Comportamiento clínico-terapéutico de Fasciola hepatica en una serie de 87 pacientes / Clinical and therapeutic behaviour of Fasciola hepatica in a series of 87 patients

Introducción: la fasciolosis, por Fasciola hepatica, muestra a escala mundial un incremento en la incidencia de enfermos en los últimos años. Cuba se encuentra entre aquellos países donde se reportan casos esporádicos y algunos brotes epidémicos. Objetivo: describir el comportamiento clínico-terapéutico de esta trematodiosis de trasmisión digestiva en una serie de 87 pacientes ingresados en el Instituto de Medicina Tropical "Pedro Kourí" desde enero de 1996 a diciembre de 2005. Método: los pacientes se dividieron en 2 grupos atendiendo al fármaco prescrito, dihidroemetina o triclabendazol. Se recogieron las variables clínicas al inicio del diagnóstico y 90 d después del tratamiento; se hallaron las medias y la desviación estándar. Resultados: el sexo masculino predominó discretamente con 54 por ciento en nuestra serie de pacientes ingresados en el servicio de medicina tropical del instituto. La ingestión de berro (Nasturtium officinale) estuvo presente en casi la mitad de los pacientes. El dolor abdominal, fiebre y astenia resultaron los síntomas de mayor frecuencia. El triclabendazol y la dihidroemetina fueron útiles en el tratamiento. Conclusiones: se comprobó la utilidad de los exámenes de laboratorio en el diagnóstico y seguimiento de los enfermos. Los antiparasitarios dihidroemetina y triclabendazol resultaron efectivos a las dosis utilizadas con efectos adversos menores.

Introduction: in the last few years, the Incidence rate of fascioliosis caused by Fasciola hepatica has increased worldwide. Cuba is one of the countries that have reported sporadic cases and also some outbreaks of fasciolosis. Objective: to describe clinical and therapeutic features of this trematodiasis of digestive transmission found in 87 patients, who had been admitted to "Pedro Kourí" Institute of Tropical Medicine from January 1996 to December 2005. Methods: patients were divided into 2 groups according to the prescribed drug, that is, triclabendazole and dihydroemetine. The clinical variables were collected at the time of diagnosis and 90 days after treatment; the means and the standard deviation were estimated. Results: males was slightly predominant (54) in our series of patients admitted to the institute service. Consumption of watercress (Nasturtium officinale) was found in almost half of the patients. Abdominal pain, fever and malaise were the most frequent symptoms. Both drugs were useful to treat F. hepatica. Conclusions: this study showed the usefulness of lab tests for diagnosis and follow-up of patients after treatment. The anti-parasitic drugs dihydroemetine and triclabendazole proved to be effective at the prescribed doses in this research with minor adverse effects.

Research on Endemic Diseases and Japanese Colonial Rule: Focusing on the Emetine Poisoning Accident in Yeongheung and Haenam Counties in 1927 / 의사학

This paper aims to examine the spread of paragonimiasis and the Japanese colonial government's response to it. To consolidate colonial rule, the Japanese colonial government needed medications to cure paragonimiasis. When Dr. Ikeda Masakata invented acid emetine to cure paragonimiasis in Manchuria in 1915, emetine treatment carried the risk of emetine poisoning such as fatigue, inappetence, heart failure, and death. Nonetheless, Japanese authorities forced clinical trials on human patients in colonial Korea during the 1910s and 1920s. The emetine poisoning accident in Yeongheung and Haenam counties in 1927 occurred in this context. The Japanese government concentrated on terminating an intermediary host instead of injecting emetine to repress endemic disease in Japan. However, the Japanese colonial government pushed ahead with emetine injections for healthy men through the Preliminary Bureau of Land Research in colonial Korea in 1917. This clinical trial simultaneously presented the effects and the side effects of emetine injection. Because of the danger emetine injections posed, the colonial government investigated only the actual condition of paragonimiasis, delaying the use of emetine injection. Kobayashi Harujiro(1884-1969), a leading zoologist and researcher of endemic disease for three decades in the Government General Hospital and Keijo Imperial University in colonial Korea, had used emetine while researching paragonimiasis, but he did not play a leading role in clinical trials with emetine injections, perhaps because he mainly researched the intermediary host. Government General Hospital and Keijo Imperial University therefore faced limitations that kept them from leading the research on endemic disease. As the health administration shifted the central colonial government to local colonial government, the local colonial government pressed ahead with emetine injections for Korean patients. Emetine poisoning had something to do with medical power's localization. Nevertheless, the central colonial government still supported emetine injections with funds from the national treasury. The emetine poisoning accident that occurred simultaneously in two different regions resulted from the Japanese colonial government's support. This accident represented the Japanese colonial rule's atrocity, its suppression of hygiene policies, and its disdain for colonial inhabitants. The colonial government sought to accumulate medical knowledge not to cure endemic disease, but to expand the Japanese Empire.

Brote epidémico de fascioliasis invasiva: estudio de una familia / Epidemic outbreak of invasive fasciolasis: study of a family

Se estudiaron 6 casos de una familia procedente del área rural, con antecedentes de ingestión de berro silvestre, para exponer nuestras observaciones clínicas y terapéuticas sobre esta infección. Se observó que unas semanas más tarde a la ingestión se presentaron síntomas de astenia, dolor en hipocondrio derecho, fiebre, hepatomegalia. Se realizó leucograma, recuento global de eosinófilos, aminotransferasas, fosfatasa alcalina, antígeno de superficie, anti HVC, serodiagnóstico para fasciola (ELISA indirecto), heces fecales seriadas, drenaje biliar, laparoscopia y biopsia hepática y colangiopancreatografía transduodenal. Se estudió solamente mediante exámenes de laboratorio el caso de un niño. Se halló un recuento global de eosinófilos elevado en todos los casos. Se detectaron huevos de fasciola en 2 casos: uno en heces fecales y otro, en bilis. Se demostró, mediante laparoscopia, la presencia de lesiones de larva migrans visceral en la superficie hepática, que se comportaron histológicamente como granulomas. La colangiopancreatografía transduodenal resultó un método útil en el diagnóstico y tratamiento de algunos casos. Se indicó tratamiento con emetina y prazicuantel indistintamente

La resistencia a múltiples drogas (MDR) en Entamoeba histolytica / Multiple drug resistance in Entamoeba histolytica

El desarrollo de mecanismos para evadir la acción de los fármacos y desarrollar resistencia a los mismos es un evento universal en los organismos vivos. Se presenta en virus, bacterias, hongos, plantas y animales. En una población de seres vivos algunos individuos son capaces de encender genes apagados, de mutar la secuencia de otros genes, de sintetizar nuevas moléculas para desarrollar los mecanismos que les permiten sobrevivir y perpetuar la especie en circunstancias adversas. La acumulación de eventos de adaptación y mutagénesis pueden dar lugar a la aparición de organismos con características diferentes a la mayoría de los individuos de su especie, las cuales al acumularse podrían constituir nuevas especies. De manera que los cambios para la adaptación y la sobrevivencia de los individuos constituyen en última instancia las bases de la evolución. Uno de los mecanismos que las células han desarrollado para sobrevivir en presencia de sustancias tóxicas es el llamado fenotipo de resistencia a múltiples drogas o MDR (por sus siglas en inglés, multidrug resistance). Este evento se caracteriza porque las células presentan resistencia a drogas con estructuras químicas y blancos de acción distintos. El fenotipo de MDR se descubrió primeramente en células transformadas de mamífero, las cuales expresan una glicoproteína de aproximadamente 170 kDa en su superficie, denominada Pgp. Posteriormente este mecanismo se ha descubierto en muchas especies, incluyendo a los protozoarios parásitos...

Studies on the Antioxidative and Cytotoxic Actions of Epigallocatechin Gallate in Murine Cerebral Cortical Cell Cultures

OBJECTIVE: Epigallocatethin gallate(EGCG) is a major green tea polyphenol and is known to have potent antioxidative and antiproliferative actions. This study is performed to investigate the antioxidative effect of EGCG on the various oxidative insults in mouse cerebral cortical cell cultures. METHODS: Mixed cortical cell cultures containing both neuron and glia prepared by plating fetal mice cortical cells on to an established glia of 24 well vessels. At 13-15 days in vitro, oxidative neuronal deaths were induced by the addition of oxidants into the cortical cultures. Iron ion(FeCl2), copper ion(CuCl2), sodium nitroprusside(SNP) and buthionine sulfoximine(BSO, a glutathione depletor) were used as oxidants. Cell death was assessed by LDH assay after microscopic examination. RESULTS: All four oxidants induced neuronal cell death associated with cell body swelling, which was markedly inhibited by Trolox(100muM), a vitamin E analog. EGCG(1-10muM) markedly inhibited the neuronal cell death induced by 20muM CuCl2, 1muM SNP, or 1mM BSO. Unexpectedly the neuronal cell death induced by 20muM FeCl2 was augmented by treatment with 1 or 3muM EGCG. EGCG itself induced concentration- and exposure time-dependent cell death at more than 30muM concentrations. EGCG(30, 100muM) injured not only neuronal cells but glial cells after 48 hour exposure. The EGCG-induced cytotoxicity was partially inhibited by protein synthesis inhibitors, cycloheximide(0.1 or 1mug/ml) and emetine (1mug/ml) or high potassium media(10 or 25mM) but was not affected by Trolox. CONCLUSION: These results suggest that the dual antioxidative-cytotoxic actions of EGCG are concentration-dependent and that the antioxidative aciton depends on the kind of oxidative insults, and that the EGCG-induced cytotoxicity be relevant to protein synthesis and/or membrane depolarization.

Isolation of emetine resistant clones of Entamoeba histolytica by petri dish agar method.

Emetine resistant clones of Entamoeba histolytica strain HM1:IMSS were isolated by using petri dish agar method after mutation with ethyl-methanesulphonate. Two emetine resistant clones were obtained and both were resistant to emetine at a concentration of 24 micrograms/ml of emetine. The 50 per cent inhibitory concentration (IC50) for both emetine sensitive and resistant clones was 5 and 14 micrograms/ml respectively. The colony forming efficiency of E. histolytica strain HM1:IMSS varied from 44 to 54 per cent. This method is useful for isolating clones from different strains of the parasite for molecular and immunological studies.

Inhibition of thymidylate synthase by pergularinine, tylophorinidine and deoxytubulosine.

The activity of thymidylate synthase (TS) purified in our laboratory from Lactobacillus leichmannii was inhibited by pergularinine (PGL) and tylophorinidine (TPD) and deoxytubulosine (DTB) isolated from the Indian medicinal plants Pergularia pallida and Alangium lamarckii respectively. Cytotoxicity studies showed that cell growth of L. leichmannii was inhibited (IC50 = 40-45 microM) by all the three alkaloids, the concentrations > 80-90 microM resulting in complete loss of the enzyme activity. Ki values of the enzyme calculated from Lineweaver-Burk and Dixon plots for PGL, TPD and DTB were 10 x 10(-6) M, 9 x 10(-6) M and 7 x 10(-6) M respectively. These are typed as 'non-competitive' inhibitors of TS. All the three alkaloids inhibited (IC50 = 50 microM) the elevated TS activity of leukocytes in cancer patients with clinically diagnosed chronic myelocytic leukemia (n = 10), acute lymphocytic leukemia (n = 8) and metastatic solid tumours (n = 3).

A Study of Epidermal Apoptosis / 대한피부과학회지

BACKGROUND: Apoptosis is a highly selective form of cell suicide with characteristic morphologieal and biochemical features, including chromatin condensation, formation of apoptotic bodies, and DNA fragmentation by the activation of endonucleases. Various cytokines and physical or chemical factors can provoke apoptotic changes in the skin. OBJECTIVE: We investigated the cytotoxic effects with epidermal cytokines and their combinations, K+ ionophores, protein synthesis inhibitor(emetine), inhibitor of endogenous endonuclease(aurintricarboxylic acid, ATA), sodium azide, and retinoic acid witp human epithelial tumor cell lines(A431 cells) to examine the degree of induction of apoptosis in the epidermal keratinocytes. METHODS: Induction of apoptosis was measured in cultured human keratinocytes, keratinocyte cell lines(A-431, HaCat, KB cells), cultured human melanocytes and malignant melanoma cell lines(SK-28, SK-30) using a mixture of ethidium bromide and acridine orange, DNA agarose gel electrophoresis and TUNEL staining. RESULTS: l. In the A-431 cells, (1 to a certain degree, the combination of IFN-gamma and TNF-alpha could only induce apoptosis. Q2 most of K+ ionophores were observed to induce necrosis rather than apoptosis. Q3 emetine, a protein synthesis blocker, was found to induce apoptosis in a dose-dependent pattern. Q4 sodium azide at a concentration of 1% .induced apoptosis rather than necrosis. Q5 retinoic acid inhibit the beuvericin induced apoptosis. 2. In human keratinocytes, Ql more resistant in the induction of apoptosis than any cultured keratinocyte cell lines p aurintricarboxylic acid(ATA)-an endonuclease inhibitor, could inhibit UV induced apoptosis 3. In human keratinocytes and cultured keratinocyte cell lines, c-PAF inhibit the beauvericin induced apoptosis. 4. Human melanocytes is very resistant for the induction of apoptosis by beauvericin. 5. In the melanocytes and melanoma cell lines, sodium azide and beauvericin induced necrosis rather than apoptosis. CONCLUSIONS: The epidermis is continuously exposed to toxic factors which might induce cell death. With the above results, the induction of appeared to be rather resistant, epidermal cell apoptosis which may reflect the existence of some endogenous protective mechanisms in the epidermis to survive at certain toxic environments; melanocytes showed high expression of bcl-2 protein which could play a role in endogenous defense against toxic environments of the epidermis.

IL-1 activity in human fascioliasis before and after treatment with bithionol and dehydroemetine

Interleukin-1 [IL-1] activity level was measured in monocyte culture supernatant of twenty patients with established fascioliasis before and after treatment with two faciolcidal drugs; bithionol and dehydroemetine [ten cases each] as well as a group of control [fifteen normal parasite free individuals]. The IL-1 mean activity level was found to be significantly higher in patients [84 +/- 21.6 micro/ml] than in normal individuals [9.4 +/- 3.7 micro/ml] This indicates increase in many immunological reactions which IL-1 is involved especially the monocyte activities and most of the inflammatory processes considering the multifunctional role of IL-1 as an inflammatory mediator. This high IL-1 activity may be due to the effect of Th1- deriven monocyte activating factors such as TNFbeta and lFNalpha stimulated by the adult worm antigens. After treatment, IL-1 activity level was significantly decreased [21.9 +/- 6.9 after bithionol, and 13.9 +/- 5.6 after dehydroemetine] than that before treatment, indicating good effectiveness of both drugs. This study also revealed a slight difference between the therapeutic effect of the two drugs which seems to be due to their different mode of action

Microbial transformation of emetine into o-methyl psychotrine

Several microorganisms [fungi and bacteria] were screened for their ability to biotransform emetine. Cunninghamella blackesleeana MR.-198 was selected for scale-up transformation, as it showed a major transformation product and a small amount of unidentified minor product, in addition to untransformed emetine. The major metabolite was characterized using one and two dimensional NMR techniques as O-methylpsychotrine. Further confirmation was carried out by direct comparison with a reference sample prepared by methylation of psychotrine

Correlation of biological activity (therapeutic and toxic) with solvochromic properties of metronidazole, emetine hydrochloride and diloxanide furoate.

Goat blood, when incubated for different periods with diloxanide furoate, metronidazole and emetine hydrochloride, underwent changes in fatty acid constituents and their peroxidation products measured as malonaldehyde. These findings, together with the changes noted in the drug-lipid partition coefficient, are discussed in an attempt to correlate the lipid constitution and biological activity of the drugs.

Amibiasis intestinal invasora: síndromes clínicos, diagnóstico y tratemiento

El espectro clínico de la infección por Entamoeba histolytica es muy amplio y abarca desde los cuadros completamente asintomáticos de los portadores sanos hasta formas graves de invasión intestinal, pasando obviamente por las presentaciones clínicas secundarias a enfermedad amibiana invasora limitada a la pared del tubo digestivo. La amibiasis asintomática fue revisada en un número previo, la etiopatogenia de la invasión amibiana fue revisada en un número anterior y en esta entrega se pasará revista al cuadro clínico, al diagnóstico y al tratamiento de la Amibiasis Intestinal Invasora. En el próximo número se revisará la amibiasis extraintestinal.

Tratamiento del absceso hepático amibiano en niños: revisión de 20 casos / Treatment of hepatic amebic abscess on children: review of 20 cases

La amibiasis hepática continúa siendo la complicación más frecuente y grave de la amibiasis intestinal, su tratamiento origina controversias. La presente serie analiza los métodos terapéuticos utilizados en 20 niños con absceso hepático amibiano. Tres de ellos ingresaron al Hospital de Especialidades No. 1 de Ciudad Obregón, Sonora, en condiciones críticas por ruptura peritoneal del absceso y fueron sometidos a laparotomía para lavado y drenaje de la cavidad abdominal, con lo que sobrevivieron dos de ellos; 15 fueron tratados con dehidroemetina y metronidazol parenterales durante 10 días, obteniéndose resultados satisfactorios sólo en 10, requiriendo los cinco casos fallidos el procedimiento de drenaje mediante guía ultrasonográfica, con el que todos sanaron. Se observó que los pacientes que mejoraron con manejo farmacológico fueron los niños mayores y con afección clínica menos grave. Con este antecedente se trataron los últimos dos casos, ambos menores de cinco años, con el procedimiento de drenaje guidado por ultrasonido a las pocas horas de haber ingresado al hospital, teniendo ambos mejoría inmediata y rápido egreso. Se concluye que el tratamiento médico del absceso hepático amibiano puede fallar con mayor frecuencia en los niños más pequeños y con ataques serios a sus condiciones clínicas. En ellos, el procedimiento de drenaje guiado por ultrasonido puede ser una magnífica alternativa terapéutica

Fasciolasis hepática aguda masiva: relato de un caso / Severe massive hepatic fasciolasis: a case report

La fasciolasis hepática afecta accidentalmente al Hombre, desconociéndose su real incidencia. Describimos un caso de fasciolasis aguda masiva, en una niña de 9 años, que presenta dolor abdominal decahimiento, fiebre y hepatomegalia. Hemograma con leucocitosis e hipereosinofilia, anemia y VHS alta, fosfatasas alcalinas altas, PT bajo, IgE elevadda. Mielograma de cresta iliaca con abundantes eosinófilos, desviación a izquierda y ausencia de blastos. Biopsia diferida: alteraciones de maduración, serie granulocítica con predominio de eosinófilos. Se plantea probable fasciolasis hepática y se obtiene, dirigidamente, antecedente de ingestión de berros. Ecografía abdominal describe hígado con áreas hipoecogénicas. TAC abdominal informa defectos focales hepáticos vascularizados y destrucción localizada del parénquima tipo microcavitaria. Biopsia hepática: hepatitis aguda necrótica con intensa infiltración eosinofílica. Parasitológico seriado de deposición (método Teleman modificado) y aspirado duodenal, negativas pafa fasciolasis hepática. El diagnóstico se confirmó por serología, reacción de ELISA y Doble Difusión, positivas para Fasciola. Se trató con dihidroemetina con muy buena respuesta

Correlation of phospholipid loss in goat whole blood with solvochromic properties of antiamebics like emetine, metronidazole and diloxanide furoate.

Phospholipid content of whole blood lipid decreases significantly when goat blood is incubated for different length of time with different amebicidal agents (e.g., emetine, metronidazole and diloxanide furoate). The plots of relative per cent phosphate loss against incubation period show biphasic nature and suggest that the rates of phospholipid loss bears some relation with the drug's lipophilicity (log P in 1 octanol/water system). The absolute phospholipid loss seems to be governed by the drug's aquasolubility. Implication of these finding were discussed in terms of their clinical profiles assuming that the loss of phospholipid is due to drug's binding with the phospholipid layer in amebic cyst-coat, being the first step which may trigger a chain of events leading to the onset of drug action.

Eficacia del triclabendazole en paragonimiasis pulmonar humana refractaria a la emetina, bithionol y praziquantel / Efficacy of triclabendazole in human pulmonary paragonimiasis refractary to emetine, bithionol and praziquantel

Dentro del estudio clínico-terapéutico para determinar la posología efectiva de triclabendazole contra Paragonimus recibieron tratamiento con esta droga tres pacientes ecuatorianos con paragonimiasis pulmonar que fracasaron al tratamiento con emetina más cloroquina, bithienol y praziquantel individualmente. En todos los síntomas de tos, expectoración herrumbrosa y la presencia de huevos de Paragonimus mexicanus en esputo estaban presentes antes del tratamiento. Dos pacientes recibieron tricabendazole a 10mg/kg en dosis única, y el tercero a 5mg/kg una vez al día por tres días . El seguimiento hasta el año 1 postratamiento demostró la desaparición de la sintomatología y cura parasitológica. Los pacientes no presentaron efectos secundarios al fármaco.

Amibiasis cutánea: presentación de dos casos / Cotaneous amebiasis: two cases report

La localización en la piel de la amiba no es tan frecuente como sus localizaciones intraintestinal o el abceso hepático amibiano. Es una enfermedad grave si el diagnóstico y el tratamiento no son realizados en forma oportuna. Se presentan dos casos de amibiasis cutánea con buena respuesta al tratamiento.

Fasciolasis humana epidémica. Cuba 1983. VI. Estudio clínico de 40 niños del Hospital provincial de Sagua la Grande / Epidemic human fascioliasis. Cuba 1983. VI. Clinical study of 40 children in the Hospital Provincial de Sagua la Grande

Se estudiaron 40 niños con "Síndrome Eosinofílico Febril" en los cuales se confirmó la infección por Fasciola Hepática por presentar la triada clásica: fiebre, eosinofilia y dolor abdominal; tener antecedentes de ingestión de berro (82%), laparoscopia y biopsias positivas (100%) y pruebas de intradermoreacción inmediata (100%) y electrocinéresis (100%) positivas a antígenos de Fasciola. Este trabajo demuestra la afectación de los niños durante el brote epidémico de Cuba en 1983