In vitro and in vivo experiments were employed in the screening of potential anthelmintic agents against Opisthorchis viverrini infection in hamsters. A few selected groups of compounds tested included those that are commercially available as well as those that are still being tested by various pharmaceutical firms. The compounds tested in the present study were praziquantel, amoscanate, albendazole, flubendazole, metrifonate, metronidazole and benzodiazepine derivatives. Results from both in vitro and in vivo experiments showed that at the dosages employed, praziquantel was the only one that gave complete cure, as judged from faecal egg examination and worm recovery at the time of sacrifice. It was therapeutically effective against different developmental stages of O. viverrini including the metacercariae. Moreover, the drug was also effective as a chemoprophylactic agent when given 6 to 12 hr prior to being exposed to infective metacercariae. Other compounds tested were considerably less active although some might have permanently damaged the fluke reproductive capacity, while others were able to suppress egg-laying capacity only temporarily. Together, results suggests that the ineffectiveness of most agents tested in this study is not related to their inability to attain concentrations high enough to kill or damage the flukes in the biliary system but is most likely due the inherent lack of capacity to kill the flukes.
A field study was designed to investigate the re-establishment of patent lungworm infections in donkeys following an anthelmintic treatment regime which was effective against Dictyocaulus arnfieldi. In April 1979 faecal samples from 259 donkeys were examined and each animal classified as a negative, low positive or high positive excretor of lungworm larvae. During the summer the control group of 126 donkeys showed an increase in the number of excretors from 80 per cent in April to 91 per cent in October. At the same time there was a rise in the faecal larval output of individual animals so that by October 59 per cent were classified as high positive compared with only 20 per cent in April. The treated group of 133 donkeys received 3.5 g mebendazole daily for 5 days during April and as a result the number of excretors fell from 66 per cent pretreatment to 23 per cent one month after treatment. Despite exposure to infected pastures throughout the summer this figure was maintained at a comparatively low level and by October patent infections had been re-established in only 15 per cent of the donkeys that were negative after treatment.
A case of Mansonella perstans infection with visual impairment and a retinal lesion is described. After a course of diethylcarbamazine and a further course of mebendazole the symptoms improved and the microfilariae blood concentration decreased. The symptoms and response to antifilarial treatment strongly suggested the intraocular localization of an M. perstans worm.
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The effect of in vivo treatment with mebendazole on the ultrastructural morphology of Ascaris suum intestine was investigated. Pigs, infected with A. suum, were fed ad libitum a medicated food containing mebendazole at a concentration of 30 ppm. Control and treated animals were killed 6, 9, 15, and 24 hr after the onset of feeding. The parasites were quickly collected from the pig intestinal tract and prepared for ultrastructural and cytochemical examination. Absence of secretory granules in the terminal web, accumulation of secretory granules in the Golgi region, formation of autophagic vacuoles in the apical cell part, and loss of glycogen were the characteristic changes observed after 6 and 9 hr of treatment. Degenerative changes were very pronounced after 15 and 24 hr and involved almost the entire cytoplasm. Microvilli were decreased in number and appeared swollen in the majority of absorptive cells. Some more severely altered cells were completely devoid of microvilli. Cytochemistry revealed that the accumulated secretory granules in the Golgi area contained glycoproteins or polysaccharides. Microvilli, lysosomes, and Golgi apparatus were reactive for acid phosphatase in the control intestinal cells. After treatment, the enzyme activity was localized in numerous autophagic vacuoles, whereas the secretory granules remained unstained. The acid phosphatase activity in the microvilli decreased or was completely absent. The possible significance of these modifications in view of mebendazole's anthelmintic activity is discussed.
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Using the Bi-Digital O-Ring Test in three clinical cases where standard Western diagnostic methods were not satisfactory; successful diagnosis and treatment were made non-invasively, quickly and inexpensively with the Bi-Digital O-Ring Test. The three cases are as follows: Tuberculosis of the urinary tract; Pleural tuberculosis; Possible parasitic infection of the liver.
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Between 1985 and 2015, 12 patients were admitted to our clinic with a possible diagnosis of cardiac hydatid disease. Of these patients, six (50%) were male and six (50%) were female. Mean age of the patients was 42.6 years.
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The Authors report their personal experience in the treatment of 70 patients with hydatid cysts of different localization with mebendazole, following protocols approved by WHO. During treatment patients were submitted to careful clinical, biochemical, radiological and immunological controls. On the whole, 150 hydatid cysts and 13 cases of widespread hydatidosis were observed. Follow-up ranged from 6 months to 5 years. Morphological and/or volumetric modifications were observed in 64.3% of the total number of cysts treated, regardless of their localization. 9 relapses were observed, and all but one case showed the same previous sensitivity to a further cycle of mebendazole. The observed side effects were not severe.
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The study included 415 female patients with the diagnosis of enterobiasis seen at the Hospital del Niño, DIF. Vulvovaginitis was found in 78 cases (18%), with definite predominance in the school-age group. The clinical manifestations in order of frequency were: perianal and vulvar pruritus, abdominal pain, leukorrhea and vulvar edema. Graham's perianal and perineal smear method was performed with 100% positiveness in personal and 85% in perineal smears. The treatment should be directed to improve the family sanitary habites and the prescription of the choice drug to the patient and to his family. The following drugs are quite as effective: piperazine citrate, pyrvinium pamoate, pyrantel pamoate and mebendazole. The physician should use the drug that better fits the patients convenience, keeping in mind the easy determination of the dose and the cost in order to offer the patient and his family the best choice.
Three groups of Trichuris trichiura-infected school-age children were treated with one dose 400mg albendazole, 100mg mebendazole twice daily for 3 d, or 100mg mebendazole twice daily for 5 d. The albendazole study investigated cure and egg reduction rates and found that only 5 of 66 infected children were egg-negative 7 d post-treatment, giving a cure rate of 8% and a geometric mean egg reduction rate of 89%. However, at day 14 post-treatment, all children were again egg-positive with significantly higher egg counts than at day 7 (P<0.001). The two mebendazole studies aimed for the recovery of adult T. trichiura worms. After the 3 d course of mebendazole treatment, only four worms were recovered on days 3-5 after start of treatment from 2 of 34 infected children. With the 5 d course of mebendazole treatment, 10 of 21 infected children expelled a total of 27 worms. In the last case the first worm appeared on day 4 post-treatment, and the highest number of worms was recovered when the study ended at day 7. In conclusion, even with the longest treatment regimen and collecting stool samples over seven consecutive days, only very few worms were recovered. The results of this study suggest that alternative drugs and/or alternative regimens in current control programmes against T. trichiura need renewed attention.
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This study re-evaluates 13 out of 48 subjects involved in a trichinellosis outbreak that occurred in Central Italy (Umbria Region) in 1988 resulting from the consumption of raw boar meat harboring Trichinella britovi. During the outbreak, 28 of 48 serologically positive subjects were asymptomatic, whereas 20 subjects presented one or more clinical signs including but not limited to fever, myalgia, periorbital oedema and conjunctivitis. Several patients were hospitalized with severe clinical signs requiring treatment with mebendazole and corticosteroids. Upon re-evaluation of 13 patients, none presented clinical signs; however, three still had increased CPK or LDH serum levels with some signs of electromyographic changes. In this study, enzyme immunoassays (EIA) were used to test the 13 positive sera for reactivity with T. britovi antigens using both excretory/secretory (E/S) antigens and a synthetic antigen composed of beta-tyvelose conjugated to bovine serum albumin. Western blots (WB) were also carried out using a commercial kit. Studies using EIA with E/S antigen identified five positive sera; however, using beta-tyvelose as antigen, only one positive sample was identified. Nearly all sera reacted positively with one or more Trichinella antigens when analyzed by WB, in particular to the 45 k Da beta-tyvelose containing glycoprotein. Results indicate that T. britovi, though less pathogenic than other Trichinella species, is clearly capable of inducing sustainable sequelae.
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Humans can acquire infection by sparganum or plerocercoid larva of the tapeworm from drinking water containing infected Cyclops species and by ingesting infected snakes, birds, or other mammals. Once infected, the plerocercoid larva migrate slowly in the tissues and present as a subcutaneous lesion, making the correct diagnosis difficult. A 38-year-old man visited our clinic due to a breast mass. Due to suspicion of gynecomastia or breast cancer, he underwent tumor excision. Unexpectedly, a long white worm was found in the breast tissue and the pathologic finding showed sparganosis. After the surgery, mebendazole was prescribed for 1 week. No recurrence of the sparganosis was found during 1-year follow-up.
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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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Acquisition of infection has been determined to be related to the consumption of koipla, a dish prepared from uncooked freshwater fish. Not unexpectedly, in the present study, it was found that this species was the most important intestinal parasite among Thai laborers and was significantly associated with the consumption of koipla.
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Low-intensity helminth infections, predominantly of A. lumbricoides and T. trichiura, do not contribute significantly to the poor growth and biochemical status of rural Bangladeshi children.
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In 11 patients with Echinococcus multilocularis infection the blood levels of alpha-interferon (alpha-IF) and gamma-interferon (gamma-IF) were measured using vesical stomatitis virus culture. In patients with the disease the contents of alpha- and gamma-IF were significantly (p less than 0.01) lower than in healthy controls: 392 +/- 101.6 and 101.6 +/- 20.9 U/ml and 1024 +/- 83.2 and 187 +/- 16.9 U/ml, respectively. The lower levels of alpha- and gamma-IF were found in patients with multiorgan damages including the lungs, as compared with the liver and abdomen infestation: alpha-IF 160 +/- 56.6, gamma-IF 88 +/- 24.0 and 525.7 +/- 124.3 and 109 +/- 18.3 (p less than 0.01), respectively. The similar data have been found in patients with hydatid disease (S. N. Suntsov et al., 1990). After 5 to 6 courses of mebendazole therapy in a dose of 50 mg/kg body weight dai y for 30 days with 30-day intervals there was a tendency to a slight elevation of cytokines levels (S. N. Suntsov et al., 1990), as seen in hydatid disease. The estimation of IF levels in multilocular echinococcosis infection may be of prognostic value and perhaps for the evaluation of the efficacy of surgical and chemotherapeutic treatment.
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Residues of growth-promoting agents, veterinary drugs and environmental contaminants in food products are routinely analyzed with chemical-analytical methods, using physical and spectrometric properties of a compound. Since residue limits are in general based on biological properties of compounds, bioassays offer in theory a good alternative. As a consequence, these assays are much more suitable for the detection of mixtures of compounds with common biological properties, including possibly unknown agonists. Using modern molecular biological techniques, a new generation of bioassays has been developed, showing in general a higher sensitivity and specificity for the target compounds. The CALUX (chemical activated luciferase expression) assay was developed for the detection of polyhalogenated compounds, based on their affinity for the aryl hydrocarbon (Ah) receptor. This paper focuses on the specificity of the assay. The benzimidazole compounds oxfendazole, fenbendazole, febantel, thiabendazole, mebendazole, omeprazole, lanzoprazole and benomyl were shown to give a positive response in the assay. Similar results were obtained with dexamethasone, corticosterone and cortisol, which in addition were able to enhance the response obtained with TCDD. Similarly to the flavonoids alpha- and beta-naphtoflavone, the reported Ah receptor antagonist 4-amino-3-methoxyflavone showed a strong positive response at a concentration of 400 microM, but failed to inhibit the response obtained with TCDD. It is concluded that the chances of false-negative results appear to be minimal and can be recognized. False-positive or, better, unwanted results are in theory more likely to occur. Possible solutions to avoid or detect these type of results are discussed. In general, these kinds of assays offer great possibilities for screening of food samples. In addition to the further optimization of these assays, future work should be focused on the development of rapid, sample and selective extraction procedures.
In February 1989 we began a combined treatment with mebendazole (3 g/day for 30 days) and praziquantel (1.8 g/day for 15 days) with variable rest periods, in a patients with hydatid disease who had been previously unsuccessful treated only with mebendazole. All the patients were monitored with serological techniques and radiography. Generally the treatment was without side-effects. According to radiography results, there was a reduction in the size of the cyst in 5 patients, in 2 there was no change and 1 patient, the cyst continued to increase in size. Results suggest that the combination of mebendazole more praziquantel could be a pharmacological alternative in the medical treatment of hydatid disease.
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The pharmacokinetics of the filaricidal benzimidazole compounds UMF-078 and UMF-289 were evaluated in beagle dogs experimentally infected with Brugia pahangi. Twenty-four infected microfilaremic beagles were selected and randomly allocated into 4 treatment groups of 6 dogs each: oral (PO) UMF-078, PO UMF-289 (the HCl salt form of UMF-078), intramuscular (IM) UMF-078, and untreated controls. Equivalent doses of 50 mg/kg of the free base were given twice a day for 3 days to the 3 groups of treated dogs. Oral absorption is rapid compared with IM dosing; the absorption half-life (K01-HL) for the IM treatment is approximately 14 hr compared with 1 and 2 hr for the PO regimen of salt and free base forms, respectively. The elimination half-lives (K10-HL) for the PO regimens are 13 and 15 hr for the salt and free base forms, respectively. Because of sustained absorption following IM dosing, the K10-HL is prolonged. In contrast to oral administration, IM dosing of UMF-078 provides sustained, relatively low plasma drug levels, with good tolerance and efficacy.
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Surgery has long been considered the first-choice treatment in patients with echinococcosis of the liver. The poorly predictable outcome of older studies using mebendazole or albendazole confirmed this belief. Since the introduction of a percutaneous technique (PAIR; puncture, aspiration, injection, reaspiration) treatment policy is changing. The actual question is which treatment is preferred in which patients.
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Seven chemotherapeutic agents (dimetridazole, metronidazole, pyrimethamine, albendazole, fenbendazole, mebendazole and magnesium sulfate) were examined for growth inhibition on the cultivation of Spironucleus vortens. Dimetridazole and metronidazole were effective in inhibiting the parasite's growth. At concentrations of 1 microgram ml-1 or higher, both dramatically decreased numbers of parasites. At 24 h exposure, 33% of parasites were inhibited when exposed to dimetridazole or metronidazole at concentrations of 2 and 4 micrograms ml-1, respectively. Dimetridazole at 4 micrograms ml-1 or higher concentrations decreased the number of organisms to 50% or less after 48 h exposure. During the same period of time, the numbers of parasites decreased to 50% or less when exposed to metronidazole at 6 micrograms ml-1 or higher. Pyrimethamine at concentrations of 1 to 10 micrograms ml-1 was not effective in inhibiting the parasite's growth. Albendazole and fenbendazole at concentrations of 0.1 and 0.5 microgram ml-1 were similar in inhibiting the growth of the organism. Both compounds suppressed parasite growth at concentrations of 1.0 microgram ml-1 or higher after 24 h exposure. Mebendazole inhibited the parasite's growth at concentrations of 0.5 microgram ml-1 or higher. At 72 h exposure, 45 to 50% of the parasites were inhibited when exposed to mebendazole at concentrations higher than 0.5 microgram ml-1. Magnesium sulfate at concentrations of 70 mg ml-1 or higher also suppressed the growth of parasites after 24 h exposure. These results indicate that dimetridazole, metronidazole and mebendazole are the most effective chemotherapeutic agents in vitro at inhibiting the growth of S. vortens.
Malnutrition, anaemia, and gut parasites are commonly interrelated. Using the Nippostrongylus brasiliensis-rat model, the effect of iron and protein deficiency on the efficacy of benzimidazole anthelmintics was studied. It was demonstrated that the anthelmintics mebendazole and fenbendazole were significantly less effective in eradicating parasites when animals were deficient in iron and protein. This decreased efficacy of anthelmintics in iron and protein deficiency could not be overcome by intraperitoneal administration of the drug. Since nutritional deficiencies may act via impairment of the immune response, anthelmintic efficacy was determined in adequately nourished rats treated with the immunosuppressive drug dexamethasone. A similar decrease in efficacy of mebendazole was shown when these animals were treated with dexamethasone. Thus it is possible that lowered anthelmintic efficacy in iron and protein deficient animals is mediated by immune deficiency. These findings may be relevant to anthelmintic programmes in malnourished communities.
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Elevated percentages of dissolved drug were obtained with RDM at 1:2.5 and 1:5 ratios of MBZ: L-HPC. Thermal analysis showed an amorphization of MBZ in the RDM by the absence of a clear MBZ melting peak in formulations. The rapid dissolution behavior could be due to the decreased drug crystallinity, the fast dissolution time of carriers as L-HPC, together with its superior dispersibility and excellent wetting properties. RDM-1:2.5 and RDM-1:5 resulted in increased maximum plasma concentration and area(s) under the curve (AUC)0-∞ values. Likewise, after oral administration of the RDM-1:2.5 and RDM-1:5 the AUC0-∞ were 2.67- and 2.97-fold higher, respectively, compared to those of pure MBZ. Therapeutic activity, assessed on the Trichinella spiralis life cycle, showed that RDM-1:5 was the most effective in reducing the number of parasites (4.56-fold) as compared to pure MBZ, on the encysted stage.
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Celiac disease is a gluten-sensitive enteropathy with a broad spectrum of clinical manifestation, and most celiac patients respond to a gluten-free diet (GFD). However, in some rare cases celiacs continue to experience GI symptoms after GFD, despite optimal adherence to diet. The aim of our study was to evaluate the causes of persistence of GI symptoms in a series of consecutive celiac patients fully compliant to GFD.
A 56-year-old woman with acquired, common variable immunodeficiency was found to have persistent gastrointestinal as well as pulmonary infection with Strongyloides stercoralis. Repeated courses of treatment with thiabendazole led to marked reduction or loss of Strongyloides stercoralis larvae, but cessation of treatment always led to recurrence of Strongyloides infection. Several small bowel biopsies showed normal villous architecture and little inflammatory response to presence of larvae. Interestingly, no definite symptomatology could be attributed to the Strongyloides infection. It was postulated that the lack of signs and symptoms of strongyloidiasis, as well as poor response to treatment, was related to the immunodeficiency state. With low-dose, long-term interrupted courses of thiabendazole treatment, the Strongyloides infection finally seemed to be cured.
To observe the effect of praziquantel, mebendazole, tribendimidine, ivermectin, artemether and dihydroartemisinin against Armillifer agkistrodontis nymphs harbored in mice.
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In this study, we investigated the anthelmintic activity of -gingerol, -shogaol, -gingerol, -shogaol and hexahydrocurcumin, a constituent isolate from the roots of ginger (Zingiber officinale), for the parasite Angiostrongylus cantonensis. This study found that the above constituents killed A. cantonensis larvae or reduced their spontaneous movements in a time- and dose-dependent manner. The larvicidal effect or ability to halt spontaneous parasite movement of -shogaol, -gingerol, -gingerol, -shogaol and hexahydrocurcumin at various concentrations was reached from 24 to 72 h, respectively. Further investigation to determine minimal effective doses of -gingerol and hexahydrocurcumin revealed -gingerol to have a greater maximum larvicidal effect and loss of spontaneous movements than hexahydrocurcumin, mebendazole and albendazole. These constituents of ginger showed effects against DPPH and peroxyl radical under larvicidal effect. Together, these findings suggest that these constituents of ginger might be used as larvicidal agents against A. cantonensis.
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The aim of this study was to explore the autophagy-related protein 4B(ATG4B) and its targeted candidate agonist in triple-negative breast cancer (TNBC) therapy. In this study, the identification of Atg4B as a novel breast cancer target for screening candidate small molecular agonists was performed by phylogenetic analysis, network construction, molecular modelling, molecular docking and molecular dynamics (MD) simulation. In vitro, MTT assay, electron microscopy, western blot and ROS measurement were used for validating the efficacy of the candidate compounds. We used the phylogenetic analysis of Atg4B and constructed their protein-protein interaction (PPI) network. Also, we screened target compounds of Atg4 proteins from Drugbank and ZINC. Flubendazole was validated for its anti-proliferative efficacy in MDA-MB-231 cells. Further MD simulation results supported the stable interaction between Flubendazole and Atg4B. Moreover, Flubendazole induced autophagy and increased ROS production. In conclusion, in silico analysis and experimental validation together demonstrate that Flubendazole can target Atg4B in MDA-MB-231 cells and induce autophagy, which may shed light on the exploration of this compound as a potential new Atg4B targeted drug for future TNBC therapy.
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Skeletal manifestation of alveolar (E. multilocularis) or cystic (E. granulosus) echinococcosis is seldom, with an incidence of less than 2% of all cases. By reporting on a rare case of bony manifestation of E. granulosus, we intend to emphasize current standards in surgical and drug management of the disease. Typical radiographic and blood-chemistry findings are highlighted on a 62-year-old Arabiqu female suffering from a cystic echinococcosis with skeletal manifestation in the left ileum and lower lumbar spine.
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We report a case of human pentastomiasis in a 70-year-old retired long-distance driver/farmer whose diagnosis was made incidentally while being investigated for a 1-month history of cough and abdominal pain. The chest X-ray revealed multiple comma-shaped and rounded opacities in keeping with Armillifer infection, most likely Armillifer armillatus. The patient made an uneventful recovery after a 10-day course of mebendazole (an antihelminthic) tablet and ciprofloxacin (antibiotic) capsules and was discharged home. He is presently being followed up. This is the first case we have seen in our medical unit thus we are reporting it.