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1.
Ann Parasitol ; 67(2): 243-248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34595511

RESUMO

Fasciolosis is considered as one of the leading causes of morbidity and mortality among ruminants in the Philippines. Though anthelmintic drugs are widely used to treat and control the condition, it is still worthwhile to search for alternative treatments especially when resistance to commonly used anthelmintic drugs has been reported. In this study, the ethanolic leaf extract of fringed spiderflower (Cleome rutidosperma) was evaluated for its in vitro anthelmintic activity against Fasciola spp. Specifically, the study compared the different concentrations of ethanolic leaf extract and the commonly used anthelmintic drug (albendazole) on the gross motility and histology of Fasciola spp. The study consisted of five treatments: treatment 1, 2, and 3 which contain 10%, 20%, and 40% leaf extract, respectively, treatment 4 with 10% albendazole as the positive control, and treatment 5 with nutrient broth as the negative control. The motility of the Fasciola spp in all treatments was visually analyzed based on the established criteria. In addition Fasciola spp. in different treatments were subjected to tissue processing and histological examination. Results showed that increasing concentrations of leaf extract resulted in a decreasing time for Fasciola spp. to have a motility score of zero. Specifically, 10%, 20%, and 40% leaf extract resulted in a cumulative time period of 55.00 ± 5.00 min, 26.67 ± 2.89 min, and 15.00 ± 0.00 min, respectively, for the Fasciola spp. to have a motility score of zero. On the other hand, albendazole resulted in a 240.00 min cumulative time before it can cause a motility score of zero. Histologic examination showed that the different concentrations of leaf extract affected the tegument and parenchyma of the Fasciola spp.


Assuntos
Anti-Helmínticos , Cleome , Fasciola , Fasciolíase , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Fasciolíase/tratamento farmacológico , Extratos Vegetais/farmacologia
2.
Trials ; 22(1): 601, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488846

RESUMO

BACKGROUND: Over 200 million individuals worldwide are infected with Schistosoma species, with over half of infections occurring in children. Many children experience first infections early in life and this impacts their growth and development; however praziquantel (PZQ), the drug used worldwide for the treatment of schistosomiasis, only has regulatory approval among adults and children over the age of four, although it is frequently used "off label" in endemic settings. Furthermore, pharmacokinetic/pharmacodynamics (PK/PD) evidence suggests the standard PZQ dose of 40 mg/kg is insufficient in preschool-aged children (PSAC). Our goal is to understand the best approaches to optimising the treatment of PSAC with intestinal schistosomiasis. METHODS: We will conduct a randomised, controlled phase II trial in a Schistosoma mansoni endemic region of Uganda and a Schistosoma japonicum endemic region of the Philippines. Six hundred children, 300 in each setting, aged 12-47 months with Schistosoma infection will be randomised in a 1:1:1:1 ratio to receive either (1) 40 mg/kg PZQ at baseline and placebo at 6 months, (2) 40 mg/kg PZQ at baseline and 40 mg/kg PZQ at 6 months, (3) 80 mg/kg PZQ at baseline and placebo at 6 months, or (4) 80 mg/kg PZQ at baseline and 80 mg/kg PZQ at 6 months. Following baseline treatment, children will be followed up for 12 months. The co-primary outcomes will be cure rate and egg reduction rate at 4 weeks. Secondary outcomes include drug efficacy assessed by novel antigenic endpoints at 4 weeks, actively collected adverse events and toxicity for 12 h post-treatment, morbidity and nutritional outcomes at 6 and 12 months, biomarkers of inflammation and environmental enteropathy and PZQ PK/PD parameters. DISCUSSION: The trial will provide valuable information on the safety and efficacy of the 80 mg/kg PZQ dose in PSAC, and on the impact of six-monthly versus annual treatment, in this vulnerable age group. TRIAL REGISTRATION: ClinicalTrials.gov NCT03640377 . Registered on 21 Aug 2018.


Assuntos
Anti-Helmínticos , Esquistossomose mansoni , Animais , Anti-Helmínticos/efeitos adversos , Criança , Pré-Escolar , Ensaios Clínicos Fase II como Assunto , Humanos , Praziquantel/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Schistosoma mansoni , Esquistossomose mansoni/diagnóstico , Esquistossomose mansoni/tratamento farmacológico , Resultado do Tratamento
3.
ACS Infect Dis ; 7(9): 2637-2649, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34467755

RESUMO

As the existing therapeutic modalities for the treatment of cryptococcal meningitis (CM) have suboptimal efficacy, repurposing existing drugs for the treatment of CM is of great interest. The FDA-approved anthelmintic benzimidazoles, albendazole, mebendazole, and flubendazole, have demonstrated potent but variable in vitro activity against Cryptococcus neoformans, the predominant fungal species responsible for CM. We performed molecular docking studies to ascertain the interaction of albendazole, mebendazole, and flubendazole with a C. neoformans ß-tubulin structure, which revealed differential binding interactions and explained the different in vitro efficacies reported previously and observed in this investigation. Despite their promising in vitro efficacy, the repurposing of anthelmintic benzimidazoles for oral CM therapy is significantly hampered due to their high crystallinity, poor pharmaceutical processability, low and pH-dependent solubility, and drug precipitation upon entering the intestine, all of which result in low and variable oral bioavailability. Here, we demonstrate that the anthelmintic benzimidazoles can be transformed into partially amorphous low-melting ionic liquids (ILs) with a simple metathesis reaction using amphiphilic sodium docusate as a counterion. In vitro efficacy studies on a laboratory reference and a clinical isolate of C. neoformans showed 2- to 4-fold lower IC90 values for docusate-based ILs compared to the pure anthelmintic benzimidazoles. Furthermore, using a C. neoformans strain with green fluorescent protein (GFP)-tagged ß-tubulin and albendazole and its docusate IL as model candidates, we showed that the benzimidazoles and their ILs reduce the viability of C. neoformans by interfering with its microtubule assembly. Unlike pure anthelmintic benzimidazoles, the docusate-based ILs showed excellent solubility in organic solvents and >30-fold higher solubility in bioavailability-enhancing lipid vehicles. Finally, the docusate ILs were successfully incorporated into SoluPlus, a self-assembling biodegradable polymer, which upon dilution with water formed polymeric micelles with a size of <100 nm. Thus, the development of docusate-based ILs represents an effective approach to improve the physicochemical properties and potency of anthelmintic benzimidazoles to facilitate their repurposing and preclinical development for CM therapy.


Assuntos
Anti-Helmínticos , Cryptococcus neoformans , Líquidos Iônicos , Preparações Farmacêuticas , Anti-Helmínticos/farmacologia , Benzimidazóis/farmacologia , Ácido Dioctil Sulfossuccínico , Simulação de Acoplamento Molecular , Solubilidade
4.
Parasite ; 28: 63, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468310

RESUMO

A questionnaire was distributed to 5487 farmers throughout Norway in order to obtain information about management practices regarding helminth infections in sheep. In addition, the farmers' perceptions of helminths and anthelmintic efficacy were investigated. Most farmers (80%) treated prophylactically against nematodes, and 24% also used prophylactic treatment against Fasciola hepatica. Overall, few farmers (11%) used parasitological analysis as a tool to assess the timing of treatment, but rather based it on other factors such as previous experience (70%). In the surveyed sheep flocks, the use of benzimidazoles was reduced from 2018 (52%) to 2019 (47%) (p < 0.01), whereas the use of macrocyclic lactones increased from 2017 (23%) to 2019 (36%) (p < 0.001). Poor anthelmintic efficacy was suspected by 10% of the farmers, and 11% reported that helminths were an increasing problem in their flocks. The majority of farmers (72%) considered their veterinarian as the most important advisor for treatment of parasites, but reported a high level of uncertainty regarding which parasites were present in their flocks, with unknown status most frequently reported for Haemonchus contortus (71.5%). This is probably related to the fact that very few farmers (15%) regularly test their animals for parasites. The present study provides up-to-date information on treatment practices for helminths in Norwegian sheep flocks.


Assuntos
Anti-Helmínticos , Helmintos , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Resistência a Medicamentos , Fezes , Ovinos , Doenças dos Ovinos/tratamento farmacológico , Doenças dos Ovinos/epidemiologia , Doenças dos Ovinos/prevenção & controle , Inquéritos e Questionários
5.
Parasite ; 28: 64, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34468311

RESUMO

This study evaluated the in vitro anthelmintic activity of a liquorice (Glycyrrhiza glabra) root aqueous extract and of glycyrrhetinic acid at 30, 10, 5, 1, and 0.5 mg/mL against sheep gastrointestinal nematodes (GINs), using the egg hatch test (EHT), the larval development test (LDT), and the larval migration inhibition test (LMIT). The compounds were applied on a mixture of GIN eggs and larvae, mainly Trichostrongylus spp. and Teladorsagia/Ostertagia spp. Cytotoxicity assays were also performed. In the EHT, both candidates showed significant concentration-dependent efficacy and were significantly more effective (p < 0.001) at the highest concentrations (30 and 10 mg/mL) than the lowest ones. In the LDT, only G. glabra showed a concentration-dependent effect (R2 = 0.924), but glycyrrhetinic acid (R2 = 0.910) had significantly higher efficacy than G. glabra root extract. Moreover, the efficacy of glycyrrhetinic acid at 30, 10, and 5 mg/mL was significantly higher (p < 0.001) than at lower concentrations. In the LMIT, G. glabra showed concentration-dependent efficacy (R2 = 0.971), while considerably reduced efficacy was observed for glycyrrhetinic acid (R2 = 0.855) at the lowest concentrations. These data suggest that the two compounds may have different mechanisms of action. In the LMIT, the 50% lethal concentration (LC50) of glycyrrhetinic acid (~5.12 mg/mL) was > 2.0-fold lower when compared to G. glabra (12.25 mg/mL). Analysis and previous findings indicated low toxicity for both compounds. The results obtained encourage in vivo studies aimed at evaluating the potential use of the tested compounds as natural de-wormers in ruminants.


Assuntos
Anti-Helmínticos , Ácido Glicirretínico , Glycyrrhiza , Nematoides , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Ácido Glicirretínico/farmacologia , Ácido Glicirretínico/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ruminantes , Ovinos , Doenças dos Ovinos/tratamento farmacológico
6.
Rev Peru Med Exp Salud Publica ; 38(2): 296-301, 2021.
Artigo em Espanhol, Inglês | MEDLINE | ID: mdl-34468579

RESUMO

The efficacy of two locally produced oxfendazole (OFZ) formulations against cysticercosis at 22,5% and 10%, versus a commercial formulation (Synanthic 9,06%) was evaluated in twenty-two naturally infected pigs that received a single oral dose of 30 mg/kg. Pigs were sacrificed at eight weeks post-treatment to evaluate the cysts found in their carcasses, and to determine the cysticidal efficacy, which was defined as the proportion of degenerated cysts over total cysts. Only degenerated cysts were found in muscle, heart, and tongue of pigs treated with OFZ in all groups, which shows an efficacy of 100%. Viable and degenerated cysts were found in brains, being the efficacy lower in all groups (65% [commercial OFZ], 47% [local OFZ 22.5%] and 31% [local OFZ 10%], p = 0.355). Locally produced OFZ formulations were similarly effective to the commercial formulation and may provide a practical alternative for the treatment of porcine cysticercosis.


Assuntos
Anti-Helmínticos , Cisticercose , Doenças dos Suínos , Taenia solium , Animais , Anti-Helmínticos/uso terapêutico , Benzimidazóis/uso terapêutico , Cisticercose/tratamento farmacológico , Cisticercose/veterinária , Suínos , Doenças dos Suínos/tratamento farmacológico
7.
Infect Dis Poverty ; 10(1): 116, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34507609

RESUMO

BACKGROUND: Soil-transmitted helminths (STH) infections still present a global health problem. Mass drug administration (MDA) is a widely applied strategy to reduce morbidity and mortality caused by STH. Yet, this approach has some shortcomings. In this study, we analyzed the impact of a multi-intervention integrated deworming approach including MDA, health education (HE), and environmental sanitation improvements (ESI) for sustained STH control in Jiangsu Province of China that was applied from 1989 to 2019. METHODS: Data, including infection rate of STH, medications used, coverage of the medication, non-hazardous lavatory rate, and household piped-water access rate in rural areas, and actions related to HE and ESI were collected (from archives) and analyzed in this retrospective descriptive study. Pearson's correlation analysis was applied to test correlations. RESULTS: There was a dramatic decline in the infection rate of STH from 1989 (59.32%) to 2019 (0.12%). From 1995 to 1999, MDA and HE were recommended in rural areas. A negative correlation was observed between infection rate and medication from 1994 to 1998 (r = - 0.882, P = 0.048). From 2000 to 2005, targeted MDA was given to high-risk populations with HE continuously promoting good sanitation behaviors. From 2006 to 2014, targeted MDA + HE and ESI were used to consolidate the control effect. ESI was strengthened from 2006, and a negative correlation was observed between the coverage rate of the non-hazardous lavatory and the infection rate from 2006 to 2019 (r = - 0.95, P < 0.001). The targeted MDA was interrupted in 2015, while continuous efforts like HE and ESI contributed in sustaining STH control. CONCLUSIONS: Multi-intervention integrated deworming strategy contributes to the reduction of STH infections. This approach is a valuable example of how different interventions can be integrated to promote durable STH control.


Assuntos
Anti-Helmínticos/uso terapêutico , Helmintíase/tratamento farmacológico , Helmintíase/epidemiologia , Helmintos/isolamento & purificação , Saneamento/métodos , Solo/parasitologia , Animais , China/epidemiologia , Estudos Transversais , Helmintíase/prevenção & controle , Helmintíase/transmissão , Helmintos/classificação , Humanos , Prevalência , Estudos Retrospectivos
8.
Infect Dis Poverty ; 10(1): 121, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556183

RESUMO

BACKGROUND: Zoonotic schistosomiasis, caused by Schistosoma japonicum, remains a major public health problem in the Philippines. This study aimed to evaluate the commercially available rapid diagnostic point-of-care circulating cathodic antigen (POC-CCA) test in detecting individuals infected with S. japonicum in a human cohort from an endemic area for schistosomiasis japonica in the Philippines. METHODS: Clinical samples were collectedin 18 barangays endemic for S. japonicum infection in Laoang and Palapag municipalities, Northern Samar, the Philippines, in 2015. The presence of CCA in filter-concentrated urine samples (n = 412) was evaluated using the commercial kits and the results were converted to images, which were further analyzed by ImageJ software to calculate R values. The diagnostic performance of the immunochromatographic POC-CCA test was compared using the Kato-Katz (KK) procedure, in-house enzyme-linked immunosorbent assays (ELISAs) and droplet digital (dd) PCR assays as reference. RESULTS: The POC-CCA test was able to detect S. japonicum-infected individuals in the cohort with an eggs per gram of faeces (EPG) more than or equal to 10 with sensitivity/specificity values of 63.3%/93.3%. However, the assay showed an inability to diagnose schistosomiasis japonica infections in all cohort KK-positive individuals, of which the majority had an extremely low egg burden (EPG: 1-9). The prevalence of S. japonicum infection in the total cohort determined by the POC-CCA test was 12.4%, only half of that determined by the KK method (26.2%). When compared with the ELISAs and ddPCR assays as a reference, the POC-CCA assay was further shown to be a test with low sensitivity. Nevertheless, the assay exhibited significant positive correlations with egg burden determined by the KK technique and the target gene copy number index values determined by the ddPCR assays within the entire cohort. CONCLUSIONS: By using in silico image analysis, the POC-CCA cassette test could be converted to a quantitative assay to avoid reader-variability. Because of its low sensitivity, the commercially available POC-CCA assay had limited potential for determining the status of a S. japonicum infection in the target cohort. The assay should be applied with caution in populations where schistosome parasites (especially S. japonicum) are present at low infection intensity.


Assuntos
Antígenos de Helmintos/sangue , Fezes/parasitologia , Sistemas Automatizados de Assistência Junto ao Leito , Schistosoma japonicum/isolamento & purificação , Esquistossomose Japônica/diagnóstico , Testes Sorológicos/métodos , Animais , Anti-Helmínticos/uso terapêutico , Antígenos de Helmintos/análise , Ensaio de Imunoadsorção Enzimática , Humanos , Doenças Negligenciadas/epidemiologia , Filipinas/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Schistosoma japonicum/imunologia , Esquistossomose Japônica/tratamento farmacológico , Esquistossomose Japônica/epidemiologia , Sensibilidade e Especificidade
9.
Rev Bras Parasitol Vet ; 30(3): e010921, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550213

RESUMO

The effectiveness of four anthelmintic classes on cattle gastrointestinal nematodes in the semi-arid region of Paraiba State, Brazil, was evaluated. Twenty farms were used, testing 40 animals in each one, totaling 800 animals. Cattle were divided into four groups composed with ten animals: I, treated with albendazole sulfoxide 15%; II, treated with ivermectin 1%; III, treated with closantel 25%; IV, treated with levamisole hydrochloride 7.5%. All treatments were administered subcutaneously. For the Fecal Egg Count Reduction Test (FECRT), individual fecal samples were collected on days 0 and 14, and sent for analysis of egg count per gram of feces (EPG) and larval cultures. It was observed that multiresistance was present in 95% (19/20) of the farms. Resistance to ivermectin and albendazole was observed in 95% (19/20), to closantel in 75% (15/20) and to levamisole in 20% (4/20). The most used management system was semi-intensive (75%; 15/20) and the ivermectin was the most reported drug for controlling helminths (65%; 13/20). Haemonchus spp. was the most prevalent helminth genus. It was concluded that the anthelmintic resistance of bovine gastrointestinal nematodes is high in the semi-arid of Paraíba State, Brazil, with multiresistance observed mainly to ivermectin, albendazole and closantel.


Assuntos
Anti-Helmínticos , Haemonchus , Nematoides , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Brasil , Bovinos , Resistência a Medicamentos , Fezes , Ivermectina/uso terapêutico , Contagem de Ovos de Parasitas/veterinária , Ovinos , Doenças dos Ovinos/tratamento farmacológico
10.
Acta Crystallogr C Struct Chem ; 77(Pt 9): 505-512, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34482293

RESUMO

A chemical study of the hydro-ethanol extract of the leaves of Combretum glutinosum resulted in the isolation of nine compounds, including 5-demethylsinensetin (1), umuhengerin (2), (20S,24R)-ocotillone (3), lupeol (4), ß-sitosterol (5), oleanolic acid (6), betulinic acid (7), corymbosin (8) and ß-sitosterol glucoside (9). Four compounds have been isolated for the first time from the genus Combretum [viz. (1), (2), (3) and (8)]. The crystal structures of flavonoid (2), C20H20O8, Z' = 2, and triterpene (3), C30H50O3, Z' = 1, have been determined for the first time; the latter confirmed the absolute configuration of native (20S,24R)-ocotillone previously derived from the crystal structures of related derivatives. The molecules of (3) are linked into supramolecular chains by intermolecular O-H...O hydrogen bonds. The crude extracts obtained by aqueous decoction and hydro-ethanolic maceration, as well as the nine isolated compounds, were tested for their anthelmintic activity on the larvae and adult worms of Haemonchus contortus, a hematophage that causes parasitic disorders in small ruminants. The evaluated anthelmintic activity showed that the extracts at different doses, as well as all the compounds tested at 150 µg ml-1, inhibited the migration of the larvae and the motility of the adult worms of the parasite compared with the phosphate buffer solution negative reference control. The best activity was obtained with flavonoids (1), (2) and (8) on both stages of the parasite. The flavones that showed good activity can be used for the further development of other derivatives, which could increase the anthelmintic efficacy.


Assuntos
Anti-Helmínticos/farmacologia , Anti-Infecciosos/farmacologia , Combretaceae/efeitos dos fármacos , Combretum/química , Flavonas/farmacologia , Flavonoides/química , Haemonchus/efeitos dos fármacos , Larva/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Animais , Anti-Helmínticos/química , Anti-Helmínticos/uso terapêutico , Anti-Infecciosos/química , Cristalografia por Raios X , Flavonas/química , Flavonoides/farmacologia , Haemonchus/crescimento & desenvolvimento , Ligação de Hidrogênio , Folhas de Planta/química
11.
Int J Mol Sci ; 22(16)2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34445640

RESUMO

4-Hexylresorcinol (4HR) has been used as a food additive, however, it has been recently demonstrated as a Class I histone deacetylase inhibitor (HDACi). Unlike other HDACi, 4HR can be taken through foods. Unfortunately, some HDACi have an influence on craniofacial growth, therefore, the purpose of this study was to evaluate the effects of 4HR on craniofacial growth. Saos-2 cells (osteoblast-like cells) were used for the evaluation of HDACi and its associated activities after 4HR administration. For the evaluation of craniofacial growth, 12.8 mg/kg of 4HR was administered weekly to 4 week old rats (male: 10, female: 10) for 12 weeks. Ten rats were used for untreated control (males: 5, females: 5). Body weight was recorded every week. Serum and head samples were collected at 12 weeks after initial administration. Craniofacial growth was evaluated by micro-computerized tomography. Serum was used for ELISA (testosterone and estrogen) and immunoprecipitation high-performance liquid chromatography (IP-HPLC). The administration of 4HR (1-100 µM) showed significant HDACi activity (p < 0.05). Body weight was significantly different in male rats (p < 0.05), and mandibular size was significantly smaller in 4HR-treated male rats with reduced testosterone levels. However, the mandibular size was significantly higher in 4HR treated female rats with increased growth hormone levels. In conclusion, 4HR had HDACi activity in Saos-2 cells. The administration of 4HR on growing rats showed different responses in body weight and mandibular size between sexes.


Assuntos
Anti-Helmínticos/farmacologia , Osso e Ossos/citologia , Ossos Faciais/crescimento & desenvolvimento , Hexilresorcinol/farmacologia , Desenvolvimento Maxilofacial/efeitos dos fármacos , Osteoblastos/citologia , Animais , Osso e Ossos/efeitos dos fármacos , Ossos Faciais/efeitos dos fármacos , Feminino , Masculino , Osteoblastos/efeitos dos fármacos , Ratos
12.
Environ Pollut ; 286: 117590, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438501

RESUMO

Anthelmintics, drugs against parasitic worms, are frequently used in livestock and might act as danger environmental microcontaminants. The present study was designed to monitor the possible circulation of common anthelmintic drug albendazole (ABZ) and its metabolites in the real agriculture conditions. The sheep were treated with the recommended dose of ABZ. Collected faeces were used for the fertilization of a field with fodder plants (alfalfa and clover) which served as feed for sheep from a different farm. The selective ultrasensitive mass spectrometry revealed surprisingly high concentrations of active ABZ metabolite (ABZ-sulphoxide) in all samples (dung, plants, ovine plasma, rumen content and faeces). Our results prove for the first time an undesirable permeation of ABZ metabolites from sheep excrement into plants (used as fodder) and subsequently to other sheep in real agricultural conditions. This circulation causes the permanent exposition of the ecosystems and food-chain to the drug and can promote the development of drug resistance in helminths.


Assuntos
Anti-Helmínticos , Drogas Veterinárias , Albendazol , Animais , Ecossistema , Fazendas , Ovinos
13.
Phytochemistry ; 190: 112887, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34339980

RESUMO

Chemical studies of the aerial parts of the Australian desert plant Eremophila microtheca afforded the targeted and known diterpenoid scaffolds, 3,7,8-trihydroxyserrulat-14-en-19-oic acid and 3-acetoxy-7,8-dihydroxyserrulat-14-en-19-oic acid. The most abundant serrulatane scaffold was converted to the poly-methyl derivatives, 3-hydroxy-7,8-dimethoxyserrulat-14-en-19-oic acid methyl ester and 3,7,8-trimethoxyserrulat-14-en-19-oic acid methyl ester using simple and rapid methylation conditions consisting of DMSO, NaOH and MeI at room temperature. Subsequently a 12-membered amide library was synthesised by reacting the methylated scaffolds with a diverse series of commercial primary amines. The chemical structures of the 12 undescribed semi-synthetic analogues were fully characterised following 1D/2D NMR, MS, UV, ECD and [α]D data analyses. All compounds were evaluated for their anthelmintic, anti-microbial and anti-viral activities. While none of the compounds significantly inhibited motility or development of the exsheathed third-stage larvae (xL3s) of a pathogenic ruminant parasite, Haemonchus contortus, the tri-methylated analogue induced a skinny phenotype in fourth-stage larvae (L4s) after seven days of treatment (IC50 = 14 µM). Anti-bacterial and anti-fungal activities were not observed at concentrations up to 20 µM. Activity against HIV latency reversal was tested in inducible, chronically-infected cells, with the tri-methylated analogue being the most active (EC50 = 38 µM).


Assuntos
Anti-Helmínticos , Diterpenos , Scrophulariaceae , Austrália , Diterpenos/farmacologia , Descoberta de Drogas
14.
Pan Afr Med J ; 39: 15, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34394806

RESUMO

Primary musculoskeletal echinococcosis is rare and accounts for 2-3% of the patients with hydatid disease. We report a case of giant primary hydatid cysts of the thigh and the gluteal region in an 82-year-old female, who presented with a painful multiple palpable mass. The diagnosis was confirmed by imaging and serology. Total resection was performed through an extended lateral approach of the thigh and intraoperative findings revealed infected giant hydatid cysts. The postoperative outcome was uneventful. Albendazole drug (400mg per day) was given for the next 3 months. At 6 months follow-up, the patient was satisfied with no complications or recurrence.


Assuntos
Albendazol/administração & dosagem , Anti-Helmínticos/administração & dosagem , Equinococose/diagnóstico , Idoso de 80 Anos ou mais , Nádegas/parasitologia , Terapia Combinada , Equinococose/terapia , Feminino , Seguimentos , Humanos , Coxa da Perna/parasitologia
15.
Parasite ; 28: 62, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34410223

RESUMO

Considerable research has been directed towards optimising in vitro tests that can diagnose resistance in pre-parasitic stages of parasites. The objective of this study was to compare the in vivo faecal egg count reduction test (FECRT), the in vitro egg hatch test (EHT), and the molecular determination of the frequency of a codon 200 allele of ß-tubulin isotype 1 associated with benzimidazole resistance in larval stages of Haemonchus contortus obtained from infected goats. Animals were infected with composite infective doses representing 10, 20, 30, 40, 60, and 80% resistant alleles. Faecal samples for the EHT were collected on 28, 33, and 35 days post-infection. The results of the in vivo FECRT indicated that albendazole treatment reduced infections consisting of composite doses of 10, 20, 30, 40, 60, and 80% larvae of the resistant isolate by 91.3, 78.0, 63.3, 48.4, 36.5, and 41.4%, respectively. The drug concentration at which 50% of the eggs were prevented from developing hatching larvae (ED50) in the in vitro EHT varied from 0.09 ± 0.01 to 15.63 ± 12.10 µg/mL thiabendazole. The results of the in vitro EHT indicated that the test could estimate in vivo resistance well. The EHT could thus accurately estimate the in vivo efficacy of the drug and percentage of the resistance allele in the population using hatching parameters in delineation doses. This finding was also supported by comparing the FECRT data to the hatching percentages in the EHT on 30 goat farms in Slovakia with natural mixed infections of gastrointestinal parasites.


Assuntos
Anti-Helmínticos , Haemonchus , Doenças dos Ovinos , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Benzimidazóis/farmacologia , Benzimidazóis/uso terapêutico , Resistência a Medicamentos , Fezes , Haemonchus/genética , Técnicas In Vitro , Contagem de Ovos de Parasitas/veterinária , Ovinos
16.
Rev Bras Parasitol Vet ; 30(3): e002521, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34406211

RESUMO

To investigate the in vitro anthelmintic efficacy of dividivi (Caesalpinia coriaria), a traditional medicinal plant used in Central America and the northern part of South America, extracts from the foliage of this plant were subjected to the egg hatching test (EHT) and larval exsheathment inhibition test (LEIT), against Haemonchus contortus. Four different extracts were evaluated: acetone-water (AW), methanol-water (MW), acetone-water-dichloromethane (AWD) and methanol-water-dichloromethane (MWD). The concentrations used for the EHT and LEIT tests ranged from 500 to 4000 µg mL-1 and six repetitions per concentration. The effective concentrations (EC50) were calculated using Probit analysis. The EC50 for EHT were 2947.0, 3347.0, 3959.6 and 4538.7 µg mL-1 for MWD, MW, AW and AWD, respectively. The EC50 for LEIT were 2883.4, 5927.4, 9876.3 and 9955.4 µg mL-1 for AWD, AW, MWD and MW, respectively. The methanol extracts were the most effective in inhibiting the hatching of eggs, while the acetone extracts showed efficacy in inhibiting larval exsheathment. This study explains the importance that C. coriaria has as a medicinal plant in Central and South American countries.


Assuntos
Anti-Helmínticos , Caesalpinia , Haemonchus , Animais , Anti-Helmínticos/farmacologia , Larva , Extratos Vegetais/farmacologia
17.
Braz J Biol ; 83: e246780, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34378684

RESUMO

Anthelmintic drugs have been used strategically in livestock reared in the tropics. These drugs have been used in the treatment of endoparasitism which have resulted in an increase in the animals' performance. The agouti (Dasyprocta leporina) is a neo-tropical rodent with the potential for domestication and has been farmed intensively in Trinidad. However, the objective of this research was to investigate the effect of anthelmintic use of the growth performance of the agouti. In searching the literature, it was found that this type of study on the agouti has not been done. In this experiment fourteen weaned agoutis weighing 1kg were divided into two groups randomly. The first group (T1) was not given any anthelmintic treatment but the second group (T2) was treated with Endovet Ces® subcutaneously every three months. There were no significant differences (p > 0.05) between the two groups in the carcass weight, weight gain, dressing percentage (hot and cold), heart, lungs, skin, head and feet. However, a significant difference (p < 0.05) was seen between groups in the weight of liver and pluck. To the authors knowledge this is the first time that carcass parameters has been presented in literature. The live weight of the animals at the end of the experiment ranged from 2.4 kg to 2.6 kg and animals had a dressing percentage of 57% to 55%. The results are suggestive that the use of anthelmintic drugs in agoutis reared intensively had no significant effect on weight gain and dressing percentage.


Assuntos
Anti-Helmínticos , Cuniculidae , Dasyproctidae , Animais , Roedores , Trinidad e Tobago
18.
Braz J Biol ; 83: e246781, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34378685

RESUMO

The agouti (Dasyprocta leporina) is a rodent that is found in the Neo-tropical region. This animal is hunted for its meat but has recently been reared in captivity as a source of meat protein in rural communities. A 20-month experiment was carried out to evaluate the effect of an anthelmintic on the reproductive performance of the agouti (Dasyprocta leporina) reared in captivity. This experiment was conducted in the humid tropics of Trinidad and Tobago. Sixteen animals (15 females, 1 male) placed in each of the two treatment groups in a completely randomized study design. In treatment 1 (T1) animals were given subcutaneous injections of Endovet Ces® (Ivermectin/Praziquantel) at 0.2 mg/kg every three months. Treatment 2 (T2) was the negative control group where animals were not exposed to an anthelmintic. Reproductive data were collected at parturition which included birth weight, litter weight, litter size and gender of offspring. The results showed that there was no statistical difference (p > 0.05) between the treatment groups with respect to birth weight, litter weight, litter size and gender. However, agoutis that were dewormed had a higher birth weight (220.24 g vs 209.1 g) and litter weight (369.8 g vs 343 g). The same values were obtained for the litter size (1.7 vs 1.7) and animals that were dewormed had a higher female offspring to male offspring (2.41:1 vs 1.11:1). This experiment demonstrated that the use of an anthelmintic strategically in the management of captive reared agoutis had no statistical effect (p > 0.05) on the reproductive parameters. Therefore, these animals can be kept in captive conditions without being dewormed and produce efficiently with proper feeding and housing management.


Assuntos
Anti-Helmínticos , Dasyproctidae , Animais , Feminino , Masculino , Reprodução , Roedores , Trinidad e Tobago
19.
Vet Parasitol ; 298: 109535, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34340009

RESUMO

The equine roundworm Parascaris univalens has developed resistance to the three anthelmintic substances most commonly used in horses. The mechanisms responsible for resistance are believed to be multi-genic, and transport proteins such as the P-glycoprotein (Pgp) family have been suggested to be involved in resistance in several parasites including P. univlaens. To facilitate further research into the mechanisms behind drug metabolism and resistance development in P. univalens we aimed to develop an in vitro model based on larvae. We developed a fast and easy protocol for hatching P. univalens larvae for in vitro studies, resulting in a hatching rate of 92 %. The expression of transport protein genes pgp-2, pgp-9, pgp-11.1, pgp-16.1 and major facilitator superfamily (MFS) genes PgR006_g137 and PgR015_g078 were studied in hatched larvae exposed to the anthelmintic drugs ivermecin (IVM) 10-9 M, pyrantel citrate (PYR) 10-6 M and thiabendazole (TBZ) 10-5 M for 24 h. In comparison, the expression of these transport protein genes was studied in the anterior end and intestinal tissues of adult worms in vitro exposed to IVM, TBZ and PYR, at the same concentrations as larvae, for 3 h, 10 h and 24 h. Larval exposure to sub-lethal doses of IVM for 24 h did not affect the expression levels of any of the investigated genes, however larvae exposed to PYR and TBZ for 24 h showed significantly increased expression of pgp-9. In vitro drug exposure of adult worms did not result in any significant increases in expression of transport protein genes. Comparisons of constitutive expression between larvae and adult worm tissues showed that pgp-9, pgp-11.1, pgp-16.1 and MFS gene PgR015_g078 were expressed at lower levels in larvae than in adult tissues, while pgp-2 and MFS gene PgR006_g137 had similar expression levels in larvae and adult worms. All investigated transport protein genes were expressed at higher rates in the intestine than in the anterior end of adult worms, except pgp-11.1 where the expression was similar between the two tissues. This high constitutive expression in the intestine suggests that this is an important site for xenobiotic efflux in P. univalens. Despite the fact that the results of this study show differences in expression of transport protein genes between larvae and adult tissues, we believe that the larval assay system described here will be an important tool for further research into the molecular mechanisms behind anthelmintic resistance development and for other in vitro studies.


Assuntos
Anti-Helmínticos , Ascaridoidea , Proteínas de Transporte , Regulação da Expressão Gênica , Animais , Anti-Helmínticos/farmacologia , Ascaridoidea/efeitos dos fármacos , Ascaridoidea/genética , Proteínas de Transporte/genética , Resistência a Medicamentos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Ivermectina/farmacologia , Larva/efeitos dos fármacos
20.
Vet Parasitol ; 298: 109534, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34343954

RESUMO

Recent reports indicate that gastrointestinal nematodes (GIN) are contributing to significant losses in deer productivity and that anthelmintic resistance has become an issue of concern for deer farmers in New Zealand. The aim of this study was to evaluate cross-grazing of deer with sheep or cattle as an aid for control of gastrointestinal and pulmonary nematode parasites of farmed red deer (Cervus elaphus) in New Zealand. This was a field study replicated over two years (2012 and 2013) for 16 weeks each year at two locations (Massey University, Palmerston North and Invermay AgResearch Centre, Mosgiel). Each farm replicate included four groups (19-20 deer) at each location: red deer cross-grazing with cattle (Deer/Cattle); red deer cross-grazing with sheep (Deer/Sheep); red deer grazing on their own (DeerOwn); and red deer grazing on their own and treated with anthelmintics every two weeks to suppress worm burdens, as a positive control (DeerSup). The key outcome was the number of anthelmintic treatments (AT) given to deer. The decision to treat individual resident deer in Deer/Cattle, Deer/Sheep and DeerOwn groups was based on "trigger" criteria including faecal egg count (FEC)≥250 eggs/g or Dictyocaulus faecal larval count (FLC)≥100 larvae/g or when growth rate was less than 80 % of the mean of the DeerSup group in the previous two weeks. In addition, to quantify the species of parasites cycling in each group, sets of three "tracer" deer were introduced to graze with each group at the mid-point and again at the end of each 16 week period in both years at both locations. Least squares means (LSM) of the number of AT given per animal for Deer/Sheep (3.4) and DeerOwn (3.3) groups were significantly higher than for the Deer/Cattle (2.7) group (p < 0.001). In tracer animals, the LSM of abomasal Trichostrongylus spp. were significantly fewer in the DeerOwn (17), Deer/Cattle (37) and DeerSup (54) groups than in the Deer/Sheep (952; p < 0.001) group. The LSM of the nematodes in the subfamily Ostertagiinae (=Ostertagia-type) were significantly more in the DeerOwn (1950) than in Deer/Sheep (370; p = 0.003) and DeerSup (238; p < 0.001) groups, but the number in the Deer/Cattle group (689) was not different to DeerOwn (p> 0.05). The LSM of lungworm were fewer in Deer/Sheep (3), Deer/Cattle (4) and DeerSup (3; p < 0.001) groups than in DeerOwn (40) group. The Deer/Cattle and DeerSup groups had significantly higher LSM of liveweight gain over the 16 weeks (p < 0.001) than the other two groups. This study demonstrated that cross-grazing with either sheep or cattle aided control of lungworm and gastrointestinal nematodes in young deer during autumn. However, the advantages varied between the use of sheep or cattle and in the ability to control different species of parasites.


Assuntos
Criação de Animais Domésticos , Controle de Doenças Transmissíveis , Cervos , Infecções por Nematoides , Doenças Parasitárias em Animais , Criação de Animais Domésticos/métodos , Animais , Anti-Helmínticos/uso terapêutico , Bovinos , Controle de Doenças Transmissíveis/métodos , Nematoides , Infecções por Nematoides/tratamento farmacológico , Infecções por Nematoides/prevenção & controle , Infecções por Nematoides/veterinária , Nova Zelândia/epidemiologia , Óvulo , Doenças Parasitárias em Animais/tratamento farmacológico , Doenças Parasitárias em Animais/prevenção & controle , Ovinos
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