Disturbance in hemoglobin metabolism and in vivo antimalarial activity of azole antimycotics / Alteración en el metabolismo de la hemoglobina y actividad antimalárica in vivo de azoles antimicóticos

Plasmodium parasites degrade host hemoglobin to obtain free amino acids, essential for protein synthesis. During this event, free toxic heme moieties crystallize spontaneously to produce a non-toxic pigment called hemozoin or ß-hematin. In this context, a group of azole antimycotics, clotrimazole (CTZ), ketoconazole (KTZ) and fluconazole (FCZ), were investigated for their abilities to inhibit ß-hematin synthesis (IßHS) and hemoglobin proteolysis (IHbP) in vitro. The ß-hematin synthesis was recorded by spectrophotometry at 405 nm and the hemoglobin proteolysis was determined by SDS-PAGE 12.5 percent, followed by densitometric analysis. Compounds were also assayed in vivo in a malaria murine model. CTZ and KTZ exhibited the maximal effects inhibiting both biochemical events, showing inhibition of β-hematin synthesis (IC50 values of 12.4 ± 0.9 µM and 14.4 ± 1.4 µM respectively) and inhibition of hemoglobin proteolysis (80.1 ± 2.0 percent and 55.3 ± 3.6 percent, respectively). There is a broad correlation to the in vivo results, especially CTZ, which reduced the parasitemia ( percentP) of infected-mice at 4th day post-infection significantly compared to non-treated controls (12.4 ± 3.0 percent compared to 26.6 ± 3.7 percent, p = 0.014) and prolonged the survival days post-infection. The results indicated that the inhibition of the hemoglobin metabolism by the azole antimycotics could be responsible for their antimalarial effect.

Los parásitos del género Plasmodium degradan la hemoglobina hospedera obteniendo aminoácidos libres para su síntesis proteica. Durante este evento, unidades de hemo libre tóxicas cristalizan espontáneamente formando un pigmento no tóxico denominado ß-hematina. En este trabajo, se investigó la capacidad de un grupo de azoles antimicóticos: clotrimazol (CTZ), ketoconazol (KTZ) y fluconazol (FCZ), en inhibir la síntesis de ß-hematina y la proteólisis de la globina. La síntesis de ß-hematina se registro por espectrofotometría a 405 nm y la proteólisis de la hemoglobina se determino por SDS-PAGE 15 por ciento seguido por análisis densitométrico de las bandas de hemoglobina intactas. Los compuestos fueron también ensayados in vivo en un modelo de malaria murina. CTZ y KTZ inhibieron la síntesis de ß-hematina con CI50 entre 10 y 15 µM y bloquearon la proteólisis de la hemoglobina (80.01 ± 2.04 por ciento y 55.33 ± 3.57 por ciento, respectivamente). En relación directa con los resultados encontrados in vitro, el CTZ redujo la parasitemia de ratones infectados en forma significativa, así como prolongó lo días de sobrevivencia post-infección en comparación con animales controles no tratados. Se sugiere así que la inhibición del metabolismo de la hemoglobina por los antimicóticos azólicos pudiera ser el mecanismo responsable de su actividad antimalárica.

Tenossinovites De Quervain: uma nova proposta no tratamento cirúrgico / De Quervain’s tenosynovitis: a new proposal of surgical treatment

Introdução: A tenossinovite estenosante De Quervain caracteriza-se por ser a inflamação da bainha do abdutor longo e extensor curto do polegar, no primeiro compartimento dorsal do punho, acometendo mais frequentemente as mulheres na faixa etária entre 30 e 50 anos. Essa doença está associada principalmente a trauma crônico secundário e sobrecarga das atividades diárias das mãos e punho, podendo também ser causada por outros fatores, mas em muitos casos não há uma causa bem definida. Objetivo: O objetivo deste trabalho é apresentar nossa casuística de tenossinovite de De Quervain no Ambulatório de Cirurgia da Mão, os diferentes tratamentos e uma nova proposta cirúrgica utilizando um retalho fáscio-gorduroso de vizinhança. Resultados: Com a técnica proposta foram obtidos resultados satisfatórios, diminuindo as recidivas, com boa recuperação funcional e rápido retorno dos pacientes às atividades cotidianas.

Introduction: De Quervain’s stenosing tenosynovitis it is characterized by being the inflammation of the hem of the long and extending abductor short of the thumb, in the 1st number compartment of the fist, more frequently attacking the women in the age group between 30 and 50 years. That pathology is associated mainly to secondary chronic trauma and overload of the daily activities of the hands and fist, could also be caused by other factors, but in many cases no there is a very defined cause. Results: All the patients had a faster and satisfactory evolution with an amazing come back to their quotidian activities.

Modification of oxidative status in Plasmodium berghei-infected erythrocytes by E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline compared to chloroquine

E-2-chloro-8-methyl-3-[(4'-methoxy-1'-indanoyl)-2'-methyliden]-quinoline (IQ) is a new quinoline derivative which has been reported as a haemoglobin degradation and ß-haematin formation inhibitor. The haemoglobin proteolysis induced by Plasmodium parasites represents a source of amino acids and haeme, leading to oxidative stress in infected cells. In this paper, we evaluated oxidative status in Plasmodium berghei-infected erythrocytes in the presence of IQ using chloroquine (CQ) as a control. After haemolysis, superoxide dismutase (SOD), catalase, glutathione cycle and NADPH + H+-dependent dehydrogenase enzyme activities were investigated. Lipid peroxidation was also assayed to evaluate lipid damage. The results showed that the overall activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase were significantly diminished by IQ (by 53.5 percent and 100 percent, respectively). Glutathione peroxidase activity was also lowered (31 percent) in conjunction with a higher GSSG/GSH ratio. As a compensatory response, overall SOD activity increased and lipid peroxidation decreased, protecting the cells from the haemolysis caused by the infection. CQ shared most of the effects showed by IQ; however it was able to inhibit the activity of isocitrate dehydrogenase and glutathione-S-transferase. In conclusion, IQ could be a candidate for further studies in malaria research interfering with the oxidative status in Plasmodium berghei infection.

Carcinoma metastático de mama para couro cabeludo / Breast carcinoma metastatic to the scalp

Apesar de as neoplasias metastáticas para a cabeça e pescoço serem raras quando comparadas com as neoplasias primárias, o carcinoma metastático de mama tem sido descrito em diversos sítios da cabeça e pescoço. Este é um caso de uma paciente com adenocarcinoma de mama que evoluiu com metástase para couro cabeludo.

Although the metastasis to head and neck are rare when compared with primary neoplasms, metastatic carcinoma from breast has been described in many sites of head and neck. This is a case of a patient with adenocarcinoma of breast that developed metastasis to the scalp.

Urban malaria in the Brazilian Western Amazon Region I: high prevalence of asymptomatic carriers in an urban riverside district is associated with a high level of clinical malaria

Cross sectional studies on malaria prevalence was performed in 2001, 2002, and 2004 in Vila Candelária, an urban riverside area of Porto Velho, Rondônia, in the Brazilian Western Amazon, followed by longitudinal surveys on malaria incidence. Vila Candelária is a working class district, provided with electricity, water supply, and basic sanitation. Previous preliminary surveys indicated high malaria incidence in this community. At the end of year 2000 regular diagnostic and treatment measures for malaria were introduced, with active search of febrile cases among residents. Despite of both rapid treatment of cases and relative good sanitary and housing conditions, the malaria incidence persisted at high levels during the following years with an annual parasite index of 150 to 300/1000 inhabitants. Parasite surveys in 2001, 2002, and 2004 achieved through microscopy and polymerase chain reaction to diagnose malaria showed a constant high prevalence of asymptomatic carriers for both Plasmodium falciparum and P. vivax parasites. It was concluded that asymptomatic carriers represent an important reservoirs of parasites and that the carriers might contribute to maintaining the high level of transmission. Comparing our findings to similar geo-demographic situations found in other important urban communities of the Brazilian Amazon, we propose that asymptomatic carriers could explain malaria's outbreaks like the one recently observed in Manaus.

Estudio por computadora de los desequilibrios electrolíticos y ácido-básicos / Study by computer of acid-base and electrolyte unbalances

Se expresa que los trastornos del equilibrio electrolítico y ácido-básico, son frecuentes e importantes en la práctica pediátrica y su solución breve cobra una mayor urgencia por tratarse de la vida de un niño; por tal motivo, se ha desarrollado un programa en la microcomputadora personal 8001 MK II que evaluá rápidamente las posibles facetas de los trastornos electrolíticos y del equilibrio ácido-básico. El programa acepta datos clínicos y de laboratorio, contiene instrucciones para realizar cálculos, transmite la evaluación del equilibrio ácido-básico y también pregunta por la concentración de los electrólitos del suero en mEq/l. Además, genera como respuesta una nota evaluatoria, una lista de posibilidades etiológicas, una breve discusión de las medidas terapéuticas sugeridas y un número de referencias de la literatura revisada si el médico lo desea. En términos generales, los propósitos del programa son proveer al pediatra de una herramienta útil para resolver en breve tiempo un problema clínico de extremada urgencia como son los trastornos electrolíticos y del equilibrio ácido-básico, así como una importante guía metodológica y docente