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1.
J Drugs Dermatol ; 22(8): 766-772, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37556520

RESUMO

BACKGROUND: This prospective, open-label study evaluated the effectiveness and safety of tildrakizumab plus topical halcinonide ointment in psoriasis patients. METHODS: Adults (age greater than or equal to 18 years) with moderate to severe plaque psoriasis (body surface area [BSA] greater than or equal to 10%, physician's global assessment [PGA] greater than or equal to 3, psoriasis area severity index [PASI] greater than or equal to 12) received tildrakizumab (100 mg; s.c.) at weeks 0, 4, and 16. Patients with BSA >3% at week 16 received additional halcinonide 0.1% twice daily for 4 weeks (week 20) and were followed for another 4 weeks (week 24); those with BSA less than or equal to 3% were followed to week 24. RESULTS: Twenty-five patients were enrolled (mean age 52.6 years; 68% male). The proportion of all patients achieving BSA less than or equal to 3% was 52.2% at week 16, 73.7% at week 20 (after 4 weeks of adjunctive halcinonide in patients with BSA >3% at week 16), and 84.2% at week 24 (4 weeks after halcinonide discontinuation). PASI 75 was attained in 60.9% of all patients at week 16, and 73.7% at weeks 20 and 24. In patients adding halcinonide, improvements from baseline in mean BSA, PGA, and PGA x BSA increased from week 16 (55%, 29%, and 64%, respectively) to week 20 (78%, 51%, and 88%, respectively), and were maintained through week 24. Quality of life improved with tildrakizumab monotherapy and further with adjunctive halcinonide. Adverse events (AEs) were infrequent. No serious AEs or discontinuations due to AEs were noted. CONCLUSION: Tildrakizumab plus topical halcinonide ointment is safe and effective in controlling psoriasis for patients inadequately responding to tildrakizumab monotherapy.Bagel J, Novak K, Nelson E. Tildrakizumab in combination with topical halcinonide 0.1% ointment for treating moderate to severe plaque psoriasis. J Drugs Dermatol. 2023;22(8):766-772. doi:10.36849/JDD.6830.


Assuntos
Anticorpos Monoclonais Humanizados , Halcinonida , Psoríase , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Halcinonida/uso terapêutico , Pomadas , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Qualidade de Vida , Índice de Gravidade de Doença , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/uso terapêutico
3.
Cell Mol Biol (Noisy-le-grand) ; 62(4): 111-5, 2016 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-27188744

RESUMO

Non-neoplastic epithelial disorders of the vulva (NNEDV) are common types of vulval lesions. Although corticosteroids represent a first-line treatment for NNEDV, concerns exist about the safety associated with long-term topical corticosteroid use. Recently, several clinical trials have identified high-intensity focused ultrasound (HIFU) as a promising treatment modality for NNEDV. The aim of this multi-center, randomized, controlled clinical trial was to investigate the efficacy of HIFU therapy in women with NNEDV based on histological alterations. We enrolled patients who were clinically diagnosed with NNEDV. They were randomized into 2 treatment groups: 1) halcinonide for 3 months or 2) HIFU once. A total of 123 patients were biopsied both prior to and after the therapy, and 62 and 61 patients were assigned to the HIFU and halcinonide groups, respectively. The histological changes were then analyzed. After the treatments, the therapeutic effects were observed in both groups. Comparing the diagnosis and alterations in lichenoid and sclerotic patterns and in chronic inflammation, we found statistically significant differences. Furthermore, when compared with the halcinonide group, the HIFU group exhibited enhanced curative effects that were statistically significant (P = 0.039). Based on the histological evidence from this randomized, controlled trial, HIFU represents an effective method for the treatment of NNEDV.


Assuntos
Epitélio/patologia , Ablação por Ultrassom Focalizado de Alta Intensidade , Doenças da Vulva/terapia , Adulto , Idoso , Feminino , Halcinonida/uso terapêutico , Humanos , Pessoa de Meia-Idade , Doenças da Vulva/tratamento farmacológico , Doenças da Vulva/patologia , Adulto Jovem
4.
Ann Transplant ; 21: 301-10, 2016 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-27170053

RESUMO

BACKGROUND Our aim was to explore the mechanism of post-transplant organ function decrease induced by brain death (BD) and discover a potential candidate drug for improving the survival and organ function after BD. MATERIAL AND METHODS The microarray data developed from the liver tissues after BD were further analyzed by bioinformatics methods. The differentially expressed genes (DEGs) were computationally predicted and the DEGs that involved biological functions were explored by gene ontology (GO) analysis. The candidate agents that could induce the reverse gene signature were predicted based on the Connectivity Map (CMap) database. RESULTS There were total 1374 DEGs, including 589 up-regulated genes and 785 down-regulated genes. Function analysis showed that DEGs were mainly enriched in biological process-related GO terms, such as regulation of transcription, DNA-dependent, inflammatory response, and regulation of phosphorus metabolic process. The down-regulated genes were significantly enriched in transcription factor activity and transcription regulator activity-related molecular function. The down-regulated GO terms exhibited close interaction with each other. CONCLUSIONS The organ function decrease may be attributed by transcription alteration, inflammation response, and metabolic alteration in liver after BD. Spaglumic acid and halcinonide may be potential drugs for preventing organ damage during the BD process.


Assuntos
Morte Encefálica , Doadores de Tecidos , Morte Encefálica/metabolismo , Biologia Computacional , Dipeptídeos/farmacologia , Perfilação da Expressão Gênica , Ontologia Genética , Sobrevivência de Enxerto/efeitos dos fármacos , Halcinonida/farmacologia , Humanos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transplante de Fígado , Análise de Sequência com Séries de Oligonucleotídeos
5.
PLoS One ; 10(12): e0144550, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26658258

RESUMO

One of the causes of permanent disability in chronic multiple sclerosis patients is the inability of oligodendrocyte progenitor cells (OPCs) to terminate their maturation program at lesions. To identify key regulators of myelin gene expression acting at the last stages of OPC maturation we developed a drug repositioning strategy based on the mouse immortalized oligodendrocyte (OL) cell line Oli-neu brought to the premyelination stage by stably expressing a key factor regulating the last stages of OL maturation. The Prestwick Chemical Library of 1,200 FDA-approved compound(s) was repositioned at three dosages based on the induction of Myelin Basic Protein (MBP) expression. Drug hits were further validated using dosage-dependent reproducibility tests and biochemical assays. The glucocorticoid class of compounds was the most highly represented and we found that they can be divided in three groups according to their efficacy on MBP up-regulation. Since target identification is crucial before bringing compounds to the clinic, we searched for common targets of the primary screen hits based on their known chemical-target interactomes, and the pathways predicted by top ranking compounds were validated using specific inhibitors. Two of the top ranking compounds, Halcinonide and Clobetasol, act as Smoothened (Smo) agonists to up-regulate myelin gene expression in the Oli-neuM cell line. Further, RxRγ activation is required for MBP expression upon Halcinonide and Clobetasol treatment. These data indicate Clobetasol and Halcinonide as potential promyelinating drugs and also provide a mechanistic understanding of their mode of action in the pathway leading to myelination in OPCs. Furthermore, our classification of glucocorticoids with respect to MBP expression provides important novel insights into their effects in the CNS and a rational criteria for their choice in combinatorial therapies in de-myelinating diseases.


Assuntos
Clobetasol/farmacologia , Proteínas do Citoesqueleto/metabolismo , Halcinonida/farmacologia , Proteínas Musculares/metabolismo , Bainha de Mielina/metabolismo , Receptor X Retinoide gama/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Proteínas do Citoesqueleto/agonistas , Reposicionamento de Medicamentos , Expressão Gênica/efeitos dos fármacos , Immunoblotting , Camundongos , Microscopia de Fluorescência , Proteínas Musculares/agonistas , Proteína Básica da Mielina/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , Receptor X Retinoide gama/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/genética
6.
Cutis ; 96(2): 135-41, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26367752

RESUMO

Fluocinonide and halcinonide are class II topical corticosteroids that are indicated for the relief of inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses and generally are applied to affected skin at least twice daily. This pilot study compared the absorption kinetics of cream formulations of fluocinonide and halcinonide in the stratum corneum within a 9-hour period following application. A dermal tape-stripping protocol was used to quantify corticosteroid concentration at 6 sequential depths in the skin of 4 sites on the forearm. Halcinonide and fluocinonide were extracted from the strips and concentrations were measured using liquid chromatography-mass spectrometry. Results demonstrated the immediate absorption of fluocinonide and halcinonide into the stratum corneum within 1 hour of application followed by a sustained release of halcinonide and a steady decline of fluocinonide after peaking.


Assuntos
Fluocinonida/farmacocinética , Glucocorticoides/farmacocinética , Halcinonida/farmacocinética , Pele/metabolismo , Administração Cutânea , Cromatografia Líquida , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacocinética , Fluocinonida/administração & dosagem , Glucocorticoides/administração & dosagem , Halcinonida/administração & dosagem , Humanos , Espectrometria de Massas , Projetos Piloto , Absorção Cutânea , Fita Cirúrgica , Fatores de Tempo
7.
J Drugs Dermatol ; 14(1): 89-90, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25607913

RESUMO

Halcinonide in Halog Cream is formulated in a unique cream base that allows a biphasic release of this Class II steroid. Halcinonide in this product exists in two phases--a solution phase that is released immediately and a suspension phase that has a delayed release over time. The goal of this study was to evaluate this biphasic release of halcinonide into the skin using a novel noninvasive method. A dermal tape stripping protocol was used to quantify halcinonide concentration at 6 sequential depths in the skin of 4 sites on the forearms of 5 subjects. D-Squame strips were sequentially applied with consistent pressure and removed at 1, 3, 6, and 9 hours after application of halcinonide. Halcinonide was extracted from the strips and quantified using liquid chromatography mass spectrometry. The highest concentration of halcinonide was detected in strip 1 from the superficial stratum corneum with subsequent reduction in deeper stratum corneum layers as expected. The concentration increased beyond the first hour after application and demonstrated a sustained release into hour 6 before beginning declining. Similarly, the average concentration of halcinonide in strips 1 to 6 peaked at hour 1 and remained elevated for 6 hours. Data collected from the tape strips demonstrated a biphasic release of halcinonide--immediate release within 1 hour of application from the solution phase and continued, sustained release from the suspension phase following the first hour of application.


Assuntos
Anti-Inflamatórios/administração & dosagem , Halcinonida/administração & dosagem , Absorção Cutânea , Pele/metabolismo , Administração Cutânea , Anti-Inflamatórios/farmacocinética , Cromatografia Líquida , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Halcinonida/farmacocinética , Humanos , Espectrometria de Massas , Creme para a Pele , Fita Cirúrgica , Fatores de Tempo
8.
Zhonghua Yi Xue Za Zhi ; 93(41): 3291-3, 2013 Nov 05.
Artigo em Chinês | MEDLINE | ID: mdl-24401626

RESUMO

OBJECTIVE: To evaluate the efficacy of high-intensity focused ultrasound (HIFU) and cortical hormone in the treatment of non-neoplastic epithelial disorders of vulva. METHODS: A total of 268 cases with pathologically diagnosed non-neoplastic epithelial disorders of vulva were randomly allocated into two groups of high-intensity focused ultrasound (HIFU) (n = 119) and cortical hormone (n = 124). And 25 cases became lost to follow-ups. Their signs, symptoms and quality-of-life were assessed before treatment, 1 month post-treatment and 3 months post-treatment. And the relationship was analyzed between pathologic type, age, course and efficacies. RESULTS: Their signs, symptoms and quality-of-life improved in both groups after 1 and 3 month. Compared with drug therapy, HIFU showed superior results in lesion amelioration at 1 month with significantly statistical difference and so did lesion amelioration and therapeutic effect at 3 month. And the efficacy of HIFU was better in those with >10-year disease course and pathologically diagnosed lichen sclerosus in 3 months. CONCLUSIONS: HIFU is both safe and effective in the treatment of non-neoplastic epithelial disorders of vulva.


Assuntos
Halcinonida/uso terapêutico , Terapia por Ultrassom , Doenças da Vulva/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Terapia por Ultrassom/métodos , Adulto Jovem
9.
Skin Res Technol ; 19(1): e279-82, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22712560

RESUMO

BACKGROUND: The application of ultrasound to enhance the transdermal transport of drugs is often referred to as 'sonophoresis'. In physiotherapy sonophoresis is applied to the skin through two different procedures: (1) the pre-treatment procedure where the skin is treated with ultrasound irradiation prior to the drug application and (2) a simultaneous treatment mode, where the skin is treated with ultrasound during the application of the pharmacologic substance. The aim of this study was to compare the bioavailability of halcinonide in the stratum corneum comparing the ultrasound pre-treatment vs. the simultaneous treatment method. METHODS: The effect of pre and simultaneous ultrasound treatment (1 MHz, 1 W/cm(2)) was evaluated on the halcinonide blanching response using tristimulus colorimetry 2 h after the initial application. RESULTS: Within the evaluation period, only the ultrasound pre-treatment method resulted in a significant blanching response. CONCLUSION: Timing of the ultrasound application seems to influence the availability and percutaneous penetration process and should be taken into account when estimating the ultrasound enhancing effect.


Assuntos
Corticosteroides/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Epiderme/diagnóstico por imagem , Epiderme/metabolismo , Halcinonida/farmacocinética , Ultrassom/métodos , Administração Cutânea , Adulto , Anti-Inflamatórios/farmacocinética , Feminino , Humanos , Masculino , Absorção Cutânea , Ultrassonografia , Adulto Jovem
10.
Proc Natl Acad Sci U S A ; 107(20): 9323-8, 2010 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-20439738

RESUMO

Regenerative medicine holds the promise of replacing damaged tissues largely by stem cell activation. Hedgehog signaling through the plasma membrane receptor Smoothened (Smo) is an important process for regulating stem cell proliferation. The development of Hedgehog-related therapies has been impeded by a lack of US Food and Drug Administration (FDA)-approved Smo agonists. Using a high-content screen with cells expressing Smo receptors and a beta-arrestin2-GFP reporter, we identified four FDA-approved drugs, halcinonide, fluticasone, clobetasol, and fluocinonide, as Smo agonists that activate Hedgehog signaling. These drugs demonstrated an ability to bind Smo, promote Smo internalization, activate Gli, and stimulate the proliferation of primary neuronal precursor cells alone and synergistically in the presence of Sonic Hedgehog protein. Halcinonide, fluticasone, clobetasol, and fluocinonide provide an unprecedented opportunity to develop unique clinical strategies to treat Hedgehog-dependent illnesses.


Assuntos
Glucocorticoides/farmacologia , Proteínas Hedgehog/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Medicina Regenerativa/métodos , Transdução de Sinais/fisiologia , Células-Tronco/fisiologia , Androstadienos/farmacologia , Arrestinas , Western Blotting , Linhagem Celular , Proliferação de Células , Clobetasol/farmacologia , Fluocinonida/farmacologia , Fluticasona , Proteínas de Fluorescência Verde , Halcinonida/farmacologia , Humanos , Estrutura Molecular , Receptor Smoothened , Células-Tronco/metabolismo , beta-Arrestinas
13.
Am J Surg ; 184(1): 74-77, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12152622

RESUMO

BACKGROUND: Systemic or intraperitoneal administration of corticosteroids has been reported to have conflicting effects on the prevention of peritoneal adhesions. Painting corticosteroid cream directly on the likely site of adhesion formation, owing to its high concentrations and persistent effects, may be a promising approach to prevent peritoneal adhesion formation. METHODS: Adhesions were induced by abrading of the cecum, followed by dropping of 95% ethanol. Sixty Wistar rats were randomly allocated to two control groups with no further treatment of the cecum and to two therapy groups treated with 0.1% halcinonide cream painted directly on the damaged surface of the cecum. After 3 and 7 days, adhesion scores, adhesion incidence, and intraperitoneal leukocytes were evaluated. RESULTS: On both postoperative days 3 and 7, halcinonide cream resulted in a significant decrease in mean adhesion scores (6.80 versus 0.67, 10.40 versus 1.26; P <0.001, P <0.001, respectively). The adhesion incidence was 43.3% for the therapy groups and 100% for controls (P <0.01). On day 3, the total numbers of intraperitoneal leukocytes were 120.73 +/- 24.01 millions for the therapy groups and 270.40 +/- 34.68 for controls (P <0.001). CONCLUSIONS: Painting halcinonide cream directly on the damaged surface of the cecum could effectively reduce the severity and incidence of adhesion, possibly by suppression of early inflammatory exudate and of late fibroblast invasion and proliferation.


Assuntos
Anti-Inflamatórios/administração & dosagem , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Halcinonida/administração & dosagem , Aderências Teciduais/prevenção & controle , Abdome , Administração Tópica , Animais , Modelos Animais de Doenças , Feminino , Glucocorticoides , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
14.
Skin Pharmacol Appl Skin Physiol ; 12(1-2): 85-9, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10325587

RESUMO

The existence of a stratum corneum reservoir for topically applied substances is well known. Data concerning the stratum corneum retention time are important for the elaboration of optimal topical treatment. We used the re-occlusion technique followed by skin colour measurements (Chromametry) for the evaluation of the stratum corneum retention time of halcinonide. We found a significant reservoir for halcinonide up to 5 days after the initial application. The retention was found to be corticosteroid concentration and formulation dependent.


Assuntos
Anti-Inflamatórios/farmacologia , Epiderme/metabolismo , Halcinonida/farmacologia , Ureia/farmacologia , Administração Tópica , Adolescente , Adulto , Colorimetria/métodos , Relação Dose-Resposta a Droga , Interações Medicamentosas , Feminino , Glucocorticoides , Humanos , Masculino , Fatores de Tempo
16.
Cutis ; 46(1): 84-8, 1990 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-2200652

RESUMO

The use of the Actiderm dermatological patch in conjunction with topical corticosteroids was evaluated in a multi-centered, paired-comparison study of 189 patients with chronic psoriasis. In each patient, two lesions of comparable severity were selected for treatment. One plaque was treated with a twice-daily application of a steroid cream (triamcinolone acetonide 0.1 percent, betamethasone valerate 0.1 percent, or halcinonide 0.1 percent) while the second plaque was treated with a forty-eight hour application of the same steroid cream under Actiderm. At follow-up visits during the three-week treatment period and at four weeks post-treatment, the lesions were evaluated for the following parameters: erythema, induration, scale, and fissuring. For each of the three steroid preparations, the Actiderm and steroid therapy produced significant improvement in all parameters compared to the steroid therapy alone. This improvement was sustained through the post-treatment phase (p is less than 0.05 in all groups). No measurable differences in therapeutic efficacy were identified among the three steroid groups. Reports of adverse experiences in the Actiderm and steroid groups were infrequent. We conclude that the Actiderm and steroid combination is a safe and highly effective treatment for psoriasis.


Assuntos
Corticosteroides/uso terapêutico , Curativos Oclusivos , Psoríase/tratamento farmacológico , Administração Tópica , Adolescente , Corticosteroides/administração & dosagem , Adulto , Idoso , Betametasona/administração & dosagem , Doença Crônica , Feminino , Halcinonida/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Veículos Farmacêuticos , Triancinolona Acetonida/administração & dosagem
17.
G Ital Dermatol Venereol ; 124(1-2): 9-12, 1989.
Artigo em Italiano | MEDLINE | ID: mdl-2767722

RESUMO

The results of a study on the percutaneous absorption of two corticosteroids, Halcinonide at 0.1% and Triamcinolone acetonide at 0.1%, employing an original thermographic method, are reported. In a first group of subjects treated with one application of the two corticosteroids a stronger activity of the Halcinonide was found than in a second group of subjects, after repeated applications, resulting progressively more evident and of longer duration in comparison with Triamcinolone.


Assuntos
Halcinonida/farmacocinética , Pregnenodionas/farmacocinética , Pele/metabolismo , Termografia , Triancinolona/farmacocinética , Administração Cutânea , Feminino , Halcinonida/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Veículos Farmacêuticos , Absorção Cutânea , Triancinolona/administração & dosagem
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