MULTIDRUG RESISTANT TUBERCULOSIS – BIOMECHANISM,EPIDEMIOLOGY AND MANAGEMENT STRATEGIES

Muitidrug resistant tuberculosis has shown an alarming increase and this assumes added importance in view of the increasing number of HIV infected patients. This article reviews the biomechanism of resistance and discusses the present stategies that are available and recommended to tackle the rising incidence of tuberculosis due to resistant mycobacteria.KEYWORDS: Antitubereular drugs, Drug resistance, Mycobacterium tuberculosis     

HPLC柱切换法血浆直接进样测定糖肾平

采用HPLC柱切换技术,以Merck Lichroprep RP2(25～40μm)为预处理柱填料,以水为预处理流动相,以0.2mol/L乙酸-乙酸铵为净化清洗液,血浆直接进样,在线富集净化样品。血浆样品以0.2ml/min慢速转移通过预处理柱,净化回收率达80%。以ShimpackCLC-ODS为分析柱(15cm×6mm,ID),甲醇-异丙醇-0.2mol/L 乙酸铵(61:5:34)为分析流动相,310nm波长检测,外标法定量测定人体血浆中糖肾平的浓度。血浆样品仅需稀释后即可进样,净化富集样品操作简便,预处理柱可长期反复进样使用。血浆中最低检测浓度为30ng/ml,日内变异系数为2.0%～5.4%,日间变异系数为2.4%～2.7%,在浓度为60～2020ng/ml血浆范围内呈线性关系。     

Gender difference in levels of alpha2-adrenoceptor mRNA in the rat tail artery

To investigate the hypothesis that differing mRNA levels underlie gender differences in the contractile response of the rat tail artery, alpha2-adrenoceptor mRNA was measured using in situ hybridization. Messenger RNA for the alpha2A- and alpha2C-adrenoceptor subtypes was found localized to the smooth muscle layer. There was no detectable mRNA present for the alpha2B-adrenoceptor subtype. Levels of alpha2C-adrenoceptor mRNA were greater in female compared to male tail arteries (417 +/- 35 vs. 263 +/- 38 dpm/mg, P = 0.01), while levels of alpha2A-adrenoceptor mRNA were the same in both sexes. Levels of alpha2-adrenoceptor mRNA may parallel levels of functioning protein present in the rat tail artery.     

Carcinogenic polycyclic aromatic hydrocarbons increase intracellular Ca2+ and cell proliferation in primary human mammary epithelial cells

Previous studies have shown that polycyclic aromatic hydrocarbons (PAHs) mobilize intracellular Ca2+ in human T cells by inositol trisphosphate-dependent mechanisms resulting from activation of phospholipase C-gamma by SRC-related protein tyrosine kinases, thereby mimicking antigen-receptor activation. Ca2+ appears to play an important second messenger role in growth factor control of cell proliferation in human mammary epithelial cells (HMEC), such as the epidermal growth factor receptor pathway. The purpose of the present studies was to determine if PAHs are able to increase intracellular Ca2+ in primary cultures of HMEC and increase cell proliferation. Two carcinogenic and two non-carcinogenic PAHs were tested for their ability to increase intracellular Ca2+ in HMEC. The carcinogenic PAHs dimethylbenz[a]anthracene (DMBA) and benzo[a] pyrene (BaP) were able to cause Ca2+ elevation in HMEC at early time points (2 h) and caused sustained alterations in Ca2+ homeostasis (18 h). DMBA showed maximal effects at early time points (2 h), while BaP showed maximal effects on sustained Ca2+ (18 h). 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), a potent dioxin and tumor promoter, produced maximal Ca2+ elevation at 2 h, with a return to near baseline levels by 6 h. The non-carcinogenic PAHs benzo[e]pyrene and anthracene did not significantly alter intracellular Ca2+ at any time point. alpha-Naphthoflavone significantly reduced the Ca2+ response induced by BaP treatment, but not by DMBA or TCDD, suggesting that P450 1A or 1B metabolism of BaP may be important in the sustained Ca2+ elevating response. In evaluating the effects of BaP on HMEC proliferation, BaP was found to increase the number of cells recovered after 4 days in culture in the absence or presence of various concentrations of epidermal growth factor. These studies provide initial evidence that Ca2+ signaling may be associated with mitogenesis in HMEC, which may play a role in tumor promotion and progression produced by PAHs.      

交流示波极谱滴定法测定盐酸环丙沙星及其制剂的含量

目的：采用交流示波极谱滴定法测定了盐酸环丙沙星及其制剂的含量。方法：在ｐＨ５．０－５．５的醋酸－醋酸钠缓冲液溶液中，环丙沙星与四苯硼钠定量反应形成１：１沉淀。过量的四苯硼钠用醋酸亚铊标准溶液回滴至示波极谱图上四苯硼钠切口消失。结果：该法平均回收率为９９．１８％，ＲＳＤ为０．４９％。结论：本法简便，快速，结果准确，可靠。     

Effect of melatonin in the rat tail artery: role of K+ channels and endothelial factors

1. The role of endothelial factors and potassium channels in the action of the pineal hormone melatonin to potentiate vasoconstrictor responses was investigated in the isolated perfused tail artery of the rat.
2. Melatonin (100 nM) potentiated contractile responses to both adrenergic nerve stimulation and α₁-adrenoceptor stimulation by phenylephrine. After removal of the endothelium, melatonin no longer caused potentiation.
3. The potentiating effect of melatonin was also lost when nitric oxide synthase was inhibited with L-NAME (10 nM). Thus potentiating effects depend on the presence of nitric oxide released by the endothelium. However, melatonin did not affect relaxation responses to acetylcholine in endothelium-intact arteries, nor did melatonin modulate relaxing responses to sodium nitroprusside in endothelium-denuded arteries. While melatonin does not appear to modulate agonist-induced release of nitric oxide nor its effect, melatonin may modulate nitric oxide production induced by flow and shear stress.
4. When the Ca²⁺-activated K⁺ channel opener, NS 1619 (10 μM), was present, potentiating effects of melatonin were restored in endothelium-denuded vessels. However, addition of the opener of ATP-sensitive K⁺ channels, cromakalim (3 μM), did not have the same restorative effect. Furthermore, addition of a blocker of Ca²⁺-activated K⁺ channels, tetraethylammonium (1 mM), significantly attenuated potentiating effects of melatonin. These findings support the hypothesis that melatonin inhibits the activity of large conductance Ca²⁺-activated K⁺ channels to produce its potentiating effects.
5. Thus in the rat perfused tail artery, potentiation of constriction by melatonin depends on the activity of both endothelial factors and Ca²⁺-activated K⁺ channels. Our findings suggest that melatonin inhibits endothelial K⁺ channels to decrease flow-induced release of nitric oxide as well as block smooth muscle K⁺ channels to enhance vascular tone.

     

睾丸酮、雌二醇和棉酚合并用药的雄性抗生育作用及其安全性的研究

睾丸酮、雌二醇和棉酚合并用药的雄性抗生育作用及其安全性的研究叶惟三，但凌，郭燕，钱晓菁，应骏，薛社普（中国医学科学院，中国协和医科大学基础医学研究所，北京１００００５）减轻有抗男性生育活性棉酚的副作用是发展棉酚成为男性避孕药急待解决的问题［１，２］。...