Antifungal Activity of Menisporopsin A against Relevant Plant Pathogens.

Current agrochemicals used in crop farming mainly consist of synthetic compounds with harmful effects on the environment and human health. Crop-associated fungal endophytes, which play many ecological roles including defense against pathogens, represent a promising source for bioactive and ecologically safer molecules in agrochemical discovery. The methanolic extract of the endophyte Menisporopsis sp. LCM 1078 was evaluated in vitro against the plant pathogens Boeremia exigua, Calonectria variabilis, Colletotrichum theobromicola, Colletotrichum tropicale, and Mycena cytricolor. Bioassay-guided isolation using chromatographic techniques followed by detailed chemical characterization by NMR and mass spectrometry led to the identification of menisporopsin A, which showed inhibitory activity in a dose-dependent manner against the five fungal pathogens including an endophytic strain (Colletotrichum tropicale), with MIC values in the range of 0.63-10.0 µg/mL showing a potency equivalent to the broadly employed agrochemical mancozeb.

Unsaturated Copolyesters from Macrolactone/Norbornene: Toward Reaction Kinetics of Metathesis Copolymerization Using Ruthenium Carbene Catalysts.

Unsaturated copolyesters are of great interest in polymer science due to their broad potential applications and sustainability. Copolyesters were synthesized from the ring-opening metathesis copolymerization of ω-6-hexadecenlactone (HDL) and norbornene (NB) using ruthenium-alkylidene [Ru(Cl2)(=CHPh)(1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene)(PCy3)] (Ru1), [Ru(Cl)2(=CHPh)(PCy3)2] (Ru2), and ruthenium-vinylidene [RuCl2(=C=CH(p-C6H4CF3))(PCy3)2] (Ru3) catalysts, respectively, yielding HDL-NB copolymers with different ratios of the monomer HDL in the feed. The activity of N-heterocyclic-carbene (NHC) (Ru1) and phosphine (Ru2 and Ru3) ligands containing ruthenium-carbene catalysts were evaluated in the synthesis of copolymer HDL-NB. The catalysts Ru1 with an NHC ligand showed superior activity and stability over catalysts Ru2 and Ru3 bearing PCy3 ligands. The incorporation of the monomers in the copolymers determined by 1H-NMR spectroscopy was similar to that of the HDL-NB values in the feed. Experiments, at distinct monomer molar ratios, were carried out using the catalysts Ru1-Ru3 to determine the copolymerization reactivity constants by applying the Mayo-Lewis and Fineman-Ross methods. The copolymer distribution under equilibrium conditions was studied by the 13C NMR spectra, indicating that the copolymer HDL-NB is a gradient copolymer. The main factor determining the decrease in melting temperature is the inclusion of norbornene units, indicating that the PNB units permeate trough the HDL chains. The copolymers with different molar ratios [HDL]/[NB] have good thermal stability up to 411 °C in comparison with the homopolymer PHDL (384 °C). Further, the stress-strain measurements in tension for these copolymers depicted the appreciable increment in stress values as the NB content increases.

Macrocyclic lactone resistance in nematodes of cattle in Brazil: Blame it to the ticks!

Strategic helminth control in adult cattle would hardly impose sufficient selection pressure to parasite populations but reports of resistance against macrocyclic lactone (ML) based-products have been confirmed worldwide. The objective of this study was to evaluate the scientific literature of ML resistance (< 90.0% efficiency) in helminths of cattle from 2001 (the first report) to 2020 in Brazil. Additional to the data, we studied the correlation of parasite control practices based on a questionnaire given to 32 farmers. The search returned 246 reports and 21 full articles were selected. From these, a Wordcloud and a Keyword Co-occurrence Network graph were created. The published data revealed that most of the studies (19/21) reported multi-species (Cooperia spp., Haemonchus sp., Oesophagostomum radiatum, Trichostrongylus sp.) resistance to ML. None of the reports described the treatment frequency in the tested farms. As for the questionnaire, the majority of farmers (> 70.0%) responded that they rotate products after treatment, animals are treated monthly or biweekly (58.0%), treatments are based on visual evaluation (coat condition, ectoparasite infestation), and that in 94.0% of the times farmers treat all animals. Moreover, farmers use ML in association with potent acaricides (cypermethrin, chlorpyriphos, fluazuron) in more than 90.0% of the times (15/16). It was observed that this regimen was used to prevent and control the cattle-tick Rhipicephalus microplus (90.0%) and the horn-fly, Haematobia irritans (30.0%) infestations. We conclude that the most important factor for nematode resistance was the high level of ML exposure of up to 16 times/year, in combination with acaricides to control ticks and to a lesser extent to control horn-flies. Therefore, selection of helminth populations in cattle in Brazil can be considered secondary to ectoparasite control. The present analysis is critical, as one the most widespread recommendations to avoid drug resistance is to reduce the use of long-acting compounds, due to their extended persistent periods, increasing parasite selection. Moreover, a more serious attitude must be taken regarding parasite control strategies for livestock, reinforcing that health protocols should be based on single acaricidal products whenever possible. Complementary, selective evaluations based on transient threshold population abundance must be enforced to reduce treatment frequency, reducing parasite selection and animal distress.

Moxidectin residues in tissues of lambs submitted to three endoparasite control programs.

The indiscriminate and continuous use of anthelmintic drugs has promoted the selection of resistant parasites population, the presence of drug residues in food products, and heavy environmental contamination. The aim of the present study was to determine the presence of antiparasitic drug residues in 42-days old lamb serum and tissues, submitted to three endoparasite control programs: preventive treatment (PT) using moxidectin (MOX) at every 28days; selective treatment (FEC) using MOX when fecal egg count was greater than or equal to 700; and selective treatment (FMC), using MOX when FAMACHA/FMC score was 3 and above. For this purpose, MOX residues were quantified in serum, muscle, fat, liver and kidney. Lambs were slaughtered when reaching 30kg of body weight, and after a 28-day MOX withdrawal period. Before slaughter, blood was collected to determine the concentration of MOX in serum. Tissues and organ samples were collected at slaughter. The quantitation of MOX residues was performed using liquid chromatography tandem mass spectrometry (LC-MS/MS). From the 756 tissue samples analyzed, only one sample of fat from the PT group showed residue levels (586.3µg/kg) above the maximum residue limit (MRL) of 500µg/kg. No treated lambs presented traces of MOX residues in fat and liver, suggesting possible environmental contamination. In conclusion, all weaned lambs, produced in continuous grazing and subjected to gastrointestinal parasite control programs via selective (FEC and FMC) or preventive (PT) treatment, displayed a low risk (<1%) of MOX residues above the MRL in muscle, fat, kidney, and liver.

Ivermectina e abamectina em diferentes doses e vias de aplicação contra larvas de Cochliomyia hominivorax em bolsas escrotais de bovinos recém-castrados, provenientes da região sudeste do Brasil / Ivermectin and abamectin administered at different doses and routes against Cochliomyia hominivorax in the scrotum of newly castrated cattle from southeast region of Brazil

Avaliou-se a eficácia preventiva da ivermectina e da abamectina, administradas em diferentes vias (subcutânea, intramuscular e pour-on) e doses (200 e 500mcg kg-1), contra larvas de Cochliomyia hominivorax em bolsas escrotais de bovinos após a castração. Foram utilizados animais de seis propriedades do estado de São Paulo e Minas Gerais, Brasil. Para cada estudo, selecionou-se de 30 a 45 bovinos não castrados, dependendo do número de grupos. No dia zero do estudo, realizou-se o processo de castração pelo método cruento, sendo os animais tratados após este processo. Avaliou-se a eficácia da ivermectina e da abamectina administradas via pour-on (500mcg kg-1), subcutanea (200mcg kg-1), bem como a eficácia da abamectina pela via intramuscular (200mcg kg-1). Em cada experimento, um grupo de animais foi mantido como controle. Os animais foram avaliados do 3° ao 14° dia após o processo de castração/tratamento. Os valores de eficácia para ambos os princípios ativos foram ≤30% próximos ao 10° dia pós-tratamento (DPT), sendo que, em cinco experimentos, tanto a ivermectina quanto a abamectina, independente da via de administração, foram ineficazes (0,0%) no 10°DPT. Com base nos resultados encontrados no presente estudo, conduzidos em diferentes propriedades da região sudeste do Brasil, tanto a ivermectina quanto a abamectina, quando utilizadas com base no protocolo apresentado, foram consideradas ineficazes na prevenção de miíases escrotais em bovinos, independente da via e dose de administração utilizada.

The preventive efficacy of ivermectin and abamectin administered in different routes (subcutaneous, intramuscular and pour-on) and doses (200 and 500mcg kg-1) against Cochliomyia hominivorax in the scrotal sac of cattle after castration, was evaluated. Animals from six different farms, in the state of São Paulo and Minas Gerais, Brazil were used. For each study, 30-45 uncastrated bulls, depending on the number of groups, were selected. On day zero of the study, the procedure was carried out by the method of bloody castration and the animals were treated after this process. The efficacy of ivermectin and abamectin administered via the pour-on (500mcg kg-1), subcutaneous (200mcg kg-1) as well as the efficacy of abamectin intramuscularly (200mcg kg-1) were evaluated. In each experiment, one group of animals was kept as control. The animals were evaluated from the 3rd to the 14th day after castration process/treatment. The efficacy values for both active principles were ≤30% the next day 10 post-treatment (PT), and in five experiments, both ivermectin and abamectin, regardless of the route of administration, were ineffective (0.0%) on the day 10th PT. Based on the results found in this study, conducted in different properties from southeastern Brazil, both ivermectin and abamectin, when used the protocol presented, were considered ineffective in preventing scrotal myiasis in bulls, irrespective of the route of administration and dose used.

Ivermectina e abamectina em diferentes doses e vias de aplicação contra larvas de Cochliomyia hominivorax em bolsas escrotais de bovinos recém-castrados, provenientes da região sudeste do Brasil

The preventive efficacy of ivermectin and abamectin administered in different routes (subcutaneous, intramuscular and pour-on) and doses (200 and 500mcg kg-1) against Cochliomyia hominivorax in the scrotal sac of cattle after castration, was evaluated. Animals from six different farms, in the state of São Paulo and Minas Gerais, Brazil were used. For each study, 30-45 uncastrated bulls, depending on the number of groups, were selected. On day zero of the study, the procedure was carried out by the method of bloody castration and the animals were treated after this process. The efficacy of ivermectin and abamectin administered via the pour-on (500mcg kg-1), subcutaneous (200mcg kg-1) as well as the efficacy of abamectin intramuscularly (200mcg kg-1) were evaluated. In each experiment, one group of animals was kept as control. The animals were evaluated from the 3rd to the 14th day after castration process/treatment. The efficacy values for both active principles were 30% the next day 10 post-treatment (PT), and in five experiments, both ivermectin and abamectin, regardless of the route of administration, were ineffective (0.0%) on the day 10th PT. Based on the results found in this study, conducted in different properties from southeastern Brazil, both ivermectin and abamectin, when used the protocol presented, were considered ineffective in preventing scrotal myiasis in bulls, irrespective of the route of administration and dose used.

Avaliou-se a eficácia preventiva da ivermectina e da abamectina, administradas em diferentes vias (subcutânea, intramuscular e pour-on) e doses (200 e 500mcg kg-1), contra larvas de Cochliomyia hominivorax em bolsas escrotais de bovinos após a castração. Foram utilizados animais de seis propriedades do estado de São Paulo e Minas Gerais, Brasil. Para cada estudo, selecionou-se de 30 a 45 bovinos não castrados, dependendo do número de grupos. No dia zero do estudo, realizou-se o processo de castração pelo método cruento, sendo os animais tratados após este processo. Avaliou-se a eficácia da ivermectina e da abamectina administradas via pour-on (500mcg kg-1), subcutanea (200mcg kg-1), bem como a eficácia da abamectina pela via intramuscular (200mcg kg-1). Em cada experimento, um grupo de animais foi mantido como controle. Os animais foram avaliados do 3° ao 14° dia após o processo de castração/tratamento. Os valores de eficácia para ambos os princípios ativos foram 30% próximos ao 10° dia pós-tratamento (DPT), sendo que, em cinco experimentos, tanto a ivermectina quanto a abamectina, independente da via de administração, foram ineficazes (0,0%) no 10°DPT. Com base nos resultados encontrados no presente estudo, conduzidos em diferentes propriedades da região sudeste do Brasil, tanto a ivermectina quanto a abamectina, quando utilizadas com base no protocolo apresentado, foram consideradas ineficazes na prevenção de miíases escrotais em bovinos, independente da via e dose de administração utilizada.

Ivermectina e abamectina em diferentes doses e vias de aplicação contra larvas de Cochliomyia hominivorax em bolsas escrotais de bovinos recém-castrados, provenientes da região sudeste do Brasil

The preventive efficacy of ivermectin and abamectin administered in different routes (subcutaneous, intramuscular and pour-on) and doses (200 and 500mcg kg-1) against Cochliomyia hominivorax in the scrotal sac of cattle after castration, was evaluated. Animals from six different farms, in the state of São Paulo and Minas Gerais, Brazil were used. For each study, 30-45 uncastrated bulls, depending on the number of groups, were selected. On day zero of the study, the procedure was carried out by the method of bloody castration and the animals were treated after this process. The efficacy of ivermectin and abamectin administered via the pour-on (500mcg kg-1), subcutaneous (200mcg kg-1) as well as the efficacy of abamectin intramuscularly (200mcg kg-1) were evaluated. In each experiment, one group of animals was kept as control. The animals were evaluated from the 3rd to the 14th day after castration process/treatment. The efficacy values for both active principles were 30% the next day 10 post-treatment (PT), and in five experiments, both ivermectin and abamectin, regardless of the route of administration, were ineffective (0.0%) on the day 10th PT. Based on the results found in this study, conducted in different properties from southeastern Brazil, both ivermectin and abamectin, when used the protocol presented, were considered ineffective in preventing scrotal myiasis in bulls, irrespective of the route of administration and dose used.

Avaliou-se a eficácia preventiva da ivermectina e da abamectina, administradas em diferentes vias (subcutânea, intramuscular e pour-on) e doses (200 e 500mcg kg-1), contra larvas de Cochliomyia hominivorax em bolsas escrotais de bovinos após a castração. Foram utilizados animais de seis propriedades do estado de São Paulo e Minas Gerais, Brasil. Para cada estudo, selecionou-se de 30 a 45 bovinos não castrados, dependendo do número de grupos. No dia zero do estudo, realizou-se o processo de castração pelo método cruento, sendo os animais tratados após este processo. Avaliou-se a eficácia da ivermectina e da abamectina administradas via pour-on (500mcg kg-1), subcutanea (200mcg kg-1), bem como a eficácia da abamectina pela via intramuscular (200mcg kg-1). Em cada experimento, um grupo de animais foi mantido como controle. Os animais foram avaliados do 3° ao 14° dia após o processo de castração/tratamento. Os valores de eficácia para ambos os princípios ativos foram 30% próximos ao 10° dia pós-tratamento (DPT), sendo que, em cinco experimentos, tanto a ivermectina quanto a abamectina, independente da via de administração, foram ineficazes (0,0%) no 10°DPT. Com base nos resultados encontrados no presente estudo, conduzidos em diferentes propriedades da região sudeste do Brasil, tanto a ivermectina quanto a abamectina, quando utilizadas com base no protocolo apresentado, foram consideradas ineficazes na prevenção de miíases escrotais em bovinos, independente da via e dose de administração utilizada.

Ação anti-helmíntica de diferentes formulações de lactonas macrocíclicas em cepas resistentes de nematódeos de bovinos / Anthelmintic action of different formulations of macrocyclic lactones on resistant strains of nematodes of cattle

As lactonas macrocíclicas (LMs) (avermectinas e milbemicinas) são endectocidas amplamente utilizados em animais e em algumas parasitoses humanas. Em bovinos, a resistência parasitária às LMs é emergente, e o surgimento de formulações que diferem nas suas propriedades farmacológicas tornou complexa a escolha da droga mais indicada a cada caso. Com o objetivo de avaliar possíveis alternativas para recuperar a eficácia de LMs sobre cepas resistentes de nematódeos gastrintestinais, testaram-se, neste estudo, dez diferentes tratamentos a base de LMs sobre uma população de nematódeos gastrintestinais de bovinos a qual, sabidamente, sofrera pressão de seleção por avermectinas a 1 por cento. Adicionalmente, testou-se um benzimidazol. A eficácia das drogas foi calculada com base na redução de ovos por grama de fezes (OPG) dos bovinos. A resistência de cada gênero foi avaliada por meio de identificação de larvas, obtidas de cultivos nas fezes, pré- e pós-tratamentos. Não se obteve a eficácia desejada com o emprego de avermectinas de longa ação - com alta concentração e em associação - ou mesmo, com a aplicação de superdoses. Os gêneros Cooperia spp., Haemonchus spp. e Trichostrongylus spp. foram resistentes às avermectinas, e Ostertagia spp. à ivermectina. Observou-se que, uma vez estabelecida a resistência parasitária a LMs a 1 por cento, a aplicação de fármacos, deste mesmo grupo químico, ainda que em formulações mais concentradas, asso-ciações ou superdoses, pode não resultar na eficácia esperada.

The macrocyclic lactones (MLs) (avermectins and milbemycins) are endectocides broadly used in livestock and in some parasitic diseases of humans. In cattle, parasite resistance to MLs is emerging, and the appearance of formulations that differ in their pharmacological properties become complex the choice of the most appropriate drug to each case. In order to evaluate possible alternatives to restore the effectiveness of MLs on resistant strains of gastrointestinal nematodes, were tested, in this study, ten different treatments based on the MLs on a population of gastrointestinal nematodes of cattle which, known, was under pressure of selection by 1 percent avermectins. Additionally, was tested a benzimidazole. The efficacy of the drugs was calculated with basis on the reduction of eggs per gram of feces (EPG) of cattle. The resistance of each genus was evaluated by identification of the larvae, obtained from culture in the feces, pre- and post-treatments. The desired efficacy was not obtained using long action avermectins - with high concentration and in association - even with the application of high doses. The genera Cooperia spp., Haemonchus spp. and Trichostrongylus spp. were resistant to avermectins, and Ostertagia spp. to ivermectin. It was observed that, once established parasite resistance to the 1 percent MLs, the application of drugs, of this same chemical group, even in formulations of high concentration, association or in high doses, may not result in the expected efficacy.

Ação anti-helmíntica de diferentes formulações de lactonas macrocíclicas em cepas resistentes de nematódeos de bovinos / Anthelmintic action of different formulations of macrocyclic lactones on resistant strains of nematodes of cattle

As lactonas macrocíclicas (LMs) (avermectinas e milbemicinas) são endectocidas amplamente utilizados em animais e em algumas parasitoses humanas. Em bovinos, a resistência parasitária às LMs é emergente, e o surgimento de formulações que diferem nas suas propriedades farmacológicas tornou complexa a escolha da droga mais indicada a cada caso. Com o objetivo de avaliar possíveis alternativas para recuperar a eficácia de LMs sobre cepas resistentes de nematódeos gastrintestinais, testaram-se, neste estudo, dez diferentes tratamentos a base de LMs sobre uma população de nematódeos gastrintestinais de bovinos a qual, sabidamente, sofrera pressão de seleção por avermectinas a 1 por cento. Adicionalmente, testou-se um benzimidazol. A eficácia das drogas foi calculada com base na redução de ovos por grama de fezes (OPG) dos bovinos. A resistência de cada gênero foi avaliada por meio de identificação de larvas, obtidas de cultivos nas fezes, pré- e pós-tratamentos. Não se obteve a eficácia desejada com o emprego de avermectinas de longa ação - com alta concentração e em associação - ou mesmo, com a aplicação de superdoses. Os gêneros Cooperia spp., Haemonchus spp. e Trichostrongylus spp. foram resistentes às avermectinas, e Ostertagia spp. à ivermectina. Observou-se que, uma vez estabelecida a resistência parasitária a LMs a 1 por cento, a aplicação de fármacos, deste mesmo grupo químico, ainda que em formulações mais concentradas, asso-ciações ou superdoses, pode não resultar na eficácia esperada.(AU)

The macrocyclic lactones (MLs) (avermectins and milbemycins) are endectocides broadly used in livestock and in some parasitic diseases of humans. In cattle, parasite resistance to MLs is emerging, and the appearance of formulations that differ in their pharmacological properties become complex the choice of the most appropriate drug to each case. In order to evaluate possible alternatives to restore the effectiveness of MLs on resistant strains of gastrointestinal nematodes, were tested, in this study, ten different treatments based on the MLs on a population of gastrointestinal nematodes of cattle which, known, was under pressure of selection by 1 percent avermectins. Additionally, was tested a benzimidazole. The efficacy of the drugs was calculated with basis on the reduction of eggs per gram of feces (EPG) of cattle. The resistance of each genus was evaluated by identification of the larvae, obtained from culture in the feces, pre- and post-treatments. The desired efficacy was not obtained using long action avermectins - with high concentration and in association - even with the application of high doses. The genera Cooperia spp., Haemonchus spp. and Trichostrongylus spp. were resistant to avermectins, and Ostertagia spp. to ivermectin. It was observed that, once established parasite resistance to the 1 percent MLs, the application of drugs, of this same chemical group, even in formulations of high concentration, association or in high doses, may not result in the expected efficacy.(AU)