Coverage of vitamin A supplementation, deworming and immunisations: Associations with nutritional status among urban children younger than 5 years in Nelson Mandela Bay, Eastern Cape Province, South Africa

Background. Even though immunisation coverage is tracked through the district health system in South Africa (SA), limited information is available regarding interventions linked to the Expanded Programme on Immunisation (EPI) and the impact on the nutritional status of children <5 years of age.Objectives. To describe coverage of immunisations, vitamin A supplementation and deworming among children <5 years old in an urban area of Nelson Mandela Bay, Eastern Cape Province, SA. A secondary objective was to investigate whether a history of missed immunisations, vitamin A supplementation or deworming was associated with wasting or stunting in children.Methods. A descriptive study was conducted between September 2015 and February 2016, where cross-sectional anthropometrical data were collected from 1 513 children in 32 pre-schools, together with a retrospective analysis of the participants' Road-to-Health/clinic cards to collect data on immunisation, vitamin A and deworming. Participants were categorised into 3-month age intervals to facilitate data analysis. Ethical approval was obtained from the Nelson Mandela University Research Ethics Committee (Human). Results. Data of 1 496 children were included in the analysis. The prevalence of underweight was 2.5% (n=37), while 11.2% (n=167) were stunted and 1.1% (n=16) were wasted. There were associations between age category and delayed vitamin A supplementation (χ2=32.105; df=19; n=836; p=0.03) and deworming (χ2=45.257; df=17; n=558; p<0.001), but there was no association between delayed vaccinations and age category. There were no significant differences in anthropometrical indicators for children with delayed vitamin A supplementation, deworming and vaccinations compared with children in this sample who were up to date regarding the relevant indicators. However, weight-for-age, height-for-age and weight-for-height z-scores and stunting risk were associated with low birthweight (LBW) (odds ratio (OR) 4.658; p<0.001). Conclusion. Coverage of vitamin A supplementation and deworming but not immunisations was poorer among children in older age categories. A history of delayed vitamin A, deworming and vaccinations was not associated with the anthropometrical status of children. Children with LBW should be considered for more rigorous follow-up, as they are at higher risk of stunting.

Compromiso neurológicoy cardiovascularen pacientes con triquinosis / Neurological and cardiovascular involventin patients with trichinosis

Introducción: La triquinosis es una infección parasitaria causada por nematodos del género Trichinella. El compromiso cardíaco no es habitual, pero representa la causa más frecuente de muerte por triquinosis, mientras que la afectación neurológica ocurre principalmente en pacientes severamente enfermos. Se sabe que a mayor cantidad de larvas ingeridas menor es el tiempo de incubación y mayor es la severidad de la enfermedad. Se presentan dos pacientes con compromiso del sistema nervioso central, uno de ellos cardiovascular, ambos pertenecientes a un brote de triquinosis ocurrido en la ciudad de Bahía Blanca.

Background: Trichinosis is a parasitic infection caused by nematodes of the genus Trichinella. Cardiac involvement is not usual but represents the most frequent cause of death by trichinosis, while neurological affectation occurs mainly in severely ill patients. A greater number of larvae ingested, the shorter the incubation time and the greater the severity of the disease. We present two patients with compromise of the central nervous system and one of them cardiovascular, both belonging to an outbreak of trichinosis in the city of Bahía Blanca

Parasitosis y antiparasitarios en niños / Parasitosis and antiparasitic treatment in children / Parasitoses e antiparasitários em crianças

Las parasitosis siguen siendo un grave problema de salud en pediatría, no tanto por la mortalidad que ocasionan sino por la morbilidad y sus secuelas en el crecimiento y desarrollo de los niños y en su desempeño en la vida adulta. Dentro de los parásitos de mayor prevalencia en los niños, están los que se transmiten por contacto con el suelo (geohelmintos o helmintos transmitidos por contacto con el suelo, HTS), dentro de los cuales, los de mayor prevalencia, son los áscaris, tricocéfalos y uncinarias. Como los parásitos intestinales no se reproducen en el organismo humano, su principal fuente de contagio se da a través del suelo que esté contaminado con materias fecales. Es por esta razón que los principales factores determinantes son: contaminación fecal del ambiente, agua contaminada, falta de excretas y malos hábitos higiénicos, especialmente en el lavado de manos. Sus manifestaciones clínicas son variables en intensidad y en signos, hay que tener presente que muchas de las personas parasitadas pueden estar asintomáticas durante mucho tiempo, pero siguen excretando huevos en las fecales, contaminando así el ambiente y perpetuando su prevalencia. Por esta razón, la Organización Mundial de la Salud (OMS) recomienda que en aquellas regiones o áreas donde la prevalencia de las geohelmintiasis sea igual o superior al 20% se debe hacer una desparasitación masiva y con una periodicidad acorde con la gravedad de esta prevalencia. En la actualidad se dispone de antiparasitarios efectivos, fáciles de suministrar (incluso por personal no médico). Los más comunes (albendazol y mebendazol) actúan inhibiendo la síntesis de adenosín trifosfato (ATP) necesario para su supervivencia. Como solamente se absorbe entre el 1% y el 5% del medicamento y su metabolismo es rápido, los efectos secundarios son leves y transitorios. Lo ideal es emplearlos en los pacientes que vivan en zonas de riesgo y en comunidades con una prevalencia igual o mayor al 20%, continuando con desparasitaciones periódicas de acuerdo al comportamiento de la prevalencia. Es evidente el impacto que se logra con la desparasitación periódica, tanto en el crecimiento y en el estado nutricional, como en el desempeño cognitivo, así como sus efectos en el campo social y ambiental.

Parasitosis continues to be a serious problem in pediatrics, not only because it is a cause of death, but because of the morbility and the long-term effects it has on growth and development in children and later on in their adult life. The most prevalent parasites in children include those transmitted by contact with the soil (geohelminths or soil-transmitted helminths, STH), amongst which the most common are the ascaris, trichocephalia, and uncinaria. Since intestinal parasites are not produced inside the human body, they are mainly contracted through soil contaminated with fecal matter. Thus, the principal determining factors include fecal contamination in the environment, contaminated water, improper excreta management, and poor personal hygiene, especially hand washing. Its clinical manifestations vary in intensity and in signs; also, many individuals with parasites may be asymptomatic for a long period of time, but their fecal matter contains eggs, thus, contaminating the environment and perpetuating its prevalence. Therefore, the World Health Organization (WHO) recommends that regions where geohelminthiasis prevalence is 20% or higher should be massively treated for parasites with a periodicity that is appropriate for the seriousness of the prevalence. Currently, there are effective antiparsitics available that are easy to administer (even by non-medical personnel). The most common medications (albendazole and mebendazole) inhibit the synthesis of adenosine triphosphate (ATP) needed for survival. Since only between 1 and 5% of the medication is absorbed and children's metabolism is fast, secondary effects are minor and transitory. It is recommended that they be used in patients that live in high-risk areas and in communities with a prevalence of 20% or higher, conducting periodic mass drug administration for parasite removal depending on the behavior of the prevalence. Regular parasite removal has an evident impact on growth, nutritional state, cognitive performance, as well as its effects on the social and environmental fields.

As parasitoses seguem sendo um grave problema de saúde em pediatria, não tanto pela mortalidade que ocasionam senão pela morbilidade e suas sequelas no crescimento e desenvolvimento das crianças e no seu desempenho na vida adulta. Dentro dos parasitos de maior prevalência nas crianças, estão os que se transmitem por contato com o solo (geohelmintos ou helmintos transmitidos por contato com o solo, HTS), dentro dos quais, os de maior prevalência, são os áscaris, tricéfalos e uncinárias. Como os parasitos intestinais não se reproduzem no organismo humano, sua principal fonte de contágio se dá através do solo que esteja contaminado com matérias fecais. É por esta razão que os principais fatores determinantes são: contaminação fecal do ambiente, água contaminada, falta de excretas e maus hábitos higiênicos, especialmente na lavagem das mãos. Suas manifestações clínicas são variáveis em intensidade e em signos, há que ter presente que muitas das pessoas parasitadas podem estar assintomáticas durante muito tempo, mas seguem excretando ovos nas fecais, contaminando assim o ambiente e perpetuando sua prevalência. Por esta razão, a Organização Mundial da Saúde (OMS) recomenda que naquelas regiões ou áreas onde a prevalência das geohelmintiase seja igual ou superior a 20% se deve fazer uma desparasitação massiva e com uma periodicidade acorde com a gravidade desta prevalência. Na atualidade se dispõe de antiparasitários efetivos, fáceis de subministrar (incluso por pessoal não médico). Os mais comuns (albendazol e mebendazol) atuam inibindo a síntese de adenosina trifosfato (ATP) necessário para sua supervivência. Como somente se absorbe entre 1% e 5% do medicamento e seu metabolismo é rápido, os efeitos secundários são leves e transitórios. O ideal é empregá-los nos pacientes que vivam em zonas de risco e em comunidades com uma prevalência igual ou maior a 20%, continuando com desparasitações periódicas de acordo ao comportamento da prevalência. É evidente o impacto que se consegue com a desparasitação periódica, tanto no crescimento e no estado nutricional, como no desempenho cognitivo, assim como seus efeitos no campo social e ambiental.

Autophagy Is a Potential Target for Enhancing the Anti-Angiogenic Effect of Mebendazole in Endothelial Cells

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.

Estudio piloto de diagnóstico de parasitosis intestinal y respuesta al uso de Mebendazol en niños de edad escolar en las escuelas Charcas II, El Sillar y la Cascada, gestión 2010 La Paz / Pilot study of intestinal parasitosis diagnostic and response to Mebendazol on school age children at schools in Charcas II, El Sillar and La Cascada, year 2010 La Paz

El proyecto IDH 09: Desparasitación de niños en escuelas rurales", llevo adelante un trabajo piloto experimental de diagnóstico sobre parásitos intestinales en niños en las Escuelas de las Comunidades: Charcas II; La Cascada y El Sillar, Provincia Sud Yungas, Departamento de La Paz, Bolivia. El análisis coproparasitológico fue en 93 muestras tomadas entre Inicial y quinto de primaria, con edades entre 5 y 12 años. En promedio, el 97,9% de las muestras indicaron presencia de Protozoarios y hasta un 54,5% de Helmintos, concomitantemente, con una relación promedio de 2,0 veces más Protozoarios. En las escuelas de Charcas II y La Cascada la relación fue de 1,8 y en El Sillar fue de 2,5. Hasta 12 parásitos fueron identificados entre los Protozoarios: Blatocystis hominis (92,7%); Entamoeba coli (50,3%); Endolimax nana (44,0%); Giardia lamblia (39,3%); Iodamoeba bütschlii (25,0%) y Chilomastix mesnili (8,3%) y entre los Helmintos: Ascaris lumbricoides (30,0%); Uncinaria spp (21,7%), Strongyloides stercoralis (9,0%); Hymenolepis nana (7,0%) y Trichuris trichiura (5,7%), en una muestra se detectó Enterobius vermicularis. En la escuela Charcas II, de acuerdo a sus programas de desparasitación, los niños recibieron tratamiento con Mebendazol y el efecto de la medicación fue evaluado, aleatoriamente, a los 7 días, sobre un total de 21 niños. El Mebendazol (1200mg) elimino 50% de los Helmintos. A. lumbricoides fue eliminado de todas las muestras, Uncinaria spp, S. stercoralisy T. trichiura fueron eliminados en un 50%, mientras que H. nana persistió en todas las muestras, mientras que los Protozoarios fueron eliminados solo en un 19% de las muestras.

The Project Deworming of children in rural schools carried out a pilot experimental field work to determine intestinal parasites levels in kids in rural schools, at Charcas II, La Cascada and El Sillar communities, South Yungas province, Department of La Paz, Bolivia. The coproparasitologic studies were carry out on 93 feces samples, from kids from initial to fifth grade, within ages from 5 to 12 years. An average of 97,9% of the samples showed presence of protozoa parasites and up to 54,5% showed, additionally, presence of Helminthes, with a general ratio of Protozoan to Helminthes of 2,0. At Charcas II School and La Cascada School the ratio was of 1,8; while at El Sillar gave a ratio of 2,5. A total of 12 parasites were identified, among the protozoa: Blatocystishominis (92,7%); Entamoeba coli (50,3%); Endolimax nana (44,0%); Giardia lamblia (39,3%); Iodamoeba bütschlii (25,0%) and Chilomastix mesnili:(8,3%) and among the Helminthes: Ascaris lumbriocoides (30,0%); Uncinaria spp (21,7%), Strongyloides stercoralis (9,0%); Hymenolepis nana (7,0%) and Trichuris trichiura (5,7%) and in one sample we detected Enterobius vermicularis. According to their deworming program, at Charcas II School, kids received treatment with Mebendazol (1200mg) and the effect was evaluated 7 days after treatment. On a total of 21 children. Mebendazol eliminated 50% of Helminthes. A. lumbricoides was eliminated from all samples; Uncinaria spp, S. stercoralis y T. trichiura only from 50% of the samples and H. nana persisted in all samples, while Protozoan parasites were eliminated on nearly 19% of the samples

Desenvolvimento de método para avaliação do perfil de dissolução de suspensões de mebendazol / Method development for dissolution profile evaluation of mebendazol suspensions

Este trabalho teve por finalidade desenvolver um método para a caracterização do perfil de dissolução de suspensões de mebendazol (MBZ), discriminatório para as formas polimórficas do fármaco. Pertencendo a classe II do Sistema de Classificação Biofarmacêutica (SCB), além da baixa solubilidade, o MBZ é bastante crítico por apresentar-se comercialmente disponível em duas formas polimórficas (A e C) e misturas destas. Além disso, pouca informação é encontrada acerca de métodos de dissolução de suspensões. O material apresentado está dividido em três capítulos, sendo o primeiro deles uma revisão da literatura sobre a dissolução de suspensões de fármacos que apresentam polimorfismo. Neste capítulo é feita uma abordagem sobre questões relacionadas ao desenvolvimento de métodos, como inserção das amostras na cuba de dissolução, agitação, uso de tensoativos no meio e a quantificação do fármaco. No segundo capítulo é apresentado o desenvolvimento do método de dissolução, com ênfase no estudo da solubilidade das formas polimórficas A e C de MBZ e sua interação com tensoativos. Foram realizados ensaios de solubilidade pelo método do equilíbrio, cálculo de concentração micelar crítica para os tensoativos lauril sulfato de sódio e polissorbato 80, sendo ao final realizado delineamento experimental (DOE) para o desenvolvimento do método. Pela avaliação do DOE, o local de inserção da amostra não influencia a dissolução de MBZ, por outro lado, a presença de tensoativo, assim como a forma polimórfica empregada, exercem efeito nos resultados apresentados. A partir destas informações, o método indicado para avaliação das suspensões de MBZ com potencial discriminatório de suas formas polimórficas foi definido pela utilização do aparato 2 (pá) a 75 rpm, com 2 litros de HCl 0,1 M sem tensoativo, como meio de dissolução. No último capítulo, o método desenvolvido foi utilizado na avaliação de especialidades farmacêuticas adquiridas no Brasil e em alguns países da América Latina, sendo os respectivos perfis de dissolução, comparados por meio de uma análise multivariada de componentes principais, com formulações contendo o MBZ em diferentes proporções de polimorfos. A partir dos resultados, foi possível observar que grande parte das formulações comercializadas não apresentaram perfil de dissolução satisfatório, isso pode estar relacionado com a presença considerável de polimorfo A nas matérias-primas utilizadas, comprometendo assim a sua solubilidade

The aim of this work was to develop a method for characterization of the dissolution profile of mebendazole (MBZ) suspensions, being discriminatory for the polymorphic forms of the drug. MBZ belongs to class II of the Biopharmaceutics Classification System (BCS), besides its low solubility, it is very critic, being commercially available in two polymorphic forms (A and C) and their mixtures. Moreover, there is low information about dissolution methods for suspensions. The text presented herein is divided into three chapters, the first chapter is a literature review about dissolution of suspensions containing drugs that present polymorphism. In this chapter is made a discussion about the variables of the method, as sample insertion in the dissolution vessel, rotation speed, use of surfactants in the dissolution medium and drug quantification. The development of the dissolution method, focused on the solubility study of MBZ polymorphic forms A and C and their interaction with surfactants is presented in the chapter 2. Some tests were performed: solubility using shake flask method, calculation of micellar critical concentration for the surfactants sodium lauryl sulphate and polysorbate 80, and an experimental design (DOE) was done for developing the method. By DOE evaluation, the sample insertion site does not influence on MBZ dissolution, but the presence of surfactant and the polymorphic form used, show effect on the results. Based on these information, the method indicated for evaluation of MBZ suspensions, with discriminatory power for its polymorphic forms was defined by using apparatus 2 (paddle) at 75 rpm and 2 L of 0.1M HCl without surfactant as dissolution medium. In chapter 3, the method developed was used to evaluate pharmaceutical suspensions from Brazil and from some countries of Latin America. The respective dissolution profiles were compared by means of multivariate analysis of principal components with formulations containing MBZ in different polymorphs ratios. From the results, it was possible to observe that a great part of the commercially available formulations do not presented a satisfactory dissolution profile, and this fact can be related to a considerable amount of the crystalline form A in the raw material, which compromises its solubility

Albendazole and Praziquantel: Review and Safety Monitoring in Korea

Albendazole (ADZ) and praziquantel (PZQT) have been used as anthelmintics for over 30 years. Worldwide, hundreds of millions tablets are administered to people and livestock every year. ADZ is poorly orally absorbed ( 75%) and uptake is enhanced by carbohydrate-rich meals. Both ADZ and PZQT are safe, but not recommended for children < 2 years or for women in the first trimester of pregnancy. Serious adverse events occur following high dose and prolonged administration of these drugs for treatment of echinococcosis or neurocysticercosis, especially in patients with poor liver function. The adverse events may be induced by the drugs, or by the dead worms themselves. The Korea Institute of Drug Safety & Risk Management monitors drug-related adverse events in Korea, and its database included 256 probable or possible ADZ-associated events and 108 PZQT-associated events between 2006 and 2015. Such low incidence rates in Korea are due to the low single dose treatments of ADZ, and the short-term use of PZQT. The number of serious adverse events due to drug interaction induced by ADZ and PZQT were six and two, respectively. We conclude that ADZ and PZQT are generally safe drugs, but they must be used with caution in people with poor liver function or those being comedicated for gastroesophageal reflux disease.

Albendazole and Praziquantel: Review and Safety Monitoring in Korea

Albendazole (ADZ) and praziquantel (PZQT) have been used as anthelmintics for over 30 years. Worldwide, hundreds of millions tablets are administered to people and livestock every year. ADZ is poorly orally absorbed ( 75%) and uptake is enhanced by carbohydrate-rich meals. Both ADZ and PZQT are safe, but not recommended for children < 2 years or for women in the first trimester of pregnancy. Serious adverse events occur following high dose and prolonged administration of these drugs for treatment of echinococcosis or neurocysticercosis, especially in patients with poor liver function. The adverse events may be induced by the drugs, or by the dead worms themselves. The Korea Institute of Drug Safety & Risk Management monitors drug-related adverse events in Korea, and its database included 256 probable or possible ADZ-associated events and 108 PZQT-associated events between 2006 and 2015. Such low incidence rates in Korea are due to the low single dose treatments of ADZ, and the short-term use of PZQT. The number of serious adverse events due to drug interaction induced by ADZ and PZQT were six and two, respectively. We conclude that ADZ and PZQT are generally safe drugs, but they must be used with caution in people with poor liver function or those being comedicated for gastroesophageal reflux disease.

Apendicitis y parásitos: a propósito de 2 casos / Appendicitis and parasites: Reporting of 2 cases

Objetivo: Enfatizar la importancia de sospechar esta etiología en la patogenia de la apendicitis aguda, especialmente en pacientes procedentes de países endémicos. Casos clínicos: Presentamos dos casos, con cursos clínicos divergentes.

Aim: We would like to emphasize the importance of having a high grade of suspect about the parasitic etiology of appendicitis acute, especially in patients from endemic countries. Case report: We present two cases with divergent clinical evolution.

Ascaris lumbricoides: una causa de pancreatitis aguda / Acute pancreatitis due to Ascaris lumbricoides

La ascariasis es una infección parasitaria causada por un helminto de distribución global, con más de 1.4 billones de personas infectadas en el mundo. La mayoría de estas infecciones ocurren en países en vías de desarrollo de América latina y Asia. El helminto usualmente se aloja en el intestino delgado en forma silente pero puede causar obstrucción intestinal o peritonitis perforativa, siendo más común en la niñez. A su vez, puede migrar a través de la ampolla de Vater y producir pancreatitis, colecistitis, colangitis y, en forma menos frecuente, absceso hepático. El objetivo de nuestra comunicación es notificar un caso de pancreatitis aguda secundaria a Ascaris lumbricoides, siendo ésta una complicación infrecuente pero grave de una enfermedad endémica como la ascariasis.

Ascariasis is a helminthic infection of global distribution with more than 1.4 billion persons infected throughout the world. The majority of infections occur in the developing countries of Latin America and Asia. This helminth usually lives harmlessly in small intestine but can also cause intestinal obstruction or perforation peritonitis that is common in childhood. Ascaris can also migrate through ampulla of Vater to produce pancreatitis, cholecystitis, cholangitis and, rarely, hepatic abscess. The main goal of this article is to present a case of an acute pancreatitis due to Ascaris lumbricoides, an uncommon but severe complication of an endemic disease such as ascariasis.

The use of the software JST-XRD for identification of crystalline phases in pharmaceutical raw materials and tablets / Uso do software JST-XRD para identifcação de fases cristalinas em insumos farmacêuticos e medicamentos

Study of polymorphism is of great importance for the pharmaceutical industry once polymorphs may display different physicochemical properties, which, in turn, may result in stability differences that can bring problems for the manufacturing stages and the quality of fnal products. Although research on organic polymorphs has greatly increased in the last decades, it still does not cover all needs for the pharmaceutical market. Techniques such as spectroscopy in the infrared region, nuclear magnetic resonance, thermal analysis, X-ray diffraction, etc., can be used to identify polymorphism. The polymorphism is a property of the crystalline solid state, and can be evaluated by X-ray diffraction once each polymorph exhibits one specifc X-ray diffraction pattern. The JST-XRD program is a tool designed to help the identifcation of crystalline phases (including polymorphs) present in pharmaceutical ingredients and tablets by using X-ray diffraction data obtained from scientifc articles and patents. This paper presents new implementations for the JST-XRD and describes its use in the analysis of active pharmaceutical ingredient and marketed tablets of norfloxacin, mebendazole and atorvastatin calcium. By the means of comparison, JSTXRD allowed identifying the crystalline phases in the diffraction patterns of the analyzed drugs, showing the program suitability for polymorphism research, pre-formulation and quality control in pharmaceutical industries. JST-XRD can also be used for educational purposes in undergraduate and graduate programs in order to show the potentiality of X-ray powder diffraction in polymorphism analysis.(AU)

O estudo do polimorfsmo é de grande importância na indústria farmacêutica porque os polimorfos podem apresentar diferentes propriedades físico-químicas, podendo resultar em diferenças na estabilidade e desse modo causar problemas nas etapas de manufatura e no produto fnal. Embora a pesquisa de moléculas orgânicas que apresentam polimorfsmo tenha aumentado bastante nas últimas décadas, ainda não contempla todas as necessidades do mercado farmacêutico. Para a identifcação de polimorfsmo podem ser utilizadas técnicas como espectroscopia na região do infravermelho, ressonância nuclear magnética, análise térmica (DSC), difração de raios X, etc. O polimorfsmo, por ser uma propriedade do estado sólido e cristalino, pode ser avaliado através da difração de raios X, já que cada polimorfo apresenta um padrão de difração de raios X único. O programa JST-XRD é uma ferramenta projetada para auxiliar a identifcação de fases cristalinas, incluindo polimorfos, presentes em insumos farmacêuticos e comprimidos, usando dados de difração de raios X obtidos em artigos científcos e patentes. Esse trabalho apresenta novas implementações no JST-XRD e descreve seu uso na análise de amostras de princípio ativo e comprimidos comerciais de norfloxacino, mebendazol e atorvastatina cálcica. Através das comparações realizadas, JSTXRD permitiu identifcar todas as fases cristalinas dos difratogramas dos fármacos analisados, mostrando que o programa é adequado para pesquisa em polimorfsmo; na pré-formulação e controle de qualidade em indústrias farmacêuticas, assim como para uso didático em cursos de graduação e pós-graduação a fm de mostrar as potencialidades da difração de raios X na análise de polimorfsmo.(AU)

Efficacy of nitazoxanide against toxocara canis: larval recovery and humoral immune response in experimentally infected mice / Eficácia da nitazoxanida contra Toxocara canis: recuperação larvária e resposta imune humoral em camundongos experimentalmente infectados

SUMMARYThe efficacy of nitazoxanide (NTZ) against toxocariasis was investigated in an experimental murine model and results were compared to those obtained using mebendazole. Sixty male BALB/c mice, aged six to eight weeks-old, were divided into groups of 10 each; fifty were orally infected with 300 larvaed eggs of T. canisand grouped as follows, G I: infected untreated mice; G II: infected mice treated with MBZ (15 mg/kg/day) 10 days postinfection (dpi); G III: infected mice treated with NTZ (20 mg/kg/day) 10 dpi; G IV: infected mice treated with MBZ 60 dpi; G V: infected mice treated with NTZ 60 dpi; GVI: control group comprising uninfected mice. Mice were bled via retro-orbital plexus on four occasions between 30 and 120 dpi. Sera were processed using the ELISA technique to detect IgG anti- Toxocaraantibodies. At 120 dpi, mice were sacrificed for larval recovery in the CNS, liver, lungs, kidneys, eyes and carcass. Results showed similar levels of anti- ToxocaraIgG antibodies among mice infected but not submitted to treatment and groups treated with MBZ or NTZ, 10 and 60 dpi. Larval recovery showed similar values in groups treated with NTZ and MBZ 10 dpi. MBZ showed better efficacy 60 dpi, with a 72.6% reduction in the parasite load compared with NTZ, which showed only 46.5% reduction. We conclude that administration of these anthelmintics did not modify the humoral response in experimental infection by T. canis. No parasitological cure was observed with either drug; however, a greater reduction in parasite load was achieved following treatment with MBZ.

RESUMOFoi investigada a eficácia da nitazoxanida (NTZ) na toxocaríase murina experimental e os resultados comparados com os obtidos usando mebendazol (MBZ). Sessenta camundongos BALB/c machos, com idade entre seis e oito semanas foram divididos em grupos de 10 cada, 50 foram infectados oralmente com 300 ovos larvados de T. canise agrupados a seguir: GI: camundongos infectados não tratados; GII: camundongos infectados tratados com MBZ (15 mg/kg/dia) 10 dias pós-infecção (dpi); GIII: camundongos infectados tratados com NTZ (20 mg/kg/dia) 10 dpi, GIV: camundongos infectados tratados com MBZ 60 dpi; GV: camundongos infectados tratados com NTZ 60 dpi; GVI: controle não infectado. Os camundongos foram sangrados via plexo retro orbitário em quatro ocasiões entre o 30º e 120º dpi. Os soros foram processados pela técnica de ELISA para detecção de anticorpos IgG anti- Toxocara.Aos 120 dpi, os animais foram sacrificados para a recuperação larvária do SNC, fígado, pulmões, rins, olhos e carcaça. Os resultados mostraram níveis similares de anticorpos IgG anti- Toxocaraentre os camundongos infectados mas não submetidos a tratamento e os grupos infectados e tratados com MBZ ou NTZ, aos 10 e 60 dpi. Os valores da recuperação larval foram similares nos grupos tratados com NTZ e MBZ 10 dpi. MBZ mostrou melhor eficácia aos 60 dpi, com redução de 72,6% da carga parasitária comparada com NTZ, que mostrou redução somente de 46,5%. Concluímos que a administração destes anti-helmínticos não modificou a resposta humoral na infecção experimental por T. canis. Não foi observada cura parasitológica com nenhuma das drogas; porém maior redução na carga parasitária foi obtida após o tratamento com MBZ.

Preparação e caracterização no estado sólido de polimorfos do mebendazol / Preparation and solid state characterization of mebendazole polymorphs

O polimorfismo é um fenômeno de grande importância no desenvolvimento de um medicamento. Os polimorfos de um fármaco podem apresentar propriedades físico-químicas diferentes. A pesquisa de polimorfos envolve a realização de experimentos e a caracterização por diferentes técnicas. Neste trabalho, o mebendazol foi escolhido para o estudo de polimorfos. Assim, experimentos de cristalização foram realizados. As amostras foram caracterizadas por diferentes técnicas. Três polimorfos foram obtidos. Os resultados evidenciaram características morfológicas e físico-químicas que permitiram diferenciar as formas cristalinas do mebendazol. Por fim, dez medicamentos comerciais foram avaliados por difração de raios X. Verificou-se a presença, em alguns casos, da forma A, ineficaz, do mebendazol. Este trabalho demonstra que variando-se as condições experimentais é possível obter polimorfos diferentes do mebendazol, inclusive a forma A, não desejada nas formulações. Os métodos analíticos utilizados possibilitam a diferenciação dos polimorfos do mebendazol.

Natural infection of Crenosoma vulpis (Nematoda: Crenosomatidae) in an urban Korean dog / 대한수의학회지

A male, 3.5 month old Pomeranian dog was diagnosed with a natural infection of Crenosoma (C.) vulpis in Daejeon, Korea. First stage larvae of C. vulpis were detected by fecal examination using the Baermann technique. Thoracic radiographs revealed mild, pervasive bronchial infiltration of the lung. Enumeration of larvae via the McMaster technique revealed 1,600 larvae per gram of feces. The dog was treated with mebendazole, and clinical symptoms were resolved 2 weeks post-treatment, as indicated by the subject presenting fecal tests negative for C. vulpis.

Current status of the efficacy and effectiveness of albendazole and mebendazole for the treatment of Ascaris lumbricoides in North-Western Indonesia

OBJECTIVE@#To investigate the efficacy and effectiveness of albendazole and mebendazole in the treatment of Ascaris lumbricoides (A. lumbricoides) in the North-Western Indonesia.@*METHODS@#229 primary school children who were positive for A. lumbricoides in their stool were recruited in the study. 123 children received single-dose of 400 mg albendazole and 106 children received single-dose 500 mg of mebendazole. After 1 week, their stools were examined for the cure rate (CR) and egg reduction rate (ERR). Egg culture was also performed and observation was made on week-1, -3, -4.@*RESULTS@#have shown a non-significant difference in CR 96.7%vs. 100% and ERR of 99.3%vs. 100.0% for albendazole and mebendazole groups respectively (P>0.05). In-vitro egg culture has shown trends of decrease in the percentage of the unfertilized eggs and in ≥ 2 cell eggs in both treatment groups (P<0.05). The embryonated eggs from the albendazole groups has shown an increase from 7.3% on week-1 to 13.8% on week-4, whilst the mebendazole group has shown a constant increase during the whole 4 weeks of culture from 7.5% to 28.3% (P<0.01).@*CONCLUSIONS@#No evidence of drug resistance is noted so far from the area of North-Western part of Indonesia. In addition, although both drugs showed incomplete ovicidal effects, single-dose albendazole is better than mebendazole in sterilizing A. lumbricoides eggs.

Eliminación de estadios juveniles de Ascaris lumbricoides (Linneo, 1758) por via oral: Reporte de un caso y algunas consideraciones epidemiológicas / Elimination of juvenile stages of Ascaris lumbricoides (Linnaeus, 1758) by mouth: Report of a case and some epidemiological considerations

Ascariosis is a parasitic disease caused by Ascaris lumbricoides, a large geohelmint endemic in our country. At present, ascariosis is a rare infection in Chile. We present a case of an adult, resident of the Villa Alemana municipality, Valparaiso Region, who spontaneously expelled two juvenile nematodes by mouth. We review the manifestations produced by the larval and adult stages of this parasite including their diagnosis, treatment, and epidemiological considerations.

La ascariosis es una parasitosis provocada por Ascaris lumbricoides, el geo-helminto de mayor tamaño que afecta al ser humano en nuestro país. En Chile, la ascariosis es una infección poco frecuente en la actualidad. Se presenta el caso de un adulto residente en la comuna de Villa Alemana, Región de Valparaíso, que eliminó en forma espontánea dos ejemplares del nemátodo en estado juvenil por vía oral. Se revisan las manifestaciones producidas por este parásito en la fase larvaria y adulta, el diagnóstico, el tratamiento y algunas consideraciones epidemiológicas.

Development and validation of a microbial counting method for mebendazole oral suspension / Desenvolvimento e validação de um método de contagem microbiana para o mebendazol suspensão oral

Mebendazole is an important medicine used to treat helminth infections. These infections affect more than two billion people worldwide. The LAFEPE® (Recife-PE, Brazil) produces the drug mebendazole oral suspension that contains the preservatives methylparaben and propylparaben in its formulation. Drugs that have antimicrobial properties due to preservatives must undergo neutralization of these compounds to allow microbial count testing according to recommendations by the official compendia. In order to obtain a validated method for microbial counting and to ensure its safety and reliability within the pharmaceutical industry, validation of preservative neutralization and of the method for microbial counting was performed according to the USP 30 and PDA Technical Report No. 33. The method used ATCC Gram positive and Gram negative microorganisms, yeasts, most and culture media Tryptic Soy Agar and Sabouraud dextrose agar. The neutralizers were polysorbate 80 and lecithin. Recovery levels of over 70 percent of the microorganisms used in the test indicated the neutralization of antimicrobial activity and proved the absence of toxicity of neutralizers. The microbial counting method validated proved accurate, precise, robust and linear and can be safely used in routine operations.

O mebendazol é um importante medicamento utilizado no tratamento de infecções por helmintos. Essas infecções afetam mais de dois bilhões de pessoas em todo o mundo. O LAFEPE (Recife-PE, Brasil) produz o medicamento mebendazol suspensão oral, que possui em sua formulação os conservantes metilparabeno e propilparabeno. Em medicamentos que possuem propriedades antimicrobianas em decorrência dos conservantes faz-se necessária a neutralização da ação desses compostos para a realização do teste de contagem microbiana segundo preconizado pelos compêndios oficiais. A fim de obter um método de contagem microbiana validado e que garanta sua segurança e reprodutibilidade dentro da indústria farmacêutica foi realizada a validação da neutralização dos antimicrobianos e validação do método de contagem microbiana de acordo com a USP 30 e PDA-Technical Report N° 33. O método desenvolvido utilizou microrganismos ATCC Gram positivos, Gram negativos, leveduras e fungos e meios de cultura Tryptic Soy Agar e Sabouraud-dextrose Agar. Os neutralizantes foram polissorbato 80 e lecitina de soja . Níveis de recuperação superiores a 70 por cento dos microrganismos utilizados no ensaio indicaram neutralização da atividade antimicrobiana e comprovou a ausência de toxicidade dos neutralizantes. O método de contagem microbiana validado revelou-se exato, preciso, robusto e linear podendo ser utilizado com segurança na rotina operacional.