Locust bean gum hydrogels are bioadhesive and improve indole-3-carbinol cutaneous permeation: influence of the polysaccharide concentration

Abstract The locust bean gum (LBG) is a polysaccharide with thickening, stabilizing and gelling properties and it has been used in the preparation of pharmaceutical formulations. Hydrogels (HGs) are obtained from natural or synthetic materials that present interesting properties for skin application. This study aimed to develop HGs from LBG using indole-3-carbinol (I3C) as an asset model for cutaneous application. HGs were prepared by dispersing LBG (2%, 3% and 4% w/v) directly in cold water. The formulations showed content close to 0.5 mg/g (HPLC) and pH ranging from 7.25 to 7.41 (potentiometry). The spreadability factor (parallel plate method) was inversely proportional to LBG concentration. The rheological evaluation (rotational viscometer) demonstrated a non-Newtonian pseudoplastic flow behavior (Ostwald De Weale model), which is interesting for cutaneous application. The HET-CAM evaluation showed the non-irritating characteristic of the formulations. The bioadhesive potential demonstrated bioadhesion in a concentration-dependent manner. Permeation in human skin using Franz cells showed that the highest LBG concentration improved the skin distribution profile with greater I3C amounts in the viable skin layers. The present study demonstrated the feasibility of preparing HGs with LBG and the formulation with the highest polymer concentration was the most promising to transport active ingredients through the skin.

Development of monolithic matrix type transdermal patches containing cinnarizine: Physical characterization and permeation studies

To overcome the problems associated with bioavailability and systemic side effects of the drug by oral administration, monolithic matrix type transdermal patches containing cinnarizine (CNZ) were developed. For this purpose, films based on hydroxypropyl methylcellulose and polyvinylpyrrolidone as matrix-forming polymers were designed. Physical characteristics of transdermal films and drug-excipient compatibility were investigated. Factors affecting in vitro drug release and ex vivo skin penetration and permeation of the drug were studied. It was confirmed that films displayed sufficient flexibility and mechanical strength for application onto the skin for a long time period. Ex vivo penetration experiments gave satisfactory results for transdermal drug delivery through rat skin. The parameters determining good skin penetration were also evaluated. The highest drug permeation rate was obtained with incorporation of Transcutol® (0.102 mg/cm2/h) into the base CNZ formulation, followed by propylene glycol (0.063 mg/cm2/h), menthol (0.045 mg/cm2/h), and glycerin (0.021 mg/cm2/h) as penetration enhancers (p < 0.05). As a result, the developed transdermal patches of CNZ may introduce an alternative treatment for various conditions and diseases such as idiopathic urticarial vasculitis, Ménière's disease, motion sickness, nausea, and vertigo. Thus, the risk of systemic side effects caused by the drug can be reduced or eliminated

Preparation of self-microemulsion gel drug delivery system of Carthamus tinctorius extract based on Mentha haplocalyx oil as oil phase / 中草药

Objective: To prepare the self-microemulsion gel drug delivery system of Carthamus tinctorius extract based on Mentha haplocalyx oil as oil phase. Methods: M. haplocalyx oil was used as the oil phase, and C. tinctorius extract was used as the water phase. The prescription of self-microemulsion were optimized by pseudo-ternary phase diagram, the process and prescription of gel were screened by single-factor method and the appearance, viscosity and pH value were evaluated. Result: The optimal formulation of CTE-SMEDDS-BGs was as following: F68 was the emulsifier, anhydrous ethanol was the co-emulsifier, the Km ratio was 1:1, and the total amount of emulsifier and co-emulsifier to M. plocalyx oil was 8:2, carbopol-980 was 2%, glycerin was 6%, and C. tinctorius extract was 5 mL. The CTE-SMEDDS-BGs was obtained by adding the CTE-SMEDDS into swelling gel matrix and triethylamine was used to adjust the pH to 6.0. The characteristics of appearance were yellow translucent, moderate viscosity, uniform and delicate, non-greasy, and easy to spread on the skin, the viscosity was 4.98 × 104 mPa•s (RSD was 1.53%), pH was 6.04 (RSD was 0.44%). Conclusion: The CTE- SMEDDS-BGs with M. plocalyx oil as oil phase is simple and stable, and meets the requirements of gel topical preparations.

Comparison of the effects of topical application of zoledronic acid and silver nanoparticles on osseointegration of immediate implant / 中国组织工程研究

BACKGROUND: Some studies have shown that topical application of zoledronic acid and topical application of silver nanoparticles can promote bone formation, but the difference between two methods has not been reported. OBJECTIVE: To investigate the effect of topical application of zoledronic acid versus topical application of silver nanoparticles on rabbit tooth extraction socket immediate implantation of titanium screw bonding. METHODS: Twenty-four New Zealand white rabbits were randomly divided into zoledronic acid and silver nanoparticles groups (n=12/group). After removing four incisors of the upper and lower jaws, the mixture of nanometer silver and nanometer hydroxyapatite and nanometer zoledronic acid hydroxyapatite were respectively filled in the tooth extraction pit of the two groups, and titanium screw was implanted at the same time. The isolated specimens of the upper and lower mandibles were taken at 4, 8 and 12 weeks after surgery. The data reflecting the osseointegration around the implant were obtained through gross observation, torque test, bone density test and histomorphological observation. The study was approved by the Ethical Committee of the Third Hospital of Hebei Medical University in December 2015, approval No. Z2015-021-1. RESULTS AND CONCLUSION: (1) The test results of torque mechanics showed that the average torque peak value of all titanium nails increased with the extension of time (the average value of torque peak value) and reached the maximum value at 12 weeks (the average value of torque peak value). At 4, 8 and 12 weeks after surgery, the torque peak value of titanium screw in the zoledronic acid group was higher than that in the silver nanoparticles group, and the stability of titanium screw in zoledronic acid group was better than that in silver nanoparticles group, but the difference was insignificant (P>0.05). (2) General observation and histological observation showed that at 4, 8 and 12 weeks after surgery, the hardness and structure of bone around the implants in the zoledronic acid group were significantly better than those in the silver nanoparticles group. (3) Bone mineral density analysis results showed that, at 4, 8 and 12 weeks after surgery, the gray value of bone tissue around the titanium screw in the zoledronic acid group was higher than that in the silver nanoparticles group at the same period (P>0.05). (4) These results suggest that the osseointegration of immediate implantation using nanometer zoledronic acid hydroxyapatite is better than that of the mixture of nanometer silver and nanometer hydroxyapatite.

Evaluating the ototoxicity of an anti-MRSA peptide KR-12-a2 / Avaliando a ototoxicidade de um peptídeo anti-MRSA KR-12-a2

Abstract Introduction Methicillin-resistant staphylococcus aureus is an emerging problem for the treatment of chronic suppurative otitis media, and also for pediatric tympanostomy tube otorrhea. To date, there are no effective topical antibiotic drugs to treat methicillin-resistant staphylococcus aureus otorrhea. Objective In this study, we evaluated the ototoxicity of topical KR-12-a2 solution on the cochlea when it is applied topically in the middle ear of guinea pigs. Methods The antimicrobial activity of KR-12-a2 against methicillin-resistant staphylococcus aureus strains was examined by using the inhibition zone test. Topical application of KR-12-a2 solution, gentamicin and phosphate buffered saline were applied in the middle ear of the guinea pigs after inserting ventilation tubes. Ototoxicity was assessed by auditory brainstem evoked response and scanning electron microscope examination. Results KR-12-a2 produced an inhibition zone against methicillin-resistant staphylococcus aureus from 6.25 µg. Hearing threshold in the KR-12-a2 and PBS groups were similar to that before ventilation tube insertion. However, the gentamicin group showed elevation of the hearing threshold and there were statistically significant differences compared to the phosphate buffered saline or the KR-12-a2 group. In the scanning electron microscope findings, the KR-12-a2 group showed intact outer hair cells. However, the gentamicin group showed total loss of outer hair cells. In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. Conclusion In our experiment, topically applied KR-12-a2 solution did not cause hearing loss or cochlear damage in guinea pigs. The KR-12-a2 solution can be used as ototopical drops for treating methicillin-resistant staphylococcus aureus otorrhea; however, further evaluations, such as the definition of optimal concentration and combination, are necessary.

Resumo Introdução O staphylococcus aureus resistente à meticilina é um problema emergente não só para a otite média supurativa crônica, mas também para casos de otorreia crônica em crianças com tubo de ventilação. Até o momento, não há antibióticos tópicos efetivos para a otorreia causada por staphylococcus aureus resistente à meticilina. Objetivo Nesse estudo, avaliamos a ototoxicidade da solução tópica de KR-12-a2 na cóclea quando aplicada topicamente na orelha média de cobaias. Método A atividade antimicrobiana de KR-12-a2 contra cepas de staphylococcus aureus resistente à meticilina foi avaliada utilizando-se o teste de zona de inibição de crescimento. Foram aplicados na orelhas médias de 3 grupos de cobaias, ou solução tópica de KR-12-a2, ou gentamicina ou solução salina tamponada com fosfato após timpanostomia. A ototoxicidade foi avaliada através do exame auditivo de potencial evocado auditivo de tronco encefálico e por microscopia eletrônica de varredura. Resultados O KR-12-a2 produziu uma zona de inibição contra o staphylococcus aureus resistente à meticilina a partir de 6,25 µg. Alterações do limiar de audição no grupo KR-12-a2 e no grupo com solução salina foram semelhantes aos observados antes da inserção do tubo de ventilação. No entanto, o grupo gentamicina apresentou um limiar auditivo mais elevado, estatisticamente significativo em comparação ao grupo solução salina ou ao grupo KR-12-a2. Nos achados da microscopia eletrônica, o grupo KR-12-a2 apresentou células ciliadas externas intactas. No entanto, o grupo gentamicina apresentou perda total das células ciliadas externas. Em nosso experimento, a solução de KR-12-a2 aplicada topicamente não causou perda auditiva ou dano coclear em cobaias. Conclusão Em nosso experimento, a solução de KR-12-a2 aplicada topicamente não causou perda auditiva ou dano coclear em cobaias. A solução de KR-12-a2 pode ser utilizada como gotas otológicas para o tratamento da otorreia causada por staphylococcus aureus resistente à meticilina; no entanto, são necessárias outras avaliações, para a definição da concentração e das associações ideais.

Randomized controlled trial to compare oral analgesic requirements and patient satisfaction in using oral non-steroidal anti-inflammatory drugs versus benzydamine hydrochloride oral rinses after mandibular third molar extraction: a pilot study

BACKGROUND: Third molar extraction is associated with considerable pain and discomfort, which is mostly managed with oral analgesic medication. We assessed the analgesic effect of benzydamine hydrochloride, a topical analgesic oral rinse, for controlling postoperative pain following third molar extraction. METHODS: A randomized controlled trial was conducted in 40 patients divided into two groups, for extraction of fully erupted third molar. Groups A received benzydamine hydrochloride mouthwash and group B received normal saline gargle with oral ibuprofen and paracetamol. Oral ibuprofen and paracetamol was the rescue analgesic drug in group A. Patients were evaluated on the 3(rd) and 7(th) post-operative days (POD) for pain using the visual analogue score (VAS), trismus, total number of analgesics consumed, and satisfaction level of patients. RESULTS: The VAS in groups A and B on POD3 and POD7 was 4.55 ± 2.54 and 3.95 ± 1.8, and 1.2 ± 1.64 and 0.95 ± 1.14, respectively and was statistically insignificant. The number of analgesics consumed in groups A and B on POD3 (5.25 ± 2.22 and 6.05 ± 2.43) was not statistically different from that consumed on POD7 (9.15 ± 5.93 and 10.65 ± 6.46). The p values for trismus on POD3 and POD7 were 0.609 and 0.490, respectively and those for patient satisfaction level on POD3 and POD7 were 0.283 and 0.217, respectively. CONCLUSIONS: Benzydamine hydrochloride oral rinses do not significantly reduce intake of oral analgesics and are inadequate for pain relief following mandibular third molar extraction.

Activity-guided isolation and identification of anti-staphylococcal components from Senecio tenuifolius Burm. F. leaf extracts

<p><b>OBJECTIVE</b>To investigate activity-guided isolation and identification of anti-Staphylococcus aures components from Senecio tenuifolius Burm. F. (S. tenuifolius).</p><p><b>METHODS</b>Hexane, chloroform, ethyl acetate, methanol and aqueous extracts of S. tenuifolius were prepared by soxilation for antimicrobial activity against one registered Staphylococcus aureus (S. aureus) (ATCC No: 25923) and two clinical isolates, methicillin resistant and methicillin sensitive S. aureus. NCCL standard methods were followed for antibacterial activity. GC-MS was performed to identify the chemical composition of bio active fraction.</p><p><b>RESULTS</b>Among all solvent extracts, methanol extract significantly reduced the growth of S. aureus (ATCC No: 25923), methicillin resistant and methicillin sensitive S. aureus with the best zone of inhibition at 16.23, 14.06 and 15.23 mm and minimum inhibition concentration (MIC) values at 426.16, 683.22 and 512.12 µg/mL, respectively. In order to detect the active component in methanol extract, it was further purified by column chromatography, which yielded four fractions (St1, St2, St3, and St4). Among these four fractions, St3 was effective against the tested strains of S. aures, with the best zone of inhibition at 15.09, 13.25 and 14.12 mm and with best MIC values at 88.16, 128.11 and 116.12 µg/mL, respectively. Effective fraction partially purified from S. tenuifolius (St3) yielded MIC's that were at least 20 fold less when compared to crude extract. GC-MS analysis of St3 revealed the presence of 3-[methyl-6,7-dihydro benzofuran-4 (5H)-one], 1,2-benzenedicarboxylic acid, hydroquinone, methyl ester and 3 unknown compounds.</p><p><b>CONCLUSIONS</b>The study provides scientific evidence for traditional and folklore medicinal use of S. tenuifolius in skin infections treatment.</p>

Activity-guided isolation and identification of anti-staphylococcal components from Senecio tenuifolius Burm. F. leaf extracts

Objective: To investigate activity-guided isolation and identification of anti-Staphylococcus aures components from Senecio tenuifolius Burm. F. (S. tenuifolius). Methods: Hexane, chloroform, ethyl acetate, methanol and aqueous extracts of S. tenuifolius were prepared by soxilation for antimicrobial activity against one registered Staphylococcus aureus (S. aureus) (ATCC No: 25923) and two clinical isolates, methicillin resistant and methicillin sensitive S. aureus. NCCL standard methods were followed for antibacterial activity. GC-MS was performed to identify the chemical composition of bio active fraction. Results:Among all solvent extracts, methanol extract significantly reduced the growth of S. aureus (ATCC No: 25923), methicillin resistant and methicillin sensitive S. aureus with the best zone of inhibition at 16.23, 14.06 and 15.23 mm and minimum inhibition concentration (MIC) values at 426.16, 683.22 and 512.12 μg/mL, respectively. In order to detect the active component in methanol extract, it was further purified by column chromatography, which yielded four fractions (St1, St2, St3, and St4). Among these four fractions, St3 was effective against the tested strains of S. aures, with the best zone of inhibition at 15.09, 13.25 and 14.12 mm and with best MIC values at 88.16, 128.11 and 116.12 μg/mL, respectively. Effective fraction partially purified from S. tenuifolius (St3) yielded MIC’s that were at least 20 fold less when compared to crude extract. GC-MS analysis of St3 revealed the presence of 3-[methyl-6,7-dihydro benzofuran-4 (5H)-one], 1,2-benzenedicarboxylic acid, hydroquinone, methyl ester and 3 unknown compounds. Conclusions:The study provides scientific evidence for traditional and folklore medicinal use of S. tenuifolius in skin infections treatment.

Chlorhexidine allergy due to topical application.

Chlorhexidine is commonly used in dentistry in various forms. Allergic reactions to chlorhexidine of both immediate and delayed type have been reported. Although the incidence is low there may be severe manifestations in some patients. This report presents a case of allergy to chlorhexidine following topical application.

A comparative study of the effects of topical application of Aloe vera, thyroid hormone and silver sulfadiazine on skin wounds in Wistar rats / 한국실험동물학회지

Many research studies report the healing effects of Aloe Vera, thyroid hormone cream and silver sulfadiazine. However, the effects of these therapeutic agents are not well understood and have not been compared in one study. This study aimed at investigating the effects of topical application of an Aloe vera gel, a thyroid hormone cream and a silver sulfadiazine cream on the healing of skin wounds surgically induced in Wistar rats for determining the treatment of choice. In a randomized controlled trial, twelve male rats, aged 120 days and with a mean weight of 250 to 300 g, were divided randomly into 5 groups based on drug treatments: Aloe vera gel (AV), thyroid hormone cream (TC), silver sulfadiazine 1% (S), vehicle (V) and control. To evaluate the efficacy of each treatment technique, a biomechanical approach was used to assess tensile stress after 14 days of treatment. Tensile stress was significantly improved in the Aloe vera gel group as compared with the other four groups (P< or =0.05). While the other treatment options resulted in better healing than the control group, this difference was not significant. We conclude that Aloe vera topical application accelerated the healing process more than thyroid hormone, silver sulfadiazine and vehicle in surgically induced incisions in rats.

A Pilot Study on the Use of Complementary and Alternative Medicine for Androgenetic Alopecia / 대한피부과학회지

BACKGROUND: Use of treatments categorized as complementary and alternative medicine (CAM) have increased considerably in the field of dermatology. However, most studies have been focused on atopic dermatitis and psoriasis, and little is known of the prevalence of use of CAM in patients with androgenetic alopecia (AGA). OBJECTIVE: We aimed to determine the frequency, type, duration, and factors associated with the use of CAM in the treatment of AGA at a dermatologic outpatient clinic. METHODS: AGA patients at the outpatient clinic (n=151) received a face-to-face structured questionnaire covering 5 types of CAM plus an open alternative labeled 'other type'. RESULTS: Overall 70.2% (106/151) of the subjects with AGA reported the current or previous use of at least 1 CAM. Topical application (85, 56.3%) was most frequently used, followed by diet therapy (35, 23.2%), health food supplements (15, 9.9%), massage therapy (13, 8.6%), and Oriental medicine (10, 6.6%). With respect to the reasons for using CAM, 'recommendation by people around the patient' (59.4%) was most commonly chosen by the patients. The subjective therapeutic effect and satisfaction with CAM were the best with health food supplements and topical application (80.0% and 21.1%, respectively). CONCLUSION: As our results indicate that the use of CAM continues to rise by patients with AGA, the need for reliable sources of information about specific CAM therapies becomes more essential. To assist AGA patients in selecting proper treatment modalities, further longitudinal and controlled studies are required to assess the efficacy and safety of CAM.

Estudio histológico del proceso de reparación alveolar después de la aplicación tópica de la solución anestésica prilocaína 3 por ciento con felipresina 003 UI/ML / Histological study of alveolar repair process after topical application of the anesthetic solution with 3 percent prilocaine Felypressin 0.03 IU / ML

El objetivo de este estudio fue evaluar la influencia de una solución anestésica, compuesta por Prilocaina 3% y felipresina 0,03 UI/ml, y el efecto que tiene sobre el proceso de reparación alveolar en ratones después de una exodoncia. Este estudio fue aprobado por el Comité de Etica en Investigación del Programa de Maestría de Cirugía y Traumatologia Bucomaxilofacial de la Universidad de Marilia (UNIMAR) Marília, São Paulo, Brasil. Este estudio fue de tipo experimental, aleatorio controlado, con análisis bifactorial (grupo control en relación al grupo experimental, en función de los tiempos operatorios (2X4)). Se utilizaron 32 ratones (Rattus norvegicus, albinus, Wistar), machos, adultos, pesando entre 280 y 320 gramos. Los animales fueron distribuidos de la siguiente forma: 16 especímenes fueron seleccionados para grupo control (Grupo I), no recibieron ningún tratamiento adicional después de la extracción del incisivo superior derecho; los otros 16 especímenes restantes, después de la exodoncia, un área de la herida quirúrgica fue tamponada con gasa embebida en la solución anestésica de Citocaína 3%® (Clorhidrato de Prilocaína 3% con Felipresina 0,03 UI/ml), y conformaron el grupo experimental (Grupo II). Los animales sufrieron eutanasia transcurridos los períodos de 3, 7, 15, 24 días post operatorios. Através del análisis histológico y con base en la metodología desarrollada, nos permitió concluir que la solución anestésica de Citocaína 3%® aplicada con compresas de gasa sobre la herida quirúrgica post-extracción dentaria, produjo eventos tisulares que comprometieron los principios básicos responsables por la regeneración del epitelio de la mucosa gingival y por el proceso de reparación alveolar. Se observó que en todos los períodos post operatorios estudiados y cuando se compararon los dos Grupos, se confirmó que el Grupo I presentó mejores resultados en relación al proceso de reparación alveolar

O objetivo deste estudo foi avaliar a influência da solução anestésica, composta por Prilocaína 3% com felipressina 0,03 UI/ml, sobre o processo de reparación alveolar em ratos, após a extração dental. O presente estudo foi previamente aprovado pelo comitê de ética em pesquisa do Programa de Mestrado em Cirurgia e Traumatologia Buço-maxilo-faciais da Universidade de Marília (UNIMAR), Marília, São Paulo, Brasil. Tratou-se de um estudo do tipo experimental, aleatório controlado, com análise bifatorial (grupo controle em relação ao grupo experimental, em função dos tempos operatórios (2x4)). Utilizou-se 32 ratos (Rattus norvegicus, albinus, Wistar), machos, adultos, pesando entre 280 e 320 gramas. Os animais foram distribuídos da seguinte forma: 16 espécimes foram selecionados para o grupo controle (Grupo I), não receberam nenhum tratamento adicional após a extração do incisivo superior direito; os outros 16 espécimes restantes, depois da exodontia, a área da ferida cirúrgica foi tamponada com gaze embebida em solução anestésica de Citocaína 3%® (Prilocaína 3% com Felipressina 0,03 UI/ml), e formaram o grupo experimental (Grupo II). Os animais sofreram eutanásia após decorrido os períodos de 3, 7, 15, 24 dias pós-operatórios. Através da análise histológica e com base na metodologia aplicada, permitiu-nos concluir que a solução de Citocaína 3%® aplicada com compressas de gaze sobre a ferida cirúrgica após extração dentária, produz eventos teciduais que comprometeram os princípios básicos responsáveis pela regeneração do epitélio da mucosa gengival e o processo de reparação alveolar em ratos. Observou-se que em todos os períodos pós-operatórios estudados e quando se compararam os dois Grupos, confirmou-se que o Grupo I apresentou melhores resultados em relação ao processo de reparo alveolar

The aim of this study was to evaluate the local anesthetic solution, composed by Prilocaine 3% and felipressin 0,03 UI/ml, influence on the alveolar repair process in rats after dental extraction. This research was previously approved by the Ethic Committee in Research of the Masters Degree Program in Oral and Maxillofacial Surgery of the Marília University (UNIMAR), Marília, São Paulo, Brazil. It was an experimental, randomly controlled study, with bifactorial analysis (group control versus experimental group, in function of the postoperative times (2 X 4)). For the accomplishment of this study 32 rats were used (Rattus norvegicus, albinus, Wistar), males, adults, weighing between 280 and 320 grams. The animals were selected and divided into Group I (control) and Group II (Citocain 3%® - Prilocaine 3% with felipressin 0,03UI/ml) with 16 rats each; being four animals of the Group I and four of the Group II, destined to the euthanasia in the postoperative periods of 3rd, 7th, 15th and 24th days. The histological analysis with base in the developed methodology, allowed us to conclude that the anesthetic solution of Citocain 3%® applied with gauze compress on the surgical dental wound, produced tissue events that committed the basic biological principles, that are responsible for the regeneration of the gingival epithelium and the alveolar process repair in rats. The Group I presented better results in the alveolar repair when compared to the Group II

Efecto de la Aplicación Tópica de una Solución Comercial de Amitraz sobre el Cronotropismo y Dromotropismo Cardiacos en Ratas Anestesiadas y Perros Conscientes / Effect of a Topical Application of Amitraz Solution on Cardiac Chronotropism and Dromotropism in Anesthetized Rats and Conscious Dogs

El amitraz es una formamidina usada como ectoparasiticida en Medicina Veterinaria. Su toxicidad intravenosa y oral ha sido reportada, aunque su prescripción se fundamenta en aplicaciones tópicas. Esta investigación evaluó los efectos cronotrópicos y dromotrópicos de la aplicación tópica de amitraz (12% v/v; 4mL/L) en ratas anestesiadas con pentobarbital sódico y en perros conscientes. Se usaron 16 ratas y 12 perros, los cuales se sometieron a un electrocardiograma (ECG) control. Subsecuentemente, a 16 ratas se les aplicó amitraz en baño de inmersión por 2 min y a 12 perros se les aplicó baños de aspersión. Posteriormente, se registraron dos ECGs consecutivos cada 30 min, durante 1 h. Como indicadores de cronotropismo y dromotropismo, se usaron la frecuencia cardiaca (FC) y el intervalo P-R, respectivamente. La FC en ratas fue reducida (control: 265,7±12,1 lat/min vs amitraz: 234, 4±13,8 lat/min) a los 30 min del baño con amitraz, alcanzando diferencias significativas (P<0,05), a los 60 min (225,0±13,6 lat/min). Se prolongó el intervalo P-R (control: 54,3±2,0 mseg vs amitraz: 67,9±2,4 mseg) (P<0,05) a los 30 min y 60 min (72,1±2,8 mseg), respectivamente. En contraste, no se observaron cambios significativos en la FC e intervalo P-R en perros. Los efectos cronotrópicos y dromotrópicos negativos observados en ratas, podrían reflejar una acción agonista a2-adrenérgica presináptica en el sistema nervioso central, con la consecuente reducción del tono simpático, sin descartar una acción parasimpaticomimética. Posiblemente, la absorción cutánea del amitraz en caninos, sería incapaz de desarrollar estos efectos. En caninos sin premedicación, pudieran desarrollarse respuestas autonómicas reflejas capaces de regular un posible efecto del amitraz sobre las variables estudiadas. Las dosis terapéuticas de amitraz, no produjeron cambios en el ECG de caninos aparentemente sanos. Se requieren experimentos adicionales para esclarecer si dosis superiores en aplicación tópica actúan en forma similar en perros con lesiones de piel producidas por ácaros o garrapatas.

Amitraz is a diamidine molecule widely used as an ectoparasiticide in Veterinary Medicine. Although amitraz is prescribed as a topical treatment, its toxicity has been reported in oral and intravenous administration. This investigation assessed the potential chronotropic and dromotropic effects of topical amitraz (12% v/v; 4mL/L) in anesthetized rats and conscious dogs. Sixteen rats and twelve dogs were used. Before treatment, body surface was moistened with water and all animals were subjected to a baseline electrocardiogram (ECG). Subsequently, amitraz was applied to rats (n=16) as an immersion bath for 2 min, or as a spray application to dogs (n=12), respectively. Two consecutive ECGs were recorded at 30 min interval for 1 h. The heart rate (HR) and the P-R intervals were calculated to estimate chronotropism and dromotropism, respectively. The HR of rats was reduced (control: 265.7±12.1 beats/min vs amitraz: 234.4±13.8 beats/min) at 30 min after amitraz application, reaching a significant (P<0,05) value at 60 min (225.0±13.6 beats/min). The P-R interval was significantly (P<0.05) prolonged at 30 min (control: 54.3±2.0 msec vs amitraz: 67.9±2.4 msec) and 60 min (72.1±2.8 msec), respectively. In contrast, no significant changes in HR and P-R interval were found in dogs treated with amitraz. The negative chronotropic and dromotropic effects observed in rats may reflect the activation of pre-synaptic a2-adrenoceptors in the central nervous system and a reduction in the sympathetic outflow, without excluding a potential parasympatomimetic effect. The lack of these effects in dogs might be related either to reduced skin absorption or to a potential autonomic regulatory reflex in conscious dogs. The therapeutic dose of amitraz used herein did not modify the ECG in apparently healthy dogs. Further experiments are required to establish the effects of higher topical doses in dogs suffering from skin diseases related to mites or ticks infestations.

The Effect of Topical Application of Heparin with Microneedling on Skin Flap Survival

PURPOSE: The objective of this study is to evaluate the heparin effect for a viability of random-pattern dorsal flap in hairless mouse. METHODS: A caudally-based random dorsal flap, measuring 1.5 x 5 m, was designed and heparin was applied topically after microneedling. Twenty five male hairless mice were randomly divided into five groups: control (Group 1, n=5); received only microneedling (Group 2, n=5), only heparin (Group 3, n=5), microneedling with saline (Group 4, n=5), and microneedling with heparin group (group 5, n=5) to the flap during 7 days. The number of the capillaries were compared between the experimental groups and control group with respect to neovascularization after heparin application using imaging analysis program under hematoxylin-eosin stain. The capillary blood flow was measured by laser Doppler flowmetry. After seven days each animal was evaluatedfor the percentage area of the flap survival. Mann- Whitnety U test and Kruskal-Wallis statistical analysis of survival relationships was performed. RESULTS: It can be observed increased number of the blood vessels in the experimental groups however it was not statistically significant. Blood flow of the haparin with microneedling group maintained higher than other experimental groups. Treated microneedling and heparin mice were significantly better flap viability than in controls (flap survival 67% and 54.4 mm2 respectively; p< 0.01). Positive correlation was shown between flap survival rate and laser Doppler flux value only at first day after surgery. CONCLUSION: Heparin has a beneficial effect on capillary flow and improve peripheral circulatory disturbances in random pattern flaps.

Effect of topical application with warm and wet carthamus tinctorius alcohol and anisodaminum on phlebitis caused by mannitol injection / 中国实用护理杂志

Objective To observe the effect of topical application with warm and wet carthamus tinctorius alcohol and anisodaminum on phlebitis caused by mannitol injection. Methods 100 patients with fractured bones suffered from phlebitis caused by mannitol injection were randomized into the observation group and the control group with 50 cases in each group. The observation group adopted topical application with warm and wet carthamus tinctorius alcohol and anisodaminum while the control received external application of 50% magnesium sulfate. The dosage was 3 hours per time,2 times a day, one time in the morning and afternoon respectively. The treatment continued till the phlebitis disappeared and the effect at the 24th,48th and 72th post treatment was compared between the two groups. Results The effect at the above mentioned time points in the obsevation group was superior to that of the control group(P＜0.05).Conclusion Topical application with warm and wet carthamus tinctorius alcohol and anisodaminum on phlebitis caused by mannitol injection proved to be safe and had no adverse effect.

Clinical Study of Chinese Medicine by Oral and Topical Application in Treating Elderly Herpes Zoster / 中国中医药信息杂志

Objective To observe the therapeutic effect of Chinese medicine in treating elderly herpes zoster, and study the clinical evaluation of the treatment with Chinese medicine from evidence-based medicine (EBM) view. Methods All the 156 elderly patients diagnosed with herpes zoster were randomly divided into treatment group (78) and control group (78). The former group was administered with Chinese medicine by oral administration and topical application, while the latter took aciclovir alone. All the case were treated for 10 days. Results The overall response rates of Chinese medicine and aciclovir in treatment herpes zoster were respectively 98.70% and 84.62% (P

Preparation of cyclosporin A polylactic acid microsphere for topical application / 医学研究生学报

Objective:To prepare the cyclosporin A(CsA) polylactic acid microspheres using solvent evaporation method from an oil-in-water system.Methods:Orthogonal experiment was used to optimize the method of CsA polylactic acid microspheres preparation.The microspheres were characterized for drug loading and entrapment efficiency by high-performance liquid chromatography(HPLC),average size by particle size analyser and surface morphology by scanning electron microscopy(SEM).In vitro the release kinetics were studied using a modified dialysis method.Results:SEM studies showed discrete and spherical particles with smooth surfaces.The average particle size was 18.234 ?m,with more than 80% of the microspheres falling in the range of 9.525-32.400 ?m.The drug loadings ranging was(34.51?0.63)% with a high encapsulation efficiency(86.12?0.77)% determined by HPLC.In vitro release study revealed a profile of sustained release of CsA from CsA-PLA-MS.The accumulated release percentage of CsA microspheres were 40.8% in 30 d.CsA release profiles show CsA release could be divided by two different phases,fast release within the first few days and the subsequent sustained release.Conclusion:CsA polylactic acid microspheres have been successfully prepared and sustained release of CsA from microspheres have been achieved.

The Effect of Topical Application of Capsaicin on the Flap Survival

Capsaicin is the principal pungent component of Capsicum fruits. Biological effect of capsaicin is various and complicated. This study was undertaken to define the effect of topical application of capsaicin on flap survival in rat. Fourty Sprague Dawley rats were divided into four groups. With ten rats in each group, group A was only flap elevation group, as the control, group B was applied 0.025% capsaicin ointment for 7 days after skin flap elevation, group C was applied 0.075% capsaicin ointment for 7 days after skin flap elevation, group D was elevated two skin flap and one flap was control, the other flap was applied 0.075% capsaicin ointment for 7 days. Group A demonstrate 46.2+ 2.5% flap survival rate. Group B demonstrate 48.8+/-7.8% of flap survival rate, group C demonstrate 53.3+/-7.0% of flap survival rate. Control flap on group D demonstrate 43.5+/-3.5% of flap survival rate, 0.075% capsaicin applied flap demonstrate 52.9+/-7.2% of flap survival rate. Compared to the control group, increase in survival rate in group B was not statistically significant. The mean flap survival rate in group C was significantly increased than control group (p < 0.05). Compared to the control flap in group D, 0.075% capsaicin applied flap showed significantly higher flap survival rate. Based upon this data, local application of 0.075% capsaicin ointment demonstrate significantly increased value of survival area and survival rate on skin flap in rat (p < 0.05). And further studies may be needed for the evaluation of correct action mechanisms of capsaicin.

Alpha Receptor Stimulation by Norepinephrine and Blockade by Benoxathian in spinal Pial Arteries of Rabbit

The effect of norepinephrine and benoxathian on the diameter of spinal pial arteries in rabbits was studied by topical microapplication of the drug to the perivascular environment. Arterial diameter was determined with the micrometer eyepiece on operating microscope through laminectomized area. Physiological parameters(PaO2, PaCO2, blood pH, and systolic blood pressure) were not significantly changed during all experiments. The results of this study are summerized as follow. 1) Application of norepinephrine over the range of 5x10(-8)M to 5x10(-3)M to spinal pial arteries resulted in significant constriction which were shown to be proportional to concentration, with exception of 5x10(-8)M. The dose response curve showed constriction of 30.5+/-7.1% at 5x10(-3)M. 2) Benoxathian produced the vasodilatation which were shown to be proportional to concentration. The dose response curve showed vasodilatation of 21.4+/-4.4% at 5x10(-3)M 3) The vasoconstriction due to microapplication of norepinephrine was prevented by the inclusion of an equimolar concentration of the alpha-adrenergic receptor blocker, benoxathian. 4) The vasoconstriction due to norepinephrine was present in the concentration of norepinephrine more than that of benoxathian, and the vasoconstriction was proportional to the concentration of norepinephrine. The results indicate that alpha-adrenergic receptor is present in the smooth muscle of spinal pial arteries for the sympathetic control of blood flow to the spinal cord.

Somatosensory Evoked Potential (SEP) and Effect of SS-cream on rabbit / 대한비뇨기과학회지

The cause of premature ejaculation (PE) has been thought to be psychological in the majority of patients but we have suggested hyperexcitability of the ejaculatory center for an organic basis of premature ejaculation, SS-cream is a topical agent containing 9 oriental herbs for treating PE. Therefore, in order to determine the effects of SS-cream on the excitability of the ejaculation center, we investigated somatosensory evoked potential (SEP) stimulated at glans penis and its effect of SS-cream on rabbits. 30 rabbits were randomly divided into two groups. Group A (n=15) was used as control, and Group B (n=15) was used with the application of SS-cream (0.1gm) on the glans penis. SEP were monitored every 30 minutes in all rabbits. Electrical stimulation was done on the glans penis with surface electrode. The latencies and amplitudes were recorded at Cz and Fz. EEG system. Throughout the studies SEP was reproducible in all rabbit, which were not significantly changed throughout the procedures. The mean latency and amplitude of SEP in control was 20.83+/-0.79msec and 2.13+/-0.10uV. After the topical application of SS-cream on the glans penis, the mean latency was prolonged and the mean amplitude was reduced significantly (p<0.001). With these results, we suggest that SS-cream with the application on the glans penis prolongs the latency and reduces the amplitude from the glans penis in the rabbit, that is, the effect of SS-cream in the treatment of premature ejaculation is testing the ejaculatory reflex from the glans penis.