Relação da pressão sistólica em artéria pulmonar com gênero, menopausa e gravidez em portadores de hipertensão arterial pulmonar associada à esquistossomose / Pulmonary artery pressure, gender, menopause, and pregnancy in schistosomiasis-associated pulmonary hypertension

FUNDAMENTO: A hipertensão arterial pulmonar associada à esquistossomose (HPAE) é uma grande preocupação no mundo todo. No entanto, o papel de fatores contribuintes específicos do gênero em HPAE é desconhecido. OBJETIVO: Investigamos os valores da pressão arterial pulmonar sistólica (PAPS) e a presença de elevação grave na PAPS relacionado ao gênero, presença de menopausa e histórico de gravidez em pacientes com HPAE. MÉTODOS: Setenta e nove pacientes diagnosticados com HPAE de 2000 a 2009 foram avaliados e 66 foram incluídos no estudo. As informações referentes à idade, status da menopausa, gravidez, PAPS derivada da ecocardiografia, e pressão arterial pulmonar média invasiva (PAPm) foram coletadas de registros médicos. A relação entre os valores de PAPS e PAPm e a correlação para doença grave foram avaliados. Os modelos de regressão avaliaram a associação de gênero, status da menopausa e histórico de gravidez com valores de PAPS e a presença de PAPS severa. RESULTADOS: Houve correlação moderada entre PAPm e PAPS, com boa concordância para classificação de doença grave. Os valores de PAPS foram semelhantes para homens e mulheres. Uma tendência a valores maiores de PAPS foi encontrada para mulheres não menopausadas em comparação a homens. Valores superiores de PAPS foram encontrados para mulheres menopausadas em comparação a mulheres não menopausadas; os valores não foram significativos após o ajuste de idade. O histórico de gravidez não teve relação com a PAPS. Presença de menopausa e passado de gravidez não mostraram associação com valores de PAPS. CONCLUSÃO: Em pacientes com HPAE, nem o gênero, nem o status da menopausa nem o histórico de gravidez apresentou uma correlação independente com valores de HPAE avaliados pela ecocardiografia.

BACKGROUND: Schistosomiasis-associated pulmonary arterial hypertension (SPAH) is a major concern worldwide. However, the role of gender-specific contributing factors in SPAH is unknown. OBJECTIVE: We investigated how systolic pulmonary artery pressure (SPAP) values and the presence of severe SPAP relate to gender, menopausal status, and pregnancy history in SPAH patients. METHODS: Seventy-nine patients diagnosed with SPAH from 2000 to 2009 were assessed and 66 were enrolled in the study. Information about age, menopausal status, pregnancy, echocardiography-derived SPAP, and invasive mean pulmonary artery pressure (mPAP) was collected from medical records. The relation between values of SPAP and mPAP and their agreement for severe disease were assessed. Regression models assessed the association of gender, menopausal status, and pregnancy history with SPAP values and the presence of severe SPAP. RESULTS: Moderate correlation and good agreement for severe disease were found between mPAP and SPAP. Mean SPAP values were similar for men and women. A trend toward higher values of SPAP was found for non-menopausal women compared to men. Higher SPAP values were found for menopausal compared to non-menopausal women; the values were non-significant after adjustment for age. Pregnancy history had no association with SPAP. Menopause and positive pregnancy had no association with severe SPAP. CONCLUSION: In SPAH patients, neither gender, nor menopausal status, nor pregnancy history showed independent correlation with SPAP values assessed by echocardiography.

Diseño, síntesis y evaluación biológica de un grupo de pirazinoisoquinolinas y quinolinas con posible actividad esquistosomicida y leishmanicida respectivamente / Design, synthesis and biological evaluation of a group of pyrazinoisoquinolines and quinolines with possible schistosomicidal and leishmanicidal activity respectively

La esquistosomiasis y la leishmaniasis son dos parasitosis con una alta incidencia en el mundo y con la menor cantidad de medicamentos disponibles para sus tratamientos. Para la esquistosomiasis, el praziquantel (PZQ) es la única droga que existe en los actuales momentos contra la enfermedad, mientras que, en el caso de la leishmaniasis, los antimoniales pentavalentes, empleados como drogas de primera línea, son altamente tóxicos o presentan problemas de resistencia. Por ello, esta tesis describe el diseño, la síntesis y los estudios de actividad biológica de un grupo de pirazinoisoquinolinas y quinolinas sustituidas con posible actividad esquistosomicida y leishmanicida respectivamente. Luego de ensayar diversas vías, se logró la síntesis del PZQ y compuestos relacionados (quince compuestos) mediante una secuencia de cinco pasos, con rendimientos entre el 20% y el 60%. El PZQ se obtuvo en un 33%, con un exceso del enantiómero levo, mostrando ser más activo que el PZQ comercial (mezcla racémica). Los compuestos obtenidos, evaluados en cepas de S. mansoni, no mostraron ser más activos que el PZQ, a las dos concentraciones evaluadas. También, se cuantificó la relación entre la estructura química y la actividad biológica (QSAR) de derivados de PZQ reportados en la literatura. En cuanto a los compuestos con posible actividad leishmanicida, también se ensayaron varios métodos de síntesis hasta lograr obtener veintidós quinolínas de los tipos 2-metil, 2-propil, 4-metil-2-propil y 2-alquildiamino con rendimientos entre un 10 y un 70%. Los compuestos evaluados que mostraron una actividad prometedora en promastigotes de L. mexicanafueron la 2-metilquinolina y 6,7-metilendioxi-2-propil-quinolina. En cuanto a los estudios QSAR, no fue posible encontrar una ecuación representativa que relacionara la actividad biológica con la estructura química.

Schistosomiasis and leishmaniasis are two parasitic diseaseswell spread in the world, and at the same time both have very few medications for their treatment. For schistosomiasis, praziquantel (PZQ) is the drug of choice for its treatment, while in the case of leishmaniasis, the pentavalent antimonials used as first line drugs are highly toxic or present resistance problems. This work describes the design, synthesis and biological activity studies of a group of pirazinoisoquinolines and substituted quinolines with a possible schistosomicidal and leishmanicidal activities, respectively. After several intents, it was possible to synthesize PZQ and some related compounds (fifteen) through a sequence of five steps, with yields between 20 and 60%. PZQ was obtained with a yield of 33%, with a levoenantiomeric excess, and showed a better activity than the commercial compound. The related compounds obtained, evaluated against S. mansonistrains did not have an activity comparable to that of PZQ, at the concentrations evaluated. Quantitative structure­activity relationships (QSAR)studieswere also performed with PZQ derivatives reported in the literature.Several ways of synthesis were also probed for the possible leishmanicidal compounds proposed, until it was possible to obtain twenty two quinoline derivatives (of the type 2-methyl-, 2-propyl-, 4-methyl-2-propyl-and 2-alquildiamino-), with yields between10 and 70%. Of the compounds evaluated, two showed promising activity against L. mexicana promastigotes, 2-iimethylquinoline and 6,7-methylendioxi-2-propyl-quinoline. QSAR studies with these compounds did not yield a representative model for the set.

Perfil hemodinâmico de gravidade ao teste de vasorreatividade pulmonar em esquistossomóticos / Hemodynamic profile of severity at pulmonary vasoreactivity test in schistosomiasis patients

FUNDAMENTO: A taxa de vasorreatividade pulmonar da Hipertensão Arterial Pulmonar Esquistossomótica (HAPE) não é conhecida. Dados hemodinâmicos obtidos pelo cateterismo cardíaco associam-se aos critérios clínicos de gravidade mais utilizados. OBJETIVO: Estimar o percentual de vasorreatividade positiva ao óxido nítrico em hipertensão arterial pulmonar esquistossomótica; verificar nesses pacientes a associação de parâmetros hemodinâmicos com a classificação funcional da OMS e teste de caminhada de seis minutos. MÉTODOS: Foram selecionados 84 pacientes portadores de hipertensão pulmonar de etiologia esquistossomótica de um banco de dados, submetidos ao cateterismo cardíaco direito e esquerdo com realização do teste de vasorreatividade pulmonar com óxido nítrico. Foram coletados os dados da classificação funcional da OMS e do teste de caminhada de seis minutos para fim de comparação com os dados invasivos. RESULTADOS: Dos 84 pacientes portadores de HAPE, três (3,5%) apresentaram os critérios para vasorreatividade pulmonar positivo. O aumento da resistência vascular pulmonar esteve associado significativamente à menor capacidade de esforço aferida pelo teste de caminhada de seis minutos (p = 0,045) e maiores sintomas de gravidade por meio de maiores classificações funcionais da OMS (classes III/IV) (p = 0,013). A diminuição da saturação de oxigênio na artéria pulmonar esteve associada significativamente a maiores classificações funcionais (p = 0,041). CONCLUSÃO: A taxa de resposta pulmonar ao teste de vasodilatação dos pacientes esquistossomóticos encontra-se abaixo dos valores encontrados para hipertensão pulmonar de etiologia idiopática. A resistência vascular pulmonar e a saturação de oxigênio na artéria pulmonar são dados hemodinâmicos que podem ser utilizados como marcadores de gravidade na hipertensão pulmonar esquistossomótica.

BACKGROUND: The pulmonary vasoreactivity rate of Schistosomal Pulmonary Artery Hypertension (SPAH) is not known. Hemodynamic data obtained by cardiac catheterization are associated with the most commonly used clinical criteria of severity. OBJECTIVE: To estimate the percentage of positive vasoreactivity to nitric oxide in schistosomal pulmonary arterial hypertension and verify the association of hemodynamic parameters with WHO functional classification and the six-minute walk test in these patients. METHODS: A total of 84 patients with schistosomal pulmonary hypertension were selected from a database, who had been submitted to the right and left cardiac catheterization and pulmonary vasoreactivity test with nitric oxide. Data on WHO functional classification and six-minute walk test were collected for comparison with invasive data. RESULTS: Of the 84 patients with SPAH, 3 (3.5%) had positive criteria for pulmonary vasoreactivity. The increase in pulmonary vascular resistance was significantly associated with lower exercise capacity measured by the six-minute walk test (p = 0.045) and greater symptom severity by higher functional classifications (WHO class III/IV) (p = 0.013). The decrease in oxygen saturation in the pulmonary artery was significantly associated with higher functional classifications (p = 0.041). CONCLUSION: The pulmonary response rate to the vasodilation test of schistosomiasis patients is below the values found for idiopathic pulmonary hypertension. Pulmonary vascular resistance and oxygen saturation in the pulmonary artery are hemodynamic data that can be used as markers of severity in schistosomal pulmonary hypertension.

Cerebral Schistosomiasis: case report and review of literature

Schistosomiasis is an infection caused by trematodes (flatworms from the phylum Platyhelminthes), which are acquired transcutaneously by swimming in contaminated waters. The central nervous system (CNS) schistosomiasis is a rare presentation of the disease. Brain infection to S. Mansoni has been rarely reported, in anedoctal fashion. It should be recognized early, since it disposes a specific treatment, and this treatment may prevent neurological deterioration. A high index of suspicion is necessary, mainly in patients coming from endemic areas, with brain or spinal cord lesions associated with eosinophilia and inflammatory CSF. Finding eggs from schistosoma into excrements or CNS biopsy confirms the diagnosis. We describe a 35-year old Brazilian man, harboring an isolated brain infection to S. mansoni.

Esquistossomose: quebrando o ciclo / Schistosomiasis: breaking the Cycle

O combate à esquistossomose esbarra nas dificuldades geradas pelas condições sanitárias a que muitas pessoas estão expostas, especialmente na região nordeste, devido à desigualdade social que ainda persiste no Brasil. Gravado na região metropolitana de Recife e Cabo de Santo Agostinho/PE, os principais objetivos deste vídeo são: oferecer aos profissionais do Sistema Único de Saúde (SUS) uma visão ampliada sobre a doença; contribuir para o conhecimento do seu ciclo; e orientar quanto ao reconhecimento do agente etiológico, bem como os fatores que mantêm a transmissão da doença.

Levels of growth hormone, albumin and ferritin in human fascioliasis and schistosomiasis

This study assessed levels of growth hormone, albumin and ferritin in human fascioliasis and schistosomiasis. Forty three patients and ten healthy parasite free subjects were included as controls. All were subjected to clinical, parasitological, and haematological examinations. Serum growth hormone [GH] levels were measured by an immunoenzymometric assay. Statistical analysis revealed significant elevation in GH levels in acute and chronic fascioliasis patients compared to controls. Serum albumin was significantly low in schistosomiasis patients compared to controls. Non-significant changes in serum ferritin were in all patients. The results were critically discussed on the light of the work done before

A Case of Combined Hepatocellular-Cholangiocarcinoma with Underlying Schistosomiasis

Combined hepatocellular-cholangiocarcinoma is a rare form of primary liver cancer showing features of both hepatocellular and biliary epithelial differentiation. We report here on a case with collision tumor, which apparently was the coincidental occurrence of both hepatocellular carcinoma and cholangiocarcinoma underlying schistosomiasis. A 39-year-old-Philippine female was transferred to our hospital for evaluation of a liver mass that was found on ultrasonography at a local hospital. HBsAg and Anti-HCV were negative and serum alpha-fetoprotein (AFP) level was normal. The tumor mass was histologically diagnosed as adenocarcinoma by sono-guided biopsy before the operation. Partial lobectomy was performed and we histologically identified the concurrent occurrence of hepatocellular carcinoma and cholangiocarcinoma, (a "collision type carcinoma").

Aspectos angiográficos das veias hepáticas na hipertensäo portal esquistosommótica: importância na medida da pressäo venosa hepática / Angiographic aspects of the hepatic veins in the portal hypertension in schistosomiasis: the importance in assessing the hepatic vein pressure

Admite-se que a pressao venosa ocluída em uma veia hepática reflita as condiçoes pressóricas do sistema portal em pacientes com cirrose hepática. No entanto, em pacientes com esquistossomose hepatoesplênica essas medidas mostram irregularidades nos resultados. A partir da análise de angiografias das veias hepáticas realizadas na avaliaçao pré-operatória de pacientes com esquistossomose hepatoesplênica complicada por hemorragia digestiva, identificamos imagens radiográficas que poderiam explicar a variabilidade dos resultados dessas medidas. As angiografias foram feitas durante a injeçao do contraste através do cateter com ponta em posiçao livre dentro da veia hepática D ou em uma veia hepática acessória do lobo D do fígado. As imagens angiográficas foram classificadas em duas categorias: a) tipo I - opacificaçao de porçao variável do território sinusoidal dependente da veia cateterizada. Presença de circulaçao através deste território ou de veias intra-hepáticas, estabelecendo comunicaçao entre a veia hepática cateterizada e veias acessórias do lobo D do fígado; b) tipo II - ausência de opacificaçao de território sinusoidal. Presença de múltiplas anastomoses intra-hepáticas entre a veia hepática D e veias acessórias do lobo D do fígado. Dada a existência dessas anastomoses no território de drenagem hepática venosa, questiona-se a validade da utilizaçao das medidas de pressao da veia hepática, na avaliaçao da pressao venosa portal em pacientes com esquistossomose hepatoesplênica, sem o controle radiográfico.

Natural killer [NK] cell activity in hepatocellular carcinoma [HCC] liver cirrhosis [LC] and schistosomiasis

Hepatocellular carcinoma [BCC] represents a major health problem in many developing countries in Asia and africa including Egypt. The role of the immune system especially natural killer [NK] cells had been poorly investigated in this disease. Our study included 67 patients [thirty seven patients with HCC, 25 with liver cirrhosis [LC] both secondary to alcoholic liver disease [ALD] and chronic viral hepatitis [CVH], and 15 patients with intestinal schistosomiasis]. The results were compared with age-and sex-matched healthy controls. Peripheral blood lymphocytes [PBL] were isolated from heparinized blood and NK cell activity was studied by the standard 4-hr Cr51 release assay using erythroleukemia cell line [K562] Results of this study revealed marked suppression of NK cell activity in HCC patients compared to that of the controls. The percent NK cytotoxicity at E: T ratio 100: 1 was 41.4 +/- 21.9 in patients and 67.9 +/- 7.7 in controls. The suppression of NK activity was stage-dependent, being more evident in advanced than earlier stages of the disease. LC patients showed lower NK activity than controls. However, there was no suppression in schistosomiasis patients. We conclude that suppression of NK cyotoxicity in LC might predispose to the development of HCC in these patients, however, with progression of cancer, the degree of suppression increases markedly leading to immune system breakdown

Estudo comparativo do fluxo portal em portadores de cirrose e esquistossomose através do ecodoppler / Comparative study of portal flow in patients with cirrhotic and schistossomotic by echo-doppler

O objetivo do trabalho foi estudar o fluxo portal em pacientes portadores de hepatopatia e indivíduos normais. Para isto, estudamos retrospectivamente 3 grupos de pacientes que haviam se submetido ao Eco-Doppler, sendo o grupo controle constituído por 10 indivíduos normais e os outros 2 grupos constituídos por 20 pacientes cirróticos e outros 20 pacientes esquistossomóticos. Os pacientes portadores de hepatopatia foram selecionados aleatoriamente e a confirmaçäo da etiologia se fez através de dados realizados com o mesmo aparelho e pelo mesmo operador tornando os resultados mais fidedignos. Como resultado verificou-se que, tanto nos portadores de cirrose quanto nos de esquistossomose, o fluxo na veia porta mantém-se no sentido centrípeto, ou seja, hepatopetal, mesmo nos portadores de hepatopatias graves. Como conclusäo contatou-se que a velocidade do fluxo na veia porta (VP) dos indivíduos cirróticos é significativamente menor do que os indivíduos do grupo controle e dos esquistossomóticos, e que a velocidade do fluxo na veia porta (VP) nos esquistossomóticos é maior que a do grupo controle

T-Lymphocyte subsets in Egyptians with schistosomal infestation

The immunoregulating mechanism in schistosomal infestation among Egyptains childern was studied by enumerating T-Iymphocyte cell subsets in peripheral blood. There was no significant difference between the mean values of absolute lymphocytic count [ALC]. T[3] and T[8] in the control group and either the urinary or intestinal bilharzial groups of cases. However, the mean value of T[4] in the bilharzial urinary and intestinal groups of cases were found to be statistically significant when compared with the control group

Decreased antithrombin III: is it a cause or a result of oesophageal varices bleeding in endemic hepatic schistosomiasis

Chronic liver disease is often associated with many hemostatic abnormalities including decreased level of antithrombin 3 [AT3]. However, the involvement of AT3, in esophageal varices bleeding has not been demonstrated before. The aim of this study is to demonstrate the hemostatic abnormalities especially the disturbance in AT3 level in patients with bleeding esophageal varices. Forty subjects were studied including 10 normal control cases, 15 cases with bleeding esophageal varices [group 1] and 15 cases with silent varices [group 2]. All cases were subjected to the following hemostatic tests: Prothrombin time [PT], partial thromboplastin time [PTT], antithrombin 3 level, fibrinogen [F] and fibrin degradation products [FDP]. All these tests were done to patients of group 1, the first during the bleeding episode [la] and the second after control of bleeding by two weeks [lb]. There was significant deterioration in all the hemostatic parameters studied in both groups 1 and 2 compared to control. Further significant impairment in some of these parameters namely PT, AT3, FDP and platelet count occurred in patients of group 1 during active bleeding [la] compared to silent varices patients [group 2]. Most of these test differences disappeared after control of bleeding by two weeks with the exception of AT3, which was still significantly lower in group 1b compared with group 2 [p <0.005]. It was concluded that AT3 might be of great value to predict hepatic patients prone to bleed through their esophageal varices. Further prospective studies are needed

Gastric emptying time in bilharzial patients with and without hepatitis-C virus infection

Eighty one adult male Egyptian bilharzial patients were subjected to the study. Their ages ranged from 25 to 45 years. Their complains were nausea, vomiting, eructation and epigastric pain. Full clinical, laboratory examination, liver biopsies, upper endoscopy, ECG and barium meal, were done to every patient. They were divided into 3 groups. Group I, bilharzial patients who were negative for hepatitis- C, group II, bilharzial patients who were positive for hepatis-C, and group III, control group [normal persons]. Gastric emptying time was prolonged in group I, but was more prolonged in group II patients. There were strong positive correlations between symptoms and gastric emptying times

On some clinical and ultrasonic correlative studies on schistosomal portal hypertension patients

Thirty patients suffering from manifestations of portal hypertension, in addition to ten controls, were assessed. Endoscopic grading of the esophageal varices, ultrasonographic examination to measure the longitudinal axis of the spleen and the diameters of the portal and splenic veins were performed in all patients. The present study derived positive linear meaningful correlations between the diameter of the portal vein, the severity of hematemesis and the grade of the esophageal varices. On the other hand, no linear correlations could be observed between the splenic vein diameter or the size of the spleen and the pattern of the esophageal varices

Acute phase proteins in endemic chronic liver diseases

Forty patients with chronic liver disease and ten normal controls were investigated for acute phase proteins. Mixed schistosomal cases with chronic hepatitis or cirrhosis showed more marked changes, while pure schistosomal group showed serum levels closer to normal values. This could be a differentiating point between the two categories. Also the more significant changes in the mixed groups indicate more involvement of the immune system in the pathogenesis of those groups