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Survey of intestinal parasites in stray dogs in the Madrid area and comparison of the efficacy of three anthelmintics in naturally infected dogs.

Using routine coprological methods, 1161 faecal samples from animal shelters located in Madrid (Spain) were analysed, showing a 28% prevalence for different intestinal parasites: Giardia duodenalis (7%), Cystoisopora spp. (3.8%), Toxocara canis (7.8%), Toxascaris leonina (6.3%), Ancylostomidae (4%), Trichuris vulpis (3.3%), Taenidae (2.9%) and Dipylidium caninum (0.9%). The therapeutic efficacies of mebendazole at a dose of 22 mg/kg once daily for 3 days, fenbendazole at a dose of 50 mg/kg once daily for 3 days and a drug combination of febantel-pyrantel-praziquantel at a dose of 15-5-5 mg/kg once were valuated and compared by collecting faecal samples on days 9 and 16 post-treatment from naturally infected dogs in field-trial conditions. From the infected dogs (321 dogs), 150 animals were selected for the study. Distribution randomly divided the animals into three study groups of ten dogs per parasite and per treatment group: group A, mebendazole; group B, fenbendazole and group C, febantel-pyrantel-praziquantel. The therapeutic efficacy against ascarids and ancylostomids (days 9-16) was very high (75-100%) for the three groups: for T. canis, 100% in group A, 80-100% in group B, 97-100% in group C; for T. leonina, 98-100% in group A, 100% in group B, 92-94% in group C and for ancylostomids, 100% in group A, 99-100% in group B, 90-100% in group C. On the other hand, the highest efficacy against Taenidae infections was in group B (90-100%), followed by groups C (73-91%) and A (70-90%).

Animals↗

In vitro anthelmintic activity of root-tuber extract of Flemingia vestita, an indigenous plant in Shillong, India.

The in vitro activity of root-tuber-peel extract of Flemingia vestita, an indigenous plant consumed by the natives in Northeast India, was tested against helminth parasites. Live parasites (nematode: Ascaris suum from pigs, A. lumbricoides from humans, Ascaridia galli and Heterakis gallinarum from domestic fowl; cestode: Raillietina echinobothrida from domestic fowl; trematode: Paramphistomum sp. from cattle) were collected in 0.9 % physiological buffered saline (PBS) and maintained at 37 +/- 1 degrees C. In vitro treatment of the parasites with the crude extract (50 mg/ml) in PBS revealed complete immobilization of the trematode and cestode in about 43 and 20 min, respectively. However, the cuticle-covered nematodes did not show any change in physical activity and remained viable even after a long period of exposure to the extract. Exposure of R. echinobothrida to genistein (0.5 mg/ml), an active principle isolated from the root-tuber peel, caused spontaneous loss of movement (paralysis) in 4.5 h, which was slower than the time required for praziquantel, the reference flukicide and cestodicide. The treated parasites showed structural alteration in their tegumental architecture. This study suggests the vermifugal activity of this plant extract against trematodes and cestodes.

Animals↗

Effects of benzimidazole anthelmintics as microtubule-active drugs on the synthesis and transport of surface glycoconjugates in Hymenolepis microstoma, Echinostoma caproni, and Schistosoma mansoni.

Hymenolepis microstoma (Cestoda), Echinostoma caproni, and Schistosoma mansoni (Digenea) were exposed to benzimidazoles to determine the influence of the drugs on the secretion of glycoconjugates that protect the worms' surface. Worms were obtained from mice treated with mebendazole or albendazole, and the glycoconjugates were localized in the parasite tissues by cytochemistry using lectin-gold conjugates. Events leading to the death of H. microstoma and E. caproni extended over a medication period for at least 2-3 days, and the following interrelated phases were discernible. Upon depolymerization of the microtubules the tegumentary cytons continued to synthesize glycoconjugates for up to about 24 h. Vesicles containing the glycans accumulated in the cytons, but their microtubule-based transport to the distal tegument was inhibited. At about 1 day the Golgi complex became fragmented and the production of glycans sharply declined. As a consequence of this and an ongoing turnover of the surface coat the contents of glycoconjugates in the distal tegument decreased. Similar effects were produced by vinblastine and colchicine in vitro. In contrast, benzimidazole treatment of S. mansoni, which is reportedly inefficacious, did not alter the replenishment of the surface glycoconjugates. Diminution of the coating with glycoconjugates of the surface of drug-sensitive species constitutes a secondary effect of benzimidazoles that might, synergistically with immune mechanisms of the host, enhance the expulsion of the worms.

Albendazole↗

Trifluoromethanesulfonamide anthelmintics. Protonophoric uncouplers of oxidative phosphorylation.

A series of trifluoromethanesulfonamides (TFMS) was synthesized and tested for uncoupling activity in rat liver mitochondria. With succinate as the mitochondrial substrate, and the respiratory control index (RCI) as an indicator of their uncoupling ability, we found that all of the TFMS tested were uncouplers of oxidative phosphorylation; the effective concentration (RCI I50) ranged from less than 1 microM to greater than 1000 microM. Correlation techniques were used to assess the strength of the relationship between the ability of a TFMS to uncouple oxidative phosphorylation and its ability to lower the electrical resistance of planar bimolecular lipid membranes. There was a highly significant (P < 0.001) positive linear relationship (r = 0.97) between the ability of a TFMS to uncouple oxidative phosphorylation and its ability to lower electrical resistance. These findings are consistent with the view that the TFMS are lipophilic protonophoric uncouplers of mitochondrial oxidative phosphorylation. Quantitative structure-activity relationship studies using experiment and semiempirical molecular orbital theory revealed that the hydrophobicity of a TFMS and its molecular dipole moment were the principal determinants of mitochondrial uncoupling activity within the pKa range examined.

Animals↗

Haemonchus contortus: the role of two beta-tubulin gene subfamilies in the resistance to benzimidazole anthelmintics.

The role of beta-tubulin genes in benzimidazole (BZ) resistance was investigated using one susceptible (S) and two resistant (Rt and Rc) strains of Haemonchus contortus. The Rt strain was isolated from the field on the basis of thiabendazole resistance. The Rc strain was derived from the S strain by treatment with cambendazole. cDNAs, derived from the S strain, encoding two isoforms of beta-tubulin (beta 12-16 and beta 8-9), alpha-tubulin and phosphofructokinase (Pfk) were used as probes for Southern hybridization analysis of genomic DNA digested by restriction enzymes. Genomic DNA was isolated from a pool of worms or single worms. The restriction-enzyme fragment length polymorphism (RFLP) differences among these strains depended on the enzyme and the probe used. When digested with Stu I or Hpa I, and probed under stringent conditions with beta 8-9 or beta 12-16, fewer fragments were seen in the Rt and Rc strains than in the S strain. Different hybridizing fragments were found in different individuals. The frequency of individuals bearing certain fragments hybridizing to beta 12-16 or beta 8-9 in the susceptible population was reduced significantly in the resistant populations. Some differences in RFLP between these strains were observed when probed with alpha-tubulin or Pfk, but the changes were not consistent with fragments being lost from the resistant strains as observed for beta-tubulin probes. These changes in RFLP pattern correlate with changes in the binding profiles of BZs and isoelectric isoform patterns reported previously for these strains. The data confirm that reduced heterogeneity within the population is associated with BZ resistance. Our results show that both the beta 8-9 and the beta 12-16 subfamilies of beta-tubulin are affected to a similar extent by this reduction in heterogeneity in a resistant population.

Animals↗