Papers by Maria Mercedes LLoberas
Frontiers in Veterinary Science, 2020
The combination of synthetic anthelmintics and bioactive phytochemicals may be a pharmacological ... more The combination of synthetic anthelmintics and bioactive phytochemicals may be a pharmacological tool for improving nematode control in livestock. Carvone (R-CNE) has shown in vitro activity against gastrointestinal nematodes; however, the anthelmintic effect of bioactive phytochemicals either alone or combined with synthetic drugs has been little explored in vivo. Here, the pharmacological interaction of abamectin (ABM) and R-CNE was assessed in vitro and in vivo. The efficacy of this combination was evaluated in lambs naturally infected with resistant gastrointestinal nematodes. Additionally, the ligand and molecular docking of both molecules to P-glycoprotein (P-gp) was studied in silico. The presence of R-CNE produced a significant (p < 0.05) increase of Rho123 and ABM accumulation in the intestinal explants. After 60 min of incubation, Rho123 incubated with R-CNE had a 67 ± 21% higher concentration (p < 0.01) than when it was incubated alone. In the case of ABM, a signifi...
Experimental Parasitology, 2019
The aim of the current work was to evaluate a potential pharmacokinetic interaction between the f... more The aim of the current work was to evaluate a potential pharmacokinetic interaction between the flukicide triclabendazole (TCBZ) and the broad-spectrum benzimidazole (BZD) anthelmintic oxfendazole (OFZ) in sheep. To this end, both an in vitro assay in microsomal fractions and an in vivo trial in lambs parasitized with Haemonchus contortus resistant to OFZ and its reduced derivative fenbendazole (FBZ) were carried out. Sheep microsomal fractions were incubated together with OFZ, FBZ, TCBZ, or a combination of either FBZ and TCBZ or OFZ and TCBZ. OFZ production was significantly diminished upon coincubation of FBZ and TCBZ, whereas neither FBZ nor OFZ affected the S-oxidation of TCBZ towards its sulfoxide and sulfone metabolites. For the in vivo trial, lambs were treated with OFZ (Vermox ® oral drench at a single dose of 5 mg/kg PO), TCBZ (Fasinex ® oral drench at a single dose of 12 mg/kg PO) or both compounds at a single dose of 5 (Vermox ®) and 12 mg/kg (Fasinex ®) PO. Blood samples were taken to quantify drug and metabolite concentrations, and pharmacokinetic parameters were calculated by means of non-compartmental analysis. Results showed that the pharmacokinetic parameters of active molecules and metabolites were not significantly altered upon coadministration. The sole exception was the increase in the mean residence time (MRT) of OFZ and FBZ sulfone upon coadministration, with no significant changes in the remaining pharmacokinetic parameters. This research is a further contribution to the study of metabolic drug-drug interactions that may affect anthelmintic efficacies in ruminants.
Veterinary Parasitology, 2017
Highlights * Replacing of IVM-resistant Cooperia spp. for IVM-susceptible population is proposed ... more Highlights * Replacing of IVM-resistant Cooperia spp. for IVM-susceptible population is proposed * Low parasite refugia at the end of summer is the key for this approach * Epidemiological knowledge is crucial for the success of this process
Veterinary Parasitology: Regional Studies and Reports, 2017
The presence of anthelmintic resistance in Argentina has experienced a marked increase in cattle,... more The presence of anthelmintic resistance in Argentina has experienced a marked increase in cattle, with numerous reports showing levels of resistance of different parasite genera to different chemical groups. The aim of this study is to update comprehensively the situation of anthelmintic resistance to the different chemical groups in the most important areas of cattle production in Argentina. The study involved the determination of anthelmintic resistance in 62 cattle farms in 7 provinces using the faecal egg count reductions test. The results showed a marked increase of anthelmintic resistance compared to previous reports; the main resistant genera were Cooperia and Haemonchus to ivermectin, Ostertagia and Cooperia to ricobendazole, and Haemonchus to fenbendazole. There was also a distinct difference in clinical efficacies between subcutaneous ricobendazole and oral fenbendazole in favour of the latter, probably attributed to the administration route. Levamisole has showed high efficacy and broad antiparasitic spectrum. Anthelmintic resistance is widely and firmly established in grazing cattle production systems in the country; the diagnosis of resistance must be done in every particular farm in order to design a sustainable parasite control based on anthelmintics use.
Revista de medicina veterinaria
Experimental Parasitology, 2012
h i g h l i g h t s " The anthelmintic action depends on the ability of the active drug to reach ... more h i g h l i g h t s " The anthelmintic action depends on the ability of the active drug to reach parasites. " Ivermectin reaches the parasites from the gastrointestinal contents or from plasma. " Ivermectin concentrations were higher in the abomasal content after its ir treatment. " Drug concentrations in Haemonchus spp were higher after the ir administration of ivermectin. " This advantageous pattern of IVM profiles may be relevant against resistant parasites.
Veterinary Parasitology, 2019
Highlights Management of parasite refugia was undertaken to restore anthelmintic efficacy Rep... more Highlights Management of parasite refugia was undertaken to restore anthelmintic efficacy Replacement of a resistant Haemonchus contortus population with a susceptible one The new benzimidazole-susceptible population was introduced in summer In vivo tests confirmed the recovery of fenbendazole efficacy on Haemonchus contortus Replacement strategy checked 16 months after introduction of susceptible population
En el presente trabajo se describe un caso de septicemia en terneros de 8 -9 meses de edad, produ... more En el presente trabajo se describe un caso de septicemia en terneros de 8 -9 meses de edad, producido por Haemophilus somnus, caracterizado por síntomas de claudicación y deformación a nivel de las articulaciones, por periartritis. Uno de los animales afectados que presentó además un cuadro nervioso severo fue necropsiado, encontrándose encefalitis necrotizante multifocal supurativa, en el sistema nervioso central, periartritis, pleuritis fibrino-hemorrágica y vasculitis necrótica. Se describen las lesiones macro y microscópicas. Los síntomas locomotrices revirtieron luego del tratamiento a base de antibióticos durante tres días consecutivos.
Balcarce 2 Residencia Interna en Sanidad Animal SDVE INTA Balcarce Diplodiosis is produced after ... more Balcarce 2 Residencia Interna en Sanidad Animal SDVE INTA Balcarce Diplodiosis is produced after consumption of mycotoxin produced by the fungus Diplodia maydis. It has been diagnosed worldwide and recently in Argentina. The toxicosis produces neurological disorders, abortion and stillborns, and death in affected animals. The aim of this trial was to experimentally reproduce this poisoning in sheep. D. maydis strain isolated from a natural poisoning outbreak was cultivated in potato-agar during 30 days at 30ºC in darkness to produce a masive spore grown. Then, it was cultivated in bottles with sterilized corn, at 28ºC in darkness during 7 weeks until administration to estimulate the production of toxin. Four female adult Frison and Texel sheep were placed in boxes with water and forage hay ad libitum. Clinical signs were observed 3 times a day during the trial. Two sheep were dosed with 9 doses of 3.3g/Kg of live weight at day 0, 1, 2, 15, 16, 17, 30, 31 y 32 using esophageal sonde....
On February of 1997, 47 red Aberdeen Angus female weaned calves were introduced in a pasture of b... more On February of 1997, 47 red Aberdeen Angus female weaned calves were introduced in a pasture of broomcorn millet (Panicum miliaceum L.) where 37 heifers were grazing. After 15 days, 100% calves showed photosensitization signs and 3 died (6%). Tissue samples were taken for histopathological analysis of one affected animal which was necropsied after euthanasia. Serum samples were taken of 3 affected calves. Also pasture samples were taken to determine the presence of Pithomyces chartarum spores. The clinical sings observed were intense pruritus, search of shadow places and lesions on unpigmented skin as well as exposed skin (necrosis and peels off leaving large raw areas). The heifers were not affected. At necropsy were observed generalized jaundice in vulvar, ocular and oral mucosal and subcutaneous tissue. Also was observed dermatitis of epithelium of mouth, neck, ears and teats. In liver was observed ocher-colored multifocal spots. During the histopathological analysis of tissues o...
Revista de medicina veterinaria
HISTORIA DEL CASO: Este trabajo describe un episodio de fotosensibilización y muerte en un establ... more HISTORIA DEL CASO: Este trabajo describe un episodio de fotosensibilización y muerte en un establecimiento de Tres Arroyos, provincia de Buenos Aires, en un lote de 47 terneras Aberdeen Angus colorado y vaquillonas pastoreando mijo (Panicum miliaceum L.). HALLAZGOS CLÍNICOS: El cuadro clínico se caracterizó por intenso prurito, búsqueda de sombra y lesiones dérmicas localizadas principalmente en áreas despigmentadas o con escasa cubierta pilosa. Los hallazgos de necropsia en un animal afectado consistían en ictericia generalizada, especialmente en las mucosas vulvar, ocular y oral. DIAGNÓSTICO: Al análisis histopatológico se observó colangiohepatitis con proliferación de conductos biliares, fibrosis periportal, degeneración grasa y necrosis de hepatocitos. La actividad de las enzimas hepáticas se encontró elevada en los 4 animales muestreados. RELEVANCIA CLÍNICA: Dado que esta forrajera pueda afectar a los teneros jóvenes con cuadros como el mencionado, se recomienda tener en cuenta este tipo de cuadros cuando se emplee dentro de los sistemas de producción bovina.
Journal of Veterinary Pharmacology and Therapeutics, 2014
Closantel (CLS) is currently used in programs for the strategic control of gastrointestinal nemat... more Closantel (CLS) is currently used in programs for the strategic control of gastrointestinal nematodes. CLS is extralabel used in different dairy goat production systems. From available data in dairy cows, it can be concluded that residues of CLS persist in milk. The current work evaluated the concentration profiles of CLS in plasma and milk from lactating orally treated dairy goats to assess the residues pattern in dairy products such as cheese and ricotta. Six (6) female Saanen dairy goats were treated orally with CLS administered at 10 mg/kg. Blood and milk samples were collected between 0 and 36 days post-treatment. The whole milk production was collected at 1, 4, 7, and 10 days post-treatment to produce soft cheese and ricotta. CLS concentrations in plasma, milk, cheese, whey, and ricotta were determined by HPLC. The concentrations of CLS measured in plasma were higher than those measured in milk at all sampling times. However, the calculated withdrawal time for CLS in milk was between 39 and 43 days postadministration to dairy goats. CLS residual concentrations in cheese (between 0.93 and 1.8 μg/g) were higher than those measured in the milk used for its production. CLS concentrations in ricotta were sixfold higher than those in the milk and 20-fold higher than those in the whey used for its production. The persistent and high residual concentrations of CLS in the milk and in the cheese and ricotta should be seriously considered before issuing any recommendation on the extralabel use of CLS in dairy goat farms.
International Journal for Parasitology: Drugs and Drug Resistance, 2013
The high level of resistance to the macrocyclic lactones has encouraged the search for strategies... more The high level of resistance to the macrocyclic lactones has encouraged the search for strategies to optimize their potential as antiparasitic agents. There is a need for pharmaco-parasitological studies addressing the kinetic-dynamic differences between various macrocyclic lactones under standardized in vivo conditions. The current work evaluated the relationship among systemic drug exposure, target tissue availabilities and the pattern of drug accumulation within resistant Haemonchus contortus for moxidectin, abamectin and ivermectin. Drug concentrations in plasma, target tissues and parasites were measured by high performance liquid chromatography. Additionally, the efficacy of the three molecules was evaluated in lambs infected with resistant nematodes by classical parasitological methods. Furthermore, the comparative determination of the level of expression of P-glycoprotein (P-gp2) in H. contortus recovered from lambs treated with each drug was performed by real time PCR. A longer persistence of moxidectin (P < 0.05) concentrations in plasma was observed. The concentrations of the three compounds in the mucosal tissue and digestive contents were significant higher than those measured in plasma. Drug concentrations were in a range between 452 ng/g (0.5 day post-treatment) and 32 ng/g (2 days post-treatment) in the gastrointestinal (GI) contents (abomasal and intestinal). Concentrations of the three compounds in H. contortus were in a similar range to those observed in the abomasal contents (positive correlation P = 0.0002). Lower moxidectin concentrations were recovered within adult H. contortus compared to abamectin and ivermectin at day 2 post-treatment. However, the efficacy against H. contortus was 20.1% (ivermectin), 39.7% (abamectin) and 89.6% (moxidectin). Only the ivermectin treatment induced an enhancement on the expression of P-gp2 in the recovered adult H. contortus, reaching higher values at 12 and 24 h post-administration compared to control (untreated) worms. This comparative pharmacological evaluation of three of the most used macrocyclic lactones compounds provides new insights into the action of these drugs. Ó
Veterinary Parasitology, 2010
The in vivo co-administration of ivermectin (IVM) with P-glycoprotein (P-gp) modulator agents has... more The in vivo co-administration of ivermectin (IVM) with P-glycoprotein (P-gp) modulator agents has been shown to enhance its systemic availability. However, there is no sufficient evidence on the impact that this type of drug-drug interaction may have on the in vivo efficacy against resistant nematodes in ruminant species. The current work reports on the effects of loperamide (LPM), a P-gp modulating agent, on both IVM kinetic behaviour and anthelmintic activity in infected lambs. Eighteen (18) lambs naturally infected with IVM-resistant gastrointestinal nematodes were allocated into three (3) experimental groups. Group A remained as untreated control. Animals in Groups B and C received IVM (200mug/kg, subcutaneously) either alone or co-administered with LPM (0.2 mg/kg, twice every 12h), respectively. Individual faecal samples were collected from experimental animals at days -1 and 14 post-treatment to perform the faecal eggs count reduction test (FECRT). Blood samples were collected between 0 and 14 days post-treatment and IVM plasma concentrations were determined by HPLC. Additionally, at day 14 post-treatment, lambs from all experimental groups were sacrificed and adult gastrointestinal nematode counts were performed. FECRT values increased from 78.6 (IVM alone) to 96% (IVM+LPM). Haemonchus contortus was highly resistant to IVM. The IVM alone treatment was completely ineffective (0% efficacy) against adult H. contortus. This efficacy value increased up to 72.5% in the presence of LPM. The efficacy against Trichostrongylus colubriformis increased from 77.9% (IVM alone) to 96.3% (IVM+LPM). The described favorable tendency towards improved anthelmintic efficacy was in agreement with the enhanced IVM plasma availability (P&lt;0.05) and prolonged elimination half-life (P&lt;0.05) induced by LPM in infected lambs. A LPM-induced P-gp modulation increases IVM systemic exposure in the host but also it may reduce P-gp efflux transport over-expressed in target resistant nematodes.
Journal of Allergy and Clinical Immunology, 1999
AIMS: To compare the pharmacokinetics, distribution and efficacy (pharmacodynamic response) of in... more AIMS: To compare the pharmacokinetics, distribution and efficacy (pharmacodynamic response) of intraruminal ivermectin (IVM) and moxidectin (MXD) administered at 0.2 and 0.4 mg/kg to naturally nematode-infected lambs, and to determine the ex vivo accumulation of these anthelmintics by Haemonchus contortus.
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Papers by Maria Mercedes LLoberas