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1.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360928

RESUMO

Xeroderma Pigmentosum protein C (XPC) is involved in recognition and repair of bulky DNA damage such as lesions induced by Ultra Violet (UV) radiation. XPC-mutated cells are, therefore, photosensitive and accumulate UVB-induced pyrimidine dimers leading to increased cancer incidence. Here, we performed a high-throughput screen to identify chemicals capable of normalizing the XP-C phenotype (hyper-photosensitivity and accumulation of photoproducts). Fibroblasts from XP-C patients were treated with a library of approved chemical drugs. Out of 1280 tested chemicals, 16 showed ≥25% photo-resistance with RZscore above 2.6 and two drugs were able to favor repair of 6-4 pyrimidine pyrimidone photoproducts (6-4PP). Among these two compounds, Isoconazole could partially inhibit apoptosis of the irradiated cells especially when cells were post-treated directly after UV irradiation while Clemizole Hydrochloride-mediated increase in viability was dependent on both pre and post treatment. No synergistic effect was recorded following combined drug treatment and the compounds exerted no effect on the proliferative capacity of the cells post UV exposure. Amelioration of XP-C phenotype is a pave way towards understanding the accelerated skin cancer initiation in XP-C patients. Further examination is required to decipher the molecular mechanisms targeted by these two chemicals.


Assuntos
Benzimidazóis/farmacologia , Miconazol/análogos & derivados , Dermatopatias/tratamento farmacológico , Raios Ultravioleta/efeitos adversos , Xeroderma Pigmentoso/tratamento farmacológico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Reposicionamento de Medicamentos , Humanos , Miconazol/farmacologia
2.
Chem Biol Interact ; 343: 109498, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33961833

RESUMO

The drug-drug interaction (DDI) risk of phenytoin with several topical formulations of miconazole is still unclear. The present investigation conducted in vitro-in vivo extrapolation to predict the potential risks. Our data indicated that miconazole potently inhibited phenytoin hydroxylation in both pooled human liver microsomes (HLMs) and recombinant cytochrome P450 2C9 (CYP2C9) with the Ki values of 125 ± 7 nM and 30 ± 2 nM, respectively. Quantitative prediction of DDI risk suggests that, beside intravenous administration or swallowed tablet, combination of phenytoin and miconazole high dose oral gel or buccal tablet may also result in a clinically significant increase of phenytoin AUC (>53%) by the inhibition of miconazole against phenytoin hydroxylation, consequently a higher frequency of adverse events, while the coadministration of miconazole vaginal formulation and phenytoin will be safe.


Assuntos
Inibidores do Citocromo P-450 CYP2C9/farmacologia , Miconazol/farmacologia , Fenitoína/metabolismo , Anticonvulsivantes/metabolismo , Antifúngicos/farmacologia , Citocromo P-450 CYP2C9/química , Citocromo P-450 CYP2C9/metabolismo , Interações Medicamentosas , Humanos , Hidroxilação/efeitos dos fármacos , Cinética , Microssomos Hepáticos/metabolismo , Medição de Risco
3.
Pan Afr Med J ; 38: 178, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995784

RESUMO

Candidiasis is an acute or subacute fungal infection caused by fungi that belongs to candida genus, with Candida albicansbeing the most frequent causative agent. Candida kefyr is a rare cause of candidiasis which has been reported in systemic candidiasis and deep infections. However, to date, it has never been reported as a cause in dermatophytosis. We report a case of candidiasis caused by Candida kefyr in a 72-year-old woman with a chief complaint of pruritic erythematous rash on the back from one day prior to admission. Diagnosis was established based on clinical features, direct microscopic examination with 10% potassium hydroxide solution, gram staining. The fungal species was determined by carbohydrate fermentation test which showed a positive result for Candida kefyr. The patient was treated with miconazole cream and fusidic cream and showed significant clinical improvement.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Cutânea/diagnóstico , Kluyveromyces/isolamento & purificação , Idoso , Candidíase Cutânea/tratamento farmacológico , Candidíase Cutânea/microbiologia , Eritema/microbiologia , Feminino , Ácido Fusídico/administração & dosagem , Humanos , Miconazol/administração & dosagem , Prurido/microbiologia , Resultado do Tratamento
4.
Future Med Chem ; 13(13): 1105-1125, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33960203

RESUMO

Background: Alzheimer's disease is a multifactorial neurological disorder seen in elderly people. Loss of cholinergic transmission and unbalanced tryptophan metabolism kynurenine pathway have been demonstrated in neuropsychiatric diseases. Methods & results: Among the two series of synthesized compounds, compounds 5c and 5h were identified as effective dual BChE/IDO1 inhibitors, with well-balanced micromolar activity. Compounds 5c and 5h exhibited promising ability to ameliorate behavioral impairment by Morris water maze. The safety of miconazole analogs was also validated by PC12 and SH-SY5Y cell lines. Conclusion: These results highlight the ability of 5c and 5h to treat Alzheimer's disease.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Miconazol/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Linhagem Celular Tumoral , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Electrophorus , Cavalos , Humanos , Masculino , Camundongos , Miconazol/síntese química , Miconazol/química , Modelos Moleculares , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Células PC12 , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Agregados Proteicos/efeitos dos fármacos , Ratos
5.
Cochrane Database Syst Rev ; 5: CD009289, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34033120

RESUMO

BACKGROUND: Otomycosis is a fungal infection of the outer ear, which may be treated with topical antifungal medications. There are many types, with compounds belonging to the azole group ('azoles') being among the most widely used. OBJECTIVES: To evaluate the benefits and harms of topical azole treatments for otomycosis. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The search date was 11 November 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in adults and children with otomycosis comparing any topical azole antifungal with: placebo, no treatment, another type of topical azole or the same type of azole but applied in different forms. A minimum follow-up of two weeks was required. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) clinical resolution as measured by the proportion of participants with complete resolution at between two and four weeks after treatment (however defined by the authors of the studies) and 2) significant adverse events. Secondary outcomes were 3) mycological resolution and 4) other less serious adverse effects. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included four studies with 559 participants from Spain, Mexico and India. Three studies included children and adults; one included only adults. The duration of symptoms was not always explicitly stated. Mycological resolution results were only reported in one study. The studies assessed two comparisons: one type of topical azole versus another and the same azole but administered in different forms (cream versus solution). A. Topical azoles versus placebo None of the studies assessed this comparison. B. Topical azoles versus no treatment None of the studies assessed this comparison. C. One type of topical azole versus another type of topical azole i) Clotrimazole versus other types of azoles (eberconazole, fluconazole, miconazole) Three studies examined clotrimazole versus other types of azoles. The evidence is very uncertain about the difference between clotrimazole and other types of azole in achieving complete clinical resolution at four weeks (risk ratio (RR) 0.80, 95% confidence interval (CI) 0.59 to 1.07; 3 studies; 439 participants; very low-certainty evidence). The anticipated absolute effects are 668 per 1000 for clotrimazole versus 835 per 1000 for other azoles. One study planned a safety analysis and reported no significant adverse events in either group. The evidence is therefore very uncertain about any differences between clotrimazole and other types of azole (no events in either group; 1 study; 174 participants; very low-certainty evidence). Clotrimazole may result in little or no difference in mycological resolution at two weeks follow-up (RR 1.01, 95% CI 0.96 to 1.06; 1 study; 174 participants; low-certainty evidence) or in other (less serious) adverse events at two weeks follow-up (36 per 1000, compared to 45 per 1000, RR 0.79, 95% CI 0.18 to 3.41; 1 study; 174 participants; very low-certainty evidence). ii) Bifonazole cream versus bifonazole solution One study compared bifonazole 1% cream with solution. Bifonazole cream may have little or no effect on clinical resolution at two weeks follow-up when compared to solution, but the evidence is very uncertain (RR 1.07, 95% CI 0.73 to 1.57; 1 study; 40 ears; very low-certainty evidence). Bifonazole cream may achieve less mycological resolution compared to solution at two weeks after the end of therapy, but the evidence for this is also very uncertain (RR 0.53, 95% CI 0.29 to 0.96; 1 study; 40 ears; very low-certainty evidence). Five out of 35 patients sustained severe itching and burning from the bifonazole solution but none with the bifonazole cream (very low-certainty evidence). AUTHORS' CONCLUSIONS: We found no studies that evaluated topical azoles compared to placebo or no treatment. The evidence is very uncertain about the effect of clotrimazole on clinical resolution of otomycosis, on significant adverse events or other (non-serious) adverse events when compared with other topical azoles (eberconazole, fluconazole, miconazole). There may be little or no difference between clotrimazole and other azoles in terms of mycological resolution. It may be difficult to generalise these results because the range of ethnic backgrounds of the participants in the studies is limited.


Assuntos
Antifúngicos/administração & dosagem , Otomicose/tratamento farmacológico , Administração Tópica , Adulto , Antifúngicos/efeitos adversos , Viés , Criança , Clotrimazol/administração & dosagem , Clotrimazol/efeitos adversos , Cicloeptanos/administração & dosagem , Cicloeptanos/efeitos adversos , Fluconazol/administração & dosagem , Fluconazol/efeitos adversos , Humanos , Imidazóis/administração & dosagem , Imidazóis/efeitos adversos , Miconazol/administração & dosagem , Miconazol/efeitos adversos , Placebos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
BMC Genomics ; 22(1): 250, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33827426

RESUMO

BACKGROUND: Trichophyton mentagrophyte (TM), a zoonotic pathogen, has been endangering public health due to emerging drug resistance. Although increased attention is paid to this issue, there is very limited research available on drug resistance in TM. In this study, we studied the gene and proteomic changes, morphological changes, cellular fat localization, fat content changes, and biofilm of TM treated with different substances. RESULTS: The TM growth curve showed a positive correlation with the concentration of Fenarimol (FE), genistein (GE), clotrimazole (KM), and Miconazole nitrate salt (MK). The morphology of TM cells changed in different degrees after treatment with different substances as observed by TEM and SEM. The results showed that under KM and berberine hydrochloride (BB) treatment, a total of 3305 differentially expressed genes were detected, with the highest number in the KM-treated group (578 up-regulated and 615 down-regulated). A total of 847 proteins and 1850 peptides were identified in TM proteomics. Nile red staining showed that the fat content of TM was significantly higher in the BB-, ethidium bromide- (EB), FE-, KM-, Adriamycin hydrochloride- (YA), and MK-treated group compared to the control group. Results of the biofilm thickness showed that it gradually increased under treatment with specific concentrations of KM or BB, which may be related to the up-regulation of ERG25 and CYP related gene proteins. CONCLUSIONS: It is suggested that in order to effectively deal with dermatomycosis caused by TM, it is necessary to inhibit the expression of ERG25 and CYP related genes and fat metabolism, which can result in the inhibition of the production of biofilm by the fungus and solve the problem of fungal drug resistance in clinical settings.


Assuntos
Proteômica , Trichophyton , Arthrodermataceae , Farmacorresistência Fúngica/genética , Miconazol , Trichophyton/genética
7.
BMJ Case Rep ; 14(3)2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33653857

RESUMO

A man in his 70s on warfarin attended the emergency department three times over a 24-hour period, complaining of a sore throat, neck swelling and difficulty swallowing. He was initially diagnosed with pharyngitis, given antibiotics and discharged home, which was reconfirmed on the second attendance after an episode of haemoptysis. On the third, he was diagnosed with a pharyngeal haematoma causing partial airway obstruction and admitted to critical care. His international normalised ratio (INR) was reported initially as unreadable by the laboratory, then eventually came back as >20. After a thorough medication history, he said that he had recently been prescribed topical miconazole oromucosal gel by his dentist for oral candidiasis, which had interacted with the warfarin to cause this life-threatening haematoma.


Assuntos
Obstrução das Vias Respiratórias , Varfarina , Obstrução das Vias Respiratórias/etiologia , Anticoagulantes/efeitos adversos , Interações Medicamentosas , Hematoma/induzido quimicamente , Humanos , Coeficiente Internacional Normatizado , Masculino , Miconazol/efeitos adversos , Varfarina/efeitos adversos
8.
Med Mycol J ; 62(1): 11-19, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642523

RESUMO

INTRODUCTION: SO-1105 is an oral mucosal adhesive tablet containing 50 mg of miconazole. It had been shown overseas that a once-daily application of the drug continues antifungal effect in the treatment of oropharyngeal candidiasis. We report the results of the phase 3 clinical study of this drug with miconazole gel as a control in Japan. METHODS: The study included patients aged 20 years or older with oropharyngeal candidiasis who had oral lesions characterized by oropharyngeal candidiasis and whose fungi was confirmed by direct microscopic examination. The primary efficacy endpoint was the clinical cure rate on Day15 after 14 days of administration. The population analyzed for efficacy was per protocol set (PPS). RESULTS: 120 subjects were included in PPS. In detail, 59 subjects were in the SO-1105 group (SO-1105 group) and 61 subjects were in the miconazole gel group (Gel group). For efficacy, the clinical cure rate on Day15 was 47.5% in SO-1105 group and 47.5% in Gel group, showing the similar efficacy between both groups. For safety, adverse drug reactions were observed in 29.0% of SO-1105 group and 24.6% of Gel group, showing the similar safety between both groups. CONCLUSION: The efficacy of SO-1105 was shown to be similar to that of miconazole gel. Meanwhile, SO-1105 is an adhesive tablet and is administered once-daily. For this, SO-1105 is expected to better compliance and useful drug for the elderly. Therefore, SO-1105 is considered to be widely used in clinical practice as one of the therapeutic drugs for oropharyngeal candidiasis.


Assuntos
Antifúngicos/administração & dosagem , Candidíase Bucal/tratamento farmacológico , Miconazol/administração & dosagem , Idoso , Feminino , Géis , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Mucosa Bucal , Segurança , Comprimidos , Resultado do Tratamento
9.
Vet Dermatol ; 32(3): 297-e81, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33739489

RESUMO

Trichophyton benhamiae was diagnosed in a 9-year-old female dog by histopathological evaluation, fungal culture and confirmation by sequencing of the internal transcribed spacer region of ribosomal DNA. Successful therapy was achieved with itraconazole, bathing with miconazole and chlorhexidine shampoo, and topical application of sodium hypochlorite as a rinse.


Assuntos
Doenças do Cão , Tinha , Animais , Arthrodermataceae , Doenças do Cão/diagnóstico , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Itraconazol/uso terapêutico , Miconazol/uso terapêutico , Tinha/diagnóstico , Tinha/tratamento farmacológico , Tinha/veterinária , Trichophyton
10.
Eur J Med Chem ; 216: 113337, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33713977

RESUMO

A series of selenium-containing miconazole derivatives were identified as potent antifungal drugs in our previous study. Representative compound A03 (MIC = 0.01 µg/mL against C.alb. 5314) proved efficacious in inhibiting the growth of fungal pathogens. However, further study showed lead compound A03 exhibited potential hemolysis, significant cytotoxic effect and unfavorable metabolic stability and was therefore modified to overcome these drawbacks. In this article, the further optimization of selenium-containing miconazole derivatives resulted in the discovery of similarly potent compound B17 (MIC = 0.02 µg/mL against C.alb. 5314), exhibiting a superior pharmacological profile with decreased rate of metabolism, cytotoxic effect and hemolysis. Furthermore, compound B17 showed fungicidal activity against Candida albicans and significant effects on the treatment of resistant Candida albicans infections. Meanwhile, compound B17 not only could reduce the ergosterol biosynthesis pathway by inhibiting CYP51, but also inhibited biofilm formation. More importantly, compound B17 also shows promising in vivo efficacy after intraperitoneal injection and the PK study of compound B17 was evaluated. In addition, molecular docking studies provide a model for the interaction between the compound B17 and the CYP51 protein. Overall, we believe that these selenium-containing miconazole compounds can be further developed for the potential treatment of fungal infections.


Assuntos
Inibidores de 14-alfa Desmetilase/química , Antifúngicos/química , Miconazol/química , Selênio/química , Esterol 14-Desmetilase/química , Inibidores de 14-alfa Desmetilase/metabolismo , Inibidores de 14-alfa Desmetilase/farmacologia , Inibidores de 14-alfa Desmetilase/uso terapêutico , Animais , Antifúngicos/metabolismo , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Sítios de Ligação , Biofilmes/efeitos dos fármacos , Candida/efeitos dos fármacos , Candida/fisiologia , Candidíase/tratamento farmacológico , Candidíase/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Modelos Animais de Doenças , Desenho de Fármacos , Meia-Vida , Humanos , Camundongos , Miconazol/metabolismo , Miconazol/farmacologia , Miconazol/uso terapêutico , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Esterol 14-Desmetilase/metabolismo , Relação Estrutura-Atividade
11.
Mar Drugs ; 19(3)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652774

RESUMO

Oceanapiside (OPS), a marine natural product with a novel bifunctional sphingolipid structure, is fungicidal against fluconazole-resistant Candida glabrata at 10 µg/mL (15.4 µM). The fungicidal effect was observed at 3 to 4 h after exposure to cells. Cytological and morphological studies revealed that OPS affects the budding patterns of treated yeast cells with a significant increase in the number of cells with single small buds. In addition, this budding morphology was found to be sensitive in the presence of OPS. Moreover, the number of cells with single medium-sized buds and cells with single large buds were decreased significantly, indicating that fewer cells were transformed to these budding patterns, suggestive of inhibition of polarized growth. OPS was also observed to disrupt the organized actin assembly in C. glabrata, which correlates with inhibition of budding and polarized growth. It was also demonstrated that phytosphingosine (PHS) reversed the antifungal activity of oceanapiside. We quantified the amount of long chain-bases (LCBs) and phytoceramide from the crude extracts of treated cells using LC-ESI-MS. PHS concentration was elevated in extracts of cells treated with OPS when compared with cells treated with miconazole and amphotericin B. Elevated levels of PHS in OPS-treated cells confirms that OPS affects the pathway at a step downstream of PHS synthesis. These results also demonstrated that OPS has a mechanism of action different to those of miconazole and amphotericin B and interdicts fungal sphingolipid metabolism by specifically inhibiting the step converting PHS to phytoceramide.


Assuntos
Antifúngicos/farmacologia , Candida glabrata/efeitos dos fármacos , Glicolipídeos/farmacologia , Esfingolipídeos/metabolismo , Anfotericina B/farmacologia , Produtos Biológicos/farmacologia , Cromatografia Líquida , Farmacorresistência Fúngica , Fluconazol/farmacologia , Espectrometria de Massas , Miconazol/farmacologia , Esfingosina/análogos & derivados , Esfingosina/metabolismo
12.
Int J Mol Sci ; 22(4)2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33546211

RESUMO

In a previous article, we reported on the higher toxicity of silver(I) complexes of miconazole [Ag(MCZ)2NO3 (1)] and [Ag(MCZ)2ClO4 (2)] in HepG2 tumor cells compared to the corresponding salts of silver, miconazole and cisplatin. Here, we present the synthesis of two silver(I) complexes of miconazole containing two new counter ions in the form of Ag(MCZ)2X (MCZ = 1-[2-(2,4-dichlorobenzyloxy)-2-(2,4-dichlorophenyl)ethyl]-1H-imidazole]; X = BF4- (3), SbF6- (4)). The novel silver(I) complexes were characterized by elemental analysis, 1H NMR, 13C NMR and infrared (IR) spectroscopy, electrospray ionization (ESI)-MS spectrometry and X-ray-crystallography. In the present study, the antimicrobial activity of all obtained silver(I) complexes of miconazole against six strains of Gram-positive bacteria, five strains of Gram-negative bacteria and yeasts was evaluated. The results were compared with those of a silver sulfadiazine drug, the corresponding silver salts and the free ligand. Silver(I) complexes exhibited significant activity against Gram-positive bacteria, which was much better than that of silver sulfadiazine and silver salts. The highest antimicrobial activity was observed for the complex containing the nitrate counter ion. All Ag(I) complexes of miconazole resulted in much better inhibition of yeast growth than silver sulfadiazine, silver salts and miconazole. Moreover, the synthesized silver(I) complexes showed good or moderate activity against Gram-negative bacteria compared to the free ligand.


Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Complexos de Coordenação/síntese química , Miconazol/química , Prata/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Leveduras/efeitos dos fármacos
13.
Am J Otolaryngol ; 42(4): 102961, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33621764

RESUMO

PURPOSE: Various agents with various antifungal properties are widely used for otomycosis eradication. However, there is still no consensus on the most effective agent. Therefore, the present study aims to investigate the efficacy of topical 1% isoconazole nitrate cream in the treatment of otomycosis. METHODS: This prospective study included 43 patients who were applied to our outpatient clinic with complaints of ear pain, itching, aural fullness, and hypoacusis, and were diagnosed with unilateral otomycosis. After aspiration and cleaning, the external ear canal was filled with 1% isoconazole nitrate cream using an iv cannula and insulin syringe. Control examinations were performed on the 5th, 10th, 15th, and 20th days. In the follow-up examinations, patients were asked about how many days after the cream administration the pain and itching completely relief and the answers were recorded. RESULTS: In the first control examination of 23 (92%) of 25 patients with pain, it was observed that the pain and otoendoscopic examination findings completely recovered. In the second control, it was found that both pain and otoendoscopic examination findings completely recovered in the remaining 2 patients (25 patients, 100%). 35 patients complained of itching and it was observed that itching and otoendoscopic examination findings completely recovered in 26 patients (75%) in the first control, 5 more patients (31 patients, 88.6%) in the second control, and 2 more patients (33 patients, 94.3%) in the third control examination. CONCLUSION: Isoconazole nitrate cream appears to be an effective and easily applicable agent for the treatment of otomycosis.


Assuntos
Antifúngicos/administração & dosagem , Miconazol/análogos & derivados , Otomicose/tratamento farmacológico , Administração Tópica , Adulto , Idoso , Endoscopia , Feminino , Seguimentos , Humanos , Masculino , Memória Episódica , Miconazol/administração & dosagem , Pessoa de Meia-Idade , Pomadas , Otomicose/diagnóstico , Otomicose/patologia , Resultado do Tratamento , Adulto Jovem
14.
Am J Med ; 134(5): e308-e312, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33176127

RESUMO

PURPOSE: Azole antimycotics and nystatin oral solution are used to treat oral candidiasis. Azoles inhibit cytochrome (CYP) P450-dependent metabolism of warfarin, which could increase the anticoagulant effect of warfarin. Nystatin is not expected to interfere with warfarin metabolism, but current data are conflicting. With this study, we aimed to explore the potential drug-drug interactions between warfarin and azole antimycotics used in the treatment of oral candidiasis, that is, systemic fluconazole, miconazole oral gel, and nystatin oral solution. METHODS: By linking clinical data on international normalized ratio (INR) measurements with administrative data on filled prescriptions of warfarin and antimycotics during 2000-2015, we explored INR changes in warfarin users relative to initiation of systemic fluconazole (n = 413), miconazole oral gel (n = 330), and nystatin oral solution (n = 399). RESULTS: We found a significant increase in mean INR of 0.83 (95% confidence interval [CI] 0.61-1.04) and 1.27 (95% CI 0.94-1.59) following initiation of systemic fluconazole and miconazole oral gel, respectively. Also, the proportion of patients experiencing an INR-value above 5 was increased after initiation of fluconazole (from 4.3% to 15.3%) and miconazole (from 5.5% to 30.1%). INR was unaffected by initiation of nystatin oral solution (mean change 0.08; 95% CI -0.10 to 0.25). CONCLUSION: Initiation of systemic fluconazole and miconazole oral gel was associated with increased INR in warfarin users. A similar association was not found for nystatin oral solution, which thus appears to be the safest alternative when treating oral candidiasis in warfarin users.


Assuntos
Anticoagulantes/efeitos adversos , Antifúngicos/uso terapêutico , Candidíase Bucal/tratamento farmacológico , Fluconazol/efeitos adversos , Coeficiente Internacional Normatizado , Miconazol/efeitos adversos , Varfarina/efeitos adversos , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/administração & dosagem , Antifúngicos/administração & dosagem , Antifúngicos/efeitos adversos , Interações Medicamentosas , Feminino , Fluconazol/administração & dosagem , Fluconazol/uso terapêutico , Géis , Humanos , Masculino , Miconazol/administração & dosagem , Miconazol/uso terapêutico , Soluções , Varfarina/administração & dosagem
15.
Surg Today ; 51(4): 568-574, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32886209

RESUMO

PURPOSE: Despite improvements in neonatal intensive care, the outcomes of extremely-low-birth-weight infants (ELBWIs) with surgical diseases remain to be improved. We started administering enteral miconazole (MCZ) to ELBWIs from 2002 to prevent fungal infection. Since then, the incidence of intestinal perforation has significantly decreased. We investigated this prophylactic effect of MCZ against necrotizing enterocolitis (NEC) and focal intestinal perforation (FIP) and explored a new prophylactic concept against intestinal perforation. METHODS: We designed a historical cohort study to evaluate the effect of MCZ for intestinal perforation in ELBWIs who underwent treatment in our neonatal intensive-care unit between January 1998 and December 2005. We divided these cases into two groups: the Pre-MCZ group and the Post-MCZ group. We compared the morbidity, clinical outcomes and pathological features of NEC and FIP. RESULTS: The rate of intestinal perforation with NEC was significantly reduced after the introduction of MCZ (p = 0.007, odds ratio; 3.782, 95% confidence interval; 1.368-12.08). The pathological findings of NEC specimens showed that the accumulation of inflammatory cells was significantly reduced in the Post-MCZ group when compared with the Pre-MCZ group (p < 0.05). CONCLUSIONS: The efficacy of the enteral administration of MCZ on intestinal perforation with NEC highlights a new prophylactic concept in the clinical management of ELBWIs.


Assuntos
Antifúngicos/administração & dosagem , Enterocolite Necrosante/complicações , Enterocolite Necrosante/prevenção & controle , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Perfuração Intestinal/complicações , Perfuração Intestinal/prevenção & controle , Miconazol/administração & dosagem , Micoses/prevenção & controle , Administração Oral , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Micoses/etiologia , Fatores de Tempo
16.
Environ Toxicol ; 36(2): 185-193, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32981224

RESUMO

Autophagy plays a dual function in cancer progression; autophagy activation can support cancer cell survival or contribute to cell death. Miconazole, a Food and Drug Administration-approved antifungal drug, has been implicated in oncology research recently. Miconazole was found to exert antitumor effects in various tumors, including bladder cancer (BC). However, whether it provokes protective autophagy has been never discussed. We provide evidence that miconazole induces protective autophagy in BC for the first time. The results indicated that 1A/1B-light chain 3 (LC3)-II processing and p62 expression were elevated after miconazole exposure. Also, adenosine monophosphate-activated protein kinase phosphorylation was increased after miconazole treatment. We also confirmed the autophagy-promoting effect of miconazole in the presence of bafilomycin A1 (Baf A1). The result indicates that a combination treatment of miconazole and Baf A1 improved LC3-II processing, confirming that miconazole promoted autophagic flux. The acridine orange, Lysotracker, and cathepsin D staining results indicate that miconazole increased lysosome formation, revealing its autophagy-promoting function. Finally, miconazole and autophagy inhibitor 3-methyladenine cotreatment further reduced the cell viability and induced apoptosis in BC cells, proving that miconazole provokes protective autophagy in BC cells. Our findings approve that miconazole has an antitumor effect in promoting cell apoptosis; however, its function of protective autophagy is needed to be concerned in cancer treatment.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Miconazol/farmacologia , Neoplasias da Bexiga Urinária/patologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Lisossomos/metabolismo , Macrolídeos/administração & dosagem , Macrolídeos/farmacologia , Miconazol/administração & dosagem , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Fosforilação , Proteínas Quinases/metabolismo , Neoplasias da Bexiga Urinária/tratamento farmacológico
17.
Drug Deliv ; 28(1): 87-99, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33342321

RESUMO

Recurrent aphthous ulcer (RAU) is a well-known painful, inflammatory disease with uncertain etiology for which local symptomatic therapy is only available. The aim of this study was to formulate and characterize muco-adhesive sponges containing a mixture of tenoxicam and miconazole nitrate to manage pain, inflammation and avoid candida infection that may accompany RAU due to poor oral hygiene. Two polymers at different concentrations were used to prepare sponges applying simple freeze-drying. Medicated chitosan (2%) sponges (mC2) showed acceptable physical appearance, surface pH (6.3 ± 0.042), porosity (25.7% ± 1.8), swelling index (5.7 ± 0.11), in-vivo and ex-vivo muco-adhesion time (115 min.±0.813 and 155 min.±1.537, respectively), ex-vivo muco-adhesion force (0.09 N ± 0.002) and scanning electron microscope (SEM) images. For concurrent clear-cut determination of tenoxicam and miconazole nitrate from mC2, a new UPLC method was developed and validated. mC2 sponges exhibited superior in-vitro drug release profiles where ∼100% of tenoxicam released within 5 min for fast pain relief with a more prolonged miconazole nitrate release. Furthermore, in-vivo animal study revealed that mC2 caused a significant decrease in the acetic acid-induced ulcer size in rats after 6 days of treatment (p < .0001) compared to negative and positive controls. Additionally, histopathological examination showed faster healing with complete restoration of the normal oral histology in rats. The present study concludes that chitosan sponge loaded with a combination of tenoxicam and miconazole nitrate could improve healing of RAU cases.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Antifúngicos/administração & dosagem , Portadores de Fármacos/química , Miconazol/administração & dosagem , Piroxicam/análogos & derivados , Estomatite Aftosa/tratamento farmacológico , Adesivos/administração & dosagem , Animais , Carboximetilcelulose Sódica/química , Quitosana/química , Relação Dose-Resposta a Droga , Liberação Controlada de Fármacos , Liofilização , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Piroxicam/administração & dosagem , Ratos , Cicatrização
18.
Vive (El Alto) ; 3(9): 227-246, dic. 2020. ilus
Artigo em Espanhol | LILACS | ID: biblio-1252340

RESUMO

INTRODUCCIÓN: las infecciones fúngicas ocasionadas por levaduras del género Cándida son extremadamente comunes en mujeres de edad reproductiva, y constituyen un motivo de atención medica de salud. OBJETIVO: evaluar la susceptibilidad de Cándidas spp, mediante el método colorimétrico (Integral Yeast System Plus). MÉTODO: fue de tipo descriptivo, transversal; se recopiló información mediante observación directa en campo y el análisis documental para obtener información bibliográfica de tipo secundaria. RESULTADOS: de los 72 casos encontrados de Cándida Albicans revela que son susceptibles a la anfotericina B (2ug/ml); de los 5 casos encontrados de Cándida Krusei revela que son sensibles a la Anfotericina B (2ug/ml); De 1 caso encontrado de Cándida Parapsilosis revela sensibilidad en la Nistatina (1.25ug/ml). En este estudio la prevalencia de la infección por Cándida fue del (44.98%). CONCLUSIONES: Cándida Albicans fue la especie más común aislada en las mujeres embarazadas representando un 72%, En la evaluación de la susceptibilidad a través del kit Integral System Yeast Plus se obtuvo que Cándida Albicans es susceptible a Anfotericina B, Flucitosina entre otros, en Cándida Glabrata se obtuvo que es sensible a la Nistatina, Anfotericina B, susceptible entre otros, en Cándida Krusei se obtuvo que es sensible a la Anfotericina B, Clotrimazol, Miconazol, susceptibles a la Nistatina, Voriconazol y resistente a la Flucitosina, Ketoconazol, Itraconazol y Fluconazol.


INTRODUCTION: fungal infections caused by yeast of the genus Candida are extremely common in women of reproductive age, and constitute a reason for medical health care. OBJECTIVE: to evaluate the susceptibility of Candida spp, using the colorimetric method (Integral Yeast System Plus). METHOD: it was descriptive, transversal; Information was collected through direct observation in the field and documentary analysis to obtain secondary bibliographic information. RESULTS: of the 72 cases found, Candida Albicans reveals that they are susceptible to amphotericin B (2ug / ml); of the 5 cases found, Candida Krusei reveals that they are sensitive to Amphotericin B (2ug / ml); Of 1 case found of Candida Parapsilosis reveals sensitivity in Nystatin (1.25ug / ml). In this study, the prevalence of Candida infection was (44.98%). CONCLUSIONS: Candida Albicans was the most common species isolated in pregnant women, representing 72%. In the evaluation of susceptibility through the Integral System Yeast Plus kit it was obtained that Candida Albicans is susceptible to Amphotericin B, Flucytosine among others, in Candida Glabrata was obtained that it is sensitive to Nystatin, Amphotericin B, susceptible among others, in Candida Krusei it was obtained that it is sensitive to Amphotericin B, Clotrimazole, Miconazole, susceptible to Nystatin, Voriconazole and resistant to Flucytosin, Ketoconazole, Itraconazole and Fluconazole.


INTRODUÇÃO: as infecções fúngicas causadas por leveduras do gênero Candida são extremamente comuns em mulheres em idade reprodutiva e constituem motivo de cuidados médicos. OBJETIVO: avaliar a suscetibilidade de Candida spp, por meio do método colorimétrico (Integral Yeast System Plus). MÉTODO: foi descritivo, transversal; as informações foram coletadas por meio de observação direta em campo e análise documental para obtenção de informações bibliográficas secundárias. RESULTADOS: Dos 72 casos encontrados, Cândida Albicans revelou ser suscetíveis à anfotericina B (2ug /ml); dos 5 casos encontrados, Candida Krusei revela que são sensíveis à Anfotericina B (2ug / ml); de 1 caso encontrado de Candida Parapsilosis revela sensibilidade na Nistatina (1,25ug / ml). Neste estudo, a prevalência de infecção por Candida foi (44,98%). CONCLUSÕES: Cândida Albicans foi a espécie mais comum isolada em gestantes, representando 72%. Na avaliação da susceptibilidade através do kit Integral System Yeast Plus foi obtido que Candida Albicans é suscetível à Anfotericina B, Flucitosina entre outras, em Cândida Glabrata foi obtido que é sensível a Nistatina, Anfotericina B, suscetível entre outras, em Candida Krusei foi obtido que é sensível a Anfotericina B, Clotrimazol, Miconazol, suscetível a Nistatina, Voriconazol e resistente a Flucitosina, Cetoconazol, Itraconazol e Fluconazol.


Assuntos
Humanos , Feminino , Gravidez , Adulto , Candida , Candida albicans , Anfotericina B , Colorimetria , Candida glabrata , Gestantes , Fluconazol , Prevalência , Clotrimazol , Itraconazol , Voriconazol , Flucitosina , Candida parapsilosis , Infecções , Miconazol
19.
Health Technol Assess ; 24(57): 1-190, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33174528

RESUMO

BACKGROUND: Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies. OBJECTIVES: The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS. DESIGN: Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England. SETTING: The randomised controlled trial was conducted in 18 neonatal intensive care units in England. PARTICIPANTS: Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size). INTERVENTIONS: The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation. MAIN OUTCOME MEASURE: Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data. RESULTS: Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n = 430; standard peripherally inserted central venous catheter, n = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days. LIMITATIONS: The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance. CONCLUSIONS: No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care. TRIAL REGISTRATION: Current Controlled Trials ISRCTN81931394. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 57. See the NIHR Journals Library website for further project information.


Assuntos
Anti-Infecciosos/administração & dosagem , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres Venosos Centrais , Unidades de Terapia Intensiva Neonatal , Sepse/prevenção & controle , Anti-Infecciosos/economia , Infecções Relacionadas a Cateter/economia , Análise Custo-Benefício , Humanos , Recém-Nascido , Miconazol/administração & dosagem , Estudos Retrospectivos , Rifampina/administração & dosagem , Fatores de Risco , Avaliação da Tecnologia Biomédica , Reino Unido
20.
AAPS PharmSciTech ; 21(7): 278, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033939

RESUMO

People with weakened immune systems are at risk of developing candidiasis which is a fungal infection caused by several species of Candida genus. In this work, polymeric nanoparticles containing miconazole nitrate and the anesthetic lidocaine clorhydrate were developed. Miconazole was chosen as a typical drug to treat buccopharyngeal candidiasis whereas lidocaine may be useful in the management of the pain burning, and pruritus caused by the infection. Nanoparticles were synthesized using chitosan and gelatin at different ratios ranging from 10:90 to 90:10. The nano-systems presented nanometric size (between 80 and 300 nm in water; with polydispersion index ranging from 0.120 to 0.596), and positive Z potential (between 20.11 and 37.12 mV). The determined encapsulation efficiency ranges from 65 to 99% or 34 to 91% for miconazole nitrate and lidocaine clorhydrate, respectively. X-ray diffraction and DSC analysis suggested that both drugs were in amorphous state in the nanoparticles. Finally, the systems fitted best the Korsmeyer-Peppas model showing that the release from the nanoparticles was through diffusion allowing a sustained release of both drugs and prolonged the activity of miconazole nitrate over time against Candida albicans for at least 24 h.


Assuntos
Candida albicans/isolamento & purificação , Candidíase/tratamento farmacológico , Lidocaína/administração & dosagem , Miconazol/administração & dosagem , Nanopartículas/química , Polímeros/química , Antifúngicos/administração & dosagem , Antifúngicos/química , Varredura Diferencial de Calorimetria , Quitosana , Humanos , Lidocaína/química , Miconazol/química , Nanopartículas/administração & dosagem , Difração de Raios X
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