RESUMO
The requirement to improve the efficiency of pesticide utilization has led to the development of sustainable and smart stimuli-responsive pesticide delivery systems. Herein, a novel avermectin nano/micro spheres (AVM@HPMC-Oxalate) with sensitive stimuli-response function target to the Lepidoptera pests midgut microenvironment (pH 8.0-9.5) was constructed using hydroxypropyl methylcellulose (HPMC) as the cost-effective and biodegradable material. The avermectin (AVM) loaded nano/micro sphere was achieved with high AVM loading capacity (up to 66.8 %). The simulated release experiment proved the rapid stimuli-responsive and pesticides release function in weak alkaline (pH 9) or cellulase environment, and the release kinetics were explained through release models and SEM characterization. Besides, the nano/micro sphere size made AVM@HPMC-Oxalate has higher foliar retention rate (1.6-2.1-fold higher than commercial formulation) which is beneficial for improving the utilization of pesticides. The in vivo bioassay proved that AVM@HPMC-Oxalate could achieve the long-term control of Plutella xylostella by extending UV shielding performance (9 fold higher than commercial formulation). After 3 h of irradiation, the mortality rate of P. xylostella treated by AVM@HPMC-Oxalate still up to 56.7 % ± 5.8 %. Moreover, AVM@HPMC-Oxalate was less toxic to non-target organisms, and the acute toxicity to zebrafish was reduced by 2-fold compared with AVM technical.
Assuntos
Ivermectina , Mariposas , Raios Ultravioleta , Ivermectina/análogos & derivados , Ivermectina/química , Ivermectina/farmacologia , Ivermectina/toxicidade , Animais , Mariposas/efeitos dos fármacos , Inseticidas/química , Inseticidas/farmacologia , Inseticidas/toxicidade , Celulose/química , Celulose/análogos & derivados , Derivados da Hipromelose/química , Concentração de Íons de Hidrogênio , Liberação Controlada de FármacosRESUMO
The red palm weevil (RPW), Rhynchophorus ferrugineus Olivier, is a devastating insect-pest of 29 plants including date palm. It feeds inside the tree bark thus it is difficult to manage using insecticides. Only a few insecticides have been found effective against RPW. Among these insecticide, emamectin benzoate (EMB) is widely used. This insecticide can pose threat human and environmental health as it is used in the form of tree injection. Thus, keeping in view its possible, its sublethal effect on RPW was studied using Age-stage, two sex life table. Life table parameters of the progeny of exposed larvae to LC10, LC25, and LC50 of EMB were computed. Statistically higher fecundity (161.12 per female) was observed in control treatment, while less fecundity was observed in LC50 treatment. Significantly higher values for intrinsic rate of increase (r), finite rate of increase (λ), and net reproductive rate (Ro) (0.0376, 1.0383, and 67.13 per day, respectively) were recorded for the control treatment. Contrarily, lower values for r, Ro, and λ i.e. 0.0318, 23.82, and 1.0324 per day, respectively were recorded in the LC50 treatment. Decreased population parameters suggest that EMB can be successfully used in for the management of RPW.
Assuntos
Inseticidas , Ivermectina , Tábuas de Vida , Gorgulhos , Animais , Gorgulhos/efeitos dos fármacos , Gorgulhos/crescimento & desenvolvimento , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Ivermectina/toxicidade , Inseticidas/farmacologia , Inseticidas/toxicidade , Feminino , Masculino , Larva/efeitos dos fármacos , Fertilidade/efeitos dos fármacos , Reprodução/efeitos dos fármacosRESUMO
The development of intelligent multifunctional nanopesticides featuring enhanced foliage affinity and hierarchical target release is increasingly pivotal in modern agriculture. In this study, a novel cationic amphiphilic comb-shaped polymer, termed PEI-TA, was prepared via a one-step Michael addition between low-molecular-weight biodegradable polyethylenimine (PEI) and tetradecyl acrylate (TA), followed by neutralization with acetic acid. Using the emulsifier PEI-TA, a positively charged avermectin (AVM) nanoemulsion was prepared via a phase inversion emulsification process. Under optimal formulation, the obtained AVM nanoemulsion (defined as AVM@PEI-TA) demonstrated exceptional properties, including small size (as low as 67.6 nm), high encapsulation efficiency (up to 87.96%), and high stability toward shearing, storage, dilution, and UV irradiation. The emulsifier endowed AVM@PEI-TA with a pronounced thixotropy, so that the droplets exhibited no splash and bounce when they were sprayed on the cabbage leaf. Owing to the electrostatic attraction between the emulsifier and the leaf, AVM@PEI-TA showed improved leaf adhesion, better deposition, and higher washing resistance in contrast to both its negatively charged counterpart and AVM emulsifiable concentrate (AVM-EC). Compared to the large-sized particles, the small-sized particles of the AVM nanoemulsion more effectively traveled long distances through the vascular system of veins after entering the leaf apoplast. Moreover, the nanoparticles lost stability when exposed to multidimensional stimuli, including pH, temperature, esterase, and ursolic acid individually or simultaneously, thereby promoting the release of AVM. The release mechanisms were discussed for understanding the important role of the emulsifier in nanopesticides.
Assuntos
Emulsificantes , Emulsões , Ivermectina , Ivermectina/análogos & derivados , Ivermectina/química , Ivermectina/farmacologia , Emulsões/química , Emulsificantes/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Folhas de Planta/química , Polietilenoimina/química , Nanopartículas/química , Brassica/química , Liberação Controlada de Fármacos , Tamanho da Partícula , Acrilatos/química , Cátions/química , Polímeros/químicaRESUMO
BACKGROUND: Osteosarcoma is the most common malignant bone tumor in children and adolescents. Conventional chemotherapy remains unsatisfactory due to drug toxicity and resistance issues. Therefore, there is an urgent need to develop more effective treatments for advanced osteosarcoma. In the current study, we focused on evaluating the anticancer efficacy of avermectin B1, a novel avermectin analog, against osteosarcoma cells. METHODS: The half-inhibitory concentration of avermectin B1 was calculated in three osteosarcoma cell lines. Then, functional experiments were conducted to evaluate the effects of avermectin B1 on cell proliferation, the cell cycle, apoptosis and autophagy. Moreover, the AMPK/ULK1 signaling pathway was detected by Western blot assay. Finally, the in vivo effect of avermectin B1 on tumor growth and metastasis was investigated using the xenograft mouse model. To examine the role of the AMPK/ULK1 pathway, an AMPK-specific inhibitor (dorsomorphin) was used in combination with avermectin B1. RESULTS: Avermectin B1 inhibited the proliferation of osteosarcoma cells in a dose-dependent manner based on CCK8 and colony formation assays. Then, it was found to inhibit migration and invasion by wound healing assay and cell migration and invasion assay. In addition, avermectin B1 induced osteosarcoma cell apoptosis and autophagy. In vivo, avermectin B1 effectively inhibited osteosarcoma cell growth and pulmonary metastasis. Mechanistically, avermectin B1 activated the AMPK/ULK1 pathway to exert antitumor activity in vitro and in vivo. Dorsomorphin significantly attenuated the Avermectin B1-induced antitumor activities. CONCLUSION: Our study suggests that avermectin B1 is a potential agent to treat osteosarcoma cells through the AMPK/ULK1 signaling pathway.
Assuntos
Proteínas Quinases Ativadas por AMP , Autofagia , Neoplasias Ósseas , Ivermectina , Osteossarcoma , Transdução de Sinais , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Camundongos Endogâmicos BALB C , Camundongos Nus , Osteossarcoma/tratamento farmacológico , Osteossarcoma/patologia , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Avermectin (AVM), a compound derived from the fermentation of Avermectin Streptomyces, has insecticidal, acaricidal, and nematicidal properties. Widely employed in agriculture, it serves as an effective and broad-spectrum insecticide for pest control. Although the toxicity of AVM at low doses may not be readily apparent, prolonged and extensive exposure can result in poisoning. To investigate the toxic effects of AVM on the body, this study established rat models of AVM poisoning with both low and high concentrations of the compound. Fifteen male rats were randomly assigned to one of three groups (n=5 per group): a control group, a low-concentration group, and a high-concentration group. The low-concentration group was administered an oral dose of 2â¯mg/kg AVM once daily for a duration of seven days, while the high-concentration group received an oral dose of 10â¯mg/kg AVM once daily for the same period. This study examined the impact of AVM on liver function and gut microbiota in rats using weight monitoring, liver function indicator detection, liver metabolomics sequencing, colon barrier function testing, and gut microbiota sequencing. The findings of this study demonstrated that exposure to 2 or 10â¯mg/kg AVM for seven days can lead to a notable decrease in rat weight, as well as induce liver dysfunction and metabolic disturbances. Additionally, AVM exposure can disrupt the composition of the intestinal microbiota and impair the integrity of the colon mucosal barrier, causing downregulation of Occludin expression and upregulation of inflammation-related protein expression levels such as IL-1ß, Myd88, and TLR4. Furthermore, bioinformatics analysis revealed a significant association between liver dysfunction and dysbiosis of the gut microbiota. These findings have implications for the agricultural use of AVM and its potential contribution to environmental pollution. Consequently, individuals involved in AVM usage should prioritize safety precautions and monitor liver function.
Assuntos
Colo , Microbioma Gastrointestinal , Inseticidas , Ivermectina , Fígado , Animais , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Masculino , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Ratos , Colo/efeitos dos fármacos , Colo/patologia , Inseticidas/toxicidade , Ratos Sprague-DawleyRESUMO
PURPOSE: Currently, for veterinary oral formulations containing one or more active pharmaceutical ingredient (API) that are not systemically absorbed and act locally within the gastrointestinal (GI) tract, the use of terminal clinical endpoint bioequivalence (BE) studies is the only option for evaluating product BE. This investigation explored the use of a totality of evidence approach as an alternative to these terminal studies. METHODS: Three formulations of tablets containing ivermectin plus praziquantel were manufactured to exhibit distinctly different in vitro release characteristics. Because these APIs are highly permeable, plasma drug concentrations served as a biomarker of in vivo dissolution. Tablets were administered to 27 healthy Beagle dogs (3-way crossover) and the rate and extent of exposure of each API for each formulation was compared in a pairwise manner. These results were compared to product relative in vitro dissolution profiles in 3 media. In vivo and in vitro BE predictions were compared. RESULTS: In vivo/in vitro inconsistencies in product relative performance were observed with both compounds when considering product performance across the 3 dissolution media. Formulation comparisons flagged major differences that could explain this outcome. CONCLUSIONS: The finding of an inconsistent in vivo/in vitro relationship confirmed that in vitro dissolution alone cannot assure product BE for veterinary locally acting GI products. However, when combined with a comparison of product composition and manufacturing method, this totality of evidence approach can successfully alert scientists to potential therapeutic inequivalence, thereby supporting FDA's efforts to Replace, Reduce, and/or Refine terminal animal studies.
Assuntos
Estudos Cross-Over , Ivermectina , Comprimidos , Equivalência Terapêutica , Cães , Animais , Ivermectina/farmacocinética , Ivermectina/administração & dosagem , Praziquantel/farmacocinética , Praziquantel/administração & dosagem , Praziquantel/química , Solubilidade , Administração Oral , Masculino , Drogas Veterinárias/farmacocinética , Drogas Veterinárias/administração & dosagem , Química Farmacêutica/métodos , Liberação Controlada de Fármacos , Feminino , Princípios AtivosRESUMO
Date palm trees, their cultivation and harvesting have become challenging due to infestations caused by some specific mites including Oligonychus afrasiaticus (McGregor) (Tetranychidae). Current research has been carried out to investigate the efficiency of nine pesticides against eggs and date palm mite, Oligonychus afrasiaticus against nine pesticides. Side effects of the nine pesticides were also examined on predatory mite, Amblyseius swirskii Athias-Henriot (Phytoseiidae). Mites and their eggs were treated with the recommended dosage of nine pesticides namely, Bifenazate 24%, Bifenthrin 10%, Matrine 0.6%, Imidacloprid 37% + Abamectin 3%, Sulphur 99.5%, Micronized Sulphur 80%, Mineral oil 95%, Pyrethrin 1.5% and Hexythiazox 10%, while they were present in their natural environment on the date palm trees in the experimental fields. Highest mortality of 91.16% was observed when O. afrasiaticus was treated with Bifenazate (24%) followed by 87.31%, 85.20%, 72.06%, 71.34%, 65.35%, 64.14%, 61.06% and 24.25% in case of Bifenthrin 10%, Matrine 0.6%, Imidacloprid 37% + Abamectin 3%, Sulphur 99.5%, Micronized Sulphur 80%, Mineral oil 95%, Pyrethrin 1.5%, and Hexythiazox 10%, respectively. A minimum hatching of 25.74% was observed when eggs of O. afrasiaticus were treated with Hexythiazox 10% and the highest success of hatching (99.07%) was seen when treatment was given with Imidacloprid 37% + Abamectin 3%. When same trials with same nine pesticides were performed on predatory mite; Amblyseius swirskii, the highest mortality in terms of percentage reduction (75.63%) was observed with Bifenthrin and the lowest (14.69%) with Matrine. Nine pesticides used in this study have distinct toxicity against targeted mite, their eggs and the predatory mite. A two steps control strategy is recommended for this treatment. First spray Hexythiazox at the egg laying stage and then at the moving stage of mites by using Matrine which is toxic to mites but negligibly toxic to predatory mites. Further studies are recommended to evaluate varied actions of the pesticide against eggs, phytophagous mites, and predatory mites.
Assuntos
Acaricidas , Ácaros , Neonicotinoides , Animais , Ácaros/efeitos dos fármacos , Phoeniceae , Tetranychidae/efeitos dos fármacos , Piretrinas , Alcaloides/farmacologia , Nitrocompostos , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Matrinas , Quinolizinas/farmacologiaRESUMO
This is the first report on high pesticide tolerance displayed by the microbiota isolated from the sediments of two high-altitude lakes, located in the Singalila National Park, Singalila Ridge of the Himalayas. Given the remote location of these lakes, direct exposure to chemical pesticides is highly unlikely. However, the high tolerance to commonly used pesticides exhibited, i.e. up to 250 mg/ml, suggests repeated exposure and contamination of the lakes. Microbial growth in the presence of varying concentrations of the pesticides, namely, emamectin benzoate, thiamethoxam, quinalphos, deltamethrin, spiromesifen, flubendiamide, monocrotophos, fipronil, fenazaquin and phorate, was tested. Results showed resistance to all pesticides except fenazaquin and fipronil, up to 250 mg/ml. For the latter two, tolerance was displayed up to a concentration of 40 mg/ml. Tolerance may potentially result from the transport and deposition of pesticides from nearby locations, particularly the tea plantations of Darjeeling and Eastern Nepal. This may create great ecological risks as these lakes are an important water source for endemic wildlife of this protected area. They also hold great significance to the religious sentiment of the local tribes who worship these lakes as sacred. The study highlights the need for monitoring pesticide contamination in such pristine high-altitude environments and the mechanisms of long-range pollutant transport.
Assuntos
Altitude , Monitoramento Ambiental , Lagos , Praguicidas , Poluentes Químicos da Água , Lagos/microbiologia , Lagos/química , Praguicidas/análise , Poluentes Químicos da Água/análise , Nepal , Nitrilas/toxicidade , Microbiota/efeitos dos fármacos , Piretrinas , Himalaia , Ivermectina/análogos & derivadosRESUMO
BACKGROUND: Human onchocerciasis remains a public health problem in Ghana. Mass drug administration (MDA) with ivermectin (IVM) has reduced disease morbidity and prevalence, but the transmission of onchocerciasis remains ongoing in several endemic foci. We investigated parasite transmission in some endemic communities in Ghana that had received > 18 rounds of annual MDA with IVM and determined the species composition of black fly (Simulium damnosum) vectors in these areas. METHODS: Adult female black flies were collected using human landing catches and identified as either forest or savanna species using morpho-taxonomic keys. The adult flies underwent dissection to determine their parity and detect any O. volvulus larvae, followed by the calculation of entomological indices. Simulium damnosum s.l. larvae were collected and preserved in freshly prepared Carnoy's fixative and were later used for cytotaxonomic studies. RESULTS: A total of 9,983 adult flies were caught: 6,569 and 3,414 in the rainy and dry seasons respectively. Black fly biting activities over the study period showed bimodal or trimodal patterns. The highest monthly biting rate (MBR) of 10,578.75 bites/person/month was recorded in July in Beposo, while the highest monthly transmission potential of 100.69 infective bites/person/month was recorded in Asubende in August. Morphological analysis of 2,032 flies showed that 99.8% (2,028) of the flies were savanna species, with only 4 (0.2%) adult flies being of the forest species. Cytogenetic studies on 114 black fly larvae revealed three cytospecies (Simulium damnosum s.s., S. sirbanum and S. sanctipauli) in the study area. CONCLUSIONS: The present studies confirmed an ongoing transmission of onchocerciasis in the study communities except Abua-1. It also provides further information on biting behaviors and onchocerciasis transmission indices in the study communities. Further, our data confirmed the savanna species (S. damnosum s.s. and S. sirbanum) of the S. damnosum s.l. to be the major vectors of onchocerciasis in the study areas, with only an occasional influx of forest cytotypes.
Assuntos
Insetos Vetores , Ivermectina , Larva , Administração Massiva de Medicamentos , Oncocercose , Simuliidae , Animais , Oncocercose/transmissão , Oncocercose/epidemiologia , Oncocercose/veterinária , Gana/epidemiologia , Simuliidae/parasitologia , Ivermectina/administração & dosagem , Ivermectina/farmacologia , Humanos , Feminino , Insetos Vetores/parasitologia , Insetos Vetores/efeitos dos fármacos , Larva/efeitos dos fármacos , Onchocerca volvulus/efeitos dos fármacos , Onchocerca volvulus/fisiologia , Mordeduras e Picadas de Insetos/epidemiologia , Estações do AnoRESUMO
INTRODUCTION: Epidemiological evidence suggests that Onchocerca volvulus is associated with epilepsy, although the exact pathophysiological mechanism is unknown. Mahenge is an endemic focus of onchocerciasis, with the longest-running ivermectin treatment intervention in Tanzania. We assessed the prevalence of onchocerciasis and epilepsy after 25 years of control using ivermectin. METHODS: This was a population-based cross-sectional study in 34 villages in Mahenge in 2021. Community health workers conducted door-to-door household surveys to enumerate the population and screen for individuals suspected of epilepsy using a standardised questionnaire. Trained physicians confirmed epilepsy. Children aged 6-11 years were screened for onchocerciasis antibodies using the Ov16 rapid test. Villages were stratified into three altitude levels (low [<400], medium [400-950], and high [>950 meters above sea level]) as a proxy for rapids, which black flies favour for breeding sites. Incidence of epilepsy was estimated as a ratio of new cases in the year preceding the survey per 100,000 population. RESULTS: 56,604 individuals (median age 20.2 years, 51.1% females) were surveyed. Onchocerciasis prevalence in children was 11.8% and was highest in villages at medium (21.7%) and lowest in low altitudes (3.2%), p<0.001. Self-reported use of ivermectin was 88.4%. Epilepsy prevalence was 21.1 (95%CI: 19.9-22.3) cases per 1000 persons and was highest in medium (29.5%) and lowest in the lowlands (12.7%). The odds ratio (OR) of having epilepsy was significantly higher in females (OR = 1.22, 95%CI: 1.08-1.38), middle altitudes (OR = 2.34 [95%CI: 2.04-2.68]), and in individuals positive for OV16 (OR = 1.98 [95%CI:1.57-2.50]). The incidence of epilepsy a year before the survey was 117 (95%CI: 99.7-160.4) cases per 100,000 person-years. CONCLUSION: Despite ivermectin use for 25 years, the prevalence of onchocerciasis and epilepsy remains high. It is crucial to strengthen bi-annual ivermectin treatment and initiate interventions targeting vectors to control onchocerciasis and epilepsy in the area.
Assuntos
Epilepsia , Ivermectina , Oncocercose , Humanos , Ivermectina/uso terapêutico , Oncocercose/epidemiologia , Oncocercose/tratamento farmacológico , Feminino , Masculino , Epilepsia/epidemiologia , Epilepsia/tratamento farmacológico , Tanzânia/epidemiologia , Criança , Estudos Transversais , Prevalência , Adolescente , Adulto , Adulto Jovem , Animais , Pré-Escolar , Onchocerca volvulus/efeitos dos fármacos , Pessoa de Meia-Idade , Antiparasitários/uso terapêutico , Lactente , IdosoRESUMO
Scabies is a prevalent ectoparasitic infectious disease, caused by the mite Sarcoptes scabiei. As a consequence of the infestation, localised cutaneous inflammation, pruritus and polymorphic skin lesions develop. The primary symptoms of scabies manifest as hypersensitivity-like reactions and immune responses, the precise mechanisms of which remain poorly defined. The objective of this study was to evaluate the effects of oral ivermectin treatment in patients with scabies on the systemic immune response and the patient's quality of life (QoL). Patients admitted to the dermatology outpatient clinic and diagnosed with scabies were administered oral ivermectin treatment following diagnosis at week 0 and 2. Laboratory tests were conducted to measure complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels before treatment and at week 4. The systemic immune-inflammation index (SII) was calculated using the platelet, neutrophil and lymphocyte counts. Additionally, data pertaining to the Dermatological Life Quality Index (DLQI) were recorded. In 119 patients (51 males) diagnosed with scabies, increases in ESR, CRP, and SII values and decreases in inflammatory cell counts and DLQI scores were observed one month after treatment with oral ivermectin. The results of the study showed that the use of oral ivermectin, a scabicidal agent, triggered the inflammatory response and improved the QoL of the patients.
Assuntos
Proteína C-Reativa , Ivermectina , Qualidade de Vida , Escabiose , Humanos , Escabiose/tratamento farmacológico , Escabiose/imunologia , Ivermectina/administração & dosagem , Ivermectina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Administração Oral , Adulto , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Idoso , Adulto Jovem , Adolescente , Antiparasitários/administração & dosagem , Antiparasitários/uso terapêutico , Sarcoptes scabiei/efeitos dos fármacos , Sarcoptes scabiei/imunologia , Sedimentação Sanguínea , Inflamação/imunologia , Inflamação/tratamento farmacológico , Resultado do Tratamento , AnimaisRESUMO
BACKGROUND: Abamectin (ABA) is considered a powerful insecticidal and anthelmintic agent. It is an intracellular product of Streptomyces avermitilis; is synthesized through complicated pathways and can then be extracted from mycelial by methanol extraction. ABA serves as a biological control substance against the root-knot nematode Meloidogyne incognita. This investigation is intended to reach a new strain of S. avermitilis capable of producing ABA effectively. RESULTS: Among the sixty actinobacterial isolates, Streptomyces St.53 isolate was chosen for its superior nematicidal effectiveness. The mycelial-methanol extract of isolate St.53 exhibited a maximum in vitro mortality of 100% in one day. In the greenhouse experiment, the mycelial-methanol extract demonstrated, for the second-stage juveniles (J2s), 75.69% nematode reduction and 0.84 reproduction rate (Rr) while for the second-stage juveniles (J2s), the culture suspension demonstrated 75.38% nematode reduction and 0.80 reproduction rate (Rr). Molecular identification for St.53 was performed using 16 S rRNA gene analysis and recorded in NCBI Genbank as S. avermitilis MICNEMA2022 with accession number (OP108264.1). LC-MS was utilized to detect and identify abamectin in extracts while HPLC analysis was carried out for quantitative determination. Both abamectin B1a and abamectin B1b were produced and detected at retention times of 4.572 and 3.890 min respectively. CONCLUSION: Streptomyces avermitilis MICNEMA2022 proved to be an effective source for producing abamectin as a biorational agent for integrated nematode management.
Assuntos
Ivermectina , Streptomyces , Tylenchoidea , Streptomyces/genética , Streptomyces/metabolismo , Ivermectina/análogos & derivados , Ivermectina/farmacologia , Ivermectina/metabolismo , Animais , Tylenchoidea/efeitos dos fármacos , RNA Ribossômico 16S/genética , Anti-Helmínticos/farmacologia , Filogenia , Antinematódeos/farmacologia , Antinematódeos/metabolismo , Doenças das Plantas/parasitologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Agentes de Controle Biológico/farmacologiaRESUMO
BACKGROUND: Loiasis is a disease caused by the nematode Loa loa. Serious adverse events sometimes occur in people with heavy L. loa microfilaremia after ivermectin treatment. In regions of Central Africa where loiasis is endemic, this significantly impedes global elimination programs for lymphatic filariasis and onchocerciasis that use mass distribution of ivermectin. Improved diagnostic tests to identify individuals at increased risk of serious adverse events could facilitate efforts to eliminate lymphatic filariasis and onchocerciasis in this region. METHODS AND FINDINGS: We previously identified the L. loa protein Ll-Bhp-1 in loiasis patient sera. Here, we further characterize Ll-Bhp-1 and report development of an antigen capture ELISA to detect this antigen. This assay detected Ll-Bhp-1 in 74 of 116 (63.8%) loiasis patient sera. Ll-Bhp-1 levels were significantly correlated with L. loa microfilarial counts, and the sensitivity of the assay was highest for samples from people with high counts, (94% and 100% in people with ≥20,000 and ≥50,000 microfilaria per milliliter of blood, respectively). The antigen was not detected in 112 sera from people with other filarial infections, or in 34 control sera from the USA. CONCLUSIONS: This Ll-Bhp-1 antigen assay is specific for loiasis, and highly sensitive for identifying people with high L. loa microfilarial counts who are at increased risk for serious adverse events after ivermectin treatment. L. loa antigen detection has the potential to facilitate loiasis mapping efforts and programs to eliminate lymphatic filariasis and onchocerciasis in Central Africa.
Assuntos
Antígenos de Helmintos , Biomarcadores , Ensaio de Imunoadsorção Enzimática , Loa , Loíase , Humanos , Loa/imunologia , Loa/isolamento & purificação , Loíase/diagnóstico , Loíase/tratamento farmacológico , Loíase/sangue , Loíase/parasitologia , Animais , Antígenos de Helmintos/sangue , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Biomarcadores/sangue , África Central , Microfilárias/imunologia , Sensibilidade e Especificidade , Ivermectina/uso terapêutico , Feminino , MasculinoRESUMO
OBJECTIVES: To review the homogeneity of pharmacological prescription and control measures applied in cases of scabies in prisons in Catalonia. MATERIAL AND METHOD: Observational, multicenter, and retrospective study. Cases of scabies from March 01, 2021 and March 01, 2022 were analyzed according to the International Alliance for the Control of Scabies (IACS) 2020 criteria: a) confirmed cases; b) clinically probable cases; and c) suspected cases.Epidemiological, clinical, therapeutic and regimental control variables were collected. We checked whether the interventions were homogeneous in each site. The mean and standard deviation were used as continuous variables and percentages and confidence interval (95%) for discrete variables. The Chi-square test was used to determine statistical association. RESULTS: 269 cases were detected (21.2% confirmed, 50.2% clinically probable and 28.6% suspected). 61.3% were treated with permethrin, 18.6% with ivermectin and 20.1% with both. 27.1% of the cases were withdrawn.There were no significant in-site differences in the study of contacts, isolation and treatment of clothing and belongings, but there were significant differences in the prescription of drugs (P <0.001), duration of treatment (P <0.001) and disinfection of the cell (P <0.001). DISCUSSION: The number of detected cases is estimated to be high, and the majority (71.4%) confirmed or clinically probable. Control measures are homogeneous, except for cell disinfection, which was conventional in 59.1%. Pharmacological treatment and its duration varied between prisons. It would be advisable to establish a protocol to standardize control measures applied to new cases in the centers of Catalonia and subsequently evaluate their efficacy.
Assuntos
Ivermectina , Escabiose , Escabiose/tratamento farmacológico , Escabiose/diagnóstico , Humanos , Espanha , Estudos Retrospectivos , Ivermectina/uso terapêutico , Masculino , Feminino , Adulto , Permetrina/uso terapêutico , Prisioneiros/estatística & dados numéricos , Pessoa de Meia-Idade , Inseticidas/uso terapêutico , PrisõesRESUMO
Changes to ivermectin (IVM [22,23-dihydro avermectin B1a + 22,23-dihydro avermectin B1b]) toxicokinetics (TK) with and without P-glycoprotein (P-gp) inhibition by cyclosporin A (CsA) were examined in rainbow trout (Oncorhynchus mykiss). Rainbow trout were injected with 175 µg/kg 3H-IVM (8.6 µCi/mg IVM) with or without co-administration of 480 µg/kg CsA into the caudal vasculature. Fish were sacrificed at various time points (0.25, 0.5, 1, 3, 24, 48, 96, and 168 h) for organ and tissue sampling (blood, liver, kidney, gill, intestines, brain [5 regions], eye, gonad, and fat) which were analyzed for IVM-derived radioactivity. The IVM concentration decreased over time in blood, liver, kidney, and gill, while concentrations in other tissues remained constant. The highest maximum IVM concentration (Cmax) was found in kidney, followed by liver; the lowest Cmax was found in eye, followed by brain and adipose tissue. The highest % of the administered dose was found in the blood 15 min post-IVM administration, followed by the intestine at 60 min post-IVM administration. P-gp inhibition by CsA did not significantly affect calculated TK parameters (AUC [7.33 ± 0.73 - 11.5 ± 2.5 mgâ¢h/kg], mean residence time [84.7 ± 21 - 125 ± 55 h], T1/2 [58.7 ± 15 - 86.8 ± 38 h], clearance rate [0.0152 ± 0.0033 - 0.0239 ± 0.0024 L/kgâ¢h], or volume of distribution [1.91 ± 0.47 - 2.02 ± 0.33 L/kg]), but resulted in small but significant changes in the % administered dose found in blood and medulla. These results suggest that P-gp plays a limited role in overall IVM TK, and that its role in xenobiotic protection may be much less robust in fish than it is in mammals.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Ciclosporina , Ivermectina , Oncorhynchus mykiss , Animais , Oncorhynchus mykiss/metabolismo , Ivermectina/análogos & derivados , Ivermectina/farmacocinética , Ivermectina/toxicidade , Ivermectina/sangue , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Ciclosporina/farmacocinética , Toxicocinética , Antiparasitários/farmacocinética , Distribuição TecidualRESUMO
The fall armyworm (FAW), Spodoptera frugiperda Smith (Lepidoptera: Noctuidae), poses a significant threat to food security, necessitating effective management strategies. While chemical control remains a primary approach, understanding the toxicity and detoxification mechanisms of different insecticides is crucial. In this study, we conducted leaf-dipping bioassays to assess the toxicity of quinalphos and beta-cypermethrin·emamectin benzoate (ß-cyp·EMB) on S. frugiperda larvae. Additionally, we assessed the response of alterations in CarE, GST, MFO, and AChE activities to sublethal concentrations of these insecticides over various treatment durations. Results indicated that ß-cyp·EMB exhibited higher toxicity than quinalphos in S. frugiperda. Interestingly, the highest activities of GST, CarE, MFO, and AChE were observed at 6â¯h exposure to LC10 and LC25 of ß-cyp·EMB, surpassing equivalent sublethal concentrations of quinalphos. Subsequently, GST and CarE activities exposure to ß-cyp·EMB steadily decreased, while MFO and AChE activities exposure to both insecticides was initially decreased then increased. Conversely, two sublethal concentrations of quinalphos notably enhanced GST activity across all exposure durations, with significantly higher than ß-cyp·EMB at 12-48â¯h. Similarly, CarE activity was also increased at various durations. Our research has exhibited significant alterations in enzyme activities exposure to both concentration and duration. Furthermore, Pearson correlation analysis showed significant correlations among these enzyme activities at different treatment durations. These findings contribute to a better understanding of detoxification mechanisms across different insecticides, providing valuable insights for the rational management of S. frugiperda populations.
Assuntos
Inativação Metabólica , Inseticidas , Ivermectina , Larva , Piretrinas , Spodoptera , Animais , Inseticidas/toxicidade , Spodoptera/efeitos dos fármacos , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Larva/efeitos dos fármacos , Piretrinas/toxicidade , Acetilcolinesterase/metabolismo , Glutationa Transferase/metabolismoRESUMO
Treatment of livestock with endectocides such as ivermectin is viewed as a complementary vector control approach to address residual transmission of malaria. However, efficacy of this treatment may vary between animal species. Hence, our purpose was to investigate the effects of ivermectin treatments of common livestock species on life history traits of the opportunistic malaria vector Anopheles coluzzii. Sheep, goats and pigs were treated using injectable veterinary ivermectin formulation at the species-specific doses (recommended dose for all species and high dose in pig). Mosquito batches were exposed to treated and control (not injected) animals at different days after treatment. Daily mosquito mortality was recorded and fecundity assessed through the count of gravid females and the number of eggs they developed. The recommended dose of ivermectin induced a significant decrease in mosquito survival for up to 7 days after injection (DAI), with a decrease of 89.7%, 66.7%, and 48.4% in treated pigs, goats and sheep, respectively, compared to control animals. In treated pigs, the triple therapeutic dose decreased mosquito survival of 68.97% relatively to controls up to 14 DAI. The average number in gravid females Anopheles that survived after feeding on treated animals were reduced when blood-meals were taken on sheep (2.57% and 42.03% at 2 and 7 DAI), or on goats (decrease of the 28.28% and 73.64% respectively at 2 and 7 DAI). This study shows that ivermectin treatments to animals negatively impacts An. coluzzii life history traits and could reduce vector densities in areas where livestock live near humans. However, due to short-term efficacy of single dose treatments, repeated treatments and potentially increased dosages would be required to span the transmission season. The use of long-acting ivermectin formulations is discussed as a mean for extending efficacy while remaining cost effective.
Assuntos
Anopheles , Ivermectina , Malária , Mosquitos Vetores , Animais , Ivermectina/farmacologia , Ivermectina/administração & dosagem , Anopheles/efeitos dos fármacos , Anopheles/fisiologia , Feminino , Mosquitos Vetores/efeitos dos fármacos , Mosquitos Vetores/fisiologia , Malária/transmissão , Malária/prevenção & controle , Ovinos , Suínos , Gado , Cabras , Inseticidas/farmacologia , Inseticidas/administração & dosagem , Controle de Mosquitos/métodosRESUMO
The present study investigated the effect of ivermectin and amitraz on the cellular architecture of vital organs of Rhipicephalus microplus. Adult female ticks were treated with lethal concentrations (LC95) of ivermectin and amitraz, and the ovaries, synganglion, and Gené's organ were processed 48 h post treatment. In both the treatment groups, the ultra-thin sections of ovary exhibited deformed oocytes, irregular plasmic membrane and chorion layer, extensive vacuolation in the cytoplasm mainly at periphery of the cell and oocyte-pedicel junction. Marked vacuolations in the cortex and neuropile region with significant structural disorganization of the neural fibers were common alterations observed in the synganglion of ticks exposed to ivermectin and amitraz. The tissue sections of Gené's organ revealed deformed tubular glands with severe loss of cellular limit of secretory epithelium and cytoplasmic vacuolations in the ivermectin treated ticks whereas, the alterations were comparatively less severe in amitraz exposed ticks. The cellular deformities in these vital organs probably impaired reproductive function, nerve signal transmission and metabolic activities and thus affected fecundity and survivability of the treated ticks. The findings suggested that the action of ivermectin and amitraz are not restricted to the nervous system of ticks, but also on other vital organs, ovary and Gené's organ affecting the oviposition. The study provided insights into the development of targeted interventions for tick control strategies.
Assuntos
Ivermectina , Ovário , Rhipicephalus , Toluidinas , Animais , Ivermectina/farmacologia , Feminino , Rhipicephalus/efeitos dos fármacos , Toluidinas/farmacologia , Ovário/efeitos dos fármacos , Acaricidas/farmacologia , Microscopia Eletrônica de TransmissãoRESUMO
Cyathostomins are the largest group of parasites in horses that can be controlled by ivermectin (IVM). This study aimed to run a four-dose titration trial of IVM in 28 naturally infected Thoroughbred yearlings. The local Strongyle population had been recorded to be resistant to IVM (200 µg/kg). The parasite fecal egg count (FEC) was performed to investigate the egg reappearance period (ERP) of two and five weeks (w2pt and w5pt) after IVM treatment. FEC was > 1000 on day zero for all groups. Although 100% FEC reduction was reported at w2pt for all concentrations, the FEC at w5pt revealed < 83% efficacy. This study reports the reduction of ERP using the label dose as well as 300, and 400 µg/kg (double dose) of IVM. The protocol allowed IVM to significantly suppress FEC w2pt although not eliminating adult worms, failing to guarantee an extension of its protection period over 8 weeks. Moreover, the FEC at w5pt possibly means the infection was not cleared, and worms reestablished egg laying. We raised the possibility of withdrawing IVM of control programs when the drug has less than 80% FEC reduction at w5pt.
Assuntos
Ivermectina , Contagem de Ovos de Parasitas , Animais , Ivermectina/uso terapêutico , Ivermectina/administração & dosagem , Cavalos/parasitologia , Brasil , Doenças dos Cavalos/parasitologia , Doenças dos Cavalos/tratamento farmacológico , Doenças dos Cavalos/diagnóstico , Feminino , Antiparasitários/uso terapêutico , Antiparasitários/administração & dosagem , Infecções Equinas por Strongyloidea/tratamento farmacológico , Infecções Equinas por Strongyloidea/parasitologia , Infecções Equinas por Strongyloidea/diagnóstico , Fezes/parasitologiaRESUMO
Avermectin is a highly effective insecticide that has been widely used in agriculture since the 1990s. In recent years, the safety of avermectin for non-target organisms has received much attention. The vasculature is important organs in the body and participate in the composition of other organs. However, studies on the vascular safety of avermectin are lacking. The vasculature of zebrafish larvae is characterized by ease of observation and it is a commonly used model for vascular studies. Therefore, zebrafish larvae were used to explore the potential risk of avermectin on the vasculature. The results showed that avermectin induced vascular damage throughout the body of zebrafish larvae, including the head, eyes, intestine, somite, tail and other vasculature. The main forms of damage are reduction in vascular diameter, vascular area and vascular abundance. Meanwhile, avermectin induced a decrease in the number of endothelial cells and apoptosis within the vasculature. In addition, vascular damage may be related to impairment of mitochondrial function and mitochondria-mediated apoptosis. Finally, exploration of the molecular mechanisms revealed abnormal alterations in the expression of genes related to the VEGF/Notch signaling pathway. Therefore, the VEGF/Notch signaling pathway may be an important mechanism for avermectin-induced vascular damage in zebrafish larvae. This study demonstrates the vascular toxicity of avermectin in zebrafish larvae and reveals the possible molecular mechanism, which would hopefully draw more attention to the safety of avermectin in non-target organisms.