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.     

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.     

Heat, cold, noise, and vibration

Exposure to a cold environment induces a number of physiological alterations, the most serious being hypothermia. This state can occur in all individuals, but the very young and the elderly are more susceptible. Environmental and industrially generated high ambient temperature can place further stress on aged individuals and workers, resulting in a complex symptom picture. Morbidity and death may result from such exposures. Causative factors have been identified. Noise exposure induces hearing losses above those secondary to the aging process. Psychophysiological effects during noise exposure are considered to result from the sympathetic activity secondary to a general stress reaction. Vibration from the use of power tools results in Raynaud's phenomenon. However, modification of power tools has reduced the symptoms associated with vibration exposure. Termination of exposure to vibration appears eventually to reduce symptoms related to white-finger spasms. Interaction between these stressors has not been clarified because of the complex effects of each. The need for additional information about the response to these stressors is evident.     

Tetracyclines, chloramphenicol, erythromycin, and clindamycin

The tetracyclines are effective in the treatment of Chlamydia, Mycoplasma pneumoniae, and rickettsial infections and may also be used for gonococcal infections in patients unable to tolerate penicillins. These drugs may cause gastrointestinal irritation, photo-toxic dermatitis, diarrhea, vestibular damage, and hepatotoxicity in pregnant women. Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and typhoid fever. The most important toxic effect of chloramphenicol is bone marrow suppression, which can be dose related or idiosyncratic. Erythromycin is the drug of choice for the treatment of infections caused by M. pneumoniae, Legionella species, group A beta-hemolytic streptococci, and Streptococcus pneumoniae. The frequency of serious untoward effects associated with the use of erythromycin is low; epigastric distress may occur. Clindamycin is active against Bacteroides fragilis and other anaerobic microorganisms. Pseudomembranous enterocolitis has developed in as many as 10% of patients taking this drug. The use of clindamycin should be discontinued promptly if diarrhea occurs.     

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.     

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.     

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...