Contact hypersensitivity to hydrocortisone-free-alcohol in patients with allergic patch test reactions to tixocortol pivalate

It has been suggested that contact allergy to hydrocortisone alcohol is a frequent phenomenon, A recent study showed that all patients with allergic patch reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium phosphate. We studied patients with positive patch test reactions to tixocortol pivalate but negative to hydrocortisone alcohol, with penetration enhancers in hydrocortisone alcohol patch tests and oral challenges with hydrocortisone alcohol. Additionally, prick and intradermal tests with hydrocortisone sodium succinate were used. Using penetration enhancers and oral challenges enabled detection of more contact allergies to hydrocortisone alcohol compared to conventional patch testing alone. 9/12 patients with allergic reactions to tixocortol pivalate reacted to intradermal hydrocortisone sodium succinate. No immediate reactions were seen in prick or intradermal tests, suggesting that hydrocortisone contact hypersensitivity is probably not associated with immediate allergy to hydrocortisone. The present study suggests that allergic patch test reactions to tixocortol pivalate are caused by hypersensitivity to hydrocortisone alcohol itself or to one of its metabolites in the skin.     

中药挥发油透皮吸收促进剂制剂技术的研究进展

经皮给药系统亟待解决的关键问题是提高药物的透皮吸收,中药挥发油作为一大类性质优良的透皮吸收促进剂,不仅能促进药物的透皮吸收,对皮肤刺激性小,而且还能起到一定的治疗效果,与透皮吸收的药物产生协同作用,但中药挥发油自身溶解度差,还存在不稳定的问题。目前应用于挥发油透皮促渗的制剂技术包括贴剂、包合物、凝胶膏剂、凝胶剂、微乳等,单独或组合使用能不同程度地增加挥发油的溶解度,提高透皮促渗效果。对目前中药挥发油透皮促渗的制剂技术进行综述,并对其今后的研究方向进行初步探讨。     

透皮促进剂对消旋延胡索乙素体外经皮渗透的影响

 目的 考察不同透皮促进剂对消旋延胡索乙素体外经皮渗透的影响。方法 采用Valia-Chien双室渗透扩散池,以大鼠离体皮肤为渗透屏障,用高效液相色谱法对延胡索乙素进行含量测定,考察月桂氮NFDB3酮、丙二醇及两者按不同比例混合对消旋延胡索乙素的促透效果。 结果 月桂氮NFDB3酮、丙二醇单独使用均对延胡索乙素有促透作用,月桂氮NFDB3酮促透效果较强,8%月桂氮NFDB3酮促透效果最好,平均渗透速率达到12.397 μg·cm^-2·h^-1 。单用丙二醇时,15%丙二醇促透效果较好,平均渗透速率为3.142 μg·cm^-2·h^-1。两者合用促透效果始终小于月桂氮NFDB3酮单独使用时效果,且与单用8%Azone有极显著性差异（P<0.01）。结论 月桂氮NFDB3酮浓度为8%时消旋延胡索乙素饱和溶液体外渗透具有最大促透效果,月桂氮NFDB3酮和丙二醇合用并未体现协同作用。     

The Role of Insulin Resistance in the Natural History of Type 1 Diabetes

It is well established that peripheral insulin sensitivity is a critical factor in the aetiology of non-insulin dependent (Type 2) diabetes mellitus (NIDDM). Insulin resistance may also play a role at various stages in the natural history of insulin dependent (Type 1) diabetes (IDDM) and this was the topic of a workshop held in London on Friday 14 July 1995. The mechanisms of insulin resistance in IDDM are ill-defined but probably include ‘glucose toxicity’. In the pre-diabetic period, insulin resistance may affect rates of progression to frank hyperglycaemia. Following the clinical onset of IDDM, insulin resistance could influence the length of the ‘honeymoon period’, diabetic control and patterns of growth during puberty, insulin requirements and blood glucose control at any time, the birth weight of infants born to diabetic mothers, and, through an effect on lipid metabolism and hypertension, ultimately contribute to the excess mortality associated with IDDM. In NIDDM, insulin resistance could influence rates of progression to insulin dependence. Treatment using insulin enhancers in NIDDM patients with autoimmune changes might delay or arrest their usual high-risk of progression to insulin dependence. As it is likely that insulin resistance has a wide-ranging influence on the natural history of diabetes in IDDM patients we suggest that treatment with insulin enhancers may prove beneficial in selected patients. © 1997 by John Wiley & Sons, Ltd.     

肉桂挥发油对阿魏酸透皮吸收影响的研究

目的:研究肉桂挥发油对阿魏酸透皮吸收的影响。方法:采用离体昆明种小白鼠皮肤为渗透屏障,以阿魏酸为指标成分,应用Tp-6型透皮吸收扩散仪和HPLC检测方法,考察肉桂挥发油对阿魏酸透皮吸收的影响。结果:肉桂挥发油对阿魏酸的透皮吸收有一定的促进作用,并强于氮酮,其中1%肉桂挥发油对阿魏酸的促进作用优于2%肉桂挥发油。结论:肉桂挥发油能促进阿魏酸的透皮吸收。     

模糊物元模型评价几种促透剂的促透效果

目的：探讨模糊物元模型在促透剂促透效果综合评价中的运用。方法：研究氮酮、薄荷醇、樟脑、油酸、丁香油、荆芥油、藿香油促透剂对模型药物扑热息痛在离体兔背部皮肤上的透皮行为,计算渗透系数、稳态流量、滞后时间、增渗倍数,运用基于变异系数权重的模糊物元模型对促透效果进行综合评价。结果：2%丁香和2%樟脑对扑热息痛的促透效果最好,1%氮酮、2%荆芥、2%薄荷醇、2%油酸次之,2%广藿香最差。结论：基于变异系数权重的模糊物元模型可客观地、公正地评价促透剂的促透效果。     

Sodium caprate-induced increases in intestinal permeability and epithelial damage are prevented by misoprostol

Epithelial damage caused by intestinal permeation enhancers is a source of debate concerning safety. The medium chain fatty acid, sodium caprate (C₁₀), causes reversible membrane perturbation at high dose levels required for efficacy in vivo, so the aim was to model it in vitro. Exposure of Caco-2 monolayers to 8.5 mM C₁₀ for 60 min followed by incubation in fresh buffer led to (i) recovery in epithelial permeability (i.e. transepithelial electrical resistance (TEER) and apparent permeability coefficient (P_app) of [¹⁴C]-mannitol), (ii) recovery of cell viability parameters (monolayer morphology, plasma membrane potential, mitochondrial membrane potential, and intracellular calcium) and (iii) reduction in mRNA expression associated with inflammation (IL-8). Pre-incubation of monolayers with a mucosal prostaglandin cytoprotectant was attempted in order to further decipher the mechanism of C₁₀. Misoprostol (100 nM), inhibited C₁₀-induced changes in monolayer parameters, an effect that was partially attenuated by the EP₁ receptor antagonist, SC51322. In rat isolated intestinal tissue mucosae and in situ loop instillations, C₁₀-induced respective increases in the [¹⁴C]-mannitol P_app and the AUC of FITC-dextran 4000 (FD-4) were similarly inhibited by misoprostol, with accompanying morphological damage spared. These data support a temporary membrane perturbation effect of C₁₀, which is linked to its capacity to mainly increase paracellular flux, but which can be prevented by pre-exposure to misoprostol.     

Enhancer and super-enhancer landscape in polycystic kidney disease

1. Download : Download high-res image (321KB)
2. Download : Download full-size image

     

Impairment of the autophagy–lysosomal pathway in Alzheimer's diseases: Pathogenic mechanisms and therapeutic potential

Alzheimer's disease (AD), the most common neurodegenerative disorder, is characterized by memory loss and cognitive dysfunction. The accumulation of misfolded protein aggregates including amyloid beta (Aβ) peptides and microtubule associated protein tau (MAPT/tau) in neuronal cells are hallmarks of AD. So far, the exact underlying mechanisms for the aetiologies of AD have not been fully understood and the effective treatment for AD is limited. Autophagy is an evolutionarily conserved cellular catabolic process by which damaged cellular organelles and protein aggregates are degraded via lysosomes. Recently, there is accumulating evidence linking the impairment of the autophagy–lysosomal pathway with AD pathogenesis. Interestingly, the enhancement of autophagy to remove protein aggregates has been proposed as a promising therapeutic strategy for AD. Here, we first summarize the recent genetic, pathological and experimental studies regarding the impairment of the autophagy–lysosomal pathway in AD. We then describe the interplay between the autophagy–lysosomal pathway and two pathological proteins, Aβ and MAPT/tau, in AD. Finally, we discuss potential therapeutic strategies and small molecules that target the autophagy–lysosomal pathway for AD treatment both in animal models and in clinical trials. Overall, this article highlights the pivotal functions of the autophagy–lysosomal pathway in AD pathogenesis and potential druggable targets in the autophagy–lysosomal pathway for AD treatment.