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

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. Methods We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. Results The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P = 0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P = 0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P = 0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. Conclusions

/pdf/rosuvastatin-to-prevent-vascular-events-in-men-and-women-1ntr1oxafj.pdf

Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

The discovery that mammalian cells have the ability to synthesize the free radical nitric oxide (NO) has stimulated an extraordinary impetus for scientific research in all the fields of biology and medicine. Since its early description as an endothelial-derived relaxing factor, NO has emerged as a fundamental signaling device regulating virtually every critical cellular function, as well as a potent mediator of cellular damage in a wide range of conditions. Recent evidence indicates that most of the cytotoxicity attributed to NO is rather due to peroxynitrite, produced from the diffusion-controlled reaction between NO and another free radical, the superoxide anion. Peroxynitrite interacts with lipids, DNA, and proteins via direct oxidative reactions or via indirect, radical-mediated mechanisms. These reactions trigger cellular responses ranging from subtle modulations of cell signaling to overwhelming oxidative injury, committing cells to necrosis or apoptosis. In vivo, peroxynitrite generation represents a crucial pathogenic mechanism in conditions such as stroke, myocardial infarction, chronic heart failure, diabetes, circulatory shock, chronic inflammatory diseases, cancer, and neurodegenerative disorders. Hence, novel pharmacological strategies aimed at removing peroxynitrite might represent powerful therapeutic tools in the future. Evidence supporting these novel roles of NO and peroxynitrite is presented in detail in this review.

/pdf/nitric-oxide-and-peroxynitrite-in-health-and-disease-3uuuqgfdcz.pdf

Nitric Oxide and Peroxynitrite in Health and Disease

In chronic inflammatory diseases, such as asthma, rheumatoid arthritis, inflammatory bowel disease, and psoriasis, several cytokines recruit activated immune and inflammatory cells to the site of lesions, thereby amplifying and perpetuating the inflammatory state.1 These activated cells produce many other mediators of inflammation. What causes these diseases is still a mystery, but the disease process results from an interplay of genetic and environmental factors. Genes, such as those for atopy in asthma and for HLA antigens in rheumatoid arthritis and inflammatory bowel disease, may determine a patient's susceptibility to the disease and the disease's severity, but environmental factors, often unknown, . . .

Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases.

The inorganic anions nitrate (NO3-) and nitrite (NO2-) were previously thought to be inert end products of endogenous nitric oxide (NO) metabolism However, recent studies show that these supposedly inert anions can be recycled in vivo to form NO, representing an important alternative source of NO to the classical L-arginine-NO-synthase pathway, in particular in hypoxic states This Review discusses the emerging important biological functions of the nitrate-nitrite-NO pathway, and highlights studies that implicate the therapeutic potential of nitrate and nitrite in conditions such as myocardial infarction, stroke, systemic and pulmonary hypertension, and gastric ulceration

The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics

Background: Measurement of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) is a quantitative, noninvasive, simple, and safe method of measuring airway inflammation that provides a complementary tool to other ways of assessing airways disease, including asthma. While FeNO measurement has been standardized, there is currently no reference guideline for practicing health care providers to guide them in the appropriate use and interpretation of FeNO in clinical practice.Purpose: To develop evidence-based guidelines for the interpretation of FeNO measurements that incorporate evidence that has accumulated over the past decade.Methods: We created a multidisciplinary committee with expertise in the clinical care, clinical science, or basic science of airway disease and/or NO. The committee identified important clinical questions, synthesized the evidence, and formulated recommendations. Recommendations were developed using pragmatic systematic reviews of the literature and the GRADE approach....

/pdf/an-official-ats-clinical-practice-guideline-interpretation-1iahut6ven.pdf

An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.

Nitrate is generally considered a water pollutant and an undesirable fertilizer residue in the food chain Research in the 1970s indicated that, by reducing nitrate to nitrite, commensal bacteria might be involved in the pathogenesis of gastric cancers and other malignancies, as nitrite can enhance the generation of carcinogenic N-nitrosamines More recent studies indicate that the bacterial metabolism of nitrate to nitrite and the subsequent formation of biologically active nitrogen oxides could be beneficial Here, we will consider the evidence that nitrate-reducing commensals have a true symbiotic role in mammals and facilitate a previously unrecognized but potentially important aspect of the nitrogen cycle

Nitrate, bacteria and human health.

Dietary inorganic nitrate improves mitochondrial efficiency in humans.

High values (800-6000 parts per billion) of nitric oxide (NO) in expelled air from the stomach were shown in humans by chemiluminescence technique. These NO values were more than 100 times higher than those found in orally exhaled air. Intragastric NO production is probably non-enzymatic, requiring an acidic environment, as NO in expelled air was reduced by 95% after pretreatment with the proton pump inhibitor omeprazole. Furthermore, large amounts of NO were formed in vitro from lettuce and saliva when placed in hydrogen chloride (pH < 2). In conclusion, large amounts of NO are formed intragastrically in humans and this source of NO may be of importance for the integrity of the gastric mucosa in health and disease. Measurements of NO in expelled air might be of value as a non-invasive method for estimation of gastric acidity.

https://gut.bmj.com/content/gutjnl/35/11/1543.full.pdf

Jon O. Lundberg

Papers

The nitrate–nitrite–nitric oxide pathway in physiology and therapeutics

An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications.

Nitrate, bacteria and human health.

Dietary inorganic nitrate improves mitochondrial efficiency in humans.

Intragastric nitric oxide production in humans: measurements in expelled air