Pharmacodynamics of mefloquine and praziquantel combination therapy in mice harbouring juvenile and adult Schistosoma mansoni

Praziquantel (PZQ) is currently the only drug widely used for the treatment of schistosomiasis, but the antimalarial drug mefloquine (Mef) possesses interesting antischistosomal properties. Combination therapy with these two drugs has been suggested as a strategy for transmission control, as PZQ is active against adult worms and Mef is active against schistosomula. To examine the efficacy of combination therapy, Schistosoma mansoni-reinfected mice were separated into seven groups: untreated (I), treated with PZQ in doses of 200 mg/kg (II) or 1,000 mg/kg (III), treated with Mef in doses of 200 mg/kg (IV) or 400 mg/kg (V); each dose was divided equally and given on two consecutive days. Group VI was treated with doses of PZQ + Mef as in groups II and IV, respectively, while group VII was treated with PZQ + Mef as in groups III and V, respectively. PZQ + Mef at the reduced doses of 200 mg/kg each enhanced the therapeutic efficacy over the reduced PZQ dose alone as shown by a very high reduction in the total numbers of mature worms (95% vs. 49%), immature worms (96% vs. 29%) and the complete eradication of immature females, mature females and immature eggs. The reduction in worm burden was associated with the healing of hepatic granulomatous lesions and the normalisation of all liver enzymes. Therefore, the use of Mef with PZQ is more effective than PZQ alone and should be considered for clinical trials in humans as a potential treatment regimen to prevent treatment failures in areas with high rates of schistosomiasis.

Advocacia em saúde no Brasil contemporâneo

Apresenta-se o conceito de advocacia em saúde, por meio da descrição de seus elementos, sua prática e seus agentes. A necessidade da formulação de tal conceito surge da função que tem a universidade, entre outras, de identificar demandas sociais e oferecer alternativas que busquem a superação de obstáculos. A ênfase é centrada na participação social, assegurada na Constituição, promulgada em 1988, e que desde então tem sido tomada como referência no desenvolvimento dos mecanismos de construção da cidadania, especialmente quando relacionada à conquista do direito à saúde.

FETO-PLACENTARY PATHOLOGY IN HUMAN PARVOVIRUS B19 INFECTION

In view of the scarce references concerning the histological data in congenital parvovirus human B19 infection, we intend to provide a description of the pathological features observed in six autopsies.The virus was detected by DNA hybridization (ISH-DBH),PCR and electronmicroscopy (EM) in paraffin-embedded feto-placentary tissues.These cases constitute a subset from 86 Non Immunologic Hydrops Fetalis (NIHF) cases, in which a systemic complex of inflammatory/degenerative lesions of unknown etiology was visualized by optical microscopy. In one case a syphilitic process was detected, typefying a double infection. All fetuses showed a similar pathology - hydrops, hepato-splenomegaly, lung hypoplasia and erythroblastemia, the specific histological feature being the presence of intranuclear inclusions in the erythroid progenitors, in the erythropoietic visceral tissue and in blood marrow. Complex cardiopathy allied to abnormal lung lobulation and polisplenia were observed once; in 2 cases endocardial fibroelastosis was diagnosed. The pulmonary lesions were represented by dysmaturity allied to interstitial mononuclear infiltration. The hepatic consisted of cholestasis, portal fibrosis, canalicular proliferation, hemossiderosis, focal necroses and giant cell transformation. The central nervous system lesions were predominantly anoxic although the autolysis impaired a correct diagnosis.

Genetic variation between susceptible and non-susceptible snails to Schistosoma infection using random amplified polymorphic DNA analysis (RAPDs)

Susceptibility of snails to infection by certain trematodes and their suitability as hosts for continued development has been a bewildering problem in host-parasite relationships. The present work emphasizes our interest in snail genetics to determine what genes or gene products are specifically responsible for susceptibility of snails to infection. High molecular weight DNA was extracted from both susceptible and non-susceptible snails within the same species Biomphalaria tenagophila. RAPD was undertaken to distinguish between the two types of snails. Random primers (10 mers) were used to amplify the extracted DNA by the polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis (PAGE) and silver staining. The results suggest that RAPD represents an efficient means of genome comparison, since many molecular markers were detected as genetic variations between susceptible and non-susceptible snails.

Does Cleome droserifolia have anti-schistosomiasis mansoni activity?

The present study was undertaken to assess the effect of the crude extract of Cleome droserifolia (CD) leaves on experimentally infected mice with Schistosoma mansoni. Two groups of mice, showing a patent infection of S. mansoni, one of them was daily treated with an alcoholic extract of CD leaves (0.31 g kg-1 body weight, i.p.) for 21 days. The schistosomicidal activity of the CD extract was evaluated, three weeks post-treatment, on some parasitological and histopathological aspects including worm load, oogram pattern, faecal eggs releasing and granuloma formation. In addition, serum thyroid hormones levels (tri-iodothyronine; T3 and tetra-iodo-thyronin; T4), serum total protein contents and hepatic reduced glutathione (GSH) were evaluated. Treatment using CD extract resulted in a weak reduction in worm burden (32.46%) and affected the viability of both mature and immature eggs as indicated by the increase in the percentage of dead eggs and the decrease in the percentage of live ones. In addition, a week post-treatment, eggs elimination was observed in the stool of the infected-treated group which was low compared to the infected group. There was a suppressive effect of the extract on granuloma formation that could be due to the antioxidant effect of the extract. These data are confirmed by increasing hepatic GSH, serum total proteins and thyroid hormone levels in the infected-treated group as compared to the infected group. Treatment significantly enhanced b globulin fractions of the protein. Based on these assumptions, CD extract has beneficial effects on thyroid hormones status and anti-schistosomiasis activity. The beneficial effects of CD extract could be related to its direct effects on the parasite, and secondary to its effect on the antioxidant capacity of the host. The present study could emphasize the precise mechanism (s) of CD extract protection.

Potential of biologically active plant oils to control mosquito larvae (Culex pipiens, Diptera: Culicidae) from an egyptian locality

The insecticidal effect of six commercially available plant oils was tested against 4th larval instars of Culex pipiens. Larvae were originally collected from Meit El-Attar, Qalyubia Governorate, Egypt, and then reared in the laboratory until F1 generation. The LC50 values were 32.42, 47.17, 71.37, 83.36, 86.06, and 152.94 ppm for fenugreek (Trigonella foenum-grecum), earth almond (Cyperus esculentus), mustard (Brassica compestris), olibanum (Boswellia serrata), rocket (Eruca sativa), and parsley (Carum ptroselinum), respectively. The tested oils altered some biological aspects of C. pipiens, for instance, developmental periods, pupation rates, and adult emergences. The lowest concentrations of olibanum and fenugreek oils caused remarkable prolongation of larval and pupal durations. Data also showed that the increase of concentrations was directly proportional to reduction in pupation rates and adult emergences. Remarkable decrease in pupation rate was achieved by mustard oil at 1000 ppm. Adult emergence was suppressed by earth almond and fenugreek oils at 25 ppm. In addition, the tested plant oils exhibited various morphological abnormalities on larvae, pupae, and adult stages. Consequently, fenugreek was the most potent oil and the major cause of malformation of both larval and pupal stages. Potency of the applied plant oils provided an excellent potential for controlling C. pipiens.

Distribuição espacial dos casos de leishmaniose tegumentar americana no município de Campinas, Estado de São Paulo, no período de 1992 a 2003

Trata-se de estudo retrospectivo com componente ecológico que descreve o padrão epidemiológico e a distribuição geográfica da leishmaniose tegumentar americana no município de Campinas, SP de 1992 a 2003. Os locais prováveis de infecção foram georeferenciados por meio de Sistema de Posicionamento Global e espacializados pelo programa Spring 4.01 do Instituto Nacional de Pesquisas Espaciais. Foi aplicado o estimador de intensidade kernel para se obter as regiões com maior freqüência de casos. Identificou-se a ocorrência de 3 surtos (região Leste e Sudoeste) nos anos de 1993/1995 e 2002/2003. Foram estudadas variáveis sócio-demográficas, proximidade do domicílio à mata, tempo de moradia e forma clínica da doença. Embora as características ecológicas e sócio-ambientais das áreas de estudo sejam diferentes, os surtos apresentaram perfil semelhante. A distribuição por sexo, idade e ocupação sugere possível transmissão peridomiciliar. A proximidade dos locais prováveis de infecção das matas foi comum a todas as áreas.

Leptospirosis in animals and human contacts in Egypt: broad range surveillance

INTRODUCTION: Leptospirosis is a re-emerging zoonotic disease of humans and animals worldwide. The disease is caused by pathogenic species of the genus Leptospira. These organisms are maintained in nature via chronic renal infection of carrier animals, which excrete the organisms in their urine. Humans become infected through direct or indirect exposure to infected animals and their urine or through contact with contaminated water and soil. This study was conducted to investigate Leptospira infections as a re-emerging zoonosis that has been neglected in Egypt. METHODS: Samples from 1,250 animals (270 rats, 168 dogs, 625 cows, 26 buffaloes, 99 sheep, 14 horses, 26 donkeys and 22 camels), 175 human contacts and 45 water sources were collected from different governorates in Egypt. The samples were collected from different body sites and prepared for culture, PCR and the microscopic agglutination test (MAT). RESULTS: The isolation rates of Leptospira serovars were 6.9%, 11.3% and 1.1% for rats, dogs and cows, respectively, whereas the PCR results revealed respective detection rates of 24%, 11.3% and 1.1% for rats, dogs and cows. Neither the other examined animal species nor humans yielded positive results via these two techniques. Only six Leptospira serovars (Icterohaemorrhagiae, Pomona, Canicola, Grippotyphosa, Celledoni and Pyrogenes) could be isolated from rats, dogs and cows. Moreover, the seroprevalence of leptospiral antibodies among the examined humans determined using MAT was 49.7%. CONCLUSIONS: The obtained results revealed that rats, dogs and cows were the most important animal reservoirs for leptospirosis in Egypt, and the high seroprevalence among human contacts highlights the public health implications of this neglected zoonosis.

Preditores de viabilidade em pacientes com resposta negativa à ecocardiografia de estresse com dobutamina de baixa dose

FUNDAMENTO: A ecocardiografia de estresse com dobutamina de baixa dose é um teste específico para predizer disfunção de contratilidade reversível, mas mesmo assim, sua sensibilidade é menor do que ideal. OBJETIVO: Avaliar os preditores de recuperação miocárdica contrátil após a revascularização, em pacientes sem viabilidade na ecocardiografia de estresse com dobutamina de baixa dose. MÉTODOS: Trinta pacientes consecutivos foram selecionados consecutivamente, que apresentavam estenose coronária/oclusão significantes, tratáveis através de revascularização, anormalidade de motilidade de parede regional na distribuição da artéria afetada e ausência de viabilidade na ecocardiografia de estresse com dobutamina de baixa dose. Os pacientes foram submetidos a estudo de imagem com 99mTc-sestamibi em repouso e então submetidos à revascularização coronária bem sucedida. A ecocardiografia de seguimento foi realizada três meses depois. Os pacientes foram classificados em 2 grupos: grupo 1: com evidência de recuperação miocárdica contrátil após a revascularização na ecocardiografia de seguimento e grupo 2: sem evidência de recuperação miocárdica. Os dois grupos foram comparados em relação aos dados clínicos, ecocardiográficos e cintilográficos. RESULTADOS: A média da idade era 52,3 ± 5,9 anos e 97% eram do sexo masculino. A porcentagem de captação total de 99mTc-sestamibi foi significantemente mais alta no grupo 1 quando comparado ao grupo 2 (p < 0,01) e foi o preditor independente mais forte de recuperação miocárdica contrátil no seguimento de 3 meses na análise de regressão multivariada. A curva ROC (Receiver Operating Characteristic) mostrou que um valor de corte da porcentagem de captação total do 99mTc-sestamibi uptake de 72%, foi o melhor preditor da recuperação miocárdica contrátil, com uma sensibilidade de 100% e especificidade de 95.7%. CONCLUSÃO: Em pacientes sem evidência de viabilidade na ecocardiografia de estresse com dobutamina de baixa dose, a porcentagem de captação total do 99mTc-sestamibi prediz, de forma independente, a recuperação miocárdica contrátil após a revascularização coronária.

Leptina e aldosterona na atividade simpática na hipertensão resistente, com ou sem Diabetes Tipo 2

FUNDAMENTO: A descoberta da leptina como um estimulador da atividade simpática trouxe uma nova perspectiva para os mecanismos fisiopatológicos da obesidade-hipertensão. OBJETIVO: Avaliamos a relação entre a atividade simpática aumentada e as concentrações plasmáticas de leptina e aldosterona em Hipertensos Resistentes (HR), comparando os grupos com e sem Diabetes Tipo 2 (DT2). MÉTODOS: Vinte e cinco pacientes HR foram avaliados por eletrocardiografia ambulatorial para análise da Variabilidade da Frequência Cardíaca (VFC) nos domínios do tempo e frequência, os quais foram estratificados em dois períodos: 24 horas e período Diurno (D), compreendendo as medidas entre 14 e 18h (domínio do tempo) e uma hora às 15h (domínio da frequência). RESULTADOS: O grupo DT2 (n = 10) apresentou maiores concentrações de aldosterona e leptina que o grupo não DT2 (n = 15) (26,0 ± 11,5 vs. 16,9 ± 7,0 ng/dL - p = 0,021; 81,368.7 ± 47,086.1 vs. 41,228.1 ± 24,523.1 pg/mL - p = 0,048, respectivamente). Houve correlação entre aldosterona e VFC no domínio da frequência em ambos os grupos. Não-DT2 apresentaram a aldosterona correlacionada com D baixa frequência em unidades normalizadas (BFnu) (r = 0,6 [0,12 - 0,85] p = 0,018) e D alta frequência em unidades normalizadas (AFnu) (r = -0,6 [-0,85 - -0,12] p = 0,018). No grupo com diabetes, a aldosterona correlacionou-se com DBFnu (r = 0,72 [0,16 - 0,93] p = 0,019) e DAFnu (r = -0,72 [-0,93 - -0,16] p = 0,019). Apesar da importância da leptina na atividade simpática aumentada na hipertensão, não houve correlação com VFC. CONCLUSÃO: A aldosterona parece estimular a atividade simpática em HR com ou sem DT2. Essa informação combinada com a eficácia clínica dos bloqueadores de receptor mineralocorticoide em HR pode reforçar a aldosterona como alvo terapêutico relevantes em HR. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0)

The value of ultrasonography in assessment of portal hypertension in hepatosplenic schistosomiasis

Ultrasonography can reveal most of the manifestations of portal hypertension complicating hepatosplenic, schistosomiasis. However, direct demonstration of gastroesophageal varices by ultrasonography is still very difficult. An attempt was done to correlate sonographic features of portal hypertension with the degree of fibrosis to screen patients having varices and predicting their chance of bleeding. The results obtained were found to be consistent with the esophagogastric endoscopy and with history of hematemesis. Four parameters were used, size of spleen, degree of periportal fibrosis, presence of collaterals and portal vein diameter. A pilot field survey was also done adopting the same principle.

Schistosomiasis control in a primary health care system

The successful implementation of a Primary Health Care System (PHC) in any country depends primarily on the ability to adapt its concepts and principles to the country's culture and development stage. Thus, the PHC system should reflect a balanced interaction between available resources, such as health manpower capabilities, and the nature and magnitude of the health problems. In addition, PHC should be viewed as the inlet to a multi-level pyramidal health system which caters to both community and individual needs in a balanced way. The adage that Ministries of Health should "work with and for the people" in health development, is especially true in the area of PHC, and hence, the health policy should aim to integrate health services in community development and involve people in its planning, implementation and evaluation.

Complete immunization against Trypanosoma cruzi verified in individual mice by complement-mediated lysis

Experimental systems to assay immunity against Trypanosoma cruzi usually demonstrate partial resistance without excluding the establishment of sub-patent infections in protected animals. To test whether Swiss mice immunized with attenuated parasites might develop complete resistance against virulent T. cruzi, experiments were performed involving challenge with low numbers of parasites, enhancement of local inflammation and the combination of natural and acquired resistance. Absence of infection was established after repeated negative parasitological tests (including xenodiagnosis and hemoculture), and lack of lytic antibody was tested by complement mediated lysis. Immunization with 10(7) attenuated epimastigotes conferred protection against the development of high levels of parasitemia after challenge with Tulahuen strain, but was unable to reduce the number of infected animals. However, when a strong, delayed-type hypersensitivity reaction was triggered at the site of infection by injecting a mixture of virulent and attenuated T. cruzi, a significant proportion of immunized animals remained totally free of virulent infection. The same result was obtained when the immunization experiment was performed in four month old Swiss mice, displaying a relatively high natural resistance and challenged with wild, vector-borne parasites. These experiments demonstrate that complete resistance against T. cruzi can be obtained in a significant proportion of animals, under conditions which replicate natural, vector delivered infection by the parasite.

Genetic markers between Biomphalaria glabrata snails susceptible and resistant to Schistosoma mansoni infection

The analysis of the genetic variability related to susceptibility to Schistosoma mansoni infection in the vector of the genus Biomphalaria is important in terms of a better understanding of the epidemiology of schistosomiasis itself, the possible pathological implications of this interaction in vertebrate hosts, and the formulation of new strategies and approaches for disease control. In the present study, the genetic variability of B. glabrata strains found to be resistant or susceptible to S. mansoni infection was investigated using DNA amplification by random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR). The amplification products were analyzed on 8% polyacrylamide gel and stained with silver. We selected 10 primers, since they have previously been useful to detect polymorphism among B. glabrata and/or B. tenagophila. The results showed polymorphisms with 5 primers. Polymorphic bands observed only in the susceptible strain. The RAPD-PCR methodology represents an adequate approach for the analysis of genetic polymorphisms. The understanding of the genetic polymorphisms associated to resistance may contribute to the future identification of genomic sequences related to the resistance/susceptibility of Biomphalaria to the larval forms of S. mansoni and to the development of new strategies for the control of schistosomiasis.