Tests to determine LC50 and discriminating doses for macrocyclic lactones against the cattle tick, Boophilus microplus

Laboratory tests were carried out on larvae and adults of the cattle tick Boophilus microplus to determine the toxicity of macrocyclic lactone acaricides (MLs). Technical and commercial MLs were used in larval packet test (LPT), larval immersion test (LIT) and adult immersion test (AIT). Tn LIT and AIT the toxicity of MLs was much higher than for LPT. In the AIT, diluting the injectable formulation of MLs in water was as effective as dilution in ethanol + Triton X-100. LC50, LC99.9 and 95% confidence limits were determined so that a discriminating dose (DD) could be set for larval and adult tests in order to diagnose potential resistance to MLs in field samples of the tick. These DDs are for Australian strains of B. microplus and may not be suitable for other strains until further work is carried out.The value of these diagnostic tests can only be verified if or when resistance to MLs emerges in ticks. (C) 2001 Elsevier B.V. B.V. All rights reserved.

Effects of macrocyclic lactones on the reproductive parameters of engorged Rhipicephalus (Boophilus) microplus females detached from experimentally infested cattle

The present study therefore assessed the deleterious effects of MLs (ivermectin, abamectin, doramectin and moxidectin) on the reproductive parameters of engorged Rhipicephalus (Boophilus) microplus females that naturally detached from experimentally infested cattle in two experiments. The following reproductive parameters of engorged female ticks were analyzed: female weight, egg mass weight, percentage of hatchability, percentage of reduction in oviposition, percentage of reduction in hatchability, reproductive efficiency and percent control/efficacy of formulations with respect to reproductive parameters. In the experiment I, statistical analysis of the data grouped into 5-days intervals revealed that pour-on application of abamectin (500. mcg/kg) had significantly (p≤. 0.05) reduced engorged female weight, egg mass weight and percent hatchability on days 6-15, 6-20 and 11-20 post-treatment (p. t.) compared to the respective data for detached and pre-selected engorged females in the control group. The abamectin, demonstrated 33.41% of reduction in oviposition, 6.77% in hatchability and abamectin efficacy was of 13.99%. In the experiment II, statistically significant reductions (p≥. 0.05) were observed in animals treated subcutaneous with ivermectin (630. mcg/kg), doramectin (700. mcg/kg) and moxidectin (1000. mcg/kg) relative to the control for days 6-40, 6-48 and 6-40 p. t., respectively. Ivermectin reduced hatchability only on days 16-20 p. t., whereas doramectin significantly reduced (p≤. 0.05) hatchability on days 6-10 and 16-35 p. t. For moxidectin, deleterious effects on hatchability were observed on days 16-35 p. t. The percent reductions in oviposition of engorged female ticks were 46.31%, 62.17% and 61.02% with ivermectin, doramectin and moxidectin treatments, respectively. The percent efficacy of the formulations on the reproductive parameters of engorged female ticks was 21.22% for ivermectin, 36.03% for doramectin and 35.45% for moxidectin. Among the MLs assessed, doramectin and moxidectin had the highest acaricidal efficacies and the most deleterious effects on the reproductive parameters of engorged R. (B.) microplus females. However, future studies will be necessary to assess the extent to which these effects, along with acaricidal activity, can be used to control the ectoparasite in cattle. © 2013 Elsevier Inc..

Dermatobia hominis: potencial risk of resistance to macrocyclic lactones

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Host-guest system of 4-nerolidylcatechol in 2-hydroxypropyl-beta-cyclodextrin: preparation, characterization and molecular modeling

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Computational analysis and physico-chemical characterization of an inclusion compound between praziquantel and methyl-beta-cyclodextrin for use as an alternative in the treatment of schistosomiasis

Schistosomiasis is still an endemic disease in many regions, with 250 million people infected with Schistosoma and about 500,000 deaths per year. Praziquantel (PZQ) is the drug of choice for schistosomiasis treatment, however it is classified as Class II in the Biopharmaceutics Classification System, as its low solubility hinders its performance in biological systems. The use of cyclodextrins is a useful tool to increase the solubility and bioavailability of drugs. The aim of this work was to prepare an inclusion compound of PZQ and methyl-beta-cyclodextrin (MeCD), perform its physico-chemical characterization, and explore its in vitro cytotoxicity. SEM showed a change of the morphological characteristics of PZQ:MeCD crystals, and IR data supported this finding, with changes after interaction with MeCD including effects on the C-H of the aromatic ring, observed at 758 cm(-1). Differential scanning calorimetry measurements revealed that complexation occurred in a 1:1 molar ratio, as evidenced by the lack of a PZQ transition temperature after inclusion into the MeCD cavity. In solution, the PZQ UV spectrum profile in the presence of MeCD was comparable to the PZQ spectrum in a hydrophobic solvent. Phase solubility diagrams showed that there was a 5.5-fold increase in PZQ solubility, and were indicative of a type A(L) isotherm, that was used to determine an association constant (K(a)) of 140.8 M(-1). No cytotoxicity of the PZQ:MeCD inclusion compound was observed in tests using 3T3 cells. The results suggest that the association of PZQ with MeCD could be a good alternative for the treatment of schistosomiasis.

Anthelmintic efficacy of oral trichlorfon solution against ivermectin resistant nematode strains in cattle

Infected calves from two different rural estates in Brazil were studied to assess the anthelmintic efficacy of oral trichlorfon against naturally occurring ivermectin resistant parasitic nematode strains. In experiment 1, infected animals were from a region where ivermectin resistant populations of Haemoncus placei, Cooperia punctata,Cooperia spatulata and Trichuris discolor have recently been identified. Six calves with natural gastrointestinal nematode infections were treated with 48.5 mg/kg aqueous trichlorfon administered orally and six calves acted as a non-treated control group. In experiment 11 24 naturally infected calves were selected to enter one of four treatment groups, six animals each received: 48.5 mg/kg oral trichlorfon; 200 mu g/kg subcutaneous 1% ivermectin; 630 mu g/kg subcutaneous 3.15% ivermectin; or no treatment (control group). Gastrointestinal helminths were counted and identified post-mortem at 7 days (trichlorfon and 1% ivermectin treated and untreated animals) or 14 days (3.15% ivermectin treated and untreated animals) after administration of the test agents. Experiment I identified a high level efficacy for oral trichlorfon against four helminth species that have previously been shown to be ivermectin resistant in this geographical region: percentage efficacy was 99.82% against adult H. placei, 99.18% against C. punctata, 99.33% against C. spatulata, 81.06% against T. axei, 98.46% against Oesophagostomum radiatum and 100% against T. discolor. Trichlorfon also showed activity against the ivermectin (1% and 3.15%) resistant helminth species identified in experiment 11, attaining efficacy levels of 99.17% against H. placei, 98.46% against C punctata and 100.00% against T. discolor. These findings indicate that oral trichlorfon is an effective treatment option in the management of cattle infected with ivermectin resistant helminths. (C) 2009 Elsevier B.V. All rights reserved.

Multiple resistance to anthelmintics by Haemonchus contortus and Trichostrongylus colubriformis in sheep in Brazil

The objective of this study was to determine the level of resistance of Haemonchus contortus and Trichostrongylus colubriformis in sheep to levamisole albendazole ivermectin moxidectin closantel and trichlorfon The parasites were isolated from sheep naturally infected by gastrointestinal nematodes and were then kept in monospecifically infected lambs for production of infective larvae (L3) of both species Forty-two lambs at three months of age were simultaneously artificially infected with 4000 L3 of H contortus and 4000 L3 of T colubriformis The animals were allocated Into seven groups with six animals each that received one of the following treatments Group 1-control no treatment Group 2-moxidectin (0 2 mg/kg body weight (BW)) Group 3-closantel (10 mg/kg BW) Group 4-trichlorfon (100 mg/kg BW) Group 5-levamisole phosphate (4 7 mg/kg BW) Group 6-albendazole (5 0 mg/kg BW) and Group 7-ivermectin (0 2 mg/kg BW) Nematode fecal egg counts (FEC) were carried out on the day of treatment and again at 3 7 10 and 14 days post-treatment on the same occasions composite fecal cultures were prepared for each group for production of L3 which were identified into genus The animals were sacrificed for worm counts at 14 days after treatment The efficacy of each treatment was calculated from the arithmetic mean of the FEC or worm burden of the treated group compared with the values of the control group Only trichlorfon and moxidectin treatments resulted in a significant reduction of H contortus recorded at necropsy (73% and 45% respectively) Moxidectin reduced T colubriformis worm burdens by 82% and albendazole by 19% All other anthelmintics resulted in no significant reduction in the numbers of worms found at necropsy In conclusion the Isolates of H contortus and T colubriformis showed multiple resistance to all groups of anthelmintics tested This is the first report based on the controlled efficacy test to show resistance of T colubriformis to macrocyclic lactones in Brazil (C) 2010 Elsevier B.V. All rights reserved

Moxidectin-resistant nematodes in cattle in Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Determination of the LC50 of selamectin (active principle of the antiparasitic Revolution (R), Pfizer) applied on engorged female of the tick Rhipicephalus sanguineus (Latreille, 1806) (Acari: Ixodidae)

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Host-guest complexation of a nitroheterocyclic compound with cyclodextrins: a spectrofluorimetric and molecular modeling study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Abamectin affects the bioenergetics of liver mitochondria: A potential mechanism of hepatotoxicity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Investigation of New Ion Conducting Ormolytes Silica-Polypropyleneglycol

Two groups of hybrid organic-inorganic composites exhibiting ionic conduction properties, so called ORMOLYTES (organically modified electrolytes), have been prepared by the sol-gel process. The first group has been prepared from mixture of a lithium salt and 3-isocyanatopropyltriethoxysilane(IsoTrEOS),O,O′-bis(2-aminopropyl) polypropyleneglycol. These materials produce chemical bonds between the organic (polymer) and the inorganic (silica) phases. The second group has been prepared by an ultrasonic method from a mixture of tetraethoxysilane (TEOS), polypropyleneglycol and a lithium salt. The organic and inorganic phases are not chemically bonded in these samples. The Li+ ionic conductivity, σ, of all these materials has been studied by AC impedance spectroscopy up to 100°C. Values of σ up to 10-6 Ω-1·cm-1 have been found at room temperature. A systematic study of the effects of lithium concentration, polymer chain length and the polymer to silica weight ratio on σ shows that there is a strong dependence of σ on the preparation conditions. The dynamic properties of the Li+ ion and the polymer chains as a function of temperature between -100 and 120°C were studied using 7Li solid-state NMR measurements. The ionic conductivity of both families are compared and particular attention is paid to the nature of the bonds between the organic and inorganic components.

Coordination of Eu3+ ions in siliceous nanohybrids containing short polyether chains and bridging urea cross-links

Infrared and photoluminescence spectroscopies have been used to investigate the local environment of the Eu3+ ions in luminescent sol-gel derived materials-di-ureasils-based on a hybrid framework represented by U(600). This host is composed of a siliceous backbone grafted, through urea cross-links, to both ends of polymer segments incorporating 8.5 oxyethylene repeat units. The active centers have been introduced as europium perchlorate, Eu(ClO4)3. Samples with compositions n = 232, 62, 23, 12, and 6 (where n denotes the ratio of (OCH2CH2) moieties per lanthanide ion) have been examined. The combination of the information retrieved from the analysis of characteristic bands of the FTIR spectra-the perchlorate and the Amide I/Amide II features-with that obtained from the photoluminescence data demonstrates that at compositions n = 232 and 62 the anions are free, whereas the Eu3+ ions are complexed by the heteroatoms of the polyether chains. At higher salt concentration, the cations are bonded, not only to the ClO4 - ions, but also to the ether oxygen atoms of the organic segments and to the carbonyl oxygen atoms of the urea linkages. The dual behavior of U(600) with respect to cation coordination has been attributed to the presence in this nanohybrid of strong hydrogen-bonded urea-urea structures, which, at low salt content, cannot be disrupted, thus inhibiting the formation of Eu3+-O=C(urea) contacts and promoting the interaction between the lanthanide ions and the (OCH2CH2) moieties. The present work substantiates the claim that the activation of the coordinating sites of the di-ureasil framework can be tuned by varying either the guest salt concentration at constant chain length or the length of the.organic segments at constant salt concentration. This relevant property opens challenging new prospects in the fields of application of this class of hybrids. © 2001 American Chemical Society.

Room temperature visible/infrared emission and energy transfer in Nd3+-based organic/inorganic hybrids

The photoluminescence features and the energy transfer processes of Nd3+-based siloxanepoly(oxyethylene) hybrids are reported. The host matrix of these materials, classed as di-ureasils, is formed by a siloxane backbone covalently bonded to polyether chains of two molecular weights by means of urea cross-links. The room-temperature photoluminescence spectra of these xerogels show a wide broad purple-blue-green band (350-570 nm), associated with the emitting centres of the di-ureasil host, and the typical near infrared emission of Nd3+ (700-1400 nm), assigned to the 4F3/2 → 4I9/2,11/2,13/2 transitions. Self-absorptions in the visible range, resonant with intra-4f3 transitions, indicate the existence of an energy conversion mechanism of visible di-ureasil emission into near infrared Nd3+ luminescence. The existence of energy transfer between the di-ureasil's emitting centres and the Nd3+ ions is demonstrated calculating the lifetimes of these emitting centres. The efficiency of that energy transfer changes both with the polymer molecular weight and the Nd3+ concentration.

Ureasil-polyether hybrid film-forming materials

The objectives of this work were to study the suitability and highlight the advantages of the use of cross-linked ureasil-polyether hybrid matrices as film-forming systems. The results revealed that ureasil-polyethers are excellent film-forming systems due to specific properties, such as their biocompatibility, their cosmetic attractiveness for being able to form thin and transparent films, their short drying time to form films and their excellent bioadhesion compared to the commercial products known as strong adhesives. Rheological measurements have demonstrated the ability of these hybrid matrices to form a film in only a few seconds and Water Vapor Transmitting Rate (WVTR) showed adequate semi-occlusive properties suggesting that these films could be used as skin and wound protectors. Both the high skin bioadhesion and non-cytotoxic character seems to be improved by the presence of multiple amine groups in the hybrid molecules. © 2012 Elsevier B.V.