Metronidazole concentration in the bloodstream following its topical application, at different concentration levels, on experimental skin wounds during healing by secondary intention

Abstract Purpose: To characterize qualitatively and quantitatively the absorption of metronidazole solution, in greater concentrations and for longer periods, when applied topically to an experimental open skin wound model. Methods: An open skin wound, 2 cm in diameter and total skin thickness was prepared, under anesthetic, in the dorsal region of 108 Wistar rats weighing between 300 and 350 grams. The animals were allocated to groups of 18 animals in accordance with the concentration of metronidazole in the solution to be applied daily to the wound. In the control group (CG), 0.9% sodium chloride solution was used for application, and in the experimental groups (GI, GII, GIII, GIV and GV) metronidazole solution at 4%, 6%, 8%, 10% and 12%, respectively, was applied. After 3, 7 and 14 days of treatment. Blood samples collected through cardiac puncture were examined for the existence or non-existence of metronidazole, using high performance liquid chromatography (HPLC). Detected metronidazole values were compared statistically within each group (temporal analysis 3 days X 7 days X 14 days) and between the groups that used topical metronidazole (4% X 6% X 8% X 10% and 12%) using the Kruskal-Wallis test, considering a statistical significance of 95% (p<0.05). Results: Metronidazole was detected in all the samples at all times in all the groups in which topical metronidazole was applied to the wounds. Characteristically, there was no significant difference between the doses obtained within each group over time (3 days X 7 days X 14 days) GI=0.461; GII=0.154; GIII=0.888; GIV= 0.264 and GV=0.152. In the evaluation between groups, a similar degree of absorption was found after 3 days (p=0.829) and 14 days (p=0.751). Conclusion: The serum concentration of metronidazole that was achieved was not influenced by the concentration of the solution applied to the skin wound, with similar extend, or by the duration of the application.

Treatment and nursing of one patient with burns on perineal region and complicated by secondary multiple organ injuries by exposing to paraquat fluid / 中华烧伤杂志

On March 18, 2016, one 53 years old man with burns on perineal region and complicated by secondary multiple organ injuries by exposing to paraquat fluid was admitted to our department. Comprehensive treatment measures including protective mechanical ventilation, intensive care, vacuum sealing drainage, anti-infection, and organ protection were conducted sequentially. Through 33 days of comprehensive treatment and nursing, the patient′s condition substantially improved and he left hospital. This case presents that paraquat fluid absorption through skin and mucosa can also lead to severe systemic poisoning, and multiple organ protection is the key to improve the prognosis of this patient.

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.

Development and in vitro evaluation of reservoir-type patch of coumarins in Angelicae Dahuricae Radix / 中草药

Objective To prepare the reservoir patch of coumarins in Angelicae Dahuricae Radix and investigate its release and transdermal absorption characteristics in vitro. The efficient enhancers were chosen to improve the drug’s permeation rate. Methods The reservoir patch was prepared using hydroxypropyl methylcellulose (HPMC) as medium and ethylene vinyl acetate (EVA) membrane to control the release of drug. The Franz diffusion cells were used and HPLC was used to determine imperatorin content and permeation rate. The content of imperatorin was determined by HPMC. The effect of the gel consumption, the content of coumarins and penetration enhancer on the transdermal flux were investigated by selecting porcine skin as model. The release of the selected patch in vitro was investigated. Results 1% HPMC, 1% coumarins in Angelicae Dahuricae Radix, 1% Isopropyl Myristate (IPM) and 3% Azone were the best permeation of the patch. The permeation rate reached 0.713 μg/(cm2•h). The release mechanisms of the patch in vitro coincided with zero-order kinetic. Conclusion The reservoir patch of coumarins in Angelicae Dahuricae Radix had high transdermal rate and complete in vitro release. It was indicated that the patch could be expected to be an effective transdermal drug delivery system.

Sensitive skin: review of an ascending concept

Abstract: Sensitive skin is a condition characterized by stinging, burning and itching sensations. The diagnosis, pathophysiology and treatment of sensitive skin are still under discussion. In the last years, studies on its epidemiology have been performed, showing a high prevalence and impact on quality of life. Brazilian population was also considered in these studies. Cosmetics, climate changes and skin barrier impairment are the main factors that contribute for skin hyperreactivity. New studies are trying to bring new knowledge about the theme. This review will describe data on epidemiology, triggering factors, pathophysiology, diagnosis and treatment.

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.

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.

Drug delevery assistido por lasers: revisão / Drug delevery assistido por lasers: revisão

A via tópica de entrega de medicamentos é essencial na dermatologia. O drug delivery otimiza a penetração de medicamentos e, realizado por lasers, ocorre de forma uniforme e controlada. O grau de evidência do drug delivery está em investigação para diversos medicamentos. Além disso, a técnica é excelente associação com a atuação dos lasers para rejuvenescimento e para tratamento de doenças dermatológicas. Conclusão: O uso de lasers para drug delivery é promissor: enquanto algumas substâncias possuem estudos clínicos que permitem indicar sua realização, outras necessitam de estudos controlados e com maior tempo de seguimento para sua avaliação.

The topical route for the delivery of drugs is essential in dermatology: it optimizes the penetration of medicaments, and when performed with the assistance of lasers, it takes place in a uniform and controlled manner. The degree of evidence of drug delivery is being investigated for many drugs. Moreover, the technique combines outstandingly with lasers for rejuvenation and treatment of skin diseases. It is therefore possible to conclude that the use of lasers for drug delivery is promising. While there are clinical studies on some substances that allow their indication and use, others require further controlled analyses, with longer follow-up periods, aimed at allowing thorough evaluations.

Modified microneedle roller enhancing percutaneous absorption of triamcinolone acetonide by human hyperplastic scar skin / 第二军医大学学报

Objective To evaluate the role of modified microneedle roller in promoting permeation of triamcinolone acetonide across human hyperplastic scar skin. Methods The morphology of human hyperplastic scar skin was visualized by methylene blue staining and H-E staining after the insertion by microneedles of different lengths. The content of triamcinolone acetonide was determined by high performance liquid chromatography (HPLC). The in vivo absorption characteristics across human hyperplastic scar skin were investigated by elution method and the homogenization method at 1 h and 12 h after drug application. Skin irritation was assessed by transepidermal water-loss (TEWL) measurement and laser Doppler flowmetry. Results The preferred microneedle length of 500 µm effectively penetrated through the stratum corneum,and the distribution of the microchannels was homogeneous. It was found that 27. 42% and 60. 64% of the drug administered entered the skin at 1 h and 12 h, respectively. The drug accumulation in the skin at 12 h decreased to 45. 98% of that at 1 h after intracutaneous injection, while the accumulation increased to 2. 73-fold and 4. 18-fold in the microneedle group and direct application of triamcinolone acetonide cream group,respectively,with the content of microneedle group being 3. 56-fold that of the direct cream application group (P<0. 05). Triamcinolone acetonide distribution was not homogeneous at 12 h after intracutaneous injection, with the level being (4. 83 ± 5. 51) µg, while the distribution in the microneedle group was homogenous, with the level being (0.93 ± 0. 14) µg. TEWL results showed no significant difference in skin irritation between microneedle and intracutaneous injection group; however, laser Doppler flowmetry showed that the skin irritation of intracutaneous injection group was 8. 40- fold that of microneedle treatment group. Conclusion Modified microneedle roller treatment followed by cream application, compared with intracutaneous injection, can yield more homogeneous distribution and less skin irritation in human hyperplastic scar skin, but its efficacy for scar treatment remains to be further verified.

Dermal Exposure Associated with Occupational End Use of Pesticides and the Role of Protective Measures

BACKGROUND: Occupational end users of pesticides may experience bodily absorption of the pesticide products they use, risking possible health effects. The purpose of this paper is to provide a guide for researchers, practitioners, and policy makers working in the field of agricultural health or other areas where occupational end use of pesticides and exposure issues are of interest. METHODS: This paper characterizes the health effects of pesticide exposure, jobs associated with pesticide use, pesticide-related tasks, absorption of pesticides through the skin, and the use of personal protective equipment (PPE) for reducing exposure. CONCLUSIONS: Although international and national efforts to reduce pesticide exposure through regulatory means should continue, it is difficult in the agricultural sector to implement engineering or system controls. It is clear that use of PPE does reduce dermal pesticide exposure but compliance among the majority of occupationally exposed pesticide end users appears to be poor. More research is needed on higher-order controls to reduce pesticide exposure and to understand the reasons for poor compliance with PPE and identify effective training methods.

Effect of transdermal penetration enhancers on permeation ability of indomethacin and salbutamol / 第二军医大学学报

Objective: To study the effect of different transdermal penetration enhancers on the skin permeation ability of indomethacin and salbutamol in vitro. Methods: Valia-Chien diffusion cell was adopted as the apparatus for in vitro skin permeation test. Excised SD-rat abdomen skin was pretreated with penetration enhancers including Azone, Propylene glycol, N-methylpyrrolidone, oleic acid, peppermint oil, and a combination of Azone and Propylene glycol. A UV method was established to determine the contents of indomethacin and salbutamol in receiver diffusion cells. Results: Compared with blank control group, all the enhancers showed significant enhancement effect on the permeability of indomethacin and salbutamol except for propylene glycol (P < 0.01). Azone combined with propylene glycol showed the greatest ability to enhance the flux of indomethacin(125.91 μg · cm-2 · h-1) and salbutamol(155.94 μg · cm-2 · h-1). Conclusion: Azone combined with Propylene glycol, Azone, N-methylpyrrolidone, Oleic acid, and Peppermint oil can be used as penetration enhancers in the transdermal preparation of compound indomethacin.

Terapia fotodinâmica com ftalocianina de zinco tópica: avaliação da intensidade de fluorescência, absorção cutânea, alterações histológicas e imuno-histoquímicas na pele do modelo animal / Topical photodynamic therapy with zinc phthalocyanine: evaluation of fluorescence intensity, skin absorption, skin histological and immunohistochemical changes in animal model

FUNDAMENTOS - Ftalocianinas são promissores agentes fotossensibilizadores na terapia fotodinâmica (TFD). OBJETIVOS - Avaliar intervalos, veículos e a incorporação de promotor de absorção na formulação tópica da ftalocianina de zinco (FC-Zn). Avaliar alterações macro e micromorfológicas e a expressão de Fas promovidas pela TFD com FC-Zn tópica no modelo murino. MÉTODOS - Por meio da espectrometria de fluorescência, foram avaliadas combinações de diferentes períodos de oclusão tópica das formulações gel ou emulsão de FC-Zn (1mg/dl), com ou sem monoleína 5 por cento, no dorso do camundongo hairless. Após oito horas das diferentes formulações, os camundongos foram expostos ao laser de diodo de 670nm, dose de 50J/cm-². RESULTADOS - A fluorescência foi discretamente superior após oito horas e com a emulsão nos intervalos de uma, duas e quatro horas de oclusão. A intensidade do edema e da erosão correspondeu à necrose da epiderme e à imunoexpressão de Fas nos cortes histológicos de pele. CONCLUSÕES - Os achados indicam a ação fotodinâmica promovida pela interação entre FC-Zn e fonte de luz de 670nm. As alterações macro e micromorfológicas foram correspondentes e mais substanciais com a emulsão FC-Zn e monoleína, sugerindo a acentuação dos efeitos com essa formulação. A imunoexpressão de Fas e as alterações histológicas sugeriram a apoptose como mecanismo de morte celular na TFD com FC-Zn tópica.

BACKGROUND - Phthalocyanines are promising photosensitizers used in photodynamic therapy (PDT). OBJECTIVES - To evaluate the following parameters: intervals, vehicles and enhancer using topical zinc-phthalocyanine (Zn-PC) formulation. To examine macro and micromorphological changes and Fas expression induced by topical Zn-PC-PDT on murine skin. MATERIAL AND METHODS - Using fluorescence spectrometry, different intervals of topical occlusion employing Zn-PC gel or emulsion, with or without monolein 5 percent were studied. After an 8-hour occlusion of different formulations, the mice were exposed to 670 nm laser, at a 50 J.cm-² dose. RESULTS - Fluorescence was slightly higher after 8 hours, and also with emulsion formulation at one-, two- and four-hour occlusion periods. The intensity of edema and erosion were correlated to epidermal necrosis and to Fas immunoexpression in skin histological specimens. CONCLUSIONS - The results show the effects of photodynamic action promoted by the interaction between Zn-PC formulation and a 670-nm light source. Macro and micromorphological alterations were correlated and more substantial with monolein and Zn-PC emulsion, suggesting more marked effects with this formulation. The Fas immunoexpression and histological changes suggested that apoptosis plays a role in the mechanism of cell death caused by PDT based in Zn-PC.

Study on effect of ultramicro-shatter technology on penetrating skin absorption of Pollen Typhae in Zhongtongxiao Cataplasm / 中华中医药杂志

Objective:To study the effect of ultramicro-shatter technology on penetrating skin absorption of isorhamnetin-3-O-neohesperidin in Zhongtongxiao Cataplasm.Methods:To apply reformed Frans penetrating skin absorption cell marching extraorgan penetrating skin experiment.HPLC method was used to determine the content of isorhamnetin-3-Oneohesperidin in ultramicro-shatter Zhongtongxiao Cataplasm and in common Zhongtongxiao Cataplasm.Results:The Q-t equation of ultramicro-shatter Zhongtongxiao Cataplasm:Q=3.0382t+47.082,penetrating skin velocity:3.0382(?g.cm2/h);the Q-t equation of common Zhongtongxiao Cataplasm:Q=2.7967t+39.752,penetrating skin velocity:2.7967(?g.cm2/h);Extraction rate of dynamic extracting micro-powder,the ephedrina hydrochloridum,glycyrrhizic acid and glycyrrhizae glycoside were higher than the trdtional cut crude drug decocting.Conclusion:The accumulating osmolality and penetrating skin velocity of isorhamnetin-3-O-neohesperidin in ultramicro-shatter Zhongtongxiao Cataplasm were all better than those in common Zhongtongxiao Cataplasm,it explained that ultramicro-shatter technology accelerate the dissolution of medicine compsitions.

Influence of Stratum Corneum on the Percutaneous Absorption of Fluorescein Sodium Liposome in Rat Skin / 中华皮肤科杂志

Objective To study the effects of stratum corneum on the percutaneous absorption of fluorescein sodium (NaFl) liposome in rat skin. Methods Stratum corneum was stripped off by Scotch adhesive tape, and the NaFl content in the stratum corneum and the skin with no stratum corneum were detected by spectrofluorimetry at regular intervals. The dynamic permeated amount of different preparations of NaFl in the skin at different intervals in Franz diffuse cell was determined and the distribution of NaFl at 4 h after stripping off the stratum corneum was observed by fluorescence microscope. Results The concentrations of NaFl in the stratum corneum and the skin with no stratum corneum after applying liposome NaFl preparation were significantly higher than those of NaFl solution and gel preparations (P 0.05). Conclusions It is suggested that liposome can increase and change the penetration of NaFl into the stratum corneum and the skin with no stratum corneum in vitro. Hair follicular structure may not play an important role in the drug diffusion when stratum corneum is removed.

Agentes promotores de la permeación percutánea

Se presenta una panorámica sobre la diversidad de agentes potenciadores de la permeación que son utilizados en la actualidad, así como los procedimientos más frecuentemente empleados para conocer el mecanismo de acción de estas sustancias; además de realizar un recorrido por aspectos teóricos concernientes a la fisiología de la piel y la absorción percutánea. También se hace referencia a los posibles modos de acción en que estos potenciadores actúan y para concluir se mencionan algunas de las técnicas más novedosas para el mejoramiento de la difusión de sustancias activas a través de la barrera cutánea.

It is presented a panorama on the diversity of those agents that enhance permeation and are used at present, as well as on the procedures most frequently used to know the mechanism of action of these substances. The theoretical aspects concerning the skin physiology and the percutaneous absorption are also approached. Reference is made to the possible modes of action in which these enhancers act. To conclude, some of the newest techniques used to improve the diffusion of active substances through the skin barrier are mentioned.