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1.
Wiad Lek ; 74(5): 1204-1207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34090291

RESUMO

OBJECTIVE: The aim is to show the effectiveness of the cultural method in the diagnosis of babesiosis. PATIENTS AND METHODS: Materials and methods: The study material was the blood from 10 healthy humans and animals, 30 humans with borreliosis, 41 animals with babesiosis. A cultural research method was used. RESULTS: Results: The use of cultural method contributed to the optimization of the etiopathogenetic diagnosis of babesiosis. The method objectively proved the ability of protozoa (Babesia spp.) to asexual reproduction in vitro on the multicomponent growth medium with erythrocytes; proved the role of erythrocytes as acceptable for Babesia spp. of target cells. Absolute and relative parameters of detection of Babesia spp. by cultural method in the blood samples of the groups of the examined persons/species were different, making on average 19.7% (with the highest rates among the domestic dogs (62.5%) and cattle (20.0%)). Negative result (0%) was identified among the patients with borreliosis. CONCLUSION: Conclusions: Detection of Babesia spp. by the cultural method objectively confirmed its value as an apparent laboratory criterion for the etiopathogenetic diagnosis of babesiosis.


Assuntos
Babesia , Babesiose , Animais , Babesiose/diagnóstico , Bovinos , Cães , Eritrócitos , Humanos
2.
Commun Biol ; 4(1): 686, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083749

RESUMO

In January 2020, the coronavirus disease was declared, by the World Health Organization as a global public health emergency. Recommendations from the WHO COVID Emergency Committee continue to support strengthening COVID surveillance systems, including timely access to effective diagnostics. Questions were raised about the validity of considering the RT-PCR as the gold standard in COVID-19 diagnosis. It has been suggested that a variety of methods should be used to evaluate advocated tests. Dogs had been successfully trained and employed to detect diseases in humans. Here we show that upon training explosives detection dogs on sniffing COVID-19 odor in patients' sweat, those dogs were able to successfully screen out 3249 individuals who tested negative for the SARS-CoV-2, from a cohort of 3290 individuals. Additionally, using Bayesian analysis, the sensitivity of the K9 test was found to be superior to the RT-PCR test performed on nasal swabs from a cohort of 3134 persons. Given its high sensitivity, short turn-around-time, low cost, less invasiveness, and ease of application, the detection dogs test lends itself as a better alternative to the RT-PCR in screening for SARS-CoV-2 in asymptomatic individuals.


Assuntos
Teste para COVID-19/métodos , COVID-19/diagnóstico , Odorantes , Cães Trabalhadores , Adulto , Idoso , Animais , Teorema de Bayes , Teste de Ácido Nucleico para COVID-19/economia , Teste de Ácido Nucleico para COVID-19/métodos , Teste para COVID-19/economia , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Odorantes/análise , SARS-CoV-2/isolamento & purificação , Sensibilidade e Especificidade , Olfato , Adulto Jovem
3.
Mem Inst Oswaldo Cruz ; 116: e210056, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34105689

RESUMO

Vector-borne transmission of Chagas disease in urban areas of Argentina has been an overlooked phenomena. We conducted the first comprehensive cross-sectional study of domestic infestation with Triatoma infestans and vector infection with Trypanosoma cruzi in a metropolitan area of San Juan, Argentina. Our results document the occurrence of T. infestans infected with T. cruzi in human sleeping quarters. In this urban setting, we also show that infestation was associated with construction materials, the presence of chickens, cats and a large number of dogs that can provide blood meals for the vector. Our findings reveal new challenges for vectorial control agencies.


Assuntos
Doença de Chagas , Triatoma , Trypanosoma cruzi , Animais , Argentina , Gatos , Galinhas , Estudos Transversais , Cães , Insetos Vetores
4.
Rev Bras Parasitol Vet ; 30(2): e001821, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076048

RESUMO

Between December 2016 and April 2017, a spate of abortions occurred in a closed dairy herd from the central eastern region of Paraná, Brazil, in which 75 cows aborted. To identify its cause, organ fragments were collected from an aborted fetus for histopathology, and the blood samples from a stillborn, 4 aborted fetuses, and 9 farm dogs for indirect fluorescent antibody technique (IFAT). These tests found multifocal non-suppurative encephalitis, periportal hepatitis, and multifocal lymphoplasmacytic myocarditis, and detected anti-Neospora antibodies in all aborted fetuses, and in 5 of the 9 dogs. DNA of Neospora caninum was detected in the brain tissue of an aborted fetus. Blood samples of 340 cows and 146 heifers showed 33.5% and 30.8% seropositivity, respectively. In this closed herd, the parasite was probably introduced by infected domesticated or wild carnivores inhabiting the farm, through the infective oocysts present in their stool.


Assuntos
Doenças dos Bovinos , Coccidiose , Doenças do Cão , Neospora , Aborto Animal , Animais , Anticorpos Antiprotozoários , Brasil , Bovinos , Doenças dos Bovinos/diagnóstico , Doenças dos Bovinos/epidemiologia , Coccidiose/diagnóstico , Coccidiose/epidemiologia , Coccidiose/veterinária , Cães , Feminino , Técnica Indireta de Fluorescência para Anticorpo/veterinária , Gravidez
5.
Rev Bras Parasitol Vet ; 30(2): e022620, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076050

RESUMO

Efforts to control a zoonotic disease such as visceral leishmaniasis (VL) caused by Leishmania infantum can be successful if they rely on comprehensive data on animal infection. In Bahia state, Brazil, human VL is endemic, yet some areas have no epidemiological data on canine L. infantum infection and canine leishmaniasis (CanL) to date. We aimed to perform an epidemiological study describing the spatial distribution and characterizing canine L. infantum infection in two districts of the municipality of Muritiba, where human cases have occurred. Brazilian official serodiagnostic protocol (ELISA and immunochromatographic tests), PCR and clinical examination were performed in 351 owned dogs. A seroprevalence of 15.7% (55/351) was found, and L. infantum identified in 88.8% (32/36) of PCR tested samples. Spatial distribution of positive dogs indicated infection in both urban and rural districts. There was no association between seropositivity and sex or breed, but dogs older than 2 years were 3.8 times more likely to be seropositive (95% CI 1.57 - 9.18) than younger dogs. Among seropositive dogs, 80% (44/55) had clinical manifestations of CanL: 75% (33/44) presented dermatopathy, 50% (22/44) emaciation, and 29.5% (13/44) ophthalmopathy. This is the first report on canine seroprevalence and natural L. infantum infection in Muritiba, Bahia.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Leishmaniose , Animais , Anticorpos Antiprotozoários , Brasil/epidemiologia , Cidades , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Cães , Humanos , Leishmaniose/veterinária , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária , Estudos Soroepidemiológicos
6.
Rev Bras Parasitol Vet ; 30(2): e023620, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34076051

RESUMO

Visceral leishmaniasis (VL) is a zoonosis with a worldwide distribution that has a major impact on public health. The aim of this study was to verify the prevalence of canine infection by Leishmania infantum, the factors associated with the infection and its spatial distribution in the municipality of Mãe D'Água, in the Sertão region of Paraíba State, Northeast Brazil. Blood samples were collected from 150 dogs for diagnosis by the DPP®, ELISA-S7®, ELISA-EIE® and qPCR assays. The prevalence was calculated considering the positivity in at least two tests. SaTScan® was used for spatial analysis. The prevalence of canine infection with Leishmania was 18.6% (28/150), with the rural area being identified as a risk factor (Odds Ratio (OR) = 2.93). The permanence of the dog loose during the night (OR = 0.33) and deworming (OR = 0.30) were identified as protective factors. A risk cluster was formed in the northern region of the urban area. Mãe D'Água showed a pattern of active transmission in the rural area, but VL control measures also need to be carried out in the urban area to prevent human cases and the spread of the disease in the risk zone.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Leishmaniose , Animais , Brasil/epidemiologia , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Cães , Leishmaniose/veterinária , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária
7.
Ugeskr Laeger ; 183(21)2021 05 24.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34060464

RESUMO

Bite wounds are common in the emergency departments in Denmark. As a result of the Covid-19 pandemic, more people are adopting pets and the number of hours spent at home with pets are increasing. This will probably result in more bite wounds and therefore, it is as important as ever for emergency doctors to be able to treat bite wounds appropriately. In this review, we summarise the most common types of bite wounds, how to make a thorough physical examination, what to focus on in the anamnesis, and how to treat bite wounds including when to suture and the indications for prophylactic antibiotics.


Assuntos
Mordeduras e Picadas , COVID-19 , Infecção dos Ferimentos , Animais , Antibacterianos/uso terapêutico , Mordeduras e Picadas/epidemiologia , Mordeduras e Picadas/terapia , Gatos , Cães , Humanos , Pandemias , SARS-CoV-2 , Infecção dos Ferimentos/tratamento farmacológico
8.
Viruses ; 13(5)2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064525

RESUMO

Mucins and mucin-like molecules are highly glycosylated, high-molecular-weight cell surface proteins that possess a semi-rigid and highly extended extracellular domain. P-selectin glycoprotein ligand-1 (PSGL-1), a mucin-like glycoprotein, has recently been found to restrict HIV-1 infectivity through virion incorporation that sterically hinders virus particle attachment to target cells. Here, we report the identification of a family of antiviral cellular proteins, named the Surface-Hinged, Rigidly-Extended Killer (SHREK) family of virion inactivators (PSGL-1, CD43, TIM-1, CD34, PODXL1, PODXL2, CD164, MUC1, MUC4, and TMEM123) that share similar structural characteristics with PSGL-1. We demonstrate that SHREK proteins block HIV-1 infectivity by inhibiting virus particle attachment to target cells. In addition, we demonstrate that SHREK proteins are broad-spectrum host antiviral factors that block the infection of diverse viruses such as influenza A. Furthermore, we demonstrate that a subset of SHREKs also blocks the infectivity of a hybrid alphavirus-SARS-CoV-2 (Ha-CoV-2) pseudovirus. These results suggest that SHREK proteins may be a part of host innate immunity against enveloped viruses.


Assuntos
COVID-19/imunologia , Infecções por HIV/imunologia , Glicoproteínas de Membrana/metabolismo , Ligação Viral , Animais , COVID-19/virologia , Cães , Células HEK293 , HIV-1/imunologia , Células HeLa , Interações entre Hospedeiro e Microrganismos , Humanos , Imunidade Inata , Células Madin Darby de Rim Canino , Mucinas/farmacologia , SARS-CoV-2/imunologia
10.
Vet Rec ; 188(11): 436, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34086314
11.
BMC Res Notes ; 14(1): 223, 2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34082832

RESUMO

OBJECTIVE: Dogs are a breed of animals that play important roles in security service, companionship, hunting, guard, work and models of research for application in humans. Intelligence is the key factor to success in life, most especially for dogs that are used for security purposes at the airports, seaports, public places, houses, schools and farms. However, it has been reported that there is correlation between intelligence, body weight, height and craniometry in human. In view of this, literatures were searched on body weight, height and body surface areas of ten dogs with intent to determining their comparative level of intelligence using encephalization quotient. RESULTS: Findings revealed that dogs have relationship of brain allometry with human as proven by encephalization quotient [Formula: see text] and Brain Mass (E) = kpß, where p is the body weight; k = 0.14 and ß = 0.528, respectively. Saganuwa's formula yielded better results as compared with the other formulas. Dogs with body surface area (BSA), weight and height similar to that of human are the most intelligent. Doberman pinscher is the most intelligent followed by German shepherd, Labrador retriever, Golden retriever, respectively.


Assuntos
Encéfalo , Cruzamento , Animais , Peso Corporal/genética , Cães
12.
J Biomed Nanotechnol ; 17(5): 910-920, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34082876

RESUMO

Cystic Echinococcosis (CE) is caused by Echinococcus granulosus (Eg), which endangers the health of the intermediate host. Therefore, effective canid vaccines against Eg infection are urgently needed to reduce the incidence of this disease. In the present work, the aim was to predict epitopes in four vaccine candidate antigens (VCAs) in Eg as a basis to design a multi-epitope canine-directed vaccine. This vaccine is based on chitosan nanoparticles (CS-NPs) and is directed against Eg infection in the definitive host. The canine-directed vaccine was designed based on Eg antigens EgM9, Eg_10196, EgA31 and EgG1Y162. Several tools in online servers were used to predict VCAs information, which was combined with B cell, CTL and Th epitopes. Considering that acquiring experimental information in canids is difficult, and that it may be possible to perform future experiments in mice, we predicted both canine and murine T cell epitopes. The multi-epitope vaccine was synthetically prepared by ionic crosslinking method, and CS-NPs was used as adjuvant. The mice were immunized by oral gavage and laser scanning confocal microscopy was used to localize the fluorescein- labeled multi-epitope peptide in the intestinal tract. The final multi-epitope vaccine was construct consist of Co1 targeting peptide, four B-cell epitopes, four canine-directed CTL epitopes and four murine-directed Th epitopes. It has been proven experimentally by this research that multi-epitope antigen concentration merged with microfold cells was high in the CS-NPs vaccine group. The present bioinformatics study is a first step towards the construction of a canine-specific multiepitope vaccine against Eg with twelve predicted epitopes. CS-NPs is a potential adjuvant with relatively safe penetration enhancement delivery and a potent immunostimulant.


Assuntos
Quitosana , Equinococose , Echinococcus granulosus , Nanopartículas , Vacinas , Animais , Cães , Camundongos
13.
Braz J Biol ; 82: e241162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34133561

RESUMO

Canine visceral leishmaniasis (CVL) caused by Leishmania (Leishmania) infantum is transmitted by phlebotomine sandflies and a major zoonotic disease in Brazil. Due to the southward expansion of the disease within the country and the central role of dogs as urban reservoirs of the parasite, we have investigated the occurrence of CVL in two municipalities Erval Velho and Herval d'Oeste in the Midwest region of Santa Catarina state. Peripheral blood samples from 126 dogs were collected in both cities and tested for anti-L. infantum antibodies by indirect enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence reaction (IIF) and for the presence of parasite DNA by polymerase chain reaction (PCR) in peripheral blood. From examined dogs, 35.71% (45/126) were positive for at least one of the three tests and two (1.6%) were positive in all performed tests. Twelve dogs (9.5%) were positive for both ELISA and IIF, while 21 dogs were exclusively positive for ELISA (16.7%), and 15 (11.9%) for IIF. L. infantum k-DNA was detected by PCR in 9 out of 126 dogs (7.1%) and clinical symptoms compatible with CVL were observed for 6 dogs. Taken together, these results indicate the transmission of CVL in this region, highlighting the needs for epidemiological surveillance and implementation of control measures for CVL transmission in this region.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Animais , Brasil/epidemiologia , Cidades , Doenças do Cão/epidemiologia , Cães , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária
14.
Rev Bras Parasitol Vet ; 30(2): e026720, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34133617

RESUMO

Dogs are the main urban reservoir of Leishmania infantum, the causative agent of visceral leishmaniasis (VL), which is transmitted by sand flies. In the state of Paraná, the first detection of a positive dog for VL was in 2014, this year Paraná lost free status for this disease (VL). The objectives of this study were to determine the prevalence of canine visceral leishmaniasis in Palotina, the occurrence of vectors that may transmit Leishmania infantum, and the number of notifications of human visceral leishmaniasis cases from period 2010 to 2020. To determine the occurrence of canine visceral leishmaniasis, blood samples from 204 dogs were analyzed using the rapid test DPP® to detect anti-L. infantum antibodies. To investigate the occurrence of potential vectors, monthly collections were made at 18 points within the urban area of the municipality. The number of human visceral leishmaniasis cases was investigated from Epidemiological Surveillance records. None of the serologically tested dogs showed positive titration. Only two specimens of Lutzomyia neivai, one of Lutzomyia sp. and four of Brumptomyia brumpti specimens were collected. No human visceral leishmaniasis cases were reported. These results suggest that there is no evidence of circulation of L. infantum in Palotina.


Assuntos
Doenças do Cão , Leishmania infantum , Leishmaniose Visceral , Saúde Única , Animais , Brasil/epidemiologia , Cidades , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologia , Cães , Insetos Vetores , Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/epidemiologia , Leishmaniose Visceral/veterinária
15.
Handchir Mikrochir Plast Chir ; 53(3): 237-244, 2021 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-34134156

RESUMO

Bite injuries are common. Along with the resulting complications, they represent approximately 1-2 % of all emergency department visits. In over 75 %, the hands are affected. In Northern Europe, bites and subsequent infections are mainly caused by dogs and cats but also by humans.Up to 40 % of all hand infections are caused to bite injuries. Due to the multiple and complex compartments as well as the low soft tissue coverage of functionally relevant structures, even the smallest and most superficial bite injuries of the hand lead to infections. Any bite injury to the hand may subsequently may result in a fulminant infection and, rarely, even death.The spectrum of pathogens from the oral flora of the biting animal or person is diverse and includes aerobic and anaerobic bacterial strains. Bite injuries represent a major challenge for both the injured person and the attending physician. The rate of complications has been shown to increase with delayed medical consultation, lack of medical care and inadequate wound care. In this review, we discuss the types and complications of bite wounds, their potential risk of infection, their pathogen spectrum and appearance, and their effective treatment.


Assuntos
Mordeduras e Picadas , Mordeduras Humanas , Doenças do Gato , Doenças do Cão , Infecção dos Ferimentos , Animais , Gatos , Cães , Europa (Continente) , Humanos
16.
Nat Commun ; 12(1): 2654, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976181

RESUMO

Most anti-influenza drugs currently used, such as oseltamivir and zanamivir, inhibit the enzymatic activity of neuraminidase. However, neuraminidase inhibitor-resistant viruses have already been identified from various influenza virus isolates. Here, we report the development of a class of macrocyclic peptides that bind the influenza viral envelope protein hemagglutinin, named iHA. Of 28 iHAs examined, iHA-24 and iHA-100 have inhibitory effects on the in vitro replication of a wide range of Group 1 influenza viruses. In particular, iHA-100 bifunctionally inhibits hemagglutinin-mediated adsorption and membrane fusion through binding to the stalk domain of hemagglutinin. Moreover, iHA-100 shows powerful efficacy in inhibiting the growth of highly pathogenic influenza viruses and preventing severe pneumonia at later stages of infection in mouse and non-human primate cynomolgus macaque models. This study shows the potential for developing cyclic peptides that can be produced more efficiently than antibodies and have multiple functions as next-generation, mid-sized biomolecules.


Assuntos
Antivirais/farmacologia , Modelos Animais de Doenças , Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Infecções por Orthomyxoviridae/tratamento farmacológico , Peptídeos/farmacologia , Pneumonia/prevenção & controle , Animais , Antivirais/química , Cães , Feminino , Células HEK293 , Humanos , Vírus da Influenza A Subtipo H1N1/metabolismo , Macaca fascicularis , Células Madin Darby de Rim Canino , Camundongos Endogâmicos BALB C , Estrutura Molecular , Peptídeos/química , Replicação Viral/efeitos dos fármacos
17.
Nat Commun ; 12(1): 2680, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976191

RESUMO

Bioluminescent imaging (BLI) is one of the most powerful and widely used preclinical imaging modalities. However, the current technology relies on the use of transgenic luciferase-expressing cells and animals and therefore can only be applied to a limited number of existing animal models of human disease. Here, we report the development of a "portable bioluminescent" (PBL) technology that overcomes most of the major limitations of traditional BLI. We demonstrate that the PBL method is capable of noninvasive measuring the activity of both extracellular (e.g., dipeptidyl peptidase 4) and intracellular (e.g., cytochrome P450) enzymes in vivo in non-luciferase-expressing mice. Moreover, we successfully utilize PBL technology in dogs and human cadaver, paving the way for the translation of functional BLI to the noninvasive quantification of biological processes in large animals. The PBL methodology can be easily adapted for the noninvasive monitoring of a plethora of diseases across multiple species.


Assuntos
Fenômenos Biológicos , Diagnóstico por Imagem/métodos , Medições Luminescentes/métodos , Modelos Animais , Animais , Animais Geneticamente Modificados , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/metabolismo , Dipeptidil Peptidase 4/química , Dipeptidil Peptidase 4/metabolismo , Cães , Luciferina de Vaga-Lumes/química , Luciferina de Vaga-Lumes/metabolismo , Humanos , Luciferases/química , Luciferases/genética , Luciferases/metabolismo , Medições Luminescentes/instrumentação , Estrutura Molecular , Reprodutibilidade dos Testes
18.
Pan Afr Med J ; 38: 235, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34046140

RESUMO

Introduction: rabies is a vaccine-preventable viral zoonotic disease. Once clinical symptoms appear, rabies is fatal in almost 100% of cases. The objective of this study was to evaluate the knowledge, attitudes and practices of students at the University of Abomey-Calavi in Benin on rabies in order to explore the factors that promote the occurrence of this zoonosis. Methods: for this purpose, a descriptive cross-sectional survey was conducted among 263 randomly-selected students. The collected data were analyzed by R software with logistic regression. Results: out of all the 263 respondents, 53.2% (n=140) of the students claimed to have heard of canine rabies, compared to 47.5% (n=125) for human rabies. Stray dogs were recognized by 49.0% (n=129) as a prevailing source of rabies infection in people; bites from these dogs were considered as a means of rabies contagion (41.4%; n=109) and vaccination of dogs was considered by 32.7% (n=86) as a means of rabies control in both people and dogs. In case of a dog bite, 60.5% (n=159) of respondents would visit a western medicine human clinic first. For the fate of the biting dog, 18.6% (n=49) and 27.4% (n=72) of respondents, respectively, prefer to euthanize the dog or take the dog to the veterinarian for observation. Regarding the perceived consequences of inaction after a dog bite, 58.2% (n=140) mentioned the risk of rabies. Students in human or animal health were 3 times more aware on rabies. Conclusion: this study identifies the gaps in students´ knowledge, attitudes and practices about effective rabies prevention and control. It will therefore be necessary to intensify awareness and education campaigns among students who could be a good relay of information to other members in their communities.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Vacinas Antirrábicas/administração & dosagem , Raiva/prevenção & controle , Estudantes/estatística & dados numéricos , Adolescente , Adulto , Animais , Benin , Mordeduras e Picadas/complicações , Mordeduras e Picadas/virologia , Estudos Transversais , Doenças do Cão/prevenção & controle , Doenças do Cão/virologia , Cães , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Raiva/transmissão , Inquéritos e Questionários , Universidades , Adulto Jovem , Zoonoses/prevenção & controle , Zoonoses/virologia
19.
J Pharm Pharm Sci ; 24: 227-236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34048668

RESUMO

PURPOSE: Remdesivir and its active metabolite are predominantly eliminated via renal route; however, information regarding renal uptake transporters is limited. In the present study, the interaction of remdesivir and its nucleoside analog GS-441524 with OATP4C1 was evaluated to provide the detailed information about its renal handling. METHODS: We used HK-2 cells, a proximal tubular cell line derived from normal kidney, to confirm the transport of remdesivir and GS-441524. To assess the involvement of OATP4C1 in handling remdesivir and GS-441524, the uptake study of remdesivir and GS-441524 was performed by using OATP4C1-overexpressing Madin-Darby canine kidney II (MDCKII) cells. Moreover, we also evaluated the IC50 and Ki value of remdesivir. RESULTS: The time-dependent remdesivir uptake in HK-2 cells was observed. The results of inhibition study using OATs and OCT2 inhibitors and OATP4C1 knockdown suggested the involvement of renal drug transporter OATP4C1. Remdesivir was taken up by OATP4C1/MDCKII cells. OATP4C1-mediated uptake of remdesivir increased linearly up to 10 min and reached a steady state at 30 min. Remdesivir inhibited OATP4C1-mediated transport in a concentration-dependent manner with the IC50 and apparent Ki values of 42 ± 7.8 µM and 37 ± 6.9 µM, respectively. CONCLUSIONS: We have provided novel information about renal handling of remdesivir. Furthermore, we evaluated the potential drug interaction via OATP4C1 by calculating the Ki value of remdesivir. OATP4C1 may play a pivotal role in remdesivir therapy for COVID-19, particularly in patients with kidney injury.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/metabolismo , COVID-19/tratamento farmacológico , Furanos/metabolismo , Túbulos Renais Proximais/metabolismo , Transportadores de Ânions Orgânicos/metabolismo , Pirróis/metabolismo , Triazinas/metabolismo , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/uso terapêutico , Alanina/metabolismo , Alanina/uso terapêutico , Animais , Antivirais/uso terapêutico , COVID-19/metabolismo , Linhagem Celular , Cães , Relação Dose-Resposta a Droga , Aprovação de Drogas , Furanos/uso terapêutico , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Túbulos Renais Proximais/efeitos dos fármacos , Células Madin Darby de Rim Canino , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Pirróis/uso terapêutico , Triazinas/uso terapêutico
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