Nitazoxanida para o tratamento de COVID-19 / Nitazoxanide for or COVID-19 treatment

CONTEXTO: A COVID-19 é uma pandemia de risco muito alto a nível global pela OMS. Até o momento não existem terapias específicas, embora diferentes tratamentos estejam em investigação. Mais recentemente, tem havido crescente interesse no uso da nitazoxanida no tratamento de COVID-19, dada sua atividade antiviral de amplo espectro. OBJETIVOS: Identificar, avaliar sistematicamente e sumarizar as melhores evidências científicas disponíveis sobre a eficácia e a segurança da nitazoxanida para COVID-19. MÉTODOS: Revisão sistemática rápida (rapid review methodology). RESULTADOS: Após o processo de seleção, foram avaliados cinco estudos clínicos em andamento. CONCLUSÃO: Cinco estudos com o objetivo de avaliar a eficácia e segurança da nitazoxanida no tratamento de COVID-19 estão em andamento. Devido à ausência de evidência sobre o uso deste medicamento para o tratamento de infecções por coronavírus que causem infecções respiratórias, não é possível recomendar seu uso como terapia para COVID-19.(AU)

Presence of benznidazole conjugated metabolites in urine identified by β-glucuronidase treatment

Chagas disease is a serious public health problem in Latin America and, due to migration, in other non-endemic regions. Benznidazole (BNZ) is first choice drug in pediatric therapeutics. However, little is known regarding its metabolism in humans. The aim of the study was to isolate and identify products of human BZN metabolism in urine samples obtained from a pediatric Chagas patient and a healthy adult volunteer both treated with BZN. Urine samples were collected after dose of BNZ. Urine was treated with β-glucuronidase followed by an extraction procedure under two different pH conditions and a HPLC/UV and MS/MS identification of BZN and its metabolites. BZN (m/z 260.09847) was identified in all urine extracts. Peaks from each extracted chromatograms were selected for MS and MS/MS identification. Three compounds structurally related to BZN were identified: BZN-Na+ (m/z 283.08009), N-amine-BZN (m/z 230.12307) and N-hydroxi-amine-BZN (m/z 246.11702). BNZ-Na+ was identified in all extracts, but N-amine-BZN and N-hydroxi-amine-BZN were only observed in those extracts treated with β-glucuronidase. This is the first experimental report showing elimination of BZN N-reduced metabolites in urine. As they were released after treatment with β-glucuronidase it can be suggested that glucuronization plays a role in BNZ metabolism and renal elimination.

Estudo comparativo da ação sanitizantes de uso caseiros em hortaliças contaminadas com Ancilostomídeos / Comparative sanitizers study of domestic aplication in vegetables contaminated with hookworms / Estudio comparativo de la acción higiénica de los cuidadores en vegetales contaminados con anquilostomas

Objetivo: O presente trabalho tem como objetivo verificar a efetividade de sanitizantes de uso caseiros quanto a capacidade de paralisar e desinfetar larvas de Ancilostomídeos. Método Para obtenção das larvas de Ancilostomídeos foi utilizado o método de Hoffman, Pons e Janer (HPJ). Em seguida, foram preparadas lâminas com o sedimento e adicionou-se concentrações diferentes de saneantes empregados na rotina doméstica. Simultaneamente, foi avaliado, através de microscopia óptica, o tempo cronometrado que cada saneante em diferentes concentrações, necessitaria para paralisação completa do helminto. Resultados: O ácido acético e o hipoclorito não apresentaram efetividade em nenhuma das concentrações testadas. Já o vinagre de álcool puro na diluição de 40% paralisou 90% das larvas em um período de 14 minutos e 31 segundos. O vinagre composto de álcool, na concentração de 40% foi capaz de paralisar mais de 90% das larvas em um tempo médio de 9 minutos e 50 segundos. Conclusão: A utilização de 40% de sanitizantes de vinagre se mostraram eficazes na desinfecção de larvas de Ancilostomídeos. No entanto, este estudo alerta que a eliminação de larvas não é segura quando se leva em conta a concentração usada na rotina doméstica atual.

Objective: The present work aims to verify the effectiveness of homemade sanitizers for the ability to paralyze and disinfect hookworm larvae. Method: To obtain hookworm larvae, the method of Hoffman, Pons, and Janer (HPJ) was applied. The next slides were prepared with the sediment, and different sanitizing concentrations, routinely used in the domestic, were added. Simultaneously, we evaluated, by optical microscopy, the chronometer time that each sanitizer in different concentrations, would require for complete helminth paralysis. Results: Acetic acid and hypochlorite were not effective in any of the tested concentrations. Pure alcohol vinegar in the 40% dilution paralyzed 90% of the larvae in 14 minutes and 31 seconds. The vinegar composed of alcohol, in the 40% concentration, was able to paralyze more than 90% of the larvae in an 9,50 minutes average. Conclusion: The use of 40% of vinegar sanitizers proved to be useful in disinfecting hookworms larvae. However, this study cautions that larvae elimination is not safe when taking into account the concentration handled in the current domestic routine.

Objetivo: el presente trabajo tiene como objetivo verificar la efectividad de los desinfectantes caseros para la capacidad de paralizar y desinfectar larvas de anquilostomas. Método: para obtener larvas de anquilostomas, se utilizó el método de Hoffman, Pons y Janer (HPJ). Luego se prepararon los portaobjetos con el sedimento y se agregaron diferentes concentraciones de agentes desinfectantes utilizados en la rutina doméstica. Simultáneamente, se evaluó, usando microscopía óptica, el tiempo cronometrado que cada desinfectante en diferentes concentraciones necesitaría para completar la parálisis del helminto. Resultados: el ácido acético y el hipoclorito no fueron efectivos en ninguna de las concentraciones probadas. El vinagre puro de alcohol en la dilución al 40% paralizó el 90% de las larvas en un período de 14 minutos y 31 segundos. El vinagre compuesto de alcohol, en la concentración del 40%, fue capaz de paralizar más del 90% de las larvas en un tiempo promedio de 9 minutos y 50 segundos. Conclusión: el uso del 40% de desinfectantes de vinagre demostró ser eficaz para desinfectar larvas de anquilostomas. Sin embargo, este estudio advierte que la eliminación de las larvas no es segura cuando se tiene en cuenta la concentración utilizada en la rutina doméstica actual.

Complete Resolution of Electrocardiographic Changes Induced by Acute Chagas Myocarditis

We present a case of a female adolescent with severe acute Chagas myocarditis, acquired by oral transmission in an endemic area in the Brazilian western Amazon, who had electrocardiographic changes normalized after empirical treatment with the antiparasitic drug benznidazole combined with conventional treatment for severe heart failure

Antiparasitic phytotherapy perspectives, scope and current development / Perspectivas, enfoque y actual desarrollo de la fitoterapia antiparasitaria

Tropical protozoan diseases are currently a major public health problem throughout the world and are strongly linked with poverty, this combined with a lack of commercial markets for potential drugs has created a large burden on the health and economic development of low-income and middle-income countries in Africa, Asia, and the Americas. Due to the low research interest and the high increase of resistance against the existing treatments, as well as increasing ineficiency, toxicity, prolonged treatment schedules and costs, there is an urgent need for cost-effective, safe and easy-to-administer, new effective compounds with novel mechanisms of action. Several studies of crude plant extracts have already identifed potential compounds to treat Chagas' disease, Leishmaniasis, Toxoplasmosis, Giardiasis, and Malaria among other protozoan parasites. Natural compounds of medicinal plants have shown lower toxicity together with higher specificity, creating an optimistic view of new treatments for diseases. Out of 1010 new active substances approved as drugs for medical conditions by regulatory agencies during the past 25 years, 490(48.5%) were from a natural origin.

Las enfermedades tropicales por protozoarios son un problema importante de salud pública en todo el mundo y están ligadas fuertemente con la pobreza. Esto lleva a que falte investigación por las empresas farmacéuticas con ánimo de lucro, que sólo se motivan por posibilidades de mercado. Adicionalmente el aumento en resistencia a los tratamientos disponibles, la toxicidad y la necesidad de largos periodos de tratamiento y los costos de muchos de ellos, hacen que exista una urgente necesidad de nuevos medicamentos costo efectivos, seguros y fáciles de administrar y que tengan mecanismos de acción novedosos. Varios extractos crudos de plantas han mostrado propiedades que permiten ser eficaces para tratar la enfermedad de Chagas, la leishmaniasis, la toxoplasmosis, la giardiasis y la malaria. Los compuestos derivados de plantas han mostrado menor toxicidad con mayor especificidad, mostrando un panorama optimista para encontrar nuevos medicamentos. Esto es evidente al analizar las cifras que muestran entre 1.010 nuevas sustancias activas aprobadas para condiciones médicas por las agencias regulatorias en los últimos 25 años, 490 (48,5%) son de origen natural.

Inclusion complexes and self-assembled cyclodextrin aggregates for increasing the solubility of benzimidazoles

Albendazole and fenbendazole are imidazole derivatives that exhibit broad spectrum activity against parasites, but the low solubility of these drugs considerably reduces their effectiveness. Complexation of albendazole and fenbendazole with cyclodextrins (ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) in both water and an aqueous solution of polyvinylpyrrolidone (PVP-k30) was studied to determine if it could increase the solubility and dissolution rate of the drugs. In an aqueous solution, ß-cyclodextrin increased the solubility of albendazole from 0.4188 to ~93.47 µg mL-1 (223×), and of fenbendazole from 0.1054 to 45.56 µg mL-1 (432×); hydroxypropyl-ß-cyclodextrin, on the other hand, increased solubility to ~443.06 µg mL-1 (1058×) for albendazole and ~159.36 µg mL-1 (1512×) for fenbendazole. The combination of hydroxypropyl-ß-cyclodextrin and polyvinylpyrrolidone enabled a solubility increase of 1412× (~591.22 µg mL-1) for albendazole and 1373× (~144.66 µg mL-1) for fenbendazole. The dissolution rate of the drugs was significantly increased in binary and ternary systems, with hydroxypropyl-ß-cyclodextrin proving to be more effective. The presence of the water-soluble PVP-k30 increased the dissolution rate and amorphization of the complexes. Analysis of the changes in displacement and the profile of the cyclodextrin bands in the 1H NMR spectra revealed a molecular interaction and pointed to an effective complexation in the drug/cyclodextrin systems. Monomeric forms and nanoclusters of cyclodextrins were observed in the drug/cyclodextrin systems, suggesting that the increase in solubility of the drugs in the presence of cyclodextrins should not be attributed only to the formation of inclusion complexes, but also to the formation of cyclodextrin aggregates

Blastocystis sp. en humanos: actualización y experiencia clínico-terapéutica

Blastocystis sp. es uno de los parásitos del humano más frecuentemente identificados en el laboratorio clínico durante el estudio parasitológico de las muestras de heces. En esta revisión se actualizan los aspectos relativos a la diversidad genética y especificidad del huésped, la taxonomía, caracterización molecular, formas clínicas y experiencia terapéutica en pacientes inmuno-competentes y comprometidos, sintomáticos y asintomáticos, de la consulta de la Sección de Geohelmintiasis del Instituto de Medicina Tropical de la Facultad de Medicina de la Universidad Central de Venezuela, proponiendo el secnidazol como droga de primera elección. Se analiza la presencia de Blastocystis como patógeno humano o como comensal, formando parte de la microbiota intestinal. Se considera la tendencia actual entre los diferentes grupos de investigación a mirar la blastocistosis como un problema de salud pública en lugar de una entidad clínica frecuente y se incluyen elementos que pudieran reforzar esta visión. Se incluyen las medidas que pudieran contribuir a prevenir la parasitosis. Dado que la investigación sobre este parásito progresa rápidamente, se recomienda realizar revisiones frecuentes para mantener actualizados los conceptos relacionados con su epidemiología, diagnóstico, tratamiento y prevención en el paciente inmunocompetente así como en el inmunosuprimido.

Blastocystis sp. is one of the human parasites most frequently identified in the clinical laboratory during the parasitological study of stool samples. This review updates the aspects related to genetic diversity and host specificity, taxonomy, molecular characterization, clinical forms and therapeutic experience in symptom free and symptomatic immune-competent and compromised patients who attended to the Soil Transmitted Helminth Section of the Institute of Tropical Medicine of the Faculty of Medicine of the Central University of Venezuela, proposing secnidazole as the drug of first choice. The presence of Blastocystis as human pathogen or as part of the gut microbiota, are analyzed. The current trend among the different research groups is to look at Blastocystosis as a public health problem rather than a common clinical entity and include elements that could reinforce this view. Measures that could help prevent parasitic disease are also included. Since research on this parasite is progressing rapidly, frequent reviews are recommended to keep the concepts related to its epidemiology, diagnosis, treatment and prevention updated in the immunocompetent as well as the immunosuppressed patient.

Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products

This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.

Interações entre antiparasitários e alimentos / Interactions between antiparasitic drugs and food

O uso, por vezes indiscriminado, de antiparasitários pode levar a consequências importantes na saúde do indivíduo, principalmente relacionadas a alterações no sistema gastrointestinal. As interações entre fármacos e nutrientes podem ocorrer quando um alimento ou nutriente altera a resposta esperada de um medicamento ou quando este interfere sobre o estado nutricional do indivíduo. Essa alteração da eficácia pode resultar em falha no tratamento ou até mesmo na toxicidade do fármaco. A fim de conhecer, identificar e prevenir interações indesejáveis entre antiparasitários e alimentos, o presente artigo de revisão aborda os principais fármacos e alimentos ou nutrientes envolvidos, bem como as consequências que tais interações podem acarretar ao indivíduo. O estado nutricional é de suma importância nas infecções parasitárias, pois é o determinante entre uma maior carga de parasitos ou a resistência total contra a infecção. De forma geral, indivíduos parasitados são inapetentes e emagrecidos, o que em crianças pode comprometer o desenvolvimento físico e intelectual. Portanto, o conhecimento e uma correta orientação médica, farmacêutica e nutricional levam a um tratamento bem sucedido...

The often indiscriminate use of antiparasitic drugs can lead to serious consequences for the health of the individual, mainly related to alterations in the gastrointestinal system. Interactions between drugs and nutrients may occur when a food or nutrient changes the expected response of a drug or when a medicine interferes with the individual's nutritional status. These changes may result in treatment failure or even toxicity of the drug. As an aid to the detection, identification and prevention of undesirable interactions between foods and antiparasite drugs, in this review we discuss the major drugs and foods or nutrients involved and the consequences that these interactions can have for the individual. Nutritional status is important in parasitic infections, as it is a factor determining the parasite load level or the total resistance against infection. Generally, individuals infected by parasites have a poor appetiteand are emaciated, which in children can damage physical and intellectual development. Therefore, knowledge of the parasite and proper medical, pharmaceutical and nutritional guidance lead to a more successful treatment...

Avaliação in vitro de diferentes propriedades físico-químicas de medicamentos de uso infantil / In vitro evaluation of different physicochemical properties of pediatric medicines

Objetivo: Avaliar in vitro o pH endógeno, a Acidez Total Titulável (ATT) e o oBrix de medicamentos infantis. Metodologia: A amostra foi constituída por 22 diferentes medicamentos de 5 distintas classes: antibióticos, anti-histamínicos, antiparasitários, antiinflamatórios não esteróides e corticóides. As medidas do pH foram determinadas utilizando-se o potenciômetro, a acidez total foi realizada utilizando o método da A.O.A.C e o oBrix foi determinado por refratometria. Os dados foram expressos em médias e analisou-se a diferença entre os grupos, através da ANOVA. A significância utilizada foi de 0,05 com 95% de grau de confiança.Resultados: Verificou-se que 59,1% dos medicamentos apresentaram um pH menor que 5,5, sendo portanto potencialmente erosivo aos tecidos dentais. A menor e maior média do pH foram encontradas para o Benflogin (1,75) e para o Predsim (7,35), respectivamente. Em relação à ATT, a menor média foi verificada para o Cataflan (0,01%), enquanto o maior valor foi registrado para o Infectrin (0,98%). A avaliação do oBrix revelou que o Alersin apresentou a menor média (6,25%), enquanto o Cataflan mostrou o maior valor (74,33%). Não se verificou diferença estatisticamente significativa entre as variáveis pH e a classe de medicamento (P=0,950) e entre o °Brix e a classe de medicamento (P=0,477). Todavia, verificou-se diferenças estatisticamente significante em relação à acidez total e a classe de medicamento (P = 0,000), de modo que as diferenças maiores ficaram entre as médias dos antibióticos com: os antiinflamatórios (P=0,002), os antiparasitários (P=0,003) e os corticóides (P=0,005)...

Objective: To evaluate in vitro the endogenous pH, the total titratable acidity (TTA) and o Brix of pediatric medicines. Method: The sample consisted of 22 pediatric medicines belonging to five classes: antibiotics, antihistamines, anthelmintics, non-steroid antiinflammatory drugs and corticoids. The pH was measured with a potentiometer, total acidity was obtained by the AOAC method and oBrix was determined by refractometry. The data were expressed as means and the differences among the groups were analyzed by ANOVA. The significance level was set at 0.05 with a 95% confidence level. Results: As much as 59.1% of the medicines presented pH lower than 5.5, being therefore potentially erosive to the dental tissues. Benflogin (1.75) and Predsim (7.35) presented the lowest and the highest pH means, respectively. As for TTA, the lowest mean was obtained for Cataflan (0.01%) and the highest for Infectrin (0.98%). Evaluation of oBrix revealed that Alersin presented the lowest mean (6.25%) and Cataflan (74.33%) presented the highest mean. There was no statistically significant difference among the medicine classes regarding the pH (p=0.950) or regarding the o Brix (p=0.477). On the other hand, there were statistically significant differences among the medicine classes for TTA (p=0.000); the greatest differences were found between the antibiotics and the anti-inflammatory drugs (p=0.002), the anthelmintics (p=0.003) and the corticoids (p=0.005). Conclusion: The pediatric medicines may be considered as potentially erosive to the dental tissues. In view of the statistically significant differences among the medicine classes regarding the TTA, it is recommended that the control and follow up be directed to the erosive potential of each class. The antibiotics are the class of medicine with the highest pH and acidity, and so its intake should be followed by an adequate oral hygiene...

Assessment of Leishmania major and Leishmania braziliensis promastigote viability after photodynamic treatment with aluminum phthalocyanine tetrasulfonate (AlPcS4)

Cutaneous leishmaniasis is an infectious disease caused by protozoans of the genus Leishmania, which is transmitted through the bite of hematophagous insects of the genus Lutzomyia. This study aimed at testing in vitro the phototoxic effect of aluminum phthalocyanine tetrasulfonate (AlPcS4) on the viability of Leishmania major and Leishmania braziliensis. Stationary phase promastigote forms were treated with AlPcS4 at 1.0 µM and 10.0 µM and incubated for one hour. Then 659 nm laser was applied at 5 and 10 J/cm². Parasite viability was determined by differential count using the trypan blue dye exclusion method and by monitoring growth curves for nine days. Trypan blue exclusion assay showed a significant reduction of viable parasites compared to controls, L. major seemed more sensitive to the toxic effects of AlPcS4 in the dark. The most effective photodynamic therapy (PDT) was obtained with AlPcS4 at 10.0 µM and 10 J/cm² whereas L. braziliensis showed the highest mortality rate after treatment.

Volatile oil of Chinese crude drug against human demodex: Effectiveness and safety / 第二军医大学学报

Objective: To search for effective volatile oil of Chinese crude drug for killing demodex in vitro. Methods: The demodex mites were collected by adhesive cellophane tape technique. The killing effects of different volatile oils against Df and Db were observed by microscope. Normal saline and Xinfu Manling Ointment were used as negative and positive controls, respectively. Skin irritation tests for normal and wounded skin and acute toxicity test were carried out using rabbit skin. Results: The volatile oils of 6 Chinese crude drugs, including clore, orange fruit, manchurian wildginger, cinnamon bark, rhizoma alpinae, and pricklyash peel, were highly potent in killing Df and Db in vitro; and the volatile oil of clore and manchurian wildginger had a better killing effect against Df than Db(P< 0.05). The scores for irritation to normal and wounded rabbit skin were 0.2 and 0.3, respectively, and acute toxicity test showed no obvious toxicity. Conclusion: The volatile oils of the 6 mentioned Chinese crude drugs have satisfactory anti-mite activities in vitro. The volatile oil of clore shows a remarkable activity against demodex in vitro, with good skin safety.

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.