NO and HNO donors,nitrones, and nitroxides: Past,present, and future

The biological effects attributed to nitric oxide (^?NO) and nitroxyl (HNO) have been extensively studied, propelling their array of putative clinical applications beyond cardiovascular disorders toward other age‐related diseases, like cancer and neurodegenerative diseases. In this context, the unique properties and reactivity of the N‐O bond enabled the development of several classes of compounds with potential clinical interest, among which ^?NO and HNO donors, nitrones, and nitroxides are of particular importance. Although primarily studied for their application as cardioprotective agents and/or molecular probes for radical detection, continuous efforts have unveiled a wide range of pharmacological activities and, ultimately, therapeutic applications. These efforts are of particular significance for diseases in which oxidative stress plays a key pathogenic role, as shown by a growing volume of in vitro and in vivo preclinical data. Although in its early stages, these efforts may provide valuable guidelines for the development of new and effective N‐O‐based drugs for age‐related disorders. In this report, we review recent advances in the chemistry of NO and HNO donors, nitrones, and nitroxides and discuss its pharmacological significance and potential therapeutic application.     

Vomiting, diarrhea, constipation, and gastroenteritis

Diseases that cause vomiting, diarrhea, constipation, and gastroenteritis are major problems for populations worldwide. Patients, particularly infants, elderly, and immunocompromised individuals, may present at any point in a wide spectrum of disease states, underscoring the need for the clinician to treat these ailments aggressively. Several promising new treatment modalities, from oral rehydration solutions to antiemetic therapies, have been introduced over the past decade. Future directions include the use of probiotic agents and better tolerated rehydration solutions. Gastrointestinal disease will continue to be a focus worldwide in the search for better ways to cure illnesses associated with vomiting and diarrhea.     

Platelets,thrombosis, coagulation,and atherosclerosis

When I first got the invitation to join a medical delegation going to Moldova, I thought for a moment that our destination was the fictional country in the old Marx Brothers movie Duck Soup. On further checking, it turns out that entertaining place was called Freedonia. I now know that Moldova is indeed a real country, bordered on the west by Romania and on the other three sides by the Ukraine. It is a proud country, rich with traditions, and its people are warm, giving, eager to learn ways to improve their healthcare system, and deeply appreciative of our attempts to help them in the task.     

Thoughts,images, worry,and anxiety

Recent models suggest that worry is primarily a verbal-linguistic process that enables images to be avoided and reduces somatic activation. Five-hundred and two subjects completed a questionnaire that assessed variables related to generalized anxiety disorder (GAD) criteria and also asked subjects to indicate the percentage of thoughts and images while worrying. Subjects were divided into excessive worriers (worry excessively about two or more topics more days than not for at least the last 6 months) and ordinary worriers (those who did not meet the previous criteria). As predicted, worry was reported as being composed predominantly of thoughts rather than images, and excessive worriers reported a significantly higher percentage of thoughts compared to ordinary worriers. The number of somatic symptoms was positively correlated with the percentage of images. This relationship was stronger among excessive worriers than ordinary worriers, specifically for autonomic hyperactivity symptoms. Further, in the excessive worry group only there was a significant negative correlation between the number of autonomic hyperactivity symptoms and the percentage of thoughts.This research was partially supported by grants from les Fonds de Recherche en Santé de Québec and the Medical Research Council of Canada. The study was completed while the first author was supported by the Medical Research Council of Canada.The authors gratefully acknowledge the assistance of France Blais for recruiting subjects, administering questionnaires, and entering data.     

Genomics, Nutrition, Obesity, and Diabetes

PURPOSE: To present evidence of genetic and environmental interactions as they relate to nutrition, diabetes, and obesity. METHODS: A review of seminal literature related to genetics, obesity, and diabetes. FINDINGS: Multifactorial interactions are important in the development of nutrition-related disorders, but the challenge remains to explain how these interactions are expressed. Treating subpopulations of people might be important and useful to some extent at present, but in the future treating people of given genetic predispositions and other personal and environmental factors will have greater effects on quality-of-life indicators and life expectancies. CONCLUSIONS: Individualization coupled with multifactorial interactions will lead to new and more effective preventive and treatment modalities of nutrition-related disorders. With obesity and diabetes, genomics will bridge the traditional use of diet, exercise, and weight reduction with other environmental factors, ultimately leading to healthier lives.     

Lipid messenger, diacylglycerol, and its regulator, diacylglycerol kinase, in cells, organs, and animals: history and perspective

Diacylglycerol kinase (DGK) metabolizes diacylglycerol (DG), a glycerolipid containing two acyl chains, to convert phosphatidic acid. DG is produced through phosphoinositide turnover within the membrane and is well known to act as a second messenger that modulates the activity of protein kinase C in the cellular signal transduction. Recent studies have revealed that DG also activates several proteins, including Ras guanine-nucleotide releasing protein and ion channels such as transient receptor potential proteins. Therefore, DGK is thought to participate in a number of signaling cascades by modulating levels of DG. Previous studies have disclosed that DGK is composed of a family of the isozymes, which differ in the structure, enzymological property, gene expression and localization, subcellular localization, and binding molecules. The present review focuses on the stories of phosphoinositide turnover and DG, including historical views, structural features, metabolism, and relevant cellular phenomena, together with the characteristics of DGK isozymes and the pathophysiological findings on animal studies using knockout mice and models for human diseases. Now it is being revealed that the structural and functional diversity and heterogeneity of and around DGK support the proper arrangement of the complex signal transduction machinery.     

Associations between craving,trauma, and the DARNU scale: Dissatisfied,anxious, restless,nervous, and uncomfortable

This study evaluated the clinical utility of a measure of negative emotionality, the DARNU scale (Dissatisfied, Anxious, Restless, Nervous, and Uncomfortable), using data from a naturalistic sample of consecutive admissions to a residential substance use treatment program. Data derived from routine clinical assessments of 124 (55.6% male) patients were analyzed to assess study aims. The DARNU scale in addition to measures of drug and alcohol craving, severity of posttraumatic stress disorder (PTSD), and severity of substance use disorder (SUD) were administered to all patients. Results revealed significant positive correlations between DARNU and PTSD (r = .783), craving (r = .366), and SUD (r = .331). The DARNU scale yielded a Cronbach’s alpha of .91. When patients were categorized into quartiles based on DARNU elevations, 88.9% of patients in the highest quartile met diagnostic criteria for PTSD, while 89.2% of patients in the lowest quartile did not receive a PTSD diagnosis. Linear regression indicated that the affective vulnerability measured by DARNU mediated the relationship between PTSD and craving. The DARNU scale may identify patients at elevated risk for relapse, and may have the potential to serve as a brief clinical indicator of PTSD without asking about a specific traumatic event.     

自立,自强,自信,再发展

2021年,世界科技、经济风云变幻,并随疫情的发展而跌宕起伏,然而,中国科技、经济的发展令人刮目相看,而我国的睡眠医学发展,正在走向自立,睡眠产业发展迅速,新的睡眠中心越建越好,中国开始拥有自己国家生产的睡眠监测设备,实现睡眠监测技术的自强,中国正在怀着极大的自信,在推进高原睡眠研究、生物节律研究以及与睡眠相应的生理学和药理学研究,脑的睡眠调控机制等方面的研究,期盼再次得到快速发展,国家开始投入资金研究破解国人亟须解决的各种睡眠障碍,世界科技也呼唤中国的睡眠科学持续发展,并加强世界各国睡眠研究者的学术交流。