Padronização dos critérios de seleção em estudos sobre medicações nasais / Standardizing selection criteria in nasal medication studies

Estudos clínicos sobre medicações tópicas nasais exigem a padronização de "normalidade nasossinusal" na constituição de grupos controle através de uma avaliação específica da via aérea superior. Objetivo: Padronizar a avaliação de candidatos a grupos controle em estudos clínicos sobre medicações tópicas nasais. Material e métodos: Voluntários do sexo masculino, de 18 a 50 anos, que se declararam saudáveis, livres de doenças e assintomáticos nasossinusais foram submetidos a uma avaliação sequencial e excludente composta de uma avaliação clínica, teste cutâneo de hipersensibilidade imediata, teste da sacarina, nasofibroscopia flexível e citograma nasal. Desenho do estudo: Coorte contemporânea com corte transversal. Resultados: Dos 33 indivíduos inicialmente incluídos, 14 (42,4 por cento) foram excluídos na avaliação clínica. Dos 19 restantes, 2 (10,5 por cento) apresentaram atopia no teste cutâneo, sendo excluídos. 17 foram submetidos ao teste da sacarina demonstrando em todos os casos uma depuração mucociliar normal, sendo avaliados por nasofibroscopia flexível que detectou anormalidade em 2 casos (11,8 por cento) e excluídos. Os 15 restantes foram submetidos ao citograma nasal, demonstrando normalidade, representando 45,5 por cento dos indivíduos inicialmente incluídos. Conclusão: O protocolo proposto de avaliação sequencial e excludente foi efetivo na definição de candidatos à constituição de grupos controle em estudos clínicos sobre medicações tópicas nasais.

Clinical studies on nasal topical medications require the standardization of "nasosinusal normality" in order to establish control groups through a specific evaluation of the upper airways. AIM: to standardize the evaluation of candidates for control groups in clinical studies on nasal topical medications. Material and methods: healthy male volunteers of 18 to 50 years of age, asymptomatic from the nasosinusal standpoint were subjected to a sequential and excluding assessment made up of clinical evaluation, immediate hypersensitivity skin test, saccharin test, flexible nasofibroscopy and nasal cytology. Study design: Cross-sectional contemporary cohort. Results: Of the 33 people originally enrolled, 14 (42.4 percent) were excluded for clinical reasons. Of the 19 remaining, 2 (10.5 percent) had atopy diagnosed in the skin test and were excluded. 17 were tested with saccharin and presented normal mucociliary clearance. Evaluation by nasal endoscopy showed abnormality in 2 cases (11.8 percent) and these were excluded. The remaining 15 were submitted to nasal cytology, which proved normal, representing 45.5 percent of those initially included. Conclusion: The proposed protocol for sequential and excluding evaluation was effective in defining candidates for the establishment of control groups in clinical studies on nasal topical medications.

Standardizing selection criteria in nasal medication studies.

UNLABELLED: Clinical studies on nasal topical medications require the standardization of 'nasosinusal normality' in order to establish control groups through a specific evaluation of the upper airways. AIM: to standardize the evaluation of candidates for control groups in clinical studies on nasal topical medications. MATERIAL AND METHODS: healthy male volunteers of 18 to 50 years of age, asymptomatic from the nasosinusal standpoint were subjected to a sequential and excluding assessment made up of clinical evaluation, immediate hypersensitivity skin test, saccharin test, flexible nasofibroscopy and nasal cytology. STUDY DESIGN: Cross-sectional contemporary cohort. RESULTS: Of the 33 people originally enrolled, 14 (42.4%) were excluded for clinical reasons. Of the 19 remaining, 2 (10.5%) had atopy diagnosed in the skin test and were excluded. 17 were tested with saccharin and presented normal mucociliary clearance. Evaluation by nasal endoscopy showed abnormality in 2 cases (11.8%) and these were excluded. The remaining 15 were submitted to nasal cytology, which proved normal, representing 45.5% of those initially included. CONCLUSION: The proposed protocol for sequential and excluding evaluation was effective in defining candidates for the establishment of control groups in clinical studies on nasal topical medications.

Losartan attenuates the antimigratory effect of diclofenac in spontaneously hypertensive rats.

Many patients with hypertension, particularly elderly patients, take nonsteroidal antiinflammatory drugs (NSAIDs) and antihypertensive agents. However, few studies describe the effect of the association of antihypertensive agents with NSAIDs on inflammatory response in hypertension. To investigate this, spontaneously hypertensive rats (SHRs) were treated with either diclofenac alone or diclofenac combined with losartan (an AT1 angiotensin II antagonist). The leukocyte-endothelial interaction was then observed using intravital microscopy. Blood pressure of SHR (169.6+/-3.6) was increased by diclofenac (186.4+/-2.9), reduced by losartan (152.6+/-3.5), and reduced by the combination of the 2 (158.9+/-3.7). All the treatments tested reduced the number of rollers, adherent and migrated leukocytes, and the expression of endothelial intercellular adhesion molecule-1 and P-selectin. The association of losartan reduced the effect of diclofenac on leukocyte migration. Neither treatment tested increased the venular shear rate or modified the venular diameters, number of circulating leukocytes, and L-selectin expression on granulocytes. The reduction of CD11/CD18 expression induced by diclofenac alone was hindered by losartan. A pharmacokinetic interference between losartan and diclofenac was ruled out since no significant differences were observed in the plasma concentrations of each drug when they were associated. In conclusion, although diclofenac does not interfere with the losartan antihypertensive effect, losartan attenuates the effect of diclofenac has on leukocyte behavior and expression of adhesion molecules. Losartan has an antimigratory effect, reducing leukocyte migration by reducing ICAM-1 and P-selectin expression. Losartan may hinder the full expression of the antimigratory effect of diclofenac.

Enalapril interferes with the effect of diclofenac on leucocyte-endothelium interaction in hypertensive rats.

Nonsteroidal anti-inflammatory drugs are known to attenuate the effects of some antihypertensive agents. However, the effect these drugs have on leukocyte migration when combined with antihypertensive agents has not been studied. To investigate this effect, we treated spontaneously hypertensive rats with saline, diclofenac, enalapril, or diclofenac combined with enalapril and observed leukocyte-endothelium interaction. Blood pressure was increased by diclofenac, reduced by enalapril and reduced by the combination of the two. Diclofenac did not interfere with the blood pressure-lowering effect of enalapril. Internal spermatic fascia venules were observed using intravital microscopy. Diclofenac reduced rollers, whereas enalapril, alone or combined with diclofenac, had no significant effect on rollers. All treatments reduced adherent and migrated leukocytes and expression of endothelial intercellular adhesion molecule-1. Venular shear rate, venular diameters, number of circulating leukocytes, and post-leukotriene B4 expression of l-selectin and CD11/CD18 integrin in leukocytes were unaffected by any treatment. Expression of P-selectin was reduced by diclofenac and unaffected by enalapril, even when combined with diclofenac. Our data suggest that, although diclofenac does not interfere with the enalapril anti-hypertensive effect, enalapril interferes with the effect diclofenac has on leukocyte rolling and endothelial P-selectin expression. Involvement of reduced endothelial intercellular adhesion molecule-1 expression might explain the lower numbers of adherent and migrated leukocytes. The anti-inflammatory properties of a nonsteroidal anti-inflammatory drug could therefore be attenuated in hypertensive patients receiving an angiotensin-converting enzyme inhibitor.