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1.
Eur J Pharm Sci ; 177: 106274, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35944878

RESUMO

A prior model that showed good predictability for fed-state and fasted-state biorelevant media was extended to predict the degree to which fed-state biorelevant media (i.e. FeSSGF and FeSSIF-V2) enhanced drug dissolution over fasted-state biorelevant media (i.e. FaSSGF and FaSSIF-V2): ϕfood=vfast1/6vfed1/6·(ff,fedDD2/3+fm,fedDD-M,fed2/3)[Dt,fed](ff,fastDD2/3+fm,fastDD-M,fast2/3)[Dt,fast] where ϕfood is the degree by which fed-state biorelevant media enhanced in vitro drug dissolution over fasted state biorelevant media, ff,fast and ff,fed are the fraction of free drug in fasted and fed biorelevant media, fm,fast and fm,fed are the fraction of drug in fasted and fed mixed micelles (or fat globules in FeSSGF), DD is the free drug diffusivity, DD-M, fast and DD-M, fed are the fasted and fed mixed micelle (or fat globule) diffusivity, and [Dt,fast] and [Dt,fed] are the total drug solubilities in fasted and fed-state biorelevant media, respectively. Solubility, particle size measurement, and intrinsic dissolution studies were performed for model BCS Class II drugs griseofulvin, ketoconazole, and ibuprofen each in FaSSGF, FeSSGF, FaSSIF-V2, and FeSSIF-V2 to compare observed versus predicted dissolution enhancement in fed-state over fasted-state biorelevant media. Relative to solubilization, in vitro dissolution was many fold lower in fed media over fasted media, indicating the compromising role of micellar and fat-globule diffusivity in attenuating dissolution rate based on solubility enhancement alone. Results of ϕfood agreed with what was observed and were also corroborated by reported food effects in vivo for griseofulvin, ketoconazole, and ibuprofen. The understanding of attenuation of in vitro dissolution in fed versus fasted biorelevant media may contribute towards predicting in vivo food effects, including lack of in vivo food effect for some poorly water soluble drugs.


Assuntos
Griseofulvina , Cetoconazol , Coloides , Liberação Controlada de Fármacos , Ibuprofeno , Micelas , Solubilidade
2.
Int J Mol Sci ; 23(13)2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35805893

RESUMO

Treatment options for Coronavirus Disease 2019 (COVID-19) remain limited, and the option of repurposing approved drugs with promising medicinal properties is of increasing interest in therapeutic approaches to COVID-19. Using computational approaches, we examined griseofulvin and its derivatives against four key anti-SARS-CoV-2 targets: main protease, RdRp, spike protein receptor-binding domain (RBD), and human host angiotensin-converting enzyme 2 (ACE2). Molecular docking analysis revealed that griseofulvin (CID 441140) has the highest docking score (-6.8 kcal/mol) with main protease of SARS-CoV-2. Moreover, griseofulvin derivative M9 (CID 144564153) proved the most potent inhibitor with -9.49 kcal/mol, followed by A3 (CID 46844082) with -8.44 kcal/mol against M protease and ACE2, respectively. Additionally, H bond analysis revealed that compound A3 formed the highest number of hydrogen bonds, indicating the strongest inhibitory efficacy against ACE2. Further, molecular dynamics (MD) simulation analysis revealed that griseofulvin and these derivatives are structurally stable. These findings suggest that griseofulvin and its derivatives may be considered when designing future therapeutic options for SARS-CoV-2 infection.


Assuntos
COVID-19 , Enzima de Conversão de Angiotensina 2 , Antivirais/química , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Griseofulvina/farmacologia , Griseofulvina/uso terapêutico , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Peptidil Dipeptidase A/metabolismo , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/metabolismo
3.
AAPS PharmSciTech ; 23(6): 199, 2022 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-35854184

RESUMO

Griseofulvin (GF) is used as an antifungal to treat superficial skin fungal infections such as tinea capitis and tinea pedis. Currently, GF is only available in traditional oral dosage forms and suffers from poor and highly variable bioavailability, hepatotoxicity, and long duration of treatment. Therefore, the main objective of this study was to reduce the side effects of the drug and to increase the concentration of the drug retained in the cutaneous stratum corneum (SC) and improve its efficacy through the preparation of drug-laden GF microsponge (GFMS). The emulsification-solvent-diffusion method was used to prepare GFMS, and the prescriptions were screened by a single-factor approach. The optimized formulation (GFF8) had a microsponge particle size (µm) of 28.36 ± 0.26, an encapsulation efficiency (%) of 87.53 ± 1.07, a yield (%) of 86.58 ± 0.42, and drug release (%) from 77.57 ± 3.88. The optimized microsponge formulation was then loaded into a Carbopol 934 gel matrix and skin retention differences between the microsponge gel formulation and normal gels were examined by performing skin retention and fluorescence microscopy tests. Finally, the hepatoprotective and cutaneous stratum corneum retention abilities of microsponge gel formulations compared to oral GF formulations were assessed by hepatotoxicity, pharmacokinetics, and tissue distribution studies. This provides a new perspective on GF dermal stratum corneum retention administration.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Griseofulvina , Sistemas de Liberação de Medicamentos , Géis , Humanos , Absorção Cutânea
4.
Nat Commun ; 13(1): 4028, 2022 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-35821013

RESUMO

Heme-biosynthetic pathway of malaria parasite is dispensable for asexual stages, but essential for mosquito and liver stages. Despite having backup mechanisms to acquire hemoglobin-heme, pathway intermediates and/or enzymes from the host, asexual parasites express heme pathway enzymes and synthesize heme. Here we show heme synthesized in asexual stages promotes cerebral pathogenesis by enhancing hemozoin formation. Hemozoin is a parasite molecule associated with inflammation, aberrant host-immune responses, disease severity and cerebral pathogenesis. The heme pathway knockout parasites synthesize less hemozoin, and mice infected with knockout parasites are protected from cerebral malaria and death due to anemia is delayed. Biosynthetic heme regulates food vacuole integrity and the food vacuoles from knockout parasites are compromised in pH, lipid unsaturation and proteins, essential for hemozoin formation. Targeting parasite heme synthesis by griseofulvin-a FDA-approved antifungal drug, prevents cerebral malaria in mice and provides an adjunct therapeutic option for cerebral and severe malaria.


Assuntos
Malária Cerebral , Parasitos , Animais , Griseofulvina/farmacologia , Heme/metabolismo , Hemoglobinas , Malária Cerebral/tratamento farmacológico , Malária Cerebral/prevenção & controle , Camundongos , Parasitos/metabolismo
5.
Dermatol Ther ; 35(7): e15582, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35561151

RESUMO

Tinea capitis (TC) is the most common dermatophyte infection in children. Fungal culture; although a gold standard of diagnosis, requires time for the final results which can favor horizontal transmission. Trichoscopy helps in rapid diagnosis and could work as a monitoring tool during antifungal therapy. The objective of this study is to provide a clinico-trichoscopic evaluation and follow-up of children presenting with TC during treatment with either griseofulvin or terbinafine. One hundred and twenty children clinically diagnosed with TC confirmed by potassium hydroxide microscopy, were divided into two groups and given either oral ultramicrosize griseofulvin (60, Group A) or terbinafine (60, Group B). Following initiation of the antifungal therapy, trichoscopic features within Groups A and B were noted at 0, 2, 4, 6, and 8 weeks. However, variation in the baseline trichoscopic features between the two groups was not statistically significant (p = 0.855). A significant reduction of corkscrew and broken hairs as well as perifollicular scales, scalp erythema, and crust was significantly observed from 2 weeks onward irrespective of the antifungal drug prescribed. Despite the paucity of data evaluating trichoscopic features in patients with TC, this tool can serve as a rapid diagnostic and monitoring tool during antifungal treatment. Trichoscopic signs of TC resolution occur before clinical improvement and can guide for treatment adjustment during the course of therapy.


Assuntos
Griseofulvina , Tinha do Couro Cabeludo , Antifúngicos/uso terapêutico , Criança , Griseofulvina/uso terapêutico , Humanos , Estudos Prospectivos , Terbinafina , Tinha do Couro Cabeludo/diagnóstico , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/microbiologia
6.
Biofouling ; 38(3): 286-297, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35450473

RESUMO

This study aimed to evaluate the effect of proteinase K on mature biofilms of dermatophytes, by assays of metabolic activity and biomass. In addition, the proteinase K-terbinafine and proteinase K-griseofulvin interactions against these biofilms were investigated by the checkerboard assay and scanning electron and confocal microscopy. The biofilms exposed to 32 µg ml-1 of proteinase K had lower metabolic activity and biomass, by 39% and 38%, respectively. Drug interactions were synergistic, with proteinase K reducing the minimum inhibitory concentration of antifungals against dermatophyte biofilms at a concentration of 32 µg ml-1 combined with 128-256 µg ml-1 of terbinafine and griseofulvin. Microscopic images showed a reduction in biofilms exposed to proteinase K, proteinase K-terbinafine and proteinase K-griseofulvin combinations. These findings demonstrate that proteinase K has activity against biofilms of dermatophytes, and the interactions of proteinase K with terbinafine and griseofulvin improve the activity of drugs against mature dermatophyte biofilms.


Assuntos
Antifúngicos , Arthrodermataceae , Antifúngicos/farmacologia , Biofilmes , Endopeptidase K/farmacologia , Griseofulvina/farmacologia , Testes de Sensibilidade Microbiana , Terbinafina/farmacologia
7.
Int J Pharm ; 615: 121498, 2022 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-35065207

RESUMO

This study evaluated the ability of different sweeteners to improve dissolution and to form and stabilize supersaturated solutions of griseofulvin (GSF), comparing a eutectic mixture and amorphous formulations. Among the sweeteners tested, only saccharin (SAC) was able to delay drug precipitation in buffer (area under the curve (AUC) increase of 40%) and in fasted state simulated intestinal Fluid (FaSSIF, AUC increase of 20%) compared to pure media. GSF solubility was not affected by the presence of isomalt (ISO), maltitol (MALT) and SAC in buffer pH 6.5 but was reduced in FaSSIF. The quenched cooled amorphous formulation GSF-SAC QC -with the carrier that forms a eutectic mixture with GSF -provided higher drug release in buffer than amorphous formulations with ISO and MALT. In FaSSIF, SAC slightly changed the microenvironment's hydrophobicity (observed in fluorescence studies) and both its amorphous formulation (GSF-SAC QC) and its eutectic mixture (GSF-SAC EM) dissolved at concentrations above drug solubility, achieving supersaturation ratio (SR, Eq. (1)) of 4.14 and 3.15, respectively. The main finding of this study was that for the first time a eutectic mixture acted as a supersaturating drug delivery system, emphasizing the importance of investigating EMs during preformulation studies of fast-crystallizing poorly water-soluble drugs.


Assuntos
Griseofulvina , Sacarina , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Solubilidade
8.
Med J Malaysia ; 77(1): 113-115, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35087009

RESUMO

This paper reports a case of Tinea imbricata in a young Orang Asli boy which was noted during his admission for severe symptomatic anemia. Upon discharge, he was started on syrup Griseofulvin 10mg/kg daily and Whitfield cream for 4 weeks. The Department of Orang Asli Development (JAKOA) and the local Health Clinic were contacted before discharge to facilitate patient's follow-up and monitoring. Outbreaks of Tinea imbricata among the Orang Asli have been known to happen from time to time. Although this dermatophyte infection is rare in the urban population, transmission among travelers has been reported. This case report highlights its unique presentation and treatment approach.


Assuntos
Tinha , Criança , Griseofulvina/uso terapêutico , Humanos , Masculino , Tinha/diagnóstico , Tinha/tratamento farmacológico , População Urbana
10.
G3 (Bethesda) ; 12(2)2022 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-34792561

RESUMO

The polyketide griseofulvin is a natural antifungal compound and research in griseofulvin has been key in establishing our current understanding of polyketide biosynthesis. Nevertheless, the griseofulvin gsf biosynthetic gene cluster (BGC) remains poorly understood in most fungal species, including Penicillium griseofulvum where griseofulvin was first isolated. To elucidate essential genes involved in griseofulvin biosynthesis, we performed third-generation sequencing to obtain the genome of P. griseofulvum strain D-756. Furthermore, we gathered publicly available genome of 11 other fungal species in which gsf gene cluster was identified. In a comparative genome analysis, we annotated and compared the gsf BGC of all 12 fungal genomes. Our findings show no gene rearrangements at the gsf BGC. Furthermore, seven gsf genes are conserved by most genomes surveyed whereas the remaining six were poorly conserved. This study provides new insights into differences between gsf BGC and suggests that seven gsf genes are essential in griseofulvin production.


Assuntos
Griseofulvina , Família Multigênica , Antifúngicos/farmacologia , Genes Fúngicos , Genoma Fúngico , Metabolismo Secundário/genética
11.
Braz. J. Pharm. Sci. (Online) ; 58: e19731, 2022. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1394038

RESUMO

Abstract Poorly water-soluble drugs, such as the antifungal drug griseofulvin (GF), exhibit limited bioavailability, despite their high membrane permeability. Several technological approaches have been proposed to enhance the water solubility and bioavailability of GF, including micellar solubilization. Poloxamers are amphiphilic block copolymers that increase drug solubility by forming micelles and supra-micellar structures via molecular self-association. In this regard, the aim of this study was to evaluate the water solubility increment of GF by poloxamer 407 (P407) and its effect on the antifungal activity against three Trichophyton mentagrophytes and two T. rubrum isolates. The GF water solubility profile with P407 revealed a non-linear behavior, well-fitted by the sigmoid model of Morgan-Mercer-Flodin. The polymer promoted an 8-fold increase in GF water solubility. Fourier-transform infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC), and 2D nuclear magnetic resonance (NMR Roesy) spectroscopy suggested a GF-P407 interaction, which occurs in the GF cyclohexene ring. These results were supported by an increase in the water solubility of the GF impurities with the same molecular structure. The MIC values recorded for GF ranged from 0.0028 to 0.0172 mM, except for T. Mentagrophytes TME34. Notably, the micellar solubilization of GF did not increase its antifungal activity, which could be related to the high binding constant between GF and P407.


Assuntos
Solubilidade , Análise Espectral/métodos , Trichophyton/classificação , Poloxâmero/análogos & derivados , Griseofulvina/agonistas , Preparações Farmacêuticas/administração & dosagem , Disponibilidade Biológica , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular , Antifúngicos/administração & dosagem
12.
Molecules ; 26(23)2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34885898

RESUMO

Three endophytic fungi isolated from Moquiniastrum polymorphum (Less.) G. Sancho (Asteraceae) were cultivated using the one strain many compounds (OSMAC) strategy to evaluate the production of griseofulvin derivatives. Extracts obtained were analyzed by HPLC-MS/MS and the chromatographic and spectrometric data used to elaborate a feature-based molecular network (FBMN) through the GNPS platform. This approach allowed the observation of differences such as medium-specific and strain-specific production of griseofulvin derivatives and variations of cytotoxic activity in most extracts. To evaluate the efficiency of the OSMAC approach allied with FBMN analysis in the prospection of compounds of biotechnological interest, griseofulvin and 7-dechlorogriseofulvin were isolated, and the relative concentrations were estimated in all culture media using HPLC-UV, allowing for the inference of the best strain-medium combinations to maximize its production. Malt extract-peptone broth and Wickerham broth media produced the highest concentrations of both secondary metabolites.


Assuntos
Asteraceae/microbiologia , Endófitos/química , Fungos/química , Griseofulvina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Griseofulvina/análise , Espectrometria de Massas em Tandem
13.
J Infect Dev Ctries ; 15(11): 1731-1737, 2021 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-34898503

RESUMO

INTRODUCTION: Difficult-to-treat dermatophytosis is an emerging public health problem in Sri Lanka. Safe, effective and affordable treatment is needed to solve this problem. Therefore this study has assessed the effectiveness and safety of modified Whitfield ointment applied twice daily with oral griseofulvin 500 mg daily given over 8 weeks in patients with difficult-to-treat dermatophytosis. METHODOLOGY: A randomized, double-blind, within-patient-placebo-controlled trial was conducted in patients with clinico- mycologically (history, physical examination, direct light microscopy examination of scales in potassium hydroxide mount) confirmed difficult-to-treat dermatophytosis. Lesions were randomized to receive modified Whitfield ointment (5% benzoic acid and 5% salicylic acid) or emulsifying ointment. All patients were given oral griseofulvin 500mg once daily. The outcome measures were clinical assessment of disease severity, the total surface area of the lesions and the patient's perception of the disease severity at baseline and every two weeks up to a maximum of 8 weeks. RESULTS: Thirty patients completed the study. At two weeks, there was a statistically significant improvement in modified Whitfield ointment arm in the clinical assessment of disease severity and the patients' perception. There was a 7.59% reduction in the surface area of lesions in modified Whitfield ointment arm and a 5.83% increase in the surface area of lesions in the emulsifying ointment arm at two weeks. The difference between the two arms in surface area changes was not statistically significant (p = 0.107, df = 29). CONCLUSIONS: A combination of modified Whitfield ointment with griseofulvin is significantly effective, safe and affordable option for treating difficult-to-treat dermatophytosis in the tropics.


Assuntos
Antifúngicos/administração & dosagem , Benzoatos/administração & dosagem , Griseofulvina/administração & dosagem , Salicilatos/administração & dosagem , Tinha/tratamento farmacológico , Método Duplo-Cego , Combinação de Medicamentos , Quimioterapia Combinada , Humanos , Pele/efeitos dos fármacos , Sri Lanka , Tinha/fisiopatologia , Resultado do Tratamento
15.
BMC Pediatr ; 21(1): 363, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34445992

RESUMO

BACKGROUND: Tinea capitis is a common cutaneous infection of the scalp and hair follicles, typically diagnosed by direct examination and culture. Treatment with oral antifungals is usually withheld until mycology results are available. In Israel, African refugee children demonstrate higher susceptibility to Tinea capitis and generally fail to undergo follow-up evaluations. METHODS: This study aimed to identify the clinical characteristics and treatment responses of refugee children in Israel with Tinea capitis, in order to formulate a treatment plan for primary care physicians. To this end, demographic, clinical and laboratory data were extracted from the electronic medical records of 76 refugee children presenting with Tinea capitis during 2016-2017. All measured variables and derived parameters are presented using descriptive statistics. The correlation between background clinical and demographic data and Tinea capitis diagnosis was assessed using the chi-squared and Wilcoxon tests. Correlations between demographic/clinical/laboratory characteristics and other types of fungi or other important findings were assessed using a T-test. RESULTS: Scaling was the most common clinical finding. Cultures were positive in 64 (84%) and direct examination in 65 (85%) cases, with a positive correlation between the methods in 75% of cases. The most common fungal strain was T. violaceum. Fluconazole treatment failed in 27% of cases. Griseofulvin 50 mg/kg/day was administered to 74 (97%) children, and induced clinical responses. No side effects were reported. CONCLUSIONS: The key aim of this study was to emphasize the importance of diagnosis and treatment of these immigrant children by their primary pediatric doctor since it takes, an average of 4.3 months until they visit a dermatologist. During this critical time period, the scalp can become severely and permanently damaged, and the infection can become systemic or cause an outbreak within the entire community. In conclusion, we recommend to relate to scaly scalp in high-risk populations as Tinea capitis, and to treat with griseofulvin at a dosage of up to 50 mg/kg/day, starting from the first presentation to the pediatrician.


Assuntos
Emigrantes e Imigrantes , Tinha do Couro Cabeludo , Antifúngicos/uso terapêutico , Criança , Fluconazol , Griseofulvina/uso terapêutico , Humanos , Tinha do Couro Cabeludo/diagnóstico , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/epidemiologia
16.
Dermatol Ther ; 34(4): e15010, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34041831

RESUMO

Tinea capitis (TC) is the most common dermatophyte infection in children. Fungal culture the gold standard diagnostic method takes several weeks and has poor yields. Trichoscopy helps in rapid diagnosis and could work as a monitoring tool during antifungal therapy. Our main objective is to document the evolution of trichoscopic features with treatment and their correlation with clinical parameters in patients of TC. Forty-six and 52 children with clinically diagnosed TC that was confirmed by potassium hydroxide microscopy, received griseofulvin and terbinafine, respectively. Recruited children were subjected to clinical and trichoscopic assessment by calculation of CASS (clinical assessment severity score) and counting of TAHC (Total Altered hair count; negative and positive), respectively, at baseline and follow-up at 2, 4, and 6 weeks. McNemar, Wilcoxon singed ranked test and Spearman-rho correlation of various parameters was evaluated. Follow-up trichoscopy revealed significant (p < 0.009) disappearance of negative TAHC like black dot (second week onward), corkscrew, horseshoe and zigzag hair at 4 weeks and short broken hair, erythema telangiectasia hemorrhage (ETH) resolved at 6 weeks. Positive TAHC (regrowing hair) shows significant increase at 6 weeks (p < 0.001). CASS and negative TAHC showed significant difference at 4 weeks (p < 0.001) by analyzing boxplot graph. Therefore, trichoscopic resolution occurred before the clinical cure. Terbinafine subjects showed a higher clinical cure rate at 4 weeks (p = 0.02) as compared to griseofulvin. To conclude, trichoscopy is a good monitoring tool that could document the disappearance of almost all dystrophic hair at 4 to 6 weeks and is a more sensitive tool than microscopic examination. Regrowing hair and perifollicular scaling are markers of recovery.


Assuntos
Tinha do Couro Cabeludo , Antifúngicos/uso terapêutico , Criança , Griseofulvina , Cabelo , Humanos , Estudos Prospectivos , Terbinafina , Tinha do Couro Cabeludo/diagnóstico por imagem , Tinha do Couro Cabeludo/tratamento farmacológico
17.
Pediatr Dermatol ; 38(4): 806-811, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33998709

RESUMO

BACKGROUND: Tinea capitis is a common fungal infection in Israel, most commonly caused by the dermatophyte Trichophyton tonsurans. OBJECTIVES: To investigate the effectiveness of oral antifungal monotherapy in producing clinical or complete cure. We also evaluated the impact of topical therapy (bifonazole 1% shampoo and/or betamethasone valerate 0.1% solution), prior to oral treatment, on patients' likelihood of clinical or complete cure. METHODS: A retrospective chart review was conducted. Patients with mycologically confirmed tinea capitis were treated with one of four regimens: (1) terbinafine (greater than 40 kg: 250 mg/day, 20 to 40 kg: 125 mg/day, less than 20 kg: 62.5 mg/day), (2) itraconazole 5 mg/kg daily, (3) fluconazole 6 mg/kg daily, or (4) griseofulvin 20 mg/kg daily. We used generalized linear models (GLM) to determine whether there was a significant association between the odds of cure and choice of treatment. RESULTS: The causative species was Trichophyton tonsurans in all but 6 cases that grew T violaceum. For pediatric patients, the odds of having complete or clinical cure within 6 weeks was greater if they used terbinafine compared to itraconazole, fluconazole, or griseofulvin (odds ratio [OR] = 9.06, P = .047). The likelihood of complete or clinical cure within 8 weeks of oral therapy was lower if topical steroids were previously used compared to if topical antifungals were used prior to systemic treatment (OR = 0.29, P = .046). CONCLUSIONS: Our findings substantiate prior literature demonstrating that terbinafine is non-inferior to griseofulvin, itraconazole, and fluconazole in the therapy of pediatric tinea capitis caused by T tonsurans.


Assuntos
Naftalenos , Tinha do Couro Cabeludo , Antifúngicos/uso terapêutico , Arthrodermataceae , Criança , Griseofulvina/uso terapêutico , Humanos , Israel/epidemiologia , Itraconazol/uso terapêutico , Naftalenos/uso terapêutico , Estudos Retrospectivos , Tinha do Couro Cabeludo/tratamento farmacológico , Tinha do Couro Cabeludo/epidemiologia
18.
J Pediatr ; 234: 269-272, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33794219

RESUMO

We examine management practices of tinea capitis at 2 US academic centers. The majority of providers treated tinea capitis with the oral antifungal agent griseofulvin and did not obtain a fungal culture. We recommend newer antifungal treatments such as terbinafine and fluconazole and obtaining a fungal culture for effective treatment.


Assuntos
Antifúngicos/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Tinha do Couro Cabeludo/diagnóstico , Tinha do Couro Cabeludo/tratamento farmacológico , Centros Médicos Acadêmicos , Adolescente , Criança , Pré-Escolar , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Fluconazol/uso terapêutico , Griseofulvina/uso terapêutico , Humanos , Masculino , Pediatria , Estudos Retrospectivos , Terbinafina/uso terapêutico , Estados Unidos
19.
Nat Commun ; 12(1): 1883, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767198

RESUMO

Natural product structure and fragment-based compound development inspire pseudo-natural product design through different combinations of a given natural product fragment set to compound classes expected to be chemically and biologically diverse. We describe the synthetic combination of the fragment-sized natural products quinine, quinidine, sinomenine, and griseofulvin with chromanone or indole-containing fragments to provide a 244-member pseudo-natural product collection. Cheminformatic analyses reveal that the resulting eight pseudo-natural product classes are chemically diverse and share both drug- and natural product-like properties. Unbiased biological evaluation by cell painting demonstrates that bioactivity of pseudo-natural products, guiding natural products, and fragments differ and that combination of different fragments dominates establishment of unique bioactivity. Identification of phenotypic fragment dominance enables design of compound classes with correctly predicted bioactivity. The results demonstrate that fusion of natural product fragments in different combinations and arrangements can provide chemically and biologically diverse pseudo-natural product classes for wider exploration of biologically relevant chemical space.


Assuntos
Produtos Biológicos/química , Produtos Biológicos/síntese química , Descoberta de Drogas/métodos , Quimioinformática , Cromonas/química , Griseofulvina/química , Indóis/química , Morfinanos/química , Quinidina/química , Quinina/química , Bibliotecas de Moléculas Pequenas/química
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