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1.
Mikrobiyol Bul ; 54(3): 479-489, 2020 Jul.
Artigo em Turco | MEDLINE | ID: mdl-32755522

RESUMO

This study was aimed to investigate the anti-leishmanial effects of bee products (honey and propolis) by using the causative agent of cutaneous leishmaniasis Leishmania tropica promastigotes, in in vitro culture. In vitro anti-leishmanial efficacy of honey (pine, flower and chestnut) and propolis used in the study were evaluated using the microdilution method. Honey, which is a bee product, was dissolved with RPMI medium containing fetal calf serum (FCS) and diluted in the same medium, and serial dilutions were prepared in concentrations between 62.5-1000 mg/ml. Propolis, on the other hand, was dissolved with ethyl alcohol and only 2.5 µl was used from all these concentrations since the alcohol content was more than 50% in these concentrations prepared and we thought that this rate would negatively effect the parasite development. Then, RPMI containing FCS was diluted in the medium and serial dilutions were prepared at concentrations between 50-800 µg/ml. To the dilutions prepared, the promastigot suspension was added so that their final concentrations in the wells were 1 x 106 promastigot/ml and then the medium was incubated for 24 and 48 hours in 26°C. After the incubation, promastigotes were determined microscopically for morphology, mobility and live parasite density, and cell viability was determined by MTS method and 50% inhibitor concentrations (IC50) were compared with control groups. Anti-leishmanial activity of propolis (50, 100, 200, 400 and 800 µg/ml) and honey (62.5, 125, 250, 500 and 1000 mg/ml) on promastigotes was evaluated in vitro. In microscopic examinations, pine honey showed anti-leishmanial activity starting from 62.5 mg/ml, flower honey 250 mg/ml, and chestnut honey 125 mg/ml, and pine honey was more effective on promastigotes (p< 0.05), and propolis was effective from 100 µg/ml concentration. It has been determined that very low concentrations of propolis caused changes in the morphological structure of the parasites and were more effective than the other bee products. The prevention of cell proliferation and decreasing of the IC50 values according with the time of pine honey (IC50= 109.28 mg/ml), flower honey (IC50= 248.07 mg/ml), chestnut honey (IC50= 147.65 mg/ml) and propolis (IC50= 82.98 µg/ml) applied on L.tropica promastigot cell culture was determined by MTS method. In this study, it was found that various concentrations of pine, flower, chestnut honey and propolis showed anti-leishmanial activity on L. tropica promastigotes. It has been observed that pine honey is more effective on promastigotes after 48 hours of incubation period, and propolis is more effective in both morphology and cell inhibition of the parasites even at very low concentrations. It is believed that these data can be used as an alternative treatment method against cutaneous leishmaniasis infections and further studies are required.


Assuntos
Mel , Leishmania tropica , Própole , Animais , Antiparasitários/farmacologia , Abelhas/química , Sobrevivência Celular/efeitos dos fármacos , Leishmania tropica/efeitos dos fármacos , Leishmaniose Cutânea/parasitologia , Estágios do Ciclo de Vida/efeitos dos fármacos , Própole/farmacologia
3.
Indian J Tuberc ; 67(3): 448-451, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32825892

RESUMO

A group of senior doctors with vast clinical experience met on 19th July'20 under the aegis of Academy of Advanced Medical Education. The panel looked at Ivermectin, one of the old molecule and evaluated it's use in COVID 19 (Novel Coronavirus Disease 2019) management. After critical panel discussion, all the attending doctors came to a conclusion that Ivermectin can be a potential molecule for prophylaxis and treatment of people infected with Coronavirus, owing to its anti-viral properties coupled with effective cost, availability and good tolerability and safety.


Assuntos
Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Ivermectina/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Antiparasitários/uso terapêutico , Humanos , Pandemias , Fatores de Risco , Resultado do Tratamento
4.
BMC Infect Dis ; 20(1): 613, 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32811453

RESUMO

BACKGROUND: Strongyloidiasis is caused by the helminth Strongyloides stercoralis and is well-recognised amongst transplant recipients. Serious complications, including Strongyloides hyperinfection which is a syndrome of accelerated autoinfection, or disseminated disease, can occur post-transplantation, resulting in significant morbidity and mortality. Here we present the first published case we are aware of, describing post-transplant Strongyloides hyperinfection in an HIV-positive kidney transplant patient. We discuss the diagnostic challenges and the role of pre-transplant screening. CASE PRESENTATION: A 58-year-old African-American male, originally from the Caribbean, received a deceased donor kidney transplant for presumed focal segmental glomerulosclerosis. He was known to be HIV-positive, with a stable CD4 count, and an undetectable viral load. Five months post-transplant, he developed gastrointestinal symptoms and weight loss. He had a normal eosinophil count (0.1-0.2 × 109/L), negative serum cytomegalovirus DNA, and negative blood and stool cultures. His Strongyloides serology remained negative throughout. A diagnosis of Strongyloides hyperinfection was made by the histological examination of his duodenum and lung, which identified the parasites. He completed his course of treatment with Ivermectin but exhibited profound deconditioning and required a period of total parenteral nutrition. He was subsequently discharged after a prolonged hospital admission of 54 days. CONCLUSIONS: This case highlights the challenges in diagnosing Strongyloides infection and the need to maintain a high index of clinical suspicion. Non-invasive techniques for the diagnosis of Strongyloides may be insufficient. Routine pre-transplant serological strongyloidiasis screening is now performed at our centre.


Assuntos
Soropositividade para HIV/fisiopatologia , HIV/imunologia , Transplante de Rim/efeitos adversos , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/diagnóstico , Estrongiloidíase/etiologia , Transplantados , Afro-Americanos , Animais , Antiparasitários/uso terapêutico , Soropositividade para HIV/virologia , Humanos , Ivermectina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/parasitologia , Doadores de Tecidos , Resultado do Tratamento
6.
Rev Chilena Infectol ; 37(1): 82-84, 2020 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-32730405

RESUMO

Male patient, with a history of alcoholic cirrhosis frequent user of anti-inflammatory drugs including corticosteroids. He consulted for digestive bleeding secondary to a bulbar ulcer. During the admission, he had fever and antibiotic treatment with ceftriaxone is started, for a urinary infection. Fever persisted for 48 hours, so a diagnostic paracentesis was made: Strongyloides stercoralis larvae were seen in the direct microscopic exam. The patient started antiparasitic treatment with ivermectin. He was discharged and did not returned for follow up. Although infection with S. stercoralis is relatively common in patients with alcoholic liver cirrhosis, ascites infected with Strongyloides corresponds to an infrequent form of presentation. This case shows the importance of diagnostic paracentesis in every cirrhotic patient. It is important to consider atypical presentation of Strongyloides infection in the immunocompromised host, considering it could be fatal without treatment.


Assuntos
Cirrose Hepática , Strongyloides stercoralis , Estrongiloidíase , Animais , Antiparasitários/uso terapêutico , Ascite/parasitologia , Líquido Ascítico/parasitologia , Humanos , Ivermectina/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/etiologia , Cirrose Hepática/parasitologia , Masculino , Strongyloides stercoralis/isolamento & purificação , Estrongiloidíase/complicações , Estrongiloidíase/tratamento farmacológico , Estrongiloidíase/fisiopatologia , Resultado do Tratamento
7.
Vet Rec ; 187(2): 75, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32723903
8.
An Acad Bras Cienc ; 92(2): e20200466, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-608501

RESUMO

COVID-19 emerged in December 2019 in China, and since then, has disrupted global public health and changed economic paradigms. In dealing with the new Coronavirus, SARS-CoV-2, the world has not faced such extreme global fragility since the "Spanish flu" pandemic in 1918. Researchers globally are dedicating efforts to the search for an effective treatment for COVID-19. Drugs already used in a clinical setting for other pathologies have been tested as a new therapeutic approach against SARS-CoV-2, setting off a frenzy over the preliminary data of different studies. This work aims to compile and discuss the data published thus far. Despite the potential effects of some antivirals and antiparasitic against COVID-19, clinical studies must confirm real effectiveness. However, non-pharmacological approaches have proven to be the most efficient strategy to date.


Assuntos
Antibacterianos/administração & dosagem , Antiparasitários/administração & dosagem , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Macrolídeos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Inibidores de Serino Proteinase/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Antivirais/química , Antivirais/farmacologia , Humanos , Macrolídeos/química , Macrolídeos/farmacologia , Pandemias , Inibidores de Serino Proteinase/química , Inibidores de Serino Proteinase/farmacologia
9.
Int J Antimicrob Agents ; 56(2): 106037, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32479893

RESUMO

Ivermectin (IVM) is a robust antiparasitic drug with an excellent tolerance and safety profile. Historically it has been the drug of choice for onchocerciasis and lymphatic filariasis global elimination programs. IVM is an oral insecticide and is a standard treatment against intestinal helminths and ectoparasites. The current humanitarian crisis in Venezuela is a regional public health threat that requires immediate action. The public health system in Venezuela has crumbled because of a 70% shortage of medicines in public hospitals, low vaccination campaigns, and the mass exodus of medical personnel. Herein we discuss the repurposing of IVM to attenuate the burden imposed by the most prevalent neglected tropical diseases (NTDs) in Venezuela, including soil-transmitted helminths, ectoparasites and, possibly, vector-borne diseases, such as malaria. In addition, novel experimental evidence has shown that IVM is active and efficacious in vitro against Chagas disease, Leishmaniases, arboviruses, and SARS-CoV-2. In crisis-hit Venezuela, all these infectious diseases are public health emergencies that have long been ignored and require immediate attention. The versatility of IVM could serve as a powerful tool to tackle the multiple overlapping endemic and emergent diseases that currently affect Venezuela. The repurposing of this multipurpose drug would be a timely therapeutic approach to help mitigate the tremendous burden of NTDs nationwide.


Assuntos
Antiparasitários/uso terapêutico , Reposicionamento de Medicamentos , Ivermectina/uso terapêutico , Doenças Parasitárias/tratamento farmacológico , Humanos , Venezuela
10.
An Acad Bras Cienc ; 92(2): e20200466, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32556054

RESUMO

COVID-19 emerged in December 2019 in China, and since then, has disrupted global public health and changed economic paradigms. In dealing with the new Coronavirus, SARS-CoV-2, the world has not faced such extreme global fragility since the "Spanish flu" pandemic in 1918. Researchers globally are dedicating efforts to the search for an effective treatment for COVID-19. Drugs already used in a clinical setting for other pathologies have been tested as a new therapeutic approach against SARS-CoV-2, setting off a frenzy over the preliminary data of different studies. This work aims to compile and discuss the data published thus far. Despite the potential effects of some antivirals and antiparasitic against COVID-19, clinical studies must confirm real effectiveness. However, non-pharmacological approaches have proven to be the most efficient strategy to date.


Assuntos
Antibacterianos/administração & dosagem , Antiparasitários/administração & dosagem , Antivirais/administração & dosagem , Betacoronavirus/efeitos dos fármacos , Infecções por Coronavirus/tratamento farmacológico , Macrolídeos/administração & dosagem , Pneumonia Viral/tratamento farmacológico , Inibidores de Serino Proteinase/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Antiparasitários/química , Antiparasitários/farmacologia , Antivirais/química , Antivirais/farmacologia , Humanos , Macrolídeos/química , Macrolídeos/farmacologia , Pandemias , Inibidores de Serino Proteinase/química , Inibidores de Serino Proteinase/farmacologia
11.
PLoS Negl Trop Dis ; 14(6): e0008298, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32511226

RESUMO

In Haiti, 22 communes still require mass drug administration (MDA) to eliminate lymphatic filariasis (LF) as a public health problem. Several clinical trials have shown that a single oral dose of ivermectin (IVM), diethylcarbamazine (DEC) and albendazole (ALB) (IDA) is more effective than DEC plus ALB (DA) for clearing Wuchereria bancrofti microfilariae (Mf). We performed a cluster-randomized community study to compare the safety and efficacy of IDA and DA in an LF-endemic area in northern Haiti. Ten localities were randomized to receive either DA or IDA. Participants were monitored for adverse events (AE), parasite antigenemia, and microfilaremia. Antigen-positive participants were retested one year after MDA to assess treatment efficacy. Fewer participants (11.0%, 321/2917) experienced at least one AE after IDA compared to DA (17.3%, 491/2844, P<0.001). Most AEs were mild, and the three most common AEs reported were headaches, dizziness and abdominal pain. Serious AEs developed in three participants who received DA. Baseline prevalence for filarial antigenemia was 8.0% (239/3004) in IDA localities and 11.5% (344/2994) in DA localities (<0.001). Of those with positive antigenemia, 17.6% (42/239) in IDA localities and 20.9% (72/344, P = 0.25) in DA localities were microfilaremic. One year after treatment, 84% percent of persons with positive filarial antigen tests at baseline could be retested. Clearance rates for filarial antigenemia were 20.5% (41/200) after IDA versus 25.4% (74/289) after DA (P = 0.3). However, 94.4% (34/36) of IDA recipients and 75.9% (44/58) of DA recipients with baseline microfilaremia were Mf negative at the time of retest (P = 0.02). Thus, MDA with IDA was at least as well tolerated and significantly more effective for clearing Mf compared to the standard DA regimen in this study. Effective MDA coverage with IDA could accelerate the elimination of LF as a public health problem in the 22 communes that still require MDA in Haiti.


Assuntos
Albendazol/administração & dosagem , Antiparasitários/administração & dosagem , Dietilcarbamazina/administração & dosagem , Ivermectina/administração & dosagem , Adolescente , Adulto , Albendazol/efeitos adversos , Animais , Antiparasitários/efeitos adversos , Criança , Pré-Escolar , Dietilcarbamazina/efeitos adversos , Quimioterapia Combinada , Filariose Linfática/tratamento farmacológico , Feminino , Haiti , Humanos , Ivermectina/efeitos adversos , Modelos Logísticos , Masculino , Administração Massiva de Medicamentos/efeitos adversos , Pessoa de Meia-Idade , Prevalência , Resultado do Tratamento , Adulto Jovem
12.
Parasitol Res ; 119(7): 2025-2037, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32504119

RESUMO

Leishmaniasis is a neglected tropical disease with no effective vaccines to date. Globally, it affects around 14 million people living in undeveloped and developing countries. Leishmania, which is the causative eukaryotic organism, possesses unique enzymes and pathways that deviates from its mammalian hosts. The control strategy against leishmaniasis currently depends on chemotherapeutic methods. But these chemotherapeutic therapies possess several side effects, and therefore, the identification of potential drug targets has become very crucial. Identification of suitable drug targets is necessary to design specific inhibitors that can target and control the parasite. These unique enzymes can be used as possible drug targets after biochemical characterization and understanding the role of these enzymes. In this review, the authors discuss various metabolic pathways that are essential for the survival of the parasite and can be exploited as potential drug targets against leishmaniasis.


Assuntos
Antiparasitários , Leishmania/metabolismo , Leishmaniose/tratamento farmacológico , Redes e Vias Metabólicas/efeitos dos fármacos , Terapia de Alvo Molecular , Animais , Antiparasitários/farmacologia , Antiparasitários/uso terapêutico , Sistemas de Liberação de Medicamentos , Humanos , Leishmania/efeitos dos fármacos
13.
J Zoo Wildl Med ; 51(2): 416-425, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32549573

RESUMO

Moxidectin is a commonly used lipophilic anthelmintic with activity against a wide range of nematodes. It is labeled for use in cattle by oral, topical, and subcutaneous routes. In semi-free ranging conditions, many anthelmintics are remotely administered intramuscularly due to an inability to administer by other routes without restraint. During 2015-2016, three animals including a roan (Hippotragus equinus), sable (Hippotragus niger), and Arabian oryx (Oryx leucoryx) treated with moxidectin developed clinical signs consistent with toxicosis. The primary sign was severe neurologic depression within 12 to 24 hr. Based on recommendations in domestic cases, animals were treated with intravenous lipid therapy and supportive care while diagnostic testing was performed. All three initially improved prior to succumbing to secondary problems associated with prolonged recumbency. Moxidectin has been administered remotely on 97 occasions in eight different exotic ruminant species at Fossil Rim, with only the above three cases showing clinical signs of toxicosis. Two potential causes in these cases include poor body condition leading to a smaller volume of distribution, thus allowing higher concentrations to overwhelm the blood-brain barrier, or a genetic defect similar to some herding dog breeds. Given that cases were seen in three different species at an overall low incidence within a given species, a genetic defect is considered unlikely. The animals affected did have significantly lower body condition score than conspecifics, and it is considered likely that this predisposed these animals to toxicosis. Therefore, caution should be used when administering moxidectin intramuscularly in animals in poor body condition.


Assuntos
Antílopes , Antiparasitários/toxicidade , Macrolídeos/toxicidade , Envenenamento/veterinária , Animais , Animais de Zoológico , Evolução Fatal , Feminino , Masculino , Envenenamento/etiologia , Texas
14.
Hautarzt ; 71(6): 447-454, 2020 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-32430543

RESUMO

BACKGROUND: The diagnosis of scabies has become surprisingly frequent in Germany in recent years and the use of scabicides has risen significantly. OBJECTIVE: The aim of our survey was to determine whether this trend can also be detected among military personnel of the German Armed Forces (Bundeswehr). METHODS: The study was conducted as a retrospective single-center study over a period of 8 years from 2012 to 2019 in the Department of Dermatology of the Armed Forces Hospital Berlin, Germany. Data were generated from the hospital information system (KIS), which was searched for all scabies-coded diagnoses according to ICD10 code B86 both as outpatients and inpatients. Only first presentations with scabies diagnosis confirmed by dermoscopy or microscopy by a dermatologist were included. Inpatient treatment was required if a patient was not cured after at least three antiscabies treatment cycles in the outpatient setting. RESULTS: The data show that there has been a steady increase in the diagnosis of scabies in Bundeswehr personnel. Moreover, our data show that the number of unsuccessfully treated outpatients increased and required in-hospital treatment. CONCLUSION: We observed an increase of scabies among German military personnel who represent a typical at-risk group. These results support the observations of an increased incidence of scabies in Germany in general and especially in an at-risk population. With the general increase in scabies cases, there are also increasing numbers of German military personnel who are refractory to treatment, which was largely attributed to inadequate treatment of contact persons and individual treatment errors. Nevertheless, the data also emphasize the low overall prevalence of scabies; therefore, all diagnoses should be confirmed by dermoscopy or microscopy after 14 days whenever possible to rule out the bias of overreporting due to false-positive cases diagnosed only by clinical examination.


Assuntos
Antiparasitários/administração & dosagem , Ivermectina/administração & dosagem , Militares/estatística & dados numéricos , Escabiose/epidemiologia , Administração Tópica , Animais , Antiparasitários/uso terapêutico , Alemanha/epidemiologia , Humanos , Ivermectina/uso terapêutico , Estudos Retrospectivos , Escabiose/diagnóstico , Escabiose/tratamento farmacológico , Resultado do Tratamento
15.
Pharmacol Res ; 157: 104874, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32360581

RESUMO

Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2; ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019. Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately widely ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2, soonest. The author also recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author suggests more trials for interferons to be tested against SARS CoV-2, especially in severe and critical COVID-19 cases.


Assuntos
Azitromicina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Quimioterapia Combinada/métodos , Pneumonia Viral/tratamento farmacológico , Tiazóis/uso terapêutico , Antiparasitários/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Humanos , Pandemias
16.
Parasitol Res ; 119(6): 1925-1941, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32279093

RESUMO

Toxoplasmosis is a common parasitic disease caused by Toxoplasma gondii. Limitations of available treatments motivate the search for better therapies for toxoplasmosis. In this study, we synthesized a series of new imidazole derivatives: bis-imidazoles (compounds 1-8), phenyl-substituted 1H-imidazoles (compounds 9-19), and thiopene-imidazoles (compounds 20-26). All these compounds were assessed for in vitro potential to restrict the growth of T. gondii. To explore the structure-activity relationships, molecular analyses and bioactivity prediction studies were performed using a standard molecular model. The in vitro results, in combination with the predictive model, revealed that the imidazole derivatives have excellent selectivity activity against T. gondii versus the host cells. Of the 26 compounds screened, five imidazole derivatives (compounds 10, 11, 18, 20, and 21) shared a specific structural moiety and exhibited significantly high selectivity (> 1176 to > 27,666) towards the parasite versus the host cells. These imidazole derivatives are potential candidates for further studies. We show evidence that supports the antiparasitic action of the imidazole derivatives. The findings are promising in that they reinforce the prospects of imidazole derivatives as alternative and effective antiparasitic therapy as well as providing evidence for a probable biological mechanism.


Assuntos
Antiparasitários/química , Antiparasitários/farmacologia , Imidazóis/química , Imidazóis/farmacologia , Toxoplasma/efeitos dos fármacos , Animais , Células Cultivadas , Humanos , Imidazóis/síntese química , Modelos Moleculares , Relação Estrutura-Atividade , Toxoplasmose/parasitologia
17.
PLoS Negl Trop Dis ; 14(4): e0008224, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32302296

RESUMO

Giardiasis and other protozoan infections are major worldwide causes of morbidity and mortality, yet development of new antimicrobial agents with improved efficacy and ability to override increasingly common drug resistance remains a major challenge. Antimicrobial drug development typically proceeds by broad functional screens of large chemical libraries or hypothesis-driven exploration of single microbial targets, but both strategies have challenges that have limited the introduction of new antimicrobials. Here, we describe an alternative drug development strategy that identifies a sufficient but manageable number of promising targets, while reducing the risk of pursuing targets of unproven value. The strategy is based on defining and exploiting the incompletely understood adduction targets of 5-nitroimidazoles, which are proven antimicrobials against a wide range of anaerobic protozoan and bacterial pathogens. Comprehensive adductome analysis by modified click chemistry and multi-dimensional proteomics were applied to the model pathogen Giardia lamblia to identify dozens of adducted protein targets common to both 5'-nitroimidazole-sensitive and -resistant cells. The list was highly enriched for known targets in G. lamblia, including arginine deiminase, α-tubulin, carbamate kinase, and heat shock protein 90, demonstrating the utility of the approach. Importantly, over twenty potential novel drug targets were identified. Inhibitors of two representative new targets, NADP-specific glutamate dehydrogenase and peroxiredoxin, were found to have significant antigiardial activity. Furthermore, all the identified targets remained available in resistant cells, since giardicidal activity of the respective inhibitors was not impacted by resistance to 5'-nitroimidazoles. These results demonstrate that the combined use of click chemistry and proteomics has the potential to reveal alternative drug targets for overcoming antimicrobial drug resistance in protozoan parasites.


Assuntos
Antiparasitários/farmacologia , Química Click/métodos , Descoberta de Drogas/métodos , Giardia lamblia/efeitos dos fármacos , Indazóis/farmacologia , Proteínas de Protozoários/metabolismo , Animais , Antiparasitários/síntese química , Antiparasitários/uso terapêutico , Modelos Animais de Doenças , Feminino , Giardíase/tratamento farmacológico , Indazóis/síntese química , Indazóis/uso terapêutico , Intestino Delgado/parasitologia , Masculino , Camundongos Endogâmicos C57BL , Carga Parasitária , Ligação Proteica , Proteômica/métodos
18.
BMC Infect Dis ; 20(1): 257, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32228484

RESUMO

BACKGROUND: Cryptosporidium sp. are common intracellular parasites responsible of severe diarrhea in T-cell-immunocompromised patients. We report the first case of a woman who contracted cryptosporidiosis after treatment with fingolimod, a drug labeled for multiple sclerosis and responsible for marked lymphopenia. CASE PRESENTATION: A 60-year-old woman was admitted for abdominal pain diarrhea and fever. The patient suffered from multiple sclerosis and had been treated with fingolimod from august 2017 to september 2018 time of occurrence of the first digestive symptoms. Stool culture was negative but parasitological examination was positive for Cryptosporidium sp. Blood biological examination profound lymphopenia of 240/mm3 [17 CD4/mm3 (7%) and 32 CD8/mm3 (14%)]. Fingolimod was stopped, and the patient was put on nitazoxanide 500 mg bid for 7 days. The diarrhea resolved and no relapse was observed. Six other cases were found in the Pharmacovigilance database. CONCLUSION: Physicians should be aware of this association and screen for Cryptosporidium in cases of diarrhea in patients treated with fingolimod. Patients should be aware of this risk and advise to take appropriate measures to avoid such contamination.


Assuntos
Criptosporidiose/tratamento farmacológico , Diarreia/parasitologia , Cloridrato de Fingolimode/efeitos adversos , Dor Abdominal/parasitologia , Animais , Antiparasitários/uso terapêutico , Criptosporidiose/parasitologia , Diarreia/etiologia , Fezes/parasitologia , Feminino , Febre/parasitologia , Cloridrato de Fingolimode/uso terapêutico , Humanos , Hospedeiro Imunocomprometido , Pessoa de Meia-Idade , Esclerose Múltipla/tratamento farmacológico , Farmacovigilância , Tiazóis/uso terapêutico
19.
Medicina (B Aires) ; 80(2): 185-188, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32282329

RESUMO

Miasis is the infestation of man and animals by larvae of flies belonging to the order Diptera, suborder Cyclorrapha. Eighty percent of miasis in Argentina is caused by Cochliomyia hominivorax, a species that induces pronounced tissue invasion and destruction, and results in severe clinical forms. Because of the aggressiveness of its larvae, it is important to reach a specific etiological diagnosis. We present four cases of miasis by C. hominivorax in two patients living in the city of Buenos Aires but working in a rural area and two patients living in the Greater Buenos Aires.


Assuntos
Miíase/parasitologia , Idoso de 80 Anos ou mais , Animais , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Antiparasitários/uso terapêutico , Argentina , Dípteros , Feminino , Humanos , Ivermectina/uso terapêutico , Larva , Masculino , Pessoa de Meia-Idade , Miíase/tratamento farmacológico , Miíase/etiologia , Toxoide Tetânico/uso terapêutico
20.
PLoS Negl Trop Dis ; 14(3): e0008106, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32176703

RESUMO

Lymphatic filariasis has remained endemic in Fiji despite repeated mass drug administration using the well-established and safe combination of diethylcarbamazine and albendazole (DA) since 2002. In certain settings the addition of ivermectin to this combination (IDA) remains a safe strategy and is more efficacious. However, the safety has yet to be described in scabies and soil-transmitted helminth endemic settings like Fiji. Villages of Rotuma and Gau islands were randomised to either DA or IDA. Residents received weight-based treatment unblinded with standard exclusions. Participants were actively found and asked by a nurse about their health daily for the first two days and then asked to seek review for the next five days if unwell. Anyone with severe symptoms were reviewed by a doctor and any serious adverse event was reported to the Medical Monitor and Data Safety Monitoring Board. Of 3612 enrolled and eligible participants, 1216 were randomised to DA and 2396 to IDA. Age and sex in both groups were representative of the population. Over 99% (3598) of participants completed 7 days follow-up. Adverse events were reported by 600 participants (16.7%), distributed equally between treatment groups, with most graded as mild (93.2%). There were three serious adverse events, all judged not attributable to treatment by an independent medical monitor. Fatigue was the most common symptom reported by 8.5%, with headache, dizziness, nausea and arthralgia being the next four most common symptoms. Adverse events were more likely in participants with microfilaremia (43.2% versus 15.7%), but adverse event frequency was not related to the presence of scabies or soil-transmitted helminth infection. IDA has comparable safety to DA with the same frequency of adverse events experienced following community mass drug administration. The presence of co-endemic infections did not increase adverse events. IDA can be used in community programs where preventative chemotherapy is needed for control of lymphatic filariasis and other neglected tropical diseases.


Assuntos
Albendazol/efeitos adversos , Antiparasitários/efeitos adversos , Dietilcarbamazina/efeitos adversos , Inseticidas/efeitos adversos , Ivermectina/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Albendazol/administração & dosagem , Antiparasitários/administração & dosagem , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas/tratamento farmacológico , Dietilcarbamazina/administração & dosagem , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Filariose Linfática/tratamento farmacológico , Feminino , Fiji , Helmintíase/tratamento farmacológico , Humanos , Lactente , Inseticidas/administração & dosagem , Ivermectina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Doenças Negligenciadas/tratamento farmacológico , População Rural , Escabiose/tratamento farmacológico , Resultado do Tratamento , Adulto Jovem
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