抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Chronic obstructive pulmonary disease (COPD) remains a major public health problem. It is the fourth leading cause of chronic morbidity and mortality in the United States, and is projected to rank fifth in 2020 in burden of disease worldwide, according to a study published by the World Bank/World Health Organization. Yet, COPD remains relatively unknown or ignored by the public as well as public health and government officials. In 1998, in an effort to bring more attention to COPD, its management, and its prevention, a committed group of scientists encouraged the U.S. National Heart, Lung, and Blood Institute and the World Health Organization to form the Global Initiative for Chronic Obstructive Lung Disease (GOLD). Among the important objectives of GOLD are to increase awareness of COPD and to help the millions of people who suffer from this disease and die prematurely of it or its complications. The first step in the GOLD program was to prepare a consensus report, Global Strategy for the Diagnosis, Management, and Prevention of COPD, published in 2001. The present, newly revised document follows the same format as the original consensus report, but has been updated to reflect the many publications on COPD that have appeared. GOLD national leaders, a network of international experts, have initiated investigations of the causes and prevalence of COPD in their countries, and developed innovative approaches for the dissemination and implementation of COPD management guidelines. We appreciate the enormous amount of work the GOLD national leaders have done on behalf of their patients with COPD. Despite the achievements in the 5 years since the GOLD report was originally published, considerable additional work is ahead of us if we are to control this major public health problem. The GOLD initiative will continue to bring COPD to the attention of governments, public health officials, health care workers, and the general public, but a concerted effort by all involved in health care will be necessary.

https://www.who.int/respiratory/copd/GOLD_WR_06.pdf

Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary.

At high concentrations, free radicals and radical-derived, nonradical reactive species are hazardous for living organisms and damage all major cellular constituents. At moderate concentrations, how...

/pdf/free-radicals-in-the-physiological-control-of-cell-function-g3w3iyr0ph.pdf

Free Radicals in the Physiological Control of Cell Function

The REDCap consortium: Building an international community of software platform partners.

Comprehensive Integration of Single-Cell Data.

The impact of cyclooxygenase‐2 selective and non‐isoform selective NSAIDs on the gut microbiota

Arachidonic acid is converted to an array of potent biological mediators such as prostaglandins, leukotrienes and thromboxane in a tissue and cell specific fashion (1,2). The enzymes that catalyze these transformations, leukocyte 5-lipoxygenase, reticulocyte/eosinophil 15-lipoxygenase, platelet 12-lipoxygenase, prostaglandin G/H synthase (cyclooxygenase) and leukotriene A4 hydrolase have been characterized and their sequences have been deduced by cloning of their respective complementary DNAs (3–10). Besides substrate availability, it has become increasingly evident that transcriptional and translational control as well as “suicide-type” inactivation are critical factors that regulate eicosanoid generation (11). We have now established a quantitative polymerase chain reaction (PCR) assay as a means to assess this regulation at the mRNA level.

Lipoxygenase, Cyclooxygenase and Leukotriene A4 Hydrolase: Quantitative Polymerase Chain Reaction and Expression Studies

An aqueous-based formulation for coating aspirin 
granules to provide granules that may be compressed into 
tablets and that show approximately zero-order release 
kinetics for release rates of 5 to 15 mg/hour over a period 
extending five to eight hours is provided. The coating 
formulation preferably consists of an acrylate/methacrylate 
copolymer, hydroxypropylmethylcellulose, sodium chloride and 
talc. A film-coated tablet comprised of the coated 
granules, filler granules, excipients, binders and 
disintegrants is also provided, as are processes for 
preparing the tablets and granules and methods for their use 
in the treatment of vascular occlusive diseases.

Controlled-release, low-dose aspirin

Inhibitors of microsomal prostaglandin E synthase-1 (mPges-1) are in the early phase of clinical development. Deletion of mPges-1 confers analgesia, restrains atherogenesis and fails to accelerate thrombogenesis, while suppressing prostaglandin (PG) E2, but increasing biosynthesis of prostacyclin (PGI2). In hyperlipidemic mice, this last effect represents the dominant mechanism by which mPges-1 deletion restrains thrombogenesis, while suppression of PGE2 accounts for its anti-atherogenic effect. However, the impact of mPges-1 depletion on blood pressure (BP) in this setting remains unknown. To address how differential effects on PGE2 and PGI2 might modulate salt-evoked BP responses in the absence of mPges-1, we generated mice lacking the I prostanoid (Ipr) receptor or mPges-1 on a hyperlipidemic background caused by deletion of the low density lipoprotein receptor (Ldlr KOs). Here, mPges-1 depletion significantly increased the BP response to salt loading in male Ldlr KO mice, whereas, despite the direct vasodilator properties of PGI2, Ipr deletion suppressed it. Furthermore, combined deletion of the Ipr abrogated the exaggerated BP response in male mPges-1 KO mice. Suppression of PGE2 biosynthesis was enough to explain the exaggerated BP response to salt loading by either mPges-1/Ldlr depletion or by an MPGES-1 inhibitor in mice expressing human mPGES-1. However, the lack of a hypertensive response to salt in Ipr-deficient mice was attributable to reactive activation of the atrial natriuretic peptide pathway. Interestingly, these unexpected BP phenotypes were not observed in female mice fed a high salt diet. This is attributable to the protective effect of estrogen in Ldlr KO mice and in Ipr /Ldlr DKOs. Thus, estrogen compensates for a deficiency in PGI2 to maintain BP homeostasis in response to high salt in hyperlipidemic female mice. In males, by contrast, augmented formation of ANP plays a similar compensatory role, restraining hypertension and oxidant stress in the setting of Ipr depletion. Hyperlipidemic males on a high salt diet might be at risk of a hypertensive response to mPGES-1 inhibitors.

/pdf/sex-dependent-compensatory-mechanisms-to-preserve-blood-3zm4eh16eg.pdf

Garret A. FitzGerald

Papers

The impact of cyclooxygenase‐2 selective and non‐isoform selective NSAIDs on the gut microbiota

Lipoxygenase, Cyclooxygenase and Leukotriene A4 Hydrolase: Quantitative Polymerase Chain Reaction and Expression Studies

Controlled-release, low-dose aspirin

Sex dependent compensatory mechanisms to preserve blood pressure homeostasis in PGI2 receptor deficient mice

Platelets in Thrombotic and Non-thrombotic Disorders: Platelet receptors: prostanoids