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[PMID]:29191265
[Au] Autor:Gobbato AAM; Gobbato CARS; Moreno RA; Antunes NJ; De Nucci G
[Ti] Título:Dapaconazole versus ketoconazole in the treatment of interdigital tinea pedis.
[So] Source:Int J Clin Pharmacol Ther;56(1):31-33, 2018 Jan.
[Is] ISSN:0946-1965
[Cp] País de publicação:Germany
[La] Idioma:eng
[Mh] Termos MeSH primário: Antifúngicos/uso terapêutico
Imidazóis/uso terapêutico
Cetoconazol/uso terapêutico
Tinha dos Pés/tratamento farmacológico
[Mh] Termos MeSH secundário: Adulto
Feminino
Seres Humanos
Masculino
Meia-Idade
Pomadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (1-(2-(2,4-dichlorophenyl)-2-(4-(trifluoromethyl)benzyloxy)ethyl)-1H-imidazole); 0 (Antifungal Agents); 0 (Imidazoles); 0 (Ointments); R9400W927I (Ketoconazole)
[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:171202
[St] Status:MEDLINE
[do] DOI:10.5414/CP203124


  2 / 5353 MEDLINE  
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[PMID]:28989052
[Au] Autor:Matowane RG; Wieteska L; Bamal HD; Kgosiemang IKR; Van Wyk M; Manume NA; Abdalla SMH; Mashele SS; Gront D; Syed K
[Ad] Endereço:Unit for Drug Discovery Research, Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9300, Free State, South Africa.
[Ti] Título:In silico analysis of cytochrome P450 monooxygenases in chronic granulomatous infectious fungus Sporothrix schenckii: Special focus on CYP51.
[So] Source:Biochim Biophys Acta;1866(1):166-177, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Sporotrichosis is an emerging chronic, granulomatous, subcutaneous, mycotic infection caused by Sporothrix species. Sporotrichosis is treated with the azole drug itraconazole as ketoconazole is ineffective. It is a well-known fact that azole drugs act by inhibiting cytochrome P450 monooxygenases (P450s), heme-thiolate proteins. To date, nothing is known about P450s in Sporothrix schenckii and the molecular basis of its resistance to ketoconazole. Here we present genome-wide identification, annotation, phylogenetic analysis and comprehensive P450 family-level comparative analysis of S. schenckii P450s with pathogenic fungi P450s, along with a rationale for ketoconazole resistance by S. schenckii based on in silico structural analysis of CYP51. Genome data-mining of S. schenckii revealed 40 P450s in its genome that can be grouped into 32 P450 families and 39 P450 subfamilies. Comprehensive comparative analysis of P450s revealed that S. schenckii shares 11 P450 families with plant pathogenic fungi and has three unique P450 families: CYP5077, CYP5386 and CYP5696 (novel family). Among P450s, CYP51, the main target of azole drugs was also found in S. schenckii. 3D modeling of S. schenckii CYP51 revealed the presence of characteristic P450 motifs with exceptionally large reductase interaction site 2. In silico analysis revealed number of mutations that can be associated with ketoconazole resistance, especially at the channel entrance to the active site. One of possible reason for better stabilization of itraconazole, compared to ketoconazole, is that the more extended molecule of itraconazole may form a hydrogen bond with ASN-230. This in turn may explain its effectiveness against S. schenckii vis-a-vis resistant to ketoconazole. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.
[Mh] Termos MeSH primário: Antifúngicos/química
Sistema Enzimático do Citocromo P-450/química
Proteínas Fúngicas/química
Genoma Fúngico
Itraconazol/química
Sporothrix/enzimologia
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Antifúngicos/farmacologia
Domínio Catalítico
Cristalografia por Raios X
Sistema Enzimático do Citocromo P-450/genética
Sistema Enzimático do Citocromo P-450/metabolismo
Farmacorresistência Fúngica/genética
Proteínas Fúngicas/antagonistas & inibidores
Proteínas Fúngicas/genética
Proteínas Fúngicas/metabolismo
Expressão Gênica
Seres Humanos
Itraconazol/farmacologia
Cetoconazol/química
Cetoconazol/farmacologia
Simulação de Acoplamento Molecular
Família Multigênica
Filogenia
Plantas/microbiologia
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Estrutura Secundária de Proteína
Alinhamento de Sequência
Sporothrix/classificação
Sporothrix/efeitos dos fármacos
Sporothrix/genética
Esporotricose/tratamento farmacológico
Esporotricose/microbiologia
Homologia Estrutural de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Fungal Proteins); 304NUG5GF4 (Itraconazole); 9035-51-2 (Cytochrome P-450 Enzyme System); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171010
[St] Status:MEDLINE


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[PMID]:28734977
[Au] Autor:Castrignanò S; D'Avino S; Di Nardo G; Catucci G; Sadeghi SJ; Gilardi G
[Ad] Endereço:Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, Torino, Italy.
[Ti] Título:Modulation of the interaction between human P450 3A4 and B. megaterium reductase via engineered loops.
[So] Source:Biochim Biophys Acta;1866(1):116-125, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Chimerogenesis involving cytochromes P450 is a successful approach to generate catalytically self-sufficient enzymes. However, the connection between the different functional modules should allow a certain degree of flexibility in order to obtain functional and catalytically efficient proteins. We previously applied the molecular Lego approach to develop a chimeric P450 3A4 enzyme linked to the reductase domain of P450 BM3 (BMR). Three constructs were designed with the connecting loop containing no glycine, 3 glycine or 5 glycine residues and showed a different catalytic activity and coupling efficiency. Here we investigate how the linker affects the ability of P450 3A4 to bind substrates and inhibitors. We measure the electron transfer rates and the catalytic properties of the enzyme also in the presence of ketoconazole as inhibitor. The data show that the construct 3A4-5GLY-BMR with the longest loop better retains the binding ability and cooperativity for testosterone, compared to P450 3A4. In both 3A4-3GLY-BMR and 3A4-5GLY-BMR, the substrate induces an increase in the first electron transfer rate and a shorter lag phase related to a domain rearrangements, when compared to the construct without Gly. These data are consistent with docking results and secondary structure predictions showing a propensity to form helical structures in the loop of the 3A4-BMR and 3A4-3GLY-BMR. All three chimeras retain the ability to bind the inhibitor ketoconazole and show an IC comparable with those reported for the wild type protein. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.
[Mh] Termos MeSH primário: Bacillus megaterium/genética
Proteínas de Bactérias/química
Inibidores do Citocromo P-450 CYP3A/química
Citocromo P-450 CYP3A/química
Cetoconazol/química
NADPH-Ferri-Hemoproteína Redutase/química
Proteínas Recombinantes de Fusão/química
[Mh] Termos MeSH secundário: Bacillus megaterium/enzimologia
Proteínas de Bactérias/antagonistas & inibidores
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Citocromo P-450 CYP3A/genética
Citocromo P-450 CYP3A/metabolismo
Inibidores do Citocromo P-450 CYP3A/metabolismo
Expressão Gênica
Seres Humanos
Cetoconazol/metabolismo
Cinética
Ligantes
Simulação de Acoplamento Molecular
NADPH-Ferri-Hemoproteína Redutase/antagonistas & inibidores
NADPH-Ferri-Hemoproteína Redutase/genética
NADPH-Ferri-Hemoproteína Redutase/metabolismo
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Engenharia de Proteínas
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes de Fusão/genética
Proteínas Recombinantes de Fusão/metabolismo
Relação Estrutura-Atividade
Especificidade por Substrato
Testosterona/química
Testosterona/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Cytochrome P-450 CYP3A Inhibitors); 0 (Ligands); 0 (Recombinant Fusion Proteins); 3XMK78S47O (Testosterone); EC 1.14.13.67 (CYP3A4 protein, human); EC 1.14.14.1 (Cytochrome P-450 CYP3A); EC 1.6.2.4 (NADPH-Ferrihemoprotein Reductase); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170724
[St] Status:MEDLINE


  4 / 5353 MEDLINE  
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[PMID]:28578073
[Au] Autor:Baravalle R; Ciaramella A; Baj F; Di Nardo G; Gilardi G
[Ad] Endereço:Department of Life Sciences and Systems Biology, University of Torino, Via Accademia Albertina 13, Torino, Italy.
[Ti] Título:Identification of endocrine disrupting chemicals acting on human aromatase.
[So] Source:Biochim Biophys Acta;1866(1):88-96, 2018 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Human aromatase is the cytochrome P450 catalysing the conversion of androgens into estrogens playing a key role in the endocrine system. Due to this role, it is likely to be a target of the so-called endocrine disrupting chemicals, a series of compounds able to interfere with the hormone system with toxic effects. If on one side the toxicity of some compounds such as bisphenol A is well known, on the other side the toxic concentrations of such compounds as well as the effect of the many other molecules that are in contact with us in everyday life still need a deep investigation. The availability of biological assays able to detect the interaction of chemicals with key molecular targets of the endocrine system represents a possible solution to identify potential endocrine disrupting chemicals. Here the so-called alkali assay previously developed in our laboratory is applied to test the effect of different compounds on the activity of human aromatase. The assay is based on the detection of the alkali product that forms upon strong alkali treatment of the NADP released upon enzyme turnover. Here it is applied on human aromatase and validated using anastrozole and sildenafil as known aromatase inhibitors. Out of the small library of compounds tested, resveratrol and ketoconazole resulted to inhibit aromatase activity, while bisphenol A and nicotine were found to exert an inhibitory effect at relatively high concentrations (100µM), and other molecules such as lindane and four plasticizers did not show any significant effect. These data are confirmed by quantification of the product estrone in the same reaction mixtures through ELISA. Overall, the results show that the alkali assay is suitable to screen for molecules that interfere with aromatase activity. As a consequence it can also be applied to other molecular targets of EDCs that use NAD(P)H for catalysis in a high throughput format for the fast screening of many different compounds as endocrine disrupting chemicals. This article is part of a Special Issue entitled: Cytochrome P450 biodiversity and biotechnology, edited by Erika Plettner, Gianfranco Gilardi, Luet Wong, Vlada Urlacher, Jared Goldstone.
[Mh] Termos MeSH primário: Inibidores da Aromatase/química
Aromatase/química
Bioensaio
Disruptores Endócrinos/química
[Mh] Termos MeSH secundário: Aromatase/genética
Inibidores da Aromatase/análise
Compostos Benzidrílicos/análise
Compostos Benzidrílicos/química
Disruptores Endócrinos/análise
Ensaio de Imunoadsorção Enzimática
Estrona/química
Expressão Gênica
Seres Humanos
Cetoconazol/análise
Cetoconazol/química
Ligantes
NADP/química
Nicotina/análise
Nicotina/química
Nitrilos/análise
Nitrilos/química
Fenóis/análise
Fenóis/química
Ligação Proteica
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Citrato de Sildenafila/análise
Citrato de Sildenafila/química
Bibliotecas de Moléculas Pequenas/análise
Bibliotecas de Moléculas Pequenas/química
Estilbenos/análise
Estilbenos/química
Triazóis/análise
Triazóis/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Aromatase Inhibitors); 0 (Benzhydryl Compounds); 0 (Endocrine Disruptors); 0 (Ligands); 0 (Nitriles); 0 (Phenols); 0 (Recombinant Proteins); 0 (Small Molecule Libraries); 0 (Stilbenes); 0 (Triazoles); 2DI9HA706A (Estrone); 2Z07MYW1AZ (anastrozole); 53-59-8 (NADP); 6M3C89ZY6R (Nicotine); BW9B0ZE037 (Sildenafil Citrate); EC 1.14.14.1 (Aromatase); EC 1.14.14.1 (CYP19A1 protein, human); MLT3645I99 (bisphenol A); Q369O8926L (resveratrol); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180208
[Lr] Data última revisão:
180208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170605
[St] Status:MEDLINE


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[PMID]:29016694
[Au] Autor:Galvão EL; Rabello A; Cota GF
[Ad] Endereço:Pesquisa Clínica e Políticas Públicas em Doenças Infecto-Parasitárias-Centro de Pesquisas René Rachou-Fundação Oswaldo Cruz, Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
[Ti] Título:Efficacy of azole therapy for tegumentary leishmaniasis: A systematic review and meta-analysis.
[So] Source:PLoS One;12(10):e0186117, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Several controlled and uncontrolled studies addressing azole antifungal drugs for cutaneous and mucosal leishmaniasis have been published with inconclusive results. We conducted a systematic literature review of studies evaluating the efficacy and toxicity associated with azole therapy for tegumentary leishmaniasis. METHODOLOGY: PRISMA guidelines for systematic reviews and the Cochrane manual were followed, and the review methodology was registered (PROSPERO; CRD42016048668). Sources included the EMBASE, Web of Science, MEDLINE, LILACS, and IBECS databases along with a manual search of references from evaluated studies. Additional resources such as Google Scholar and clinicaltrials.gov were also searched. We included all studies reporting cure rate after cutaneous or mucosal leishmaniasis treatment with systemic azole drugs, regardless of their design. R software was used to estimate global rates of success and adverse events with each drug. The main outcome of interest was clinical cure, defined as complete re-epithelialization of all lesions. RESULTS: A total of 37 studies involving 1259 patients that reported outcomes after fluconazole (9), ketoconazole (14) and itraconazole (15) treatments were included. Only 14 (38%) were randomized controlled trials (RCT). The pooled azole final efficacy rate was 64% (CI95%: 57-70%) for all studies and 60% (CI95%: 50-70%) (p = 0.41) if only RCTs studies were considered. Twenty-four studies were conducted in the Old World and 13 studies in the Americas. The final efficacy rate according to New and Old World were 62% (CI95%: 43-77%) and 66% (CI95%: 58-73%), respectively. The final efficacy rate of azoles according to species were 89% (CI95%: 50-98%) for L. mexicana; 88% for L. infantum (CI95%: 27-99%); 80% for L. donovani; 53% (CI95%: 29-76%) for L. major; 49% for L. braziliensis (CI95%: 21-78%); and 15% (CI95%: 1-84%) for L. tropica. The cure rates were similar among the fluconazole, ketoconazole and itraconazole group arms (p = 0.89), specifically 61% (CI95%: 48-72%), 64% (CI95%: 44-80%) 65% (CI95%: 56-72%), respectively. Adverse events during fluconazole, itraconazole and ketoconazole therapy were reported in 7% (CI95%: 3-14%), 12% (CI95% 8-19%) and 13% (CI95%: 6-29%) of treated patients, respectively, without difference among them (p = 0.35). This systematic review included studies with small samples and both non-comparative and non-randomized studies and the main limitation was the low quality of the available studies. CONCLUSIONS: Available evidence suggests that fluconazole, ketoconazole and itraconazole have similar and modest efficacy rates for tegumentary leishmaniasis treatment. There is insufficient evidence to support the exclusive use of azole therapy as a single agent for leishmaniasis treatment.
[Mh] Termos MeSH primário: Antifúngicos/uso terapêutico
Azóis/uso terapêutico
Leishmaniose Cutânea/tratamento farmacológico
Leishmaniose Mucocutânea/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Cutânea
Administração através da Mucosa
Antifúngicos/efeitos adversos
Azóis/efeitos adversos
Bases de Dados Factuais
Seres Humanos
Itraconazol/efeitos adversos
Itraconazol/uso terapêutico
Cetoconazol/efeitos adversos
Cetoconazol/uso terapêutico
Leishmaniose Cutânea/epidemiologia
Leishmaniose Cutânea/parasitologia
Leishmaniose Mucocutânea/epidemiologia
Leishmaniose Mucocutânea/parasitologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; META-ANALYSIS; REVIEW
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Azoles); 304NUG5GF4 (Itraconazole); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171011
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186117


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[PMID]:28717101
[Au] Autor:Kawamoto T; Ito Y; Morita O; Honda H
[Ad] Endereço:Safety Science Research, Kao Corporation.
[Ti] Título:Mechanism-based risk assessment strategy for drug-induced cholestasis using the transcriptional benchmark dose derived by toxicogenomics.
[So] Source:J Toxicol Sci;42(4):427-436, 2017.
[Is] ISSN:1880-3989
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Cholestasis is one of the major causes of drug-induced liver injury (DILI), which can result in withdrawal of approved drugs from the market. Early identification of cholestatic drugs is difficult due to the complex mechanisms involved. In order to develop a strategy for mechanism-based risk assessment of cholestatic drugs, we analyzed gene expression data obtained from the livers of rats that had been orally administered with 12 known cholestatic compounds repeatedly for 28 days at three dose levels. Qualitative analyses were performed using two statistical approaches (hierarchical clustering and principle component analysis), in addition to pathway analysis. The transcriptional benchmark dose (tBMD) and tBMD 95% lower limit (tBMDL) were used for quantitative analyses, which revealed three compound sub-groups that produced different types of differential gene expression; these groups of genes were mainly involved in inflammation, cholesterol biosynthesis, and oxidative stress. Furthermore, the tBMDL values for each test compound were in good agreement with the relevant no observed adverse effect level. These results indicate that our novel strategy for drug safety evaluation using mechanism-based classification and tBMDL would facilitate the application of toxicogenomics for risk assessment of cholestatic DILI.
[Mh] Termos MeSH primário: Clorpromazina/administração & dosagem
Clorpromazina/toxicidade
Colestase/induzido quimicamente
Ciclosporina/administração & dosagem
Ciclosporina/toxicidade
Diclofenaco/administração & dosagem
Diclofenaco/toxicidade
Medição de Risco/métodos
Toxicogenética/métodos
[Mh] Termos MeSH secundário: Administração Oral
Animais
Colesterol/biossíntese
Relação Dose-Resposta a Droga
Flutamida/administração & dosagem
Flutamida/toxicidade
Expressão Gênica
Seres Humanos
Imipramina/administração & dosagem
Imipramina/toxicidade
Inflamação/genética
Cetoconazol/administração & dosagem
Cetoconazol/toxicidade
Fígado
Metiltestosterona/administração & dosagem
Metiltestosterona/toxicidade
Estresse Oxidativo/genética
Ratos
Sulindaco/administração & dosagem
Sulindaco/toxicidade
Tamoxifeno/administração & dosagem
Tamoxifeno/toxicidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
094ZI81Y45 (Tamoxifen); 144O8QL0L1 (Diclofenac); 184SNS8VUH (Sulindac); 76W6J0943E (Flutamide); 83HN0GTJ6D (Cyclosporine); 97C5T2UQ7J (Cholesterol); OGG85SX4E4 (Imipramine); R9400W927I (Ketoconazole); U42B7VYA4P (Chlorpromazine); V9EFU16ZIF (Methyltestosterone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171005
[Lr] Data última revisão:
171005
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.2131/jts.42.427


  7 / 5353 MEDLINE  
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[PMID]:28662149
[Au] Autor:Nunes DCO; Bispo-da-Silva LB; Napolitano DR; Costa MS; Figueira MMNR; Rodrigues RS; Rodrigues VM; Yoneyama KAG
[Ad] Endereço:Instituto de Genética e Bioquímica, Universidade Federal de Uberlândia, Uberlândia, Minas Gerais, Brazil.
[Ti] Título:In vitro additive interaction between ketoconazole and antimony against intramacrophage Leishmania (Leishmania) amazonensis amastigotes.
[So] Source:PLoS One;12(6):e0180530, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Leishmaniasis is a group of diseases caused by protozoa of Leishmania genus. The currently available treatments for this disease are expensive, present high toxicity and are associated to difficulties of healing and parasite resistance. Therefore, the development of strategies for leishmaniasis treatment is indispensable and includes reposition of existing drugs, as well as drug combination therapy. The aim of this study was to assess the nature of ketoconazole and antimony association on the cytotoxic effect against Leishmania (Leishmania) amazonensis amastigotes. The calculated mean sum of fractional 50% inhibitory concentration ([Formula: see text]ΣFIC50) was 2.54 and 1.43 for free and intracellular amastigotes, respectively, values that suggest an additive interaction between ketoconazole and antimony concerning to Leishmania toxicity only in the intramacrophage parasite form. Despite the clinical efficacy of ketoconazole-antimony combination has been shown in the literature, our study is the first to describe the nature of ketoconazole-antimony interaction against L. (L.) amazonensis amastigotes. Moreover, our results point out the need for future in vivo studies to confirm the nature of ketoconazole-antimony interaction and also to determine possible effective dosage regimens related to ketoconazole administration in association with the optimal lower dose of antimony.
[Mh] Termos MeSH primário: Antimônio/farmacologia
Cetoconazol/farmacologia
Leishmania/efeitos dos fármacos
[Mh] Termos MeSH secundário: Animais
Antimônio/administração & dosagem
Sinergismo Farmacológico
Feminino
Técnicas In Vitro
Cetoconazol/administração & dosagem
Camundongos
Camundongos Endogâmicos BALB C
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
9IT35J3UV3 (Antimony); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170630
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180530


  8 / 5353 MEDLINE  
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[PMID]:28614003
[Au] Autor:Geer EB; Shafiq I; Gordon MB; Bonert V; Ayala A; Swerdloff RS; Katznelson L; Lalazar Y; Manuylova E; Pulaski-Liebert KJ; Carmichael JD; Hannoush Z; Surampudi V; Broder MS; Cherepanov D; Eagan M; Lee J; Said Q; Neary MP; Biller BMK
[Ti] Título:BIOCHEMICAL CONTROL DURING LONG-TERM FOLLOW-UP OF 230 ADULT PATIENTS WITH CUSHING DISEASE: A MULTICENTER RETROSPECTIVE STUDY.
[So] Source:Endocr Pract;23(8):962-970, 2017 Aug.
[Is] ISSN:1530-891X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Cushing disease (CD) results from excessive exposure to glucocorticoids caused by an adrenocorticotropic hormone-secreting pituitary tumor. Inadequately treated CD is associated with significant morbidity and elevated mortality. Multicenter data on CD patients treated in routine clinical practice are needed to assess treatment outcomes in this rare disorder. The study purpose was to describe the burden of illness and treatment outcomes for CD patients. METHODS: Eight pituitary centers in four U.S. regions participated in this multicenter retrospective chart review study. Subjects were CD patients diagnosed at ≥18 years of age within the past 20 years. Descriptive statistical analyses were conducted to examine presenting signs, symptoms, comorbidities, and treatment outcomes. RESULTS: Of 230 patients, 79% were female (median age at diagnosis, 39 years; range, 18 to 78 years). Length of follow-up was 0 to 27.5 years (median, 1.9 years). Pituitary adenomas were 0 to 51 mm. The most common presenting comorbidities included hypertension (67.3%), polycystic ovary syndrome (43.5%), and hyperlipidemia (41.5%). Biochemical control was achieved with initial pituitary surgery in 41.4% patients (91 of 220), not achieved in 50.0% of patients (110 of 220), and undetermined in 8.6% of patients (19 of 220). At the end of follow-up, control had been achieved with a variety of treatment methods in 49.1% of patients (110 of 224), not achieved in 29.9% of patients (67 of 224), and undetermined in 21.0% of patients (47 of 224). CONCLUSION: Despite multiple treatments, at the end of follow-up, biochemical control was still not achieved in up to 30% of patients. These multicenter data demonstrate that in routine clinical practice, initial and long-term control is not achieved in a substantial number of patients with CD. ABBREVIATIONS: BLA = bilateral adrenalectomy CD = Cushing disease CS = Cushing syndrome eCRF = electronic case report form MRI = magnetic resonance imaging PCOS = polycystic ovary syndrome.
[Mh] Termos MeSH primário: Adenoma Hipofisário Secretor de ACT/terapia
Adenoma/terapia
Hipersecreção Hipofisária de ACTH/terapia
[Mh] Termos MeSH secundário: Inibidores de 14-alfa Desmetilase/uso terapêutico
Adenoma Hipofisário Secretor de ACT/complicações
Adenoma Hipofisário Secretor de ACT/metabolismo
Adenoma Hipofisário Secretor de ACT/patologia
Adenoma/complicações
Adenoma/metabolismo
Adenoma/patologia
Adolescente
Adrenalectomia
Adulto
Idoso
Antineoplásicos/uso terapêutico
Comorbidade
Inibidores Enzimáticos/uso terapêutico
Ergolinas/uso terapêutico
Feminino
Seguimentos
Hirsutismo/etiologia
Antagonistas de Hormônios/uso terapêutico
Hormônios/uso terapêutico
Seres Humanos
Hiperlipidemias/epidemiologia
Hipertensão/epidemiologia
Hipoglicemiantes/uso terapêutico
Cetoconazol/uso terapêutico
Masculino
Metirapona/uso terapêutico
Meia-Idade
Mifepristona/uso terapêutico
Debilidade Muscular/etiologia
Atrofia Muscular/etiologia
Procedimentos Neurocirúrgicos
Obesidade Abdominal/etiologia
Hipersecreção Hipofisária de ACTH/complicações
Hipersecreção Hipofisária de ACTH/epidemiologia
Hipersecreção Hipofisária de ACTH/metabolismo
Irradiação Hipofisária
Síndrome do Ovário Policístico/epidemiologia
Estudos Retrospectivos
Somatostatina/análogos & derivados
Somatostatina/uso terapêutico
Estrias de Distensão/etiologia
Tiazolidinedionas/uso terapêutico
Resultado do Tratamento
Carga Tumoral
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (14-alpha Demethylase Inhibitors); 0 (Antineoplastic Agents); 0 (Enzyme Inhibitors); 0 (Ergolines); 0 (Hormone Antagonists); 0 (Hormones); 0 (Hypoglycemic Agents); 0 (Thiazolidinediones); 05V02F2KDG (rosiglitazone); 320T6RNW1F (Mifepristone); 51110-01-1 (Somatostatin); 98H1T17066 (pasireotide); LL60K9J05T (cabergoline); R9400W927I (Ketoconazole); ZS9KD92H6V (Metyrapone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171012
[Lr] Data última revisão:
171012
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE
[do] DOI:10.4158/EP171787.OR


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[PMID]:28479418
[Au] Autor:Valdez BC; Hassan M; Andersson BS
[Ad] Endereço:Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas M.D. Anderson Cancer Center, Houston, TX. Electronic address: bvaldez@mdanderson.org.
[Ti] Título:Development of an assay for cellular efflux of pharmaceutically active agents and its relevance to understanding drug interactions.
[So] Source:Exp Hematol;52:65-71, 2017 Aug.
[Is] ISSN:1873-2399
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Drug interactions may dictate the failure or success of a treatment. Patients undergoing hematopoietic stem cell transplantation (HSCT) are exposed to various types of drugs, and understanding how these drugs interact is of the utmost importance. The pharmacokinetics of busulfan, melphalan, and cyclophosphamide, drugs commonly used for HSCT, are known to be affected by a variety of other drugs with differing molecular structures. We hypothesized that these structurally unrelated drugs affect the transport of DNA-alkylating agents. To test this hypothesis, we developed a flow cytometry assay that used 5-carboxyfluorescein diacetate acetoxymethyl ester, which is cleaved by nonspecific intracellular esterases to 5-carboxyfluorescein (5-CF), a fluorescent ligand for the drug transporter MRP1. A decreased 5-CF efflux in the presence of a test compound suggests competitive inhibition. We demonstrated that chlorambucil, 4-hydroperoxycyclophosphamide, ketoconazole, ethacrynic acid, everolimus, and sirolimus strongly inhibited 5-CF efflux in lymphoma and leukemia cell lines. The efflux of these drugs partially depends on the glutathione (GSH) level, and their cytotoxicity is synergistic with inhibited GSH synthesis. This is consistent with the hypothesis that their GSH-conjugated products are ligands of a common cellular drug transporter. Our results may explain clinical observations on the effects of various drugs on the pharmacokinetics and pharmacodynamics of alkylating agents, and the assay may be used to deduce interaction mechanisms of drugs transported by a common system.
[Mh] Termos MeSH primário: Ciclofosfamida/farmacologia
Interações Medicamentosas
Citometria de Fluxo/métodos
Fluoresceínas/metabolismo
[Mh] Termos MeSH secundário: Antineoplásicos Alquilantes/farmacocinética
Antineoplásicos Alquilantes/farmacologia
Transporte Biológico/efeitos dos fármacos
Bussulfano/farmacocinética
Bussulfano/farmacologia
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Clorambucila/farmacocinética
Clorambucila/farmacologia
Ciclofosfamida/análogos & derivados
Ciclofosfamida/farmacocinética
Ácido Etacrínico/farmacocinética
Ácido Etacrínico/farmacologia
Everolimo/farmacocinética
Everolimo/farmacologia
Fluoresceínas/química
Seres Humanos
Cetoconazol/farmacocinética
Cetoconazol/farmacologia
Melfalan/farmacocinética
Melfalan/farmacologia
Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo
Reprodutibilidade dos Testes
Sirolimo/farmacocinética
Sirolimo/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (5-carboxyfluorescein diacetate acetoxymethyl ester); 0 (Antineoplastic Agents, Alkylating); 0 (Fluoresceins); 0 (Multidrug Resistance-Associated Proteins); 18D0SL7309 (Chlorambucil); 76823-03-5 (4-carboxyfluorescein); 8N3DW7272P (Cyclophosphamide); 9HW64Q8G6G (Everolimus); G1LN9045DK (Busulfan); M5DP350VZV (Ethacrynic Acid); Q41OR9510P (Melphalan); R9400W927I (Ketoconazole); U880A4FUDA (perfosfamide); W36ZG6FT64 (Sirolimus); Y49M64GZ4Q (multidrug resistance-associated protein 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171023
[Lr] Data última revisão:
171023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170509
[St] Status:MEDLINE


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[PMID]:28443986
[Au] Autor:Almeida-Paes R; Brito-Santos F; Figueiredo-Carvalho MHG; Machado ACS; Oliveira MME; Pereira SA; Gutierrez-Galhardo MC; Zancopé-Oliveira RM
[Ad] Endereço:Fundação Oswaldo Cruz-Fiocruz, Instituto Nacional de Infectologia Evandro Chagas, Laboratório de Micologia, Rio de Janeiro, RJ, Brasil.
[Ti] Título:Minimal inhibitory concentration distributions and epidemiological cutoff values of five antifungal agents against Sporothrix brasiliensis.
[So] Source:Mem Inst Oswaldo Cruz;112(5):376-381, 2017 May.
[Is] ISSN:1678-8060
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sporothrix brasiliensis is the most virulent sporotrichosis agent. This species usually responds to antifungal drugs, but therapeutic failure can occur in some patients. Antifungal susceptibility tests have been performed on this species, but no clinical breakpoints (CBPs) are available. In this situation, minimal inhibitory concentration (MIC) distributions and epidemiological cutoff values (ECVs) support the detection of identification of resistant strains. OBJECTIVES: To study the MIC distributions of five antifungal drugs against S. brasiliensis and to propose tentative ECVs. METHODS: MICs of amphotericin B (AMB), itraconazole (ITR), ketoconazole (KET), posaconazole (POS), and terbinafine (TRB) against 335 S. brasiliensis strains were determined by the Clinical and Laboratory Standards Institute broth microdilution method. FINDINGS: The proposed ECV, in µg/mL, for AMB, ITR, KET, POS, and TRB were 4.0, 2.0, 1.0, 2.0, and 0.25, respectively. Percentages of wild-type strains in our population for the above antifungal drugs were 98.48, 95.22, 95.33, 100, and 97.67%, respectively. MAIN CONCLUSIONS: These ECVs will be useful to detect strains with resistance, to define CBPs, and to elaborate specific therapeutic guidelines for S. brasiliensis. Rational use of antifungals is strongly recommended to avoid the emergence of resistant strains and ensure the therapeutic effectiveness of sporotrichosis.
[Mh] Termos MeSH primário: Antifúngicos/farmacologia
Sporothrix/efeitos dos fármacos
[Mh] Termos MeSH secundário: Anfotericina B/farmacologia
Animais
Gatos
Farmacorresistência Fúngica
Seres Humanos
Itraconazol/farmacologia
Cetoconazol/farmacologia
Testes de Sensibilidade Microbiana
Naftalenos/farmacologia
Sporothrix/isolamento & purificação
Triazóis/farmacologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Naphthalenes); 0 (Triazoles); 304NUG5GF4 (Itraconazole); 6TK1G07BHZ (posaconazole); 7XU7A7DROE (Amphotericin B); G7RIW8S0XP (terbinafine); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170427
[St] Status:MEDLINE



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