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1.
Anticancer Res ; 39(10): 5597-5604, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570455

RESUMO

BACKGROUND: Bilateral asynchronous renal cell carcinoma (RCC) is infrequent. Immunotherapy is the first-line treatment for advanced RCC not controlled by locoregional therapy. Viscum album extracts (VAE) have been shown to improve quality of life as well as immunological and antineoplastic properties in different types of cancers. CASE REPORT: A 67-year-old man was diagnosed with Fuhrman grade 3/4 RCC, stage pT1bN0M0 in the right kidney. During the subsequent 6 years, he underwent a right nephrectomy and two metastasectomies (lung). Then an RCC lesion of the left kidney was detected. The patient refused a second nephrectomy and was treated solely with high-dose intravenous and subsequent subcutaneous VAE. A central necrotic area and a peritumoral halo were seen on an ultrasound follow-up from month 7. The patient showed no further progression of RCC during the next 2.5 years. CONCLUSION: As far as we are aware of, this is the first report of a patient with metastatic RCC with an RCC lesion of the second kidney treated solely with high-dose intravenous and subcutaneous VAE, associated with 2.5 years of progression-free survival and a good quality of life. The use of VAE in RCC should be carefully documented and published to determine future research.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Viscum album/química , Administração Cutânea , Administração Intravenosa/métodos , Idoso , Humanos , Rim/efeitos dos fármacos , Masculino , Intervalo Livre de Progressão , Qualidade de Vida
2.
Int J Nanomedicine ; 14: 5849-5863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440050

RESUMO

Background: Topical application of tacrolimus (FK506) was effective in treating atopic dermatitis (AD); however, the therapeutic efficiency is hampered by its poor penetration into the skin and local side effects of transient irritation symptoms with a burning sensation, a feeling of warmth or heat. Menthol and camphor have been widely used in topical compound formulations for adjunctive pharmacotherapy for antipruritics and analgesics owing to their cool nature, and both present skin penetration enhancing effects. Moreover, they can form a liquid eutectic oil to solubilize hydrophobic drugs. Purpose: Taking advantages of menthol/camphor eutectic (MCE), this work aims to integrate FK506 into MCE to construct a microemulsion system, i.e., FK506 MCE ME, which simultaneously enhances the percutaneous delivery and treatment efficacy, while reduces the side effects of FK506. Methods: The formulation of FK506 MCE ME was optimized and characterized. Different formulations containing FK506 were topically administered to treat 1-chloro-2, 4-dinitrobenzene (DNCB)-induced murine AD. Results: MCE solubilized FK506. FK506 in MCE ME penetrated skin in vitro more than in the commercial ointment, and MCE predominantly exerted the enhancing effects in MCE ME. FK506 MCE ME or FK506 MCE ME gel had greater effects on clinical symptoms, histological analysis, and IgE than did commercial FK506. The anti-pruritic and down-regulation of substance P effects of MCE ME vehicle mitigated the side effects of FK506 application. Conclusion: MCE ME presented the excellent properties of simultaneously enhancing the percutaneous delivery and treatment efficacy, while reducing the side effects of FK506 for AD. Therefore, MCE ME is a promising nanoscale system for FK506 to effectively treating AD with low irritation and high medication adherence. Chemical compounds studied in this article: Tacrolimus (PubChem CID: 445643); menthol (PubChem CID: 1254); camphor (PubChem CID: 2537).


Assuntos
Dermatite Atópica/tratamento farmacológico , Emulsões/química , Óleos/química , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Administração Cutânea , Animais , Cânfora/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dermatite Atópica/induzido quimicamente , Regulação para Baixo/efeitos dos fármacos , Orelha/patologia , Humanos , Imunoglobulina E/sangue , Imunossupressores/administração & dosagem , Masculino , Mentol/química , Camundongos , Camundongos Endogâmicos BALB C , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Baço/efeitos dos fármacos , Substância P/metabolismo , Tacrolimo/administração & dosagem , Tacrolimo/farmacologia , Resultado do Tratamento , Perda Insensível de Água/efeitos dos fármacos
3.
Int J Nanomedicine ; 14: 6135-6150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447556

RESUMO

Background: Nanostructured lipid carriers (NLCs) are emerging as attractive drug carriers in transdermal drug delivery. The surface modification of NLCs with cell-penetrating peptides (CPPs) can enhance the skin permeation of drugs. Purpose: The objective of the current study was to evaluate the ability of the cell-penetrating peptide (CPP) polyarginine to translocate NLCs loaded with lornoxicam (LN) into the skin layers and to evaluate its anti-inflammatory effect. Methods: The NLCs were prepared using an emulsion evaporation and low temperature solidification technique using glyceryl monostearates, triglycerides, DOGS-NTA-Ni lipids and surfactants, and then six histidine-tagged polyarginine containing 11 arginine (R11) peptides was modified on the surface of NLCs. Results: The developed NLCs formulated with LN and R11 (LN-NLC-R11) were incorporated into 2% HPMC gels. NLCs were prepared with a particle size of (121.81±3.61)-(145.72±4.78) nm, and the zeta potential decreased from (-30.30±2.07) to (-14.66±0.74) mV after the modification of R11 peptides. The encapsulation efficiency and drug loading were (74.61±1.13) % and (7.92±0.33) %, respectively, regardless of the surface modification. Cellular uptake assays using HaCaT cells suggested that the NLC modified with R11 (0.02%, w/w) significantly enhanced the cell internalization of nanoparticles relative to unmodified NLCs (P<0.05 or P<0.01). An in vitro skin permeation study showed better permeation-enhancing ability of R11 (0.02%, w/w) than that of other content (0.01% or 0.04%). In carrageenan-induced rat paw edema models, LN-NLC-R11 gels inhibited rat paw edema and the production of inflammatory cytokines compared with LN-NLC gels and LN gels (P<0.01). Conclusion: In our investigation, it was strongly demonstrated that the surface modification of NLC with R11 enhanced the translocation of LN across the skin, thereby alleviating inflammation.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Edema/tratamento farmacológico , Lipídeos/química , Nanoestruturas/química , Peptídeos/farmacologia , Piroxicam/análogos & derivados , Administração Cutânea , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carragenina , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/farmacologia , Edema/induzido quimicamente , Edema/metabolismo , Emulsões/química , Endocitose/efeitos dos fármacos , Géis/química , Humanos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/ultraestrutura , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , Piroxicam/administração & dosagem , Piroxicam/farmacologia , Piroxicam/uso terapêutico , Coelhos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele
4.
An Bras Dermatol ; 94(3): 313-319, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365660

RESUMO

BACKGROUND: Actinic keratosis (AK) represents a risk of progression to squamous cell carcinoma. Ingenol mebutate gel is a novel therapeutic option for field-directed treatment. OBJECTIVES: To evaluate the safety, tolerability and patients' perspectives, related to the therapeutic success of managing AKs on the face and scalp with ingenol mebutate gel in Brazilian individuals. METHODS: This was an observational, retrospective and descriptive study of 68 areas of actinic keratosis on the face and scalp treated with Ingenol mebutate gel involving a total of 37 patients. The drug was applied for three consecutive days on an area of of 25 cm2 and documentation was performed on baseline and days 4, 8, 15, 60 and 180. On day 4, the composite local skin reaction score was calculated. At the end, a questionnaire was applied to evaluate patients' perspectives about the treatment. RESULTS: Adherence was 100%, no serious adverse events were recorded and the mean composite local skin reaction score (standard deviation) was 8.61±4.22. The treatment was considered optimum by 75.68% of the patients. STUDY LIMITATIONS: Calculation of composite local skin reaction score performed only on the fourth day. CONCLUSIONS: Treatment with ingenol mebutate gel was considered safe and tolerable in Brazilian subjects. Patients had a maximum adherence rate and a great improvement in self-esteem. The results of this research reproduce the findings of the literature.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Diterpenos/uso terapêutico , Géis/uso terapêutico , Ceratose Actínica/tratamento farmacológico , Administração Cutânea , Idoso , Idoso de 80 Anos ou mais , Brasil , Dermatoses Faciais/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Dermatoses do Couro Cabeludo/tratamento farmacológico , Inquéritos e Questionários , Resultado do Tratamento
5.
Medicine (Baltimore) ; 98(34): e16865, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441861

RESUMO

RATIONALE: In assisted reproductive technology, a persistently thin endometrial lining represents a huge challenge during frozen embryo transfer (FET) cycles. PATIENT CONCERNS: Three patients who had a persistently thin endometrial lining despite the use of several medical agents known to improve endometrial lining thickness. DIAGNOSES: Infertility undergoing FET cycles. INTERVENTIONS: A combination of transdermal and intravaginal ozone therapy along with Pulsed Electro-Magnetic Field (PEMF) therapy. OUTCOMES: Ozone with PEMF, both of which are known to have vasodilatatory, anti-inflammatory, and anti-oxidant actions, were successful in improving the thickness of the endometrial lining in all 3 patients. Two out of 3 patients became pregnant following single embryo transfer. LESSONS: Ozone with PEMF constitute a novel experimental approach for women with persistently thin endometrial lining undergoing FET. This novel approach needs validation by large well-designed studies.


Assuntos
Endométrio/efeitos dos fármacos , Terapia de Campo Magnético , Oxidantes Fotoquímicos/administração & dosagem , Ozônio/administração & dosagem , Administração Cutânea , Administração Intravaginal , Adulto , Criopreservação , Transferência Embrionária/métodos , Endométrio/patologia , Feminino , Humanos , Oxidantes Fotoquímicos/farmacologia , Ozônio/farmacologia , Gravidez
6.
Adv Clin Exp Med ; 28(9): 1229-1235, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31464109

RESUMO

BACKGROUND: Subcutaneous methotrexate (sMTX) administration is considered more effective than the oral route due to better bioavailability and a lower rate of adverse drug reactions (ADRs); however, clinical data supporting this hypothesis is scarce. OBJECTIVES: The aim of the study was to evaluate the efficacy and tolerability of sMTX in patients with active rheumatoid arthritis (RA), including a subset classified as an early stage of RA. MATERIAL AND METHODS: A post-marketing, multicenter, open-label, non-randomized, non-interventional study enrolled 771 adult patients with active RA treated with sMTX (Metex®) for 2-6 weeks. The evaluation of therapy effectiveness (DAS28-ESR or DAS28-CRP) and monitoring of ADRs was an element of routine patient management. Therapy effectiveness was scored as the achievement of remission or response (according to European League Against Rheumatism (EULAR)). RESULTS: Among 761 (98.7%) patients that continued sMTX (after 25-31 weeks), clinical response was achieved by 69.5%, remission by 19.2% and low disease activity by 34.2%. Patients aged >60 years were less likely to achieve both remission (odds ratio (OR) = 0.61 (95% confidence interval (95% CI) = 0.39-0.93)) and clinical response (OR = 0.82 (95% CI = 0.71-0.95)), while overweight/obese patients (OR = 1.11 (95% CI = 1.00-1.24)) and those with early RA had greater chance to reach a clinical response (OR = 1.18 (95% CI = 1.03-1.34)). There were 16 ADRs (no serious or severe). In addition, at least 2-fold increase in alanine transaminase (ALT) activity was noted in 10 patients (1.3%). CONCLUSIONS: After 6-month therapy with sMTX, about 70% of patients with RA achieve a clinical response, and remission was observed in 20%. Younger age, overweight/obesity and an early stage of the disease are factors increasing therapy effectiveness; sMTX is well tolerated.


Assuntos
Antirreumáticos , Artrite Reumatoide , Metotrexato/uso terapêutico , Administração Cutânea , Adulto , Idoso , Antirreumáticos/administração & dosagem , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Sobrepeso , Vigilância de Produtos Comercializados , Resultado do Tratamento
7.
Ther Umsch ; 76(2): 92-97, 2019 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-31429392

RESUMO

Modern concept of pruritus diagnosis and therapy Abstract. Pruritus can be best treated when the cause of itching is known, allowing a targeted treatment. To find the cause of itching it is recommended to consult the itch classification system of the «International Forum for the Study of Itch¼ (IFSI). In here three groups of conditions are distinguished: Pruritus on diseased (inflamed) skin (group I) is caused by a pruritic skin disorder that has to be diagnosed properly; correct treatment of the skin disorder will be the treatment of pruritus. Pruritus on non-diseased (non-inflamed) skin (group II) can be due to an internal disease or a consequence of drugs; elimination of the cause - as far as possible - will also eliminate itch. In pruritus presenting with severe chronic secondary scratch lesions (group III) the aim will be to prevent patients from further scratching. If causative treatment is not possible or the cause of itch remains unknown a symptomatic treatment will be seeked following a step-by-step procedure. In a step 1 a basic therapy with moisturizers and anthistamines is recommended. Step 2 comprises a symptomatic causative adapted therapy. In step 3 phototherapy and systemic treatments are considered including the use of anticonvulsants, antidepressants or anti-inflammatory agents.


Assuntos
Prurido , Dermatopatias , Administração Cutânea , Humanos , Fototerapia , Prurido/diagnóstico , Prurido/terapia , Pele , Dermatopatias/diagnóstico , Dermatopatias/terapia
8.
Int J Nanomedicine ; 14: 5381-5396, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31409994

RESUMO

Background: Tacrolimus (TCR), also known as FK-506, is a biopharmaceutics classification system (BCS) class II drug that is insoluble in water because of its high log P values. After dermal application, TCR remains in the stratum corneum and passes through the skin layers with difficulty. Purpose: The objectives of this study were to develop and evaluate solid lipid nanoparticles (SLNs) with thermosensitive properties to improve penetration and retention. Methods: We prepared TCR-loaded thermosensitive solid lipid nanoparticles (TCR-SLNs) with different types of surfactants on the shell of the particle, which conferred the advantages of enhancing skin permeation and distribution. We also characterized them from a physic point of view and performed in vitro and in vivo evaluations. Results: The TCR contained in the prepared TCR-SLN was in an amorphous state and entrapped in the particles with a high loading efficiency. The assessment of ex vivo skin penetration using excised rat dorsal skin showed that the TCR-SLNs penetrated to a deeper layer than the reference product (0.1% Protopic®). In addition, the in vivo skin penetration test demonstrated that TCR-SLNs delivered more drug into deeper skin layers than the reference product. FT-IR images also confirmed drug distribution of TCR-SLNs into deeper layers of the skin. Conclusion: These results revealed the potential application of thermosensitive SLNs for the delivery of difficult-to-permeate, poorly water-soluble drugs into deep skin layers.


Assuntos
Derme/metabolismo , Lipídeos/química , Nanopartículas/química , Tacrolimo/farmacologia , Temperatura Ambiente , Administração Cutânea , Animais , Varredura Diferencial de Calorimetria , Derme/efeitos dos fármacos , Liberação Controlada de Fármacos , Irritantes/toxicidade , Nanopartículas/ultraestrutura , Tamanho da Partícula , Coelhos , Ratos Sprague-Dawley , Absorção Cutânea/efeitos dos fármacos , Testes Cutâneos , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química , Difração de Raios X
9.
Pharm Res ; 36(10): 138, 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31350675

RESUMO

PURPOSE: This study aimed to incorporate ondansetron hydrochloride (ODS), a water-soluble drug into nanostructured lipid carriers (NLCs) to improve the pharmacokinetic properties of the drug. METHODS: NLCs were produced by solvent injection method. Various parameters of formulation and process were assessed to enhance the drug incorporation into NLCs. Physicochemical analyses, in vitro drug release, and pharmacokinetic studies were performed. RESULTS: Entrapment efficiency (EE) of ODS was considerably improved (>90%) by increasing pH of the aqueous phase. The use of an appropriate level of liquid lipid resulted in small, monodispersed NLCs with the enhanced EE and drug loading (DL). The optimized NLCs formulation exhibited particle size of 185.2 ± 1.9 nm, polydispersity index of 0.214 ± 0.006, EE of 93.2 ± 0.5%, and DL of 10.43 ± 0.05% as well as an in vitro sustained-release profile of ODS. Differential scanning calorimetry and X-ray powder diffraction suggested the amorphous state of ODS in the NLCs. The pharmacokinetic study in rats exhibited the sustained-release characteristic of the optimized ODS-loaded NLCs following subcutaneous administration with an extended Tmax and mean residence time as well as the enhanced systemic exposure compared to the ODS solution. CONCLUSIONS: The ODS-loaded NLCs appear potential for prolongation of drug action and reduction in dosing frequency.


Assuntos
Antieméticos/farmacocinética , Lipídeos/química , Nanocápsulas/química , Ondansetron/farmacocinética , Solventes/química , Administração Cutânea , Animais , Antieméticos/administração & dosagem , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Masculino , Ondansetron/administração & dosagem , Tamanho da Partícula , Ratos Sprague-Dawley , Resultado do Tratamento
10.
Zhongguo Zhong Yao Za Zhi ; 44(12): 2486-2492, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31359715

RESUMO

To establish a determination method for the contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid of Baimai Ointment,and investigate the percutaneous permeability of Baimai Ointment and the effects of two kinds of penetration enhancers on percutaneous absorption of three components. The contents of ammonium glycyrrhetate,nardosinone,and curcumin in transdermal receptor liquid were determined by high pressure liquid chromatography( HPLC). The vertical modified Franz diffusion cell was used to perform a transdermal experiment in vitro with the abdominal skin of mice( treated and untreated). The transdermal receptor liquid was preferably used to investigate the transdermal absorption rule of the Baimai Ointment and the effect of the penetration enhancer. The results showed that the comprehensive solubility of PEG-ET-NS( 3 ∶3 ∶4) was best among three types of receptor liquid PG-ET-NS( 3 ∶3 ∶4),PEG-ET-NS( 3 ∶3 ∶4),ET-NS( 3 ∶7). PEG-ET-NS was used as the receptor liquid for in vitro transdermal experiments. The cumulative permeation area of ammonium glycyrrhetate,nardosinone and curcumin within 24 h was 5. 73,18. 99,0. 38 µg·cm~(-2)respectively. Taking QEFand ER as comprehensive evaluation indicators of permeation performance,the comprehensive penetration-promoting performance of ammonium glycyrrhizinate: 3% PEG 400-ethanol-normal saline ≈ 1. 19 times( 3%azone) = 1. 94 times( blank); comprehensive penetration-promoting performance of nardosinone: 3% PEG 400-ethanol-normal saline≈1. 28 times( 3% azone) = 1. 37 times( blank); the comprehensive penetration performance of curcumin: 3% PEG 400-ethanol-normal saline≈1. 77 times( 3% azone) ≈3. 42 times( blank). The comprehensive penetration enhancement properties of the two penetration enhancers were as follows: 3% PEG 400-ethanol-normal saline>3%azone>blank. The transdermal absorption curve of ammonium glycyrrhetate,nardosinone and curcumin in Baimai Ointment were consistent with the zero-order equation,indicating that the transdermal absorption process was irrelevant to the concentration of three components,and its was a diffusion process. This experiment provides reference for the study of ointment transdermal preparations.


Assuntos
Administração Cutânea , Pomadas/farmacocinética , Absorção Cutânea , Pele , Animais , Camundongos , Permeabilidade
11.
Medicine (Baltimore) ; 98(29): e16368, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335684

RESUMO

BACKGROUND: Acupoint herbal patching (AHP) is widely used for symptom management in patients with acute and chronic bronchitis. The purpose of this protocol review is to evaluate the safety and efficacy of AHP for the treatment of bronchitis. METHODS AND ANALYSIS: This protocol of systematic review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P). The databases searched will include PubMed, Embase, CENTRAL, Web of Science, 3 Korean medical databases (OASIS, Korea Med, and KMBASE), and the Chinese database China National Knowledge Infrastructure (CNKI). Randomized controlled trials (RCTs) or quasi-RCTs using AHP for bronchitis will be considered. The selection of the studies, data abstraction, and validations will be performed independently by 3 researchers. CONCLUSION: The conclusion of the review will provide evidence that AHP is an effective intervention in patients with bronchitis. ETHICS AND DISSEMINATION: As individuals were not involved, ethical approval is not required. Findings will be published in a peer-reviewed journal. This systematic review may inform the treatment of bronchitis patients in clinical practice. REGISTRATION: This systematic review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO). The reference number is CRD42018110380.


Assuntos
Pontos de Acupuntura , Bronquite/terapia , Terapias Complementares/métodos , Medicina Herbária/métodos , Administração Cutânea , Protocolos Clínicos , Humanos , Medicina Tradicional do Leste Asiático , Resultado do Tratamento
12.
J Drugs Dermatol ; 18(5): 514, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31251543

RESUMO

Background: Patients with skin of color (SOC) and Fitzpatrick skin types (FST) IV­VI frequently develop acne. Objective: Evaluate subject-reported outcomes after treatment with adapalene 0.3%/ benzoyl peroxide 2.5% gel (0.3% A/BPO) in subjects with SOC and moderate to severe acne vulgaris. Methods: This was an open-label interventional study conducted in 3 countries (Mauritius, Singapore, and USA) in subjects of Asian, Latin-American, or black/African-American ethnicity, with an Investigator's Global Assessment (IGA) of moderate or severe facial acne (enrollment 2:1), and FST IV to VI. For 16 weeks, subjects applied 0.3% A/BPO (once daily) and utilized a skin care regimen (oil control foam wash and oil control moisturizer SPF30). Assessments included quality of life (QoL) and subject questionnaires, IGA, Investigator's Global Assessment of Improvement (GAI), postinflammatory hyperpigmentation (PIH; if present at baseline), and safety. Results: Fifty subjects were enrolled: 20 Asians, 17 black/African-Americans, and 13 Latin-Americans. Most had FST IV (74%) or V (22%), with moderate (70%; IGA 3) or severe (30%; IGA 4) acne. At week 16, 77% of subjects were satisfied or very satisfied with treatment, 56% of subjects had an IGA of 0 or 1 (clear/almost clear), and 87% had a good to excellent improvement in GAI. QoL improved throughout the study for all subjects; subject selection of "no effect at all" of acne on QoL increased from 16% of subjects at baseline to 55% at week 16. Of those with baseline PIH (60%), all were rated very mild to moderate. By week 16, the majority (75%) had no or very mild PIH, and the mean decrease in PIH was 27%. There were no adverse events leading to study discontinuation. Conclusion: Patients with SOC and moderate or severe facial acne reported high satisfaction with 0.3% A/BPO treatment and experienced good tolerability, improved QoL, treatment efficacy, and improvement in PIH. Clinicaltrials.gov number: NCT02932267 J Drugs Dermatol. 2019;18(6):514-520.


Assuntos
Acne Vulgar/tratamento farmacológico , Combinação Adapaleno e Peróxido de Benzoil/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Medidas de Resultados Relatados pelo Paciente , Pigmentação da Pele/efeitos dos fármacos , Acne Vulgar/diagnóstico , Combinação Adapaleno e Peróxido de Benzoil/efeitos adversos , Administração Cutânea , Adulto , Afro-Americanos , Grupo com Ancestrais do Continente Asiático , Fármacos Dermatológicos/efeitos adversos , Face , Feminino , Hispano-Americanos , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente/estatística & dados numéricos , Fotografação , Estudos Prospectivos , Qualidade de Vida , Índice de Gravidade de Doença , Pele/diagnóstico por imagem , Pele/efeitos dos fármacos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
13.
Gen Physiol Biophys ; 38(3): 237-244, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31184310

RESUMO

Hyperglycemia impairs oxidative capacity in skeletal muscle. Muscle oxidative capacity is regulated by peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α). Transcutaneous carbon dioxide (CO2) enhances PGC-1α expression in skeletal muscle. Therefore, the aim of this study was to clarify the effects of CO2 therapy on muscle oxidative capacity impaired by streptozotocin (STZ)-induced hyperglycemia. Eight-week-old male Wistar rats were randomly divided into 4 groups: control, CO2 treatment, STZ-induced hyperglycemia, and STZ-induced hyperglycemia treated with CO2. STZ-induced hyperglycemia resulted in a decrease of muscle oxidative capacity and decreased PGC-1α and cytochrome c oxidase subunit 4 (COX-4) expression levels; while, application of transcutaneous CO2 attenuated this effect, and enhanced the expression levels of endothelial nitric oxide synthesis (eNOS). These results indicate that transcutaneous CO2 improves impaired muscle oxidative capacity via enhancement of eNOS and PGC-1α-related signaling in the skeletal muscle of rats with hyperglycemia.


Assuntos
Dióxido de Carbono/administração & dosagem , Dióxido de Carbono/farmacologia , Hiperglicemia/metabolismo , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Administração Cutânea , Animais , Modelos Animais de Doenças , Masculino , Oxirredução/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Wistar
14.
Pharm Res ; 36(8): 124, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227928

RESUMO

PURPOSE: The aim of this work was to evaluate the use of short durations of externally applied heat with chemical penetration enhancers to improve delivery of isotretinoin to the skin and in particular via the follicular route. METHODS: A range of chemical penetration enhancers were screened for their ability to improve isotretinoin delivery into human skin with heat using infinite dose, Franz cell experiments conducted in a water bath at a higher temperature to simulate heated conditions. Following this a prototype external heating system was developed that provided short durations of heat and its ability to improve delivery of finite doses into the skin and hair follicles was assessed. RESULTS: The magnitude of the effect of heat on drug delivery was influenced by the choice of vehicle with changes in isotretinoin flux across skin ranging from not statistically significant to 25 fold increases with heat in the infinite dose studies. The prototype heating system provided significant increases in the total delivery of isotretinoin into the skin from an optimised vehicle. Drug distribution in the skin revealed significant increases in isotretinoin delivery to the hair follicles, and deeper skin layers, but not to the stratum corneum, providing strong evidence that the enhancement in delivery occurred mainly via the hair follicles. CONCLUSION: These data indicate that the use of short durations of heat combined with chemical penetration enhancers offers a valuable strategy for improving the delivery of drugs such as isotretinoin to the skin via the hair follicles. Graphical Abstract Schematic illustration of the sodium thiosulphate heating system on a Franz diffusion cell and the subsequent impact of a short burst of heat on the delivery of isotretinoin into human skin.


Assuntos
Fármacos Dermatológicos/farmacologia , Portadores de Fármacos/química , Folículo Piloso/química , Isotretinoína/farmacologia , Administração Cutânea , Fármacos Dermatológicos/administração & dosagem , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Folículo Piloso/citologia , Temperatura Alta , Humanos , Isotretinoína/administração & dosagem , Permeabilidade , Pele/metabolismo , Absorção Cutânea , Tiossulfatos/química
15.
Ceska Slov Farm ; 68(1): 12-26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31163963

RESUMO

Transdermal Therapeutic Systems (TTS) improve patient compliance especially due to its simple application and long-term action with the need to exchange the system every 12 hours to several days. The advantages also include elimination of first-pass effect, avoidance of gastrointestinal adverse effects, stable drug levels in the blood and simple discontinuation of therapy by patch removing. However, most drugs do not have the appropriate physicochemical properties to achieve therapeutic levels by transdermal application, therefore only a limited amount of drugs administered by this route is available on the market. Microneedles (MI) by their painless application appear to increase drug permeation when applied transdermally. In this review work, various types of MI (solid, coated, hollow, matrix, hydrogel forming) their size, shape, grouping, but also materials and technologies used in MI production are described. Finally, the work is focused on current clinical trials in which MI have been tested. MI with their unique properties have potential to increase the range of transdermally administered drugs currently applied by another route of administration. MI can simply pave the way for transdermal delivery to poorly penetrating small molecules as well as large molecules such as vaccines, monoclonal antibodies, or siRNA.


Assuntos
Sistemas de Liberação de Medicamentos , Agulhas , Preparações Farmacêuticas/administração & dosagem , Administração Cutânea , Humanos
16.
Int J Nanomedicine ; 14: 3955-3966, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31239665

RESUMO

Background: Sulconazole (SCZ) is a broad-spectrum transdermally administered anti-fungicidal agent. However, the therapeutic effect of SCZ is generally limited by its poor water solubility. This present study aimed to develop and evaluate sulconazole-loaded nanoemulsions (SCZ-NEs) for enhancement of the transdermal permeation and antifungal activity. Methods: A spontaneous titration method was applied to prepare the SCZ-NEs. And the optimized formulation of SCZ-NEs was screened by central composite design (CCD). In addition, the characteristics of the SCZ-NEs were evaluated, including particle size, zeta potential, drug loading (DL%) and encapsulation efficiency (EE%). The morphology of SCZ-NEs was observed by transmission electron microscopy (TEM). Franz diffusion cells were used to evaluate the transdermal permeability of the SCZ-NEs. The antifungal activity of the SCZ-NEs was measured by a zone of inhibition (ZOI) test. Results: The optimized SCZ-NEs possessed a moderate particle size of 52.3±3.8 nm, zeta potential of 23.3±1.2 mV, DL% of 0.47±0.05% and EE% of 87.1±3.2%. The ex vivo skin permeation study verified that the cumulative permeability (Qn) and penetration rate (Js) of the optimized SCZ-NEs were about 1.7-fold higher than that of a commercial reference, miconazole (MCZ) cream and 3-fold higher than that of SCZ-DMSO solution. The optimized SCZ-NEs exhibited zone of inhibition (ZOI) values of 23.5±2.4 and 20.4±2.5 mm against C. albicans and T. rubrum, which were larger compared with these of the MCZ cream and SCZ-DMSO solution. Conclusion: SCZ-NEs were effectively developed to overcome the poor solubility of SCZ, promote SCZ permeation through the skin and improve its antifungal activity. Thus, the SCZ-NEs are a promising percutaneous administration for skin fungal infections induced by C. albicans and T. rubrum.


Assuntos
Antifúngicos/farmacologia , Emulsões/química , Imidazóis/farmacologia , Nanopartículas/química , Absorção Cutânea/efeitos dos fármacos , Administração Cutânea , Análise de Variância , Animais , Candida albicans/efeitos dos fármacos , Fungos/efeitos dos fármacos , Masculino , Testes de Sensibilidade Microbiana , Nanopartículas/ultraestrutura , Óleos/química , Tamanho da Partícula , Permeabilidade/efeitos dos fármacos , Transição de Fase , Ratos Sprague-Dawley , Solubilidade , Tensoativos/química
17.
J Biomed Nanotechnol ; 15(3): 417-430, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31165689

RESUMO

In this study, a cell-penetrating peptide named Acylated Steric acid-9 poly-arginine (r9-SA) was sucessfully synthesized. High performance liquid chromatography (HPLC) and mass spectrometry (MS) were used to characterize the structural formula of r9-SA. Diclofenac sodium was chosen as a model drug, and the transdermal permeation-enhancing effect of r9-SA was estimated in vitro. Skin irritation experiment and histopathological observation of tissue sections with HE and Masson staining were performed to analyze the security of r9-SA. The possible penetration-enhancing mechanism of r9-SA was characterized with laser scanning confocal microscopy (LSCM), differential scanning calorimetry (DSC), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and laser Raman spectroscopy, respectively. The in vitro penetration study showed that r9-SA has a promoting effect for enhancing the transdermal penetration of diclofenac sodium. Skin irritation experiment and histopathological observation results showed that r9-SA has good biocompatibility with skin. The experiments were carried on to characterize the penetration mechanism of r9 -SA. It was found that r9-SA may react with the keratin in the stratum corneum (SC), changing its secondary structure and so that drugs can penetrate through SC. In conclusion, all data showed that the r9-SA could be a safe and effective penetration enhancer for topical delivery of drug.


Assuntos
Peptídeos Penetradores de Células/administração & dosagem , Administração Cutânea , Arginina , Pele , Absorção Cutânea , Espectroscopia de Infravermelho com Transformada de Fourier
19.
J Dermatol ; 46(6): 526-530, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31106878

RESUMO

Scalp dysesthesia may be underrecognized but is an important condition which requires special management strategies. Through our case series of four patients, we have noted that patients were frequently misdiagnosed with seborrheic dermatitis and failed standard treatment. However, patients did benefit from low doses of oral pregabalin and a topical compound of amitriptyline, lidocaine and ketamine. Oral antihistamines and topical corticosteroids did not work sufficiently on their own but added value when used in conjunction with analgesic agents. Our experience and published work also suggest the association of cervical spinal changes, psychiatric disorders, and other environmental and habitual factors.


Assuntos
Analgésicos/administração & dosagem , Glucocorticoides/administração & dosagem , Antagonistas dos Receptores Histamínicos/administração & dosagem , Parestesia/diagnóstico , Administração Cutânea , Administração Oral , Idoso , Vértebras Cervicais , Dermatite Seborreica/diagnóstico , Erros de Diagnóstico , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Transtornos Mentais/complicações , Pessoa de Meia-Idade , Parestesia/tratamento farmacológico , Parestesia/etiologia , Parestesia/psicologia , Couro Cabeludo , Dermatoses do Couro Cabeludo/diagnóstico , Doenças da Coluna Vertebral/complicações , Resultado do Tratamento
20.
J Dermatol ; 46(7): 622-625, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31106887

RESUMO

Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a recently recognized syndrome caused by mutations in the desmoglein 1 (DSG1) and desmoplakin (DSP) genes. Only two cases of SAM-DSP have been reported. We report on a 2-year-old girl presenting with pustular lakes within areas of erythema and large accumulations of intraepidermal neutrophils, which initially led to our misdiagnosis of generalized pustular psoriasis. No mutation was found in either the IL36RN or CARD14 genes by Sanger sequencing. The distinctive manifestations of erythroderma with severe itching, hypotrichosis, enamel defects, onychodystrophy, palmoplantar keratoderma and the crucial result of de novo missense mutation in exon 14 of the DSP gene (c.1828T>C, p.S610P) discovered by next-generation sequencing finally confirmed the diagnosis of SAM syndrome. The eruptions significantly improved after a 4-week treatment with oral acitretin and topical pimecrolimus. Oral gabapentin was prescribed simultaneously for 4 months, relieving her skin pruritus and suggesting that early treatment with pimecrolimus, acitretin and gabapentin for SAM-DSP syndrome is effective. It may even inhibit multiple allergies induced by skin barrier injury. In this work we also review the clinical features, differential diagnoses and pathological manifestations of SAM-DSP syndrome.


Assuntos
Acitretina/administração & dosagem , Dermatite Esfoliativa/diagnóstico , Desmoplaquinas/genética , Gabapentina/administração & dosagem , Hipersensibilidade/diagnóstico , Síndrome de Emaciação/diagnóstico , Administração Cutânea , Administração Oral , Pré-Escolar , Análise Mutacional de DNA , Dermatite Esfoliativa/tratamento farmacológico , Dermatite Esfoliativa/genética , Dermatite Esfoliativa/patologia , Diagnóstico Diferencial , Erros de Diagnóstico , Feminino , Humanos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/genética , Hipersensibilidade/patologia , Mutação de Sentido Incorreto , Psoríase/diagnóstico , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/patologia , Síndrome , Tacrolimo/administração & dosagem , Tacrolimo/análogos & derivados , Resultado do Tratamento , Síndrome de Emaciação/tratamento farmacológico , Síndrome de Emaciação/genética , Síndrome de Emaciação/patologia
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