Dissolution profile of different brands of low solubility drugs available in the Nigerian and Brazilian pharmaceutical markets / Dissolution profile of different brands of low solubility drugs available in the Nigerian and Brazilian pharmaceutical markets

The purpose of this work was to elaborate a diagnosis of the dissolution test in Africa in comparison with Brazil, evaluating the dissolution profile of low solubility drugs such as albendazole, ibuprofen, furosemide, glibenclamide, hydrochlorothiazide and carvedilol to ascertain their quality. The dissolution profiles were evaluated by utilizing the United States Pharmacopeia (USP). The glibenclamide medicine was evaluated according to the Food and Drug Administration (FDA), while a dissolution method was developed for the carvedilol medicine. A filter selection test for all the drugs showed that cannula is suitable for all, except for carvedilol, which is centrifuged. The various brands of Nigerian and Brazilian medicines tested showed some statistical differences. The suitable conditions that allowed the dissolution of carvedilol to be determined were the USP type II apparatus at 75 rpm containing 900 mL of acetate buffer, pH 4.5. The results of the dissolution test showed that out of the 17 different brands of Brazilian medicines and 17 different products from Nigeria, 94.12% and 58.82% passed respectively

O objetivo deste trabalho foi elaborar um diagnóstico do teste de dissolução na África em comparação ao Brasil, avaliando o perfil de dissolução de medicamentos de baixa solubilidade como albendazol, ibuprofeno, furosemida, glibenclamida, hidroclorotiazida e carvedilol para verificar sua qualidade.Os perfis de dissolução foram avaliados utilizando a Farmacopeia dos Estados Unidos (USP). O medicamento glibenclamida foi avaliado de acordo com a Food and Drug Administration (FDA), enquanto um método de dissolução foi desenvolvido para o medicamento carvedilol.Um teste de seleção de filtro para todos os medicamentos mostrou que a cânula é adequada para todos, exceto para o carvedilol, que é centrifugado. As diversas marcas de medicamentos Nigerianos e Brasileiros testadas apresentaram algumas diferenças estatísticas. As condições adequadas que permitiram a determinação da dissolução do carvedilol foram o aparelho USP tipo II a 75 rpm contendo 900 mL de tampão acetato, pH 4,5. Os resultados do teste de dissolução mostraram que das 17 diferentes marcas de medicamentos brasileiros e 17 diferentes produtos da Nigéria, 94,12% e 58,82% foram aprovados, respectivamente

Characterisation of the in vitro activity of a Nitazoxanide-N-methyl-1H-benzimidazole hybrid molecule against albendazole and nitazoxanide susceptible and resistant strains of Giardia intestinalis and its in vivo giardicidal activity

BACKGROUND It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB strain than metronidazole and albendazole and similar to nitazoxanide. OBJETIVES To evaluate the in vitro activity of CMC-20 against G. intestinalis strains with different susceptibility/resistance to albendazole and nitazoxanide and evaluate its effect on the distribution of parasite cytoskeletal proteins and its in vivo giardicidal activity. METHODS CMC-20 activity was tested against two isolates from patients with chronic and acute giardiasis, an experimentally induced albendazole resistant strain and a nitazoxanide resistant clinical isolate. CMC-20 effect on the distribution of parasite cytoskeletal proteins was analysed by indirect immunofluorescence and its activity was evaluated in a murine model of giardiasis. FINDINGS CMC-20 showed broad activity against susceptible and resistant strains to albendazole and nitaxozanide. It affected the parasite microtubule reservoir and triggered the parasite encystation. In this process, alpha-7.2 giardin co-localised with CWP-1 protein. CMC-20 reduced the infection time and cyst load in feces of G. muris infected mice similar to albendazole. MAIN CONCLUSIONS The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis.

Characterisation of the in vitro activity of a Nitazoxanide-N-methyl-1H-benzimidazole hybrid molecule against albendazole and nitazoxanide susceptible and resistant strains of Giardia intestinalis and its in vivo giardicidal activity

BACKGROUND It was previously demonstrated that CMC-20, a nitazoxanide and N-methyl-1H-benzimidazole hybrid molecule, had higher in vitro activity against Giardia intestinalis WB strain than metronidazole and albendazole and similar to nitazoxanide. OBJETIVES To evaluate the in vitro activity of CMC-20 against G. intestinalis strains with different susceptibility/resistance to albendazole and nitazoxanide and evaluate its effect on the distribution of parasite cytoskeletal proteins and its in vivo giardicidal activity. METHODS CMC-20 activity was tested against two isolates from patients with chronic and acute giardiasis, an experimentally induced albendazole resistant strain and a nitazoxanide resistant clinical isolate. CMC-20 effect on the distribution of parasite cytoskeletal proteins was analysed by indirect immunofluorescence and its activity was evaluated in a murine model of giardiasis. FINDINGS CMC-20 showed broad activity against susceptible and resistant strains to albendazole and nitaxozanide. It affected the parasite microtubule reservoir and triggered the parasite encystation. In this process, alpha-7.2 giardin co-localised with CWP-1 protein. CMC-20 reduced the infection time and cyst load in feces of G. muris infected mice similar to albendazole. MAIN CONCLUSIONS The in vitro and in vivo giardicidal activity of CMC-20 suggests its potential use in the treatment of giardiasis.

In vitro evaluation of ivermectin, moxidectin, albendazole and pyrantel against cyathostomins of horses / Avaliação in vitro da ivermectina, moxidectina, albendazole e pirantel contra ciatostomíneos de equinos

Abstract Cyathostomins are the most prevalent nematodes of horses, and multidrug resistance has been reported worldwide. There is a need to implement alternative drug monitoring analytical tests. The objective of this study was to determine the consistency (5 repetitions) of the larval migration on agar test (LMAT) using ivermectin, moxidectin, pyrantel or albendazole against cyathostomin infective-stage larvae in eight different concentrations. LMAT showed a strong coefficient of determination (R2 > 0.91), between the test repetitions (n=5). The average 50% effective concentration (EC50) for ivermectin, moxidectin, pyrantel and albendazole were 0.0404, 0.0558, 0.0864 and 0.0988 nMol, respectively. The results of the EC50 for albendazole showed the greatest range of concentration. Ivermectin and moxidectin had the lowest in between-test variation. In the future, internationally certified susceptible isolates could be used for screening new drug candidates, or to follow up the pattern of drug efficacy from field populations.

Resumo Ciatostomíneos são os nematodas mais prevalentes em equinos e a resistência múltipla foi relatada em todo o mundo. Existe a necessidade de implementar o monitoramento dos produtos com testes analíticos alternativos. O objetivo deste estudo foi determinar a consistência (5 repetições) do teste de migração larval em ágar (TMLA) usando ivermectina, moxidectina, pirantel e albendazole contra larvas infectantes de ciatostomíneos em oito concentrações diferentes. O TMLA demonstrou um coeficiente de determinação (R2) acima de 0,91 entre as repetições do teste. A concentração efetiva para 50% (CE50) para ivermectina, moxidectina, pirantel e albendazole foi de 0,0404; 0,0558; 0,0864 e 0,0988 nMol, respectivamente. A CE50 do albendazole demonstrou a maior amplitude entre os testes. A ivermectina e a moxidectina tiveram as menores variações das doses entre as repetições. No futuro, isolados certificados susceptíveis poderão ser testados com o TMLA para indicação de novos produtos e mesmo para acompanhar o perfil de eficácia de populações do campo.

In vitro susceptibility of nematophagous fungi to antiparasitic drugs: interactions and implications for biological control / Suscetibilidade in vitro de fungos nematófagos à antiparasitários: interações e implicações para o controle biológico

Abstract The fast anthelmintic resistance development has shown a limited efficiency in the control of animal's endoparasitosis and has promoted research using alternative control methods. The use of chemicals in animal anthelmintic treatment, in association with nematophagous fungi used for biological control, is a strategy that has proven to be effective in reducing the nematode population density in farm animals. This study aims to verify the in vitro susceptibility of the nematophagous fungi Arthrobotrys oligospora, Duddingtonia flagrans and Paecilomyces lilacinus against the antiparasitic drugs albendazole, thiabendazole, ivermectin, levamisole and closantel by using the Minimum Inhibitory Concentration (MIC). MICs ranged between 4.0 and 0.031 µg/mL for albendazole, thiabendazole and ivermectin, between 0.937 and 0.117 µg/mL for levamisole, and between 0.625 and 0.034 µg/mL for closantel. The results showed that all antiparasitic drugs had an in vitro inhibitory effect on nematophagous fungi, which could compromise their action as agents of biological control. D. flagrans was the most susceptible species to all drugs.

Resumo O desenvolvimento rápido da resistência anti-helmíntica demonstrou a eficiência limitada no controle de endoparasitoses em animais, e promoveu a investigação em métodos de controles alternativos. O uso de produtos químicos no tratamento anti-helmíntico animal, em associação com fungos nematófagos utilizados para o controlo biológico, é uma estratégia que tem provado ser eficaz na redução da densidade da população de nematódeos em animais agrícolas. Este estudo teve como objetivo verificar a suscetibilidade in vitro dos fungos nematófagos Arthrobotrys oligospora, Duddingtonia flagrans e Paecilomyces lilacinus frente aos antiparasitários albendazol, tiabendazol, ivermectina, levamisol e closantel, usando a concentração inibitória mínima (MIC). Os MICs variaram entre 4,0 e 0,031 μg/mL para albendazol, tiabendazol e ivermectina, entre 0,937 e 0,117 μg/mL para o levamisol, e entre 0,625 e 0,034 μg/mL para closantel. Os resultados mostraram que todos os antiparasitários tiveram um efeito inibidor in vitro sobre os fungos nematófagos, o que poderia comprometer suas atividades como agentes de controle biológico. D. flagrans foi a espécie mais sensível a todas as drogas.

Antiparasitic drugs: in vitro tests against nematophagous fungi / Antiparasitários: teste in vitro contra fungos nematófagos

Abstract The use of biological agents has been intensified in recent years against eggs and larvae of gastrointestinal nematodes as an alternative control method in pasture plant health management, with the concomitant use with antiparasitic drugs still occurring. The aim of this study was to test the in vitro activity of the following antiparasitic drugs: Ivermectin and albendazole against the following nematophagous fungi: Paecilomyces fumosoroseus, Paecilomyces lilacinus and Paecilomyces variotii. The agar diffusion test was performed using an initial concentration of 0.0016g/mL of each drug, after solidification of the culture medium containing the drug concentration each nematophagous fungi was inoculated. The results showed that in a concentration of 80μg/mL, the fungal growth decreased, however, with the concentration of 160μg/mL, there was no fungal growth in both drugs, compared to the control, which indicates an inhibition in the development of the nematophagous fungi studied when they come in contact with ivermectin and albendazole.

Resumo O uso de agentes biológicos que atuam em ovos e larvas de nematódeos gastrintestinais como uma alternativa para o manejo de pastagens de saúde tem se intensificado nos últimos anos, bem como o uso concomitante com outros medicamentos antiparasitários. O objetivo deste estudo foi testar o efeito in vitro dos fármacos Ivermectina e Albendazol em fungos nematófagos Paecilomyces fumosoroseus, Paecilomyces lilacinus e Paecilomyces variotii. Foi utilizada a técnica de difusão em agar, sendo preparado a partir de uma concentração inicial de 0,0016g/mL de cada uma das drogas e diluídas em meio de cultura, com posterior semeadura dos fungos nematófagos. Os resultados mostraram que na concentração de 80μg/mL, o crescimento diminuiu, no entanto, com a concentração de 160μg/mL de ambas as drogas, não houve crescimento de fungos durante o período de estudo, em comparação com o controle, indicando a inibição do desenvolvimento dos fungos nematófagos estudados quando em contato com a Ivermectina e Albendazol.

Effect of myrrh and thyme on Trichinella spiralisenteral and parenteral phases with inducible nitric oxide expression in mice

Trichinellosis is a serious disease with no satisfactory treatment. We aimed to assess the effect of myrrh (Commiphora molmol) and, for the first time, thyme (Thymus vulgaris L.) against enteral and encysted (parenteral) phases of Trichinella spiralis in mice compared with albendazole, and detect their effect on inducible nitric oxide synthase (iNOS) expression. Oral administration of 500 mg/kg of myrrh and thyme led to adult reduction (90.9%, 79.4%), while 1,000 mg/kg led to larvae reduction (79.6%, 71.3%), respectively. Administration of 50 mg/kg of albendazole resulted in adult and larvae reduction (94.2%, 90.9%). Positive immunostaining of inflammatory cells infiltrating intestinal mucosa and submucosa of all treated groups was detected. Myrrh-treated mice showed the highest iNOS expression followed by albendazole, then thyme. On the other hand, both myrrh and thyme-treated groups showed stronger iNOS expression of inflammatory cells infiltrating and surrounding encapsulated T. spiralis larvae than albendazole treated group. In conclusion, myrrh and thyme extracts are highly effective against both phases of T. spiralis and showed strong iNOS expressions, especially myrrh which could be a promising alternative drug. This experiment provides a basis for further exploration of this plant by isolation and retesting the active principles of both extracts against different stages of T. spiralis.

Pharmacodynamics studies on ricobendazole in male rats

The present study was conducted to study the effect of ricobendazole on male fertility, as well as its effects on the liver and kidney functions tests, some hematological parameters and histopathological changes. Forty-five mature male albino rats were used and divided into 3 equal groups. The first group was kept as control and subcutaneously injected with proplyene glycol [2 ml /kg b.wt.]. The second group was received a single subcutaneous injection of ricobendazole at a dose of 7.5 mg/kg bwt. The third group was subcutaneously injected with 7.5 mg / kg bwt twice within 3 weeks interval. The obtained results showed that administration of ricobendazole as single or repeated dose induced a variety of side effects on male reproduction as reduction of testes, epididymis, and accessory sex organs weights and change in sperm characters; decease of sperm count and motility, and increase in sperm abnormalities. liver functions test values such as Serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST] and alkaline phosphatase [AlP] were significantly increased. Moreover, administration of ricobendazole induced histopathological alterations in reproductive organs, liver and kidney. The adverse effects of ricobendazole was more pronounced in repeated dose group. Therefore, caution is required when using repeated doses of ricobendazole

Simple and rapid spectrophotometric assay of albendazole in pharmaceuticals using iodine and picric acid as CT complexing agents

Two simple, rapid and inexpensive spectrophotometric methods are described for the determination of albendazole (ALB) in bulk drug and in tablets. The methods are based on charge-transfer (CT) complexation reaction involving ALB as n-donor and iodine as σ-acceptor (method A) in dichloromethane or picric acid (PA) as π-acceptor (method B) in chloroform. The absorbance of CT complexes was measured at 380 nm for method A, and 415 nm for method B. The optimization of the experimental conditions is described. Under optimum conditions, Beer's law obeyed over the concentration ranges 8.0-240 and 2.4-42 μg mL-1 for method A and method B, respectively. The apparent molar absorptivity of CT complexes at the respective λmax are calculated to be 1.17×103 and 5.22×103 L mol-1 cm-1 respectively, and the corresponding Sandell sensitivity values are 0.2273 and 0.0509 ng cm-2. The limits of detection (LOD) and quantification (LOQ) are calculated to be (0.69 and 2.08), and (0.10 and 0.30) μg mL-1 with method A, and method B, respectively. The intra-day and inter-day accuracy expressed as % RE and precision expressed as % RSD were less than 3%. The methods were applied to the determination of ALB in tablets.

Dois métodos espectrofotométricos, simples, rápidos e de baixo custo são descritos para a determinação do albendazol (ALB) como fármaco e em comprimidos. Os métodos baseiam-se em reação de complexação de transferência de carga (TC) envolvendo ALB como n-doador e iodo como aceptor de σ (método A) em diclorometano ou ácido pícrico como π-aceptor (método B), em clorofórmio. A absorção de complexos TC foi medida em 380 nm para o método A e 415 nm para o método B. A otimização das condições experimentais é descrita. Sob condições ideais, a lei de Beer é obedecida nas concentrações entre 8,0 e 240 e 2,4 e 42 μg mL-1 para os métodos A e B, respectivamente. A absortividade molar aparente dos complexos de TC no respectivo λ max foi calculada como sendo 1,17×103 e 5,22×103 L mol-1 cm-1, respectivamente, e os valores de sensibilidade de Sandell correspondentes são 0,2273 e 0,0509 ng cm-2. Os limites de detecção (LOD) e quantificação (LOQ) calculados são (0,69 e 2,08) e (0,10 e 0,30) μg mL-1, com o método A e o método B, respectivamente. A exatidão intra-dia e inter-dia, expressa como % de erro relativo e precisão expressa como % DPR foi inferior a 3%. Os métodos foram aplicados para a determinação de ALB em comprimidos.

Effects of albendazole sulphoxide on embryonic, foetal and placental parameters in Wistar rats / Efectos de albendazol sulfóxido sobre parámetros embrionarios, fetales y placentarios en ratas Wistar

The aim of this work was to evaluate the effect of albendazole sulphoxide (ABZSO), administered to Wistar rats during pregnancy on embryonic, foetal and placental parameters. A colpocytological control was performed daily and detection of spermatozoa in the vaginal smear was considered as day 0 of pregnancy. For the preimplantational study, ABZSO (10 mg/kg) was orally administered at day 2 of pregnancy; at day 4 the embryos were collected. For the postimplantational study, ABZSO (10 mg/kg) was orally administered by gavages at day 2, 6 or 10 of pregnancy (G2, G6 and G10 Groups respectively); the control group was administered the same volume of carboxymethylcellulose vehicle used to prepare the drug suspension. Fetuses were obtained from pregnant rats sacrificed on day 20 of gestation. Maternal body weight gains were analyzed using the one-way ANOVA test. Embryonic and foetal variables were analized on a per litter basis by the Kruskal-Wallis test. Skeletal anomalies were analyzed using an X² test. The significance level accepted was established at P<0.05. In the preimplantational analysis, the cleavage rate was lower in the experimental group (P<0.05). In the postimplantational analysis there were no differences in the net weight increase among females of the different groups (P>0.05). The number of fetuses and the foetal vesicles weight were lower in the G10 group (P<0.05). This group showed the highest percentage of resorptions (P<0.05) and fetuses morphologically abnormal. An increase in the number of bones affected in fetuses of G6 and G10 groups was observed. The most common malformations were at vertebral, costal and head level. Weights and placental diameters were lower in the G10 group (P<0.05). We conclude that ABZSO at the dose used in this study affects the cleavage rate in preimplantational embryo development, without interrupting pregnancy. Furthermore; the developmental toxicity is related to day of administration.

El objetivo de este trabajo fue caracterizar los efectos de albendazol sulfóxido (ABZSO) durante la gestación de ratas Wistar, sobre parámetros embrionarios, fetales y placentarios. Se efectuó colpocitología diaria de las hembras considerándose día 0 de gestación el día de aparición de espermatozoides en vagina. Estudio preimplantacional: ABZSO (10 mg/kg) fue dosificado oralmente el día 2 de gestación; el día 4 de gestación se realizó la recolección de embriones. Estudio post-implantacional: ABZSO (10 mg/kg) fue dosificado oralmente los días 2, 6 ó 10 de gestación (Grupos G2, G6 y G10, respectivamente). Hembras controles recibieron carboximetilcelulosa, vehículo usado para solubilizar la droga. Las hembras fueron sacrificadas al día 20 de gestación. Variables embrionarias y fetales fueron analizadas sobre la base de las camadas mediante test de Kruskal-Wallis; ganancia de peso de las madres por ANOVA y porcentaje de fetos con alteraciones esqueléticas mediante X2. Estudio preimplantacional: la tasa de recolección embrionaria, el número de embriones recolectados y el porcentaje de diferenciación fueron similares entre grupos (P>0,05). La velocidad de clivaje fue menor en el grupo experimental (P<0,05). Estudio post-implantacional: la ganancia de peso de las madres no difirió entre grupos (P>0,05), el número de fetos y el peso de las vesículas fetales fueron menores en el grupo G10 (P<0,05). Los porcentajes de reabsorciones y de fetos con características morfológicas anormales fueron mayores en el grupo G10 (P<0,05). Las alteraciones esqueléticas fueron mayores en los grupos G6 y G10 (P<0,05) observándose con mayor frecuencia en vértebras, costillas y cabeza. Pesos y diámetros placentarios fueron menores en el grupo G10 (P<0,05). Se concluye que, bajo las condiciones del presente estudio, el ABZSO administrado en la etapa preimplantacional afecta la velocidad de clivaje sin detener la gestación mientras que su efecto en el desarrollo post-implantacional...

An allele specific PCR assay for screening for drug resistance among Wuchereria bancrofti populations in India.

Background & objectives: Albendazole, a commonly used anthelminthic drug that targets the polymerization of α- and β-tubulin dimer is currently co-administered with the antifilarial drug, diethylcarbamazine citrate (DEC) in the ongoing Global Programme for Elimination of Lymphatic Filariasis (GPELF). The experience in veterinary field has shown that there can be a rapid development of resistance to this drug, which therefore, needs to be monitored regularly in GPELF. Hence, we investigated the nucleotide polymorphism in the albendazole-binding domain of the isotype 1 β-tubulin gene from several populations of Wuchereria bancrofti and developed an AS-PCR assay useful in screening for sensitive/resistance alleles among parasite populations and also evaluated its utility. Methods: For studying the polymorphism of isotype 1 β-tubulin gene, a 475 bp fragment spanning exon 5 and 6 of the gene was amplified and sequenced from the genomic DNA of W. bancrofti collected from six geographic regions of India. An allele specific (AS) PCR for screening albendazole sensitivity/resistance was developed and a total of 55 mf samples from blood smears on slides collected from Thiruvannamalai, Thanjavur and Puducherry were screened. Selective therapy with DEC was in place in three areas, mass drug administration (MDA) with DEC alone was implemented in four areas, while DEC plus albendazole was administered in one district. Results: The analysis of the nucleotide sequence of the fragment from 20 W. bancrofti populations showed the domain to be highly conserved. An allele-specific PCR assay developed was used to detect sensitive/ resistance alleles among 55 isolates of W. bancrofti and no albendazole resistance alleles were detected among the populations tested. Interpretation & conclusion: The drug-binding domain of isotype 1 β-tubulin gene of W. bancrofti from different geographical locations was highly conserved. The AS-PCR developed showed potential application as a tool for monitoring albendazole sensitivity/resistance alleles among W. bancrofti populations, in areas where combination therapy of DEC-albendazole is being mass administered in the LF elimination programme.

Tricobezoar gástrico e intestinal en adolescente femenina de 15 años: a propósito de un caso clínico IVSS "Dr. Tulio Carnevali Salvatierra" Mérida-Venezuela / Gastric and intestinal trichobezoar female teenager about 15 years: a purpose of case clinical in IVSS Dr. Tulio Carnevali Salvatierra

Los tricobezoar son recolecciones de material ingerido (pelos, fibras) que se acumulasn en estómago e intestino. Se originan de la tricotilomanía más tricofagia, cuando el tricobezoar se acumula en duodeno recibe el nombre de Sídrome de Rapunzel, más frecuente en el sexo femenino. Adolescente de 15 años, quien presentó dolor abdominal de aparición insidiosa acompañada de naúseas y vómitos incontables que se irradian a hipocondrio y fosa iliaca izquierda, su evolución fue torpida presentando signos de irritación peritoneal. Se realiza laparatomía exploradora hallándose tumor de contenido de pelo a nivel del Ángulo de Treitz, y cámara gástrica. Siendo egresada y referida al servicio de psiquiatría infanto-juvenil.

Biochemical, haematological and parasitological evaluation of Nigella sativa efficacy against nematode in sheep as compared with albendazole

Twenty six balady sheep were used to compare the efficacy of Nigella sativa with albendazole against nematodiasis. The blood and faecal samples were collected from all animals just before treatment and after 7, 14 and 21 days of treatment. Parasitological examination revealed the presence of Trichostrongylus sp. [100%], Haemonchus sp. [75%], Ostertagia sp. [50%] and Oesophagostomum sp. [25%]. The present results revealed that, anthelmintic efficacy was on 14th day for albendazole and on 21 st day for Nigella sativa Nematode infestation leads to significant increases in serum activities of AST, ALT and ALP, in addition to significant decreases in total protein and albumin. However, the parasitism resuited in significant decreases in serum levels of Cu, Fe, Zn, Ca and P as well as significant decreases in RBCs, Hb and PCV values associated with significant increases in TLC, neutrophils, eosinophils and monocytes count with significant decrease in lymphocytic count. These parameters began to corrected toward normality on 7th day post-treatment with albendazole or Nigella sativa. The data declared a good efficacy of albendazole and Nigella sativa respectively where the derangements were, corrected on the 7 th day. The use of Nigella sativa in correct dose as anthelmintic drug may reduce egg counts and can overcome parasitic infestation in sheep

Scanning electron microscopic observations on advanced third-stage larva of Gnathostoma spinigerum after in vitro exposure to albendazole sulphoxide.

Gnathostomiasis is the parasitic disease caused by the migration of an advanced third-stage larva of Gnathostoma spinigerum. To date, albendazole is claimed to be the effective drug in preventing the reoccurrence of migratory swelling in patients. After being exposed to 1 and 2 micrograms/ml albendazole sulphoxide (AlbSO) in vitro, the parasites moved deteriorately, however, no dead larva was found even exposed to these concentrations for 21 consecutive days. The topographical alterations after 21 days of albendazole sulphoxide exposure are described using a scanning electron microscope. The marked changes in surface morphology were observed in both neck and body regions. The tegumental surface on the neck region was swollen and covered with fuzzy materials, whereas, the spines on the posterior region of the body were dislodged. These changes would probably lead to reduction of intermittent cutaneous migratory swelling in human gnathostomiasis patients.

Movability of advanced third-stage larva of Gnathostoma spinigerum exposed to albendazole sulphoxide in vitro.

Movability of advanced third-stage larvae of Gnathostoma spinigerum exposed to albendazole sulphoxide (AlbSO), the active metabolite of albendazole, was determined in vitro. Larvae in control groups moved actively with the whole body for all 21 days of the study period. In larvae treated with AlbSO 1 microg/ml, the movement was significantly reduced after 11 days exposed to the drug and to be only a part of body on the 15th-21st days. In larvae treated with AlbSO 2 microg/ml, the movement was initiated in decreasing after 9th days and to be only a part of body on the 12th-17th days. Finally, worms were immobile but not dead on the 20th-21st days. Although there was no larvae died at 21st days exposed to AlbSO in both concentrations; but all worms were sluggish and may die later. These lethargic worms may not be able to migrate in patients and leading to cure. Albendazole may not be benefit for acute symptom clearance; however, it can prevent the recurrent migratory swelling after the treatment of 21 day-course.

Albendazol como tratamiento coadyuvante en la cirugía del quiste hidatídico hepatoabdominal / Albendazol as coadyuvant treatment in hepato-abdominal hydatidic cyst surgery

El objetivo de la presente investigación es la de presentar los resultados tras 13 años de uso del Albendazol en concomitancia a la cirugía, con el fin de disminuir la recidiva hidatídica. Con tal propósito, es que desde marzo de 1985 hemos utilizado el Albendazol en 43 pacientes, siendo 14 de ellos en forma preoperatoria (grupo A) y 29 postoperatoria (grupo B). Los ciclos de Albendazol fueron de 30 días, con descanso de 15. La dosis fue de 400 mg c/12 horas en el adulto y de 10 mg x kg x día en los niños. Los criterios de inclusión para el tratamiento pre y postquirúrgico fueron: a) hidatidosis hepática múltiple, en la cual no se practicó cirugía resectiva, b) hidatidosis hepatoabdominal, c) ruptura del quiste y d) recidiva hidatidica. Todos los pacientes del grupo A fueron intervenidos quirúrgicamente y los del grupo B se controlaron mediante ecotomografía. La recidiva global de la serie fue de 13,8 por ciento y el tiempo de aparición varió entre los 28 y 75 meses de practicada la intervención quirúrgica. El seguimiento promedio fue de 51,8 meses, teniendo el 76 por ciento más de 4 años de control. Se concluye que el uso del Albendazol en concomitancia con la cirugía disminuye la posibilidad de recidiva hidatídica

Experiencia clinica en el tratamiento de la neurocisticercosis con albendazol / Clinical experience of neurocysticercosis treatment with albenzazol

Se presenta una experiencia clinica de tratamiento de 57 pacientes portadores de neurocisticercosis, tratados con administracion de albenzadol a dosis de 15 a 20 mg/kg. peso durante 20 dias, en el transcurso de 1993 a 1996 en los Hospitales San Gabriel y Hospital Virgen de Copacabana de la ciudad de La Paz, Todos los casos con evolucion satisfactoria y desaparicion total de los quistes de cisticerco. En cinco de los casos fue necesario el tratamiento quirurgico por presentar hidrocefalia, a los que se les implanto una derivacion ventriculo peritoneal. El albendazol es un antiparasitario economicamente accesible a grandes estratos sociales, aspecto muy importante puesto que esta enfermedad es mas comun en poblaciones de escasos recursos economicos. El tratamiento fundamental debe ser de sanidad publica debido a que la cisticercosis es un problema endemico en los paises del tercer mundo, por las malas condiciones de vida, el bajo nivel socioeconomico y cultural y la miseria en la que vive la mayor parte de la poblacion de los paises en vias de desarrollo

The anthelmintic albendazole affects in vivo the dynamics and the detyrosination-tyrosination cycle of rat brain microtubules

Albendazole (ABZ) is an anthelmintic benzimidazole drug widely used in human and veterinary medicine. ABZ has binding affinity to both mammalian and helminth parasite tubulin. In the current work, we have performed in vitro assays and in vivo experiments in which rats were given ABZ orally to better characterize the action of the drug on the polymerization of rat brain microtubules and on the detyrosination/tyrosination cycle that occurs on the COOH-terminal end of alpha-tubulin. The results showed that ABZ inhibits brain microtubule polymerization in vitro, and significantly delayed microtubule assembly in vivo. The tyrosination reaction cycle was not affected in vitro; however, in rats to which the drug was administered orally, the levels of in vitro tyrosination were reduced when compared to the controls with mock treatment. These results suggest that this apparent inhibition would be due to a decrease in the amount of substrate caused by the depolymerizing effect of ABZ and the subsequent tyrosination in the intact brain with endogenous tyrosine. In conclusion, ABZ strongly affects tubulin dynamics both in vivo and in vitro. The outcome of these experiments is a contribution to the understanding of the molecular mechanisms involved in the antimicrotubular action of benzimidazole compounds.

Desenvolvimento de metodologia para o estudo da estabilidade de suspensöes orais de albendazol / Metodology development for the study of albendazole oral suspensions stability

O albendazol é um potente anti-helmíntico benzimidazólico largamente utilizado em helmintíase intestinal humana, sendo também o medicamento de escolha no tratamento de cisto hidático e neurocisticercose. Apesar de amplamente estudado do ponto de vista clínico, existem poucas referências a respeito da metodologia analítica, sendo que nenhuma delas é oficial, como também näo há informaçöes sobre sua estabilidade na forma de suspensäo oral. O presente trabalho padronizou dois métodos para determinaçäo do teor albendazol em suspensöes farmacêuticas e estudou a estabilidade química, física e sensorial de formulaçöes contendo diferentes agentes suspensores, armazenadas a temperaturas de 4ñ 1ºC, 26ñ 1ºC, 37ºC, 50ºC e 65ºC e avaliado nos tempos 0, 1, 3 e 6 meses...

Drug treatment of neurocysticercosis.

Neurocysticercosis, the most common parasitic disease of the central nervous system, was treated surgically for a long time. Praziquantel (an isoquinolone) and albendazole (an imidazole) are anticysticercal drugs that are currently being used for the treatment of neurocysticercosis. Both have been reported to eliminate or markedly reduce the number and size of cysticerci. Albendazole is less expensive than praziquantel, and is as effective when given for 8 days as compared to longer periods. In a small number of comparative trials, albendazole appeared to be slightly more effective than praziquantel for the treatment of parenchymal cysticercosis. Albendazole has also been found effective in ventricular, subarachnoidal and racemose forms of the disease. However, the response to treatment is not universal. Treatment with these drugs has been associated with a high frequency of adverse reactions, probably due to the host's inflammatory reaction to the dying parasites. Headache, nausea and seizures are common but usually transient. Steroids appear to ameliorate these effects and their concomitant administration has been advocated. However, no data are available to support this view. The rationale of medical therapy in spinal cysticercosis is presently based on the reported efficacy of anticysticercal drugs in cerebral cysticercosis. A marked improvement in an associated seizure disorder following anticysticercal therapy has been observed. Though seizure control is better, the total duration of anti-epileptic drug therapy has not been determined. Some single enhancing computed tomography lesions in patients of epilepsy may be benign forms of neurocysticercosis. The spontaneous resolution of a majority of these lesions has led to doubts of them being merely infective in aetiology. Also, a controlled trial could not demonstrate any beneficial effect of albendazole on such lesions. Hence, most authors recommend that these patients should be treated with anti-epileptic drugs only. Doubts persist about the efficacy of anticysticercal drugs in altering the natural course of the disease and the reported tendency of cysticercus lesions to resolve.