Abstract:
: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.
journal_name
Int J Parasitol Drugs Drug Resistauthors
Lloberas M,Alvarez L,Entrocasso C,Virkel G,Ballent M,Mate L,Lanusse C,Lifschitz Adoi
10.1016/j.ijpddr.2012.11.001subject
Has Abstractpub_date
2012-12-03 00:00:00pages
20-7issn
2211-3207pii
S2211-3207(12)00033-4journal_volume
3pub_type
杂志文章abstract::Neglected tropical diseases are of growing worldwide concern and schistosomiasis, caused by parasitic flatworms, continues to be a major threat with more than 200 million people requiring preventive treatment. As praziquantel (PZQ) remains the treatment of choice, an urgent need for alternative treatments motivates re...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.05.002
更新日期:2020-08-01 00:00:00
abstract::Haemonchus contortus is a critical parasite of goats and sheep. Infection by this blood-feeding gastrointestinal nematode (GIN) parasite has significant health consequences, especially in lambs and kids. The parasite has developed resistance to virtually all known classes of small molecule anthelmintics used to treat ...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.11.004
更新日期:2020-12-01 00:00:00
abstract::We examined faecal egg count reduction tests (FECRTs) conducted with hookworm-infected humans in Ghana in 2007 (study 1) and 2010 (study 2) in order to explore aspects of the test analysis. Some subjects showed increased FEC following drug treatment. This occurred mostly in <150 epg pre-treatment FEC subjects. We soug...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.01.001
更新日期:2014-01-31 00:00:00
abstract::The effect of Camellia sinensis (green tea) on the growth of Acanthamoeba castellanii trophozoites was examined using a microplate based-Sulforhodamine B (SRB) assay. C. sinensis hot and cold brews at 75% and 100% concentrations significantly inhibited the growth of trophozoites. We also examined the structural altera...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.05.001
更新日期:2020-08-01 00:00:00
abstract::Cryptosporidium and Toxoplasma are parasites that have caused problems worldwide. Cryptosporidium causes severe watery diarrhoea and may be fatal in immunocompromised patients and in infants. Nitazoxanide is the only agent currently approved by the FDA, but its efficacy is limited. Toxoplasmosis is also a problem in t...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.10.004
更新日期:2020-12-01 00:00:00
abstract::Nematode cys-loop ligand-gated ion channels (LGICs) have been shown to be attractive targets for the development of novel anti-parasitic drugs. The ACC-1 family of receptors are a unique group of acetylcholine-gated chloride channels present only in invertebrates, and sequence analysis suggests that they contain a nov...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.09.004
更新日期:2018-12-01 00:00:00
abstract:OBJECTIVES:This study evaluated the implications of clinically acquired miltefosine resistance (MIL-R) by assessing virulence in mice and sand flies to reveal the potential of MIL-R strains to circulate. METHODS:Experimental infections with the MIL-R clinical Leishmania infantum isolate MHOM/FR/2005/LEM5159, having a ...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.04.004
更新日期:2020-08-01 00:00:00
abstract::Infections with parasitic nematodes are among the most significant of the neglected tropical diseases affecting about a billion people living mainly in tropical regions with low economic activity. The most effective current strategy to control nematode infections involves large scale treatment programs with anthelmint...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2019.04.001
更新日期:2019-08-01 00:00:00
abstract::Histone deacetylase (HDAC) enzymes work together with histone acetyltransferases (HATs) to reversibly acetylate both histone and non-histone proteins. As a result, these enzymes are involved in regulating chromatin structure and gene expression as well as other important cellular processes. HDACs are validated drug ta...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2015.05.004
更新日期:2015-06-20 00:00:00
abstract::Malaria, schistosomiasis and leishmaniases are among the most prevalent tropical parasitic diseases and each requires new innovative treatments. Targeting essential parasite pathways, such as those that regulate gene expression and cell cycle progression, is a key strategy for discovering new drug leads. In this study...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2016.12.005
更新日期:2017-04-01 00:00:00
abstract::Leishmania panamensis is a relevant causative agent of tegumentary leishmaniasis in several Latin American countries. Available antileishmanial drugs have several limitations including relatively high toxicity, difficult administration, high production costs and the emergence of resistance in circulating strains. Ther...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.08.002
更新日期:2020-12-01 00:00:00
abstract::Dirofilaria immitis is a filarial nematode causing infection and heartworm disease in dogs and other canids, cats, and occasionally in humans. Prevention with macrocyclic lactones (ML) is recommended during the mosquito transmission season. Recently, ML resistance has been reported. ABC-B transporter genes are thought...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2016.04.001
更新日期:2016-08-01 00:00:00
abstract::Toxoplasma gondii, an obligate intracellular protozoan, is the causative agent of toxoplasmosis, which can cause serious public health problems. The current drugs used to treat toxoplasmosis have many limitations. This study evaluated the anti-T. gondii activity and potential mechanism of Licochalcone A (Lico A) in vi...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.02.006
更新日期:2018-08-01 00:00:00
abstract::The control of parasitic nematodes impacting animal health relies on the use of broad spectrum anthelmintics. However, intensive use of these drugs has led to the selection of resistant parasites in livestock industry. In that respect, there is currently an urgent need for novel compounds able to control resistant par...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.11.003
更新日期:2018-12-01 00:00:00
abstract::The need for new antimalarials is persistent due to the emergence of drug resistant parasites. Here we aim to identify new drug targets in Plasmodium falciparum by phylogenomics among the Plasmodium spp. and comparative genomics to Homo sapiens. The proposed target discovery pipeline is largely independent of experime...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2012.07.002
更新日期:2012-07-17 00:00:00
abstract::The Coenzyme A (CoA), as a cofactor involved in >100 metabolic reactions, is essential to the basic biochemistry of life. Here, we investigated the CoA biosynthetic pathway of Entamoeba histolytica (E. histolytica), an enteric protozoan parasite responsible for human amebiasis. We identified four key enzymes involved ...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.02.004
更新日期:2018-04-01 00:00:00
abstract::Anthelmintic resistance has emerged as an important problem in animal industries. Understanding resistance mechanisms, especially against macrocyclic lactones (MLs), is the first step in developing better diagnostic tools. Effects of several MLs including ivermectins and milbemycins were tested using two well establis...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2013.04.002
更新日期:2013-05-24 00:00:00
abstract::Anthelmintic resistant gastrointestinal helminths have become a major cause of poor health in sheep and goats. Sensitive and specific molecular markers are needed to monitor the genotypic frequency of resistance in field parasite populations. Gastrointestinal nematode resistance to benzimidazole is caused by a mutatio...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2019.08.003
更新日期:2019-08-01 00:00:00
abstract::Schistosomiasis is a neglected tropical disease caused by blood-dwelling flukes of the genus Schistosoma. While the disease may affect as many as 249 million people, treatment largely relies on a single drug, praziquantel. The near exclusive use of this drug for such a prevalent disease has led to concerns regarding t...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.09.006
更新日期:2014-09-26 00:00:00
abstract::The apicomplexan parasite Sarcocystis neurona is the primary etiologic agent of equine protozoal myeloencephalitis (EPM), a serious neurologic disease of horses. Many horses in the U.S. are at risk of developing EPM; approximately 50% of all horses in the U.S. have been exposed to S. neurona and treatments for EPM are...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.02.002
更新日期:2018-04-01 00:00:00
abstract::Soil-transmitted helminths cause more than 1 billion human infections globally, mostly in the poorest regions of the world. Control relies essentially on a limited panel of four drugs, and drug resistance might be inescapable. Nitazoxanide, an anti-infective drug, has been shown to exert anthelmintic activity in human...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2012.02.004
更新日期:2012-03-10 00:00:00
abstract::Millions of people are treated with anthelmintics to control soil-transmitted helminth infections; yet, drug distribution in the plasma and gastrointestinal tract compartments and the pathway of drug uptake into gastrointestinal nematodes responsible for the pharmacological effect are unknown. We assessed the distribu...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2017.03.005
更新日期:2017-08-01 00:00:00
abstract::Macrocyclic lactone (ML) anthelmintics are the most important class of anthelmintics because of our high dependence on them for the control of nematode parasites and some ectoparasites in livestock, companion animals and in humans. However, resistance to MLs is of increasing concern. Resistance is commonplace througho...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章,评审
doi:10.1016/j.ijpddr.2019.06.002
更新日期:2019-08-01 00:00:00
abstract::Drug resistance is a problem wherever livestock are raised under intensive conditions and drugs are used to combat parasitic infections. This is particularly true for the anticoccidial agents used for the prevention of coccidiosis caused by protozoa of the apicomplexan genus Eimeria in poultry. Resistance has been doc...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.10.002
更新日期:2014-10-25 00:00:00
abstract::It is recognized that the clinical efficacy of single dose benzimidazoles (BZs) against the nematode, Trichuris suis of pigs and the closely related Trichuris trichiura in humans is only poor to moderate. Recent in vitro studies have indicated that a low uptake of fenbendazole (FBZ) in T. suis may be responsible for i...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2014.03.003
更新日期:2014-04-08 00:00:00
abstract::Toxoplasma gondii and Cryptosporidium parvum are protozoan parasites that are highly prevalent and opportunistically infect humans worldwide, but for which completely effective and safe medications are lacking. Herein, we synthesized a series of novel small molecules bearing the diacyl urea scaffold and related struct...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.08.006
更新日期:2020-12-01 00:00:00
abstract::The major human soil-transmitted helminths (STH), Ascaris lumbricoides, hookworms (Necator americanus and Ancylostoma duodenale) and Trichuris trichiura have a marked impact on human health in many parts of the world. Current efforts to control these parasites rely predominantly on periodic mass administration of anth...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章,评审
doi:10.1016/j.ijpddr.2011.09.002
更新日期:2011-10-14 00:00:00
abstract::Acanthamoeba castellanii is a free-living protozoan pathogen capable of causing a blinding keratitis and fatal granulomatous encephalitis. Current treatment generally involves an hourly application of polyhexamethylene biguanide (PHMB) over a period of several days but this is not entirely effective against all strain...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2016.11.001
更新日期:2016-12-01 00:00:00
abstract::Clinical studies suggest that outcomes for hospitalised malaria patients can be improved by managed hypothermia during treatment. We examined the impact of short pulses of low temperature on ring-stage susceptibility of Plasmodium falciparum to artemisinin in vitro. The usually artemisinin-sensitive clone 3D7 exhibite...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2018.12.003
更新日期:2019-04-01 00:00:00
abstract::Toxicity and poor adherence to treatment that favors the generation of resistance in the Leishmania parasites highlight the need to develop better alternatives. Here, we evaluated the in vitro effectiveness of hydrazone derived from chromanes 2-(2,3-dihydro-4H-1-benzothiopyran-4-ylidene) hydrazide (TC1) and 2-(2,3-dih...
journal_title:International journal for parasitology. Drugs and drug resistance
pub_type: 杂志文章
doi:10.1016/j.ijpddr.2020.06.004
更新日期:2020-08-01 00:00:00