Non-diuretic-based antihypertensive therapy and potassium homeostasis in elderly patients

Aging and hypertension are associated with a progressive decline in renal blood flow and renal function. As a result, physicians planning therapeutic strategies to control blood pressure need to consider these changes and how they relate to potassium homeostasis, particularly in elderly patients. Commonly used antihypertensive drugs such as beta-blockers, angiotensin converting enzyme inhibitors and potassium-sparing diuretics need to be used with increasing caution in patients with declining renal function. This is especially important in patients with diabetes who may also have type IV renal tubular acidosis, and in patients given concomitant therapy with non-steroidal anti-inflammatory drugs. Other therapies such as calcium channel blockers, particularly those that gate atrioventricular nodal conduction, also need to be used with care in people with significant renal insufficiency and hyperkalemia, as this clinical scenario may result in a greater risk of complete heart block.     

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism symptoms in man, has been examined as a substrate of recombinant human cytochrome P450 2D6. When cumene hydroperoxide is used as an oxygen and electron donor, a single product is formed, identified as 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) for formation of this product (130 microM) is in agreement with the dissociation constants for MPTP binding to the enzyme determined by optical and nuclear magnetic resonance (NMR) spectroscopy. When the reaction is carried out with nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and recombinant human NADPH-cytochrome P450 reductase, a second product, identified as 1-methyl-4-(4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine, is formed in addition to 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) values for formation of these two products are 19 microM and 120 microM, respectively. Paramagnetic relaxation experiments have been used to measure distances between the protons of bound MPTP and the heme iron, and these have been used to construct models for the position and orientation of MPTP in the active site. For the cytochrome alone, a single mode of binding was observed, with the N-methyl close to the heme iron in a position appropriate for the observed N-demethylation reaction. In the presence of the reductase, the data were not consistent with a single mode of binding but could be explained by the existence of two alternative orientations of MPTP in the active site. One of these, characterized by a dissociation constant of 150 microM, is essentially identical to that observed in the absence of the reductase. In the second, which has a K(d) of 25 microM, the MPTP is oriented so that the aromatic ring is close to the heme iron, in a position appropriate for p-hydroxylation leading to the formation of the product seen only in the presence of the reductase. In the case of codeine, another substrate for cytochrome P450 2D6, the addition of reductase had no effect on the nature of the product formed, the dissociation constant, or the orientation in the binding site. These observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cytochrome P450 2D6 that affects the binding of some substrates but not others.     

Subtitled interaction: complementary support as an alternative to localization

Many computer users face problems in their interaction as a result of the native language employed by the application. The language of the application is often at variance with the native language of its users. This issue is frequently addressed through localization. In turn, localization generates a range of new problems. We propose an alternative to localization that is analogous to cinematic subtitles. This has the potential to reduce the user interaction defects that otherwise arise with localization whilst benefiting users through an additional channel of information in their own language. This paper outlines a prototype implementation and describes our initial evaluation of this approach. We suggest that our complementary ‘subtitles’ promise consistent support for all applications in the user's computing environment and yield a system that is expandable and much easier to maintain than pre-localized software.     

用白色LED做背光照明需考虑的事项

在过去几年中,小型彩屏从稀有物品变成了便携式消费电子产品(如手机、PDA和数字照相机)的主流特性。把彩屏集成进小型便携式设备的挑战之一是需要白光作为背光。对于如手提电脑的大型显示屏,通常使用的冷阴极荧光灯(CCFL),但因在其尺寸方面的限制和设计复杂性,很难用于更小型的应用。而白色LED具有优异的光学特性,因此成为小型显示屏背光显示的首选解决方案。此外,白色LED也可以用作键盘的背光。将白色LED与光导相配合,可提供均匀的白色背光。白色LED方案面临的挑战设计师在集成白色LED时所面临的挑战在于有如下几方面。(1) LED具…     

Access to hypertensive care. Effects of income, insurance, and source of care

BACKGROUND: This study examines the relationship between income, health insurance, and usual source of care characteristics and screening and management of hypertension. METHODS: This is a secondary analysis of data from the 1987 National Medical Expenditure Survey. Adult survey respondents constitute a sample representative of the total adult noninstitutionalized US population. Screening, follow-up care, and pharmacologic treatment for hypertension were examined among low income individuals, the uninsured, those without a usual source of care place, and those without a particular usual source of care physician. RESULTS: The uninsured, individuals without a usual source of care place, and those without a particular usual source of care physician received less screening, follow-up care, and pharmacologic treatment for hypertension. Income did not affect receipt of hypertensive care. CONCLUSIONS: Lack of health insurance and lack of a usual source of care are barriers to hypertensive care. Policies that increase access to health insurance or to usual source of care physicians may enable more individuals to attain control of hypertension.