Microspheres of essential oil in polylactic acid and poly(methyl methacrylate) matrices and their blends

This study is focussed on micro-encapsulation of essential oils in polylactic acid (PLA) and a poly(methyl methacrylate) (PMMA) matrix as well as blends of the same. Microspheres were prepared by the solvent evaporation technique and characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier transform infra-red spectroscopy (FTIR). The encapsulation efficiencies and release profiles of the essential oils were studied by gas chromatography mass spectrometry (GC-MS) and head-space solid-phase microextraction GC-MS, respectively. Furthermore, the microspheres were tested for antibacterial activity against both Gram-negative and Gram-positive bacterial strains.

The results showed that the microspheres compositions (PLA/PMMA ratio) have significant effect on their characteristics. The process adopted for preparing the microspheres promoted formation of spherical particles at the sizes of 1.5–9.5?µm. The highest encapsulation efficiency of the prepared microspheres was observed in systems consisting of linalool (81.10?±?10.0?wt. % for PLA system and 76.0?±?3.3?wt. % for PMMA system). Confirmation was also made that the release rate of the microspheres was affected by the size of the same.     

Symptoms During or Shortly After Isolated Carpal Tunnel Release and Problems Within 24?hours After Surgery

This study used the National Survey of Ambulatory Surgery (NSAS) database to measure the incidence of and risk factors for symptoms in the ambulatory surgery center and problems within 24 h after isolated carpal tunnel release (CTR). The NSAS contained records on 400,000 adult patients with carpal tunnel syndrome who were treated with CTR in 2006, based on ICD-9 codes. The type of anesthesia used and factors associated with symptoms and problems were sought in bivariate and multivariable statistical analyses. The mean duration of the procedure was 16 ± 8.8 min. Only 5 % were performed under local anesthesia without sedation, 45 % with IV sedation, 28 % regional anesthesia, and 19 % general anesthesia. Symptoms in the ambulatory surgery center or a problem within 24 h after discharge were recorded in 10 % of patients, all of them minor and transient, including difficulties with pain and its treatment. The strongest risk factors were male sex, age of 45 years and older, and participation of an anesthesiologist. Local anesthesia and regional anesthesia were associated with more perioperative symptoms and postoperative problems. Most CTR are performed with some sedation in the United States. CTR is a safe procedure: one in 10 patients will experience a minor issue in the perioperative or immediate postoperative period.     

The surgical management of resistant club foot by rotation skin flap and extensive soft tissue release

Summary Resistant club foot remains an unsolved problem because of the complex aetiological and pathological factors, and is still seen quite frequently, especially in developing countries. The posteromedial skin contracture is a potent deforming force which is responsible for many failures or relapses. I report the results of an operation in which a rotation skin flap was combined with an extensive soft-tissue release. The age of the children was from 9 months to 10 years. The follow-up period was from one to 9 years with an average of 43 months, and in 50 cases for more than 5 years. I consider that the outcome has been excellent or good in 94 out of 100 feet.

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Résumé Le pied bot invétéré demeure un problème mal résolu en raison de la complexité des facteurs étiologiques et anatomiques et il est encore bien souvent rencontré, notamment dans les pays en voie de développement. La rétraction cutanée postéro-interne représente un puissant élément de la déformation, qui est responsable de bon nombre d'échecs ou de récidives. Nous rapportons les résultats d'une opération qui associe un lambeau cutané de rotation à la libération des parties molles. L'âge des enfants était compris entre neuf mois et dix ans. Le recul est de un à neuf ans, avec une moyenne de 43 mois. Cinquante enfants ont été suivis plus de cinq ans. Les résultats sont excellents ou bons dans 94% des cas.

     

Poor association between allergen-specific serum immunoglobulin E levels, skin sensitivity and basophil degranulation: a study with recombinant birch pollen allergen Bet v 1 and an immunoglobulin E detection system measuring immunoglobulin E capable of binding to FcɛRI

BACKGROUND: Results from several studies indicate that the magnitude of immediate symptoms of type I allergy caused by allergen-induced cross-linking of high-affinity Fc epsilon receptors on effector cells (mast cells and basophils) is not always associated with allergen-specific IgE levels. OBJECTIVE: To investigate the association of results from intradermal skin testing, basophil histamine release and allergen-specific IgE, IgG1-4, IgA and IgM antibody levels in a clinical study performed in birch pollen-allergic patients (n = 18). METHODS: rBet v 1-specific IgEs were measured by quantitative CAP measurements and by using purified Fc epsilon RI-derived alpha-chain to quantify IgE capable of binding to effector cells. Bet v 1-specific IgG subclasses, IgA and IgM levels were measured by ELISA, and basophil histamine release was determined in whole blood samples. Intradermal skin testing was performed with the end-point titration method. RESULTS: Our study demonstrates on the molecular level that the concentrations of allergen-specific IgE antibodies capable of binding to Fc epsilon RI and biological sensitivities are not necessarily associated. A moderate association was found between cutaneous and basophil sensitivity. CONCLUSION: Our results highlight the quantitative discrepancies and limitations of the present diagnostic tools in allergy, even when using a single allergenic molecule. The quantity of allergen-specific serum IgE is only one component of far more complex cellular systems (i.e. basophil-based tests, skin tests) used as indirect diagnostic tests for IgE-mediated allergic sensitivity.     

In Vitro and in Vivo Evaluation of Whole and Half Tablets of Sustained-Release Adinazolam Mesylate

The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.     

In vivo electrochemical demonstration of potassium-evoked monoamine release from rat cerebellum

In vivo electrochemical methods were employed to study the potassium (K⁺-evoked release of monoamines from the cerebellum of the chloral hydrate anesthetized rat. K⁺-evoked releases were elicited using micropipette-Nafion-coated graphite epoxy electrode arrays in the granule/Purkenje cell layer, molecular layer, and white matter. These recorded releases were generally found to be reversible, moderately dose-dependent, and reproducible. However, the temporal dynamics of the releases were different for the cell layer versus molecular layer records. Releases were infrequently observed in cerebellar white matter, an area which is relatively devoid of monoamine containing terminals. The signals recorded from the cell and molecular layers were significantly attenuated by pretreatment with nomifensine, a potent catecholamine reuptake blocker, significantly prolonged the K⁺-evoked signals observed in both the granule/Purkenje cell and molecular layers. These data, taken together with earlier reports on the electrophysiological responses to activation of cerebellar noradrenergic inputs, support the conjecture that in vivo electrochemical recording methods have the sensitivity and spatial resolution for studies of functional monoamine release from brain regions that have a diffuse or laminated monoamine innervation.     

大颗粒小泡非突触部位的胞吐——论神经肽释放的另一种形式

本文在以前的工作基础上,进一步用电镜及免疫细胞化学方法,研究了大颗粒小泡非突触部位胞吐作用。实验结果表明,切除大鼠刚髭部皮肤1—24小时之后,术侧延髓后角浅层大颗粒小泡胞吐比对照侧明显增多(P<0.01),术后3—9天复又下降(近似对照动物),术后14—15天又急剧上升(P<0.01)。这些胞吐大部分出现于延髓后角浅层四种轴突终末的非突触部位,少最也发生于树突及轴突中。从术后第6天开始,术侧P物质明显减弱,而甲硫-脑腓肽略有增强。研究结果提示;1)后角浅层胞吐增多,P物质下降及脑腓肽增高,反映了中枢内不同神经元对去传入神经的功能调整作用;2)大颗粒小泡在非突触部位释放神经肽,弥散地作用于远距离的受体,可能起着神经调制物的作用。     

In vitro/in vivo correlation of prolonged release dosage forms containing diltiazem HCl

Six preparations were considered: three multiple unit dosage forms (micropellets in capsules) (D, E and G) and one matrix tablet (B) were experimental prolonged release formulations, two non-disintegrating tablets (A and C) were commercial products. The in vitro dissolution behaviour of the differing formulations was investigated using the USP XXII paddle apparatus. The in vivo study was effected on a panel of 12 healthy volunteers. The two commercial tablets (A and C) showed mean dissolution time (MDT) of 1.34 and 1.44 h and t_d of 91 and 92 min, respectively; for prolonged release formulations (B, E, D, and G) MDT ranged between 2.28 and 4.23 h and t_d between 149 and 291 min. The mean residence time (MRT) was 8.68 and 6.47 h for tablets A and C, respectively; it ranged between 9.62 and 10.24 h for the multiple unit formulations E, D, and G and was 11.27 h for matrix B. Formulation B also showed the higher apparent elimination half-life t_1/2 (7.12 h), while apparent t_1/2 for all the other formulations were very similar, ranging between 5.04 and 5.28 h. High variability between the various formulations was found for C_max and AUC values, and no relationships could be established with the type of formulation. An in vitro/in vivo correlation was found for all the formulations examined on the basis of analogous parameters (MDT and MRT); (r = 0.83, p <0.05). In a few cases the Wagner-Nelson deconvolution method was applied to individual plasma level versus time curves and the corresponding absorption curves were obtained. In these cases the in vitro/in vivo correlation was tested on the basis of the comparison of the in vivo absorption curves with the in vitro dissolution profiles. This was accomplished using the ‘Levy's plot’ (per cent released versus per cent absorbed) approach and provided further support for the correlation found.     

Codeine-induced histamine release in intact human skin monitored by skin microdialysis technique: comparison ofintradermal injections with an atraumatic intraprobe drug delivery system

Background The skin microdiallysis technique makes it possible to measure histamine release in intact human skin in vivo directly. In this study we have used the microdialysis technique to characterize histamine release by codeine after intracutaneous injectioin and following skin challenge by a novel atraumatic delivery technique. Objective The purpose of the study was to compare histamine release in human skin by codeine. delivered by an intraprobe drug delivery system (IPD) and intracutaneous injections (ICT), with respect to dose-response relations, kinetics of histamine appearance and decay, corelations between histamine release and skin respones, and reproducibility. Methods Hollow dialysis fibres were inserted intradermally in 12 healthy subjects. Twelve fibres were inserted in each subjects, six fibres in each arm. Each fibre was perfused at a rate of 3 μL/min, and samples were collected in 2 min fractions. By the IPD technique, codeine was administrered to the skin by adding codeine to the perfusion medium. Sequential IPD challenges were performed in one arm. and ICTs were done on the other arm. Results Sixfold serial dilutions of codeine (0.01-3 mg/mL) caused a significant doserelated histamine release by ICT and IPD. Peak histamine release was found within the first 4 min after skin challenge by ICT and IPD, followed by a fast decline with a dialysate histamine half life of approximately 2-3 min. Peak hisamine release was linearly correlates with cumulative release of the 20 min sampling period, and histamine release correlated with weal soze. The coefficient of variation on peak histamine releae was 18.9% and 4.8% for codeine ICT and IPD, respectively. Conclusioin We have described in detail codeine-induced histamine release in intact human skin in vivo by the microdialysis technique. It was possible to administer codeine atraumaticallyl to the skin by intraprobe delivery. The skin microdialysis codeine atraumaticallly to the skin by intraprobe delivery. The skin microdialysis technique opens up possibilities for measurement of infllammatory mediators release in normal and diseases skin, and it will be possible to deliver immunopharmacologically active drugsto the skin by intraprobe delivery.