High-conductance calcium-activated potassium channels; Structure,pharmacology, and function

High-conductance calcium-activated potassium (maxi-K) channels comprise a specialized family of K⁺ channels. They are unique in their dual requirement for depolarization and Ca²⁺ binding for transition to the open, or conducting, state. Ion conduction through maxi-K channels is blocked by a family of venom-derived peptides, such as charybdotoxin and iberiotoxin. These peptides have been used to study function and structure of maxi-K channels, to identify novel channel modulators, and to follow the purification of functional maxi-K channels from smooth muscle. The channel consists of two dissimilar subunits, and . The subunit is a member of theslo Ca²⁺-activated K⁺ channel gene family and forms the ion conduction pore. The subunit is a structurally unique, membrane-spanning protein that contributes to channel gating and pharmacology. Potent, selective maxi-K channel effectors (both agonists and blockers) of low molecular weight have been identified from natural product sources. These agents, together with peptidyl inhibitors and site-directed antibodies raised against and subunit sequences, can be used to anatomically map maxi-K channel expression, and to study the physiologic role of maxi-K channels in various tissues. One goal of such investigations is to determine whether maxi-K channels represent novel therapeutic targets.     

银杏叶的研究开发概况

本文对银杏叶的化学、药理、临床和制剂等进行了综述。     

Evaluation of the effects of cosmetic or dermo-pharmaceutical products on cutaneous energy metabolism using the Episkin model of reconstructed epidermis

This study was implemented to test the Episkin model of reconstructed epidermis in the evaluation of the efficacy of cosmetic or dermopharmaceutical products on cutaneous energy metabolism. The energy metabolism is evaluated by measuring the concentration of intracellular ATP by a method using an ultrasensitive bioluminescent reaction. The work presented compares results obtained in reconstructed epithelium and monolayer primary cultures of human keratinocytes.After application of a hydrosoluble product, the increase in intracellular ATP is identical in a monolayer culture of keratinocytes (+239±18% versus control) and in Episkin (+248±21% versus control). An emulsion was also tested on the two models. It is only possible to test the emulsion at a dilution of under 0.05% on a keratinocyte culture, and this means that the real efficacy of the product is underestimated (+145±18% versus control). The three-dimensional model enables the application of the undiluted emulsion, and the results show an increase in intracellular ATP of +420±80% versus control: products in final formulation can be tested in normal conditions of use.Abbreviations BPE bovine pituitary extract - DMEM Dulbecco's modified Eagle's medium - EDTA ethylene diamine tetraacetic acid - EGF epidermal growth factor - K-SFM keratinocytes serum free medium - MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide - O/W oil in water - PBS phosphate-buffered saline     

By-Products of Zea mays L.: A Promising Source of Medicinal Properties with Phytochemistry and Pharmacological Activities: A Comprehensive Review

Zea mays (Z. mays) is one of the main cereal crops in the world, and it′s by-products have exhibited medicinal properties to explore. This article intends to review the chemical compositions and pharmacological activities of by-products of Z. mays (corn silks, roots, bract, stems, bran, and leaves) which support the therapeutic potential in the treatment of different diseases, with emphasis on the natural occurring compounds and detailed pharmacological developments. Based on this review, 231 natural compounds are presented. Among them, flavonoids, terpenes, phenylpropanoids, and alkaloids are the most frequently reported. The by-products of Z. mays possess diuretic effects, hepatoprotective, anti-diabetic, antioxidant, neuroprotective, anti-inflammatory, anti-cancer, plant protection activity, and other activities. This article reviewed the phytochemistry and pharmacological activities of Z. mays for comprehensive quality control and the safety and effectiveness to enhance future application.     

中药金樱子的研究应用概况

本文就国内外对中药金樱子的化学成分及其提取分离方法、药理学研究和临麻应用作了综述,为金樱子的综合开发提供依据。     

Neuropeptide Y modulates the action of vasodilator agents in guinea-pig epicardial coronary arteries

Recently, we have demonstrated that guinea-pig epicardial coronary arteries are supplied by numerous nerve fibres containing neuropeptide Y (NPY) immunoreactivity. However, examination of vasomotor responses revealed that NPY did not elicit a contractile response in these arteries. In contrast, acetylcholine (ACh), calcitonin gene-related peptide (CGRP), substance P and vasoactive intestinal polypeptide (VIP) all relaxed precontracted arteries. In the present study, we have used histochemical, immunohistochemical and in vitro pharmacological techniques, in order to further investigate the possible role of NPY in guinea-pig epicardial coronary arteries. A double-immunofluorescence staining technique revealed that CGRP and substance P were co-localized in nerve fibres distinct from those displaying NPY immunoreactivity. Furthermore, using a method combining immunofluorescence and histochemical techniques, we observed that putative cholinergic nerve fibres (identified by their acetylcholinesterase content) and NPY-immunoreactive nerve fibres are two different nerve populations. An in vitro pharmacological method demonstrated that NPY markedly inhibited the relaxant responses mediated by ACh, VIP, substance P and isoprenaline but had no effect on CGRP. These results suggest that NPY-containing nerves associated with guinea-pig epicardial coronary arteries may be predominantly involved in modulating the action of vasodilator agents.     

Should biochemical markers of bone turnover be considered standard practice for safety pharmacology?

The success in biomedical sciences such as genomics and proteomics is not paralleled in the medical product development methods. The consequence of this is a lack of translation into improved drug safety and efficacy. Therefore the US Food and Drug Administration (FDA) introduced the Critical Path Initiative in 2004 to modernize drug development and safety pharmacology. Bone is that largest tissue by weight, and is continuously remodelled. Changes in bone turnover lead to complications such as osteoporosis and fracture, that is associated with an increased mortality. Recent findings have identified bone as a possible endocrine organ and the availability of valid biochemical bone markers suggests that assessing bone turnover should also play an important role in general safety pharmacology.