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.

Arachidonic acid is a constituent of the phospholipid domain of biological membranes. Activation of phospholipases results in its release into the intracellular milieu where it is subject to metabolism to biologically active compounds. In most cell types, including the platelet (1), the predominant enzyme involved in catalyzing arachidonate release is phospholipase A2 rather than phospholipase C (2). It has recently been shown that arachidonate may be subject to direct oxygenation within the cell membrane (3); the biological role of this process remains speculative.

The molecular, biochemical and human pharmacology of thromboxane A2 in renal disease.

A 25-y-old woman, who had been on an oral contraceptive pill for 3 years, presented with pulmonary embolism. One month prior to presentation she had been started on valdecoxib for neck pain.

/pdf/pulmonary-embolism-in-a-woman-taking-oral-contraceptives-and-1gbs0z1vo0.pdf

Pulmonary embolism in a woman taking oral contraceptives and valdecoxib.

Chapter 6 – Prostaglandins and Other Lipid Mediators in Reproductive Medicine

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a wide spectrum of symptom severity, which is manifested at different phases of infection and demands different levels of care. Viral load, host innate-immune response to SARS-CoV-2, and comorbidities have a direct impact on the clinical outcomes of COVID-19 patients and determine the diverse disease trajectories. The initial SARS-CoV-2 penetrance and replication in the host causes death of infected cells, determining the viral response. SARS-CoV-2 replication in the host triggers the activation of host antiviral immune mechanisms, determining the inflammatory response. While a healthy immune response is essential to eliminate infected cells and prevent spread of the virus, a dysfunctional immune response can result in a cytokine storm and hyperinflammation, contributing to disease progression. Current therapies for COVID-19 target the virus and/or the host immune system and may be complicated in their efficacy by comorbidities. Here we review the evidence for use of two classes of anti-inflammatory drugs, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of COVID-19. We consider the clinical evidence regarding the timing and efficacy of their use, their potential limitations, current recommendations and the prospect of future studies by these and related therapies.

Nonsteroidal anti-inflammatory drugs and glucocorticoids in COVID-19.

Before menopause, women are relatively protected against cardiovascular disease. Although estrogen (E 2 ) retards atherogenesis in animal models and improves endothelial function in women with hyperlipidemia, the mechanisms of atheroprotection remain to be defined completely. The prostaglandin PGI 2 inhibits platelet activation, vascular smooth muscle contraction, leukocyte-endothelial cell interactions, and cholesteryl ester hydrolase. PGI 2 analogs limit atherogenesis, and atherosclerotic lesions have a reduced ability to produce PGI 2 . Cyclooxygenase 2 (COX-2), expressed in vascular endothelial cells, catalyzes the formation of prostaglandin endoperoxide from arachidonic acid, and this subsequently is transformed to PgI 2 in endothelial cells by the action of PGI 2 synthase. Selective COX-2 inhibitors retard the excretion of PGI 2 metabolites. These mechanisms may be relevant to atheroprotection in women because E 2 increases the expression of COX-2 in vascular tissues and promotes the in vitro production of PGI 2 . Male mice lacking low-density lipoprotein receptor (LDLR) developed atherosclerosis more rapidly than did females, despite the lack of differences in total plasma cholesterol or high-density lipoprotein cholesterol. Female mice lacking both PGI 2 receptor and the LDLR developed more prominent aortic lesions than did LDLR-knockout females (ie, lacking the gene for the LDL receptor). This effect was not gene dose-dependent and was not apparent in male mice. Further observations indicated that PGI 2 decreases the platelet activation that characterizes early atherogenesis in female mice. It appears that PGI 2 serves as an antioxidant in female LDLR-knockout mice before atherogenesis and at its earliest stage. Adding hydrogen peroxide to cultured mouse aortic smooth muscle cells increased synthesis of PGI 2 and lipid peroxidation. There was no change in the expression of COX-2. Peroxide increased reactive oxygen species, and this effect was augmented by the lack of PGI 2 receptor expression. These observations suggest that the PGI 2 receptor modulates oxidant stress under baseline conditions. Importantly, E 2 stimulated COX-2 expression and PGI 2 formation. These findings suggest that E 2 receptor alpha-mediated COX-2 stimulation of PGI 2 makes a substantial contribution to atheroprotection in female LDLR-knockout mice. It is possible that ongoing treatment of patients with selective COX-2 inhibitors might undermine protection from cardiovascular disease in premenopausal females.

Garret A. FitzGerald

Papers

The molecular, biochemical and human pharmacology of thromboxane A2 in renal disease.

Pulmonary embolism in a woman taking oral contraceptives and valdecoxib.

Chapter 6 – Prostaglandins and Other Lipid Mediators in Reproductive Medicine

Nonsteroidal anti-inflammatory drugs and glucocorticoids in COVID-19.

Cyclooxygenase-2-derived prostacyclin confers atheroprotection on female mice