Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug Reactions

OBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.

Under-Report and Underdiagnosis of Chronic Respiratory Diseases in an African Country

BACKGROUND: Chronic respiratory diseases (CRD) are greatly underestimated. The aim of this study was to assess the burden associated with reported CRD and chronic obstructive pulmonary disease, as defined on the basis of various standardized criteria, by estimating their point prevalence in a sample of individuals attending the Primary Health Care (PHC) level and Emergency Room (ER) Departments in Cape Verde (CV) archipelago. The second aim of the study was to identify factors related to airways obstruction and reported CRD in this population. METHODS: A cross-sectional study was carried out in CV during 2 weeks. Outpatients aged more than 20 years seeking care at PHC level and ER answered a standardized questionnaire and were subjected to spirometry, independently of their complaint. Two criteria for airways obstruction were taken into account: forced expiratory volume (FEV(1)) <80% of the predicted value and FEV(1)/forced vital capacity (FVC) ratio <0.70. RESULTS: A total of 274 individuals with a satisfactory spirometry were included. 22% of the individuals had a FEV(1) < 80%. Individuals older than 46 years had a higher risk of having airways obstruction. Asthma diagnosis (11%) had a clear association with airways obstruction. Smoking was a risk factor for a lower FEV(1). Working in a dust place and cooking using an open fire were both related to chronic bronchitis and asthma diagnosis. CONCLUSION: Under-report and underdiagnosis of chronic respiratory conditions seem to be a reality in CV just as in other parts of the world. To improve diagnosis, our results reinforce the need of performing a spirometry

Métodos de avaliação da frequência de eventos adversos em contexto hospitalar : contributos de uma revisão sistemática

RESUMO - Os eventos adversos (EA) hospitalares constituem um problema sério dos cuidados de saúde com consequências clínicas, económicas e sociais para a Saúde Pública. Nas últimas décadas foram realizados diversos estudos com o objetivo de conhecer de forma mais pormenorizada esta realidade, nomeadamente no que diz respeito à frequência, tipologia, evitabilidade e impacte dos EA. De entre as diferentes metodologias que têm sido utilizadas parece existir algum consenso em torno da análise retrospetiva de processos clínicos como a que oferece maior garantia de fiabilidade e reprodutibilidade, não obstante as limitações conhecidas. Assim, propusemo-nos com este trabalho, analisar as vantagens e desvantagens dos métodos mais comummente utilizados para caraterizar a ocorrência de EA e, concomitantemente elaborar uma revisão sistemática (RS) dos estudos que aplicaram o método de revisão retrospetiva de processos clínicos na caraterização e avaliação dos EA em contexto hospitalar. Para definir a nossa amostra, realizámos uma pesquisa formal nas bases de dados MEDLINE e Web of Knowledge, e foi realizado um cruzamento manual de referências dos artigos elegíveis para identificar estudos adicionais relevantes. Os artigos selecionados foram revistos independentemente no que diz respeito à metodologia, aos critérios de elegibilidade e aos objetivos. Durante a fase de revisão e aplicação dos critérios de inclusão e exclusão foram selecionados os artigos que abordassem a frequência/incidência e a percentagem de evitabilidade dos EA hospitalares, através da aplicação do método de revisão retrospetiva de processos clínicos. Após a fase de pesquisa e revisão dos artigos, foram selecionados para a nossa amostra oito estudos que incluíram um total de 28.862 processos clínicos revistos. De entre os principais resultados encontrados destaca-se: i) A mediana de incidência de EA hospitalares de 9.5%; Universidade Nova de Lisboa – Escola Nacional de Saúde Pública ii) O valor de mediana de EA considerados evitáveis de 45.5%; iii) No que se refere ao impacte clínico dos EA, mais de metade dos doentes (56.3%) não experienciou incapacidade ou experienciou incapacidade menor; iv) Em 8% dos casos de EA ocorreu a morte dos doentes. v) Quanto ao impacte económico evidencia-se o facto de, nos doentes em que se confirmou EA, o período de internamento se ter prolongado, em média, por 7.1 dias com consequentes e previsíveis custos adicionais. Tendo em consideração as vantagens e desvantagens de cada método, os sistemas de informação existentes em Portugal e a realidade das instituições de saúde, parece-nos plausível destacar o método de revisão dos processos clínicos como o que melhor se adapta para caraterizar os EA no contexto hospitalar português.

Course of infection and histopathological lesions in mice infected with seventeen Trypanosoma cruzi strains isolated from chronic patients

Mice were infected with blood forms of 17 Trypanosoma cruzi strains recently isolated from chronic patients, which were dassified as of low, medium or high virulence on grounds of the prepatent period, parasitemia and mortality at the acute phase. A total of 212 mice were studied after 3, 6, 9 and 12 months of infection. In the chronic phase, intracellular parasites were detected in 11.0%,27.9%and 54.0,% of mice inoculated, respectively, with the low, medium and high virulent strains (r= 0.98, p < 0.005). Heart fibrosis was also related to virulence, affecting 5.7%, 11.6%and30.8% (r = 0.98, p < 0.001) of the mice inoculated with the above strains; a similar relationship was observed between intensity and frequency of the heart inflammatory reaction and the severity of infection at its early stage. Necrotizing arteritis was detected in 12.2% of the inoculated animals and this lesion was related to the infection duration rather than to strain characteristics. Inflammatory lesions and tissue parasitism were stable within the period of observation, whereas fibrosis was Progressive. The findings suggest that mice may reproduce heart lesions resembling human pathology and that organ damage apparently depends on the parasite virulence.

The impact of corporate social responsibility on consumer behavior: The role of profit-seeking and altruistic perceived motives

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Epidemiologic studies of chagas' disease in the urban zone of Teresina. State of Piauí, northeastern Brazil

The triatomine species Rhodnius nasutus and Triatoma pseudomaculata were captured on palm trees Orbignya martiana "babaçu ", in the urban zone of Teresina. This kind of palm tree is largely distributed in Piauí State. The predominant species was R. nasutus; the young in stars predominated. The infestation index of palm trees and the infection index of triatomines by flagellates were 96.0 ana 29.1%, respectively. Marsupiais, bats and a rodent were captured in palm trees. The flagellates found in both triatomines ana marsupiais were morphologically and biologically indistinguishable from Trypanosoma cruzi. Forty seven percent (481/1,025) of triatomines were found concentrated in six palm trees where marsupiais circulated. Of the total of 1,025 triatomines 230 (22%) were infected by flagellates and 53.0% (123/230) of these infected triatomines were present in the same six palm trees. No evidence of triatomine domiciliation or human transmission was observed in the houses in the vicinity of palm trees. The results suggest that marsupiais play an important role in the life-cycle of T. cruzi in this region. The natural focus of Chagas' disease, demonstrated in the present study could represent a potential epidemiological threat.

Malaria in humait a county, state of Amazonas, Brazil. XIX - evaluation of clindamycin for the treatment of patients with Plasmodium falciparum infection

A total of 207 patients with malaria caused by Plasmodium falciparum were submitted to 5 different treatment schedules with clindamycin from 1981 to 1984: A - 89 patients were treated intravenously and orally, or intramuscularly and orally with 20 mg/kg/day divided into two daily applications for 5 to 7 days; B-40 patients were treated orally with 20 mg/kg/day divided into two daily doses for 5 to 7 days; C-27 patients were treated with 20 mg/kg/day intravenously or orally divided into two daily applications for 3 days; D-16 patients were treated orally and/or intravenously with a single daily dose of 20 to 40 mg/kg/day for 5 to 7 days; E-35 patients were treated orally with 5 mg/kg/day divided into two doses for 5 days. Patients were examined daily during treatment and reexamined on the 7th, 24th, 21st, 28th and 35th day both clinically and parasitologically (blood test). Eighty three (40.1%) had moderate or severe malaria, and 97 (46.8%) had shown resistance to chloroquine or to the combination ofsulfadoxin and pyrimethamine. The proportion of cured patients was higher than 95% among patients submitted to schedules A and B. Side effects were only occasional and of low intensity. Three deaths occurred (1.4%), two of them involving patients whose signs and symptoms were already very severe when treatment was started. Thus, clindamycin proved to be very useful in the treatment of patients with malaria caused by Plasmodium falciparum and we recommend schedule A for moderate and severe cases and Bfor initial cases.

Evaluation of a direct immunofluorescent antibody (difma) test using Leishmania genus - specific monoclonal antibody in the routine diagnosis of cutaneous leishmaniasis

A direct immunofluorescent antibody (DIFMA) test using a Leishmania genus- specific monoclonal antibody was evaluated in the routine diagnosis of cutaneous leishmaniasis (CL) in Ecuador. This test was compared with the standard diagnostic techniques of scrapings, culture and histology. Diagnostic samples were taken from a total of 90 active dermal ulcers from patients from areas of Ecuador known to be endemic for cutaneous leishmaniasis. DIFMA was positive in all lesions. It was shown to be significantly superior to standard diagnostic methods either alone or in combination. The sensitivity of DIFMA did not diminish with chronicity of lesions. This test proved to be extremely useful in the routine diagnosis of CL because it is highly sensitive, is easy to use and produces rapid results.

Influence of abiotic stress factors on VOCs emission from Portuguese rice paddy fields: relation with increased climate change

Dissertação para obtenção do Grau de Mestre em Engenharia do Ambiente Perfil de Gestão de Sistemas Ambientais

Frequency of Mycoplasma hominis and Ureaplasma urealyticum infections in women with systemic lupus erythematosus

Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) have been detected in the urine of women with systemic lupus erythematosus (SLE). We evaluated the presence of these mycoplasma in the endocervix of women presenting SLE. A total of 40 SLE patients (mean age 40.2 years), and 51 healthy women (mean age 30.9 years), were studied. Endocervical swabs were cultured in specific liquid media for MH or UU, detected by a quantitative color assay, and considered positive at >10³ dilutions. Statistical analysis was performed using the two-tailed Fisher test. UU was detected in 52.5 % of patients and in 11.8% of controls (p= 0.000059). MH was detected in 20% of patients and 2% controls (p=0.003905). Both mycoplasmas were detected in 7.3% patients and 0% controls (p<0.000001). The results reported here corroborate the association of the mycoplasma infection and SLE. Thus, these agents may stimulate the production of autoreactive clones.

Ecology of Phlebotomine sandflies (Diptera, Psychodidae) in Brazilian Atlantic Forest

The phlebotomine sandfly fauna of a primary forest reserve at Morretes (eastern Paraná State) was studied, using CDC-like light traps, one night per month, at canopy and ground level, between April 1995 and March 1996. A total of 3,106 insects were collected, identified as belonging to nine species. Lutzomyia ayrozai and Lu.geniculata were predominant, seven other species also being present. Monthly mean temperature, rainfall and the temperature of the collection night significantly influenced the numbers of Lu. ayrozai while the two first factors influenced the numbers of Lu. geniculata, besides the collected quantities of females of the two species. The influence of the factors on Lu. ayrozai numbers was more immediate than in those of Lu. geniculata. Numbers of both species and of the females of Lu. geniculata collected in different seasons, but not at the different heights, varied significantly. Differences between the behaviour of Lu. ayrozai in Morretes and in other regions could be attributed to environmental differences and/or to regional variations in the species, which could constitute species complexes. Hourly variations of collections were different in the species and seasons.

Impact of the HRM content (i.e. practices) and process (i.e. strength) on individual and organizational outcomes, in the hotel industry

A Work Project, presented as part of the requirements for the Award of a Masters Degree in Management from the NOVA – School of Business and Economics

Seroprevalence of human Trypanosoma cruzi infection in diferent geografic zones of Chiapas, Mexico

A serologic survey was carried out in four different geographic zones of Chiapas, Mexico. A total of 1,333 samples were collected from residents of thirteen communities located on the Coast, Central Mountain, Lacandon Forest and a zone called Mesochiapas. One hundred and fifty one seropositive individuals (11.3%) were identified. Human Trypanosoma cruzi infection was influenced by geography. In the Lacandon Forest and Central Mountains there was a higher seroprevalence 32.1 and 13.8% respectively, than on the coast (1.2%). In Mesochiapas there were no seropositive individuals among the 137 persons tested. An active transmission is probably continuing because seropositive cases (13.8%) were detected in children under 10 years of age. The vector recognized on the Coast was Triatoma dimidiata while in the Lacandon Forest it was Rhodnius prolixus.

Viral etiology of acute respiratory infections among children in Porto Alegre, RS, Brazil

Although acute respiratory infections (ARIs) are a major cause of child morbidity and mortality in Southern Brazil, little information is available on their seasonality and viral etiology. This study was conducted on children under 5 years of age with ARI to assess viral etiology in the State of Rio Grande do Sul, from 1990 to 1992. A total of 862 nasopharyngeal secretion (NPS) samples were tested using indirect immunofluorescence. The results showed that 316 (36.6%) NPS samples were positive: 26.2% for RSV, 6% for adenovirus, 1.7% for influenzaviruses, 1.5% for parainfluenzaviruses, and 1.2% for mixed infection. The mean viral prevalence rates in out-patient services, emergency wards, and in-patient hospital wards were 26.7%, 53% and 42.3%, respectively. Respiratory syncytial virus (RSV) and adenovirus accounted for 91.4 % of the viral diagnoses. RSV was more frequent in children under one year of age at the three levels of health care and was prevalent in infants under six months. Adenovirus was the most prevalent pathogen in hospitalized children, in 1992. Influenza A virus showed an increased prevalence with age among out-patient children. This study shows the annual occurence of viral respiratory infections in the coldest months, with a significant annual variation in the frequency of RSV infection.

Capillaria hepatica-induced hepatic fibrosis in rats: paradoxical effect of repeated infections

Multiple exposures to parasitic agents are considered an important factor in the genesis of the most severe forms of the diseases they cause. Capillaria hepatica-induced septal fibrosis of the liver in rats usually runs without signs of portal hypertension or hepatic failure. After determining the hepatic profile of 15 animals during the course of a single infection, we submitted 20 rats to multiple Capillaria hepatica infections to determine whether repeated exposures would augment fibrosis production, transforming septal hepatic fibrosis into a true cirrhosis. Ten single-infection rats served as controls. A total of 5 exposures, with 45-day intervals, were made. Histological changes were followed by means of surgical liver biopsies, collected prior to infection and to each re-infection. Functional changes were minimal and transient. Although a slight recrudescence of fibrosis was observed after the first two re-infections and when the single-infected control group was re-infected at the end of the experiment, subsequent re-infections failed to increase the amount of fibrosis. On the contrary, there occurred quantitative and qualitative evidence of collagen degradation and suppression of parasite development. These paradoxical results are in keeping with the hypothesis that a complex immunological modulation participates in the mechanism of hepatic fibrosis induced by Capillaria hepatica infection in rats.