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Echinococcus granulosus cyst wall possess high biochemical activities of malate dehydrogenase (MD) and fumarate reductase (FR), but low activity of succinate dehydrogenase (SD), suggesting that the cyst wall may utilize a partial reverse tricarboxylic acid cycle. When infected mice were given intragastrically with mebendazole, 25-50 mg.kg-1.d-1, albendazole 300 mg.kg-1.d-1 or praziquantel 500 mg.kg-1.d-1 for 7-14 d, no apparent effects on SD and FR activities of the cyst wall were found, while the MD activity was suppressed by all the 3 drugs, the inhibition rates being 34.6-61.6%, 59.8%, and 50.6%, respectively. The results suggested that MD may not be an important target for the antihydatidosis drugs.
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The present study was carried out to evaluate the effectiveness of nitazoxanide compared with that of quinfamide, mebendazole, or both in the treatment of intestinal protozoa and helminthic infections. A total of 677 stool specimens from children aged 2-12 years living in 3 communities of Colima, México, were analyzed in order to detect the presence of cysts, trophozoites, eggs, or larvae of intestinal protozoa or helminths. A total of 275 infected children were enlisted in a double-blind controlled study and randomly assigned to one of 2 treatment groups: Group A, nitazoxanide (200 mg for 3 days) and Group B, quinfamide (100 mg for 1 day), mebendazole (200 mg for 3 days), or both. A posttreatment fecal examination was conducted on Day 14 from treatment initiation. In Group A (n = 143), the parasitosis eradication rate was superior to that of Group B (n = 132). However, there was no significant difference between the 2 groups (P > 0.05).
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This study was designed to examine airway goblet cell response during the course of N. brasiliensis infection in rats and to characterize these goblet cells.
Several drugs are available for mass campaigns against enteric helminths. Mebendazole and pyrantel pamoate are quite effective against ascariasis and reasonably effective against the hookworms. Only mebendazole is effective against trichuriasis. Two drugs have recently been introduced for mass therapy of schistosomiasis, but they remain experimental, pending further evaluation. Other drugs are mentioned, and possible adverse metabolic effects are discussed. The fundamental question remaining is whether the eradication of certain parasites will improve the nutritional status of the infected populations.
614 preschool children aged 6-59 months.
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To test the hypothesis that the deworming stray dogs around the temple premises effectively reduces the prevalence of CLM among devotees.
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In an experimental patent infection of Ancylostoma ceylanicum in golden hamsters the efficacy of seven anthelmintics was tested; bephenium hydroxynaphthoate, tetramisole, tetrachlorethylene, phenylene 1,4-diisothiocyanate, thiabendazole, parbendazole and mebendazole were studied. Mebendazole was the most effective, with parbendazole, phenylene 1,4-diisothiocyanate, thiabendazole and bephenium hydroxynaphthoate also satisfactory. Tetrachlorethylene and tetramisole were the least effective in our screen.
Three multivariate calibration methods, Principal Component Regression (PCR), the K-matrix method and Q-mode factor analysis followed by varimax and Imbrie's oblique rotations were applied to the simultaneous spectrophotometric determinations of mebendazole (MBZ)-cambendazole (CBZ) and thiabendazole (TBZ)-mebendazole in commercial samples of Exelmin and Helmiben. The calibration set concentrations were selected to contain a +/-10% variation in the quantity of active ingredients as declared by the manufacturer. The Q-mode factor analysis provides superior results for the two pharmaceutical formulations. The K-matrix method proved to be totally inadequate for these determinations. Almost all Q-mode results have relative errors much smaller than 5% of the active ingredient contents. This investigation shows that PCR and Q-mode factor analysis can be used to determine MBZ-CBZ and TBZ-MBZ in commercial drugs.
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Mebendazole (MBZ) is an anthelmintic drug which inhibits tubulin polymerization and eventually causes apoptosis in target organisms. Antitumor activity of MBZ has been reported in various cancers. The aim of this study was to investigate the effect of MBZ on cholangiocarcinoma (CCA) cells in vitro and in vivo. MBZ reduced cell proliferation in the KKU-M213 cell line associated with a remarkable enhancement of caspase-3 gene expression and enzyme activity. Oral administration of MBZ slightly reduced the growth rate of subcutaneously xeno-grafted KKU-M213 in nude mice. The TUNEL assay showed an increase of apoptotic cell numbers in the xenograft tumor tissue of MBZ-treated mice. The data obtained in this study suggested that MBZ can suppress CCA cell proliferation via caspase-3 activated apoptosis. Further investigation of the antitumor effects of MBZ might support the use of MBZ as an alternative drug for CCA treatment.
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Two cases of cerebral echinococcosis in children emphasize the need to consider the Echinococcus in the differential diagnosis of children with CNS signs and symptoms. One patient died because of delay in seeking medical attention. The other is now a 22-year-old college student with no evidence of recurrence more than five years after removal of Echinococcus cysts from both brain and liver. The newer modalities available for diagnosis are discussed. Therapy with mebendazole is reviewed; this relatively new, highly effective anthelmintic is well tolerated and has been apparently highly effective in a small number of cases.
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To investigate the effects of mebendazole at high dose on the haematology of macropods. Experimental.
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The therapeutic efficacy of Mebendazole (Vermox) was studied in 13 patients: 8 with liver and 5 with pulmonary echinococcosis. The drug was given in a dose of 50-70 mg/kg body mass. Good therapeutic effect was found in 4 patients (2 with liver nad 2 with pulmonary echinococcosis), partial therapeutic efficiency was registered also in 4 patients (2 with liver and 2 with pulmonary echinococcosis) and failure in 5 patients. The drug was more effective in pulmonary echinococcosis, in younger and smaller cysts than in older cysts with thick walls and presence of filial cysts. The efficacy of the treatment is related to the drug plasma concentration but the results depend on the cysts condition, too. The careful examination of the patients--X-ray, ultrasonography and computer tomography--before, during and after the treatment ensures objective evaluation of the treatment results.
Prospective and randomized.
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The assessment of a ten-year clinical trial of continuous therapy in eight patients revealed further evidence of a significant therapeutic effect of mebendazole on alveolar hydatid disease. Life-expectancy was increased when compared to untreated historical controls, especially in the patients over 55 years of age. All symptomatic patients showed subjective improvement. In four patients, three had a 50% or greater reduction in the diameter of massive hepatic lesions, and in the fourth, progressively enlarging metastases were arrested. Fall in the IHA titre suggested that the causative organism had been destroyed in two additional patients. Of greater significance was the absence of progression of the disease process as measured by changes in the size of the hepatic lesion or lack of development of distant metastases in patients under therapy. In contrast, progressive enlargement of hepatic lesions or the appearance of distant metastases were cardinal features of untreated cases (15 of the 16 cases followed). In vivo determination of viability of tissues of the larval Echinococcus multilocularis from patients receiving long-term therapy was considered important in evaluating efficacy of the drug. Such tissues, obtained by autopsy from two patients under continuous therapy for four and ten years, failed to proliferate when inoculated into rodents (red-backed voles), whereas similar inoculations from untreated patients or those receiving 15 months' or less of therapy brought about production of vesicles in rodents in eight of 11 tests (73%). These two deaths, unrelated to therapy, resulted from late fibrotic constriction of end-stage parasitic lesions about the portal vein and major bile ducts. The clinical findings in combination with negative in vivo tests and other data indicate that the mebendazole therapy significantly alters the clinical course of alveolar hydatid disease. The evidence strongly indicates that long-term therapy may eventually have a lethal effect on the larval cestode in advanced disease.
Aplastic anemia has been linked to environmental exposures, from chemicals and medical drugs to infectious agents. The disease occurs more frequently in Asia than in the West, with incidence rates 2- to 3-fold higher. We report updated results of an epidemiologic study conducted in Thailand from 1989 to 2002, in which 541 patients and 2261 controls were enrolled. Exposures were determined by in-person interview. We observed significantly elevated relative risk estimates for benzene (3.5) and other solvents (2.0) and for sulfonamides (5.6), thiazides (3.8), and mebendazole (3.0). Chloramphenicol use was infrequent, and no significant association was observed. Agricultural pesticides were implicated in Khonkaen (northeastern Thailand). There were significant associations with organophosphates (2.1), DDT (6.7), and carbamates (7.4). We found significant risks for farmers exposed to ducks and geese (3.7) and a borderline association with animal fertilizer (2.1). There was a significant association in Khonkaen with drinking other than bottled or distilled water (2.8). Nonmedical needle exposure was associated in Bangkok and Khonkaen combined (3.8). Most striking was the large etiologic fraction in a rural region accounted for by animal exposures and drinking of water from sources such as wells, rural taps, and rainwater, consistent with an infectious etiology for many cases of aplastic anemia in Thailand.
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The recurrence rate was investigated in 19 patients with non-resectable alveolar echinococcosis after discontinuation of a long-term therapy with mebendazole (average treatment 4.3 years). A control group consisted of 14 patients who underwent radical surgery and finished a course of prophylactic postoperative mebendazole treatment of 2 years. In the controls, no recurrence was observed after a post-therapy period averaging 3.5 years. In contrast, recurrence occurred in 7/19 patients (37%) with non-resectable alveolar echinococcosis an average of 1.6 years after discontinuation of the long-term mebendazole therapy. The absence of clinically detectable recurrence in the remaining 12 patients seems to be due either to spontaneous inactivation of alveolar echinococcosis preceding chemotherapy or too short post-therapy surveillance. The patients with recurrence responded favorably to reintroduction of chemotherapy. The data indicate that mebendazole therapy is parasitostatic rather than parasiticidal.
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A survey was conducted to determine the prevalence of benzimidazole (BZ)-resistant small strongyles in horses in a southeastern Pennsylvania practice. Resistant parasites were found in 291 of 342 horses surveyed. Anthelmintic practices and pasture management factors in use for 3 to 6 years did not correlate with the presence of resistant small strongyles. Benzimidazole-resistant small strongyles were recovered in horses that had been treated alternately with BZ and non-BZ products and in horses receiving BZ products as infrequently as twice a year. However, inasmuch as the horses may have been infected with resistant small strongyles before the various anthelmintic schedules were implemented, it was not possible to attribute BZ-resistance to any particular pattern of drug use. Fifty-one (14.9%) horses had BZ-susceptible small strongyles: these horses were on poor overall parasite control programs and had received BZ products no more than once a year. Benzimidazole-piperazine and non-BZ drugs were effective in herds infected with BZ-resistant small strongyles.
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In the present study, extraction of mebendazole across a supported-liquid membrane (SLM) was performed based on two different driving forces: (1) pH gradient over the SLM, and (2) electrical field sustained over the SLM. The extracted drug concentration was studied using reversed-phase HPLC-UV. At passive extraction conditions, mebendazole was extracted from alkaline samples (0.01 mmol L(-1) NaOH) into 1-undecanol immobilized in the pores of a porous hollow fiber of polypropylene (SLM), and then transported into 25 μL of 100mM HCl as the acceptor solution. Under electrokinetic migration conditions, mebendazole transported under applied voltage from acidic solutions (100 mmol L(-1) HCl) through 2-nitrophenyl octyl ether (NPOE) immobilized in the pores of hollow fiber, into 25 μL of 100 mmol L(-1) HCl as the acceptor solution. The effects of several factors including the nature of organic solvent, pH of donor and acceptor solutions, extraction time and stirring speed on the extraction efficiency of the drug were investigated and optimized. Under optimal conditions, preconcentration factors (PF) of 211 and 190 were obtained for the drug based on passive transport and electromembrane extraction (EME), respectively. Also, linear range of 0.5-1000 μg L(-1) with estimation of coefficient higher than 0.994 was obtained for both of the proposed methods. The results showed that EME has higher speed in comparison with simple passive transport. The methods were successfully applied to extract mebendazole from plasma and urine samples and satisfactory results were obtained.
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The common anthelmintics, oxantel, mebendazole, albendazole and pyrantel were assessed for their comparative activity against Trichuris muris in mice. Mice were infected with T. muris and the infection was maintained by a brief cortisone administration during the second week of infection. Mice carrying the infection with different life cycle stages, viz. fourth stage larvae (L4), pre-adult and adult stages were dosed with anthelminitics. The worm burdens in control infection groups varied although infection dose and other conditions were uniformly followed. With various dose regimens tested, oxantel was highly potent; it eliminated completely pre-adult and adult stages, respectively at 25 and 12.5 mg kg-1 dose levels with significant activity also against adult worms at a 1.56 mg kg-1 dose level and against pre-adults at a 6.25 mg kg-1 level. Pre-adults required twice the dose given to that of adults for complete (100%) activity. Mebendazole was the next most active; a dosage of 37.5 mg kg-1 was completely active against pre-adults whereas a dosage of 2 x 50 mg kg-1 was required for complete elimination of adult worms. In addition, about 90% of the worms were eliminated with a single dose of 150 mg kg-1. However, a significant activity was seen against adults at a 25 mg kg-1 level and pre-adults at 37.5 mg kg-1, the lowest level tested. In comparison, albendazole did not induce complete clearance of pre-adult and adult stages even when tested at dose levels as high as 150 and 2 x 75 mg kg-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Undergraduate students had inadequate knowledge, moderately accurate beliefs and inappropriate practices concerning antibiotics, and a high rate of self-medication. This highlights the need for focused educational intervention and stricter governmental regulation concerning antibiotic use and sale in retail pharmacies.
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The development of anthelmintic chemotherapy has provoked re-evaluation of the management of hydatid disease. We reviewed the case records of 74 patients with 93 episodes admitted to hospitals in Auckland, New Zealand, between 1967 and 1982. Median stay was 29 d (range 1-172). 46 (62%) of the patients were male: 34 (45%) were European and 38 (51%) Maori. The median age was 39 years (range 14-85). The majority of patients presented with symptoms and signs related to local effects of the cyst. 57 (77%) patients had at least one operation and while 34 (60%) had a major surgical complication, only 3 died. At follow-up in 1984, 38 (67%) of the surgical patients and 10 of the 17 (65%) who were not operated on were alive. 9 mebendazole recipients were evaluated: 5 (55%) responded symptomatically, but only one was cured by mebendazole alone. One stopped mebendazole because of side-effects. 2 patients took albendazole: one was cured and one had a symptomatic response. Thus surgery is not always needed. The role of chemotherapy requires further evaluation.
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Although Strongyloides stercoralis (S. stercoralis) infection rate in Okinawa Prefecture was less than 2% by the traditional method, it has been proven to be 6.2% by the new technique--agar plate method. Thiabendazole has strong activity to eradicate the organism, but it is well known that the rate of severe side effects is extremely high. Therefore, we attempted to evaluate the new treatment for the infection by mebendazole and its combination with thiabendazole. The reason for use of the drug is based on the reports of successful treatment of S. stercoralis infection in humans with the mild and infrequent side effects produced by the drug. Thirty three patients were orally given mebendazole 100 mg twice daily for 28 days. Twenty six patients were given thiabendazole 500 mg thrice daily for 5 days and after that, mebendazole 100 mg twice daily for 9 days. This combination therapy was repeated twice. The following results were obtained: 1) Out of a total of 59 patients, the cure rate was 83.3% (20/24) in single use of mebendazole and 100.0% (22/22) in the combination therapy. 2) Constipation (9.1%) and headache (9.1%) were of relatively high incidence in the mebendazole group, but they were mild. Nausea (19.2%) and headache (15.4%) were observed in the combination therapy group and the drug was discontinued in 2 patients. 3) The incidence of the elevation of S-GOT, S-GPT was noted in 71.4% (20/28) for the mebendazole group and 52.2% (12/23) for combination therapy group. All 13 patients of the mebendazole group were negative in lymphocyte stimulation test for mebendazole.(ABSTRACT TRUNCATED AT 250 WORDS)
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The effects of some parasitic infection (bilharziasis, toxocariasis and trichinosis) on the brain of experimentally infected mice were investigated. Eighty animals were classified into four groups, group I contained five non infected animals as a control group. The other groups each contained twenty-five mice infected with Schistosoma mansoni (group II), Toxocara canis (group III) and Trichinella spiralis (group IV). Each infected group was divided into two subgroups (a,b). Subgroup (a) left untreated and subgroups (b) treated by praziquantel (in group II) and mebendazole (in group III and IV). Histopathological and immunological examination using peroxidase antiperoxidase (PAP) technique and neurotransmitters estimation (nor-epinephrine, dopamine and serotonine) were carried. In the untreated animals, there were mild histopathological changes and mild antigenic deposition in subgroups (IIa and IIIa) and marked changes in subgroup (IVa). There were significant decrease in dopamine in subgroup (IIIa), not improved after treatment (subgroup IIIb) and significant decrease in nor-epinephrine and serotonine in subgroup (IVa) improved after treatment in subgroup (IVb). The neurotransmitters changes may explain the motor, behavioural and emotional changes that occurred with these parasites.
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Three different benzimidazole derivatives, albendazole [methyl-5-(propylthio)-2-benzimidazolcarbamate], mebendazole (methyl-5-benzoyl-2-benzimidazolcarbamatic acid methyl ester), and fenbendazole [methyl-5-(phenylthio)-2-benzimidazolcarbamate] were tested in vivo against Glugea anomala parasitizing the connective tissue of sticklebacks (Gasterosteus aculeatus). Naturally infected sticklebacks were incubated in aerated plastic aquaria (10 1) at 22 degrees C in water containing 0, 1, 5, 10, or 50 micrograms of either albendazole, mebendazole or febendazole for 2 or 6 h. For intermittent treatment, 2 micrograms substance was administered three times for 6 h at intervals of 36 h. At the ultrastructural level, at all developmental stages of G. anomala there were no significant differences in the kind of damage caused by either albendazole, mebendazole, or febendazole. Starting with a dose of 1 microgram/ml for 2 h, each of the drugs irreversibly damaged uni- and multinucleate meronts, sporogonial plasmodia, and sporoblasts. Disorganized spores were also observed. Treatment with higher doses (10 micrograms/ml, 2 or 6 h) caused malformations of the merogonic and the sporogonic stages, a significant reduction in the number of ribosomes, and disruptions of the nuclear membranes. The first recognizable treatment effect was an enlargement of the smooth endoplasmic reticulum. In the sporogonial plasmodia, the membranes of the sporophorous vesicle envelopes were lumpy or even completely destroyed. After incubation with the highest dose (50 micrograms/ml, 6 h), microtubules were apparent within the karyoplasm of the uninucleate meronts. After interval treatment, all forms of damage were intensified, especially in the mature spores. When treatment was done three times at low doses (3 x 2 micrograms/ml, 6 h, 36-h intervals), spore infectivity was drastically lowered. Therefore, it seems likely that an intermittent regimen of medicinal baths can be successfully applied against susceptible Microsporidia in fish.
A rational strategy for chemotherapy demands that dosage schedules be based on an adequate knowledge of clinical and biochemical pharmacology. Many anthelmintic drugs (e.g. suramin, diethylcarbamazine, hycanthone) were introduced before modern techniques for drug evaluation (controlled clinical trials) and before the development of specific and sensitive analytical methods for the assay of drugs and metabolites in biological fluids. Thus, many of the regimens used today for the treatment of parasitic diseases are largely empirically derived. By means of specific analytical methodology (high performance liquid chromatography, gas chromatography and mass-spectrometry) introduced in the 1960s, it is now possible to measure drugs and their metabolites with specificity and sensitivity. Much of this review deals with compounds which are active against the major systemic helminths, i.e., filariae (diethylcarbamazine, ivermectin and suramin) and schistosomes (niridazole, metrifonate, oxamniquine and praziquantel), but recent advances in the treatment of hydatid disease involving the benzimidazole carbamates albendazole and mebendazole are also discussed. Among the imidazole derivatives, mebendazole, a broad-spectrum anthelmintic, is poorly absorbed from the gastrointestinal tract after a therapeutic dose, but that fraction which is absorbed and escapes hepatic first-pass extraction is pharmacologically active against systemic helminths. Albendazole is more completely absorbed, but is almost undetectable in plasma due to its rapid conversion to an active sulphoxide metabolite. This compound may well become the drug of choice for the chemotherapy of echinococcosis. Levamisole, the 1-isomer of tetramisole, is rapidly and completely absorbed, but has not been widely used in systemic helminthiases because of severe side effects associated with prolonged dosage. Diethylcarbamazine is microfilaricidal against Onchocerca volvulus, but its use has been associated with major adverse effects resulting from its action on the microfilariae. These effects are related to the concentration of the drug in the plasma which, in turn, is influenced by urinary pH. The elimination half-life of diethylcarbamazine is prolonged and renal clearance reduced in alkaline urine. Under these conditions the microfilaricidal effect is enhanced, but the adverse reactions to treatment are more severe. Suramin is the only available antifilarial agent with macrofilaricidal activity. It has a long elimination half-life (36 to 54 days), and is highly (99.7%) bound to plasma protein which limits its removal from the blood.(ABSTRACT TRUNCATED AT 400 WORDS)