Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has recently been noted as a repositioning candidate for angiogenesis inhibition and cancer therapy. However, the definite anti-angiogenic mechanism of MBZ remains unclear. In this study, we explored the inhibitory mechanism of MBZ in endothelial cells (ECs) and developed a novel strategy to improve its anti-angiogenic therapy. Treatment of ECs with MBZ led to inhibition of EC proliferation in a dose-dependent manner in several culture conditions in the presence of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF) or FBS, without selectivity of growth factors, although MBZ is known to inhibit VEGF receptor 2 kinase. Furthermore, MBZ inhibited EC migration and tube formation induced by either VEGF or bFGF. However, unexpectedly, treatment of MBZ did not affect FAK and ERK1/2 phosphorylation induced by these factors. Treatment with MBZ induced shrinking of ECs and caused G2-M arrest and apoptosis with an increased Sub-G1 fraction. In addition, increased levels of nuclear fragmentation, p53 expression, and active form of caspase 3 were observed. The marked induction of autophagy by MBZ was also noted. Interestingly, inhibition of autophagy through knocking down of Beclin1 or ATG5/7, or treatment with autophagy inhibitors such as 3-methyladenine and chloroquine resulted in marked enhancement of anti-proliferative and pro-apoptotic effects of MBZ in ECs. Consequently, we suggest that MBZ induces autophagy in ECs and that protective autophagy can be a novel target for enhancing the anti-angiogenic efficacy of MBZ in cancer treatment.
Apoptosis ; Autophagy* ; Caspase 3 ; Chloroquine ; Endothelial Cells* ; Fibroblast Growth Factor 2 ; Helminths ; Intercellular Signaling Peptides and Proteins ; Mebendazole* ; Microtubules ; Phosphorylation ; Phosphotransferases ; Receptors, Vascular Endothelial Growth Factor ; Vascular Endothelial Growth Factor A

Albendazole (ADZ) and praziquantel (PZQT) have been used as anthelmintics for over 30 years. Worldwide, hundreds of millions tablets are administered to people and livestock every year. ADZ is poorly orally absorbed (< 5%), and its uptake is enhanced by high-fat meals, while PZQT is well absorbed (> 75%) and uptake is enhanced by carbohydrate-rich meals. Both ADZ and PZQT are safe, but not recommended for children < 2 years or for women in the first trimester of pregnancy. Serious adverse events occur following high dose and prolonged administration of these drugs for treatment of echinococcosis or neurocysticercosis, especially in patients with poor liver function. The adverse events may be induced by the drugs, or by the dead worms themselves. The Korea Institute of Drug Safety & Risk Management monitors drug-related adverse events in Korea, and its database included 256 probable or possible ADZ-associated events and 108 PZQT-associated events between 2006 and 2015. Such low incidence rates in Korea are due to the low single dose treatments of ADZ, and the short-term use of PZQT. The number of serious adverse events due to drug interaction induced by ADZ and PZQT were six and two, respectively. We conclude that ADZ and PZQT are generally safe drugs, but they must be used with caution in people with poor liver function or those being comedicated for gastroesophageal reflux disease.
Albendazole* ; Anthelmintics ; Child ; Drug Interactions ; Echinococcosis ; Female ; Gastroesophageal Reflux ; Humans ; Incidence ; Korea* ; Liver ; Livestock ; Meals ; Mebendazole ; Neurocysticercosis ; Praziquantel* ; Pregnancy ; Pregnancy Trimester, First ; Risk Management ; Tablets

Albendazole (ADZ) and praziquantel (PZQT) have been used as anthelmintics for over 30 years. Worldwide, hundreds of millions tablets are administered to people and livestock every year. ADZ is poorly orally absorbed (< 5%), and its uptake is enhanced by high-fat meals, while PZQT is well absorbed (> 75%) and uptake is enhanced by carbohydrate-rich meals. Both ADZ and PZQT are safe, but not recommended for children < 2 years or for women in the first trimester of pregnancy. Serious adverse events occur following high dose and prolonged administration of these drugs for treatment of echinococcosis or neurocysticercosis, especially in patients with poor liver function. The adverse events may be induced by the drugs, or by the dead worms themselves. The Korea Institute of Drug Safety & Risk Management monitors drug-related adverse events in Korea, and its database included 256 probable or possible ADZ-associated events and 108 PZQT-associated events between 2006 and 2015. Such low incidence rates in Korea are due to the low single dose treatments of ADZ, and the short-term use of PZQT. The number of serious adverse events due to drug interaction induced by ADZ and PZQT were six and two, respectively. We conclude that ADZ and PZQT are generally safe drugs, but they must be used with caution in people with poor liver function or those being comedicated for gastroesophageal reflux disease.
Albendazole* ; Anthelmintics ; Child ; Drug Interactions ; Echinococcosis ; Female ; Gastroesophageal Reflux ; Humans ; Incidence ; Korea* ; Liver ; Livestock ; Meals ; Mebendazole ; Neurocysticercosis ; Praziquantel* ; Pregnancy ; Pregnancy Trimester, First ; Risk Management ; Tablets

A male, 3.5 month old Pomeranian dog was diagnosed with a natural infection of Crenosoma (C.) vulpis in Daejeon, Korea. First stage larvae of C. vulpis were detected by fecal examination using the Baermann technique. Thoracic radiographs revealed mild, pervasive bronchial infiltration of the lung. Enumeration of larvae via the McMaster technique revealed 1,600 larvae per gram of feces. The dog was treated with mebendazole, and clinical symptoms were resolved 2 weeks post-treatment, as indicated by the subject presenting fecal tests negative for C. vulpis.
Animals ; Dogs* ; Feces ; Humans ; Korea ; Larva ; Lung ; Male ; Mebendazole

Praziquantel is the drug of choice for clonorchiasis. Since clonorchiasis is endemic in most river basins, praziquantel has been widely used for 30 years in Korea. A 54-year-old Korean woman suffered from hypersensitive reactions, such as nausea, dyspnea, rash, and urticaria after taking the first dose of praziquantel to treat clonorchiasis. She ingested one dose again and the same symptoms appeared, and she was treated at a clinic with anti-histamines. She tried one more dose with anti-histamines but found the same symptoms. Later, she was found to pass eggs of Clonorchis sinensis and medicated with flubendazole. The hypersensitive reaction to praziquantel is rare but occurs. This is the 5th case report in the world.
Animals ; Anthelmintics/*administration & dosage/*adverse effects ; Clonorchiasis/*complications/*drug therapy ; Clonorchis sinensis/isolation & purification ; Drug Hypersensitivity/*diagnosis/drug therapy/pathology ; Feces/parasitology ; Female ; Histamine Antagonists/administration & dosage ; Humans ; Mebendazole/administration & dosage/analogs & derivatives ; Middle Aged ; Praziquantel/*administration & dosage/*adverse effects ; Republic of Korea

The recent trends of parasitic infections in Korea include remarkable decreases of soil-transmitted nematode infections and elimination of lymphatic filariasis. In comparison, enterobiasis (pinworm infection) continues to be prevalent among children and the cases of zoonotic tissue-invading nematode infection are slightly increasing or they are being increasingly diagnosed. In addition, imported parasitoses continue to be problems from the clinical and public health points of view. In this review, the advances in the management and anthelmintic treatment of these nematode infections are briefly reviewed. Albendazole, mebendazole, thiabendazole, flubendazole, pyrantel pamoate, pyrvinium pamoate, oxantel pamoate, levamisole, ivermectin, and diethylcarbamazine are the examples of anti-nematode anthelmintics that are currently being used. Although several of these drugs are known to be broad-spectrum anthelmintics, selection of each drug should be done specifically for each nematode infection, and with consideration of the specific conditions of each patient and the purposes, for example, when performing individual or mass treatment. It is hoped that the chemotherapy regimens reviewed here will help physicians to treat their patients infected with nematode parasites.
Albendazole ; Anthelmintics ; Child ; Diethylcarbamazine ; Elephantiasis, Filarial ; Enterobiasis ; Humans ; Ivermectin ; Korea ; Levamisole ; Mebendazole ; Nematode Infections ; Parasites ; Public Health ; Pyrantel Pamoate ; Pyrvinium Compounds ; Thiabendazole

Pelvic masses, especially hydatid disease, rarely present with sciatica (1, 2). We present the computed tomography (CT) and the magnetic resonance imaging (MRI) findings of a 49-year-old female patient with presacral hydatid disease, who was evaluated for her sciatica. We also want to emphasize the importance of assessing the pelvis of patients with symptoms and clinical findings that are inconsistent and that cannot be satisfactorily explained by the spinal imaging findings.
Animals ; Anthelmintics/administration & dosage ; Contrast Media/administration & dosage ; Diagnosis, Differential ; Echinococcosis/complications/*diagnosis/surgery ; Echinococcus/drug effects ; Female ; Humans ; Lumbosacral Plexus/parasitology/pathology/radiography ; Magnetic Resonance Imaging/*methods ; Mebendazole/administration & dosage ; Middle Aged ; Pain/etiology ; Pelvis/*pathology/*radiography/surgery ; Radiographic Image Enhancement/methods ; Recurrence ; Sciatica/*parasitology/surgery ; Tomography, X-Ray Computed/*methods

Cutaneous gnathostomiasis has also been called larva migrans profundus and nodular migratory eosinophilic panniculitis. Human gnathostomiasis is caused mainly by the nematode Gnathostoma spinigerum. It causes migratory cutaneous, erythematous, indurated plaques and serious visceral sequelae. Medical treatment with mebendazole, albendazole, and ivermectin has been disappointing. Surgical excision of the parasite is the treatment of choice when possible.
Albendazole ; Eosinophils ; Gnathostoma ; Gnathostomiasis* ; Humans* ; Ivermectin* ; Larva Migrans ; Mebendazole ; Panniculitis ; Parasites

The study was conducted in 300 people above 16 year old in Yen Phong district, Bac Ninh province from December 2003 to June 2004, using cross-sectional descriptive method and data processed by software EPI-INFO 6.04. Results: 19% of ancylostomiasis infected, 38.6% of anaemia; a hypoglobulia occurred at mild level in 80% of male and 62.2% of female, at medium level in 20% of male and 16.2% of female, and no cases at severe level. Hemoglobin level reduced lightly in 50% male; 32.4% female and no cases at severe level. After 4 weeks of treatment with mebendazol 500mg, the rate of patients without any larvae account for 91.2%. After 6 month of the treatment, almost patients had erythrocyte value and hemoglobin level close to the normal. After 6 months, the recurrent rate was 15.8%
Ancylostomiasis ; Therapeutics ; Mebendazole

The study was conducted from September 2003 to April 2005 to assess results of the mass deworming campaign in 5 primary schools in Quynh Luu district, central province of Nghe An. A pre-intervention survey showed a cumulative worm prevalence of 98%, of which the highest rate was Trichuris infection: 85.1% followed by Ascaris: 83.6% and hookworm 30.3%. No difference of infection between females and males was found. Mixed infection was high with 54.3% had co-infection with Ascaris and Trichuris (88%), and 24.8% had triple infection, while a low single infection rate (20.8%) of which Trichuris was predominant, was found. A low prevalence of high intensity of infections was found with Ascaris (6.5%), hookworm (1 %), Trichuris (0.5%) while a high prevalence of low intensity was found with all examined samples. The worm prevalence was found reduced after periodical mass deworming (every six months) with mebendazole 500mg, single dose. The cumulative infection reduced from 98% to 84.5% after six months and 72.2% after 18 months. Similarly, the Ascaris infection came down from 83.6% to 52.7% and 32.7%, the Trichuris from 85.1% to 70.6% and 56.1%. However, hookwonn infection remained nearly unchanged (30.3% to 31.3% and 31.1 %). The high and moderate intensity of infection was also reduced after intervention. The egg counts were reduced by 60% after 6 months, 73% after 18 months (after the third treatment) with Ascaris. Accordingly, it was reduced by 40% and 70%, respectively with Trichuris. No changes were found with hookwonn. The intestinal wonn infection control project supported by WHO has been a successful project in tenn of both technical and social aspects. The project was performed with good compliance of school children, their parents and teachers. Expertise and qualification of the provincial staffs were also enhanced with regard to public health in general, and intestinal worm infection control, in particular.
Helminths ; Mebendazole ; Therapeutics