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[PMID]:26964843
[Au] Autor:Alarfaj NA; El-Tohamy MF
[Ad] Endereço:King Saud University, College of Science, Department of Chemistry, PO Box 22452, Riyadh 11495, Saudi Arabia.
[Ti] Título:Eu(III)-Sensitized Luminescence Probe for Determination of Tolnaftate in Pharmaceuticals and Biological Fluids.
[So] Source:J AOAC Int;99(2):380-5, 2016 Mar-Apr.
[Is] ISSN:1060-3271
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A highly selective, sensitive, accurate, and reproducible luminescence procedure for determination of antifungal drug tolnaftate was developed. The introduced method was based on the formation of Europa Universalis III (Eu(III))-tolnaftate complex using sodium sulfite as a deoxygenated agent in the presence of acetate buffer (pH = 6) and micellar solution of anionic surfactant sodium dodecyl sulfate. The optimum conditions (effect of pH, buffer, surfactant, Eu(III), and sodium sulfite concentrations) for the luminescence signal were investigated and optimized. The luminescence signals were recorded at λex = 270 nm and λem = 460 nm. The method has a good linear response (0.2-130 µg/mL(-1)) between the luminescence intensity and the concentrations of the drug (r = 0.999), with a LOD 0.07 µg/mL(-1) and LOQ 0.2 µg/mL(-1). The luminescence signals of Eu (III)-tolnaftate-sodium dodecyl sulfate were found to be 200-fold more sensitive without the presence of micelle solution. The interferences of some additives, metals, amino acids, sugars, and other related pharmacological action drugs were examined and no interference was recorded. The proposed method was used for quick and simple determination of tolnaftate in its pharmaceuticals and biological fluids.
[Mh] Termos MeSH primário: Líquidos Corporais/química
Európio/química
Substâncias Luminescentes/química
Preparações Farmacêuticas/química
Tolnaftato/análise
[Mh] Termos MeSH secundário: Seres Humanos
Luminescência
Medições Luminescentes
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Luminescent Agents); 0 (Pharmaceutical Preparations); 06KB629TKV (Tolnaftate); 444W947O8O (Europium)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170208
[Lr] Data última revisão:
170208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160312
[St] Status:MEDLINE
[do] DOI:10.5740/jaoacint.15-0218


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[PMID]:25624145
[Au] Autor:Thoma C
[Ti] Título:Prostate cancer: BAT-ting CRPC.
[So] Source:Nat Rev Urol;12(3):121, 2015 Mar.
[Is] ISSN:1759-4820
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Neoplasias da Próstata
Tolnaftato
[Mh] Termos MeSH secundário: Seres Humanos
Masculino
Antígeno Prostático Específico
[Pt] Tipo de publicação:COMMENT; JOURNAL ARTICLE
[Nm] Nome de substância:
06KB629TKV (Tolnaftate); EC 3.4.21.77 (Prostate-Specific Antigen)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150128
[St] Status:MEDLINE
[do] DOI:10.1038/nrurol.2015.6


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[PMID]:24156554
[Au] Autor:Grabke A; Fernández-Ortuño D; Amiri A; Li X; Peres NA; Smith P; Schnabel G
[Ti] Título:Characterization of iprodione resistance in Botrytis cinerea from strawberry and blackberry.
[So] Source:Phytopathology;104(4):396-402, 2014 Apr.
[Is] ISSN:0031-949X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gray mold, caused by the fungal pathogen Botrytis cinerea, is one of the most destructive diseases of strawberry. Control of the disease in commercial fields is largely dependent on the application of fungicides, including the dicarboximide iprodione. Single-spore isolates were collected from strawberry fields in Florida, North Carolina, and South Carolina and subjected to an assay using conidial germination that distinguished sensitive (S) isolates from isolates with various levels of resistance to iprodione. Of the 245 isolates, 1 was highly resistant (HR), 5 were moderately resistant (MR), and 43 had low resistance (LR) to iprodione. LR and MR strains were found in the Florida population and in 9 of 11 locations from North Carolina and South Carolina, indicating that resistance was widespread but accounted for only a relatively small percentage of the B. cinerea population. Sequence analysis of the target gene bos1, which codes for a class III histidine kinase, revealed that the MR phenotype was associated with Q369P and N373S mutations and that the LR phenotype was associated with either a I365S or a I365N mutation. The I365S and I365N mutations were also present in five additionally included HR isolates from North Carolina and South Carolina blackberry fields and one HR isolate from a Virginia strawberry field but no mutation or mutation combinations in bos1 were uniquely associated with the HR phenotype. Expression analysis of bos1 in S and HR isolates did not reveal convincing evidence of the gene's involvement in HR resistance either. The six HR isolates had three different phenotypes with respect to their sensitivity to fludioxonil; two were S, two were LR, and two were MR. The fludioxonil LR and MR isolates were also resistant to tolnaftate, an indication of multidrug efflux pump activity. These data suggest that, in addition to point mutations in bos1, drug efflux pump activity and potentially a third mechanism of resistance may be contributing to the iprodione HR phenotype. Detached fruit studies showed that field rates of Rovral 4 Flowable (iprodione) did not control iprodione MR and HR isolates.
[Mh] Termos MeSH primário: Aminoimidazol Carboxamida/análogos & derivados
Botrytis/genética
Farmacorresistência Fúngica/genética
Fragaria/microbiologia
Hidantoínas/farmacologia
Doenças das Plantas/microbiologia
Rosaceae/microbiologia
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Aminoimidazol Carboxamida/farmacologia
Sequência de Bases
Botrytis/efeitos dos fármacos
Botrytis/fisiologia
Primers do DNA/genética
DNA Fúngico/química
DNA Fúngico/genética
Dioxóis/farmacologia
Florida
Frutas/microbiologia
Proteínas Fúngicas/genética
Fungicidas Industriais/farmacologia
Testes de Sensibilidade Microbiana
Mutação de Sentido Incorreto
Micélio
North Carolina
Pirróis/farmacologia
Tolnaftato/farmacologia
Virginia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (DNA Primers); 0 (DNA, Fungal); 0 (Dioxoles); 0 (Fungal Proteins); 0 (Fungicides, Industrial); 0 (Hydantoins); 0 (Pyrroles); 06KB629TKV (Tolnaftate); 360-97-4 (Aminoimidazole Carboxamide); ENS9J0YM16 (fludioxonil); S3AYV2A6EU (iprodione)
[Em] Mês de entrada:1406
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:131026
[St] Status:MEDLINE
[do] DOI:10.1094/PHYTO-06-13-0156-R


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[PMID]:23713459
[Au] Autor:Gillespie C; Kennedy AR; Edwards D; Dowden L; Daublain P; Halling P
[Ad] Endereço:WestCHEM, The Department of Pure and Applied Chemistry, University of Strathclyde, Thomas Graham Building, 295 Cathedral Street, Glasgow, G1 1XL, UK. cheska.gillespie@strath.ac.uk
[Ti] Título:Detailed study of precipitation of a poorly water soluble test compound using methodologies as in activity and solubility screening - mixing and automation effects.
[So] Source:Comb Chem High Throughput Screen;16(8):636-43, 2013 Sep.
[Is] ISSN:1875-5402
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Storage of pharmaceutical discovery compounds dissolved in dimethylsulfoxide (DMSO) is commonplace within industry. Often, the DMSO stock solution is added to an aqueous system (e.g. in bioassay or kinetic solubility testing)- since most test compounds are hydrophobic, precipitation could occur. Little is known about the factors affecting this precipitation process at the low (µM) concentrations used in screening analyses. Here, a poorly water soluble test compound (tolnaftate) was used to compare manual and automated pipetting, and explore the effect of mixing variables on precipitation. The amount of drug present in the supernatant after precipitation and centrifugation of the samples was quantified. An unusual result was obtained in three different laboratories: results of experiments performed initially were statistically significantly higher than those performed after a few days in the same lab. No significant differences were found between automated and manual pipetting, including in variability. Vortex mixing was found to give significantly lower supernatant amounts compared to milder mixing types. The mixing employed affects the particle growth of the precipitate. These findings are of relevance to discovery stage bioassay and kinetic solubility analyses.
[Mh] Termos MeSH primário: Antifúngicos/química
Tolnaftato/química
Água/química
[Mh] Termos MeSH secundário: Precipitação Química
Dimetil Sulfóxido/química
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antifungal Agents); 059QF0KO0R (Water); 06KB629TKV (Tolnaftate); YOW8V9698H (Dimethyl Sulfoxide)
[Em] Mês de entrada:1403
[Cu] Atualização por classe:130805
[Lr] Data última revisão:
130805
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:130530
[St] Status:MEDLINE


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[PMID]:22804826
[Au] Autor:Loock JW
[Ad] Endereço:Division of Otorhinolaryngology, Faculty of Health Sciences, University of Stellenbosch/Tygerberg Hospital, Cape Town, South Africa. jwl@sun.ac.za
[Ti] Título:A randomised controlled trial of active chronic otitis media comparing courses of eardrops versus one-off topical treatments suitable for primary, secondary and tertiary healthcare settings.
[So] Source:Clin Otolaryngol;37(4):261-70, 2012 Aug.
[Is] ISSN:1749-4486
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Primary: to compare one-off administration of boric acid powder with courses of 1% acetic acid and ciprofloxacin eardrops in treating active chronic otitis media. Secondary: to evaluate the effectiveness of Quadriderm® cream in resistant active chronic otitis media; and to document side effects of these treatments, especially hearing loss. STUDY DESIGN: Randomised controlled trial. SETTING: Outpatient department of a tertiary ENT unit. PARTICIPANTS: Hundred and fifty-nine patients over 6 years old with active chronic mucosal (without cholesteatoma) otitis media randomised to receive one of the three primary agents. METHOD: All techniques employed were suitable for primary healthcare givers as well as specialists. After confirming eligibility, patients were randomly allocated to treatment. All ears underwent toilet with irrigation using clean water, a syringe and ambient light, with or without dry mopping, until the perforation was visible. The randomised solution was flushed through the middle ear and eustachian tube using a 'tragal pump' technique: saline was used as the solution for flushing in the boric acid powder arm. Patients allocated topical ear medication were given a bottle of eardrops to administer (six drops twice daily, 'pumped in') until finished. Those allocated boric acid powder had the external ear canals filled as a one-off treatment. Patients were followed up monthly thereafter. OUTCOME MEASURES: Primary: Dry (inactive) middle ears as assessed by the doctor. Secondary: Patient assessment of success; microbiologic culture and sensitivity; audiologic changes because of treatment; complications of treatment; costs of therapies. RESULTS: Ciprofloxacin eardrops and boric acid powder were statistically superior to 1% acetic acid eardrops in rendering active chronic otitis media inactive (73% dry ears for ciprofloxacin; 67% for boric acid powder; and 24% for acetic acid). There was no difference between the success rates of ciprofloxacin eardrops and boric acid powder. Quadriderm cream was effective in 85% of patients failing first-line therapy. No agent caused significant complications and specifically no hearing loss. CONCLUSIONS: This study showed a single application of boric acid powder following external auditory canal irrigation until the perforation was visible to be as effective as the current best practice of topical quinolone eardrops in active chronic otitis media. Boric acid powder is inexpensive and does not require patient compliance. Boric acid powder is a viable, less costly alternative to topical antibiotic/steroid ear drops in the developing world for active chronic otitis media. Acetic acid eardrops 1% are ineffective. Quadriderm cream, given as a one-off therapy, also appears to be effective.
[Mh] Termos MeSH primário: Ácido Acético/administração & dosagem
Ácidos Bóricos/administração & dosagem
Ciprofloxacino/administração & dosagem
Otite Média/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Tópica
Adulto
Análise de Variância
Anti-Infecciosos/administração & dosagem
Audiometria
Valerato de Betametasona
Distribuição de Qui-Quadrado
Doença Crônica
Clioquinol
Farmacorresistência Bacteriana
Feminino
Gentamicinas
Perda Auditiva/epidemiologia
Seres Humanos
Masculino
Otite Média/microbiologia
Estudos Prospectivos
Tolnaftato
Resultado do Tratamento
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Infective Agents); 0 (Boric Acids); 0 (Gentamicins); 0 (quadriderm); 06KB629TKV (Tolnaftate); 5E8K9I0O4U (Ciprofloxacin); 7BHQ856EJ5 (Clioquinol); 9IFA5XM7R2 (Betamethasone Valerate); Q40Q9N063P (Acetic Acid); R57ZHV85D4 (boric acid)
[Em] Mês de entrada:1302
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:120719
[St] Status:MEDLINE
[do] DOI:10.1111/j.1749-4486.2012.02532.x


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[PMID]:22125963
[Au] Autor:Kezutyte T; Drevinskas T; Maruska A; Rimdeika R; Briedis V
[Ad] Endereço:Department of Pharmaceutical Technology and Social Pharmacy, Faculty of Pharmacy, Lithuanian University of Health Sciences, A. Mickeviciaus 9, 44307 Kaunas, Lithuania. tomakezutyte@yahoo.com
[Ti] Título:Study of tolnaftate release from fatty acids containing ointment and penetration into human skin ex vivo.
[So] Source:Acta Pol Pharm;68(6):965-73, 2011 Nov-Dec.
[Is] ISSN:0001-6837
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:Five fatty acids (oleic, linoleic, myristic, lauric and capric) were incorporated in 10% (w/w) into ointment formulation and their influence on lipophilic model drug tolnaftate release in vitro and enhancing effect on tolnaftate penetration into epidermis and dermis of human skin ex vivo were investigated. The prepared ointments were tested for homogeneity, pH and theological properties. In vitro release studies and ex vivo skin penetration experiments were carried out using Hanson and Bronaugh-type flow-through diffusion cells, respectively. Tolnaftate cumulative amount liberated from semisolids was assayed using UV-Vis spectrophotometer. After in vitro skin penetration studies, appropriately extracted human skin layers were analyzed for tolnaftate content using a validated HPLC method. Statistical analysis revealed that release rate of tolnaftate from control ointment and ointments with fatty acids was not significantly different and only 7.34-8.98% of drug was liberated into an acceptor medium after 6 h. Tolnaftate amount penetrating into 1 cm2 of epidermis from ointments containing oleic, linoleic, myristic and lauric acids was significantly greater (p < 0.05) than from the control ointment. Penetration enhancing ratios for these fatty acids for tolnaftate penetration into epidermis ranged from 1.48 to 1.75. In conclusion, fatty acids did not increase the liberation of tolnaftate from ointment formulation, but demonstrated their enhancing effect on tolnaftate penetration into human epidermis in vitro. Results from in vitro release experiments do not suit for prediction of the situation in the skin in vitro, if chemical penetration enhancers are incorporated into the ointment formulation.
[Mh] Termos MeSH primário: Antifúngicos/metabolismo
Ácidos Graxos/farmacologia
Absorção Cutânea/efeitos dos fármacos
Pele/efeitos dos fármacos
Tolnaftato/metabolismo
[Mh] Termos MeSH secundário: Administração Cutânea
Adulto
Antifúngicos/administração & dosagem
Antifúngicos/química
Química Farmacêutica
Cromatografia Líquida de Alta Pressão
Ácidos Decanoicos/farmacologia
Composição de Medicamentos
Ácidos Graxos/administração & dosagem
Ácidos Graxos/química
Feminino
Seres Humanos
Concentração de Íons de Hidrogênio
Cinética
Ácidos Láuricos/farmacologia
Ácido Linoleico/farmacologia
Meia-Idade
Ácido Mirístico/farmacologia
Pomadas
Ácido Oleico/farmacologia
Permeabilidade
Reologia
Pele/metabolismo
Solubilidade
Espectrofotometria Ultravioleta
Tecnologia Farmacêutica/métodos
Tolnaftato/administração & dosagem
Tolnaftato/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Decanoic Acids); 0 (Fatty Acids); 0 (Lauric Acids); 0 (Ointments); 06KB629TKV (Tolnaftate); 0I3V7S25AW (Myristic Acid); 1160N9NU9U (lauric acid); 2UMI9U37CP (Oleic Acid); 4G9EDB6V73 (decanoic acid); 9KJL21T0QJ (Linoleic Acid)
[Em] Mês de entrada:1112
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:111201
[St] Status:MEDLINE


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[PMID]:21565546
[Au] Autor:Dhas DA; Joe IH; Roy SD; Balachandran S
[Ad] Endereço:Department of Physics, Nesamony Memorial Christian College, Marthandam 629 165, Tamil Nadu, India.
[Ti] Título:Nonplanar property study of antifungal agent tolnaftate-spectroscopic approach.
[So] Source:Spectrochim Acta A Mol Biomol Spectrosc;79(5):993-1003, 2011 Sep.
[Is] ISSN:1873-3557
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Vibrational analysis of the thionocarbamate fungicide tolnaftate which is antidermatophytic, antitrichophytic and antimycotic agent, primarily inhibits the ergosterol biosynthesis in the fungus, was carried out using NIR FT-Raman and FTIR spectroscopic techniques. The equilibrium geometry, various bonding features, harmonic vibrational wavenumbers and torsional potential energy surface (PES) scan studies have been computed using density functional theory method. The detailed interpretation of the vibrational spectra has been carried out with the aid of VEDA.4 program. Vibrational spectra, natural bonding orbital (NBO) analysis and optimized molecular structure show the clear evidence for electronic interaction of thionocarbamate group with aromatic ring. Predicted electronic absorption spectrum from TD-DFT calculation has been compared with the UV-vis spectrum. The Mulliken population analysis on atomic charges and the HOMO-LUMO energy were also calculated. Vibrational analysis reveals that the simultaneous IR and Raman activation of the C-C stretching mode in the phenyl and naphthalene ring provide evidence for the charge transfer interaction between the donor and acceptor groups and is responsible for its bioactivity as a fungicide.
[Mh] Termos MeSH primário: Antifúngicos/química
Antifúngicos/farmacologia
Fungos/efeitos dos fármacos
Modelos Químicos
Espectroscopia de Infravermelho com Transformada de Fourier
Tolnaftato/química
Tolnaftato/farmacologia
[Mh] Termos MeSH secundário: Conformação Molecular
Estrutura Molecular
Teoria Quântica
Análise Espectral Raman
Vibração
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antifungal Agents); 06KB629TKV (Tolnaftate)
[Em] Mês de entrada:1112
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:110514
[St] Status:MEDLINE
[do] DOI:10.1016/j.saa.2011.04.011


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[PMID]:20635527
[Au] Autor:Kezutyte T; Kornysova O; Maruska A; Briedis V
[Ad] Endereço:Department of Pharmaceutical Technology and Social Pharmacy, Faculty of Pharmacy, Kaunas University of Medicine, A. Mickevidiaus 9, 44307 Kaunas, Lithuania. tomakezutyte@yahoo.com
[Ti] Título:Assay of tolnaftate in human skin samples after in vitro penetration studies using high performance liquid chromatography.
[So] Source:Acta Pol Pharm;67(4):327-34, 2010 Jul-Aug.
[Is] ISSN:0001-6837
[Cp] País de publicação:Poland
[La] Idioma:eng
[Ab] Resumo:Abstract: Tolnaftate, an antifungal of thiocarbamate class, is used topically in 1% formulations. Its penetration into skin layers is a prerequisite for tolnaftate action against dermatophytes. The aim of this work was to optimize and validate a simple, rapid, accurate and reproducible procedure for tolnaftate assay in human skin samples and to apply this procedure for in vitro tolnaftate penetration studies. High performance liquid chromatography (HPLC) method with UV detection was used to validate tolnaftate assay for linearity, specificity, accuracy, precision, limit of quantitation, limit of detection, drug extraction recovery and stability in skin extracts. In vitro tolnaftate penetration studies were carried out using flow-through diffusion cells, mounted with human skin. Epidermis and dermis, separated by heat-separation method, were extracted using ultrasonication in methanol. Linear range of the analytical procedure was within 0.6-100 pg/mL. The assay was specific, accurate (within-day and between-day recovery values were 98.2-104.2% and 98.7-101.4%, respectively) and precise (within-day and between-day imprecision was = 3.8%). Mean extraction recoveries of tolnaftate from epidermis and dermis were satisfactory and reaching 90%. In vitro skin penetration studies revealed that after application of 1% (w/w) tolnaftate solution in polyethylene glycol 400 for 24 hours, the mean amount of tolnaftate penetrating into the epidermis and dermis was 2.60 +/- 0.28 microg/cm2 and 0.92 +/- 0.12 microg/cm2, respectively. A validated reliable HPLC method could be recommended for biopharmaceutical evaluation of tolnaftate preparations and studies of pharmacokinetics in human skin after in vitro penetration studies.
[Mh] Termos MeSH primário: Antifúngicos/análise
Antifúngicos/farmacocinética
Absorção Cutânea/fisiologia
Pele/química
Tolnaftato/análise
Tolnaftato/farmacocinética
[Mh] Termos MeSH secundário: Adulto
Calibragem
Química Farmacêutica
Cromatografia Líquida de Alta Pressão
Derme/metabolismo
Epiderme/metabolismo
Feminino
Seres Humanos
Técnicas In Vitro
Indicadores e Reagentes
Unhas/metabolismo
Controle de Qualidade
Padrões de Referência
Reprodutibilidade dos Testes
Pele/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Indicators and Reagents); 06KB629TKV (Tolnaftate)
[Em] Mês de entrada:1008
[Cu] Atualização por classe:141120
[Lr] Data última revisão:
141120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100720
[St] Status:MEDLINE


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[PMID]:20434536
[Au] Autor:Lipinski RJ; Bushman W
[Ad] Endereço:Molecular and Environmental Toxicology Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 27599, USA. Lipinski@med.unc.edu
[Ti] Título:Identification of Hedgehog signaling inhibitors with relevant human exposure by small molecule screening.
[So] Source:Toxicol In Vitro;24(5):1404-9, 2010 Aug.
[Is] ISSN:1879-3177
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In animal models, chemical disruption of the Hedgehog (Hh) signaling pathway during embryonic development causes severe birth defects including holoprosencephaly and cleft lip and palate. The exact etiological basis of correlate human birth defects remains uncertain but is likely multifactorial, involving the interaction of genetic and environmental or chemical influences. The Hh transduction mechanism relies upon endogenous small molecule regulation, conferring remarkable pathway sensitivity to inhibition by a structurally diverse set of exogenous small molecules. Here, we employed small molecule screening to identify human exposure-relevant Hh signaling inhibitors. From a library of 4240 compounds, including pharmaceuticals, natural products, and pesticides, three putative Hh pathway inhibitors were identified: tolnaftate, an antifungal agent; ipriflavone, a dietary supplement; and 17-beta-estradiol, a human hormone and pharmaceutical agent. Each compound inhibited Hh signaling in both mouse and human cells. Dose-response assays determined the three compounds to be 8- to 30-fold less potent than the index Hh pathway inhibitor cyclopamine. Despite current limitations in chemical library availability, which narrowed the scope of this study to only a small fraction of all human exposure-relevant small molecules, three structurally diverse environmental Hh signaling inhibitors were identified, highlighting an inherent pathway vulnerability to teratogenic influences.
[Mh] Termos MeSH primário: Proteínas Hedgehog/antagonistas & inibidores
Transdução de Sinais/efeitos dos fármacos
Testes de Toxicidade/métodos
[Mh] Termos MeSH secundário: Animais
Antifúngicos/toxicidade
Células Cultivadas
Suplementos Nutricionais/toxicidade
Relação Dose-Resposta a Droga
Exposição Ambiental
Estradiol/toxicidade
Estrogênios/toxicidade
Seres Humanos
Isoflavonas/toxicidade
Chumbo/toxicidade
Camundongos
Proteínas Oncogênicas/metabolismo
Receptores Patched
Receptores de Superfície Celular/metabolismo
Bibliotecas de Moléculas Pequenas
Tolnaftato/toxicidade
Transativadores/metabolismo
Proteína GLI1 em Dedos de Zinco
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Antifungal Agents); 0 (Estrogens); 0 (Hedgehog Proteins); 0 (Isoflavones); 0 (Oncogene Proteins); 0 (Patched Receptors); 0 (Receptors, Cell Surface); 0 (Small Molecule Libraries); 0 (Trans-Activators); 0 (Zinc Finger Protein GLI1); 06KB629TKV (Tolnaftate); 2P299V784P (Lead); 4TI98Z838E (Estradiol); 80BJ7WN25Z (ipriflavone)
[Em] Mês de entrada:1009
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100504
[St] Status:MEDLINE
[do] DOI:10.1016/j.tiv.2010.04.011


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[PMID]:20347665
[Au] Autor:Millikan LE
[Ad] Endereço:Department of Dermatology, Tulane University School of Medicine, New Orleans, LA 70112, USA. millikanmd@gmail.com
[Ti] Título:Current concepts in systemic and topical therapy for superficial mycoses.
[So] Source:Clin Dermatol;28(2):212-6, 2010 Mar 04.
[Is] ISSN:1879-1131
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There presently exists a wide selection of choices in the treatment of superficial mycoses. The main categories of broad-spectrum agents are the allylamines and imidazoles, which have been tried and proven over more than 2 decades of usage with good safety. Nystatin and griseofulvin have even longer experience of about 5 decades but have niche usage for yeasts and dermatophytes, respectively. Although no new therapeutic groups have appeared, extensive development of vehicles and delivery systems has enhanced therapeutic results and increased patient compliance.
[Mh] Termos MeSH primário: Antibacterianos/uso terapêutico
Antifúngicos/uso terapêutico
Azóis/uso terapêutico
Dermatomicoses/tratamento farmacológico
[Mh] Termos MeSH secundário: Administração Oral
Administração Tópica
Antifúngicos/economia
Azóis/economia
Dermatomicoses/economia
Dermatomicoses/epidemiologia
Esquema de Medicação
Farmacorresistência Fúngica/efeitos dos fármacos
Fluconazol/uso terapêutico
Griseofulvina/uso terapêutico
Seres Humanos
Itraconazol/uso terapêutico
Cetoconazol/uso terapêutico
Morfolinas/uso terapêutico
Tolnaftato/uso terapêutico
Estados Unidos/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Antifungal Agents); 0 (Azoles); 0 (Morpholines); 06KB629TKV (Tolnaftate); 304NUG5GF4 (Itraconazole); 32HRV3E3D5 (Griseofulvin); 8VZV102JFY (Fluconazole); R9400W927I (Ketoconazole)
[Em] Mês de entrada:1006
[Cu] Atualização por classe:131121
[Lr] Data última revisão:
131121
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:100330
[St] Status:MEDLINE
[do] DOI:10.1016/j.clindermatol.2009.12.016



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