLUSION: This study indicates that a lower dosage (for example, one drop) is also efficacious and has the added benefit of fewer side effects.

A double-blind, placebo-controlled study comparing mianserin and amitriptyline in moderately depressed outpatients.

We report on the results of a study comparing mianserin with amitriptyline and placebo, in outpatients with major depression (DSM-III 296.2 or 296.3). One hundred and forty-nine patients were randomized to mianserin (n = 50), amitriptyline (n = 50) or placebo (n = 49). Medication was taken in a nightly (qhs) dose. During Week 1, the maximum dose was 60 mg mianserin, 120 mg amitriptyline or two placebo capsules. Beginning at Day 7 (through Day 42) maximum dosages were 150 mg mianserin, 300 mg amitriptyline or five placebo capsules. At multiple weeks and endpoint, statistically significant reductions in the Hamilton Depression Scale (HAM-D) 17- and 21-item scores were recorded for both active drugs compared with placebo. Positive results with the HAM-D were corroborated by other measures of efficacy. There were no statistically significant differences between mianserin and amitriptyline in terms of efficacy; however, the results do suggest a more rapid therapeutic response for mianserin compared with amitriptyline, in terms of percentage of patients showing > or = 50% improvement at Weeks 2 (30% vs 23%) and 4 (61% vs 44%). The most common adverse experiences were somnolence (amitriptyline and mianserin 60%, placebo 31%) and dry mouth (amitriptyline 76%, mianserin 30% and placebo 20%). Our results indicate that mianserin is clearly superior to placebo, compares favorably with amitriptyline, and is a safe, well-tolerated, effective medication in the treatment of depressed outpatients.

Increasing ethnic diversity and managed care: how will they influence research patient recruitment in the nineties?

The challenge of research patient recruitment is intensifying in the 1990s. Relevant factors include the often negative impact of the press, increasing competition for patients, an increasingly ethnically diverse population, and a pervasive trend toward managed care. Based on preliminary findings from a patient focus group, 550 patients were contacted by mail and asked to complete a 25-item questionnaire. Survey results indicate that for most study patients initial telephone contact with a health care professional is not as important as the perception of a genuinely caring (i.e., "non-guinea pig") environment. Office location and other intangibles also affect recruitment; furthermore, several of the benefits sought by volunteers transcend ethnicity. The trend toward managed care will not impede and may enhance research patient recruitment. This research provides information and data that will enable investigators and sponsors to better meet the challenges of patient recruitment in the 1990s.