Editorial

Although many attempts have been made, stroke treatment options are still extremely limited and brain ischemia remains the leading cause of death and disability worldwide. Two major strategies for ischemic stroke, reperfusion and neuroprotection, are currently being evaluated. Autophagy is a bulk protein degradation system that is involved in multiple cellular processes. Increasing data suggest that activation of autophagy in ischemic brain may contribute to neuroprotection. However, it should also be noted that there are evidences that autophagy is a process involved in neurodegeneration. Targeting signaling pathways related to autophagy might be a promising option in the treatment of cerebral ischemia, but the exact role of autophagy activation due to ischemic episodes and its potential applications in pharmacotherapy are still to be determined. In this paper we review recent evidences for cerebral ischemia-induced autophagy, briefly discuss mechanisms and signaling pathways that lead to this activation and we analyze its potential roles.     

Editorial

Abstract

A novel ethylcellulose (EC) capsule which releases drug with a time-controlled fashion has been prepared. This capsule is composed of four parts, drug container, swellable substance, capsule body and cap. At the bottom of the body, micropores are made. As water penetrates through these micropores, the swellable substance such as low substituted hydroxypropyl cellulose (L-HPC) swells. When the cap made of water-insoluble macromolecular substance such as EC cannot persist the swelling pressure, the EC cap disintegrates and the drug in the container is released from the capsule. The lag-time is utilized for the delivery of drug to the colon. The release time of the drug from the capsule was measured both in vitro and in vivo experiments. In the case of an in vitro experiment, after 12mg of fluorescein as a model drug and 238mg of starch were filled into the container, caps having different thickness were attached to the capsule body and release study was performed. The release time of the drug was mainly dependent on the thickness of the cap. Using test capsules of which mean cap thickness were 39.1 ± 2.3 (SE)μm, 63.1 ± 5.0μm and 75.6 ± 4.1μm, the in vivo release time was estimated after administration to beagle dogs. As a parameter, the peak time (t_max) when plasma fluorescein concentration reached to its maximum level was determined for the estimation of the release time of the drug from the capsule in the gastrointestinal tract. The in vivo t_max was well correlated with the cap thickness. These results show the possibility of new EC capsule for the colon delivery of drugs.     

Editorial

1. Gas chromatographic/mass spectroscopic analysis of a mixture of ¹⁴C-nonylphenols produced by alkylation of ¹⁴C-RUL-phenol with n-1-nonene indicated that the radio-synthesis produced three major isomers, 2-(4-hydroxyphenyl)-nonane, 3-(4-hydroxy-phenyl)-nonane and 4-(4-hydroxyphenyl)-nonane.

2. Bile from rainbow trout exposed to a mixture of these isomers of ¹⁴C-nonylphenol was found to contain the glucuronic acid conjugates of three radiolabelled metabolites, which were more polar than their parent compounds.

3. Incubation of trout hepatic microsomes with NADPH and the ¹⁴C-nonylphenol isomers resulted in the production of three radiolabelled metabolites whose mobility on silica thin layer chromatography were similar to the deglucuronidated metabolites recovered from trout bile.

4. Metabolism of the ¹⁴C-nonylphenol isomers by trout hepatic microsomes was inhibited by omission of NADPH from the incubations as well as by addition of a P450 inhibitor, piperonyl butoxide to the incubations.

5. Analysis of the metabolites extracted from the microsomal incubations by gas chromatography/mass spectroscopy indicated that the parent isomers had been hydroxy-lated in the C-8 position on the nonane chain to give 2-(4-hydroxyphenyl)-8-hydroxy-nonane, 3-(4-hydroxyphenyl)-8-hydroxynonane and 4-(4-hydroxyphenyl)-8-hydroxy-nonane.     

Editorial

A themed section in this issue of Br J Pharmacol, on ‘Advances in Nutritional Pharmacology’, provides a valuable and timely update on progress in this area.The value of dietary components to improvement in health and, particularly, to prevention of cardiovascular disease and cancer, is frequently reported in the media and therefore often captures the attention of the wider public. Understanding the pharmacological mechanisms by which nutritional elements confer their health benefits enables us to keep the public informed, but also aids in the identification of new targets for drug development. In recent years there has been significant progress in this field.Four rapidly developing areas are reviewed. Vosper (2009) covers the identification of a receptor for niacin and the subsequent development of selective agonists as lipid lowering agents. Wu-Wong (2009) describes the development of new Vitamin D analogues for the treatment of cardiovascular disease. de Roos et al. (2009) provide detailed insight into how omega-3 fatty acids, also known as longchain n-3 polyunsaturated fatty acids (PUFAs) protect against cardiovascular disease. Zhou et al. (2009) cover the mechanisms underlying the beneficial effects of resveretrol in protection against cancer.These reviews are complimented by three key original articles focusing on endogenous mechanisms of weight control involving endocannabinoids (Izzo et al., 2009), a circulating protein, the soluble leptin receptor (Zhang & Scarpace, 2009) and a treatment, zinc plus cyclo-(His-Pro) (CHP), known to increase insulin metabolism (Song et al., 2009).The value of dietary components to improvement in health and, particularly, to prevention of cardiovascular disease and cancer, is frequently reported in the media and therefore often captures the attention of the wider public. Understanding the pharmacological mechanisms by which nutritional elements confer their health benefits enables us to keep the public informed, but also aids in the identification of new targets for drug development. In recent years there has been significant progress in this field.A themed section in this issue of Br J Pharmacol, on ‘Advances in Nutritional Pharmacology’, edited by Cherry Wainwright, aims to provide a valuable and timely update on progress in this area.This issue includes several reviews that provide an update in four rapidly developing areas. Vosper (2009) has written a narrative tracking the research that led to the identification of a receptor for niacin and the subsequent development of selective agonists as lipid lowering agents. Within this review, the benefits and pitfalls of niacin receptor agonists are discussed, alongside a consideration of the impact of blocking their undesirable effects, such as skin flushing. Two further reviews describe the development of new Vitamin D analogues for the treatment of cardiovascular disease(Wu-Wong, 2009) and provide detailed insight into how omega-3 fatty acids, also known as longchain n-3 polyunsaturated fatty acids (PUFAs) protect against cardiovascular disease (de Roos et al., 2009). The fourth review provides greater understanding of the mechanisms underlying the beneficial effects of resveretrol in protection against cancer (Zhou, 2009).These reviews are complimented by three key original articles focusing on endogenous mechanisms of weight control. In an elegant study in lean and fatty mice with diet induced obesity, Izzo et al. (2009) have provided evidence to support the idea that dysregulation of peripheral endocannabinoids can contribute to obesity. In a further in vivo study, direct evidence is provided that a circulating protein, the soluble leptin receptor, may play a regulatory role in energy homeostasis and weight gain by neutralizing leptin (Zhang & Scarpace, 2009). Finally Song et al. (2009) have demonstrated in both diabetic and non-diabetic overweight aged rats that zinc plus cyclo-(His-Pro) (CHP), a treatment known to increase insulin metabolism, improves weight control through reducing food intake and altering the balance between plasma leptin and adiponectin levels, suggesting this may be a possible treatment for overweight and obese patients.