Skin permeation enhancement by sucrose esters: a pH-dependent phenomenon

The purpose of the present study was to evaluate the effect of sucrose esters (particularly, sucrose laureate and sucrose oleate in Transcutol) on the percutaneous penetration of a charged molecule as a function of ionization. We have investigated the influence of these sucrose esters on the in vitro diffusion profiles of lidocaine hydrochloride, a weak ionizable base (pKa=7.9), at different pH values, using porcine ear skin as the barrier membrane. As expected, lidocaine flux in the absence of an enhancer, increased from pH 5 to 9 with a corrresponding increase in the level of the unionized base. However, when skin was pretreated with 2% laureate in Transcutol (2% L-TC), drug permeation was higher at pH 5.0 and 7.0 than at 9.0. A different trend was observed in experiments with 2% oleate in Transcutol (2% O-TC), where skin flux was maximal at a more basic pH, when the degree of ionization is low. The results suggest that sucrose laureate enhances the penetration of the ionized form of the drug (12-fold greater flux relative to control), whereas sucrose oleate is more effective in promoting permeation of the unionized species. The structural properties of the sucrose esters as well as the degree of ionization of the drug are important characteristics affecting the transdermal flux of lidocaine.     

The orthopedic and renal manifestations of idiopathic carpal tarsal osteolysis

Idiopathic carpal tarsal osteolysis (ICTO) is a rare congenital disorder that results in the destruction and resorption of bone, leading to severe functional deficits and cosmetic deformities. This report includes a literature review describing the orthopedic and renal manifestations of ICTO. An additional case report of ICTO with atypical features is included.     

Do autologous mesenchymal stem cells augment bone growth and contact to massive bone tumor implants?

This study investigated the hypothesis that spraying autologous mesenchymal stem cells (MSCs) onto grooved hydroxyapatite (HA) coated collars of segmental bone tumor implants would increase bone growth and contact to the implant surface in an ovine model. Autologous MSCs were isolated from bone marrow, grown in culture and during surgery implants in group 1 were sprayed with MSCs, suspended within fibrin glue. Implants in group 2 received no MSC therapy and acted as control. Implants remained in vivo for 6 months. New bone area and contact to the implant was quantified on radiographs and histologically. Radiographic analysis demonstrated greater total bone area in the MSC treated group in both ML (MSC = 79.738 mm2 +/- 22.964; control = 30.135 mm2 +/- 6.717) (p = 0.018) and AP (MSC = 90.338 +/- 19.361 mm2; control = 57.384 +/- 9.035 mm2 (p = 0.074) radiographs at 6 months. Results demonstrated significantly increased bone growth in the MSC group at 2 (p = 0.03) and 3 months (p < 0.05). Histological analysis demonstrated significantly greater bone area adjacent to the collars in the treated group (53.994 +/- 10.641 mm2) when compared with the control group 21.069 +/- 7.339 mm2 (p = 0.020). Increased bone contact in the MSC group (19.833 +/- 8.729 %) was observed when compared with controls (8.667 +/- 8.667%). This novel application of spraying MSCs onto the implant surface has significant implications for the future of successful implant fixation.     

Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol

Vitamin E homologues, specifically tocotrienols, have been shown to have favorable effects on bone. They possess properties that are indicative of anti-resorptive activity, suggesting the potential for vitamin E in preventing bone loss. To investigate the anti-resorptive activity of the various vitamin E homologues, we cultured human osteoclasts from blood-derived CD14+ cells on collagen, dentin, and calcium phosphate substrates, with some samples supplemented with vitamin E homologues in their cell culture medium. These were compared to the clinically used bisphosphonate, pamidronate. Compounds were either added at the start of culture to study effects on osteoclast formation, or at the start of osteoclastic resorption to determine their effects on activity. The alpha- and gamma-tocotrienol isomers inhibited osteoclast formation without consequent reduction in total cell number. Only gamma-tocotrienol inhibited osteoclast activity without toxicity. Gamma-tocotrienol was the most potent inhibitor of both osteoclast formation and activity and requires further investigation into its anti-resorptive effects on bone.     

Stratum Corneum Thickness and Apparent Water Diffusivity: Facile and Noninvasive Quantitation In Vivo

Pharmaceutical Research -     

丙型肝炎病毒准种多样性与病毒血症水平、疾病活动度及干扰素疗效的关系

目的　了解丙型肝炎病毒 (HCV)准种变异与病毒血症水平、疾病活动度及干扰素疗效的关系。方法　采用针对HCVE2高变区 1 (HVR1 )的单链构象多态性分析法 (SSCP)对 68例慢性丙型肝炎患者进行HCV准种检测 ,分析准种数目与HCVRNA、ALT、AST水平及肝组织活动指数 (HAI)的相关性。对其中 48例给予干扰素治疗 ,分析准种数目对干扰素应答效果的影响。结果　 61例HVR1SSCP阳性 ,HCV准种数目为 (6 2± 2 4)条。准种数量与HCVRNA水平显著相关 (P <0 0 1 ) ,与ALT、AST及HAI无明显相关 (P >0 0 5)。干扰素治疗患者中 ,43例HVR1阳性 ,持续应答者治疗前HCV准种数量 (3 3± 1 2 ,n =1 1 )显著少于获得治疗终点应答 (ETR)伴复发者 (6 3± 2 2 ,n =1 2 ,P <0 0 5)或无应答者 (8 0± 3 3 ,n=2 0 ,P <0 0 1 )。治疗结束时 ,干扰素组仍有 1 6例检测出HCV准种 ,但准种条数降为 (3 4± 1 2 )条 ,与未接受干扰素治疗病例的准种数目 (6 8± 2 5)相比差异有显著性 ,P <0 0 1 ) ,且其中 1 0例准种模式发生了改变。结论　HCV准种多样性可引起较高的病毒血症水平 ,但与疾病活动度无关 ;准种数目可作为预测慢性丙型肝炎干扰素疗效的指标。