Preparation of Huoluo Xiaoling gel plaster and its transdermal penetration in vitro / 中国中药杂志

Huoluo Xiaoling Dan is a classical prescription commonly used for blood circulation and pain relief in clinic with obvious effects. To make it directly treat lesion and improve the effect, this research optimized the preparation process of Huoluo Xiaoling gel paste and further evaluated its in vitro transdermal absorption performance, so as to provide a scientific basis for its development and utilization. Using primary viscosity, holding viscosity, and sensory score as evaluation indexes, the matrix amount of gel paste was determined by the single factor test and Box-Behnken response surface method. The ultra-performance liquid chromatography(UPLC) method was established to determine the content of eight active ingredients, including Danshensu, ferulic acid, salvianolic acid B, salvianolic acid A, ligustilide, tanshinone Ⅱ_A, 11-keto-β-boswellic(KBA), and 3-acetyl-11-keto-β-boswellic acid(AKBA). A mo-dified Franz diffusion cell method was used to evaluate and compare the absorption properties of the gel paste without volatile oil and with volatile oil microemulsion. The results showed that the optimal prescription for Huoluo Xiaoling gel paste matrix was NP700(1.35 g), glycerol(7.00 g), micropowder silica gel(1.25 g), sodium carboxymethyl cellulose(0.20 g), tartaric acid(0.06 g), and glyceryl aluminum(0.04 g). The mass fractions of eight active ingredients in the paste were successively 0.48, 0.014, 0.95, 0.39, 0.57, 0.055, 0.35, and 0.97 mg·g~(-1). The results of the in vitro transdermal absorption test showed that the addition of the volatile oil or the volatile oil microemulsion promoted the transdermal absorption of the active ingredients, and the law of drug penetration conformed to the zero equation or the Higuchi equation. The gel paste prepared by the optimal prescription has good appearance and adhesion, with no residue, and has the characteristics of skeletal slow-release preparation, which is easy to reduce the number of administration, la-ying a foundation for the development of new external dosage forms of Huoluo Xiaoling Dan.

Challenges of nanotechnology in cosmetic permeation with caffeine / Desafios da nanotecnologia na permeação cosmética com cafeína

The evolution of beauty market and personal care is constant in Brazil as well in the rest of the world. Technological advances have brought up nanotechnology to the cosmetological field, employing active principles at atoms enveloped by vesicles, in order to take the active principle precisely to the target tissue to optimize the results achieved because of the considerable ease to cross skin barriers. Manufacturing of nanotechnology cosmetics is confronted with low absorption capacity. One of the many active principle found in cosmetic industry is caffeine, a pseudoalkaloid from the xanthine group used as a stimulant with the mechanism of the lipolytic action. This active is widely used in a esthetics and cosmetics field in treatments involving dysfunctions such as localized fat and fibroedema geloid. To work out perfectly, the principle active need to interact and create a set of factors that includes lipolysis intensification. The caffeine encapsulation in gel-based nanocosmetics has the purpose of taking this active up to the adipocyte, the target cell, for mentioned dysfunctions treatment. Thus, we aim to present a review of how has been, the use of caffeine in the production of cosmetics.

A evolução do mercado de beleza e cuidados pessoais é constante no Brasil e no resto do mundo. Os avanços tecnológicos trouxeram a nanotecnologia para o campo cosmetológico, empregando princípios ativos em átomos envolvidos por vesículas, a fim de levar o princípio ativo precisamente ao tecido alvo para otimizar os resultados alcançados devido à considerável facilidade de atravessar barreiras cutâneas. A fabricação de cosméticos nanotecnológicos é confrontada com baixa capacidade de absorção. Um dos muitos princípios ativos encontrados na indústria cosmética é a cafeína, um pseudoalocalóide do grupo xantina usado como estimulante no mecanismo da ação lipolítica. Este ativo é amplamente utilizado no campo da estética e dos cosméticos em tratamentos que envolvem disfunções, como gordura localizada e fibroedema gelóide. Para funcionar perfeitamente, o princípio ativo precisa interagir e criar um conjunto de fatores que inclui a intensificação da lipólise. O encapsulamento de cafeína em nanocosméticos à base de gel tem o objetivo de levar esse ativo até o adipócito, a célula alvo, para o tratamento de disfunções mencionado. Assim, objetivamos apresentar uma revisão de como tem sido o uso de cafeína na produção de cosméticos.

Comparative study on in vivo and in vitro permeability of Huoxue Zhitong gel patch and microemulsion gel / 中国中药杂志

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_n and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.

Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism / 中国中药杂志

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

Enhancing effect and mechanism of muscone on transdermal penetration of traditional Chinese medicine ingredients with different log P value / 中国中药杂志

This study aimed to investigate the enhancing effect of muscone on the transdermal penetration of traditional Chinese medicine ingredients and explore its possible mechanism of action. The Franz diffusion cells were employed to investigate the effect of muscone on the transdermal permeation of a series of model drugs with a wide range of log P values. The solubilities at saturation and the stratum corneum(SC)/vehicle partition coefficients of model drugs were measured to evaluate the effect of muscone on drug thermodynamic activities and partition of drugs into SC. Attenuated total reflectance-Fourier transform infrared spectroscopy(ATR-FTIR) was employed to explore the effect of muscone on the molecular structure of SC. The results showed that muscone significantly promoted the transdermal penetration of hydrophilic and lipophilic drugs, and the enhancement ratio(ER) increased with the decrease in the log P. Muscone could interact with the SC lipids to increase the disorder and fluidity of lipid bilayer packing, which improved skin permeability and promoted transdermal absorption of drugs. This study provides a scientific basis for the application of muscone in traditional Chinese medicine topical preparations.

Desenlaces clínicos y radiológicos de las fracturas de maléolo lateral manejadas de forma percutánea. Serie de casos / Clinical and radiological outcomes of percutaneously managed lateral malleolar ankle fractures. Case series

Introducción El estándar de manejo para las fracturas del peroné distal es la reducción abierta más fijación interna con placa y tornillos (bloqueados o no), sin embargo, existen complicaciones asociadas a este tipo de intervención. En pacientes ancianos con mala calidad de tejidos blandos o en quienes presentan traumas de alta energía como etiología de las fracturas en el tobillo, la tasa de complicaciones previamente mencionadas aumenta, por lo que el manejo de las fracturas de peroné distal con tornillos percutáneos representa una alternativa con menor riesgo de complicaciones y con desenlaces similares al manejo convencional. Materiales y métodos Se realiza una serie de casos de pacientes con fractura de peroné manejados de forma percutánea. Se obtuvo una muestra de 17 pacientes por un año, a quienes se les realizó seguimiento sobre tasa de consolidación, funcionalidad y complicaciones postoperatorias. Resultados Diez (62,5%) fueron hombres, con una media de edad de 59 años (rango entre 24 y 90). El 100% fueron secundarios a traumas de alta energía, 10 (62,5%) fueron izquierdas, 14 (87,5%) se clasificaron como Weber B y 7 casos (56,25%) se presentaron concomitantemente con fracturas abiertas. Conclusiones Con el fin de evitar complicaciones, se debe considerar este abordaje en pacientes con comorbilidades, de edad avanzada o con tejidos blandos lesionados severamente o de mala calidad

Background The standard management for distal fibula fractures is open reduction plus internal fixation with plate and screws (blocked or not), however, there are complications associated with this type of intervention. In elderly patients with poor soft tissue quality or in those with high-energy trauma as the etiology of ankle fractures, the rate of previously mentioned complications increases, so that the management of distal fibula fractures with percutaneous screws represents a alternative with lower risk of complications and similar outcomes to conventional management. Methods A series of cases of patients with fibula fracture managed percutaneously was carried out. A sample of 17 patients was obtained for one year, who were followed up on consolidation rate, functionality, and postoperative complications. Results 10 (62.5%) were men, with a mean age of 59 years (range between 24 and 90). 100% were secondary to high-energy trauma, 10 (62.5%) were left, 14 (87.5%) were classified as Weber B and 7 cases (56.25%) presented concomitantly with open fractures. Discussion In order to avoid complications, this approach should be considered in patients with comorbidities, the elderly, or those with severely injured or poor-quality soft tissues.

Preparation of compound liquorice microemulsion gel and its pharmacodynamics evaluation / 中国中药杂志

Based on the previous study of compound liquorice microemulsion, this paper aims to prepare the compound liquorice microemulsion gel and investigate its pharmacodynamics of chronic eczema. The type, dosage and adding method of gel matrix, and formula dosage of humectant were optimized by single factor method to obtain the formula and preparation technique of the gel. With glycyrrhizic acid, glycyrrhetin and oxymatrine used as evaluation indexes, the Franz diffusion cell method was adopted to monitor the in vitro release profile of the gel. Eczema model of delayed-type hypersensitivity in mice was chosen to detect the ear swelling rate, degree of inflammatory cell infiltration of ear pieces, and pathological changes of ear pieces, so as to investigate the therapeutic effect of the microemulsion gel. The preparation process of the compound liquorice microemulsion gel was stable. The release of glycyrrhizin and oxymatrine was most consistent with the Hixcon-Crowell kinetic model, while the release of glycyrrhizic acid was most consistent with the Ritger-Peppas kinetic model. The pharmacodynamics studies proved that compound liquorice microemulsion gel could significantly reduce the ear swelling rate in mice, with good anti-inflammatory effect as well as the ability to resist the pathological changes of chronic eczema and inhibit the infiltration of dermal inflammatory cells. Therefore, the preparation process of compound liquorice microemulsion gel is feasible, with stable drug release and a significant therapeutic effect on chronic eczema.

Preclinical studies of hydroalcoholic extract of Calea uniflora Less / Estudios preclínicos de extracto hidroalcohólico de Calea uniflora Less

Calea uniflora Less known popularly as Arnica in Brazil, is a native plant from Brazil, popular used by coastal populations from south of Santa Catarina. The purpose of this study was to verify the safety profile in of hydroalcoholic extract of C. uniflora in florescences.The hydroalcoholic extract of C. uniflora in florescences was evaluated for its acute and sub-acute toxicity. Acute topical toxicity was performed using the methodology of guideline 402 from OECD. Acute oral toxicity was performed using the methodology of guideline 423 from OECD and sub-acute toxicity was performed using the methodology adapted of guideline 407 from OECD. The single dose for oral or topical administration of C. uniflora showed DL50> 5000 mg/kg b.w. The sub-acute treatment induced animal death in groups, which was administered extract in the doses 100, 250, 500 and 1000 mg/kg. The main signs of toxicity observed were respiratory difficulty, increase in lung weigh, lung damage and muscular relation. The topical or oral administration of C. uniflora extract in short period did not caused toxicological effects in animals, however, when administered for a longer period and in concentrations of 250, 500 and 1000 mg/kg (oral.) caused lung damage and even the death of the animal.

Calea uniflora Less conocida popularmente como Arnica en Brasil, es una planta nativa de Brasil, popularmente utilizada por poblaciones costeras del sur de Santa Catarina. El objetivo de este estudio fue verificar el perfil de seguridad del extracto hidroalcoólico de inflorescencias de C. uniflora. El extracto hidroalcoólico de inflorescencias de C. uniflora fue evaluado en cuanto a su toxicidad aguda y subaguda. La toxicidad tópica aguda se realizó utilizando la metodología de la directriz 402 de la OECD. La toxicidad oral aguda fue realizada usando la metodología de la directriz 423 de la OECD y la toxicidad subaguda fue realizada usando la metodología adaptada de la directriz 407 de la OECD. La dosis única para administración oral o tópica de C. uniflora mostro DL50> 5000 mg/kg. El tratamiento subagudo indujo la muerte de animales en grupos a los que se administró extracto en las dosis de 100, 250, 500 y 1000 mg/kg. Los principales signos de toxicidad observados fueron dificultad respiratoria, aumento del peso del pulmón, daño pulmonar y relación muscular. La administración tópica oral del extracto de C. uniflora a corto plazo no causó efectos toxicológicos en los animales, mientras que, cuando se administró por un período mayor y en las concentraciones de 250, 500 y 1000 mg/kg (oral) causaron danos en los pulmones y hasta la muerte del animal.

Effects of pungent essential oil from three Chinese herbs on percutaneous absorption of alkaloids from Sophorae Flavescentis Radix / 中国中药杂志

To investigate the effects of essential oil from three kinds of pungent herbs,namely Menthae Haplocalycis Herba,Atractylodis Rhizoma and Cnidii Fructus,on the transdermal absorption in vitro of alkaloids from Sophorae Flavescentis Radix. The modified vertical Franz diffusion cell was used to conduct a transdermal experiment in vitro with the isolated abdominal skin of the SD rats as the transdermal absorption barrier. The effects of such three kinds of pungent essential oil on percutaneous absorption of alkaloids from Sophorae Flavescentis Radix were investigated by determining the content of 6 alkaloids( oxymatrine,oxysophocarpine,N-methylcytisine,sophoridine,matrine,and sophocarpidine) in the transdermal acceptor with ultra-performance liquid chromatography-triple quadruple mass spectrometry( UPLC-TQ-MS) technique simultaneously. With enhancement ratio( ER) as the index,their effects on promoting penetration was as follows: 1% Atractylodis Rhizoma oil > 1% Cnidii Fructus oil > 3% Azone ≈ 3% Atractylodis Rhizoma oil > 5%Atractylodis Rhizoma oil > 3% Cnidii Fructus oil ≈ 5% Cnidii Fructus oil > 3% Menthae Haplocalycis Herba oil > 5% Menthae Haplocalycis Herba oil > 1% Menthae Haplocalycis Herba oil > Blank. The results showed that these three kinds of pungent essential oil could be used as enhancers for alkaloids of Sophorae Flavescentis Radix,providing scientific guidance for improving percutaneous absorption of alkaloids from Sophorae Flavescentis Radix.

In vitro transdermal permeation of main compositions in Baimai Ointment / 中国中药杂志

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.

Efetividade das técnicas de restauração de barreira cutânea "Wet Wraps" e "Soak and Smear" na dermatite atópica grave: relato de caso e revisão da literatura / Effectiveness of skin barrier repair techniques "Wet Wraps" and "Soak and Smear" in severe atopic dermatitis: a case report and literature review

A restauração da barreira cutânea é o primeiro passo para o controle da dermatite atópica (DA) em todas as suas formas. O tratamento da DA grave ou refratária em crianças apresenta alguns desafios, devido principalmente aos efeitos colaterais das drogas imunossupressoras. Como alternativa, as técnicas "Wet Wraps" e "Soak and Smear" são intervenções seguras e eficazes em casos em que a xerose é fator determinante de agravamento da doença. Relata-se o caso de um menino de 5 anos com DA grave (SCORAD = 54) não controlada, com prurido intenso e distúrbio do sono. Houve tratamento prévio com corticoide tópico e sistêmico, diversos emolientes, uso repetido de antibióticos tópicos e sistêmicos, e restrição de leite de vaca, sem resultado. As comorbidades incluíam rinite alérgica (sensibilizado para ovo, leite, epitélio de cão e ácaros) e transtorno do espectro autista. Foi realizado tratamento tópico com ácido fusídico e corticoide de média potência, além de otimização das técnicas de restauração de barreira cutânea. Após um mês, o paciente retornou com melhora quase completa das lesões, SCORAD de 17 (leve), referindo intensa melhora na qualidade de vida, com resolução do distúrbio do sono. Este caso demonstrou a efetividade das técnicas "Wet Wraps" e "Soak and Smear" em criança com DA grave. A boa adesão e a correta execução são fundamentais para o resultado, ressaltando a importância da atenção médica quanto à educação da equipe e dos pais sobre o tratamento. Essas técnicas são bem estudadas e podem ser realizadas como resgaste na DA grave, mesmo em crianças com alterações comportamentais, e, se adequadamente utilizadas, podem evitar a prescrição de imunossupressores.

Skin barrier repair is the first step to control all forms of atopic dermatitis (AD). Treatment of severe or refractory AD in children poses some challenges, mainly due to the side effects of immunosuppressive drugs. As an alternative treatment, "Wet Wraps" and "Soak and Smear" techniques are safe and effective interventions when xerosis is an aggravating factor of the disease. We report the case of a 5-year-old boy with severe AD (SCORAD = 54), showing severe pruritus and sleep disorder. Prior treatment involved topical and systemic corticosteroids, several emollients, repeated use of topical and systemic antibiotics, and restriction to cow's milk, without any positive result. Comorbidities included allergic rhinitis (sensitized to egg, milk, dog epithelium and mites) and autism spectrum disorder. Topical treatment with fusidic acid and medium-potency corticoid was performed, in addition to optimization of skin barrier repair techniques. After one month, the patient returned with clinical improvement, SCORAD of 17 (mild), reporting a strong improvement in quality of life and no sleep disorder. This case demonstrates the effectiveness of the "Wet Wraps" and "Soak and Smear" techniques when applied to children with severe AD. Good adherence and correct execution are fundamental to outcomes, stressing the importance of medical care in the education of team and parents about the treatment. These techniques are well studied and can be performed as rescue therapy in severe AD, even in children with behavioral disorders, and, if properly used, may avoid prescription of immunosuppressants.

Urinary cotinine in tobacco farmers in Southern Brazil

ABSTRACT OBJECTIVE To describe urinary cotinine levels in tobacco farmers. METHODS A cross-sectional study was conducted in 2,570 tobacco farmers. All participants that reported green tobacco sickness in the week prior to the interview plus a subsample of 492 pesticide applicators were included. We collected urinary samples and information about sociodemographic, behavioral, dietary, occupational characteristics, and pesticide poisoning during their lifetime. Stratification by sex and smoking was performed and the Wilcoxon and Kruskal-Wallis non-parametrical tests were used to analyze cotinine means. RESULTS This study included 582 individuals. There was no difference in urinary cotinine means between green tobacco sickness symptomatic and asymptomatic individuals. Among non-smokers, having picked tobacco in the previous week was associated with higher cotinine means in both genders. Cotinine levels were higher on the first day of symptoms and reduced exponentially with each day in female non-smokers. Male non-smokers had higher levels on the second day and a more gradual reduction. The cotinine level rose up to 15 cigarettes/day of consumption. CONCLUSIONS The urinary cotinine measures exposure to nicotine up to its saturation point; while green tobacco sickness, affected by tolerance, indicates nicotine poisoning. Strategies to reduce nicotine exposure in tobacco production are needed. Mechanization could be an alternative, as long as it overcame the challenge of irregular terrain and did not affect the quality of the leaf. More studies are needed to evaluate the chronic effect of nicotine exposure.

Percutaneous golfer's elbow release under local anesthesia: a prospective study / Liberação percutânea do cotovelo de golfista sob anestesia local: um estudo prospectivo

ABSTRACT OBJECTIVES: To evaluate the results of percutaneous golfer's elbow release under local anesthesia. METHODS: From December 2010 to December 2013, 34 elbows in 34 patients (10 males and 24 females) that presented golfer's elbow for over one year were recruited from the outpatient department. All patients were operated under local anesthesia and were followed-up for 12 months. The functional outcome was evaluated through the Mayo Elbow Performance Index (MEPI). RESULTS: Pain relief was achieved on average eight weeks after surgery. The results were excellent in 88.23% (30/34) cases and good in 11.76% (4/34) cases. Neither wound-related complications nor ulnar nerve complications were observed. On subjective evaluations, 88.23% (30/34) patients reported full satisfaction and 11.76% (4/34) patients reported partial satisfaction with the results of treatment. CONCLUSION: Percutaneous golfer's elbow release under local anesthesia is a minimally invasive procedure that can be performed in an outpatient setting. This procedure is easy, quick, and economical, presenting a low complication rate with good results.

RESUMO OBJETIVO: Avaliar os resultados da liberação percutânea do cotovelo de golfista sob anestesia local. MÉTODOS: Entre dezembro de 2010 e dezembro de 2013, 34 cotovelos em 34 pacientes (10 homens e 24 mulheres) que apresentavam cotovelo de golfista havia mais de um ano foram recrutados do ambulatório. Todos os pacientes foram operados sob anestesia local e foram acompanhados por 12 meses. O resultado funcional foi avaliado pelo Mayo Elbow Performance Index (MEPI). RESULTADOS: O alívio da dor foi alcançado em média oito semanas após a cirurgia. Os resultados foram excelentes em 88,23% (30/34) dos casos e bons em 11,76% (4/34) dos casos. Não se observaram complicações relacionadas à ferida nem complicações do nervo ulnar. Em avaliações subjetivas, 88,23% (30/34) dos pacientes relataram satisfação total e 11,76% (4/34) dos pacientes relataram satisfação parcial com os resultados do tratamento. CONCLUSÃO: A liberação percutânea do cotovelo de golfista sob anestesia local é um procedimento minimamente invasivo que pode ser feito em ambulatório. Esse procedimento é fácil, rápido e econômico, apresenta um baixo índice de complicações e bons resultados.

The measurement of serum corticosteroid level in atopic dermatitis patients associated with application of topical corticosteroids

PURPOSE: Most of the atopic dermatitis (AD) patients and their parents refuse topical treatment because of concern about generalized side effect due to systemic absorption of topical corticosteroids. Therefore, a large number of studies reported difficulty in properly controlling in AD. However, investigations of the percutaneous absorption of topical corticosteroids are still insufficient. METHODS: One hundred nine patients who visited our atopy clinic and diagnosed as AD by a physician from January 2005 to January 2012 were enrolled. We examined serum corticosteroid (clobetasol propionate, hydrocortisone) level by liquid chromatography (LC) coupled with a tandem mass spectrometric (MS/MS) method. RESULTS: We developed the LC-MS/MS method to determine corticosteroids (clobetasol propionate, hydrocortisone) in sera of AD patients. Also, we confirmed precision, accuracy, limit of detection, limit of quantification, absolute recovery, and relative recovery of the experimental methods. We could not detect clobetasol propionate or hydrocortisone in sera of 109 AD patients using the newly developed LC-MS/MS method. CONCLUSION: Regardless of age, the severity and illness duration of AD, clobetasol and hydrocortisone were not detected in sera. Although there are many other factors of determining systemic absorption of topical medications, our results showed that topical corticosteroids applied for several years in AD patients may be under the limit of detection in their sera by the LC-MS/MS method.

Promotion of cutaneous penetration of nifedipine for nanoemulsion

ABSTRACT This article reports the development and characterization of a nanoemulsion (NE) able to improve the cutaneous penetration of nifedipine. NE with nifedipine was development and characterized, presenting droplet size of 20 nm with low polydispersity index (IP<0.1), spherical shape without aggregation, pH compatible with typical skin levels and stability evaluated by seven months. In the permeation studies, a classical formulation based in an oil/water cream containing nifedipine was used for comparison with NE. Nanoemulsion promoted and improved the retention of nifedipine in the epidermis and dermis in relation to classical formulation. This promoting effect is related to the nanometric size of the droplets of the NE (20 nm), which give him a large superficial area, favoring the contact of the nanocarrier with the skin surface. The NE was efficient in promoting accumulation of nifedipine in the dermis, which is the site of vasodilation action. NE was not irritating according to the primary dermal irritation tests. NE is a promising release system to promote cutaneous penetration of nifedipine and can be used in the future in clinical trials to promote healing of lesions caused by peripheral vascular diseases.

Evaluation of skin absorption of drugs from topical and transdermal formulations

ABSTRACT The skin barrier function has been attributed to the stratum corneum and represents a major challenge in clinical practice pertaining to cutaneous administration of drugs. Despite this, a large number of bioactive compounds have been successfully administered via cutaneous administration because of advances in the design of topical and transdermal formulations. In vitro and in vivo evaluations of these novel drug delivery systems are necessary to characterize their quality and efficacy. This review covers the most well-known methods for assessing the cutaneous absorption of drugs as an auxiliary tool for pharmaceutical formulation scientists in the design of drug delivery systems. In vitro methods as skin permeation assays using Franz-type diffusion cells, cutaneous retention and tape-stripping methods to study the cutaneous penetration of drugs, and in vivo evaluations as pre-clinical pharmacokinetic studies in animal models are discussed. Alternative approaches to cutaneous microdialysis are also covered. Recent advances in research on skin absorption of drugs and the effect of skin absorption enhancers, as investigated using confocal laser scanning microscopy, Raman confocal microscopy, and attenuated total reflectance Fourier-transform infrared spectroscopy, are reviewed.

Enhancing Effect of Chiral Enhancer Linalool on Skin Permeation of Naproxen / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the permeation-enhancing effect of dl-linalool, d-linalool, and l-linalool on model drugs across excised rat skin and the effect of linalool on the ceramides in stratum corneum lipids.</p><p><b>METHODS</b>In vitro skin permeation studies were performed with Valia-Chien diffusion cells, and the permeation samples were analyzed by high performance liquid chromatography with chiral stationary phase. Infrared spectroscopy was used to investigate the effect of linalool on stratum corneum lipids.</p><p><b>RESULTS</b>When the donor vehicles added with 1% dl-linalool, 1% d-linalool, or 1% l-linalool, the steady-state skin permeation rate of naproxen was (2.47±0.63), (1.53±0.54), (1.73±0.48) μg·cm(-2)·h(-1), respectively, which is 2.49, 1.55, and 1.75 times (all P<0.05) compared with control group [(0.99±0.42)μg·cm(-2)·h(-1)], and the differences were statistically significant (all P<0.05). The permeation-enhancing effect of dl-linalool on naproxen was found significantly greater than that of d-linalool and l-linalool (both P<0.05). Compared with the control group, the stratum corneum treated with dl-linalool shifted to higher wave number on 2.09 cm(-1) of asymmetric CH2 stretching vibrations in attenuated total reflection-fourier transform infrared spectroscopy analysis. However, stratum corneum treated with d-linalool and l-linalool did not display this phenomenon.</p><p><b>CONCLUSION</b>The disturbing degree of dl-linalool on stratum corneum lipids (ceramides) is different from that of linalool enantiomers, suggesting their different enhancing effect on the same drug.</p>

Permeação cutânea: desafios e oportunidades / Skin permeation: challenges and opportunities

O transporte de fármacos pela via transdérmica tem vindo a despertar um grande interesse, uma vez que constitui uma alternativa para ultrapassar as limitações de outras vias, como a oral e parenteral. No entanto, esta via ainda se destina apenas a um grupo restrito de fármacos, devido ao fato de que a pele apresenta uma baixa permeabilidade ao movimento de moléculas estranhas, como consequência da função barreira desempenhada pela camada córnea. Diversas estratégias têm sido desenvolvidas para contornar a barreira da pele com o objetivo de aumentar a permeação de fármacos, abrangendo métodos passivos ou ativos. O presente trabalho visa à revisão dessas estratégias, abordando os respetivos mecanismos de ação, bem como algumas combinações entre os diferentes métodos que têm demonstrado um efeito sinérgico e abordando, ainda, o problema da irritação da pele que pode advir da administração de fármacos por esta via.

Transdermal drug delivery has shown to be an interesting alternative to overcome limitations of conventional routes, such as the oral and parenteral ones. Nonetheless, the practical applications still remains limited to a narrow range of drugs, due to the skin barrier layer of the stratum corneum, which provides a low permeability to exogenous molecules. This review focuses on the strategies developed to enhance drug permeation, which include passive and active methods, and their respective mechanisms of action, as well as the combination of different methods that have shown to work in synergy. The problem of skin irritation that may result from the administration of drugs by this route is also addressed.

Preliminary study on transdermal characteristics and sunface anesthetic effects of lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome in animals / 中华口腔医学杂志

<p><b>OBJECTIVE</b>To prepare a new dental topical anesthetics, lidocaine hydrochloride loaded trans-activator of transcription peptide conjugated nano-niosome (LID-TAT-N), and to evaluate its transdermal properties and topical anesthesia effects.</p><p><b>METHODS</b>LID-TAT-N was prepared using reverse-phase evaporation method, and lidocaine loaded conventional liposome (LID-CL) was prepared in the same manner as positive control. The diameter, ζ potential and encapsulation efficiency of LID-TAT-N and LID-CL were measured. The skin permeation of LID-TAT-N was examined, and compared with LID-CL and lidocaine injection (LID-IJ, as negative control), using a Franz diffusion cell mounted with depilated mouse skin in vitro for 12 hours. Each experiment was repeated six times. The anesthetic effect of the new topical anesthetic was investigated on the cornea of rabbits.</p><p><b>RESULTS</b>The mean diameter of LID-TAT-N was smaller than that of LID-CL [(152.7 ± 10.6) nm vs. (259.5 ± 15.5) nm, P < 0.01]. The 12 h cumulative permeation amount was significantly higher in LID-TAT-N group [(1 340.0 ± 97.5) µg · cm(-2)] than those of LID-CL and LID-IJ groups [(1 060.6 ± 80.2), (282.6 ± 65.1) µg · cm(-2), respectively, P < 0.05]. Rabbit corneal reflex results showed that LID-TAT-N had anesthetic effect and the duration of analgesia [(24.8 ± 2.8) min] was also longer than that of LID-IJ [(14.5 ± 2.3) min, P < 0.05].</p><p><b>CONCLUSIONS</b>LID-TAT-N had good transdermal ability, and the advanced skin penetration feature can improve its tropical anesthetic effect.</p>

Effect of terpene penetration enhancer and its mechanisms on membrane fluidity and potential of HaCaT keratinocytes / 中国中药杂志

The aim of this paper was to investigate the effect of terpene penetration enhancers on membrane fluidity and membrane potential using HaCaT keratinocytes, and study the potential mechanisms of these terpene compounds using as natural transdermal penetration enhancer. Six terpene compounds, namely menthol, limonene, 1,8-cineole, menthone, terpinen-4-ol and pulegone, were chosen in this study on account of their good penetration-enhancement activities. The cytotoxicity of these terpene compounds was measured using an MTT assay. The fluorescence recovery after photobleaching (FRAP) technique was employed to measure the change of membrane fluidity of HaCaT cells. The flow cytometer was used to study the alteration of membrane fluidity of HaCaT cells, and investigate the effect of terpene compounds on intracellular Ca2+. It was found that 6 terpene compounds possessed low cytotoxicity in comparison to the well-established and standard penetration enhancer azone. Those terpene compounds could significantly enhance HaCaT cells membrane fluidity and decrease HaCaT cells membrane potentials. Meanwhile, after treated with various terpene compounds, the Ca2(+)-ATPase activity and intracellular Ca2+ of HaCaT cells was decreased significantly. Terpene penetration enhancers perhaps changed the membrane fluidity and potentials of HaCaT cells by altering the Ca2+ balance of the cell inside and outside, resulting in the low skin permeability to increase the drug transdermal absorption.