Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new vermox research articles will be listed here shortly after becoming available to us.
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Medical research on vermox
Spherical Crystallization of Mebendazole to Improve Processability.
Pharm Dev Technol. 2008 Aug 20; 1-10
Kumar S, Chawla G, Bansal AK
Spherical crystallization technique combines crystallization and agglomeration directly to generate spherical crystals with improved micromeretic properties, thus obviating need for further processing by granulation and agglomeration. The present study was focused on spherical crystallization of an antihelmentic drug - Mebendazole (MBZ) - using spherical agglomeration technique. Apart from being poorly water-soluble, MBZ exhibits poor flow and compressibility owing to its needle shaped crystal habit and electrostatic charge. Spherical agglomeration was carried out in the presence of different bridging liquids (hexane, octanol, toluene, dichloromethane) and polymers (polyethylene glycol, cross-povidone, starch, cross carmellose sodium, hydroxyl propyl methyl cellulose (HPMC), hydroxyl propyl cellulose (HPC), ethyl cellulose (EC), Eudragit(R)S100, Eudragit(R)RLPO, Eudragit(R)RD100, Eudragit(R)E), by employing different crystallization conditions such as variation of polymer type, polymer concentration, and rate of stirring. The final parameters were optimized to obtain crystals with an aspect ratio in the range of 1-2 compared to a value of 12 for untreated MBZ. These agglomerates retained form C of MBZ, and exhibited good flow properties, high bulk density and improved compressibility. Lower elastic:plastic energy (EE/PE) ratio for spherical crystals generated in the presence of Eudragit(R)-S100 and Hydroxypropylcellulose (HPC) indicated better compressibilty of spherical crystals.
A Large-Scale Outbreak of Trichinellosis Caused by Trichinella britovi in Turkey.
Zoonoses Public Health. 2008 Aug 14;
Akkoc N, Kuruuzum Z, Akar S, Yuce A, Onen F, Yapar N, Ozgenc O, Turk M, Ozdemir D, Avci M, Guruz Y, Oral AM, Pozio E,
An outbreak of trichinellosis occurred in Izmir, Turkey, between January and March 2004. The outbreak was caused by the consumption of raw meat balls made of beef deceptively mixed with pork infected with Trichinella britovi. A total of 1098 people who had consumed this food either in 14 restaurants or from the street vendors located in three different neighbourhoods, consulted six different healthcare centres with a wide range of clinical signs and symptoms. Of them, 418 (38.1%) patients fulfilled the criteria for the diagnosis of acute trichinellosis. The most commonly observed signs and symptoms were myalgia (89.2%), arthralgia (69.9%) and eyelid (67%) and facial oedema (65.8%). High levels of creatinine kinase (69.3%) and lactate dehydrogenase (93.8%) with leucocytosis (>10 000/mm(3), 58.9%) and eosinophilia (>1000/mm(3), 60.5%) were the most prominent laboratory findings. All, but 13 of these patients were treated with mebendazole or albendazole. Based on the physicians' assessments of disease severity, 78 (19%) patients were additionally given prednisolone in whom a significantly more rapid recovery of clinical signs and symptoms (e.g. fever, myalgia, facial and eyelid oedema) was observed, with a rapid improvement in leucocytosis, eosinophilia and muscle enzymes, compared with those, who had not received corticosteroids (P < 0.05). Beef illegally mixed with pork of unknown origin, by a wholesale butcher who had sold this product to restaurants and street vendors at a lower price than the prevailing market price of beef, was the cause of this large-scale outbreak in a country with a predominantly Muslim population.
Curr Drug Discov Technol. 2008 Jun; 5(2): 146-53
Bernad-Bernad MJ, Gracia-Mora J, Díaz D, Castillo-Blum SE
The main purpose of this work was to accomplish a comparative study about cyclodextrins complexation equilibria with three benzimidazolic antihelmintics: albendazole (Alb), mebendazole (Meb) and thiabendazole (Thiab). The complexation process with four different cyclodextrins (alpha-, beta-, gamma-, and HP-beta-CDs) was investigated under various temperatures and different reaction media (aqueous solution buffered at pH 7.5, dimethylsulfoxide (DMSO) and DMSO/water at 25/75, 50/50, 75/50 (w/w) mixtures). It was studied by electronic absorption and 1H NMR (NOESY) spectroscopy. Binding constants were determined by electronic absorption spectroscopic method, the DeltaH and DeltaS complexation values were evaluated and discussed according to the diverse factors that affect the chemical interactions in these systems. Solubility has also been determined by the Higuchi and Connors method. In general, albendazole and mebendazole exhibit similar complexation behavior, while thiabendazole acts differently. Classic and non-classic solvophobic effects are mainly the driving and stabilizing forces for complex formation, with the exception in some Thiab-CDs interactions. In all cases, DMSO, an aprotic solvent, should be considered as an active component of the reaction systems.
Hepatic and extra-hepatic metabolic pathways involved in flubendazole biotransformation in sheep.
Biochem Pharmacol. 2008 Jul 11;
Maté L, Virkel G, Lifschitz A, Ballent M, Lanusse C
Flubendazole (FLBZ) is a broad-spectrum benzimidazole anthelmintic compound used in pigs, poultry and humans. Its potential for parasite control in ruminant species is under investigation. The objective of the work described here was to identify the main enzymatic pathways involved in the hepatic and extra-hepatic biotransformation of FLBZ in sheep. Microsomal and cytosolic fractions obtained from sheep liver and duodenal mucosa metabolised FLBZ into a reduced FLBZ metabolite (red-FLBZ). The keto-reduction of FLBZ led to the prevalent ( approximately 98%) stereospecific formation of one enantiomeric form of red-FLBZ. The amounts of red-FLBZ formed in liver subcellular fractions were 3-4-fold higher (P
Mebendazole Induces Apoptosis via Bcl-2 Inactivation in Chemoresistant Melanoma Cells.
Mol Cancer Res. 2008 Aug; 6(8): 1308-15
Doudican N, Rodriguez A, Osman I, Orlow SJ
Most metastatic melanoma patients fail to respond to available therapy, underscoring the need for novel approaches to identify new effective treatments. In this study, we screened 2,000 compounds from the Spectrum Library at a concentration of 1 mumol/L using two chemoresistant melanoma cell lines (M-14 and SK-Mel-19) and a spontaneously immortalized, nontumorigenic melanocyte cell line (melan-a). We identified 10 compounds that inhibited the growth of the melanoma cells yet were largely nontoxic to melanocytes. Strikingly, 4 of the 10 compounds (mebendazole, albendazole, fenbendazole, and oxybendazole) are benzimidazoles, a class of structurally related, tubulin-disrupting drugs. Mebendazole was prioritized to further characterize its mechanism of melanoma growth inhibition based on its favorable pharmacokinetic profile. Our data reveal that mebendazole inhibits melanoma growth with an average IC(50) of 0.32 mumol/L and preferentially induces apoptosis in melanoma cells compared with melanocytes. The intrinsic apoptotic response is mediated through phosphorylation of Bcl-2, which occurs rapidly after treatment with mebendazole in melanoma cells but not in melanocytes. Phosphorylation of Bcl-2 in melanoma cells prevents its interaction with proapoptotic Bax, thereby promoting apoptosis. We further show that mebendazole-resistant melanocytes can be sensitized through reduction of Bcl-2 protein levels, showing the essential role of Bcl-2 in the cellular response to mebendazole-mediated tubulin disruption. Our results suggest that this screening approach is useful for identifying agents that show promise in the treatment of even chemoresistant melanoma and identifies mebendazole as a potent, melanoma-specific cytotoxic agent. (Mol Cancer Res 2008;6(8):1308-15).
Arch Biochem Biophys. 2008 Jul 17;
Torres-Rivera A, Landa A
Glutathione transferases (GSTs) are essential enzymes in many organisms due their diverse functions and, in helminths they are the main detoxification system. For Taenia solium, two cytosolic GSTs with molecular masses of 25.5 and 26.5kDa (Ts26GST) have been found. Ts26GST was cloned to be studied in its recombinant form (recTs26GST). Although the primary structure is related to the mu class, the kinetic parameters for CDNB (V(max)=51.5mumolmin(-1)mg(-1); K(m)=1.06mM; k(cat)= 22.2s(-1)) are related with some alpha GSTs. The substrate and inhibitor class markers reaffirmed these bimodal characteristics. Inhibition studies with anthelminthics indicate that recTs26GST is sensitive to mebendazole, displaying a non competitive inhibition pattern suggesting that at least two molecules are binding to recTs26GST. On the other hand, the kinetic curves for CDNB and GSH showed a positive cooperativity that was corroborated using fluorometric assays. Those assays indicate that CDNB binding is highly influenced by GSH, probably by modulation of the Ts26GST conformational ensamble.
Eur J Pharm Sci. 2008 Sep 2; 35(1-2): 127-35
Van Eerdenbrugh B, Froyen L, Van Humbeeck J, Martens JA, Augustijns P, Van den Mooter G
d-alpha-Tocopherol polyethylene glycol 1000 succinate (TPGS)-stabilized nanosuspensions (25wt%, relative to the drug weight) were produced by media milling for 9 model drug compounds [cinnarizine, griseofulvin, indomethacin, itraconazole, loviride, mebendazole, naproxen, phenylbutazone and phenytoin]. After 3 months of storage at room temperature, Ostwald ripening occurred in all of the samples, except for indomethacin. Whereas lowering the temperature could slow down the ripening, it markedly increased upon storage at 40 degrees C. As for ripening, settling generally became more pronounced at 40 degrees C compared to 4 degrees C. As the nanosuspensions were afflicted by Ostwald ripening and settling, we explored nanosuspension drying as a strategy to circumvent these stability issues. Spray-drying and freeze-drying were evaluated for nanosuspensions and coarse reference suspensions of the compounds. Nanoparticle agglomeration could be visually observed in all of the powders. To evaluate the effect of agglomeration on the key characteristic of drug nanocrystals (i.e. rapid dissolution), dissolution experiments were performed under poor sink conditions. It was found that the compounds could be categorized into 3 groups: (i) compounds for which it was impossible to differentiate between coarse and nanosized products (griseofulvin, mebendazole, naproxen), (ii) compounds that gave clear differences in dissolution profiles between the nanosized and the coarse products, but for which drying of the nanosuspensions did not decrease the dissolution performance of the product (indomethacin, loviride, phenytoin) and (iii) compounds that showed differences between coarse and nanosized products, but for which drying of the nanosuspensions resulted in a significant decrease of the dissolution rate (cinnarizine, itraconazole, phenylbutazone). To gain insight on the influence of the drug compound characteristics on the dissolution of the dried products, the dissolution behavior of the compounds of the second and the third group was linked to the compound's characteristics. It was found that compounds with a more hydrophobic surface resulted in agglomerates which were harder to disintegrate, for which dissolution was compromised upon drying. The same was found for compounds having higher logP values.
[Trichinosis in the Kherson Region]
Med Parazitol (Mosk). 2008 Apr-Jun; 15-7
Koval' AA, Pankratov SM, Dzhiganskaia LV, Sosnovskaia EI, Dudnik NN, Sanzharovskaia LI
The paper describes the 2003-2004 outbreak oft richinosis in 2 districts of the Kherson Region. Pork was a source of infection. The disease occurred with the ingestion ofshashlik, raw meat, lard, or minced meat. The diagnosis of trichinosis was established 1-1.5 months after the onset of the disease. The patients received a course of therapy and were discharged in a satisfactory condition. The members of their families were prophylactically treated. Meats were bought at the markets and had negative veterinary sanitary tests. A package of antiepidemic and antiepizootic measures was implemented in the foci of trichinosis.
Int J Pharm. 2008 Sep 1; 361(1-2): 245-50
Agatonovic-Kustrin S, Glass BD, Mangan M, Smithson J
The objective of this study was to develop a simple, direct and non-destructive method to assess crystal purity of mebendazole raw material and to establish its stability in a suspension formulation using diffuse reflectance ultraviolet (DRA-UV) spectroscopy and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy. Quantitation of mebendazole, found to exhibit polymorphism with three polymorphic forms A, B and C identified, was carried out with ATR-FTIR spectroscopy. Artificial neural network (ANN) was employed as a data-modelling tool. The developed ANN models confirmed that the characteristic absorptions in the infrared (IR) spectral region are directly proportional to the measured amounts of mebendazole crystal forms present in the samples (r(2)>0.94), which was confirmed with X-ray diffraction (XRD) at r(2)>0.97. These models also predicted that the mebendazole raw material contained 7.21+/-1.25% (ATR-FTIR data) and 10.38+/-0.18% (XRD data) of form A as an impurity. ATR-FTIR data for the suspension formulation showed some dissolution of form C and recrystalisation as the more stable form A. These quantitative results obtained for the binary crystal form mixtures clearly demonstrate the strong potential of ATR-FTIR for use in the determination of the polymorphic content not only in bulk pharmaceuticals but also in liquid formulations.
Coverage and costs of a school deworming programme in 2007 targeting all primary schools in Lao PDR.
Trans R Soc Trop Med Hyg. 2008 Jun 11;
Phommasack B, Saklokham K, Chanthavisouk C, Nakhonesid-Fish V, Strandgaard H, Montresor A, Shuey DA, Ehrenberg J
Infections with soil-transmitted helminths (STHs) are among the commonest infections in Lao PDR. Recent investigation in this country showed that intestinal helminths currently infect the majority of school-aged children. The Lao Government has addressed the problem by organizing regular anthelminthic chemotherapy with mebendazole 500mg for school and pre-school children in conjunction with health education activities incorporated into the national school curriculum. The school deworming campaign in Lao PDR reached a national coverage rate of 95% at a cost of US$0.124/head for two rounds of deworming per year. The programme operates under the umbrella of the national school health programme. After 1 year (two rounds of deworming) the intervention reduced the prevalence of Ascaris lumbricoides from 60% to 20% and of Trichuris trichiura from 42% to 31%. Although infection was not eliminated by the deworming interventions, over 90% of those children who remain infected had a 'light' infection. The virtual absence of high and moderate intensity infection demonstrates the effectiveness of periodical deworming in reducing morbidity due to STHs. We expect that additional rounds of deworming will further reduce the STH prevalence in Lao PDR.