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1.
Am J Audiol ; 28(2): 308-314, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31046392

RESUMO

Purpose We retrospectively studied the efficacy of intratympanic steroid administration in comparison with hyperbaric oxygen (HBO) therapy for idiopathic sudden sensorineural hearing loss (ISSNHL) with negative prognostic factors. Method We enrolled 301 patients (302 ears) with ISSNHL (average hearing level at 250-4000 Hz ≥ 40 dB; time from onset to treatment ≤ 30 days). From August 2002 to March 2009, 174 patients (174 ears) received systemic steroid plus HBO therapy (HBO group), and from June 2015 to January 2018, 127 patients (128 ears) received systemic plus intratympanic steroid (IT group). Hearing outcomes were evaluated by 6 indices: cure rate, marked-recovery rate (percent of patients with hearing gain ≥ 30 dB), recovery rate (percent of patients with hearing gain ≥ 10 dB), hearing gain, hearing level after treatment, and percent hearing improvement compared to the unaffected contralateral ear. Results The recovery rate was significantly higher in the IT group than in the HBO group (80.5% vs. 68.4%, p = .019). The IT group showed a higher recovery rate than the HBO group in patients aged ≥ 60 years ( p = .010), patients with early (≤ 7 days from onset) treatment ( p = .005), patients with initial hearing levels ≥ 90 dB ( p = .037), and patients with vertigo/dizziness ( p = .040). The IT group also showed higher hearing gain and percent hearing improvement than the HBO group in patients with vertigo/dizziness ( p = .046 and p = .026, respectively). Conclusions Systemic plus intratympanic steroid is more effective for ISSNHL than systemic steroid plus HBO, particularly in patients with negative prognostic factors, such as old age, profound hearing loss, and/or presence of vertigo/dizziness.


Assuntos
Dexametasona/análogos & derivados , Glucocorticoides/uso terapêutico , Perda Auditiva Neurossensorial/terapia , Perda Auditiva Súbita/terapia , Oxigenação Hiperbárica/métodos , Anti-Inflamatórios/uso terapêutico , Audiometria , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Feminino , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Súbita/complicações , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/uso terapêutico , Injeção Intratimpânica , Masculino , Pessoa de Meia-Idade , Ventilação da Orelha Média , Prednisolona/uso terapêutico , Prognóstico , Recuperação de Função Fisiológica , Estudos Retrospectivos , Tempo para o Tratamento , Resultado do Tratamento , Vertigem/complicações
2.
Hypertension ; 73(6): 1283-1290, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31006333

RESUMO

Peripheral 18-oxocortisol (18oxoF) level could contribute to the detection of aldosterone-producing adenoma (APA) in patients with primary aldosteronism. However, peripheral 18oxoF varies among such patients, which is a big drawback concerning its clinical application. We studied 48 cases of APA, 35 harboring KCNJ5 mutation, to clarify the significance of clinical and pathological parameters about peripheral 18oxoF. Peripheral 18oxoF concentration ranged widely from 0.50 to 183.13 ng/dL and correlated positively with intratumoral areas stained positively for steroidogenic enzymes ( P<0.0001). The peripheral 18oxoF level also correlated significantly with that of circulating aldosterone ( P<0.0001) but not with that of cortisol, a precursor of 18oxoF. However, a significant correlation was detected between peripheral 18oxoF and intratumoral glucocorticoids ( P<0.05). In addition, peripheral 18oxoF correlated positively with the number of hybrid cells double positive for 11ß-hydroxylase and aldosterone synthase ( P<0.0001). Comparing between the cases with and those without KCNJ5 mutation, the KCNJ5-mutated group demonstrated a significantly higher concentration of peripheral 18oxoF (28.4±5.6 versus 3.0±0.9 ng/dL, P<0.0001) and a larger intratumoral environment including the hybrid cells ( P<0.001), possibly representing a deviation from normal aldosterone biosynthesis. After multivariate analysis, KCNJ5 mutation status turned out to be the most associated factor involved in 18oxoF synthesis in APA ( P<0.0001). Results of our present study first revealed that enhanced 18oxoF synthesis in APA could come from a functional deviation of aldosterone biosynthesis from the normal zona glomerulosa and the utility of peripheral 18oxoF measurement could be influenced by the prevalence of KCNJ5 mutation in an APA.


Assuntos
Neoplasias do Córtex Suprarrenal/genética , Adenoma Adrenocortical/genética , Aldosterona/metabolismo , DNA de Neoplasias/genética , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/genética , Hidrocortisona/análogos & derivados , Mutação/genética , Neoplasias do Córtex Suprarrenal/metabolismo , Adenoma Adrenocortical/metabolismo , Análise Mutacional de DNA , Feminino , Canais de Potássio Corretores do Fluxo de Internalização Acoplados a Proteínas G/metabolismo , Humanos , Hidrocortisona/biossíntese , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
J Chromatogr Sci ; 57(6): 495-501, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30941396

RESUMO

A new simple and robust HPLC-DAD method was developed for the concurrent analysis of hydroquinone (HQ), hydrocortisone acetate (HCA) and tretinoin (TRN) triple combination for the first time using an Inertsil ODS 3-C18 column (150 mm × 4.6 mm, 5 µm particle size) column with 0.05 M phosphate buffer (pH 5.0) and acetonitrile at a ratio of (10:90, v/v) as a mobile phase, eluted by an isocratic elution mode at a flow rate of 1.0 mL/min and detected at 265 nm. Mefenamic acid was used as an internal standard (I.S.). The method produced linear responses in the concentration range of 10-200, 5-100 and 1-40 µg/mL, with detection limits of 2.01, 1.13 and 0.28 × 10-3 and quantitation limits of 6.11, 3.41 and 0.87 × 10-3 µg/mL for HQ, HCA and TRN, respectively, and a correlation coefficient higher than 0.9998. All validation requirements were satisfied by proving its linearity, precision, accuracy, robustness and specificity. The method was extended for application in triple combination cream, HQ/TRN co-formulated cream and HQ and TRN single ingredient cream with a recovery >97%.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fármacos Dermatológicos/análise , Hidrocortisona/análogos & derivados , Hidroquinonas/análise , Tretinoína/análise , Combinação de Medicamentos , Humanos , Hidrocortisona/análise , Limite de Detecção , Modelos Lineares , Ácido Mefenâmico , Melanose , Reprodutibilidade dos Testes
5.
Environ Pollut ; 247: 953-963, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30823350

RESUMO

Chronic ambient fine particulate matter (PM2.5) exposure correlates with various adverse health outcomes. Its impact on the circulating metabolome-a comprehensive functional readout of the interaction between an organism's genome and environment-has not however been fully understood. This study thus performed metabolomics analyses using a chronic PM2.5 exposure mouse model. C57Bl/6J mice (female) were subjected to inhalational concentrated ambient PM2.5 (CAP) or filtered air (FA) exposure for 10 months. Their sera were then analyzed by liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). These analyses identified 2570 metabolites in total, and 148 of them were significantly different between FA- and CAP-exposed mice. The orthogonal partial least-squares discriminant analysis (OPLS-DA) and heatmap analyses displayed evident clustering of FA- and CAP-exposed samples. Pathway analyses identified 6 perturbed metabolic pathways related to amino acid metabolism. In contrast, biological characterization revealed that 71 differential metabolites were related to lipid metabolism. Furthermore, our results showed that CAP exposure increased stress hormone metabolites, 18-oxocortisol and 5a-tetrahydrocortisol, and altered the levels of circadian rhythm biomarkers including melatonin, retinal and 5-methoxytryptophol.


Assuntos
Poluentes Atmosféricos/toxicidade , Redes e Vias Metabólicas/efeitos dos fármacos , Material Particulado/toxicidade , Filtros de Ar , Animais , Biomarcadores/metabolismo , Cromatografia Líquida , Feminino , Filtração , Cromatografia Gasosa-Espectrometria de Massas , Hidrocortisona/análogos & derivados , Hidrocortisona/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Espectrometria de Massas , Metabolômica , Camundongos Endogâmicos C57BL
6.
Biopharm Drug Dispos ; 40(2): 81-93, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30724384

RESUMO

CYP3A probe drugs such as midazolam and endogenous markers, and plasma 4ß-hydroxycholesterol (4ß-OHC) and urinary 6ß-hydroxycortisol-to-cortisol ratios (6ß-OHC/C) have been used as markers of CYP3A induction in cynomolgus monkeys, as with humans. However, there is limited information on their sensitivity and ability to detect CYP3A induction, as most studies were evaluated only at a high dose of the inducer, rifampicin (RIF; 20 mg/kg). In the present study, the CYP3A induction by RIF over a range doses of 0.2, 2 and 20 mg/kg (n = 4) was examined using CYP3A probe drugs (midazolam, triazolam and alprazolam) and the plasma and urinary endogenous CYP3A markers (4ß-OHC and 6ß-OHC/C). The sensitivity and relationship for detecting CYP3A induction was compared among the markers. Four days repeated oral administration of rifampicin to cynomolgus monkeys reduced the area under the plasma concentration-time curve of all CYP3A probe drugs in a rifampicin dose-dependent manner. Although the endogenous CYP3A markers (4ß-OHC and 6ß-OHC/C) were also changed for the middle (2 mg/kg) and high (20 mg/kg) doses of rifampicin, the fold-changes were relatively small, and CYP3A induction could not be detected at the lowest dose of rifampicin (0.2 mg/kg). In conclusion, CYP3A probe drugs are more sensitive for detecting CYP3A induction than endogenous CYP3A markers in cynomolgus monkeys, even for a short experimental period.


Assuntos
Alprazolam/farmacologia , Indutores do Citocromo P-450 CYP3A/farmacologia , Citocromo P-450 CYP3A/biossíntese , Midazolam/farmacologia , Rifampina/farmacologia , Triazolam/farmacologia , Alprazolam/sangue , Animais , Área Sob a Curva , Biomarcadores/sangue , Biomarcadores/urina , Indutores do Citocromo P-450 CYP3A/metabolismo , Relação Dose-Resposta a Droga , Interações de Medicamentos , Hidrocortisona/análogos & derivados , Hidrocortisona/urina , Hidroxicolesteróis/sangue , Macaca fascicularis , Masculino , Midazolam/sangue , Rifampina/sangue , Triazolam/sangue
7.
Talanta ; 196: 231-236, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30683357

RESUMO

We used rapid one-step derivatization of 6ß-hydroxylated hydrocortisone by sulfuric acid for fluorimetric determination of CYP3A4-dependent hydroxylase reaction in the electrochemical system. We have shown that CYP3A4 substrate - hydrocortisone - and its 6ß-hydroxylated product have different emission wavelengths at an excitation λex = 365 nm after treatment with sulfuric acid:ethanol (3:1) mixture (λem = 525 ±â€¯2 nm and λem = 427 ±â€¯2 nm, respectively). The detection limit for 6ß-hydroxycortisol was estimated to be 0.32 µM (corresponding to 0.095 nmol in 300 µL sample) (S/N = 3). Using the fluorimetric method of 6ß-hydroxycortisol detection following the electrolysis of hydrocortisone with CYP3A4 immobilized on a screen-printed graphite electrode modified by didodecyldimethylammonium bromide we have calculated the steady-state kinetic parameters of CYP3A4 for hydrocortisone: the maximal rate of the reaction (Vmax) as 89 ±â€¯5 pmol of product per min per pmol of electroactive enzyme and the Michaelis constant (KM) as 10 ±â€¯2 µM. In our system, ketoconazole inhibited hydroxylase activity of CYP3A4 towards hydrocortisone with the IC50 value of 70 ±â€¯5 nM. The approach proposed for determination of the CYP3A4 electrocatalytic activity can be used for throughput screening of different modulators of this cytochrome P450 isozyme during drug development.


Assuntos
Citocromo P-450 CYP3A/química , Enzimas Imobilizadas/química , Hidrocortisona/análogos & derivados , Hidrocortisona/química , Ácidos Sulfúricos/química , Catálise , Eletrólise , Fluorometria
8.
Cutan Ocul Toxicol ; 38(2): 182-189, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30678496

RESUMO

PURPOSE: The etiopathogenesis of steroid-induced cataracts is unknown. One hypothesis is that the higher reactive oxygen species (ROS) levels play an important role in the pathogenesis of several disorders, including the evolution of cataracts. This study investigated the antioxidant effects of piperine in our steroid-induced chick embryo lens model. METHODS: The study included 36 specific pathogen-free (SPF) fertilized eggs divided into six groups: phosphate buffer saline (PBS, pH 7.4 Saline Solution (0.9%) isotonic) group (G1), hydrocortisone succinate sodium (HC)-treated group (G2), 100 mg/kg piperine and HC treated group (G3), 50 mg/kg piperine and HC treated group (G4), 25 mg/kg piperine and HC treated group (G5), and 10 mg/kg piperine and HC treated group (G6). On the 15th day of incubation, the SPF eggs in the six groups were removed from the incubator; all were injected using insulin injectors into the chorioallantoic membrane. On day 17, all of the chick embryos were removed from the eggs and all lenses were dissected from the embryos. Cataract formation was evaluated in all lenses, and total antioxidant status (TAS), total oxidant status (TOS), reduced glutathione (GSH), and lipid peroxidation (MDA, malondialdehyde) levels were measured in all lens. RESULTS: The lenses in the G1 group had higher levels of GSH and TAS (p < 0.01), and lower levels of MDA and TOS than the G2 group (p < 0.05 and p < 0.01, respectively). Group 3 had higher levels of GSH and TAS (p < 0.001 and p < 0.001 respectively), and lower levels of MDA and TOS than the G2 group (p < 0.01 and p < 0.001, respectively). CONCLUSION: Steroid therapy causes a decrease in GSH and TAS levels and an increase in TOS and MDA levels in lens tissues, indicating increased oxidative stress. Piperine exerts its effects as an antioxidant substance, in increasing doses.


Assuntos
Alcaloides/uso terapêutico , Antioxidantes/uso terapêutico , Benzodioxóis/uso terapêutico , Catarata/tratamento farmacológico , Piperidinas/uso terapêutico , Alcamidas Poli-Insaturadas/uso terapêutico , Alcaloides/farmacologia , Animais , Antioxidantes/farmacologia , Benzodioxóis/farmacologia , Catarata/induzido quimicamente , Catarata/metabolismo , Catarata/patologia , Embrião de Galinha , Glutationa/metabolismo , Hidrocortisona/análogos & derivados , Cristalino/efeitos dos fármacos , Cristalino/metabolismo , Cristalino/patologia , Malondialdeído/metabolismo , Piperidinas/farmacologia , Alcamidas Poli-Insaturadas/farmacologia
9.
J Obstet Gynaecol ; 39(1): 82-85, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29884087

RESUMO

The aim of this study was to assess the efficacy of a postoperative steroid regimen in maintaining vulvovaginal architecture and vaginal patency following surgical adhesiolysis in severe erosive lichen planus (ELP) and genital graft versus host disease (GVHD). Sixteen women applied potent topical steroids to the vulva and vagina from 48 hours after surgery. Sexual and urinary function and vulvovaginal anatomy were assessed at 6 weeks, 6, 12 and 24 months. All of the patients had failed sexual function due to vaginal stenosis. Eleven patients were unable to have cervical smears and three had associated haematocolpos. Vaginal adhesiolysis achieving complete patency occurred in all patients with stenosis. Fifteen (93.7%) patients were compliant with the regimen. After two years, 12 (75%) patients had maintained complete vaginal patency. Four patients (25%) developed vaginal restenosis. This study demonstrates that the potent topical steroids used post-operatively are very effective in maintaining vaginal patency and function. Impact statement What is already known on this subject? Potent topical steroids are the first line treatment for ELP and GVHD and have been reported to be helpful after surgery to release adhesions. What do the results of this study add? Topical steroids used immediately after surgical adhesiolysis in patients with vulvo-vaginal lichen planus and graft-versus-host disease improves the outcomes and maintains function, which can give a prolonged benefit. What are the implications of these findings for clinical practice and/or further research? The use of potent topical steroids should be considered as routine practice after surgery in erosive inflammatory disease to control inflammation and improve the long term outcomes for these patients.


Assuntos
Anti-Inflamatórios/administração & dosagem , Clobetasol/administração & dosagem , Hidrocortisona/análogos & derivados , Líquen Plano/tratamento farmacológico , Doenças da Vulva/tratamento farmacológico , Administração Cutânea , Feminino , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Hidrocortisona/administração & dosagem , Líquen Plano/etiologia , Líquen Plano/fisiopatologia , Líquen Plano/cirurgia , Cuidados Pós-Operatórios/reabilitação , Estudos Retrospectivos , Disfunções Sexuais Fisiológicas/etiologia , Doenças Vaginais/terapia , Doenças da Vulva/etiologia , Doenças da Vulva/fisiopatologia , Doenças da Vulva/cirurgia
10.
J Biomol Struct Dyn ; 37(3): 623-640, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29375009

RESUMO

Our study focus on the biological importance of synthesized 5ß-dihydrocortisol (Dhc) and 5ß-dihydrocortisol acetate (DhcA) molecules, the cytotoxic study was performed on breast cancer cell line (MCF-7) normal human embryonic kidney cell line (HEK293), the IC50 values for MCF-7 cells were 28 and 25 µM, respectively, whereas no toxicity in terms of cell viability was observed with HEK293 cell line. Further experiment proved that Dhc and DhcA induced 35.6 and 37.7% early apoptotic cells and 2.5, 2.9% late apoptotic cells, respectively, morphological observation of cell death through TUNEL assay revealed that Dhc and DhcA induced apoptosis in MCF-7 cells. The complexes of HSA-Dhc and HSA-DhcA were observed as static quenching, and the binding constants (K) was 4.7 ± .03 × 104 M-1 and 3.9 ± .05 × 104 M-1, and their binding free energies were found to be -6.4 and -6.16 kcal/mol, respectively. The displacement studies confirmed that lidocaine 1.4 ± .05 × 104 M-1 replaced Dhc, and phenylbutazone 1.5 ± .05 × 104 M-1 replaced by DhcA, which explains domain I and domain II are the binding sites for Dhc and DhcA. Further, FT-IR, synchronous spectroscopy, and CD results revealed that the secondary structure of HSA was altered in the presence of Dhc and DhcA. Furthermore, the atomic force microscopy and transmission electron microscopy showed that the dimensions like height and molecular size of the HSA-Dhc and HSA-DhcA complex were larger compared to HSA alone. Detailed analysis through molecular dynamics simulations also supported greater stability of HSA-Dhc and HSA-DhcA complexes, and root-mean-square-fluctuation interpreted the binding site of Dhc as domain IB and domain IIA for DhcA. This information is valuable for further development of steroid derivative with improved pharmacological significance as novel anti-cancer drugs.


Assuntos
Acetatos/química , Antineoplásicos/farmacologia , Hidrocortisona/análogos & derivados , Albumina Sérica Humana/metabolismo , Acetatos/síntese química , Acetatos/farmacologia , Sítios de Ligação , Morte Celular/efeitos dos fármacos , Dicroísmo Circular , Células HEK293 , Humanos , Hidrocortisona/síntese química , Hidrocortisona/química , Hidrocortisona/farmacologia , Células MCF-7 , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Secundária de Proteína , Albumina Sérica Humana/química , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Análise Espectral , Termodinâmica
11.
J Dermatolog Treat ; 30(6): 529-533, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30582717

RESUMO

Background: It is important to determine the vasoconstrictor potencies of topical corticosteroids used to treat psoriasis to ensure appropriate clinical use. Objective: To compare the vasoconstrictive potencies of fixed-dose combination calcipotriol (50 µg/g) and betamethasone dipropionate (0.5 mg/g) (Cal/BD) cutaneous foam with other topical corticosteroids. Methods: In this Phase I, single-center, healthy volunteer study, Cal/BD foam, clobetasol propionate 0.05% cream (CP; very potent), BD 0.05% ointment (potent), mometasone furoate 0.1% cream (MF; potent), hydrocortisone-17-butyrate 0.1% ointment (HB; moderately potent), and foam vehicle were applied, then removed after 16 h. Skin blanching was visually assessed 2 h later (scale of 0-4). Results: Thirty-six volunteers were randomized. Skin blanching with Cal/BD foam (median [range], 2.00 [0.75-3.00]) was significantly lower than CP cream (3.00 [1.75-4.00]; p < .001), was not significantly different from BD ointment (1.75 [0.75-3.00]; p = .30) and MF cream (2.00 [1.00-3.75]; p = .22), and was significantly greater than HB ointment (1.25 [0.50-3.00]; p < .001) and vehicle (0 [0-0.50]; p < .001). There were no local tolerability reactions or adverse events. Conclusions: The corticosteroid potency of Cal/BD foam was not significantly different from BD ointment and MF cream, significantly stronger than HB ointment, but weaker than CP cream in healthy volunteers.


Assuntos
Betametasona/análogos & derivados , Calcitriol/análogos & derivados , Psoríase/tratamento farmacológico , Vasoconstritores/uso terapêutico , Administração Tópica , Adulto , Betametasona/uso terapêutico , Calcitriol/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/uso terapêutico , Masculino , Pessoa de Meia-Idade , Furoato de Mometasona/uso terapêutico , Pomadas/química , Creme para a Pele/química , Resultado do Tratamento , Adulto Jovem
12.
Hypertension ; 72(6): 1345-1354, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30571232

RESUMO

Primary aldosteronism is a secondary hypertensive disease caused by autonomous aldosterone production that often caused by an aldosterone-producing adenoma (APA). Immunohistochemistry of aldosterone synthase (CYP11B2) shows the presence of aldosterone-producing cell clusters (APCCs) even in non-primary aldosteronism adult adrenal cortex. An APCC-like structure also exists as possible APCC-to-APA transitional lesions (a speculative designation) in primary aldosteronism adrenals. However, whether APCCs produce aldosterone or 18-oxocortisol, a potential serum marker of APA, remains unknown because of lack of technology to visualize adrenocorticosteroids on tissue sections. To address this obstacle, in this study, we used highly sensitive Fourier transform ion cyclotron resonance mass spectrometry to image various adrenocorticosteroids, including 18-oxocortisol, in adrenal tissue sections from 8 primary aldosteronism patients with APCC (cases 1-4), possible APCC-to-APA transitional lesions (case 5), and APA (cases 6-8). Further analyses by tandem mass spectrometry imaging allowed us to differentially visualize aldosterone from cortisone, which share identical mass-to-charge ratio value ( m/z). In conclusion, these advanced imaging techniques revealed that aldosterone and 18-oxocortisol coaccumulated within CYP11B2-expressing lesions. These imaging outcomes along with a growing body of aldosterone research led us to build a progressive development hypothesis of an aldosterone-producing pathology in the adrenal glands.


Assuntos
Neoplasias das Glândulas Suprarrenais/metabolismo , Glândulas Suprarrenais/metabolismo , Adenoma Adrenocortical/metabolismo , Aldosterona/metabolismo , Hidrocortisona/análogos & derivados , Hiperaldosteronismo/metabolismo , Neoplasias das Glândulas Suprarrenais/patologia , Adenoma Adrenocortical/patologia , Adulto , Feminino , Humanos , Hidrocortisona/metabolismo , Hiperaldosteronismo/patologia , Hipertensão/metabolismo , Hipertensão/patologia , Masculino , Pessoa de Meia-Idade
14.
J Food Drug Anal ; 26(3): 1160-1170, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29976408

RESUMO

In the present study, we compare the performance of two reversed-phase liquid chromatographic approaches using different eluents either conventional hydro-organic eluent or micellar one for simultaneous estimation of hydrocortisone acetate and pramoxine hydrochloride in presence of their degradants and process-related impurities; hydrocortisone and 4-butoxyphenol, respectively. For conventional reversed-phase liquid chromatography (RPLC), separation of the studied compounds was completed on an Inertsil ODS 3-C18 column (150 mm × 4.6 mm, 5 µm particle size) with a mobile phase consists of 50 mM phosphate buffer (pH 5.0): acetonitrile (50: 50, v/v). For micellar liquid chromatography (MLC), an Eclipse XDB-C8 column (150 mm × 4.6 mm, 5 µm particle size) was chosen for the separation with a green mobile phase consists of 0.15 M sodium dodecyl sulfate, 0.3% triethylamine and 10% n-butanol in 20 mM orthophosphoric acid (pH 5.0). Both methods were extended to analyze hydrocortisone acetate and pramoxine hydrochloride in their co-formulated cream. RPLC was superior to MLC with regard to sensitivity for the estimation of impurities. While, MLC represents an eco-friendly, less hazardous and biodegradable approach. Furthermore, the direct injection of the cream to the system without the need to laborious samples pretreatment, excessive amount of analysis time and/or use of large amount of toxic organic solvents is one of the outstanding advantages of MLC.


Assuntos
Cromatografia de Fase Reversa/métodos , Hidrocortisona/análogos & derivados , Morfolinas/análise , Contaminação de Medicamentos , Hidrocortisona/análise
15.
Rev Chil Pediatr ; 89(3): 368-372, 2018 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-29999143

RESUMO

INTRODUCTION: Cushing's syndrome (CS) is an endocrine disease by to glucocorticoids excess, depen dent or independent of adrenocorticotropic hormone (ACTH). The main cause is iatrogenic due to excessive use of glucocorticoids. OBJECTIVE: To show the association between prolonged use of topical corticosteroids and the development of CS. CLINICAL CASE: An infant treated with topical corticosteroids due to seborrheic dermatitis. Due to long-term unsupervised use, he develops Cushing's syndrome characterized by obesity and compromised growth rate. Topical use of corticosteroids was discontinued and physiological replacement therapy was initiated with descending doses, achieving clinical improvement. DISCUSSION: Topical corticosteroids are widely used in clinical practice for management of dermatological pathologies. These are available in various presentations with va riable efficiency. The main determining factors in its action are the characteristics of the skin, the active principle of the drug, the potency and application technique, so that the adverse effects are observed more frequently in the use due to diaper dermatitis. The main adverse effect of long-term use is Cushing's syndrome which can be prevented through supervised use and progressive decrease. CONCLUSION: The rational and careful use of topical corticosteroids is essential to take advantage of the beneficial effects and avoid adverse effects.


Assuntos
Anti-Inflamatórios/efeitos adversos , Síndrome de Cushing/induzido quimicamente , Hidrocortisona/análogos & derivados , Administração Cutânea , Síndrome de Cushing/diagnóstico , Humanos , Hidrocortisona/efeitos adversos , Doença Iatrogênica , Lactente , Masculino
16.
Molecules ; 23(7)2018 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-29933599

RESUMO

The objective of this study was to establish a novel method for rapid detection of six glucocorticoids (prednisone, prednisone acetate, prednisolone, hydrocortisone, hydrocortisone acetate, and dexamethasone) added illegally in dietary supplements simultaneously by combining thin layer chromatography (TLC) with spot-concentrated Raman scattering (SCRS). The doping ingredients were separated by TLC, and viewed and located with UV light (254 nm), enriched by chromatography, then Raman spectra were directly detected by a Raman Imagine microscope with 780 nm laser source. This method had complementary advantages of TLC and Raman spectroscopy, which enhanced the specificity of the test results. The limit of detection (LOD) of the reference substances were 4 µg, 4 µg, 4 µg, 6 µg, 6 µg, and 4 µg, respectively. The method was used to study the six glucocorticoids added illegally in five dietary supplements. Fake drugs had been detected. The study showed that the TLC-SCRS method is simple, rapid, specific, sensitive, and reliable. The method could be used for effective separation and detection of six chemical components used in dietary supplement products, and would have good prospects for on-site qualitative screening of dietary supplement products for adulterants.


Assuntos
Dexametasona/isolamento & purificação , Suplementos Nutricionais/análise , Hidrocortisona/análogos & derivados , Hidrocortisona/isolamento & purificação , Substâncias para Melhoria do Desempenho/isolamento & purificação , Prednisolona/isolamento & purificação , Prednisona/isolamento & purificação , Cromatografia em Camada Delgada/métodos , Doping nos Esportes/prevenção & controle , Humanos , Limite de Detecção , Análise Espectral Raman/métodos
17.
Drug Metab Pers Ther ; 33(2): 65-73, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29727298

RESUMO

BACKGROUND: Phenazepam (bromdihydrochlorphenylbenzodiazepine) is the original Russian benzodiazepine tranquilizer belonging to 1,4-benzodiazepines. There is still limited knowledge about phenazepam's metabolic liver pathways and other pharmacokinetic features. METHODS: To determine phenazepam's metabolic pathways, the study was divided into three stages: in silico modeling, in vitro experiment (cell culture study), and in vivo confirmation. In silico modeling was performed on the specialized software PASS and GUSAR to evaluate phenazepam molecule affinity to different cytochromes. The in vitro study was performed using a hepatocytes' cell culture, cultivated in a microbioreactor to produce cytochrome P450 isoenzymes. The culture medium contained specific cytochrome P450 isoforms inhibitors and substrates (for CYP2C9, CYP3A4, CYP2C19, and CYP2B6) to determine the cytochrome that was responsible for phenazepam's metabolism. We also measured CYP3A activity using the 6-betahydroxycortisol/cortisol ratio in patients. RESULTS: According to in silico and in vitro analysis results, the most probable metabolizer of phenazepam is CYP3A4. By the in vivo study results, CYP3A activity decreased sufficiently (from 3.8 [95% CI: 2.94-4.65] to 2.79 [95% CI: 2.02-3.55], p=0.017) between the start and finish of treatment in patients who were prescribed just phenazepam. CONCLUSIONS: Experimental in silico and in vivo studies confirmed that the original Russian benzodiazepine phenazepam was the substrate of CYP3A4 isoenzyme.


Assuntos
Benzodiazepinas/metabolismo , Simulação por Computador , Citocromo P-450 CYP3A/metabolismo , Hepatócitos/enzimologia , Hipnóticos e Sedativos/metabolismo , Fígado/enzimologia , Modelos Biológicos , Biomarcadores/sangue , Reatores Biológicos , Técnicas de Cultura de Células/instrumentação , Células Cultivadas , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/sangue , Hipnóticos e Sedativos/sangue , Hipnóticos e Sedativos/farmacocinética , Isoenzimas , Especificidade por Substrato
18.
Drug Des Devel Ther ; 12: 1147-1156, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29780235

RESUMO

Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction. In clinical practice, the process of phenotyping of CYP isoenzymes and some endogenous substrates in the ratio of cortisol to 6ß-hydroxycortisol in urine for the evaluation of CYP3A4 activity has been deemed to be a quite promising, safe and minimally invasive method for patients nowadays.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Hidrocortisona/análogos & derivados , Hidrocortisona/metabolismo , Biotransformação , Interações de Medicamentos , Humanos , Isoenzimas/metabolismo , Fenótipo
19.
J Mass Spectrom ; 53(8): 665-674, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29766610

RESUMO

CYP3A phenotyping provides a means for personalized drug therapy. We focused our attention on the plasma 6ß-hydroxycortisol (6ß-OHF) to cortisol ratio as an index for CYP3A phenotyping. In the present study, we developed a sensitive and reliable method for the simultaneous determination of 6ß-OHF and cortisol in human plasma using high-performance liquid chromatography/tandem mass spectrometry together with picolinylester derivatization or nonderivatization methods and 6ß-[9,11,12,12-2 H4 ]hydroxycortisol and [1,2,4,19-13 C4 ]cortisol as internal standards for in vivo CYP3A phenotyping in humans. The lower limits of quantification were 38.513 pg/mL for 6ß-OHF and 38.100 pg/mL for cortisol. The relative error and relative standard deviation of the lower limits of quantification were <5% for both methods. The intra-day and inter-day assay reproducibilities of the determined 6ß-OHF and cortisol concentrations were consistent with the actual amounts added as relative errors and relative standard deviations for both methods, which were <5.4% and <3.9%, respectively. Both methods were applied for the quantification of plasma 6ß-OHF and cortisol concentrations in healthy subjects taking oral contraceptives. The absolute concentrations and time course of 6ß-OHF and cortisol were found to be consistent when measured using the 2 methods. The ratio as an index for in vivo CYP3A activity decreased after 21 days of taking oral contraceptives for both methods. To the best of our knowledge, this is the first study reporting the detailed investigation of accuracy and precision in the simultaneous measurement of 6ß-OHF and cortisol in human plasma using liquid chromatography/tandem mass spectrometry coupled with stable isotope dilution method, which can be applied to CYP3A phenotyping.


Assuntos
Hidrocortisona/análogos & derivados , Hidrocortisona/sangue , Espectrometria de Massas em Tandem/métodos , Calibragem , Cromatografia Líquida de Alta Pressão , Citocromo P-450 CYP3A/análise , Humanos , Marcação por Isótopo , Limite de Detecção
20.
Pediatr Dermatol ; 35(2): e124-e127, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29436009

RESUMO

Oral lesions are rarely reported in patients with pityriasis rosea. We report a case of a 3-year-old boy with clinical evidence of generalized pityriasis rosea who developed asymptomatic oral lesions similar in appearance to geographic tongue. The generalized eruption and tongue lesions resolved simultaneously within 4 weeks. We also review the literature on the oral manifestations of Pityriasis rosea.


Assuntos
Anti-Inflamatórios/uso terapêutico , Hidrocortisona/análogos & derivados , Pitiríase Rósea/diagnóstico , Pré-Escolar , Diagnóstico Diferencial , Glossite Migratória Benigna/etiologia , Humanos , Hidrocortisona/uso terapêutico , Masculino , Mucosa Bucal/patologia , Pitiríase Rósea/tratamento farmacológico
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