Protective Environmental Factors and Opioid Use Among Sexual Minority Youth.

Objectives: Nonmedical use of prescription opioids (NMUPO) is a pressing public health concern and affects sexual minority youth (SMY) at greater rates than heterosexual youth. We investigated whether protective environmental factors-(1) Human Rights Campaign's state equality index (SEI) and (2) supportive school environments for LGBTQ youth, influenced NMUPO among SMY and non-SMY students. Methods: We combined data from the 2017-2019 Youth Risk Behavior Survey, 2016-2018 School Health Profiles, state-level socio-demographic and SEI data across 24 states (N=156,149). Generalized linear mixed models examined associations between (1) SEI and (2) supportive school environments for LGBTQ youth, with NMUPO, accounting for clustering at the school-and state-level. Results: Before adjustment, we found that youth in states with higher SEI were significantly less likely to engage in NMUPO compared to students in states with lower SEI, a relationship that became non-significant after adjustment. After adjusting for individual-and state-level indicators, SMY in states with supportive school environments for LGBTQ youth were less likely to engage in NMUPO. Conclusions: Supportive school environments for LGBTQ youth may play an important role in the health of SMY. Establishing more inclusive policies and supportive environments within schools may reduce NMUPO among SMY.

Adverse childhood experiences, antenatal stressful life events, and marijuana use during pregnancy: A population-based study.

Cumulative exposure to adverse childhood experiences (ACEs) and antenatal stressful life events (ASLEs) are independently associated with marijuana use during pregnancy. However, research has not explored how both exposures may influence marijuana use jointly. Assessing the joint associations of ACEs and recent ASLEs on marijuana use can identify people who may benefit from early intervention. Data come from the Nevada Pregnancy Risk Assessment Monitoring System, 2017-2020 (N = 2483). We assessed eight measures of ACEs before age 18 and fourteen measures of ASLEs twelve months before giving birth. Generalized estimating equations estimated the direct and joint associations (additive and multiplicative interaction) of ACEs and ASLEs on marijuana use during pregnancy. 9.8% used marijuana during the most recent pregnancy. Compared to people who reported no ACEs, those reporting 1 ACE (adjusted prevalence ratio[aPR] = 1.96, 95% confidence interval [CI] = 1.30-2.94), 3 ACEs (aPR = 3.58, 95%CI = 2.69-4.77), and 4+ ACEs (aPR = 3.67, 95%CI = 2.36-5.72) were more likely to use marijuana. Compared to people reporting no ASLEs, those reporting 4+ ASLEs (aPR = 3.12, 95% CI = 1.64-5.92) were more likely to use marijuana. There was evidence of interaction for high ACE and ASLE exposure on an additive scale. ACEs and ASLEs were independently associated with marijuana use during pregnancy, and there was evidence of additive interaction. Screening for ACEs and ASLEs during pregnancy, referrals to appropriate behavioral health services, and trauma-informed approaches are important to address marijuana use during pregnancy.

Associations between Circumstances Surrounding Overdose and Underlying Classes of Polysubstance Overdose Deaths.

BACKGROUND: The overdose crisis is worsening, with polysubstance overdose deaths involving psychostimulants increasing in the U.S. Substance-specific prevention and intervention activities may not be as effective for polysubstance use, so we sought to classify substances used among overdose decedents to identify unique factors related to these classes. METHODS: We used data from the Nevada State Unintentional Drug Overdose Reporting System, Jan 2019-Jun 2021, which comes from death certificates, coroner/medical examiner reports, and postmortem toxicology. Latent class analysis, multinomial logistic regression, and Chi-squared tests determined underlying drug use classes, differences in characteristics and circumstances surrounding overdose, and assessed relationships between circumstances and drug use classes. RESULTS: We identified four latent classes: (1) prescription drugs (19.1%), (2) predominately methamphetamine (31.4%), (3) multi-drug (28.9%), and (4) opioid and stimulant (20.6%). Compared to other classes, the prescription drug class had a higher percentage of female decedents, from rural counties, with mental health diagnoses, who died at home. The predominately methamphetamine class had a higher percentage of decedents experiencing homelessness. The multi-drug use class had higher percentage of younger and Hispanic decedents. Those in the opioid and stimulant class had higher odds of being recently released from an institutional setting, compared to the multi drug class. CONCLUSIONS: These underlying classes were associated with several characteristics and circumstances that can prove useful for prevention, treatment, and harm reduction agencies when designing programs and interventions to target specific groups of people at-risk for drug overdose.

Antioxidants: Looking Forward after a Decade.

As our journal, Antioxidants, celebrates its tenth year, I want to express my gratitude to our publisher, MDPI, the editorial staff, our editors and reviewers, and the many authors for making it possible for Antioxidants to become a respective premier journal [...].

Caveats for the Good and Bad of Dietary Red Meat.

Red meat and its constituents of heme iron or free iron have been the target of scrutiny related to their purported association to many chronic diseases. However, in contrast, red meat provides a rich source of nutrition. In 2007, Al Tappel hypothesized that the mechanistic explanation for the adverse impact of iron and heme iron could be the strong influence these substances have in initiating and promoting oxidative stress. Also, there is an emphasis on the importance of dietary antioxidants in the modulation of these adverse effects. The goal of this argumentative review is to provide an update of the importance of dietary red meat for health, and the hypothesis that oxidative stress initiated by dietary iron and heme iron may be related to chronic diseases, with a particular emphasis on recent research that impacts the paradigm. We also examine potential dietary changes that could substantially modify the potential adverse outcomes of chronic diseases initiated by heme iron mechanisms, e.g., consumption of antioxidant-rich fruits and vegetables.

Use of Saliva Biomarkers to Monitor Efficacy of Vitamin C in Exercise-Induced Oxidative Stress.

Saliva is easily obtainable for medical research and requires little effort or training for collection. Because saliva contains a variety of biological compounds, including vitamin C, malondialdehyde, amylase, and proteomes, it has been successfully used as a biospecimen for the reflection of health status. A popular topic of discussion in medical research is the potential association between oxidative stress and negative outcomes. Systemic biomarkers that represent oxidative stress can be found in saliva. It is unclear, however, if saliva is an accurate biospecimen as is blood and/or plasma. Exercise can induce oxidative stress, resulting in a trend of antioxidant supplementation to combat its assumed detriments. Vitamin C is a popular antioxidant supplement in the realm of sports and exercise. One potential avenue for evaluating exercise induced oxidative stress is through assessment of biomarkers like vitamin C and malondialdehyde in saliva. At present, limited research has been done in this area. The current state of research involving exercise-induced oxidative stress, salivary biomarkers, and vitamin C supplementation is reviewed in this article.

Vitamin and Trace Element Loss from Negative-Pressure Wound Therapy.

OBJECTIVE: This study investigated select vitamin and trace element loss from wound exudates in burn and trauma patients treated with negative-pressure wound therapy (NPWT). DESIGN: A prospective observational study was performed using wound exudate samples. SETTING: A level I trauma center acute care hospital. PARTICIPANTS: The study was composed of 8 patients with open abdomens and 9 patients with 12 soft-tissue wounds. MAIN OUTCOME MEASURES: The goal was to collect wound exudate samples daily for 3 days, then every other day to day 9 or until NPWT was discontinued, and to analyze for vitamins A (retinol), C, and E and zinc (Zn), iron (Fe), and copper (Cu). Daily loss of each micronutrient was calculated from their concentration and 24-hour volumes of the exudates. MAIN RESULTS: Exudate loss in the open-abdomen group was significantly higher than in the patients with soft-tissue wounds (900 ± 547 vs 359 ± 246 mL/d). The mean 24-hour loss of vitamins A, C, and E were 0.3, 2.8, and 11 mg, respectively, in the open-abdomen group. Over the same period, the losses of Zn, Fe, and Cu were 0.5, 0.4, and 0.25 mg, respectively, in these patients. Micronutrient 24-hour loss was significantly lower in the soft-tissue wound patients than in the open-abdomen group. CONCLUSIONS: The data support the concept that significant amounts of micronutrients can be lost from NPWT wound exudates, particularly in open abdomens. These losses should be considered in the nutritional support of these patients who typically are in a hypermetabolic and catabolic state.

Metabolic diseases and pro- and prebiotics: Mechanistic insights.

Metabolic diseases, such as obesity and type 2 diabetes, are world-wide health problems. The prevalence of metabolic diseases is associated with dynamic changes in dietary macronutrient intake during the past decades. Based on national statistics and from a public health viewpoint, traditional approaches, such as diet and physical activity, have been unsuccessful in decreasing the prevalence of metabolic diseases. Since the approaches strongly rely on individual's behavior and motivation, novel science-based strategies should be considered for prevention and therapy for the diseases. Metabolism and immune system are linked. Both overnutrition and infection result in inflammation through nutrient and pathogen sensing systems which recognize compounds with structural similarities. Dietary macronutrients (fats and sugars) can induce inflammation through activation of an innate immune receptor, Toll-like receptor 4 (TLR4). Long-term intake of diets high in fats and meats appear to induce chronic systemic low-grade inflammation, endotoxicity, and metabolic diseases. Recent investigations support the idea of the involvement of intestinal bacteria in host metabolism and preventative and therapeutic potentials of probiotic and prebiotic interventions for metabolic diseases. Specific intestinal bacteria seem to serve as lipopolysaccharide (LPS) sources through LPS and/or bacterial translocation into the circulation due to a vulnerable microbial barrier and increased intestinal permeability and to play a role in systemic inflammation and progression of metabolic diseases. This review focuses on mechanistic links between metabolic diseases (mainly obesity and type 2 diabetes), chronic systemic low-grade inflammation, intestinal environment, and nutrition and prospective views of probiotic and prebiotic interventions for the diseases.

Modulation of oxidative stress by γ-glutamylcysteine (GGC) and conjugated linoleic acid (CLA) isomer mixture in human umbilical vein endothelial cells.

Individually, γ-glutamylcysteine (GGC), a dipeptide and precursor of glutathione (GSH), and conjugated linoleic acid (CLA), a trans-fatty acid, exhibit antioxidant properties. The objective of this study was to compare effects of co-administration of GGC and CLA to treatment with GGC alone on oxidative stress and GSH synthesis in human endothelial cells. Changes in levels of 8-epi-PGF2α, thiobarbituric acid reactive substances (TBARS), GSH, total antioxidants, GSH synthetase (GSS) expression, and transcription factor DNA binding were assessed in human umbilical vein endothelial cells (HUVEC) treated with GGC alone (100 µmol/L) or combined with CLA isomer mixture (10, 50, 100 µmol/L) for 24h. Significantly higher levels of TBARS, 8-epi-PGF2α, GSH, and GSS protein were found in cells treated with GGC and 10 µmol/L CLA, compared to cells treated with GGC alone, indicative of prooxidant effects of CLA. Approximately 40% cell death was microscopically observed in cells incubated with GGC and 100 µmol/L CLA. Despite lower levels of GSH, treatment with GGC and 50 µmol/L CLA appeared to be protective from oxidative stress similar to treatment with GGC alone, as indicated by lower levels of TBARS, compared to control cells not treated with GGC and CLA.

γ-Glutamylcysteine inhibits oxidative stress in human endothelial cells.

AIMS: γ-Glutamylcysteine (GGC) is a dipeptide and substrate for synthesis of the antioxidant glutathione (GSH), whose health promoting properties include reducing risks of oxidative stress-related injuries and diseases. The objective of this study was to investigate the efficacy of GGC on GSH synthesis and oxidative stress in human endothelial cells. MAIN METHODS: We assessed oxidative stress, GSH, GSH synthetase (GSS) expression, and transcription factor DNA binding levels in human umbilical vein endothelial cells (HUVEC). KEY FINDINGS: We found significantly higher levels of PPARγ DNA binding and lower levels of GSH, GSS protein, NF-κB p65 DNA binding, thiobarbituric acid reactive substances (TBARS), and 8-epi-PGF(2α) in a concentration-dependent manner, compared with the control. GSH and GSS protein levels showed a negative correlation with PPARγ DNA binding levels and positive correlation trends with NF-κB p65 DNA binding, TBARS, and 8-epi-PGF(2α) levels. A putative binding site for NF-κB was found at 4 227 bases upstream from the transcription start site of GSS gene, but none for PPARs. These findings suggest the involvement of NF-κB in regulation of GSS expression. Subsequent GSH synthesis might be affected by the suppression of GSS expression in tested conditions. SIGNIFICANCE: Besides its substrate role in GSH synthesis, GGC may play a role in protection against oxidative stress by serving as an antioxidant and modulating the expression of protein(s) related to antioxidant defense. Thus, we speculate that GGC may serve as a novel intra- and intercellular therapeutic dipeptide for oxidative stress-related injuries and diseases.

Antioxidants to Supplement or Not to Supplement That Is the Question.

Antioxidants, whether from diet or pharmacological supplementation, gained significant popularity among scientists and lay public in recent years, and was claimed to protect or treat numerous ailments. [...].

Safety of vitamins and minerals: controversies and perspective.

Available information suggests that currently over 47% of males and 59% of females use dietary supplements for health benefits, and the number of users is rapidly increasing. However, numerous studies published over more than a decade have linked some supplements (including vitamins E, C, D, A, and B, as well as selenium) to no health benefits or even to adverse health effects. Recent studies with negative results, which drew media attention, include the following: a 2008 study on the ability of vitamin E and selenium to lower the risk of prostate cancer was halted amidst fear of potential harm; vitamin C may do more harm than good as it may protect cancer cells; intake of vitamins E and C by 15,000 male physicians for 10 years had no health benefits. In contrast, there are compelling cause and effect data linking the use of folic acid with consistent and significant reductions in fetal adverse pregnancy outcomes, demonstrating no beneficial effects of calcium and vitamin D supplements in improving bone strength and reducing fractures. These equivocal and conflicting findings on the effects of supplements on health outcomes have left consumers confused about their benefits and wary of the possible adverse effects of vitamin and mineral supplementation. The objectives of this session are to characterize the current state of the science as it relates to the impact of vitamin and mineral supplementation on human health, review the statutory and regulatory perspective of vitamin use from a safety perspective, assess the credibility of meta-analysis in the safety assessment of vitamins, and elicit the mechanisms of these interactions-pro-oxidant versus antioxidant effects and beneficial versus adverse effects.

Lipophilic compound-mediated gene expression and implication for intervention in reactive oxygen species (ROS)-related diseases: mini-review.

In addition to exhibiting antioxidant properties, conjugated linoleic acid (CLA) and vitamin E may modulate gene expression of endogenous antioxidant enzymes. Depending on cellular microenvironments, such modulation reflects either antioxidant or prooxidant outcomes. Although epidemiological/experimental studies have indicated that CLA and vitamin E have health promoting properties, recent findings from clinical trials have been inconclusive. Discrepancies between the results found from prospective studies and recent clinical trials might be attributed to concentration-dependent cellular microenvironment alterations. We give a perspective of possible molecular mechanisms of actions of these lipophilic compounds and their implications for interventions of reactive oxygen species (ROS)-related diseases.

Conjugated linoleic acid isomers' roles in the regulation of PPAR-gamma and NF-kappaB DNA binding and subsequent expression of antioxidant enzymes in human umbilical vein endothelial cells.

OBJECTIVE: Conjugated linoleic acid (CLA) isomers have shown health benefits. Because CLA isomers may act as activators for peroxisome proliferator-activated receptors and may induce antioxidant enzymes, this study was conducted to examine the effects of CLA isomers on the gene expression of antioxidant enzymes, copper/zinc superoxide dismutase, and catalase in human umbilical vein endothelial cells. METHODS: Human umbilical vein endothelial cells were treated with graded concentrations of the 9-cis, 11-trans or the 10-trans, 12-cis-CLA isomer for 24 h. RESULTS: The 9-cis, 11-trans-CLA treatments resulted in increases in transcription factor DNA binding activities and expression of antioxidant enzymes at 0-25 micromol/L and an increase in lipid peroxidation only at the lowest concentrations (5 micromol/L). The 10-trans, 12-cis-CLA treatments resulted in increases in transcription factor DNA binding activities at 0-25 micromol/L and highest levels of mRNA of both antioxidant enzymes, superoxide dismutase protein, and lipid peroxidation only at the lowest concentrations (5 micromol/L). The 9-cis, 11-trans-CLA treatments produced expression of antioxidant enzymes, except catalase protein, that were positively correlated with lipid peroxidation. Positive correlations were found between expression of antioxidant enzymes, except catalase protein, and lipid peroxidation for 10-trans, 12-cis-CLA treatments. Although CLA isomers exhibit mostly stimulatory effects in expression of antioxidant enzymes, interestingly, the lowest concentrations of both CLA isomers resulted in increases in thiobarbituric acid-reactive substance levels. CONCLUSION: An understanding of the optimal concentrations of CLA isomers, which stimulate the benefits of antioxidant enzyme induction, may require careful CLA titration to determine predictable and dependable therapeutic strategies against adverse effects, such as pro-oxidants.

Air pollutants, oxidative stress and human health.

Air pollutants have, and continue to be, major contributing factors to chronic diseases and mortality, subsequently impacting public health. Chronic diseases include: chronic obstructive pulmonary diseases (COPD), cardiovascular diseases (CVD), asthma, and cancer. Byproducts of oxidative stress found in air pollutants are common initiators or promoters of the damage produced in such chronic diseases. Such air pollutants include: ozone, sulfur oxides, carbon monoxide, nitrogen oxides, and particulate matter. Interaction between oxidative stress byproducts and certain genes within our population may modulate the expression of specific chronic diseases. In this brief review we attempt to provide some insight into what we currently know about the health problems associated with various air pollutants and their relationship in promoting chronic diseases through changes in oxidative stress and modulation of gene expression. Such insight eventually may direct the means for effective public health prevention and treatment of diseases associated with air pollution and treatment of diseases associated with air pollution.

Alpha-tocopherol modulates human umbilical vein endothelial cell expression of Cu/Zn superoxide dismutase and catalase and lipid peroxidation.

Recent studies suggest the potential of alpha-tocopherol as a gene regulator, possibly through peroxisome proliferator-activated receptor gamma (PPARgamma) activation due to the structural similarity of alpha-tocopherol to a PPARgamma ligand, troglitazone. Other investigators have suggested that a link exists between induction of the antioxidant enzymes Cu/Zn superoxide dismutase (SOD) and catalase and PPARgamma activation. This study was designed to examine whether alpha-tocopherol modulates expression of Cu/Zn SOD and catalase in human umbilical vein endothelial cells through redox-sensitive transcription factors, PPARgamma, and nuclear factor-kappaB (NF-kappaB). Alpha-tocopherol treatments showed significant increases in both PPARgamma (1.4- to 2.2-fold, P < .01) and NF-kappaB p50 (1.3- to 1.5-fold, P < .005) DNA binding activities compared with vehicle control. Significant increases in Cu/Zn SOD mRNA levels (6.0-fold, P < .005) and catalase mRNA (8.0-fold, P < .005) and its protein levels (2.3-fold, P < .005) and lipid peroxidation levels (5.3-fold, P < .005) were observed at the lowest concentration (10 mumol/L) of alpha-tocopherol treatments. Both mRNA and protein levels of these 2 antioxidant enzymes were positively associated with lipid peroxidation (P < .05). Alpha-tocopherol may play a role not only in preventing against oxidative damage as an exogenous antioxidant by scavenging free radicals and superoxide but also in modulating the expression of the endogenous antioxidant enzymes as a gene regulator through PPARgamma and NF-kappaB in the vascular cells. The alpha-tocopherol-mediated gene expression is either stimulatory or inhibitory, depending on its oxidative status or its concentrations.

Conjugated linoleic acid modulation of risk factors associated with atherosclerosis.

Conjugated linoleic acid (CLA) has been the subject of extensive investigation regarding its possible benefits on a variety of human diseases. In some animal studies, CLA has been shown to have a beneficial effect on sclerotic lesions associated with atherosclerosis, be a possible anti-carcinogen, increase feed efficiency, and act as a lean body mass supplement. However, the results have been inconsistent, and the effects of CLA on atherogenesis appear to be dose-, isomer-, tissue-, and species-specific. Similarly, CLA trials in humans have resulted in conflicting findings. Both the human and animal study results may be attributed to contrasting doses of CLA, isomers, the coexistence of other dietary fatty acids, length of study, and inter-and/or intra-species diversities. Recent research advances have suggested the importance of CLA isomers in modulating gene expression involved in oxidative damage, fatty acid metabolism, immune/inflammatory responses, and ultimately atherosclerosis. Although the possible mechanisms of action of CLA have been suggested, they have yet to be determined.

Concentration-dependent antioxidant activities of conjugated linoleic acid and α-tocopherol in corn oil.

BACKGROUND: Antioxidants prevent rancidity (lipid peroxidation) and natural antioxidants, e.g., α-tocopherol, likely provide additional value to oil-based food products because of their health benefits. Conjugated linoleic acid (CLA) has potential health benefits and may exhibit antioxidant properties. The main aim of this study was to compare the antioxidant efficacy of α-tocopherol, trans-10, cis-12-CLA and cis-9, trans-11-CLA (in graded concentrations) added to antioxidant-stripped corn oil. RESULTS: As compared to α-tocopherol, both CLA isomers displayed significant inhibition of corn oil lipid peroxidation induced by copper. Inhibition of thiobarbituric acid reactive substances (TBARS) were CLA concentration dependent for both isomers but with significant inhibition occurring at 0.1 and 1 ppm of CLA isomers or α-tocopherol, respectively (P < 0.05). Graded concentrations of α-tocopherol, and for both CLA isomers and time, had significant effects on TBARS formation (P < 0.0001). There were significant effects in interactions between graded concentrations and time for both CLA isomers (P < 0.0001) but not for α-tocopherol (P > 0.05). CONCLUSION: CLA compounds could serve as useful food antioxidants and provide additional value because of their potential bioactivity in disease prevention. Copyright © 2007 Society of Chemical Industry.

Oxidation of serum low-density lipoprotein (LDL) and antioxidant status in young and elderly humans.

The incidence of atherosclerosis increases with age, as do various indices of free-radical mediated damage, e.g., lipid peroxidation. Because lipid peroxidation plays a prominent role in lipoprotein oxidation, likely a prelude to atherosclerosis, we compared the susceptibility of lipoproteins to oxidation in young (19-30 years) and elderly (59-86 years) groups. Although we found no significant differences in serum malondialdehyde (MDA) or oxidized LDL antibodies (OLAB) between young and elderly lipoproteins, MDA was directly related to OLAB regardless of age (r = 0.322, p = 0.005) and there was a trend for lower OLAB levels (30.5%, p = 0.079) in the elderly compared to the young population. Overall, serum antioxidant status was either similar or greater in the elderly group compared to the young group, likely reflecting antioxidant supplementation by the elderly group. OLAB was inversely related to Vitamin C (r = -0.310, p = 0.008) and Vitamin E intake (r = -0.277, p = 0.018) from foods and supplements. Serum levels of Vitamin C and Vitamin E were significantly higher (18.5%, p = 0.021 and 58.1 %, p < 0.001, respectively) in the elderly group compared to the young group and the ratio of Vitamin E to Vitamin C was significantly higher (30.4%, p = 0.042) in the serum of the elderly group. Oxidation of serum LDL and antioxidant status were not affected by age; however, the ratio of serum Vitamin E to Vitamin C was higher in the elderly group which may affect Vitamin E recycling.

Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation.

The in vitro assessment of the antioxidant capacity of four phenolic compounds; catechin, hesperidin, ferulic acid, and quercetin was evaluated by the examination of their ability to inhibit copper (Cu(2+))-mediated human low density lipoprotein (LDL) oxidation by using the thiobarbituric acid-reactive substances (TBARS) assay. Individually, the enrichment of LDLs with various concentrations of catechin, hesperidin, ferulic acid, and quercetin produced both antioxidant and prooxidant effects depending on enrichment concentrations of the polyphenolic compounds. Catechin and hesperidin had predominantly antioxidant effects (51.1%, 76.9%, respectively) while ferulic acid and quercetin had mostly prooxidant effects (166.4%; 191.8%, respectively) on LDL oxidation. However, when the mixture of the four phenolic compounds was used to enrich the LDLs, significant antioxidant capacity was demonstrated at all enrichment levels with a dose-response. Synergistic effects of the polyphenolic compounds as mixtures in preventing human LDL oxidation may reflect that nutritional advantages are found in the consumption of a variety of fruits and vegetables in preventing LDL oxidation and perhaps a host of cardiovascular diseases.