Abraham Z Reznick’s research while affiliated with Rambam Medical Center and other places

Acrolein is a highly reactive unsaturated aldehyde widely present in the environment, particularly as a product of tobacco smoke. Our previous studies indicated the adverse consequences of even short-term acrolein exposure and proposed a molecular mechanism of its potential harmful effect on oral cavity keratinocytic cells. In this paper we chose to review the broad spectrum of acrolein sources such as pollution, food, and smoking. Consequently, in this paper we consider a high level of oral exposure to acrolein through these sources and discuss the noxious effects it has on the oral cavity including on salivary quality and contents, oral resistance to oxidative stress, and stress mechanism activation in a variety of oral cells.

The history of stress research - milestones and people. Definitions and modern concepts of stress as well as the conflict between Hans Selye and the psychologists are described in this review. The molecular and physiological mechanisms of stress and their possible pharmacological intervention are introduced. The cycle of stress is presented as a new concept of the stress reaction, trying to bridge the gap between physiology and psychology. The cycle is a circular event in life, composed of 4 phases: (1) the resting ground phase, (2) the tension phase, (3) the response phase, and (4) the relief phase. In each phase, both physiological and psychological components can be assessed. These components are the basis for the proper handling of each phase and provide a unified model for the psycho-biological response to stress. In addition, parameters of the cycle such as frequency, duration, and intensity can be measured, providing an effective tool for stress management. Finally, modern techniques and mechanisms for coping with stress are discussed like the Norwegian Gate Theory and Lazarus Dichotomy Model for the Stress Reaction. In the above models, specific examples of how people respond to the first time encounter of stressful events and how soldiers cope with stress are presented.

The ubiquitin-proteasome system (UPS) is the main regulatory mechanism of protein degradation in skeletal muscle. The ubiquitin-ligase enzymes (E3s) have a central role in determining the selectivity and specificity of the UPS. Since their identification in 2001, the muscle specific E3s, muscle RING finger-1 (MuRF-1) and muscle atrophy F-box (MAFbx), have been shown to be implicated in the regulation of skeletal muscle atrophy in various pathological and physiological conditions. This review aims to explore the involvement of MuRF-1 and MAFbx in catabolism of skeletal muscle during various pathologies, such as cancer cachexia, sarcopenia of aging, chronic kidney disease (CKD), diabetes, and chronic obstructive pulmonary disease (COPD). In addition, the effects of various lifestyle and modifiable factors (e.g. nutrition, exercise, cigarette smoking, and alcohol) on MuRF-1 and MAFbx regulation will be discussed. Finally, evidence of potential strategies to protect against skeletal muscle wasting through inhibition of MuRF-1 and MAFbx expression will be explored.

Oxidative stress (OS) is common in inflammatory conditions and may be important in atopic dermatitis (AD) etiology. The aim of this project was to study the involvement of oxidation in FSL-1 (deacylated lipoprotein)-triggered signaling pathways leading to AD-typical cytokine expression in HaCaT keratinocytes. HaCaT keratinocytes, pretreated with the inhibitor to OS N-acetylcysteine (NAC), were exposed to FSL-1, a stimulator of AD-related cytokines. Cytokines expression was studied by real time polymerase chain reaction (PCR); nuclear factor-kappa B (NF-κB) and p38 mitogen activated protein kinase (MAPK) activities were studied by western blotting; and the oxidative state of cells was determined by the dichlorofluorescein (DCF) assay. We found that endogenous OS in keratinocytes appeared 4 h after FSL-1 administration. OS activated NF-κB, but not p38 MAPK, and the inhibition of OS reduced FSL-1 induced interleukin (IL) 33, thymic stromal lymphopoietin (TSLP) and TNFα mRNA expression. We conclude that FSL-1 triggers an OS reaction in HaCaT keratinocytes, which is probably a secondary event affecting the expression of specific AD typical cytokines, possibly through the NF-κB pathways. This role of OS in the inflammatory response in AD is worth further investigating.

Oxidative stress (OS), an imbalance in the oxidant-antioxidant equilibrium, is thought to be involved in the development of many seemingly unrelated diseases. Oral cavity tissues are a unique environment constantly exposed to internal and external compounds and material hazards as almost no other part of the human body. Some of the compounds are capable of generating OS. Here, the main groups of endogenous as well as exogenous OS sources are presented, followed by their oxidative effect on the salivary contents and function. The oxidative mechanisms in oral cells and their pathologic influence are also discussed.

AimsTo examine the effects of smoking cessation on body composition and muscle strength in comparison with continued smoking.Design and SettingA 12 month longitudinal study of adult smokers conducted in Haifa, Israel.ParticipantsEighty-one smokers recruited from a smoking cessation program combining group counseling and Varenicline treatment.MeasurementsMeasurements were taken at the beginning of the program and after 12 months. Body composition was assessed by dual-energy X-ray absorptiometry. Muscle strength was measured by handgrip dynamometry and predicted one-repetition maximum tests. Dietary intake and physical activity levels were estimated using questionnaires. Smoking status was determined by urine cotinine. The effect of smoking cessation was assessed using univariate and multivariable linear regression analyses.FindingsForty-one participants (age 44 ± 12 y) completed all baseline and follow-up measurements (76% continued smokers; 24% quitters). All measures of body composition and muscle strength were increased among quitters when compared with continued smokers. Adjusted differences (95% CI) between quitters and smokers were: body weight 4.43 kg (1.56 – 7.31 kg); lean mass 1.26 kg (0.24 – 2.28 kg); fat mass 3.15 kg (0.91 – 5.39 kg); bone mineral content 48.76 g (12.06 – 85.54 g); bone mineral density 0.024 g/cm2 (0.004 – 0.043 g/cm2); handgrip strength 3.6 kg (1.12 – 6.08 kg); predicted one-repetition maximum of chest press 7.85 kg (1.93 – 13.76 kg); predicted one-repetition maximum of leg press 17.02 kg (7.29 – 26.75 kg).Conclusions Smoking cessation is associated with weight gain mainly through accumulating extra fat but is also associated with increased muscle mass, muscle strength, and bone density.

Aging and obesity are linked to oxidative stress. Oxidative stress may mediate age related cardiovascular diseases. Though the body mass index (kg/m2) defines obesity (≥30) and overweight (25-29.9) it may fail to detect crucial differences in body fat content in elders. Consequently, we have measured body fatness in 42 healthy elders and evaluated their cardiovascular risk factors and the extent of their physical activity. We have assessed plasma, erythrocytes and saliva oxidative stress biomarkers in this population. A higher fat mass was associated with a less active lifestyle, more metabolic syndrome components, an enhanced Framingham 10-year risk score and augmented insulin resistance. Individuals with excessive body fat had significantly less oral peroxidase enzymes activity than those with normal body fat. Erythrocyte susceptibility to oxidative hemolysis previously reported to be elevated with physical activity, was marginally lower in the higher fat group. Other biomarkers of oxidative stress in saliva, plasma and erythrocytes were similar in both groups. A 6% elevation in body fat with a less active life style and an increased cardiovascular risk is associated with a decline in salivary anti-oxidative activity. Such reduced activity may contribute to the deteriorating oral health in obese elders. Thus, this study provides novel information on the contribution of excessive body fat to oxidative status and cardiovascular risk in old age.

Aldehydes and reactive nitrogen species (RNS) are important chemically active agents in cigarette smoke (CS). Salivary lactate dehydrogenase (LDH) originates predominantly from oral epithelium and was identified as an oral state marker. Its activity in saliva decreases after CS exposure. The aims of the current study were to identify the specific damaging agents in CS responsible for this activity reduction and to understand the mechanisms participating in CS oxidative damage to the salivary enzymes. Purified and salivary LDH samples were exposed to different levels of CS, pure acrolein, acetaldehyde, peroxynitrite and RNS donors. Each response of the isolated agent to the exposure was examined by a spectrophotometric enzyme activity assay and a Western blot. CS exposure caused a 34% reduction in LDH activity. Isolated treatment with unsaturated-aldehydes (acrolein, 10μmol) caused a 61% reduction, while saturated-aldehydes (acetaldehyde, 200μmol), peroxynitrite (200μM) and RNS donor (SIN-1, 2mM) caused no substantial effect. All five LDH isoenzymes reacted similarly. The carbonyl immunoblotting assay revealed a fourfold increase in carbonyl content when treated with CS and a sevenfold increase when treated with acrolein. α,β-Unsaturated-aldehydes were identified as the main CS ingredient responsible for salivary LDH activity diminution. The effect of saturated-aldehydes and RNS donors was negligible. Unsaturated-aldehydes are capable of introducing carbonyl group into proteins, causing their dysfunction. This provides a molecular explanation for a decrease in LDH enzymatic activity in saliva.