Anti-pinworm activity of novel coumarin-based trisubstituted methanes in Syphacia obvelata-infected mice.

The control of pinworms mainly relies on use of anthelmintic drugs. At present, there exists only few medications against pinworms, and their repeated use pose a serious risk of resistance development. Therefore, new anti-pinworm drugs are required to overcome the risk of resistance. This study reports the anti-pinworm activity of three novel coumarin-based trisubstituted methanes (TRSMs), i.e., 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-fluoro-phenyl)methyl)-1,3-dimethyl-pyrimidine-2,4(1H,3H)-dione (1), 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-chlor-ophenyl)methyl)-1,3-dimethyl-pyrimidine-2,4(1H,3H)-dione (2) and 6-Amino-5-((4-hydroxy-2-oxo-2H-chromen-3-yl)(4-bromophenyl)methyl)-1,3-dimethyl-pyrimidine-2,4(1H,3H)-dione (3) in Syphacia obvelata-infected mice. The oral acute toxicity of compounds was examined using the OECD guidelines. The findings of this study reveal that TRSM analogues 1 and 2, at a single 80 mg/kg dose given for 5 days, can reduce about 90% of pinworm worm burden in mice, compared to 98% worm reduction shown by 20 mg/kg dose of albendazole, the reference drug, on the 12 day of infection. In particular, the fluoro-and bromo-substituents in the phenyl ring of synthesized derivatives greatly influence the efficacy of candidates. The oral acute toxicity of TRSMs was observed to be greater than 2000 mg/kg body weight for mice. Taken together, our study suggests that studied novel coumarin-based trisubstituted methanes could serve as suitable candidates for the development of new anti-pinworm drugs.

Effective eradication of pinworms (Syphacia obvelata and Aspiculuris tetraptera) with Polygonum cognatum Meissn.

Polygonum cognatum Meissn. (Polygonaceae) is a wild edible plant known locally as "solucanotu, madimak" in Turkey and it has been used for various purposes, such as diuretic and antidiabetic, as well to treat oxyuris and worms internally in humans. The present study was carried out to investigate the anthelmintic activity of various extracts were obtained from the aerial parts of P. cognatum in order to justify its traditional usage in Turkish folk medicine. n-Hexane, ethyl acetate and methanol extracts were prepared from the aerial parts of the plant, successively. The anthelmintic potentials of these extracts were evaluated on mice naturally infected with Syphacia obvelata and Aspiculuris tetraptera. Cellophane perianal tape test and fecal flotation test were used for the activity screening. The results were compared with control and reference groups. In addition to all these experiments, the total amount of phenolic compounds and tannin contents thought to be responsible for the activity were evaluated for all extracts. According to the results, it has been found that the methanolic extract reduced the number of S. obvelata (66.8%) and A. tetraptera (73.4%) eggs. Moreover, the methanolic extract include higher amount of total phenolic compound (48.75 ±â€¯0.82 mg of GA/g of extract) and tannin (30.04 ±â€¯0.22 mg TA/g of extract) than n-Hexane (17.21 ±â€¯0.75 mg of GA/g of extract; 6.82 ±â€¯0.41 mg TA/g of extract) and ethyl acetate (25.06 ±â€¯0.94 mg of GA/g of extract; 10.29 ±â€¯0.34 mg TA/g of extract); therefore the anthelmintic activity could be related to these constituents. The present study explored the anthelmintic potential of P. cognatum. Further studies should be conducted into the mechanism of these compounds' against helminths. This study can be an important step in the discovery of new anthelmintic agents.

Evaluation of Anthelmintic Resistance and Exhaust Air Dust PCR as a Diagnostic Tool in Mice Enzootically Infected with Aspiculuris tetraptera.

The entry of infectious agents in rodent colonies occurs despite robust sentinel monitoring programs, strict quarantine measures, and stringent biosecurity practices. In light of several outbreaks with Aspiculuris tetraptera in our facilities, we investigated the presence of anthelmintic resistance and the use of exhaust air dust (EAD) PCR for early detection of A. tetraptera infection. To determine anthelmintic resistance, C57BL/6, DBA/2, and NCr nude mice were experimentally inoculated with embryonated A. tetraptera ova harvested from enzootically infected mice, followed by treatment with 150 ppm fenbendazole in feed, 150 ppm fenbendazole plus 5 ppm piperazine in feed, or 2.1 mg/mL piperazine in water for 4 or 8 wk. Regardless of the mouse strain or treatment, no A. tetraptera were recovered at necropsy, indicating the lack of resistance in the worms to anthelmintic treatment. In addition, 10 of 12 DBA/2 positive-control mice cleared the A. tetraptera infection without treatment. To evaluate the feasibility of EAD PCR for A. tetraptera, 69 cages of breeder mice enzootically infected with A. tetraptera were housed on a Tecniplast IVC rack as a field study. On day 0, 56% to 58% of the cages on this rack tested positive for A. tetraptera by PCR and fecal centrifugation flotation (FCF). PCR from EAD swabs became positive for A. tetraptera DNA within 1 wk of placing the above cages on the rack. When these mice were treated with 150 ppm fenbendazole in feed, EAD PCR reverted to pinworm-negative after 1 mo of treatment and remained negative for an additional 8 wk. The ability of EAD PCR to detect few A. tetraptera positive mice was investigated by housing only 6 infected mice on another IVC rack as a field study. The EAD PCR from this rack was positive for A. tetraptera DNA within 1 wk of placing the positive mice on it. These findings demonstrate that fenbendazole is still an effective anthelmintic and that EAD PCR is a rapid, noninvasive assay that may be a useful diagnostic tool for antemortem detection of A. tetraptera infection, in conjunction with fecal PCR and FCF.

Efficacy and security of ivermectin given orally to rats naturally infected with Syphacia spp., Giardia spp. and Hymenolepis nana.

The results of this study show that the oral administration of ivermectin (48 mg/L) repeatedly for 72 h used in accordance with the present protocol is a safe and highly effective treatment for Giardia spp. and Hymenolepis nana in laboratory rat colonies. The drug can be easily and safely administered using drinking water. This simple regimen should control pinworm infection (Syphacia muris), a problem that can be endemic in laboratory colonies. Experiments using healthy animals are likely to generate more consistent results, thereby requiring a reduced number of animals per group.

Exposure to chlorine dioxide gas for 4 hours renders Syphacia ova nonviable.

The purpose of our study was to evaluate the efficacy of chlorine dioxide gas for environmental decontamination of Syphacia spp. ova. We collected Syphacia ova by perianal cellophane tape impression of pinworm-infected mice. Tapes with attached ova were exposed to chlorine dioxide gas for 1, 2, 3, or 4 h. After gas exposure, ova were incubated in hatching medium for 6 h to promote hatching. For controls, tapes with attached ova were maintained at room temperature for 1, 2, 3, and 4 h without exposure to chlorine dioxide gas and similarly incubated in hatch medium for 6 h. Ova viability after incubation was assessed by microscopic examination. Exposure to chlorine dioxide gas for 4 h rendered 100% of Syphacia spp. ova nonviable. Conversely, only 17% of ova on the 4-h control slide were nonviable. Other times of exposure to chlorine dioxide gas resulted in variable effectiveness. These data suggest that exposure to chlorine dioxide gas for at least 4 h is effective for surface decontamination of Syphacia spp. ova.

The in vivo anthelmintic efficacy of some Verbascum species growing in Turkey.

Verbascum L. (Scrophulariaceae) species are used for desiccating wounds and as a fish poison in Anatolia as well as for diarrhea and dysentery of animals in several countries. To further evaluate their activity, methanolic extracts obtained from 13 Verbascum species growing in Turkey, including V. chionophyllum Hub.-Mor., V. cilicicum Boiss., V. dudleyanum (Hub.-Mor.) Hub.-Mor., V. lasianthum Boiss., V. latisepalum Hub.-Mor., V. mucronatum Lam., V. olympicum Boiss., V. pterocalycinum var. mutense Hub.-Mor., V. pycnostachyum Boiss. & Heldr., V. salviifolium Boiss., V. splendidum Boiss., V. stachydifolium Boiss. & Heldr. and V. uschackense (Murb.) Hub.-Mor. were evaluated for their in vivo anthelmintic activity. The extracts from V. lasianthum, V. latisepalum, V. mucronatum and V. salviifolum showed the highest inhibitory rates against Aspiculuris tetraptera at 100mg/kg in mice. Additionally, extracts from V. dudleyanum and V. pterocalycinum var. mutense were found generally highly effective. The remaining species did not show any activity. Results of the present study support the utilization of these plant species employed in Turkish folk medicine.

The effect of levamisole and levamisole+vitamin C on oxidative damage in rats naturally infected with Syphacia muris.

This study was performed to determine the effects of levamisole and levamisole+vitamin C against Syphacia muris naturally infection in rats and to detect its effect on the oxidative parameters in blood and tissues of host. For this purpose, natural infection was diagnosed using the cellophane tape method on the perianal region of rats. Infected rats (total 18) were divided into three groups. On the other hand six without helminth rats were used in this study as negative control group. Group 2 was given an orally levamisole HCl treatment with gastric gavage at a dose level of 20mg/kg body weight in distilled water, every alternate day. Group 3 was given levamisole HCl via gastric gavage at a dose level of 20mg/kg and vitamin C was given 1g/L added to the drinking water. All the treatments continued for a period of 7 days. As a result; levamisole administered to rats at dose of 20mg/kg orally 98.34% was found to be effective against adult S. muris in the rats. In addition to levamisole+vitamin C is effective to alleviate the oxidative damage in rats infected with S. muris.

The acute effects of single-dose orally administered doramectin, eprinomectin and selamectin on natural infections of Syphacia muris in rats.

This study was designed to determine the acute effects of a single-dose of orally administered doramectin, eprinomectin and selamectin on Syphacia muris infection in rats. Rats, naturally infected with S. muris, were divided into four groups: three different treatment groups (n=7) and one positive control (n=7). Cellophane tape preparations were obtained from the treated rats on day 0 pre-treatment and on days 2, 4 and 6 post-treatment. Syphacia sp. eggs were counted. Eprinomectin was found to be 100% effective in eliminating eggs on two post-treatment. However when egg counts on day 6 post-treatment were compared with pre-treatment egg counts, doramectin and selamectin were found to be 99.32 and 98.77% effective in eliminating eggs, respectively. On day 7 post-treatment, blood samples were obtained from all groups, and then the rats were necropsied. Doramectin, eprinomectin and selamectin were found to be 100% effective in eliminating adult S. muris, when compared with the positive control group.

Comparison of the effects of local and uncontrolled levamisole preparations on mice naturally infected with Aspiculuris tetraptera.

This study was performed to compare effectiveness of two levamisole preparations prepared in two different countries (Iran and Turkey) in mice naturally infected with Aspiculuris tetraptera. For this purpose, natural infection was diagnosed using the cellophane tape method on the perianal region and centrifugal flotation technique on the feces of mice obtained from the experimental Animal Unit of the Faculty of Medicine, University of Yüzüncü Yil, Van. Mice naturally infected with A. tetraptera were then divided in three groups. Animals in Group 1 (8 animals) received levamisole prepared in Iran, animals in Group 2 (8 animals) received levamisole prepared in Turkey and animals in Group 3 (6 animals) were used as untreated controls. Both levamisole preparations were used in a 10 mg/kg dose. After drug administrations, stool samples of the animals in all groups were examined for seven days. On the eighth day, the animals were humanely destroyed using inhalation anesthesia. After euthanasia, parasites in the intestine were also counted. As a result; levamisole coming through uncontrolled border trade from Iran was 69.3% effective against A. tetraptera and the levamisole prepared in Turkey was 91.7% effective in naturally infected mice. Results obtained from this study compared statistically and the differences were found to be significant (p < 0.001).

Antihelminthic activity of some newly synthesized 5(6)-(un)substituted-1H-benzimidazol-2-ylthioacetylpiperazine derivatives.

Piperazine derivatives of 5(6)-substituted-(1H-benzimidazol-2-ylthio)acetic acids were synthesized by using two methods and studied for antihelminthic activity. The antiparasitic screening showed that compounds 18-24 exhibited higher activity against Trichinella spiralis in vitro in comparison to methyl 5-(propylthio)-1H-benzimidazol-2-yl-carbamate (albendazole). Most active were compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21 and 2-{[2-oxo-2-(4-benzhydrylpiperazin-1-yl)ethyl]thio}-5(6)-methyl-1(H)-benzimidazole 19 as well as 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 with efficacy of 96.0%, 98.4% and 100%, respectively. The tested derivatives 15-19 and 20-23 were less active against Syphacia obvelata in vivo than albendazole and exhibited the same efficacy as piperazine, but in twice lower concentration.Compounds 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-1H-benzimidazole 21, 1,4-bis[(5(6)-methyl-1(H)-benzimidazol-2-ylthio)acetyl]piperazine 17 and 2-({2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxoethyl}thio)-5(6)-methyl-1(H)-benzimidazole 23 had higher efficacies of 73%, 76%, and 77%, respectively.

Evaluation of some plants used in Turkish folk medicine against parasitic infections for their in vivo anthelmintic activity.

Ethanolic and aqueous extracts obtained from nine plant species from seven families selected depending on their use in Turkish folk medicine, including Citrillus lanatus (Thunb.) Matsum. (seed), Jasminum fruticans L. (branches), Juniperus drupacea Labill. (fruits), Juniperus nana L. (fruit and leaves), Juniperus oxcycedrus L (fruit and leaves), Mentha longifolia L. (herba), Pinus nigra ssp. pallasiana (Lamb.) Richt. (fruits), Plantago lanceolata L. (leaves), and Zea mays L. (seed) were evaluated for their in vivo anthelmintic activity. Among the plant extracts studied, both ethanolic and aqueous extracts of Jasminum fruticans, Mentha longifolia and Pinus nigra ssp. pallasiana, the aqueous extracts of Zea mays, the ethanolic extracts of Citrillus lanatus, Juniperus drupacea (fruit), Juniperus oxcycedrus and Plantago lanceolata displayed significant anthelmintic activity against pinworms, Syphacia obvelata and Aspiculuris tetraptera, in mice. Rest of the extracts from plants did not show any remarkable anthelmintic activity. The results were considered significant at p<0.05.

Efficacy and safety of topical selamectin to eradicate pinworm (Syphacia spp.) infections in rats (Rattus norvegicus) and mice (Mus musculus).

We evaluated the efficacy and safety of topical selamectin, a novel avermectin, in eliminating naturally acquired Syphacia muris infections in rats and S. obvelata infections in mice. S. muris-positive rats were assigned randomly to 4 groups: selamectin (0.6 mg/kg), selamectin (6.0 mg/kg), fenbendazole-medicated (150 ppm) chow, and untreated. S. obvelata-positive mice were allocated into 4 groups similar to those for rats. Animals not exposed to pinworm-contaminated bedding were designated as negative controls. Treatment success was assessed weekly by anal tape impressions and by necropsy examinations at the end of week 9. Evaluations of intestinal contents at necropsy revealed that, although safe, topical selamectin was 100% ineffective in eliminating Syphacia spp. infections in rats and mice. Treatment with fenbendazole-medicated chow resulted in negative anal tape impressions beginning at week 2 in rats and week 1 in mice. Negative anal tape impressions in fenbendazole-treated animals were confirmed by negative intestinal content evaluations. Of the 2 treatments evaluated, fenbendazole-medicated chow remains an effective and practical method to eliminate pinworm infections in mice and rats.

Eradication of Syphacia muris from food-restricted rats without environmental decontamination.

Rodent pinworms rarely cause clinical disease, but infestation can affect experimental results. Our facility maintained a colony of Wistar rats for behavioral pharmacology studies that had been infested with Syphacia muris for > 15 years. The laboratory in which the animals were housed encompassed several rooms and contained a variety of complex behavioral equipment, including > 60 operant chambers. Several prior attempts to eliminate the pinworms were unsuccessful because of inadequate duration of treatment and incomplete environmental decontamination. Many of the rats in this colony were food-restricted as part of behavioral studies. Pinworms were eliminated from these animals by treating them with 450 ppm fenbendazole-containing feed for 3 consecutive weeks followed by 6 weeks of alternating every other week with standard rodent diet. Rats not on food restriction protocols were treated on the same schedule with 150 ppm fenbendazole-containing feed. Environmental decontamination of eggs from the behavioral equipment was not attempted. One year after treatment, the colony has remained free of S. muris. We adapted previously published protocols to our situation, including the problem of food-restricted rats and unfeasible environmental decontamination, to eradicate S. muris from our colony.

[Morphofunctional changes in the digestive system of the nematode Passalurus ambiguus (Rudolphi, 1819) after use of the anthelmintics albendazole, fenbendazole, and ivermectin]. / Morfofunktsional'nye izmeneniia v pishchevaritel'noi sisteme nematody Passalurus ambiguus (Rudolphi, 1819) posle primeneniia antigel'mintikov albendazola, fenbendazola i ivermektina.

The paper presents the results of histological and electron microscopic studies of the tissues of the digestive system of the nematode Passalurus ambiguus (Rudolphi, 1819) after use of the anthelminthics albendazole, fenbendazole, and ivermectine. They demonstrate that albendazole and fenbendazole cause irreversible structural changes. Less pronounced destruction of different parts of the digestive system occurs after the use of ivermectine. All the drugs affect the mid-gut of Passalurus.

The effect of doramectin, moxidectin and netobimin against natural infections of Syphacia muris in rats.

In this study, the effect of doramectin, moxidectin and netobimin was investigated in naturally infected Syphacia muris in rats. The natural infection was determined by the use of cellophane tape method on the perianal region and by the technique of centrifugal flotation of feces. The infected rats were divided into three treated and one control group (N = 10). Doramectin and moxidectin at the dose of 0.2 mg/kg per day and netobimin at the dose of 7.5 mg/kg per day were given in the diet for 4 days. Cellophane tape preparations were performed in all groups on 4th and 7th day after the last treatment. The rats of treated groups were necropsied on 7th day after the last treatment together with that of control group. While doramectin and netobimin were highly effective against S. muris, moxidectin was not found to be effective for eradication of S. muris.

Effective eradication of pinworms (Syphaciamuris, Syphacia obvelata and Aspiculuris tetraptera) from a rodent breeding colony by oral anthelmintic therapy.

An oral combination of piperazine and ivermectin was used over a 6-week period for treating three different colonies of mice or rats infested with Syphacia obvelata, Syphacia muris or Aspiculuris tetraptera. No acute toxic effect was found in transgenic lines of mice or rats with these products in a preliminary trial. The colonies were treated with piperazine, 2.1 mg/ml in tap water for 2 weeks, then with ivermectin, 0.007 mg/ml, in tap water for the third and fourth weeks, and finally with piperazine for two further weeks. Hygiene measures such as a complete cage change, thorough disinfection and cleaning of the rooms were associated with the treatment. All examinations subsequent to completion of treatment have proved negative for further parasites.

Ivermectin eradication of pinworms from rats kept in ventilated cages.

Studies using rats that were naturally infested with Syphacia muris and kept in forced-air, individually ventilated cages showed that ivermectin given orally at a dose of 2 mg/kg for three treatments at 7- or 9-day intervals was eradicative. Paired ivermectin treatments given at 7- or 9-day intervals were ineffective in eliminating parasitism. Pinworm eggs persisted on the perianal region of rats for up to 17 days and eggs were also present in soiled contact bedding within cages and on surfaces within the animal room. Anal tapes as a diagnostic test had 88% sensitivity in detecting pinworms.

Anthelmintic activity of some 3-substituted phenyl-1-alkyl or phenyl propenones and propenamides.

In a search for new anthelmintic compounds, a,beta-unsaturated ketones and amides were synthetized. Their anthelmintic activity was tested against two gastrointestinal worms, a nematode Syphacia obvelata and a cestode Hymenolepis nana. Structure-activity relationships are discussed.

Electrochemical reduction of arylethenylpyridinium salts: relation to structure and anthelmintic activity.

Cyclic voltammetry data were obtained for a series of 1(1-)- and 1(2-arylethenyl)pyridinium salts. The 1(1-arylvinyl) salts exhibited more negative reduction potentials than their N-beta-styryl counterparts. Rationalizations of the reduction values are provided. Differences in reduction potentials within a series are discussed utilizing substituent constant effects. Correlations exist for the electrochemical data and anthelmintic activity.

N3-arylspiroimidazolidine-2,4-diones N3-arylspiroimidazolidine-2-thio-4-ones and 4-hydroxy derivatives. Synthesis and anthelmintic activity.

The synthesis of new N3-arylciclohexanespiroimidazolidine-2,4-diones, N3-arylciclohexanespiroimidazolidine-2-tio-4-ones and the 4-hydroxy derivatives is described and their structures discussed on the basis of I.R. and 1H-N.R.M. data. The anthelmintic activity of these compounds was tested.