Effect of stearic acid on enalapril stability and dissolution from multiparticulate solid dosage forms.

Enalapril maleate (EM) is a widely used anti-hypertensive drug which is unstable when mixed with excipients. Enalaprilate and diketopiperazine (DPK) are the main degradation products of enalapril. The in situ preparation of enalapril sodium salt (NaE) has been used to improve drug stability in dosage forms; however, gas release and product rejection ensue when the chemical reaction for obtaining the sodium salt is not completely finished before packaging. This study evaluated the effect of stearic acid (SA) on enalapril stability in microcrystalline cellulose (MCC) pellets containing EM or NaE. MCC pellets containing SA were prepared by the extrusion-spheronization technique and characterized. Enalapril stability and dissolution were then evaluated. DPK and enalaprilate formation were reduced by the addition of SA in pellets containing EM. The overall enalapril degradation in these formulations was lower when compared with pellets containing EM or even NaE prepared without SA. The immediate-release characteristic was maintained by the addition of 5% crospovidone to all the formulations tested. The incorporation of SA into NaE pellets resulted in unexpected enalapril degradation, caused by the interaction of these compounds, as suggested by a thermal analysis of the SA-NaE binary mixture. The findings presented here showed that formulations containing SA could substitute the formation of NaE, since they provide better enalapril stability in solid dosage forms. In addition, it is suggested that the stabilization effects would be observed for other N-carboxyalkyl dipeptide analogs with angiotensin converting enzyme inhibition activity, since these new entities share the same degradation pathway of enalapril.

Phylogenetic relationship of the Brazilian isolates of the rat lungworm Angiostrongylus cantonensis (Nematoda: Metastrongylidae) employing mitochondrial COI gene sequence data.

BACKGROUND: The rat lungworm Angiostrongylus cantonensis can cause eosinophilic meningoencephalitis in humans. This nematode's main definitive hosts are rodents and its intermediate hosts are snails. This parasite was first described in China and currently is dispersed across several Pacific islands, Asia, Australia, Africa, some Caribbean islands and most recently in the Americas. Here, we report the genetic variability among A. cantonensis isolates from different geographical locations in Brazil using mitochondrial cytochrome c oxidase subunit I (COI) gene sequences. METHODS: The isolates of A. cantonensis were obtained from distinct geographical locations of Brazil. Genomic DNAs were extracted, amplified by polymerase reaction, purified and sequenced. A partial sequence of COI gene was determined to assess their phylogenetic relationship. RESULTS: The sequences of A. cantonensis were monophyletic. We identified a distinct clade that included all isolates of A. cantonensis from Brazil and Asia based on eight distinct haplotypes (ac1, ac2, ac3, ac4, ac5, ac6, ac7 and ac8) from a previous study. Interestingly, the Brazilian haplotype ac5 is clustered with isolates from Japan, and the Brazilian haplotype ac8 from Rio de Janeiro, São Paulo, Pará and Pernambuco states formed a distinct clade. There is a divergent Brazilian haplotype, which we named ac9, closely related to Chinese haplotype ac6 and Japanese haplotype ac7. CONCLUSION: The genetic variation observed among Brazilian isolates supports the hypothesis that the appearance of A. cantonensis in Brazil is likely a result of multiple introductions of parasite-carrying rats, transported on ships due to active commerce with Africa and Asia during the European colonization period. The rapid spread of the intermediate host, Achatina fulica, also seems to have contributed to the dispersion of this parasite and the infection of the definitive host in different Brazilian regions.

First report of Angiostrongylus cantonensis (Nematoda: Metastrongylidae) in Achatina fulica (Mollusca: Gastropoda) from Southeast and South Brazil.

The rat lungworm Angiostrongylus cantonensis is a worldwide-distributed zoonotic nematode that can cause human eosinophilic meningoencephalitis. Here, for the first time, we report the isolation of A. cantonensis from Achatina fulica from two Brazilian states: Rio de Janeiro (specifically the municipalities of Barra do Piraí, situated at the Paraiba River Valley region and São Gonçalo, situated at the edge of Guanabara Bay) and Santa Catarina (in municipality of Joinville). The lungworms were identified by comparing morphological and morphometrical data obtained from adult worms to values obtained from experimental infections of A. cantonensis from Pernambuco, Brazil, and Akita, Japan. Only a few minor morphological differences that were determined to represent intra-specific variation were observed. This report of A. cantonensis in South and Southeast Brazil, together with the recent report of the zoonosis and parasite-infected molluscs in Northeast Brazil, provide evidence of the wide distribution of A. cantonensis in the country. The need for efforts to better understand the role of A. fulica in the transmission of meningoencephalitis in Brazil and the surveillance of molluscs and rodents, particularly in ports, is emphasized.

First report of Angiostrongylus cantonensis (Nematoda: Metastrongylidae) in Achatina fulica (Mollusca: Gastropoda) from Southeast and South Brazil

The rat lungworm Angiostrongylus cantonensis is a worldwide-distributed zoonotic nematode that can cause human eosinophilic meningoencephalitis. Here, for the first time, we report the isolation of A. cantonensis from Achatina fulica from two Brazilian states: Rio de Janeiro (specifically the municipalities of Barra do Piraí, situated at the Paraiba River Valley region and São Gonçalo, situated at the edge of Guanabara Bay) and Santa Catarina (in municipality of Joinville). The lungworms were identified by comparing morphological and morphometrical data obtained from adult worms to values obtained from experimental infections of A. cantonensis from Pernambuco, Brazil, and Akita, Japan. Only a few minor morphological differences that were determined to represent intra-specific variation were observed. This report of A. cantonensis in South and Southeast Brazil, together with the recent report of the zoonosis and parasite-infected molluscs in Northeast Brazil, provide evidence of the wide distribution of A. cantonensis in the country. The need for efforts to better understand the role of A. fulica in the transmission of meningoencephalitis in Brazil and the surveillance of molluscs and rodents, particularly in ports, is emphasized.

Induçäo inalatória gradativa com sevoflurano em pacientes adultas para cirurgias ginecológicas videolaparoscópicas / Induction and recovery characteristics with gradative increasing inhaled induction of sevoflurane in adults

Justificativa e objetivos: a literatura relata que a induçäo inalatória única de altas doses de sevoflurano está associada com alta incidência de complicaçöes, como tosse, laringoespamo, parada respiratória, obstruçäo de vias aéreas, excesso de secreçäo, excitaçäo e tremores. Este trabalho visou avaliar a induçäo inalatória através do aumento gradativo da concentraçäo do sevoflurano em pacientes adultos, com o intuito de comparar com os dados da literatura. A manutençäo e repercussöes no pós-operatório foram também avaliada. Método: fizeram parte do estudo 35 pacientes (16-42 anos) submetidas à laparoscopia para procedimentos ginecológicos. A medicaçäo pré-anestésica constou de midazolam (0,05mg.kg(elevado a menos um) por via venosa. Após a administraçäo venosa de alfentanil 25µg.kg(elevado a menos um), a induçäo inalatória foi feita com doses crescentes de sevoflurano asssociado ao oxigênio a 100 por cento (aumento de 1 por cento a cada inspiraçäo profunda). Após a perda do reflexo corneano foi repetido alfentanil (25µg.kg(elevado a menos um) por via venosa e a intubaçäo orotraqueal foi facilitada pelo atracúrio (0,5mg.kg(elevado a menos um). A manutençäo foi realizada com oxigênio e sevoflurano suficiente para manter os níveis pressóreos ñ 15 por cento abaixo dos valores iniciais. Foram avaliados o tempo para perda do reflexo corneano, efeitos adversos na induçäo, tempo para extubaçäo desde o desligamento do sevoflurano, tempo para alta hospitalar, analgesia e efeitos adversos no período pós-operatório. Resultados: a perda do reflexo corneano ocorreu entre a segunda e a quinta inspiraçäo profunda em todas as pacientes (1,5ñ0,8 minutos) e a concentraçäo média de sevoflurano utilizada durante a induçäo enalatória foi 3,5 ñ 0,7 por cento. Quatroze por cento as pacientes apresentaram tosse ou certa agitaçäo que cedeu com o aumento da concentraçäo de sevoflurano. As pacientes permaneceram estáveis durante o período per-operatório. O tempo desde o desligamento do sevoflurano até extubaçäo foi de 5,7 ñ 2,3 minutos. No período pós-operatório uma das pcientes apresentou náusea à retirada do tubo orotraqueal e outra peciente apresentou náusea e vômitos durante 120 minutos na recuperaçäo pós-operatória, tendo recebido 20mg de metoclopramida e 8mg de ondansetron por via venosa, O tempo médio para alta da sala de recuperaçäo pós-anestésica foi de 90 ñ 28 minutos. Conclusöes: o aumento gradativo da concentraçäo de sevoflurano resultou em maior tempo de induçäo...

Estudo comparativo in vitro entre biopróteses de pericárdio bovino e porcinas / In vitro comparative study between bovine pericardial and porcine bioprosthesis

A maioria dos implantes valvulares cardíacos realizados no Brasil é representada pelas válvulas de pericárdio bovino, seguidas por próteses porcinas. Na avaliaçao de válvulas biológicas, deve-se considerar: desempenho hidrodinâmico, resistência à fadiga e processo de calcificaçao. No presente estudo, foi avaliado o desempenho hidrodinâmico de biopróteses de pericárdio bovino (Biopro-PB-Braile Biomédica) comparativamente às válvulas porcinas (Biopro-PP-Braile Biomédica) através do gradiente médio transvalvular. Os testes hidrodinâmicos foram realizados em próteses de diâmetros variando de l9 a 35 mm, submetidas ao Sistema Duplicador de Pulsos Shelhigh (Shelhigh Inc.). O volume de ejeçao foi mantido constante em 90 ml, com freqüência de pulso de 60, 70, 80, 90 e l00 ciclos por minuto, possibilitando fluxos entre 5 e 9 litros por minuto, equivalentes a fluxos contínuos aproximados de 8 a 18 litros por minuto. Houve tendência à diminuiçao dos gradientes pressóricos à medida em que aumenta o diâmetro externo das próteses. O gradiente pressórico médio encontrado em próteses de pericárdio bovino foi significativamente menor que o de próteses porcinas (p

Comparaçäo in vitro entre bioproteses de pericardio bovino e porcinas / In vitro comparasion among bovine pericardium and porcine bioprosthesis

No presente estudo foi avaliada a performance hidrodinâmica de bioprótese de pericárdio bovino comparativamente às válvulas porcinas, ambas produzidas no Brasil. Os testes hidrodinâmicos foram realizados em próteses de diâmetros variando de 19 a 35 mm em um sistema duplicador de pulso. O gradiente pressórico médio das próteses de pericárdio bovino foi significativamente menor que o de prótese porcinas (p<0,01) para todos os diâmetros estudados.

Abstract - ln the present study hydrodynamic performance of bioprostheses of bovine pericardium and procine valve were evaluated. The hydrodynamic test were performed in a pulse duplicator system using valves of different diameters from 19 to 35 mm. Pressure gradients measured in bovine pericardium prostheses were significantly (p<0.01) lower than those of porcine valves for all studied valve diameter