Compostos carbonílicos α, ß-insaturados e hidrazonas sintéticas como antiparasitários / α, ß-Unsaturated carbonyl compounds and Synthetic hydrazones as antiparasitics

Apesar da grande relevância médica e social, e por serem responsáveis por grande parte das mortes em países subdesenvolvidos e em desenvolvimento as doenças negligenciadas (DN), ainda, não apresentam terapêutica eficaz. Dentre as diversas DN, doenças como a doença de Chagas, a Leishmaniose visceral e a malária, se destacam no cenário nacional, por terem alta incidência e prejuízos sociais. Os fármacos disponíveis para o tratamento destas parasitoses, apresentam alta toxicidade e, em alguns casos, resistência por parte dos parasitas. Assim sendo, faz-se necessário o planejamento e desenvolvimento de novos agentes quimioterápicos mais seguros e eficazes. Dentre as diferentes estratégias de planejamento de fármacos, selecionamos o planejamento de fármacos baseado na estrutura do ligante - LBDD (Ligand-Based Drug Design) - como base para desenvolvimento deste trabalho. Nesta estratégia, utiliza-se o conhecimento de moléculas (ligantes) e de suas atividades biológicas conhecidas previamente determinadas experimentalmente, como protótipos para a busca de novas entidades químicas com atividade biológica semelhante ou melhorada. Sendo assim, o presente trabalho teve como objetivo a síntese e avaliação biológica de moléculas bioativas para o tratamento de doenças parasitárias. Baseando-se no conhecimento prévio da atividade antiparasitária de compostos carbonílicos α,ß-insaturados e hidrazonas, foram sintetizados séries de compostos destas classes químicas na busca de novos agentes quimioterápicos. Os compostos obtidos foram avaliados contra a forma epimastigota de Trypanosoma cruzi, promastigota de Leishmania donovani, amastigota de Leishmania infantum e, também, determinou-se o seu grau de citotoxicidade (CC50) frente a células de macrófago humanos diferenciado (THP-1). As 31 moléculas obtidas foram caracterizadas por técnicas de ponto de fusão, RMN 1H e RMN 13C e avaliada sua pureza por HPLC. Os compostos da classe da cinamoil-hidrazonas apresentaram-se como promissores antiparasitários, mostrando atividade frente a forma promastigota (Leishmania donovani), 4 dos 12 compostos foram ativos (IC50= 1,27 - 13,68 µM) e frente a forma amastigota (Leishmania infantum), 10 dos 12 compostos apresentaram atividade (9,09 - 63,5 µM). Mesmo apresentando citotoxicidade moderada (CC50 = 8,83 - 87,47 µM), os compostos obtiveram valores inferiores ao fármaco de referência (doxorubicina: CC50 = 0,26 µM). Diante do exposto, o planejamento de fármacos realizado por LBDD mostrou-se bem-sucedido, pois a classe de cinamoil-hidrazonas mostrou-se promissora como antiparasitários, visto sua atividade na escala de baixo micromolar e moderada citotoxicidade em células humanas. Esses resultados assinalam que a classe de compostos descrita está passível a continuar sendo investigada no intuito de aprimorar os protótipos obtidos na busca de novos agentes quimioterápicos antiparasitários e desvendar os mecanismos de ação leishmanicida

Despite to the great medical and social relevance and the amount of deaths in underdeveloped and developing countries, neglected diseases (ND) still do not have an effective therapy. Among the various ND, illnesses such as Chagas disease, visceral leishmaniasis and malaria holds a great importance in the Brazilian scenario due to high incidence and social damage. The drugs available for the treatment of these parasitosis present high toxicity and, in some cases, resistance by the pathogens. Thus, the planning and development of new, safer and more effective chemotherapeutic substances are urgent needed. Among the different drug planning strategies, we selected ligand-based drug design (LBDD) as the basis for the development of this work. In this strategy, we use the knowledge of molecules (ligands) and their known biological activities previously determined experimentally, as prototypes to search for new chemical entities with similar or improved biological activity. Therefore, the present work aimed the synthesis and biological evaluation of bioactive molecules for the treatment of parasitic diseases. Based on previous knowledge of the antiparasitic activity of α,ß-unsaturated and hydrazone carbonyl compounds, series of compounds of these chemical classes were synthesized in search of new chemotherapeutic agents. The compounds obtained were evaluated against the epimastigote form of Trypanosoma cruzi, Leishmania donovani promastigote, Leishmania infantum amastigote and their cytotoxicity (CC50) against differentiated human macrophages (THP-1). The 31 molecules obtained were characterized by melting point, 1 H NMR and 13C NMR techniques and their purity were characterized by HPLC. The cinnamoyl hydrazone class compounds showed promising antiparasitic activity, showing activity against promastigote form (L. donovani), 4 of 12 compounds were active (IC50 = 1.27 - 13.68 µM) and amastigote form (L. infantum), 10 of the 12 compounds showed activity (9.09 - 63.5 µM). Even presenting moderate cytotoxicity (CC50 = 8.83 - 87.47 µM), the compounds had values below the reference drug (doxorubicin: CC50 = 0.26 µM). Considering the results, LBDD drug planning proved to be successful and the class of cinnamoyl hydrazones were promising as antiparasitics due to its activity in low micromolar scale and moderate cytotoxicity in human cells. These results indicate that the described class of compounds can be further investigated in order to improve the prototypes obtained in the search for new antiparasitic chemotherapeutic agents and to unravel the mechanisms of action of leishmanicidal molecules

Synthesis of leading chalcones with high antiparasitic, against Hymenolepis nana, and antioxidant activities

The hymenolepiosis by Hymenolepis nana is a major public health problem in developing countries, and the commercial drugs against this parasitosis are not enough effective. The combination of antiparasitic and antioxidant agents has improved the treatment of some parasitoses. Thus, the development of new cestocidal and antioxidant agents to treat the hymenolepiosis cases is important. In the present study, four hydroxy- and four dihydroxy-chalcones were synthesized using the catalyst boron trifluoride diethyl etherate (BF3•OEt2). The antioxidant activity and antiparasitic against H. nana of chalcones were tested, as well as the toxicity by the brine shrimp lethality bioassay and the method of Lorke. The antioxidant activity was measured by three radical scavenging assays: 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP). The hydroxyl substitution pattern (number and position), mainly in ring B, was responsible for the chalcone antiparasitic activity. At least one meta or para hydroxyl group in ring B was essential for activity of the synthetic chalcones against H. nana; The time taken for the parasite to die by the 3b and 3e chalcones (20 mg/mL) treatment was up to six times lower than the control drug Praziquantel. On the other hand, chalcones with catechol structure in ring B (3g and 3h) showed the highest antioxidant values. The toxicity evaluations suggests that synthetic hydroxychalcones with cestocidal (3b and 3e) and antioxidant (3g and 3h) activities are safe compounds and potential in vivo agents to treat this parasitosis

Influência do grupo genético, condição sexual e tratamento antiparasitário nas medidas de área de olho do lombo e espessura de gordura in vivo e na carcaça de bovinos de corte / Influence of breed, gender condition, and anti-parasitic treatment on the measurements of in vivo rib eye area and fat thickness and on the carcass of beef cattle

Foram estudados 48 bovinos machos oriundos de inseminação artificial, criados em pasto, sendo 24 (12 Nelore e 12 F1 ½ Red Angus-Nelore ) tratados com antiparasitários alopáticos e 24 (mesmo número de puros e cruzados) tratados com o antiparasitário bioterápico Fator C&MC. Os animais foram desmamados aos oito meses, metade de cada subgrupo genético (6) foi castrado aos 13 meses e todos abatidos aos 32 meses, com o objetivo de verificar a influência do tratamento antiparasitário, do grupo genético e da condição sexual sobre as medidas de área de olho de lombo (AOL) e espessura de gordura de lombo (EGL). Usaram-se medidas de ultrassonografia no animal vivo (AOLU e EGLU) e na carcaça, plástico quadriculado e paquímetro (AOLC e EGLC). Os animais F1, os inteiros e os tratados com alopatia apresentaram peso vivo maior quando comparados aos Nelores, castrados e tratados com bioterápicos. Não houve diferença da AOLU e AOLC entre os grupos genéticos. EGLC foi mais alta nos cruzados. Os animais inteiros apresentaram AOLU e AOLC maiores que os castrados, e EGLU e EGLC menores. Foram altamente significativos os coeficientes de correlação entre as medidas por ultrassom e na carcaça para área de olho de lombo (0,87) e espessura de gordura do lombo (0,95).

Forty-eight male bovines, products of artificial insemination and raised on pasture, were studied, being 24 (12 Nelore, 12 F1 ½ Nelore ½ Red Angus) treated with allopathic antiparasitic drugs and 24 (same number of pure and crossbred) treated with a biotherapic antiparasitic drug Factor C&MC. Animals were weaned at eight months of age and half of each genetic subgroup (six) was castrated at 13 months of age. All animals were slaughtered at 32 months of age, in an attempt to evaluate the influence of antiparasitic treatment, genetic group, and gender condition in the measurements of rib eye area (AOL) and fat thickness (EGL) of loin. Measurements of ultrasonography were used for live animals (AOLU and EGLU), whereas a direct plastic grid reading of the eye muscle and a pachymeter (AOLC and EGLC) were used for carcasses. F1 animals, non-castrated, and those treated with allopathic drugs showed higher live weight when compared with Nelore, castrated, and biotherapic treated animals. There were no differences between genetic groups of AOLU and AOLC. EGLC was higher in crossbred animals. Non-castrated animals showed higher AOLU and AOLC when compared with castrated animals, and lower EGLU and EGLC. Correlation coefficients for ultrasound and carcass measurements were highly significant for rib eye area (0.87) and fat thickness (0.95).

Adverse reactions from community directed treatment with ivermectin (CDTI ) for onchocerciasis and loiasis in Ondo State, Nigeria

Onchocerciasis is an endemic disease in Ondo state, Nigeria. Community directed distribution of ivermectin is currently on-going in some local government areas of the state. Randomly selected persons (2 331 males and 2 469 females) were interviewed using a modified rapid assessment procedure for Loa loa (RAPLOA) to assess community directed treatment with ivermectin. The retrospective study evaluated the coverage, impacts and adverse reactions to the drug treatment. A questionnaire was administered by house-to-house visit in six local government areas, implementing community directed treatment with ivermectin (CDTI) in this bioclimatic zone. A total of 2,398 respondents were reported to have participated in the treatment. The overall ivermectin coverage of 49.96% was recorded (range 0 - 52% in different communities). Adverse reactions from ivermectin administration were experienced in 38% of individuals. Diverse adverse reactions experienced included predominantly itching (18.50%); oedema, especially of the face and the limbs (8.2%); rashes (3.4%) and body weakness (2.4%). Expulsion of intestinal worms occurred in 0.96% of the respondents. The occurrence of adverse reactions in relation to age categories was statistically significant. Neither fatal nor severe adverse reactions were reported by respondents. Significantly, despite experienced adverse reactions, continued participation, acceptability and compliance to ivermectin treatment was expressed by the various communities. This attitude is in consonance with the African Programme for Onchocerciasis Control (APOC) objectives. Rev. Biol. Trop. 56 (4): 1635-1643. Epub 2008 December 12.

La oncocercosis es endémica en el estado Ondo, Nigeria. Se seleccionaron 4 800 personas al azar para evaluar con encuesta retrospectiva la cobertura, efectos y reacciones al tratamiento farmacológico con ivermectina administrado por la misma comunidad. La cobertura global de ivermectina fue 50 % con reacciones adversas en 38 % de los individuos. Estas fueron comezón picazón (18%), edema, especialmente de la cara y las extremidades (8%), erupciones cutáneas (3%) y debilidad (2%); dependieron de la edad y no hubo reacciones más graves. La expulsión de las lombrices intestinales se produjo en 96% de los encuestados. A pesar de las reacciones adversas, hubo continuidad, aceptación y cumplimiento del tratamiento con ivermectina, en consonancia con los objetivos del Programa Africano para el Control de Oncocercosis (APOC).

Estudo comparativo da intoxicação experimental por amitraz entre cães e gatos / Comparative study of experimental amitraz intoxication betweendogs and cats

O objetivo do presente trabalho foi estudar as características em comum e as diferenças observadas na intoxicação induzida por 1 mg/kg de amitraz, IV, em cães e gatos. Os principais sinais clínicos observados em comum foram sedação, hipotermia, bradicardia, bradiarritmias, hipotensão, bradipnéia, midríase e hiperglicemia transitória, porém a intensidade destes sinais foi diferente entre as espécies. A hipotermia foi mais acentuada em gatos. Os cães foram mais sensíveis às alterações cardiorespiratórias apresentando diminuição mais significativa na freqüência cardíaca e respiratória, além de ocorrência de maior número de bradiarritmias. Os gatos apresentaram midríase mais prolongada do que os cães. Observou-se hiperglicemia e hipoinsulinemia transitórias e diminuição transitória dos níveis plasmáticos de cortisol em ambas espécies, porém os gatos apresentaram um pico de hiperglicemia maior e mais precoce do que os cães, e com relação aos níveis plasmáticos de cortisol, os cães apresentaram uma diminuição mais acentuada do que os gatos. O tempo médio de retorno da sedação foi mais prolongado em gatos. Estes resultados mostraram que a intoxicação por amitraz entre cães e gatos é muito similar, porém os gatos demonstraram maior sensibilidade à indução de hipotermia e hiperglicemia, além de midríase e um tempo médio de retorno da sedação mais prolongado, enquanto os cães apresentaram diminuição mais acentuada nos parâmetros cardiorespiratórios e dos níveis plasmáticos de cortisol do que os gatos.

The objective of the present work was to study the characteristics in common and the differences observed in the intoxication by amitraz 1 mg/kg, IV, in dogs and cats. The main clinical signs observed in common were sedation, hypothermia, bradycardia, bradyarrhytmia, hypotension, bradypnea, mydriasis and transitory hyperglycemia, however the intensity of these signs was different among the species. he hypothermia was more accentuated in cats than in dogs. The dogs were more sensitive to the cardiorespiratory alterations presenting more significant decrease in the heart and breathing frequency, besides occurrence of larger bradyarrhytmia number. The cats presented more prolong mydriasis than the dogs. It was observed hyperglycemia and transitory hypoinsulinemia and transitory decrease of the plasmatic levels of cortisol, however the cats presented a hyperglycemia pick more accentuated and more precocious than the dogs, and regarding the plasmatic levels of cortisol, the dogs presented a decrease more accentuated than the cats. In the medium time of return of the sedation smaller in cat. These results demonstrated that the amitraz intoxication between dogs and cats is very similar, however the cats showed more sensibility to the hypothermia and hyperglycemia induction, besides mydriasis and the medium time of return of sedation more prolong, while the dogs presented a decrease more accentuated in the cardiorespiratory parameters and of the plasmatic levels of cortisol than the cats.

Efficacy of ivermectin treatment of cutaneous gnathostomiasis evaluated by placebo-controlled trial.

Previous studies have revealed that ivermectin treatment for gnathostomiasis can reduce parasitic loads in animals and make recurrent subcutaneous swelling subside in 76% of patients. Our study aimed to evaluate the efficacy of ivermectin for cutaneous gnathostomiasis treatment in a placebo-controlled trial. This study was a prospective randomized placebo-controlled study performed at The Bangkok Hospital for Tropical Diseases, Mahidol University, Thailand. Thirty patients with a serologically confirmed diagnosis of cutaneous gnathostomiasis were enrolled. Seventeen patients in the ivermectin treated group received a single dose of 12 mg ivermectin (200 microg/kg bodyweight), while 13 patients in the control group received a single dose of 40 mg of vitamin B1. The follow-up period was 1 year. Of the 17 patients, 7 (41.2%) responded to ivermectin, while no patient responded to placebo. The mean (95% Cl) time to the first recurrence of subcutaneous swelling with ivermectin and in the placebo groups were 257 (184-331) and 146 (42-250) days, respectively, (p=0.102). Although this study revealed no significant difference in the mean time to first recurrence of swelling between the ivermectin and placebo groups, there was a trend towards ivermectin efficacy against gnathostomiasis in previous animal and human studies. Further studies with different doses of ivermectin and larger sample sizes, and close monitoring for ivermectin tolerability and treatment response are necessary to confirm an efficacy of ivermectin.

Gestação e doenças parasitárias / Pregnancy and parasitic diseases

Parasitismo é toda relação desenvolvida entre indivíduos de espécies diferentes, em que se observa dependência metabólica de grau variado. Há maior prevalência de indivíduos infectados por parasitos na população brasileira do que está descrito. O efeito das infecções parasitárias na nutrição materna pode comprometer o desenvolvimento fetal. Mulheres que engravidam com desnutrição, anemia ou infecções crônicas apresentam risco maior de terem filhos com baixo-peso ao nascimento e no parto pré-termo. O diagnóstico e o tratamento de pacientes com essas condições deveriam ser realizados antes da gestação. Nenhuma droga antiparasitária é considerada segura na gestação. Pacientes com parasitos intestinais só devem ser tratados na gravidez quando o quadro clínico é exuberante ou as infecções maciças. Não se recomenda o tratamento durante o primeiro trimestre da gestação. Medidas profiláticas, como educação sanitária, higiene correta das mãos, controle da água, alimentos e solo, devem ser encorajadas devido ao impacto positivo que geram sobre a ocorrência de parasitoses intestinais. Enfocaremos os aspectos clínicos das infecções parasitárias na gestação e seus tratamentos.

Estudios preclínicos de cucurbita máxima (semilla de zapallo) un antiparasitario intestinal tradicional en zonas urbano rurales / Preclinics studies of Cucurbita maxima (zapallo seed) a traditional intestinal antiparasite in zones urban rural

Estudio experimental realizado en los laboratorios de Parasitología y Química de la Universidad Nacional Jorge Basadre Grohman - Tacna. El proceso involucró dos fases: 1. determinación de la Concentración Mínima Inhibitoria (CMI) de Cucúrbita máxima como antiparasitario, se usó tenias caninas con tiempo 5 a 6 horas de aislamiento intestinal y 2. Determinación de la Reacción adversa de Cucúrbita máxima en ratas albinas expuestas. Se halló que la CMI de semilla de zapallo a razón de 23g. en 100 ml de agua destilada es capaz de producir un efecto antihelmíntico, concentración equivalente a más menos 73 semillas de zapallo (x2 = 5.6, P menor 0.01). Macroscópicamente a dosis de 23 g. a más se hallan alteraciones en la motilidad del helminto, hay un efecto proteolítico con un tiempo promedio de supervivencia de 38.4 minutos. Macroscópicamente los proglótidos maduros presentan destrucción del tegumento con compromiso de la membrana basal. En los proglótidos grávidos hay destrucción de huevos, hallazgos mucho más acentuados a concentraciones de 30 y 32 g. de cucúrbita experimentados. Se halló gastritis no erosiva superficial en ratas weys a dosis de 9 g/kg posterior a las 4 horas de administración.

Experimental research was carried out at the Parasitology and Chemistry laboratories of the Jorge Basadre Grohmann National University, in Tacna.The process involved two phases: (1) determination of the minimum inhibitory concentration (MIC) of Cucurbita Maxima as an antiparasitic agent using canine tapeworms with an intestinalisolation of 5 to 6 hours, and (2) determination of the side-effects of Curbita Maxima on exposed albino rats.It was found that the MIC of 23 gr. of pumpkin seed in 100 ml. of distilled water can produce an antihelminthic effect. This concentration is equivalent to ± 73 pumpkin seeds (x2 = 5.6, p<0.01). Macroscopically, alterations in helminthic motility are present at a dose of > 23 gr. There is a protheolithic effect with an average survival time of 38.4 minutes. Microscopically the mature proglottids present a destruction of the tegument involving the basal membrane. In the gravid proglottids there is egg destruction. These findings are accentuated when experimenting with Cucurbita Maxima in a concentration of 30 and 32 gr. Superficial non-erosive gastritis was found in weys rats after 4 hours of administering 9 gr/kg.

Evaluación de la nitazoxanida en dosis única y por tres días en parasitosis intestinal / Nitazoxanide vs albendazole against intestinal parasites in a single dose and for three days

OBJETIVO: Evaluar la utilidad de nitazoxanida en dosis habitual con esquema de tres días y en dosis única, para la erradicación masiva de parásitos intestinales en la población pediátrica, comparando su efecto con el del albendazol en dosis única. MATERIAL Y MÉTODOS: Se realizó un ensayo clínico aleatorizado, en tres comunidades rurales de la región central de México, durante el periodo 2001-2003, para incluir tres posibles alternativas de tratamiento en 786 sujetos de entre 5 y 11 años de edad, de los cuales 92 tuvieron un examen parasitológico positivo (15.1 por ciento). El grupo 1 incluyó 27 pacientes que recibieron 400 mg de albendazol en dosis única; el grupo 2 incluyó 34 pacientes a quienes se administró nitazoxanida en dosis de 15 mg/kg/día durante tres días consecutivos; y el grupo 3 incluyó 31 pacientes que recibieron 1.2 g de nitazoxanida en dosis única. Se evaluó diferencia de proporciones mediante prueba exacta de Fisher. RESULTADOS: No existieron diferencias estadísticamente significativas en la efectividad de los tres esquemas de tratamiento: (80.5 por ciento) con albendazol, comparado con las dos alternativas adicionales de nitazoxanida (67.6 por ciento y 71 por ciento, respectivamente). Se observó una mayor prevalencia de efectos secundarios con nitazoxanida por kg /día (26.5 por ciento) y en dosis única (32.2 por ciento), en comparación con la dosis única de albendazol (7.4 por ciento). CONCLUSIONES: Las evidencias en cuanto a la efectividad y elevada prevalencia de efectos secundarios de la nitazoxanida no justifican aún su utilización como quimiopreventivo masivo para el control de parasitosis intestinal en áreas endémicas. En países con elevada prevalencia de parasitosis intestinal las medidas de prevención primaria que continúan vigentes, y que deben priorizarse, están relacionadas con sanidad pública, introducción de agua potable y drenaje, cloración de agua y manejo adecuado de excretas de animales domésticos, así como educación para la salud.

Human strongyloidiasis in AIDS era: its zoonotic importance.

Human strongyloidiasis is caused by a nematode Strongyloides stercoralis. Many species cause strongyloidiasis in animals. The parasite has predilection to one host only but the host specificity is not strict. When animal species infects humans there is intense allergic reaction in the form of cutaneous larva currens and larva migrans. Therefore, strongyloidiasis in strict terms is a zoonotic disease. The strongyloides species have three stages. The parasitic form inside the host, the free form stage in the soil or water that moults to infective third stage. The later infects the host through skin and migrate to the heart and lung and finally swallowed back to cause intestinal infection. However, in some cases intense pulmonary manifestations may take place. The Strongyloides stercoralis has unique feature of moulting from parasitic form to infective stage within the body, rather than coming out and forming free living stage and causing autoinfection. This may lead to latent infection for indefinite period in an immunocompetant person but fatal hyper or disseminated infection in immunocompromised person like patients of AIDS, organ transplant recipients, cancer and other patients put on immunosuppressive therapy, in whom it can involve any organ of the body. Because this group of patients in last few years have increased tremendously in Africa and South-East Asia, more and more cases of strongyloidiasis are being reported in english literature. The diagnosis of intestinal strongyloidiasis is made by repeated stool smear examinations and in extraintestinal strongyloidiasis the appropriate specimen is examined for the rhabditiform larvae. Recently serological tests have also been developed that can be used for epidemiological purposes. The drug of choice for the treatment of strongyloidiasis remains thiabendazole but due to its unacceptable side effects other medicines like albendazole and ivermectine are being used more frequently. The prevention of the infection is possible by adopting good personal hygiene and safe drinking water supply.

Eficácia e tolerabilidade do secnidazol suspensão versus tinidazol suspensão no tratamento da giardíase em crianças / Efficacy and tolerability of secnizadol and tinizadol both in the suspension form in the treatment of giardiasis in children

Objetivo: Comparar a eficácia e tolerabilidade do secnidazol(SEC) e tinidazol(TIN) no tratamento da giardíase em crianças. Métodos: Em estudo multicêntrico, aberto, randomizado, 321 crianças de 2 a 14 anos de idade, dos sexos feminino e masculino e portadores de giardíase, receberam secnidazol suspensäo, 30mg/kg(N=160) ou tinidazol suspensäo, 50mg/kg(N=161), ambos em dose única. Todas as crianças apresentavam exame protoparasitológico positivo par Giardia lambia antes do tratamento e foram reavaliadas laboratorialmente (métodos Faust e Kato-Katz) 7, 14 e 21 dias após a administraçäo das drogas. Resultados: Cura parasitológica foi obtida em 95 porcento dos pacientes do grupo SEC e 97 porcento dos pacientes do grupo TIN, näo apresentando diferença estatística significativa (p=0,430). Eventos adversos, possível ou provavelmente relacionados ao medicamento em estudo, ocorreram em 7 porcento dos pacientes do grupo SEC versus 16 porcento do grupo TIN, uma diferença estatisticamente significativa (p=0,009). Os eventos individuais "gosto amargo" (1,9 porcento SEC vs 7,5 porcento TIN, p=0,018) e "vômito" (0,6 porcento SEC versus 4,3 porcento TIN, p=0,032) também tiveram uma incidência significativamente diferente nos dois grupos. Conclusöes: Secnidazol e tinidazol foram igualmente eficazes no tratamento da giardíase, mas o secnidazol apresentou melhor perfil de tolerabilidade nesta faixa etária

efficacy and side effect of some antiparasitic drugs in normal and S. mansoni infected mice

The present work aims to study the schistosomicidal and side effects of two antibilharzial drugs, the Praziquantel and Anthiomaline beside Fasinex which is used in this field for the first time and was effective in the treatment of fascioliasis. For this purpose, eight groups each of 30 mice were selected, then four groups were infected with S. mansoni cercariae. The treatment started at seven weeks postinfestation when the eggs were detected in the faeces for groups [I, II and III]. Praziquantel, [7.5 mg / mouse] and Fasinex [0.02 ml/mouse] were given per os as a single dose while Anthiomaline [6.5 mg / mouse] was given intramuscularly 3 injections / week for three weeks. The sacrifice of 8 mice for each group was carried out at one week post - treatment for worm load and biochemical analysis of SGOT and SGPT and after four weeks for histopathological examination of the liver and counting worms. The results showed that Praziquantel reduced the worm load by 97.65% and 99.73% at one and four weeks post treatment and had no destructive effect on normal liver function or hepatic-tissues. Also, it improved the liver function and the pathological picture of the liver, leaving only fibrosed egg granulomes, in the infected mice. Anthiomalin reduced the worm load by 81.86% and 96.27% after the same periods. It had slight destructive effect on the liver function in both normal and infected mice [elevation of SGOT and SGPT, also produced some swelling, vacuolation and hydropic changes in the hepatocytes of these groups]. Fasinex reduced the worm load by 52% and 60.33%. It had slight destructive effect in the liver function for normal and infected groups, but the drug had no toxic effect on the liver tissues in these groups

Estudio de la irritabilidad oftalmica del extracto fluido de Indigofera suffruticosa / Study of ophthalmic irritability of fluid extract from Indigofera suffruticosa

Se realizo un estudio de la irritabilidad oftalmica de un extracto fluido de Indigofera suffruticosa Mill, obtenido en nuestro laboratorio, ya que por sus posiblidades como agente antiparasitario de uso externo, pudiera tener contacto eventual con los ojos. El estudio se realizo mediannte la tecnica de Draize y se calculo el indice de irritabilidad oftalmica segun lo establecido por el Anteproyecto de Metodo Cubano