Antimalarial and anti-inflammatory activities of new chloroquine and primaquine hybrids: Targeting the blockade of malaria parasite transmission.

Malaria is a disease that requires new drugs not only to fight Plasmodium but also to reduce symptoms of infection such as fever and inflammation. A series of 21 hybrid compounds were designed from chloroquine (CQ) and primaquine (PQ) linked to the pharmacophoric group present in phenylacetic anti-inflammatory drugs. These compounds were designed to have dual activity: namely, to be capable of killing Plasmodium and still act on the inflammatory process caused by malaria infection. The compounds were assayed with nine different biological methods. The carbonylated CQ derivative 6 (n = 3; R1 = Cl) was more potent than CQ in vitro, and 8 (n = 4; R1 = H) reduced P. berghei parasitemia up to 37% on day 7. The carbonylated PQ derivative 17 (R = Br) was slightly less potent than PQ. The gem-difluoro PQ derivative 20 (R = Cl) exhibited high transmission blockade of the malaria sporogonic cycle in mosquitoes. Compounds 6 and 20 dose-dependently reduced nitric oxide (NO) production and inhibited TNFα production by LPS-stimulated J774A.1 macrophages. Our results indicate a viable and interesting approach in planning new chemical entities that act as transmission-blocking drugs for treating malaria caused by P. falciparum and P. vivax and the anti-inflammatory process related to this disease.

Entropy Analysis for the Evaluation of Respiratory Changes Due to Asbestos Exposure and Associated Smoking.

Breathing is a complex rhythmic motor act, which is created by integrating different inputs to the respiratory centres. Analysing nonlinear fluctuations in breathing may provide clinically relevant information in patients with complex illnesses, such as asbestosis. We evaluated the effect of exposition to asbestos on the complexity of the respiratory system by investigating the respiratory impedance sample entropy (SampEnZrs) and recurrence period density entropy (RPDEnZrs). Similar analyses were performed by evaluating the airflow pattern sample entropy (SampEnV') and recurrence period density entropy (RPDEnV'). Groups of 34 controls and 34 asbestos-exposed patients were evaluated in the respiratory impedance entropy analysis, while groups of 34 controls and 30 asbestos-exposed patients were investigated in the analysis of airflow entropy. Asbestos exposition introduced a significant reduction of RPDEnV' in non-smoker patients (p < 0.0004), which suggests that the airflow pattern becomes less complex in these patients. Smoker patients also presented a reduction in RPDEnV' (p < 0.05). These finding are consistent with the reduction in respiratory system adaptability to daily life activities observed in these patients. It was observed a significant reduction in SampEnV' in smoker patients in comparison with non-smokers (p < 0.02). Diagnostic accuracy evaluations in the whole group of patients (including non-smokers and smokers) indicated that RPDEnV' might be useful in the diagnosis of respiratory abnormalities in asbestos-exposed patients, showing an accuracy of 72.0%. In specific groups of non-smokers, RPDEnV' also presented adequate accuracy (79.0%), while in smoker patients, SampEnV' and RPDEnV' presented adequate accuracy (70.7% and 70.2%, respectively). Taken together, these results suggest that entropy analysis may provide an early and sensitive functional indicator of interstitial asbestosis.

Transmission-Blocking Potential of MEFAS, a Hybrid Compound Derived from Artesunate and Mefloquine.

Most antimalarial drugs target asexual parasites without reducing gametocyte formation or development. Drugs with dual roles, i.e., those that can target both asexual parasites and gametocytes, would improve the control of malaria. In the current study, MEFAS, a hybrid drug derived from mefloquine and artesunate that has been shown to be an active blood schizonticidal drug, was assessed to determine its ability to block the infectivity of Plasmodium falciparum gametocytes. MEFAS was 280 and 15 times more effective than mefloquine alone and artesunate alone, respectively.

Epistaxe tardia secundária a pseudoaneurisma intracavernoso de carótida interna / Delayed epistaxis secondary to intracavernous pseudoaneurysm of internal carotid artery

Pseudoaneurisma traumático da artéria carótida interna é uma causa rara de epistaxe, porém potencialmente fatal. O diagnóstico precoce é essencial para um adequado manejo da patologia. Os autores relatam um caso de pseudoaneurisma da carótida interna que se apresentou como epistaxe maciça após seis meses de trauma craniano prévio

Estenose subglótica como manifestação clínica da granulomatose de Wegener em adolescentes: relato de caso e revisão de literatura / Subglottic stenosis as a clinical manifestation of Wegener's granulomatosis in adolescents: report of a case and review of literature

A Granulomatose de Wegener é uma patologia caracterizada por vasculite sistêmica e inflamaçäo granulomatosa necrotizante que compromete o trato respiratório alto, pulmöes e rins, cujas manifestaçöes iniciais, na maioria das vezes, ocorre em maiores de 20 anos de idade. As queixas clínicas otorrinolaringológicas estäo, com freqüência, presentes nas fases iniciais da doença, sendo rinite, sinusopatia de repetiçäo e epistaxe as mais comuns. A estenose subglógica parece estar correlacionada com a Granulomatose de Wegener em adolescentes. Relatamos o caso de uma paciente portadora de Granulomatose de Wegener cujo início dos sintomas foi na infância, tendo evoluído com estenose laríngea durante o curso da doença