Efficacy and safety evaluation of three medicated eye patches in Demodex blepharitis: a multicenter, double-blind, randomized controlled clinical trial / 中华实验眼科杂志

Objective:To evaluate and compare the clinical efficacy and safety of three different medicated eye patches in the treatment of Demodex blepharitis. Methods:A multicenter, randomized, double-blind, parallel-controlled clinical trial was conducted.A total of 140 patients (280 eyes) with Demodex blepharitis were recruited in Shanghai Jing'an District Shibei Hospital, Xi'an Fourth Hospital and Kunming First People's Hospital from July 2021 to December 2022.The affected eyes were randomly divided into tea tree oil group, okra oil group, basal fluid control group and metronidazole group by the random number table method.Eye patches containing 20% tea tree oil, 1% okra oil, prepared base solution and 2% metronidazole were applied to the eyes for 28 days by the double-blind method.The count of Demodex was evaluated before treatment and on days 14 and 28 of treatment.Ocular surface symptoms were scored according to Ocular Surface Disease Index (OSDI). The degree of congestion at the eyelid margin and cylindrical dandruff at the root of eyelashes were scored under a slit lamp microscope.The effective rate was calculated according to the comprehensive scores above, and the adverse reactions of the subjects were observed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Jing'an District Shibei Hospital (No.YL-20200320-05). All the subjects were informed of the significance, purpose and method of the study.Written informed consent was obtained from each subject before any medical examination. Results:All subjects completed the treatment and follow-up, and the loss to follow-up rate was 0%.After 14 and 28 days of treatment, the Demodex count was significantly decreased in all groups compared with before treatment (all at P<0.05). After 28 days of treatment, the number of Demodex in tea tree oil group, okra oil group and metronidazole group were significantly lower than that in basal fluid control group, with statistically significant differences (all at P<0.05). The OSDI score, palpebral margin congestion score and cylindrical dandruff score on 14 and 28 days after treatment in tea tree oil group, okra oil group and metronidazole group were significantly lower than before treatment, showing statistically significant differences (all at P<0.05). After 28 days of treatment, the effective rates of tea tree oil group, okra oil group and metronidazole group were 71.4%, 71.4% and 62.9%, respectively, which were significantly higher than 25.7% in basal solution control group.No serious local or systemic adverse reactions were found during the treatment and follow-up. Conclusions:Eye patches containing tea tree oil, okra oil and metronidazole have significant effects on the treatment of Demodex blepharitis, which can improve the biological environment of the palpebral margin and eliminate the inflammation related to blepharitis.

Purpurolide C-based microneedle promotes macrophage-mediated diabetic wound healing via inhibiting TLR4-MD2 dimerization and MYD88 phosphorylation

Delayed wound healing in diabetes is a global challenge, and the development of related drugs is a clinical problem to be solved. In this study, purpurolide C (PC), a small-molecule secondary metabolite of the endophytic fungus Penicillium purpurogenum, was found to promote diabetic wound healing. To investigate the key regulation targets of PC, in vitro RNA-seq, molecular docking calculations, TLR4-MD2 dimerization SDS-PAGE detection, and surface plasmon resonance (SPR) were performed, indicating that PC inhibited inflammatory macrophage activation by inhibiting both TLR4-MD2 dimerization and MYD88 phosphorylation. Tlr4 knockout in vivo attenuated the promotion effect of PC on wound healing. Furthermore, a delivery system consisting of macrophage liposome and GelMA-based microneedle patches combined with PC (PC@MLIP MN) was developed, which overcame the poor water solubility and weak skin permeability of PC, so that successfully punctured the skin and delivered PC to local tissues, and accurately regulated macrophage polarization in diabetic wound management. Overall, PC is an anti-inflammatory small molecule compound with a well-defined structure and dual-target regulation, and the PC@MLIP MN is a promising novel biomaterial for the management of diabetic wound.

Comparison on Skin Permeability of Corydalis Rhizoma Total Alkaloid Patches at Shenque Acupoint and Non-acupoint Administration / 中国实验方剂学杂志

ObjectiveTo compare the differences in resistance and structure of skin between acupoints and non-acupoints， and to study the difference in skin permeability characteristics of Corydalis Rhizoma total alkaloid patches （CTTP） after administration at Shenque acupoint and non-acupoint， so as to provide experimental support for its clinical acupoint application to prevent and treat chronic pain. MethodTaking corydaline （CD）， tetrahydropalmatine （THP） and corydalis L （CDL） as evaluation indexes， and the quantitative analysis was carried out by high performance liquid chromatography （HPLC）. The mobile phase was methanol-0.04 mol·L-1 phosphoric acid aqueous solution （70∶30， pH 6.0 adjusted with triethylamine）， the detection wavelength was 281 nm. In vitro transdermal test in Franz diffusion cell and in vivo transdermal test were used to study the skin permeability characteristics of CTTP through Shenque acupoint and non-acupoint administration. At the same time， the skin resistance between Shenque acupoint and non-acupoint was measured before and after the administration， and the distribution of the drug in each layer of the skin was compared by freezing sectioning， and visual verification was performed with fluorescence inverted microscope. ResultAfter 24 h of administration， the results of in vivo and in vitro experiments showed that the cumulative permeation and retention of CD， THP and CDL at Shenque acupoint skin were higher than those at non-acupoint skin （P<0.05， P<0.01）， the skin resistance of Shenque acupoint was lower than that of non-acupoint at all time points. The fluorescence microscopic observation results showed that the drug content of each layer of the skin was all Shenque acupoint>non-acupoint， indicating that the skin of Shenque acupoint had better effect on drug penetration and storage than non-acupoint. ConclusionThe 24 h cumulative permeation and retention of CTTP in Shenque acupoint skin are higher than those in non-acupoint skin， and the mechanism may be related to the thin skin， low electrical resistance and large number of hair follicle bodies at Shenque acupoint.

Comparison on Skin Permeability of Corydalis Rhizoma Total Alkaloid Patches at Shenque Acupoint and Non-acupoint Administration / 中国实验方剂学杂志

ObjectiveTo compare the differences in resistance and structure of skin between acupoints and non-acupoints， and to study the difference in skin permeability characteristics of Corydalis Rhizoma total alkaloid patches （CTTP） after administration at Shenque acupoint and non-acupoint， so as to provide experimental support for its clinical acupoint application to prevent and treat chronic pain. MethodTaking corydaline （CD）， tetrahydropalmatine （THP） and corydalis L （CDL） as evaluation indexes， and the quantitative analysis was carried out by high performance liquid chromatography （HPLC）. The mobile phase was methanol-0.04 mol·L-1 phosphoric acid aqueous solution （70∶30， pH 6.0 adjusted with triethylamine）， the detection wavelength was 281 nm. In vitro transdermal test in Franz diffusion cell and in vivo transdermal test were used to study the skin permeability characteristics of CTTP through Shenque acupoint and non-acupoint administration. At the same time， the skin resistance between Shenque acupoint and non-acupoint was measured before and after the administration， and the distribution of the drug in each layer of the skin was compared by freezing sectioning， and visual verification was performed with fluorescence inverted microscope. ResultAfter 24 h of administration， the results of in vivo and in vitro experiments showed that the cumulative permeation and retention of CD， THP and CDL at Shenque acupoint skin were higher than those at non-acupoint skin （P<0.05， P<0.01）， the skin resistance of Shenque acupoint was lower than that of non-acupoint at all time points. The fluorescence microscopic observation results showed that the drug content of each layer of the skin was all Shenque acupoint>non-acupoint， indicating that the skin of Shenque acupoint had better effect on drug penetration and storage than non-acupoint. ConclusionThe 24 h cumulative permeation and retention of CTTP in Shenque acupoint skin are higher than those in non-acupoint skin， and the mechanism may be related to the thin skin， low electrical resistance and large number of hair follicle bodies at Shenque acupoint.

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

Dolor neuropático localizado / Localized neuropathic pain

Resumen El dolor neuropático localizado (DNL) es de origen periférico y se caracteriza por áreas circunscritas de dolor con sensibilidad anormal de la piel o síntomas espontáneos característicos de dolor neuropático, por ejemplo, dolor urente. Se debe resaltar que el DNL está confinado a un área específica no mayor a una hoja de papel tamaño carta. El DNL representa 60 % de las condiciones de dolor neuropático. No existe una única etiología. El abordaje diagnóstico es similar al de otros síndromes dolorosos neuropáticos. Se utilizan herramientas diagnósticas generales para evaluar las características clínicas. En la actualidad no existen guías específicas de manejo del DNL, por lo que se utilizan las guías para dolor neuropático en general. En las guías de la Sociedad Canadiense de Dolor se incluyen los tratamientos tópicos como parte de las estrategias de segunda línea. Pese a la falta de guías, los parches de lidocaína a 5 % y los parches de capsaicina a 8 % han demostrado ser efectivos en modelos de DNL.

Abstract Localized neuropathic pain (LNP) is of peripheral origin and is characterized by circumscribed areas of pain with abnormal skin sensitivity or spontaneous symptoms that are characteristic of neuropathic pain, e.g. burning pain. It should be noted that LNP is confined to a specific area no larger than a letter size sheet of paper. LNP accounts for 60 % of neuropathic pain conditions. There is no single etiology of LNP. The diagnostic approach is similar to that for other neuropathic pain syndromes. General diagnostic tools are used to assess clinical features. So far, there are no specific guidelines for the management of LNP; for this reason, guidelines for general neuropathic pain are used. Topical treatments are included as part of second-line strategies in the Canadian Pain Society guidelines. Despite the lack of guidelines, 5 % lidocaine patches and 8 % capsaicin patches have been proven effective in LNP models.

Exploración de la eficacia analgésica de dos parches transdérmicos analgésicos de opioides, buprenorfina y fentanilo, según sus variaciones de dosis en el control del dolor en pacientes paliativos oncológicos / Exploration of the analgesic efficacy of two-transdermal analgesic patches of opioids, buprenorphine and fentanyl, according to their dose variations in pain control in palliative cancer patients

Objetivo: El presente trabajo de investigación tuvo como objetivo explorar la eficacia analgésica mediante la comparación de la respuesta analgésica de los parches transdérmicos (PTD) de buprenorfina y fentanilo en dolor oncológico y patrón de uso. Material y Método: Se obtuvieron los datos y variables desde los registros clínicos de pacientes ingresados a la Unidad de Cuidados Paliativos (UCP) del Instituto Nacional del Cáncer (INC) que estaban bajo tratamiento en mayo del 2017. Se incluyó en este estudio a 78 pacientes con PTD, que representan el 13% de los pacientes en control mensual. De estos, 66 estaban bajo tratamiento con buprenorfina y 8 bajo tratamiento con fentanilo. Resultados: Los resultados mostraron que el PTD de buprenorfina se utiliza más frecuentemente que el de fentanilo. El principal motivo de rotación fue dolor no controlado, seguido por imposibilidad de contar con la administración por vía oral. En pacientes con mayores intensidades de dolor somático o visceral se indicó fentanilo y en aquellos con componente neuropático se prefirió el uso de buprenorfina. PTD de fentanilo fue indicado en dosis mayores que buprenorfina, incluso al comparar sus dosis equianalgésicas, siendo la variación de dosis alta para ambos parches: aumentó en promedio 257%. Se logró una mejor respuesta analgésica con buprenorfina, con una variación de intensidad de escala numérica verbal (ENV) de 2,94 y 1,88 puntos de promedio para buprenorfina y fentanilo, respectivamente. Adicionalmente, se presentó mayor reacción local dérmica con fentanilo. Conclusiones: Se evidenció diferencias en patrón de uso y, a diferencia de lo esperado, se obtuvo una mejor eficacia analgésica con buprenorfina. Datos que deben ser corroborados en estudios con mayor número de pacientes bajo tratamiento con fentanilo.

Objective: This study aims to explore analgesic efficacy comparisons of buprenorphine and fentanyl transdermal patches (TDP) in cancer pain and it's usage pattern. Material and Method: Data and variables were collected from patient's clinical reports who were admitted in the National Cancer Institute's (NCI) Palliative Care Unit (PCU) and were under treatment with TDP in May 2017. 78 TDP patients were studied and represented 13% of the monthly control patients in the PCU. Of these, 66 were under buprenorphine treatment and 8 under fentanyl treatment. Results: The results showed that buprenorphine TDP is more frequently used than fentanyl TDP, and the main reason for exchange between them was uncontrolled pain, followed by oral administration impossibility. Fentanyl TDP was indicated in patients with higher somatic or visceral pain intensities and Buprenorphine TDP was preferred in patients with neuropathic pain. Fentanyl TDP was indicated in higher doses than buprenorphine, even when comparing its equianalgesic doses, the dose variation was high for both patches throughout the treatment: it increased on average by 257%. A better analgesic response was achieved with buprenorphine, with a variation of intensity of the Verbal Numerical Scale (VNS) of 2.94 and 1.88 average points, for buprenorphine and fentanyl respectively. Additionally, there was a higher local dermal reaction with fentanyl TDP. Conclusions: Differences in usage patterns were evidenced and, unlike what was expected, better analgesic efficacy was obtained with buprenorphine TDP. This data should be corroborated in receiving fentanyl treatment.

Pathological Mechanism of PPs in Immune-related Enteropathy and Regulatory Effect of Traditional Chinese Medicine Polysaccharides / 中国实验方剂学杂志

Intestinal Peyer's patches （PPs） are local immune tissues of the intestine， which are considered to be the main induction site of the intestinal mucosal immune response， and closely related to immune-related refractory enteropathies， such as ulcerative colitis and Crohn's disease. In recent years， more and more scholars have tried to find a new breakthrough for treating refractory enteropathies with a limited efficacy of clinical interventions through in-depth study of the relationship between PPs and enteropathy. Traditional Chinese medicine （TCM） polysaccharides are considered to be a key component for immune regulation with TCM. Modern studies show that TCM polysaccharides have a significant positive intervention effect on the structure and function of PPs， with good development prospects. Based on this， this paper focuses on PPs and intestinal-related diseases， and systematically introduces the physiological structure of PPs and their drug delivery mechanism， and summarizes the interactions of PPs with effect on immune-related enteropathies， analyze of current studies and prospects of effect of TCM polysaccharides in intervening intestinal disease and its dysfunction by regulating PPs， with the aim to provide new strategies for basic studies and clinical treatment of immune-related refractory enteropathies from the perspective of PPs， and new ideas for basic studies and clinical studies on effect of TCM polysaccharides in intervening enteropathies.

Self-assembled aggregations in Coptidis Rhizoma decoction dynamically regulate intestinal tissue permeability through Peyer's patch-associated immunity / 中草药·英文版

Objective: To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying. Methods: The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in Coptidis Rhizoma decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results: SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion: SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.

Priorización de nuevas vacunas e innovación al servicio de estrategias de vacunación / New vaccines prioritization and immunization-related innovation

La vacunación es el medio más efectivo para controlar la morbilidad y mortalidad relacionadas con enfermedades infecciosas. Para lograr esto, necesitamos vacunas inmunogénicas y seguras que faciliten y mejoren sus condiciones de transporte, almacenamiento y administración. Gracias a los avances en inmunología y bioinformática, es posible impulsar el descubrimiento de nuevas vacunas para enfrentar la tuberculosis, el virus respiratorio sincicial, el Streptococcus agalactiae, la enfermedad meningocócica invasora, entre otros. Así también, nuevas tecnologías, como la producción de vacunas utilizando plantas transgénicas y parches de microagujas, los cuales podrían facilitar la producción, disminuir los costos y efectos adversos. Sin embargo, no solo necesitamos las vacunas, sino que debemos conocer la epidemiología de las enfermedades prevenibles con vacuna para tomar decisiones fundadas, con el objetivo de planificar estrategias sanitarias, medir su impacto y evaluar la seguridad de su utilización, para alcanzar las metas de salud pública y la confianza de la población.

Vaccination is the most effective strategy to avoid morbidity and mortality related to infectious diseases. To achieve this, we need immunogenic and safe vaccines that facilitate and improve its transport, storage and administration conditions. Thanks to current advances in immunology and bioinformatics, it is possible to boost the discovery of new vaccines to deal with tuberculosis, the respiratory syncytial virus, Streptococcus agalactiae, meningococcal invasive disease, among others. In addition to new technologies such as the production of plant-based vaccines, and microneedles patches, which can facilitate its production, reducing costs and adverse effects. However, vaccines is not the only thing that we need, because we must know the epidemiology and burden of disease to take informed decisions to design optimal strategies, measuring their impact and assessing the safety of their use in order to achieve the goals health and population confidence.

Cefixime and ornidazole combination induced fixed drug eruption: a case report

Cefixime, a third generation cephalosporin and ornidazole, a nitroimidazole is used for a wide variety of conditions like urinary tract infections, otitis media, pharyngitis, uncomplicated gonorrhea and anaerobic infections. Fixed drug eruption (FDE) is commonly associated with anticonvulsants, antimicrobials and NSAIDs. Here we report a case of a rare cefixime and ornidazole combination induced fixed drug eruption. A 39 year old male developed hyper-pigmented patches over both forearms and left thigh after consuming fixed dose combination of cefixime and ornidazole tablet for the treatment of urinary tract infection.

Preparation of Cangai oil transfersomes patches and its in vitro evaluation / 中国中药杂志

L_9(3~4) orthogonal experiment design was used to optimize the preparation of the patches,and investigate its affecting factors and skin irritation. Eugenol was taken as the index component to study the release behavior in vitro and percutaneous penetration of Cangai oil transfersomes patches by HPLC.The results showed that the optimal prescription for preparing Cangai oil transfersomes patches were Eudragit E100 0.6 g, succinic acid 0.08 g,triethyl citrate 0.25 g,glycerol 0.2 g.Patches prepared by the preferred preparation had a flat appearance without obvious bubbles.The initial adhesion was 18.33±2.52, the stickiness was(30.01±2.45) min,and the peel strength was(5.62±0.95) kN·m~(-1).The results of affecting factors experiment showed the order of factors affecting its adhesion was humidity>temperature>lighting,and the skin irritation test results showed no significant skin irritation after 24 h of single administration. The results of drug release behavior in vitro showed that the release and the percutaneous penetration of both Cangai oil patches and Cangai oil transfersomes patches conformed to the Higuchi equation.The release amount of eugenol were 80.66% and 82.25% at 72 h, with no significant difference. The cumulative permeation area of eugenol per unit area reached(0.195 6±0.065 9),(0.131 0±0.045 5) mg·cm~(-2) at 72 h, with significant differences(P<0.05).The experiment results proved that the preparation process of Cangai oil transfersomes patches was stable,and the prepared patches had a good adhesion. At the same time,the preparation of transfersomes patches could alleviate and control the release of the drug to a certain extent, and provide a certain experimental basis for clinical pediatric drug safety.

Safe-by-design development of a topical patch for drug delivery

Few topical products have been developed specifically to treat acute and chronic arthritis and inflammation, using non-steroidal anti-inflammatory drugs (NSAIDs). The lack of dosing accuracy commonly found in locally applied semisolid products for cutaneous use is a critical issue that leads to treatment failure. The aim of the present work is to develop a differentiated and innovative topical patch based on a monolithic hydrogel for ibuprofen skin delivery, in order to provide a safer and accurate way of drug administration along with improved treatment compliance. Topical patches based on hydroxypropylmethylcellulose (HPMC) were optimized in composition, in terms of enhancer and adhesive, supported on a systematic assessment of in vitro release and permeation behavior and adhesion properties. Several mathematical models were used to scrutinize the release mechanisms from the patches. In vitro release kinetics was shown to be mainly driven by diffusion. However, other mechanisms seemed to be also present, supporting the feasibility of using patches for sustained drug delivery. PEG 200 provided the best permeation rate, with a permeation enhancement ratio of ca. 3 times higher, than the commercial reference. The addition of Eudragit L30D 55 to the formulation led to the best adhesion profile, thus achieving a successful development based on a safe-by-design concept.

Effect of Chronic Commercial Sweeteners Consumption in Lymphocytes of Peyer’s Patches

Aims: To know the effect of chronic commercial sweeteners consumption in lymphocytes of Peyer’s patches. Study Design: A prospective, longitudinal, comparative and experimental study. Place and Duration of Study: The study was conducted in the Nutrition Research Laboratory of the Faculty of Medicine of Universidad Autónoma del Estado de México (UAEMéx) between August 2018 and May 2019 and was approved by the Bioethics Committee. Materials and Methods: Two groups of male mice of different strains were used: 1) Balb/c and 2) CD1, both at 8 weeks-old age. The groups were divided into 4 subgroups: 1) Control (without sweetener), 2) Sucrose (table sugar, 41.66 mg/mL), and two groups of commercial sweeteners 3) Splenda® (sucralose 1.2%, with a concentration of 4.16 mg/mL), and 4) Svetia® (Steviol glycoside 0.025 g with a concentration of 4.16 mg/mL). The mice consumed the supplementation for 6 weeks. Also, were quantified plasma glucose, percentage of lymphocytes from Peyer’s patches, water and food consumption weekly. Results: Mice increased their body weight after 6 weeks of treatment. The animals of Control and Sucrose subgroups showed a significant body weight gain of 5 g compared with the Splenda® and Svetia® subgroups, which increased only 4 g. In the subgroup treated with Splenda®, the blood glucose was reduced significantly. Svetia® and Control groups consumed more water without sweetener. The differences in food consumption were between the subgroups, not between the strains. By the end, the percentage of lymphocytes from Peyer´s patches increased in the Sucrose subgroup but decreased significantly in other subgroups. Conclusion: The consumption of sweeteners may modify the lymphocyte population of Peyer's patches in the small intestine and this variation depends on the frequency of consumption the strain of the rodents and the type of sweetener.

Pharmaceutical research of Ligusticum chuanxiong oil microcapsule analgesic gel patch by D-optimal mixture design / 中草药

Objective: The volatile oil of Ligusticum chuanxiong was made into microcapsule as intermediate and applied to gel paste to solve the instability characteristics of L. chuanxiong oil (LCO). The formulation and in vitro transdermal rate were optimized and the pharmacodynamics was preliminary studied. Methods: D-optimal mixture design was adopted, and initial adhesion, adhesion holding and peeling strength were used as evaluation indexes to optimize the preparation process. The in vitro transdermal behavior of ligustilide was studied by Franz in vitro transdermal test instrument. The efficacy was evaluated by acetic acid writhing experiment. Results: The optimal prescription of LCO microcapsule analgesic gel patch was as follow: NP700, glycerin, hydroxyaluminum, kaolin, azone, tartaric acid, microcapsule PVPK30, 0.5% capom 940 was 1.250, 5.000, 0.025, 0.250, 0.600, 0.025, 1.000, and 2.700 g, respectively. Ligustilide transdermal rate in the gel patch was 5.129 7 μg/(cm2∙h). The retention rate of high temperature, high humidity and strong light irradiation on the 5th and 10th day was 93.17%, 91.21%, 98.94%, 92.36%, 68.03%, and 60.78%, respectively, and the analgesic rate was 63.14%. Conclusion: The optimal prescription of the gel patch had good viscosity, which solved the problem that ligustilide was difficult to be applied to the gel patches due to the instability of LCO and provided a reference for the application of volatile oil to new dosage forms such as gel patch.

Recent advances of microneedles for biomedical applications: drug delivery and beyond

The microneedle (MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing (3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.

Spatial distribution of dairy heifers' dung in silvopastoral systems / Distribuição espacial de fezes de novilhas leiteiras em sistemas silvipastoris

ABSTRACT: Ruminants vary their walking trajectory according to the positioning of the trees in integrated systems, which can determine the concentration of dung deposition at certain locations. The aim of this study was to map the distribution of feces and the behavior of dairy heifers in sunny and shaded areas. This experiment was carried out in Mato Grosso, Brazil, where the main grazing conditioner is shade due to the presence of trees in the pastures. Shading levels used were: full sunlight (control), moderate shade (338 trees ha−1) and intensive shade (714 trees ha−1) in randomized complete blocks. The experimental period was divided into three evaluation periods based on rainfall distribution: rainy period = December 2012; transition period = March 2013 and dry period = June 2013. Animal behavior assessments and dung distribution mapping were performed. The full sunlight system displayed a higher concentration of feces patches at sites near the gate, cow drinkers and fences opposite the gate. Heifers picked shaded places for ruminating and idleness. The major concentration was reported in the central area and under trees, in shaded systems. There were places with greater feces concentrations, but when the pasture had trees, deposition did not only happen underneath trees but also in places under their influence. The distribution was more homogeneous when trees were present in large quantities. The shaded area available in pastures affects spatial distribution of dung, stimulating uniformity.

RESUMO: Os ruminantes variam a trajetória de sua caminhada de acordo com o posicionamento das árvores em sistemas integrados. A deposição de fezes pode estar mais ou menos concentrada em determinados locais, de acordo com a disposição desses condicionadores de pastejo que definem o caminhamento animal. O objetivo deste experimento foi mapear a localização e a distribuição de fezes de bezerras leiteiras de acordo com seu comportamento afetado pela disponibilidade de áreas ensolaradas e sombreadas. Este experimento foi conduzido em Mato Grosso, no Brasil. O principal condicionador de pastejo foi o sombreamento promovido pela presença de árvores nas pastagens. Foram impostos níveis de sombreamento: pleno sol (controle), sombreamento moderado (338 árvores ha− 1) e sombreamento intenso (714 árvores ha− 1) em blocos completos casualizados. O período experimental foi dividido em períodos de avaliação com base na distribuição das chuvas: Período Chuvoso = dezembro de 2012; Período de Transição = Março de 2013 e Período Seco = Junho de 2013. Foram realizadas avaliações de comportamento animal e mapeamento da distribuição das placas de fezes na área. Para atividades de ruminação e lazer, as novilhas preferiram os locais mais sombreados. O sistema pleno sol promoveu maior concentração de placas de fezes em locais próximos a porteiras e bebedouros, no lado oposto ao da porteira. Nos sistemas sombreados, a maior concentração foi na área central e sob sombra. Havia locais com maior concentração de fezes, mas quando havia árvore na pastagem, a deposição não acontecia apenas abaixo da árvore, mas também nos locais sob sua influência. A distribuição foi mais homogênea quando as árvores estavam em maiores quantidades. A área de sombra disponível no pasto afeta a distribuição espacial do esterco estimulando a uniformidade.

Relación especie-área y distribución de la abundancia de especies en una comunidad vegetal de un inselberg tropical: efecto del tamaño de los parches / Species-area relation and species abundance distribution in a plant community on a tropical inselberg: effect of patch size

Resumen Aunque los inselbergs son afloramientos rocosos icónicos con un alto valor biogeográfico, poco se conoce sobre los mecanismos responsables de la estructuración de comunidades vegetales. El objetivo de esta investigación fue evaluar cómo el tamaño de los parches de vegetación influye en la relación especie-área y distribución de la abundancia de especies de una comunidad en un inselberg del Monumento Natural "Piedra La Tortuga", región Guayana, Venezuela. Por este motivo, se establecieron tres preguntas de investigación: ¿Cuál es el efecto del tamaño de los parches sobre la riqueza de especies? ¿Qué tipo de modelo especie-área (SAR) presenta mejor ajuste en esos parches de vegetación? ¿Cómo es la distribución de las abundancias de las especies (SADs) es inducida por el tamaño de los parches? Se realizó un muestreo aleatorio estratificado en parches que oscilaron entre 0.34 y 14.8 m2, totalizando 40 unidades muestrales (226 m2). Todos los individuos encontrados en los 40 parches fueron identificados a nivel de especie. La composición florística en las diferentes muestras estuvo representada por 19 familias, 22 géneros y 24 especies, de las cuales 50 % son endémicas de inselbergs y dos están amenazadas de extinción. Se identificaron dos grupos de tamaños de parches (grandes 8-15 m2 y pequeños ≤ 7.9 m2) en relación a la abundancia y composición de especies, con diferencias significativas entre los grupos. Las curvas de acumulación de especies para cada grupo de tamaño de parche muestran una tendencia contrastante con marcadas diferencias en la riqueza observada entre los grupos de tamaños de parches. Las curvas de los modelos SADs tuvieron un ajuste significativo de la serie geométrica en las dos categorías de parches. El modelo SAR de la función potencia presentó los mejores ajustes especie-área, donde el aumento del área de los parches explicó un 82 % de la variación en el aumento del número de especies. Los resultados de este estudio demuestran por primera vez como el tamaño de los parches de vegetación de un inselberg tropical tiene una fuerte influencia sobre la riqueza, distribución de la abundancia y composición de especies. Así mismo, se determinó que el modelo geométrico SAD presentó el mejor ajuste en la comunidad en función del tamaño de los parches como un indicador de recursos, donde la abundancia de una especie puede ser equivalente a una proporción del espacio ocupado. También se presume que los cambios de tamaño de los parches, podría estar asociado con la disponibilidad de nutrientes y agua, como ha sido demostrado en otros ambientes de tierras secas. En algunos estudios se ha argumentado que la variación en la composición de especies entre los perfiles de vegetación de inselbergs tropicales está condicionada principalmente por la estructura del hábitat y el déficit hídrico. Sin embargo, no se había discutido cómo el tamaño de los parches de vegetación tiene un efecto en la riqueza. Los análisis SADs y SAR pueden proporcionar explicaciones complementarias sobre la estructuración de comunidades vegetales en inselbergs.

Abstract Although inselbergs are iconic rock outcrops with a high biogeographic value, little is known about drivers responsible for the plant community assembly. The aim of this research was to evaluate how the patch size distribution of vegetation influences the species-area relationship and species abundance distribution of a community in an inselberg of the "Piedra La Tortuga" Natural Monument of the Guayana region, Venezuela. In this context, three research questions were established: What is the effect of patch size on species richness? What species-area model (SAR) has the best fit in those vegetation patches? How is the distribution of species abundances (SADs) induced by the patch size distribution? A stratified random sampling was performed in patches ranging from 0.34 to 14.8 m2, totaling 40 sampling units (226 m2). All individuals found in the 40 patches were identified at species level. The floristic composition in the different samples was represented by 19 families, 22 genera and 24 species, of which 50 % are endemic to inselbergs and two, are threatened of extinction. Two groups of patch sizes were identified (large 8-15 m2 and small ≤ 7.9 m2) in relation to the abundance and composition of species. The species accumulation curves for each patch size group show a contrasting tendency with marked differences in the observed richness among patch size groups. The curves of the SADs models had a significant adjustment of the geometric series in the two categories of patches. The SAR model of the power function presented the best species-area adjustments, where the increase in patch area accounted for 82 % of the variation in the increase in the number of species. The results of this study demonstrate for the first time how vegetation patches of a tropical inselberg have a strong influence on richness, abundance distribution and species composition. Likewise, it was determined that the SAD geometric model presented the best fit in the community as a function of patch size as a resource indicator, where the abundance of a species can be equivalent to a proportion of the space occupied. It is also presumed that changes in patch sizes could be associated with nutrient and water availability, as has been demonstrated in other dryland environments. In some studies it has been argued that variation in species composition among vegetation profiles of tropical inselbergs is mainly conditioned by habitat structure and water deficit. However, it had not been discussed how the size of patches of vegetation has an effect on richness. SADs and SAR analyzes can provide complementary explanations on community assembly in inselbergs. Rev. Biol. Trop. 66(2): 937-951. Epub 2018 June 01.

Uso de parches protectores faciales no reduce la presión facial en un modelo simulado de ventilación mecánica no invasiva / Face protective patches do not reduce facial pressure ulcers in a simulated model of non-invasive ventilation

La ventilación mecánica no invasiva (VMNI) tiene como complicación frecuente el desarrollo de úlceras faciales por presión (UPP). Su prevención considera el uso empírico de parches protectores entre piel y mascarilla, para disminuir la presión ejercida por ésta. Objetivos: Evaluar el efecto de los parches protectores sobre la presión ejercida por la mascarilla facial, y su impacto en los parámetros ventilatorios programados. Método: Modelo simulado de VMNI binivelada usando mascarilla facial total en fantoma con vía aérea fisiológica (ALS PRO+) en posición supina. Se midió la presión en frente, mentón y pómulos, usando 3 tipos de parches protectores de uso habitual versus un grupo control, utilizando sensores de presión (Interlinks Electronics®). Se evaluaron los valores obtenidos con el modelo de mascarilla-parches protectores en las variables programadas flujo máximo inspiratorio (FMI), volumen corriente espirado (Vte) y presión positiva inspiratoria (IPAP), con ventilador Trilogy 100, Respironics®. La programación y registro de las variables fue efectuada en 8 oportunidades en cada grupo por operadores independientes. Resultados: No se observó disminución de la presión facial con ninguno de los parches protectores respecto al grupo control. Moltoprén aumentó la presión facial en todos los puntos de apoyo (p < 0,001), aumentó fuga, disminuyó FMI, Vte e IPAP (p < 0,001). Parches de hidrocoloide aumentaron la presión facial sólo en pómulo izquierdo, aumentaron la fuga y disminuyeron FMI. Parches de poliuretano no generaron cambios en la presión facial ni en variables ventilatorias. Conclusión: El uso de parches protectores de moltoprén, hidrocoloide y poliuretano transparente no contribuyó a la disminución de la presión facial. Se observó un efecto deletéreo de los parches de moltoprén e hidrocoloide sobre la administración de variables ventilatorias, concluyendo que el no uso de los parches protectores permitió una mejor administración de los parámetros programados.

Noninvasive ventilation (NIV) frequently involves the development of facial pressure ulcers (FPU). Its prevention considers the empirical use of protective patches between skin and mask, in order to reduce the pressure exerted by it. Objectives: To evaluate the effect of protective patches on the pressure exerted by the facial mask, and its impact on the programmed ventilatory parameters. Method: Bilevel NIV simulated model using full face mask in phantom with a physiological airway (ALS PRO +) in supine position. Forehead, chin and cheekbones pressure were measured using 3 types of standard protective patches versus a control group using pressure sensors (Interlinks Electronics®). The values obtained with the protective patches-mask model were evaluated in the programmed variables maximum inspiratory flow (MIF)), expired tidal volume (Vte) and positive inspiratory pressure (IPAP), with Trilogy 100 ventilator, Respironics®. The programming and recording of the variables was carried out in 8 opportunities in each group by independent operators. Results: There was no decrease in facial pressure with any of the protective patches compared to the control group. Moltopren increased facial pressure at all support points (p < 0.001), increased leakage, it decreased MIF, Vte and IPAP (p < 0.001). Hydrocolloid patches increased facial pressure only in the left cheekbone, increased leakage and decreased MIF. Polyurethane patches did not produce changes in facial pressure or ventilatory variables. Conclusion: The use of protective patches of moltopren, hydrocolloid and polyurethane transparent did not contribute to the decrease of the facial pressure. A deleterious effect of the moltopren and hydrocolloid patches was observed on the administration of ventilatory variables, concluding that the non-use of the protective patches allowed a better administration of the programmed parameters.