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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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Brief notes are given on drugs which have been tested at the Onchocerciasis Chemotherapy Research Centre at Tamale and Hohoe and found to have activity against Onchocerca volvulus. Ivermectin in single doses as high as 800 micrograms/kg was found to be no more effective than the standard dose of 150 micrograms/kg. The benzimidazole carbamates, mebendazole and albendazole, differ in their effects on O. volvulus. The former has microfilaricidal effects and is toxic to developing embryos surrounded by an egg shell but not the stretched microfilariae. Albendazole has no microfilaricidal activity but is toxic to all intra-uterine stages. The reasons for these differences are unclear. Early studies with amocarzine are described; the maximum tolerable dose is 20 mg/kg and the predominant activity, against the microfilariae, is marked only at doses greater than 12 mg/kg. None of the drugs tested has macrofilaricidal activity.
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Patent infections of adult dogs with Toxocara canis induced by transplantation of immature, intestinal stages were examined for their suitability for testing of anthelmintics. Each of 5 dogs were infected four times by transplantation of 80 immature, intestinal stages of Toxocara canis. The dogs were treated with various anthelmintics of well established efficacy (pyrantel, nitroscanate, mebendazole, piperazine) 20 dpi. All anthelmintics tested showed the same efficacy as had been assessed earlier by treatment of dogs infected prenatally with Toxocara canis.
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Flubendazole was shown to exert anti-leukaemia and anti-myeloma activity through inhibition of microtubule function. Here, flubendazole was tested for its effects on the viability of in total 461 cancer cell lines. Neuroblastoma was identified as highly flubendazole-sensitive cancer entity in a screen of 321 cell lines from 26 cancer entities. Flubendazole also reduced the viability of five primary neuroblastoma samples in nanomolar concentrations thought to be achievable in humans and inhibited vessel formation and neuroblastoma tumour growth in the chick chorioallantoic membrane assay. Resistance acquisition is a major problem in high-risk neuroblastoma. 119 cell lines from a panel of 140 neuroblastoma cell lines with acquired resistance to various anti-cancer drugs were sensitive to flubendazole in nanomolar concentrations. Tubulin-binding agent-resistant cell lines displayed the highest flubendazole IC50 and IC90 values but differences between drug classes did not reach statistical significance. Flubendazole induced p53-mediated apoptosis. The siRNA-mediated depletion of the p53 targets p21, BAX, or PUMA reduced the neuroblastoma cell sensitivity to flubendazole with PUMA depletion resulting in the most pronounced effects. The MDM2 inhibitor and p53 activator nutlin-3 increased flubendazole efficacy while RNAi-mediated p53-depletion reduced its activity. In conclusion, flubendazole represents a potential treatment option for neuroblastoma including therapy-refractory cells.
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School children, aged six to nineteen years.
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An approach has been made to develop an in vitro screening system to evaluate antifilarial efficacy of compounds and an effort has been made to establish correlation between in vivo and in vitro screening technique. The in vitro experiments were conducted simultaneously using three life-forms (adult, microfilaria and infective larva) of Acanthocheilonema viteae using five antifilarial agents representing four chemical groups. All the selected antifilarials were known to be active against one or more life-stages of human lymphatic or animal filariids. Diethylcarbamazine and Centperazine showed 100% microfilaricidal and infective larvicidal actions at concentrations of 0.5 and 0.25 mg/ml and 0.5 and 0.0313 mg/ml respectively with no effect on adult worms even at 1 mg/ml. Levamisole was effective against all the three life-stages killing 100% adult worms at 1 mg/ml, infective larvae at 0.0625 mg/ml and microfilariae at 0.0125 mg/ml, while mebendazole exhibited activity only against adult worms (100% at 0.5 mg/ml). Ivermectin killed adult females and microfilariae at 0.063 and 0.5 mg/ml respectively but did not affect infective larvae even up to 1 mg/ml concentration. The study indicated that in vitro screening system can be used for primary screening of potential antifilarial agents provided three life-forms of A. viteae are used simultaneously to avoid false negative results. It would however be more appropriate if a few compounds of a particular chemical class are initially assessed both in vivo and in vitro for validity of subsequent test results in vitro.
The assay presented here is inexpensive, rapid, can be used in 24- and 96-well formats and will serve as an ideal tool for first-round in vitro tests on the efficacy of large numbers of antiparasitic compounds.
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We have studied the effectiveness of pharmacologic prophylaxis of experimental peritoneal hydatidosis. Mice (n = 140, divided in ten groups) suffered intraperitoneal contamination with protoscoleces of E. granulosus from sheep. Each group received different treatment (mebendazole, praziquantel, or both), in three different schedules (during 3 days before contamination, during 7 days after contamination, or both before and after Mebendazole 150 mg/kg-day), praziquantel (25 mg/kg-day) were given in three daily doses. Mice were sacrificed six months later and the number and type of existing peritoneal cysts was recorded. Prophylaxis prior to contamination was shown ineffective. Early treatment greatly decreased the severity of the peritoneal hydatidosis. The administration of the drug before and after contamination, did not improve the results obtained when the drug was given after contamination. Both mebendazole and praziquantel were effective, though the former obtained better results. The association of both drugs does not improve the results obtained with mebendazole alone. These experimental results recommend the early use of mebendazol or praziquantel after open surgery for hydatidosis, in order to prevent the occurrence of secondary peritoneal hydatidosis.
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In the last decade, pharmaceutical companies, governments and global health organisations under the leadership of the World Health Organization (WHO) have pledged large-scale donations of anthelmintic drugs, including ivermectin (IVM), praziquantel (PZQ), albendazole (ALB) and mebendazole (MEB). This worldwide scale-up in drug donations calls for strong monitoring systems to detect any changes in anthelmintic drug efficacy. This review reports on the outcome of the WHO Global Working Group on Monitoring of Neglected Tropical Diseases Drug Efficacy, which consists of three subgroups: (i) soil-transmitted helminthiases (ALB and MEB); (ii) onchocerciasis and lymphatic filariasis (IVM); and (iii) schistosomiasis (PZQ). Progress of ongoing work, challenges and research needs for each of the four main drugs used in helminthic preventive chemotherapy (PC) are reported, laying the ground for appropriate implementation of drug efficacy monitoring programmes under the co-ordination and guidelines of the WHO. Best practices for monitoring drug efficacy should be made available and capacity built as an integral part of neglected tropical disease (NTD) programme monitoring. Development of a disease-specific model to predict the impact of PC programmes, to detect outliers and to solicit responses is essential. Research studies on genetic polymorphisms in relation to low-efficacy phenotypes should be carried out to identify markers of putative resistance against all NTD drugs and ultimately to develop diagnostic assays. Development of combination and co-administration of NTD drugs as well as of new drug entities to boost the armamentarium of the few drugs available for NTD control and elimination should be pursued in parallel.
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A sensitive method is described for the simultaneous determination of mebendazole and hydroxymebendazole using flubendazole as an internal standard. The analytes were isolated with a single chloroform extraction from 1.0 ml of alkalinized plasma or cyst liquid samples. Separation and quantitation were performed with high-performance liquid chromatography with electrochemical detection. The limit of detection for mebendazole and hydroxymebendazole was approximately 5 and 2.5 ng/ml, respectively. The accuracy of the method was confirmed for mebendazole by a good correlation with an existing radioimmunoassay method. The method was applied for monitoring mebendazole therapy in echinococcosis patients. The results presented support the necessity of such monitoring, as most of the observed peak plasma concentrations did not reach the level regarded as minimal for therapeutic effect.
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The efficacies and side effects of single dose treatments with 500 mg mebendazole (Janssen Pharmaceutica) and 400 mg albendazole (SmithKline Beecham) against intestinal nematodes were compared in a single-blind, randomized controlled trial among 2294 children aged 6 to 12 years on Pemba Island, Zanzibar, among whom infections with Ascaris, hookworms and Trichuris were highly prevalent. Both drugs were highly effective against Ascaris, with cure rates of over 97%. The cure rates for Trichuris were low, but mebendazole was significantly better than albendazole and produced a greater reduction in the geometric mean egg count. Mebendazole was inferior to albendazole in curing hookworm infections and in reducing the geometric mean egg count. There was no difference in the frequency of side effects reported by heavily infected children treated with either drug. In a trial on 402 children, 500 mg mebendazole (Janssen) was compared with a generic version of the drug, 500 mg mebendazole (Pharmamed). No difference was apparent in the efficacies of the 2 treatments against any of the 3 parasites studied.
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From 168 studies, 20 randomized controlled trials were included.
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Gastrodiscoides hominis is a large fluke of pig and human and constitutes an important parasite of human in Assam, Indian, the Philippines and Southeast Asia. This parasite has not been reported in Nigeria and possibly other parts of Africa. This is a case report of a seven year old Nigerian child who presented with features of malnutrition and anaemia and was found to have Gastrodiscoides hominis and Ascaris lumbricoides. Following clearance of the worms there was tremendous improvement of the health status of the child. The detailed epidemiology of this parasite still remains to be studied in this environment.
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To observe the effect of praziquantel, mebendazole, tribendimidine, ivermectin, artemether and dihydroartemisinin against Armillifer agkistrodontis nymphs harbored in mice.
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Concerted efforts by food safety and public health authorities lead to timely outbreak control and facilitated the provision of early PEP. PEP appears to be effective in preventing trichinellosis when given early, preferably within 6 days. We therefore recommend initiating PEP without delay in similar settings and encourage public health professionals to fast-track this intervention.
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Ascaris pneumonitis in areas of endemic infestation is considered a benign condition. Smoke inhalation with any burn injury can be potentially fatal. A heavy infestation of Ascaris could further exacerbate the smoke-induced lung injury. After ingested eggs hatch in the small intestine, the larvae penetrate the mucosa and invade the blood stream and are then carried to the lungs. The larvae break out into the aveolar spaces as they are too large to cross the capillary bed and are carried up the bronchial tree and eventually swallowed. This study describes three cases of Ascaris infection in thermally injured children. While the burns were < 30 per cent total body surface area, two patients who were injured in the same fire had a further complication of smoke inhalation which necessitated sophisticated therapy in order to promote survival. All patients were treated initially with Vermox. The one patient without smoke inhalation did not develop ascariasis pneumonitis even with positive stool samples and was discharged with no complications, whereas the two with smoke inhalation developed severe pneumonitis. One patient was placed on ECMO and did not receive a full course of the Vermox treatment. This patient died after several weeks of ECMO treatment. The third patient received a full course of Vermox, slowly recovered, and went home. Supportive therapy only is recommended during the lung migration phase of the Ascaris lifecycle. We feel that continuation of chemotherapy (Vermox) would have been beneficial in the fatal case based on the survival of the second patient.(ABSTRACT TRUNCATED AT 250 WORDS)
A 16-year-old female from Rantau Panjang, Kelantan reported having diarrhoea for three months. During this period, she lost 15 lb in weight and was treated with antibiotics and anti-spasmodic tablets with no improvement. Stool examinations by private laboratories revealed "worm-like eggs". She was treated for worms with mebendazole which helped to reduce the symptoms but not completely. The patient continued passing out the abnormal "worm-like eggs" which were later identified as pollen grains.
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A 24-year-old lady presented to an evening genitourinary (GU) clinic with a short history of vulval and anal irritation. On perianal examination, several threadworms were visible. Symptoms resolved with oral mebendazole and strict personal and environmental hygiene. Threadworm is a common and easily treatable cause of pruritus ani, yet is underreported in GU literature. If the history is suggestive, consider performing the diagnostic cellophane test and/or prescribing empirical treatment.
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A 14-year-old male child was hospitalized with complaints of a bronchial wheezing, cough, dyspnea, and sputum and a preliminary diagnosis of bronchial asthma and pneumonia. The patient was treated empirically for bronchial asthma and pneumonia, but gave neitherr clinical nor radiological response to treatment. On the high-resolution computerized tomography, a typical spiral image of Ascaris lumbricoides was identified inside a cavity in the upper lobe of the left lung with a diameter of 8x7 cm. Also,migratory pneumonic infiltrations progressing between the lower lobe and hilary region of the left lung were seen. Examination of the peripheral blood smear of the patient revealed eosinophilia (40%), while IgE was measured as 350 IU/mL. The patient was diagnosed as "Loeffler's syndrome" due to A. lumbricoides", and successfully treated with mebendazole 2x100 mg/day for three days. Loeffler's pneumonia should be considered when patients with bronchial asthma and pneumonia do not respond to specific treatment in developing countries. Radiological investigations may be available in the diagnosis of parasitic infections. In this case, early diagnosis by radiologic methods have prevented unnecessary drug use and related complications.
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A single-blind randomised trial in children with a documented moderate infection of T. trichiura. Ova were counted in stool specimens before and 10 days after treatment by the formal-ether concentration method.
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Cure rates and egg reduction rates calculated from egg counts of pre- and post-treatment stool samples using the quantitative Kato-Katz technique.
It is widely recognized that only a handful of drugs are available against soil-transmitted helminthiasis, all of which are characterized by a low efficacy against Trichuris trichiura, when administered as single doses. The re-evaluation of old, forgotten drugs is a promising strategy to identify alternative anthelminthic drug candidates or drug combinations.
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We retrospectively studied patients with hypereosinophilia (>5 × 10(9)/L) and described the characteristics, natural history and treatment of those with eosinophilia of uncertain aetiology.
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.
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Capillaria philippinensis eggs, larvae, and adults were identified in the stool of a 41-year-old female physician from Cairo, Egypt, who had never traveled abroad. She had eaten local and imported fish. She suffered from borborygmi, abdominal pain, severe diarrhea, vomiting, and loss of weight for greater than 3 months. Treatment with Flubendazole (R17889-Janssen) 200 mg twice daily for 30 days resulted in clinical and parasitological cure.
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The median MPR of retail prices to patients was 3.7 for OB (range 0.23-20) and 1.35 for LPG (range 0.05-3.75). MPR >5 was observed for OBs of 5 medicines: ceftriaxone injection, diazepam injection, mebendazole syrup, mebendazole chewable tablet and metronidazole tablet whereas MPR >2.5 was observed only for LPGs of 3 medicines: chlorphenamine syrup, clotrimazole topical cream, and paracetamol syrup. Mean percent difference in price between OB and LPG products was 365 % (range -21, 2343). Rational treatment for acute infections such as mild lower respiratory tract infections and acute gastroenteritis seems to be affordable but treatment for chronic illnesses requiring liquid or inhaled dosage forms were largely unaffordable.
We treated 125 patients with strongyloidiasis (78 males and 47 females) by 2 oral doses of ivermectin (6 mg) at 2-week interval, and obtained the following results: 1. Eradication rate after treatment was 86.4% (108 of 125 patients), responsively. Out of the total 17 patients were resistant (non-responsive) to treatment, 8 patients received a further course of ivermectin and all Strongyloides stercoralis in their feces were eradicated. 2. Side effects were observed in 7.2% of the patients after the first dose treatment and in 3.2% after the second dose. But all symptoms were mild and self-limited. Although liver disfunction developed in 13.6% of the patients, no symptoms occurred and no special treatment was required. 3. Positive rate of anti-HTLV-I antibody in the resistant group was significantly higher (80.0%) than in the eradicated group (29.2%) and in the stool-negative group (0%). 4. Although eosinophils before treatment in the eradicated group was significantly higher than that of controls, there was no significant difference between the resistant group and controls. IgE levels in the resistant group was significantly lower than in the eradicated group. We would like to conclude that IVM is the best drug for treatment of the patient with Strongyloides stercoralis not only from this results but also our previous reports which had investigated the clinical efficacy on thiabendazole, mebendazole and albendazole.
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The improvement of reporting of serious or unrecognized (unlabeled) anthelmintic-induced ADRs will increase our knowledge of the benefit/risk ratio associated with these agents and optimize their use.
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The number of children who showed reduced T. trichiura ova counts after the treatments, and reductions in ova counts, both expressed as percentages. Statistical analysis using the Wilcoxon 2-sample test and the chi-square test.
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The external location of the zebrafish lateral line makes it a powerful model for studying mechanosensory hair cell regeneration. We have developed a chemical screen to identify FDA-approved drugs and biologically active compounds that modulate hair cell regeneration in zebrafish. Of the 1680 compounds evaluated, we identified two enhancers and six inhibitors of regeneration. The two enhancers, dexamethasone and prednisolone, are synthetic glucocorticoids that potentiated hair cell numbers during regeneration and also induced hair cell addition in the absence of damage. BrdU analysis confirmed that the extra hair cells arose from mitotic activity. We found that dexamethasone and prednisolone, like other glucocorticoids, suppress zebrafish caudal fin regeneration, indicating that hair cell regeneration occurs by a distinctly different process. Further analyses of the regeneration inhibitors revealed that two of the six, flubendazole and topotecan, significantly suppress hair cell regeneration by preventing proliferation of hair cell precursors. Flubendazole halted support cell division in M-phase, possibly by interfering with normal microtubule activity. Topotecan, a topoisomerase inhibitor, killed both hair cells and proliferating hair cell precursors. A third inhibitor, fulvestrant, moderately delayed hair cell regeneration by reducing support cell proliferation. Our observation that hair cells do not regenerate when support cell proliferation is impeded confirms previous observations that cell division is the primary route for hair cell regeneration after neomycin treatment in zebrafish.
Ascariasis and hookworm (ancylostomiasis) remain the most common intestinal nematodes in the world with significant economic, social, and medical impact. An understanding of the transmission and pathogenesis of ascariasis and hookworm are necessary to recognize their clinical manifestations and to manage the pulmonary sequelae of infection. Transmission occurs predominantly in the tropics and rural areas where there is suboptimal sanitation, personal hygiene, and education regarding these parasites. Ascariasis generally occurs through hand-to-mouth ingestion of agricultural products or food contaminated with parasite eggs. Hookworm is transmitted through larval penetration of the skin. Larval pulmonary migration generally is asymptomatic. However, symptomatic pulmonary disease may occur with fever, cough, chest pain, hemoptysis, dyspnea, and wheezing due to (1) Loffler's syndrome, (2) the effects of larval tissue migration, (3) airway reactivity or bronchospasm, (4) infectious bacterial complications from parasitic migration and associated aspiration, and rarely (5) chronic eosinophilic pneumonia, transdiaphragmatic penetration, or symptoms of upper airway obstruction. Clinical evaluation shows pulmonary opacities on chest radiograph, peripheral blood eosinophilia, and larvae in respiratory or gastric secretions. Symptomatic treatment may be necessary with bronchodilators and systemic steroids or antibiotics for bacterial complications. The drug of choice is mebendazole (Vermox) 100 mg twice a day for 3 days. Alternatives include a single dose of pyrantel pamoate (Antiminth) 11 mg/kg (maximum dose, 1 g) or albendazole (Zentel) 400 mg orally once. Invermectin (Mectizan) is available through the World Health Organization, and, in the United States, through the manufacturer on a compassionate-use basis. Ivermectin is as effective as currently available drugs against Ascaris but shows only partial efficacy against hookworms, which infest humans. Preventive measures, improvement of sanitary facilities, education, and school screening may be important in the endemic areas to control these parasitic infections.
To evaluate the safety and efficacy of percutaneous drainage of pulmonary hydatid cysts.
These studies demonstrate that tubulin-binding drugs can activate a component of the hypoxic adaptive response, specifically the stabilization of HIF-1α and its downstream targets. Tubulin-binding drugs, including antihelminthic benzimidazoles, also abrogate oxidative neuronal death in primary neurons. Given their safety in humans and known ability to penetrate into the central nervous system, antihelminthic benzimidazoles may be considered viable candidates for treating diseases associated with oxidative neuronal death, including stroke.
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Behavior, even in simple metazoans, depends upon integrated processes at the subcellular, cellular, and organismal level, and thus is susceptible to disruption by a broad spectrum of chemicals. Locomotor behavior (movement) of the small free-living nematode Caenorhabditis elegans has proven to be useful in assessing toxicity. Recently reported observations suggest that behavioral change (reduced movement) occurs after 4 h of exposure to heavy metals, and that with abbreviated exposure, the concentration-response relationship for Pb (a known neurotoxic metal) differs from that for Cu. In this study, movement was evaluated after 4-h exposures for nine compounds from three chemical classes: organic pesticides, organic solvents, and heavy metals. Concentration-dependent reduction of movement was observed for all test compounds with the exception of mebendazole, for which test concentrations were limited by solubility. Within each chemical class, movement was more sensitive to the neurotoxic compounds than to substances not believed to be neurotoxic, as evidenced by behavioral effective concentration to reduce average worm movement to 50% of the control movement values (e.g., levamisole and chlorpyrifos < mebendazole, ethanol and acetone < dimethylsulfoxide, and Pb and Al < Cu). These observations are discussed as they relate to the use of acute behavioral tests in assessing general chemical toxicity, and the enhanced value of 4-h testing for the detection of neural toxicants.
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Hydatid cysts are formed in human body can be treated clinically by surgery or drugs such as albendazole (ABZ) and mebendazole (MBZ). The purpose of this study was comparing the effects of ABZ and MBZ on glutathione-S-transferase, alkaline phosphatase and protease enzymes activities in protoscoleces of hydatid cyst.
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To evaluate the knowledge, attitude and behaviours of university students on the use of antibiotics.