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Postgraduate Medical Journal Aug 2007Bone hydatid disease lacks a typical clinical appearance and image characteristics on x ray or CT are similar to those of tuberculosis, metastases and giant cell tumour... (Review)
Review
Bone hydatid disease lacks a typical clinical appearance and image characteristics on x ray or CT are similar to those of tuberculosis, metastases and giant cell tumour or bone cysts. However, MRI does show distinctive diagnostic features of bone hydatid disease, especially in the spine. Until recently, treatment of osseous hydatid disease has been entirely surgical. Effective chemotherapy using benzimidazoles, particularly mebendazole, albendazole and combination treatments, has now been achieved in experimental studies and clinical practice. However, most of these drugs are still in the experimental stage or are in the early stages of clinical use.
Topics: Animals; Anthelmintics; Bone Diseases, Infectious; Diagnostic Imaging; Drug Combinations; Echinococcosis; Echinococcus; Humans; Serologic Tests
PubMed: 17675547
DOI: 10.1136/pgmj.2007.057166 -
Open Access Macedonian Journal of... Apr 2019Helminthiasis in school-aged children potentially causing physical growth and intellectual development retardation. Trichuriasis was the most common type of...
BACKGROUND
Helminthiasis in school-aged children potentially causing physical growth and intellectual development retardation. Trichuriasis was the most common type of helminthiasis in children.
AIM
To investigated the efficacy and side effects of albendazole, albendazole combined with levamisole and mebendazole combined with levamisole for trichuriasis and ascariasis.
METHODS
This study was conducted as a double-blind, randomised clinical trial by comparing the efficacy and side effects of albendazole, albendazole combined with levamisole and mebendazole combined with levamisole for trichuriasis. The sample of this study were 180 elementary school students at Deli Serdang Regency State Elementary School, Medan, Indonesia. The study was conducted from April to June 2015.
RESULT
The cure rate of helminthiasis on the 7th day was 81.7% after albendazole therapy, 88.3% after albendazole levamisole therapy, and 83.3% after mebendazole combined with levamisole therapy (p = 0.577). Cure rate on the 14th day was 88.3%, 95%, and 91.7% for albendazole, albendazole combined with levamisole, and mebendazole combined with levamisole therapy, respectively (p = 0.418). On the 21th day, the cure rate was 88.3%, 96.7%, and 91.7% (p = 0.230). Combination of albendazole and levamisole showed the highest cure rate, despite the statistically insignificant difference for all groups (p > 0.05). Combination of albendazole combined with levamisole showed better cure rate for mild trichuriasis (95.8%) than albendazole therapy (46.2%) and mebendazole combined with levamisole (83.3%), (p < 0.05).
CONCLUSION
Single-dose albendazole, a combination of albendazole and levamisole, and a combination of mebendazole and levamisole had similar efficacy in reducing egg count in helminthiasis. Combination of albendazole and levamisole showed better cure rate for mild trichuriasis and mixed infections. Side effects were similar in all treatment groups.
PubMed: 31110573
DOI: 10.3889/oamjms.2019.299 -
Journal of Fungi (Basel, Switzerland) Mar 2023Histoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if...
Histoplasmosis is a frequent mycosis in people living with HIV/AIDS and other immunocompromised hosts. Histoplasmosis has high rates of mortality in these patients if treatment is unsuccessful. Itraconazole and amphotericin B are used to treat histoplasmosis; however, both antifungals have potentially severe pharmacokinetic drug interactions and toxicity. The present study determined the minimal inhibitory and fungicidal concentrations of mebendazole, a drug present in the NIH Clinical Collection, to establish whether it has fungicidal or fungistatic activity against . Protein extracts from yeasts, treated or not with mebendazole, were analyzed by proteomics to understand the metabolic changes driven by this benzimidazole. Mebendazole inhibited the growth of 10 strains, presenting minimal inhibitory concentrations ranging from 5.0 to 0.08 µM. Proteomics revealed 30 and 18 proteins exclusively detected in untreated and mebendazole-treated yeast cells, respectively. Proteins related to the tricarboxylic acid cycle, cytoskeleton, and ribosomes were highly abundant in untreated cells. Proteins related to the nitrogen, sulfur, and pyrimidine metabolisms were enriched in mebendazole-treated cells. Furthermore, mebendazole was able to inhibit the oxidative metabolism, disrupt the cytoskeleton, and decrease ribosomal proteins in . These results suggest mebendazole as a drug to be repurposed for histoplasmosis treatment.
PubMed: 36983553
DOI: 10.3390/jof9030385 -
International Journal of Molecular... Dec 2022Breast cancer is the most commonly diagnosed cancer worldwide and ranks first in terms of both prevalence and cancer-related mortality in women. In this study, we aimed...
Mebendazole Increases Anticancer Activity of Radiotherapy in Radiotherapy-Resistant Triple-Negative Breast Cancer Cells by Enhancing Natural Killer Cell-Mediated Cytotoxicity.
Breast cancer is the most commonly diagnosed cancer worldwide and ranks first in terms of both prevalence and cancer-related mortality in women. In this study, we aimed to evaluate the anticancer effect of mebendazole (MBZ) and radiotherapy (RT) concomitant use in triple-negative breast cancer (TNBC) cells and elucidate the underlying mechanisms of action. Breast cancer mouse models and several types of breast cancer cells, including TNBC-derived RT-resistant (RT-R) MDA-MB-231 cells, were treated with MBZ and/or RT. In mice, changes in body weight, renal and liver toxicity, tumor volume, and number of lung metastases were determined. In cells, cell viability, colony formation, scratch wound healing, Matrigel invasion, and protein expression using western blotting were determined. Our findings showed that MBZ and RT combined treatment increased the anticancer effect of RT without additional toxicity. In addition, we noted that cyclin B1, PH2AX, and natural killer (NK) cell-mediated cytotoxicity increased following MBZ + RT treatment compared to unaided RT. Our results suggest that MBZ + RT have an enhanced anticancer effect in TNBC which acquires radiation resistance through blocking cell cycle progression, initiating DNA double-strand breaks, and promoting NK cell-mediated cytotoxicity.
Topics: Humans; Female; Mice; Animals; Mebendazole; Cell Line, Tumor; Triple Negative Breast Neoplasms; Apoptosis; Killer Cells, Natural; Cell Proliferation
PubMed: 36555137
DOI: 10.3390/ijms232415493 -
Medicina (Kaunas, Lithuania) Sep 2022Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic,... (Review)
Review
Over the last years, repurposed agents have provided growing evidence of fast implementation in oncology treatment such as certain antimalarial, anthelmintic, antibiotics, anti-inflammatory, antihypertensive, antihyperlipidemic, antidiabetic agents. In this study, the four agents of choice were present in our patients' daily treatment for nonmalignant-associated pathology and have known, light toxicity profiles. It is quite common for a given patient's daily administration schedule to include two or three of these drugs for the duration of their treatment. We chose to review the latest literature concerning metformin, employed as a first-line treatment for type 2 diabetes; mebendazole, as an anthelmintic; atorvastatin, as a cholesterol-lowering drug; propranolol, used in cardiovascular diseases as a nonspecific inhibitor of beta-1 and beta-2 adrenergic receptors. At the same time, certain key action mechanisms make them feasible antitumor agents such as for mitochondrial ETC inhibition, activation of the enzyme adenosine monophosphate-activated protein kinase, amelioration of endogenous hyperinsulinemia, inhibition of selective tyrosine kinases (i.e., VEGFR2, TNIK, and BRAF), and mevalonate pathway inhibition. Despite the abundance of results from in vitro and in vivo studies, the only solid data from randomized clinical trials confirm metformin-related oncological benefits for only a small subset of nondiabetic patients with HER2-positive breast cancer and early-stage colorectal cancer. At the same time, clinical studies confirm metformin-related detrimental/lack of an effect for lung, breast, prostate cancer, and glioblastoma. For atorvastatin we see a clinical oncological benefit in patients and head and neck cancer, with a trend towards radioprotection of critical structures, thus supporting the role of atorvastatin as a promising agent for concomitant association with radiotherapy. Propranolol-related increased outcomes were seen in clinical studies in patients with melanoma, breast cancer, and sarcoma.
Topics: Adenosine Monophosphate; Adrenergic beta-Antagonists; Anthelmintics; Anti-Bacterial Agents; Antihypertensive Agents; Antimalarials; Antineoplastic Agents; Atorvastatin; Breast Neoplasms; Cholesterol; Diabetes Mellitus, Type 2; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypoglycemic Agents; Male; Mebendazole; Metformin; Mevalonic Acid; Propranolol; Protein Kinases; Proto-Oncogene Proteins B-raf; Receptors, Adrenergic, beta-2; Tyrosine
PubMed: 36143915
DOI: 10.3390/medicina58091239 -
BioMed Research International 2021Soil-transmitted helminths (STHs) and are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and...
BACKGROUND
Soil-transmitted helminths (STHs) and are the main causes of morbidity among schoolchildren in the tropics. A school-based deworming program was launched to control and eliminate the infection in endemic countries including Ethiopia. Although periodic deworming is conducted in endemic areas, the prevalence of the infection is high in the country. In addition, periodic evaluation of the efficacy of the anthelminthic drug is limited.
OBJECTIVE
This study is aimed at checking the efficacy of mebendazole and praziquantel with the respective STHs and parasites.
METHODS
A longitudinal study was conducted from February to March 2018 among 422 schoolchildren. Stool samples were collected at baseline and at 2 and 4 weeks posttreatment and were processed using the Kato-Katz technique. Schoolchildren positive for STHs were treated with mebendazole and those positive for with praziquantel. After two weeks, a second round of stool was collected and examined, and then, single-dose redosing was given to each positive child. Lastly, the third stool sample was collected two weeks after the initiation of the redosing and checked for STHs and parasites. A close follow-up of students who were treated was done. All the data were entered and analyzed using SPSS version 20 for analysis. Descriptive statistics was used to compute the cure rate and egg reduction rate of mebendazole and praziquantel.
RESULTS
Among 422 participants, the prevalence of STHs, hookworm, , and was 44.7%, 35.1%, 21.1%, and 13.9%, respectively. The cure rate of mebendazole against increased from 60% in the single dose to 100% in redosing after two weeks. The cure rate of mebendazole against hookworm also increased from 32.4% in the single dose to 91.0% in the redosing. The cure rate of praziquantel against -infected children was 91.5% in the first round and 100% in the redosing phase. There was a 98.6-100% egg reduction rate in the redosing regimen of both drugs.
CONCLUSION
The cure and egg reduction rates of single-dose mebendazole in the treatment of hookworm and are lower at week two than at redosing, while cure and egg reduction rates of single-dose praziquantel are satisfactory to treat . Therefore, single-dose praziquantel to and redosing of single-dose mebendazole to and hookworm infections can be used for treatment purposes.
Topics: Adolescent; Animals; Child; Ethiopia; Female; Geography; Helminthiasis; Helminths; Humans; Male; Mebendazole; Ovum; Praziquantel; Schistosoma mansoni; Schistosomiasis mansoni; Schools; Soil; Students; Treatment Outcome
PubMed: 34327236
DOI: 10.1155/2021/6682418 -
The Cochrane Database of Systematic... Dec 2012Giardiasis infection may be asymptomatic, or can cause diarrhoea (sometimes severe), weight loss, malabsorption, and, in children, failure to thrive. It is usually... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Giardiasis infection may be asymptomatic, or can cause diarrhoea (sometimes severe), weight loss, malabsorption, and, in children, failure to thrive. It is usually treated with metronidazole given three times daily for five to 10 days.
OBJECTIVES
To evaluate the relative effectiveness of alternative antibiotic regimens for treating adults or children with symptomatic giardiasis.
SEARCH METHODS
We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 6 2012); MEDLINE, EMBASE, LILACS and the International Clinical Trials Registry Platform Search Portal (3 July 2012).
SELECTION CRITERIA
We included randomized controlled trials (RCT) comparing metronidazole administered for five to 10 days with any of the following drugs: metronidazole (single dose), tinidazole, albendazole, mebendazole, and nitazoxanide. The primary outcomes were parasitological and clinical cure.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed studies for inclusion, performed the risk of bias assessment, and extracted data. We summarized data using risk ratios and mean differences and we presented the results in forest plots and performed meta-analyses where possible. We assessed heterogeneity using the Chi(2) test, I(2) statistic and visual inspection; and we explored this by using subgroup analyses.We assessed the quality of evidence by using the GRADE approach.
MAIN RESULTS
We included 19 trials, involving 1817 participants, of which 1441 were children. Studies were generally small, with poor methods reporting. . Most reported parasitological outcomes rather than clinical improvement.Ten trials, from India, Mexico, Peru, Iran, Cuba, and Turkey, compared albendazole (400 mg once daily for five to 10 days) with metronidazole (250 mg to 500 mg three times daily for five to 10 days). This once-daily regimen of albendazole is probably equivalent to metronidazole at achieving parasitological cure (RR 0.99, 95% CI 0.95 to 1.03; 932 participants, 10 trials; moderate quality evidence), and improving symptoms (RR 0.98, 95% confidence interval (CI) 0.93 to 1.04; 483 participants, five trials; moderate quality evidence), but the duration of follow-up was short (two to three weeks). Albendazole probably has fewer side effects than metronidazole (gastrointestinal side effects: RR 0.29, 95% CI 0.13 to 0.63; 717 participants, eight trials; moderate quality evidence; neurological side effects: RR 0.34, 95% CI 0.18 to 0.64; 453 participants, five trials; low quality evidence).Five trials from Turkey, Spain and the UK compared mebendazole (200 mg three times daily for five to 10 days) with metronidazole (5 mg/kg (or 250 mg) three times daily for five to 10 days). These trials were small in size, and at high risk of bias. Consequently, reliable conclusions on the relative effectiveness cannot be made (very low quality evidence).Five further trials, from Iran, Spain and Peru, have evaluated shortened regimens of tinidazole (single dose; 179 participants, three trials), metronidazole (single dose; 55 participants, one trial), and nitazoxanide (three days; 55 participants, one trial). Again, these trials were at high risk of bias and too small to reliably detect or exclude important differences (very low quality evidence).
AUTHORS' CONCLUSIONS
Albendazole may be of similar effectiveness to metronidazole, may have fewer side effects, and has the advantage of a simplified regimen. Large, high quality trials, assessing clinical outcomes (such as diarrhoea) will help assess further alternatives.
Topics: Adult; Albendazole; Antiparasitic Agents; Child; Giardiasis; Humans; Mebendazole; Metronidazole; Nitro Compounds; Randomized Controlled Trials as Topic; Thiazoles; Tinidazole
PubMed: 23235648
DOI: 10.1002/14651858.CD007787.pub2 -
Membranes Sep 2022The idea of using drugs from the benzimidazole group as potential antitumor agents is becoming increasingly popular and widespread in research. However, their use as...
The idea of using drugs from the benzimidazole group as potential antitumor agents is becoming increasingly popular and widespread in research. However, their use as antiparasitics and in cancer treatment will increase their already recorded occurrence in the aquatic environment. In this study, the removal of the anthelmintic mebendazole from aqueous solution was investigated using nanofiltration and reverse osmosis membranes, adsorption on granular activated carbon (GAC), and photolytic degradation. The dense NF90 and reverse osmosis XLE membranes showed almost complete removal (>97.7%), while the NF270 membrane showed a large dependence of removal on initial concentration from 41.9% to 96.6%. Adsorption in the column resulted in complete removal of mebendazole at the highest GAC height used (40 cm) from the solution with the lowest concentration (1 mg/L). Photolytic degradation by artificial light for 2 and 12 h resulted in photodegradation of mebendazole in the range of 23.5−61.4%, forming a new degradation or transformation compound with an m/z ratio of 311. Mebendazole is a photosensitive drug whose photodegradation follows first-order kinetics and depends on the drug concentration. Toxicity was studied with Vibrio fischeri before and after photolysis, and showed a decrease in inhibition after 12 h.
PubMed: 36135907
DOI: 10.3390/membranes12090888 -
Biomedicine & Pharmacotherapy =... Jun 2023The continuing heavy toll of the COVID-19 pandemic necessitates development of therapeutic options. We adopted structure-based drug repurposing to screen FDA-approved...
The continuing heavy toll of the COVID-19 pandemic necessitates development of therapeutic options. We adopted structure-based drug repurposing to screen FDA-approved drugs for inhibitory effects against main protease enzyme (Mpro) substrate-binding pocket of SARS-CoV-2 for non-covalent and covalent binding. Top candidates were screened against infectious SARS-CoV-2 in a cell-based viral replication assay. Promising candidates included atovaquone, mebendazole, ouabain, dronedarone, and entacapone, although atovaquone and mebendazole were the only two candidates with IC50s that fall within their therapeutic plasma concentration. Additionally, we performed Mpro assays on the top hits, which demonstrated inhibition of Mpro by dronedarone (IC50 18 µM), mebendazole (IC50 19 µM) and entacapone (IC50 9 µM). Atovaquone showed only modest Mpro inhibition, and thus we explored other potential mechanisms. Although atovaquone is Dihydroorotate dehydrogenase (DHODH) inhibitor, we did not observe inhibition of DHODH at the respective SARS-CoV-2 IC50. Metabolomic profiling of atovaquone treated cells showed dysregulation of purine metabolism pathway metabolite, where ecto-5'-nucleotidase (NT5E) was downregulated by atovaquone at concentrations equivalent to its antiviral IC50. Atovaquone and mebendazole are promising candidates with SARS-CoV-2 antiviral activity. While mebendazole does appear to target Mpro, atovaquone may inhibit SARS-CoV-2 viral replication by targeting host purine metabolism.
Topics: Humans; Antiviral Agents; SARS-CoV-2; COVID-19; Dihydroorotate Dehydrogenase; Drug Repositioning; Dronedarone; Pandemics; Atovaquone; Mebendazole; Purines; Molecular Docking Simulation; Protease Inhibitors; Molecular Dynamics Simulation
PubMed: 37068330
DOI: 10.1016/j.biopha.2023.114614 -
Parasite (Paris, France) 2014The search for novel therapeutic options to cure alveolar echinococcosis (AE), due to the metacestode of Echinococcus multilocularis, is ongoing, and these developments... (Review)
Review
The search for novel therapeutic options to cure alveolar echinococcosis (AE), due to the metacestode of Echinococcus multilocularis, is ongoing, and these developments could also have a profound impact on the treatment of cystic echinococcosis (CE), caused by the closely related Echinococcus granulosus s.l. Several options are being explored. A viable strategy for the identification of novel chemotherapeutically valuable compounds includes whole-organism drug screening, employing large-scale in vitro metacestode cultures and, upon identification of promising compounds, verification of drug efficacy in small laboratory animals. Clearly, the current focus is targeted towards broad-spectrum anti-parasitic or anti-cancer drugs and compound classes that are already marketed, or that are in development for other applications. The availability of comprehensive Echinococcus genome information and gene expression data, as well as significant progress on the molecular level, has now opened the door for a more targeted drug discovery approach, which allows exploitation of defined pathways and enzymes that are essential for the parasite. In addition, current in vitro and in vivo models that are used to assess drug efficacy should be optimized and complemented by methods that give more detailed information on the host-parasite interactions that occur during drug treatments. The key to success is to identify, target and exploit those parasite molecules that orchestrate activities essential to parasite survival.
Topics: Albendazole; Animals; Anthelmintics; Cell Division; Clarithromycin; Cytostatic Agents; Drug Design; Drug Evaluation, Preclinical; Echinococcosis; Echinococcosis, Hepatic; Echinococcus multilocularis; Forecasting; Guanidines; Helminth Proteins; Host-Parasite Interactions; Humans; Imidazoles; Larva; Mebendazole; Mefloquine; Mice; Molecular Targeted Therapy; Nitro Compounds; Thiazoles; Thiophenes
PubMed: 25526545
DOI: 10.1051/parasite/2014073