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[PMID]:29332223
[Au] Autor:Togasaki E; Shimizu N; Nagao Y; Kawajiri-Manako C; Shimizu R; Oshima-Hasegawa N; Muto T; Tsukamoto S; Mitsukawa S; Takeda Y; Mimura N; Ohwada C; Takeuchi M; Sakaida E; Iseki T; Yoshitomi H; Ohtsuka M; Miyazaki M; Nakaseko C
[Ad] Endereço:Department of Hematology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.
[Ti] Título:Long-term efficacy of partial splenic embolization for the treatment of steroid-resistant chronic immune thrombocytopenia.
[So] Source:Ann Hematol;97(4):655-662, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Thrombopoietin-receptor agonists have been recently introduced for a second-line treatment of immune thrombocytopenia (ITP). Splenectomy has tended to be avoided because of its complications, but the response rate of splenectomy is 60-80% and it has still been considered for steroid-refractory ITP. We performed partial splenic embolization (PSE) as an alternative to splenectomy. Between 1988 and 2013, 91 patients with steroid-resistant ITP underwent PSE at our hospital, and we retrospectively analyzed the efficacy and long-term outcomes of PSE. The complete response rate (CR, platelets > 100 × 10 /L) was 51% (n = 46), and the overall response rate (CR plus response (R), > 30 × 10 /L) was 84% (n = 76). One year after PSE, 70% of patients remained CR and R. The group with peak platelet count after PSE ≥ 300 × 10 /L (n = 29) exhibited a significantly higher platelet count than the group with platelet count < 300 × 10 /L (n = 40) at any time point after PSE. The failure-free survival (FFS) rates at 1, 5, and 10 years were 78, 56, and 52%, respectively. Second PSE was performed in 20 patients who relapsed (n = 14) or had no response to the initial PSE (n = 6), and the overall response was achieved in 63% patients. There were no PSE-related deaths. These results indicate that PSE is a safe and effective alternative therapy to splenectomy for patients with steroid-resistant ITP as it generates long-term, durable responses.
[Mh] Termos MeSH primário: Embolização Terapêutica
Púrpura Trombocitopênica Idiopática/terapia
Baço/irrigação sanguínea
[Mh] Termos MeSH secundário: Adolescente
Corticosteroides/uso terapêutico
Adulto
Idoso
Idoso de 80 Anos ou mais
Intervalo Livre de Doença
Resistência a Medicamentos
Resistência a Múltiplos Medicamentos
Embolização Terapêutica/efeitos adversos
Feminino
Seguimentos
Hospitais Universitários
Seres Humanos
Japão
Masculino
Meia-Idade
Tamanho do Órgão
Púrpura Trombocitopênica Idiopática/diagnóstico por imagem
Púrpura Trombocitopênica Idiopática/tratamento farmacológico
Púrpura Trombocitopênica Idiopática/patologia
Estudos Retrospectivos
Baço/diagnóstico por imagem
Baço/efeitos dos fármacos
Baço/patologia
Esteroides/uso terapêutico
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Adrenal Cortex Hormones); 0 (Steroids)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180115
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-018-3232-x


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[PMID]:29429191
[Au] Autor:Zhang YY; Lou HF; Wang CS; Zhang L
[Ad] Endereço:Deparment of Otorhinolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China; Beijing Key Laboratory of Nasal Diseases, Beijing Institude of Otorhinolaryngology, Beijing 100005, China.
[Ti] Título:[Mechanisms underlying glucocorticoid resistance in chronic rhinosinusitis with nasal polyps].
[So] Source:Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi;53(2):154-160, 2018 Feb 07.
[Is] ISSN:1673-0860
[Cp] País de publicação:China
[La] Idioma:chi
[Ab] Resumo:Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease that occurs in the nasal and sinus mucosa, which is a common disease in otorhinolaryngology. At present, CRSwNP can be effectively treated by glucocorticoids (GC). GC binds to GC receptors in the nasal mucosa, affects the expression of inflammatory genes, inhibits the activation and action of eosinophils, T cell-associated inflammatory responses in nasal polyps, as well as tissue remodeling. However, there are some patients fall reponse to GC, so called GC resistance. The study suggests that the possible mechanism of CRSwNP GC resistance is mainly related to GC receptor abnormal, the role of cytokines and transcription factors, such as Th cells and IL-8. In addition, MAPK-related kinases and histone deacetylase in the GC signaling pathway also play important roles in the GC resistance process. This paper reviews the mechanism of GC treatment of CRSwNP, the mechanism of GC resistance and alternative treatment of GC.
[Mh] Termos MeSH primário: Glucocorticoides/uso terapêutico
Erros Inatos do Metabolismo
Pólipos Nasais/tratamento farmacológico
Receptores de Glucocorticoides/deficiência
Rinite/tratamento farmacológico
Sinusite/tratamento farmacológico
[Mh] Termos MeSH secundário: Doença Crônica
Citocinas/metabolismo
Resistência a Medicamentos
Glucocorticoides/metabolismo
Seres Humanos
Mucosa Nasal/metabolismo
Pólipos Nasais/complicações
Rinite/complicações
Transdução de Sinais
Sinusite/complicações
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cytokines); 0 (Glucocorticoids); 0 (Receptors, Glucocorticoid); 0 (Transcription Factors)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180213
[St] Status:MEDLINE
[do] DOI:10.3760/cma.j.issn.1673-0860.2018.02.017


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[PMID]:28460112
[Au] Autor:Aponte S; Guerra ÁP; Álvarez-Larrotta C; Bernal SD; Restrepo C; González C; Yasnot MF; Knudson-Ospina A
[Ad] Endereço:Grupo de Bioquímica y Biología Celular, Instituto Nacional de Salud, Bogotá, D.C., Colombia.
[Ti] Título:Baseline in vivo, ex vivo and molecular responses of Plasmodium falciparum to artemether and lumefantrine in three endemic zones for malaria in Colombia.
[So] Source:Trans R Soc Trop Med Hyg;111(2):71-80, 2017 02 01.
[Is] ISSN:1878-3503
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Background: Colombia began using artemisinin-based combination therapies for the treatment of uncomplicated Plasmodium falciparum malaria in 2006. It is necessary to implement resistance surveillance to antimalarial drugs in order to promptly detect changes in parasite susceptibility. The aim of this study was to establish a susceptibility baseline of P. falciparum to artemether-lumefantrine using three monitoring tools. Methods: Patients with uncomplicated malaria treated with artemether-lumefantrine underwent clinical and parasitological follow-up over 28 days. Ex vivo test was performed using the microtest technique for chloroquine, arthemeter, dihydroartemisinin and lumefantrine. Pfmdr1 copy number and polymorphisms in Pfk13, Pfatp6, Pfcrt and Pfmdr1 genes were analyzed. Results: From a total of 150 screened patients, 49 completed follow-up for 28 days. All treated patients had adequate clinical and parasitological responses. Parasitic clearance showed a drastic reduction of parasite biomass at 24 hours and complete elimination at 48 hours. One hundred eleven isolates were processed, all exhibited high susceptibility to artemisinins and a slight decrease in susceptibility to lumefantrine. No genetic polymorphisms associated with resistance to artemisinin were found. Conclusion: This study generated a susceptibility baseline in response to therapy with Coartem (artemether-lumefantrine) with numerical reference values, which will allow data comparison with future studies to systematically monitor changes in the parasite and to provide an early alert to the health authorities.
[Mh] Termos MeSH primário: Antimaláricos/uso terapêutico
Artemisininas/uso terapêutico
Etanolaminas/uso terapêutico
Fluorenos/uso terapêutico
Malária/tratamento farmacológico
Plasmodium falciparum/efeitos dos fármacos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Antimaláricos/farmacologia
Artemisininas/farmacologia
Criança
Colômbia
Variações do Número de Cópias de DNA
Combinação de Medicamentos
Resistência a Medicamentos/efeitos dos fármacos
Resistência a Medicamentos/genética
Quimioterapia Combinada
Etanolaminas/farmacologia
Feminino
Fluorenos/farmacologia
Seres Humanos
Malária/parasitologia
Masculino
Meia-Idade
Parasitemia/tratamento farmacológico
Plasmodium falciparum/isolamento & purificação
Polimorfismo Genético
Proteínas de Protozoários/genética
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 0 (Drug Combinations); 0 (Ethanolamines); 0 (Fluorenes); 0 (Protozoan Proteins); 0 (artemether-lumefantrine combination); C7D6T3H22J (artemether); F38R0JR742 (lumefantrine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE
[do] DOI:10.1093/trstmh/trx021


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[PMID]:28453841
[Au] Autor:Requena-Méndez A; Goñi P; Rubio E; Pou D; Fumadó V; Lóbez S; Aldasoro E; Cabezos J; Valls ME; Treviño B; Martínez Montseny AF; Clavel A; Gascon J; Muñoz J
[Ad] Endereço:Barcelona Institute for Global Health, ISGlobal-CRESIB, Universitat de Barcelona, Barcelona , Spain.
[Ti] Título:The Use of Quinacrine in Nitroimidazole-resistant Giardia Duodenalis: An Old Drug for an Emerging Problem.
[So] Source:J Infect Dis;215(6):946-953, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: There is little evidence regarding the management of refractory giardiasis after treatment with nitroimidazoles. This study estimates the proportion of persistent giardiasis in 3 hospitals in Barcelona, describes associated risk factors and genotype, and evaluates the efficacy rate of quinacrine in those with persistent giardiasis. Methods: A clinical, prospective, observational study was conducted in patients with giardiasis treated with nitroimidazoles. Those with persistent giardiasis were provided quinacrine. Molecular characterization of Giardia isolates was performed by polymerase chain reaction amplification of a fragment of tpi and bg genes. Results: Seventy-seven patients were recruited and treated with nitroimidazoles, and in 14 of 71 (20%) of patients followed up, Giardia persisted. Refractory giardiasis was associated with malaise (P = .007) and anorexia (P = .02), with previous giardiasis (P = .03), and with previous antibiotic (P = .02) or antiparasitic(P = .04) use. Quinacrine had an effectiveness rate of 100% in refractory giardiasis (n = 13; 95% confidence interval = 75-100). Molecular characterization showed that 17 (25%) Giardia isolates belonged to assemblage A, and 31 (43%) belonged to assemblage B. In refractory giardiasis, assemblage A and B were found responsible in 4 and 6 cases, respectively. Conclusions: Almost 20% of patients presented persistent giardiasis, belonging to both assemblages A and B, after nitroimidazole. Short course of quinacrine was effective in treating refractory cases. Further controlled studies should evaluate its efficacy and safety.
[Mh] Termos MeSH primário: Giardia lamblia/genética
Giardíase/tratamento farmacológico
Nitroimidazóis/uso terapêutico
Quinacrina/uso terapêutico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Criança
Pré-Escolar
DNA de Protozoário/genética
Resistência a Medicamentos
Fezes/parasitologia
Feminino
Genótipo
Giardia lamblia/efeitos dos fármacos
Giardia lamblia/isolamento & purificação
Seres Humanos
Lactente
Recém-Nascido
Modelos Logísticos
Masculino
Análise Multivariada
Nitroimidazóis/efeitos adversos
Filogenia
Estudos Prospectivos
Quinacrina/efeitos adversos
Espanha
Viagem
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (DNA, Protozoan); 0 (Nitroimidazoles); H0C805XYDE (Quinacrine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix066


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[PMID]:28452903
[Au] Autor:Maschio M; Dinapoli L; Zarabla A; Maialetti A; Giannarelli D; Fabi A; Vidiri A; Cantelmi T
[Ad] Endereço:*Center for Tumor-Related Epilepsy, UOSD Neurology, †Biostatistic Unit, Departments of ‡Oncology, §Radiology, and ∥Service of Psychiatry, Regina Elena National Cancer Institute, Rome, Italy.
[Ti] Título:Zonisamide in Brain Tumor-Related Epilepsy: An Observational Pilot Study.
[So] Source:Clin Neuropharmacol;40(3):113-119, 2017 May/Jun.
[Is] ISSN:1537-162X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: Epilepsy heavily affects the quality of life (QoL) of patients with brain tumor because in addition to taking treatments for the oncological illness, patients are required to live with the long-term taking of antiepileptic drugs (AEDs). The AEDs' adverse effects are common in these patients and can negatively influence their perceptions of their QoL.We conducted an observational pilot study in patients with brain tumor-related epilepsy to verify efficacy, tolerability, and impact on QoL and global neurocognitive performances of zonisamide (ZNS) in add-on. MATERIALS AND METHODS: We recruited 13 patients (5 females, 8 males; mean age, 49.6 years) presenting uncontrolled seizures. At first visit and at final follow-up at 6 months, patients underwent neurological examination, evaluation of adverse events, and cognitive and QoL tests. A seizure diary was given. RESULTS: Eight patients underwent chemotherapy, 3 underwent radiotherapy, and 5 had disease progression. Mean dosage of ZNS at final follow-up was 300 mg/d.Of 9 patients who reached the sixth month follow-up, the mean weekly seizure number before ZNS had been 3.2 ± 5.0, and at final follow-up, the mean weekly seizure number was 0.18 ± 0.41 (P = 0.05).Compared with baseline, we observed stability in all cognitive domains, except for verbal fluency that significantly worsened.Results on QoL tests showed that QoL remained unchanged over time, which could indicate that ZNS did not influence the patients' perceived QoL. CONCLUSIONS: Zonisamide as add-on in our patients seems to be well tolerated and efficacious in controlling seizures. Despite having limitations represented by the fact that our study is observational, with a small study population and a short follow-up period, our results confirm that when choosing an AED, in addition to efficacy, the drug's effect on patients' QoL also needs to be considered, especially for patients facing many psychosocial challenges, such as those with brain tumor-related epilepsy.
[Mh] Termos MeSH primário: Anticonvulsivantes/uso terapêutico
Neoplasias Encefálicas/fisiopatologia
Disfunção Cognitiva/prevenção & controle
Epilepsia/tratamento farmacológico
Isoxazóis/uso terapêutico
Nootrópicos/uso terapêutico
Qualidade de Vida
[Mh] Termos MeSH secundário: Antineoplásicos/efeitos adversos
Antineoplásicos/uso terapêutico
Neoplasias Encefálicas/tratamento farmacológico
Neoplasias Encefálicas/radioterapia
Disfunção Cognitiva/induzido quimicamente
Disfunção Cognitiva/etiologia
Disfunção Cognitiva/fisiopatologia
Terapia Combinada/efeitos adversos
Resistência a Medicamentos
Quimioterapia Combinada/efeitos adversos
Epilepsia/induzido quimicamente
Epilepsia/etiologia
Epilepsia/fisiopatologia
Feminino
Seguimentos
Seres Humanos
Itália
Transtornos da Linguagem/induzido quimicamente
Transtornos da Linguagem/etiologia
Transtornos da Linguagem/fisiopatologia
Transtornos da Linguagem/prevenção & controle
Masculino
Meia-Idade
Projetos Piloto
Radioterapia/efeitos adversos
Índice de Gravidade de Doença
Comportamento Verbal/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Anticonvulsants); 0 (Antineoplastic Agents); 0 (Isoxazoles); 0 (Nootropic Agents); 459384H98V (zonisamide)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1097/WNF.0000000000000218


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[PMID]:29326268
[Au] Autor:Cowell AN; Istvan ES; Lukens AK; Gomez-Lorenzo MG; Vanaerschot M; Sakata-Kato T; Flannery EL; Magistrado P; Owen E; Abraham M; LaMonte G; Painter HJ; Williams RM; Franco V; Linares M; Arriaga I; Bopp S; Corey VC; Gnädig NF; Coburn-Flynn O; Reimer C; Gupta P; Murithi JM; Moura PA; Fuchs O; Sasaki E; Kim SW; Teng CH; Wang LT; Akidil A; Adjalley S; Willis PA; Siegel D; Tanaseichuk O; Zhong Y; Zhou Y; Llinás M; Ottilie S; Gamo FJ; Lee MCS; Goldberg DE; Fidock DA; Wirth DF; Winzeler EA
[Ad] Endereço:School of Medicine, University of California San Diego (UCSD), 9500 Gilman Drive, La Jolla, CA 92093, USA.
[Ti] Título:Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.
[So] Source:Science;359(6372):191-199, 2018 01 12.
[Is] ISSN:1095-9203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Resistência a Medicamentos/genética
Genoma de Protozoário
Plasmodium falciparum/efeitos dos fármacos
Plasmodium falciparum/genética
[Mh] Termos MeSH secundário: Ativação Metabólica
Alelos
Variações do Número de Cópias de DNA
Evolução Molecular Direcionada
Resistência a Múltiplos Medicamentos/genética
Genes de Protozoários
Metabolômica
Mutação
Plasmodium falciparum/crescimento & desenvolvimento
Seleção Genética
Fatores de Transcrição/química
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antimalarials); 0 (Transcription Factors)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180113
[St] Status:MEDLINE
[do] DOI:10.1126/science.aan4472


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[PMID]:29280362
[Au] Autor:Zhang J; Feng GH; Zou CY; Su PC; Liu HE; Yang ZQ
[Ad] Endereço:Department of Pathogen Biology and Immunology, Kunming Medical University, Kunming Yunnan 650500, China.
[Ti] Título:Overview of the improvement of the ring-stage survival assay-a novel phenotypic assay for the detection of artemisinin-resistant .
[So] Source:Zool Res;38(6):317-320, 2017 Nov 18.
[Is] ISSN:2095-8137
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Artemisinin resistance in threatens the remarkable efficacy of artemisinin-based combination therapies worldwide. Thus, greater insight into the resistance mechanism using monitoring tools is essential. The ring-stage survival assay is used for phenotyping artemisinin-resistance or decreased artemisinin sensitivity. Here, we review the progress of this measurement assay and explore its limitations and potential applications.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Artemisininas/farmacologia
Resistência a Medicamentos
Plasmodium falciparum/efeitos dos fármacos
[Mh] Termos MeSH secundário: Bioensaio/métodos
Seres Humanos
Malária Falciparum/parasitologia
Plasmodium falciparum/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antimalarials); 0 (Artemisinins); 9RMU91N5K2 (artemisinine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171228
[St] Status:MEDLINE
[do] DOI:10.24272/j.issn.2095-8137.2017.075


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[PMID]:29370857
[Au] Autor:Järhult JD
[Ad] Endereço:Zoonosis Science Center, Department of Medical Sciences, Uppsala University, 75185, Uppsala, Sweden. josef.jarhult@medsci.uu.se.
[Ti] Título:Environmental resistance development to influenza antivirals: a case exemplifying the need for a multidisciplinary One Health approach including physicians.
[So] Source:Acta Vet Scand;60(1):6, 2018 Jan 25.
[Is] ISSN:1751-0147
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:A multidisciplinary approach is a prerequisite for One Health. Physicians are important players in the One Health team, yet they are often hard to convince of the benefits of the One Health approach. Here, the case for multidisciplinarity including physicians is made using the example of environmental resistance development to influenza antivirals. Neuraminidase inhibitors are the major class of anti-influenza pharmaceuticals, and extensively stockpiled globally as a cornerstone of pandemic preparedness, especially important in the first phase before vaccines can be mass-produced. The active metabolite of oseltamivir that is excreted from treated patients degrades poorly in conventional sewage treatment processes and has been found in river waters. Dabbling ducks constitute the natural influenza A virus reservoir and often reside near sewage treatment plant outlets, where they may be exposed to neuraminidase inhibitor residues. In vivo experiments using influenza-infected Mallards exposed to neuraminidase inhibitors present in their water have shown resistance development and persistence, demonstrating that resistance may be induced and become established in the influenza strains circulating in natural hosts. Neuraminidase inhibitor resistance genes may become part of a human-adapted influenza virus with pandemic potential through reassortment or direct transmission. A pandemic caused by a neuraminidase inhibitor-resistant influenza virus is a serious threat as the first line defense in pandemic preparedness would be disarmed. To assess the risk for environmental influenza resistance development, a broad multidisciplinary team containing chemists, social scientists, veterinarians, biologists, ecologists, virologists, epidemiologists, and physicians is needed. Information about One Health early in high school and undergraduate training, an active participation of One Health-engaged physicians in the debate, and more One Health-adapted funding and publication possibilities are suggested to increase the possibility to engage physicians.
[Mh] Termos MeSH primário: Antivirais/análise
Antivirais/metabolismo
Resistência a Medicamentos/fisiologia
Saúde Única
Médicos
[Mh] Termos MeSH secundário: Animais
Antivirais/uso terapêutico
Reservatórios de Doenças/virologia
Patos
Seres Humanos
Influenza Humana/tratamento farmacológico
Comunicação Interdisciplinar
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antiviral Agents)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1186/s13028-018-0360-1


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[PMID]:29324340
[Au] Autor:Brandão GC; Rocha Missias FC; Arantes LM; Soares LF; Roy KK; Doerksen RJ; Braga de Oliveira A; Pereira GR
[Ad] Endereço:Departamento de Farmácia, Escola de Farmácia, UFOP, Campus Morro do Cruzeiro, s/n, Balxita, CEP 35400-000, Ouro Preto, MG, Brazil.
[Ti] Título:Antimalarial naphthoquinones. Synthesis via click chemistry, in vitro activity, docking to PfDHODH and SAR of lapachol-based compounds.
[So] Source:Eur J Med Chem;145:191-205, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Lapachol is an abundant prenyl naphthoquinone occurring in Brazilian Bignoniaceae that was clinically used, in former times, as an antimalarial drug, despite its moderate effect. Aiming to search for potentially better antimalarials, a series of 1,2,3-triazole derivatives was synthesized by chemical modification of lapachol. Alkylation of the hydroxyl group gave its propargyl ether which, via copper-catalyzed cycloaddition (CuAAC) click chemistry with different organic azides, afforded 17 naphthoquinonolyl triazole derivatives. All the synthetic compounds were evaluated for their in vitro activity against chloroquine resistant Plasmodium falciparum (W2) and for cytotoxicity to HepG2 cells. Compounds containing the naphthoquinolyl triazole moieties showed higher antimalarial activity than lapachol (IC 123.5 µM) and selectivity index (SI) values in the range of 4.5-197.7. Molecular docking simulations of lapachol, atovaquone and all the newly synthesized compounds were carried out for interactions with PfDHODH, a mitochondrial enzyme of the parasite respiratory chain that is essential for de novo pyrimidine biosynthesis. Docking of the naphthoquinonolyl triazole derivatives to PfDHODH yielded scores between -9.375 and -14.55 units, compared to -9.137 for lapachol and -12.95 for atovaquone and disclosed the derivative 17 as a lead compound. Therefore, the study results show the enhancement of DHODH binding affinity correlated with improvement of SI values and in vitro activities of the lapachol derivatives.
[Mh] Termos MeSH primário: Antimaláricos/farmacologia
Naftoquinonas/farmacologia
Plasmodium falciparum/efeitos dos fármacos
[Mh] Termos MeSH secundário: Antimaláricos/síntese química
Antimaláricos/química
Sobrevivência Celular/efeitos dos fármacos
Cloroquina/farmacologia
Química Click
Relação Dose-Resposta a Droga
Resistência a Medicamentos/efeitos dos fármacos
Células Hep G2
Seres Humanos
Modelos Moleculares
Estrutura Molecular
Naftoquinonas/química
Testes de Sensibilidade Parasitária
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antimalarials); 0 (Naphthoquinones); 886U3H6UFF (Chloroquine); B221938VB6 (lapachol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE


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[PMID]:29241036
[Au] Autor:Rea E; Holder AA; Tewari R
[Ad] Endereço:School of Life Sciences, Queens Medical Centre, University of Nottingham, Nottingham, UK.
[Ti] Título:Plasmodium Peekaboo: PK4 Mediates Parasite Latency.
[So] Source:Cell Host Microbe;22(6):724-725, 2017 12 13.
[Is] ISSN:1934-6069
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In this issue of Cell Host & Microbe, Zhang et al. (2017) show that translational repression through eIF2α phosphorylation mediated by PK4 kinase activity plays a key role in artemisinin resistance in recrudescent malaria infections. Targeting this druggable process could extend the lifespan of current frontline treatments.
[Mh] Termos MeSH primário: Parasitos
Plasmodium
[Mh] Termos MeSH secundário: Animais
Antimaláricos
Resistência a Medicamentos/efeitos dos fármacos
Fator de Iniciação 2 em Eucariotos
Malária
Malária Falciparum
Fosforilação
Plasmodium falciparum
[Pt] Tipo de publicação:JOURNAL ARTICLE; COMMENT
[Nm] Nome de substância:
0 (Antimalarials); 0 (Eukaryotic Initiation Factor-2)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180227
[Lr] Data última revisão:
180227
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171215
[St] Status:MEDLINE



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