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Psychiatric and behavioural side effects are common, undesirable effects associated with antiseizure medication use. Temporal lobe epilepsy is the most common focal epilepsy in adults and it is frequently associated with drug resistance. Patients with intractable epilepsy are more likely to have psychiatric and behavioural side effects when taking antiseizure medications and seem to be at higher risk for psychiatric comorbidities. Perampanel is a novel anti-seizure medication approved for focal and generalised epilepsies as add-on therapy. This is a 12-week short-term observational prospective study on people with focal epilepsy consecutively recruited from an Italian tertiary epilepsy centre, aimed to compare incidence and severity of psychiatric and behavioural side effects associated with perampanel use in patients with temporal lobe epilepsy as compared to other focal epilepsies. All patients received add-on perampanel according to indication and clinical judgement. Incidence and severity of psychiatric and behavioural side effects were rated by Neuropsychiatric Inventory Questionnaire. All patients enrolled answered the questionnaire before starting perampanel and after 12 weeks of treatment. We found no significant difference in terms of incidence and severity of psychiatric and behavioural side effects associated with perampanel in patients with temporal lobe epilepsy as compared to other focal epilepsies. In line with the literature, the most common adverse effects were "irritability" for both groups and "aggression" for patients with other focal epilepsies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mammì, Ferlazzo, Gasparini, Bova, Neri, Labate, Mastroianni, Bianco, Cianci and Aguglia.)

Older adults with serious mental illness (SMI) experience increased medical comorbidities, disability, and early mortality, but little is known about how they perceive the process of aging. This study explored attitudes and beliefs about aging among n = 20 middle aged and older adults (M = 59.8 years; range 47-66) with SMI in a state psychiatric hospital. We conducted semistructured interviews using the Attitudes to Ageing Questionnaire (AAQ) and analyzed narrative accounts using a grounded theory approach. The mean scores of overall attitudes toward aging and of the subscale of perception of psychological growth were both positive compared to a neutral rating (p = 0.026 and p = 0.004, respectively). Study participants rated their experience on the subscales of psychosocial loss and physical health change as neutral. Despite substantial psychiatric, medical, and functional disabilities, older adults with SMI in this study of psychiatric inpatients perceived the process of aging as generally positive, suggesting resilience and potential positive emotional growth in older age., (Copyright © 2021 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

Individuals with serious mental illness (SMI) experience a 10- to 25-year reduced life expectancy compared with the general population. Early mortality for people with SMI has mainly been attributed to unhealthy behaviors (e.g., poor diet, sedentary lifestyle), which has led to the development of health promotion and self-management interventions specifically for people with SMI to promote health behavior change. Yet after decades of research, the mortality gap between people with SMI and the general population is increasing. To address this early mortality disparity for individuals with SMI, a new paradigm must be explored. In this article, we present the social processes impacting early mortality in people with SMI paradigm, which highlights the powerful role of social processes in shaping the health and health behaviors of people with SMI. This paradigm explores how loneliness, stigma (social and self), trauma, social exclusion, social isolation, and social norms are related to early mortality in people with SMI. This new paradigm is an important step in understanding and potentially addressing early mortality in people with SMI.

Adherence research commonly happens in a silo, focused on a particular disease state or type of therapy. Learning from outside disciplines can bring new insights and ideas. This article presents adherence research as related to people with a diagnosis of a serious mental illness (SMI) and medication adherence through smartphone applications (apps). Individuals with SMI have high rates of not taking medication, increasing risks of relapse and hospitalization. Advances in technology may be advantageous in promoting taking medication. Smartphones apps have been designed for people with SMI. Further research is needed to evaluate their efficacy on improving rates of taking medication., Competing Interests: Disclosure The authors have no relevant financial disclosures to report. Dr K.L. Fortuna was funded by a K01 award from the National Institute of Mental Health (K01MH117496)., (Copyright © 2020 Elsevier Inc. All rights reserved.)

To explore the association between loneliness and efficacy to engage in health behaviors that are known to reduce the risk of early mortality in people with serious mental illness (SMI). This secondary data analysis was based on a cross-sectional study of 113 participants with SMI residing in New Hampshire. Ordinary Least Squares regressions were used to examine bivariate relationships between variables of interest. Participants had a primary mental health diagnosis of major depressive disorder (37.2%), schizophrenia spectrum disorder (28.3%), bipolar disorder (29.2%), or posttraumatic stress disorder (5.3%). High levels of loneliness were associated with low levels of self-efficacy to manage chronic diseases (p = 0.0001), as well as low levels of self-efficacy to manage psychological well-being (R 2  = .31; F = 9.49, p = 0.0001; RMSE = 1.66). Loneliness may serve as a barrier to healthy behaviors, and thus, contribute to early mortality among people with SMI. The growing body of literature that demonstrates the importance of addressing loneliness in people with SMI should stimulate policymakers and researchers to target loneliness as a mechanism to address early mortality in people with SMI.

Background: Peer support is recognized globally as an essential recovery service for people with mental health conditions. With the influx of digital mental health services changing the way mental health care is delivered, peer supporters are increasingly using technology to deliver peer support. In light of these technological advances, there is a need to review and synthesize the emergent evidence for peer-supported digital health interventions for adults with mental health conditions., Objective: The aim of this study was to identify and review the evidence of digital peer support interventions for people with a lived experience of a serious mental illness., Methods: This systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) procedures. The PubMed, Embase, Web of Science, Cochrane Central, CINAHL, and PsycINFO databases were searched for peer-reviewed articles published between 1946 and December 2018 that examined digital peer support interventions for people with a lived experience of a serious mental illness. Additional articles were found by searching the reference lists from the 27 articles that met the inclusion criteria and a Google Scholar search in June 2019. Participants, interventions, comparisons, outcomes, and study design (PICOS) criteria were used to assess study eligibility. Two authors independently screened titles and abstracts, and reviewed all full-text articles meeting the inclusion criteria. Discrepancies were discussed and resolved. All included studies were assessed for methodological quality using the Methodological Quality Rating Scale., Results: A total of 30 studies (11 randomized controlled trials, 2 quasiexperimental, 15 pre-post designs, and 2 qualitative studies) were included that reported on 24 interventions. Most of the studies demonstrated feasibility, acceptability, and preliminary effectiveness of peer-to-peer networks, peer-delivered interventions supported with technology, and use of asynchronous and synchronous technologies., Conclusions: Digital peer support interventions appear to be feasible and acceptable, with strong potential for clinical effectiveness. However, the field is in the early stages of development and requires well-powered efficacy and clinical effectiveness trials., Trial Registration: PROSPERO CRD42020139037; https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID= 139037., (©Karen L Fortuna, John A Naslund, Jessica M LaCroix, Cynthia L Bianco, Jessica M Brooks, Yaara Zisman-Ilani, Anjana Muralidharan, Patricia Deegan. Originally published in JMIR Mental Health (http://mental.jmir.org), 03.04.2020.)

The purpose of this study was to explore the relationships between self-reported hopelessness and risk factors for premature mortality in people with serious mental illness (SMI). Data were extracted from the 2014 Health Center Patient Survey ( N = 5,592). Having a diagnosis of SMI was significantly associated with self-reported hopelessness. Hypertension or high blood pressure, congestive heart failure, and chronic obstructive pulmonary disorder were significantly associated with self-reported hopelessness. Higher levels of hopelessness were found to be significantly associated with increased alcohol consumption. Hopelessness may be an important dimension of health in people with SMI., Competing Interests: Disclosure statement On behalf of all authors, the corresponding author states that there are no conflicts of interest.

Objective: Despite the important impact of sexuality on quality of life in adults, there is a paucity of research on this topic for people with schizophrenia. This study examined predictors of sexual interest among adults with schizophrenia., Methods: Using data from three studies with similar measures and participants with similar characteristics (N=231), the authors conducted a secondary analysis to examine the relationships among sexual interest, demographic characteristics (gender, age, living situation, and marital status), and clinical factors (sexual self-efficacy, symptom severity, and medications). Sexual interest was measured by using one item from the Scale to Assess Negative Symptoms. Binomial logistic regressions were conducted to explore factors most associated with level of sexual interest., Results: Separately, cardiovascular medications, gender, age, sexual self-efficacy, and negative symptoms were associated with sexual interest. In a logistic regression model that included all of these factors, only sexual self-efficacy and gender were significantly associated with sexual interest. Higher levels of sexual self-efficacy were associated with lower levels of impairment in sexual interest (odds ratio [OR]=0.98, 95% confidence interval [CI]=0.98-0.99, p<0.001), and males were less likely than females to have impaired sexual interest (OR=0.38, 95% CI=0.20-0.73, p=0.004)., Conclusions: The strength of the relationship between sexual self-efficacy and sexual interest warrants development of interventions to address sexuality among people with serious mental illness, at least for those who are interested in developing or maintaining intimate relationships. An intervention that teaches skills needed to successfully pursue and navigate intimate relationships could positively influence overall quality of life for many.

Objective: People with mental illness have high rates of cigarette smoking, but many wish to quit. Electronic cigarette (e-cigarette) use has become increasingly common, especially among smokers who wish to quit, but research on whether this facilitates quitting has been mixed, and little research has examined e-cigarette use among smokers with mental illness. This secondary analysis examined the associations between spontaneous e-cigarette use during cessation treatment and 6-month outcomes within a cessation trial among Medicaid beneficiaries with mental illness. Main outcomes were previously reported. Methods: Adult Medicaid beneficiaries receiving mental health services were recruited between 2012 and 2015. Eligible daily smokers were randomized, using equipoise stratification, to one of six cessation treatment conditions (combinations of prescriber visit for pharmacotherapy, behavioral interventions, and abstinence incentives; e-cigarette use was not a recommended intervention). Presence of any self-reported e-cigarette use, all tobacco product use, quit attempts, and biologically verified abstinence were assessed at 3, 6, 9, and 12 months. The 456 participants who completed the 6-month assessment were included in logistic regressions, adjusting for subject characteristics and treatment condition, examining associations between self-reported, spontaneous e-cigarette use and 6-month outcomes. We evaluated three outcomes: biologically verified abstinence at 6 months, quit attempts over the treatment period, and heavy smoking (≥20 cigarettes per day) at 6 months. Results: Any use of e-cigarettes was reported by 192 participants (42.1%) during the treatment period. Use of pharmacotherapy was not different between those who used e-cigarettes and those who did not use e-cigarettes. A total of 13.5% of participants ( n  = 61) had achieved biologically verified abstinence at the 6-month assessment. E-cigarettes were not significantly associated with biologically verified abstinence, use of cessation pharmacotherapy, self-reported quit attempts, or heavy smoking at the 6-month assessment. Conclusions: Spontaneous e-cigarette use during cessation treatment was common among smokers with mental illness and was not associated with positive or negative treatment outcomes. The high rate of naturalistic e-cigarette use in this group suggests that e-cigarettes are an appealing strategy to obtain nicotine during cessation treatment that could be harnessed as a smoking cessation tool or for harm reduction.

We previously reported that 9,10-phenanthraquinone (9,10-PQ), an atmospheric electron acceptor, undergoes redox cycling with dithiols as electron donors, resulting in the formation of semiquinone radicals and monothiyl radicals; however, monothiols have little reactivity. Because persulfide and polysulfide species are highly reducing, we speculate that 9,10-PQ might undergo one-electron reduction with these reactive sulfides. In the present study, we explored the redox cycling capability of a variety of quinone-related electron acceptors, including 9,10-PQ, during interactions with the hydropersulfide Na 2 S 2 and its related polysulfides. No reaction occurred when 9,10-PQ was incubated with Na 2 S; however, when 5 μM 9,10-PQ was incubated with either 250 μM Na 2 S 2 or Na 2 S 4 , we detected extensive consumption of dissolved oxygen (84 μM). Under these conditions, both the semiquinone radicals of 9,10-PQ and their thiyl radical species were also detected using ESR, suggesting that a redox cycle reaction occurred utilizing one-electron reduction processes. Notably, the perthiyl radicals remained stable even under aerobic conditions. Similar phenomenon has also been observed with other electron acceptors, such as pyrroloquinoline quinone, vitamin K 3 , and coenzyme Q10. Our experiments with N-methoxycarbonyl penicillamine persulfide (MCPSSH), a precursor for endogenous cysteine persulfide, suggested the possibility of a redox coupling reaction with 9,10-PQ inside cells. Our study indicates that hydropersulfide and its related polysulfides are efficient electron donors that interact with quinones. Redox coupling reactions between quinoid electron acceptors and such highly reactive thiols might occur in biological systems.

Introduction: Electronic cigarette (e-cig) use has increased dramatically over the past decade, rates of e-cig use among those with a chronic mental illness has largely been unexplored. Exploring this relationship for adults with a mental illness is necessary when examining the health needs of this population., Methods: Data from the 2016 National Health Interview Survey (NHIS) was used to explore associations between e-cig use and chronic mental illness. E-cig use was explored in two different contexts, having tried an e-cig at least once and current e-cig use. Chronic mental illness was categorized as depression, anxiety, emotional disorder, or ADD, bipolar, schizophrenia, other disorder., Results: Rates of ever trying an e-cig and current e-cig use were higher among those with a chronic mental illness. Complex logistic regressions suggested having a chronic mental illness significantly increases the likelihood of both trying an e-cig and being an e-cig user., Conclusions: Increased likelihood of e-cig use in chronic mental illness supports previous findings. This may be due to perceptions that e-cigs are less harmful and they provide ways of socially connecting with others., Implications: Current knowledge surrounding e-cig use in this population is lacking. The 2016 NHIS allows for a nationally representative prediction of e-cig use in this population. This data is relevant in monitoring potential harm caused by e-cigs, in addition it may be helpful when assessing the value of e-cigs as a smoking cessation tool for those with a mental illness., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Purpose: The signalling associated with hydrogen sulfide (H 2 S) remains to be established, and recent studies have alluded to the possibility that H 2 S-derived species play important roles. Of particular interest are hydropersulfides (RSSH) and related polysulfides (RSS n R, n > 1). This work elucidates the fundamental chemical relationship between these sulfur species as well as examines their biological effects., Experimental Approach: Using standard analytical techniques ( 1 H-NMR and MS), the equilibrium reactions between H 2 S, disulfides (RSSR), RSSH, dialkyltrisulfides (RSSSR) and thiols (RSH) were examined. Their ability to protect cells from electrophilic and/or oxidative stress was also examined using cell culture., Key Results: H 2 S, RSSR, RSSH, RSSSR and RSH are all in a dynamic equilibrium. In a biological system, these species can exist simultaneously, and thus, it is difficult to discern which species is (are) the biological effector(s). Treatment of cells with the dialkyl trisulfide cysteine trisulfide (Cys-SSS-Cys) resulted in high intracellular levels of hydropersulfides and protection from electrophilic stress., Conclusions and Implications: In aqueous systems, the reaction between H 2 S and RSSR results in the formation of equilibria whereby H 2 S, RSH, RSSR, RSSH and RSSSR are present. In a biological system, any of these species can be responsible for the observed biological activity. These equilibrium species can also be generated via the reaction of RSH with RSSSR. Due to these equilibria, Cys-SSS-Cys can be a method for generating any of the other species. Importantly, HEK293T cells treated with Cys-SSS-Cys results in increased levels of hydropersulfides, allowing examination of the biological effects of RSSH., Linked Articles: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc., (© 2018 The British Pharmacological Society.)

The chemical biology of thiols (RSH, e.g., cysteine and cysteine-containing proteins/peptides) has been a topic of extreme interest for many decades due to their reported roles in protein structure/folding, redox signaling, metal ligation, cellular protection, and enzymology. While many of the studies on thiol/sulfur biochemistry have focused on thiols, relatively ignored have been hydropersulfides (RSSH) and higher order polysulfur species (RSS n H, RSS n R, n > 1). Recent and provocative work has alluded to the prevalence and likely physiological importance of RSSH and related RSS n H. RSSH of cysteine (Cys-SSH) has been found to be prevalent in mammalian systems along with Cys-SSH-containing proteins. The RSSH functionality has not been examined to the extent of other biologically relevant sulfur derivatives (e.g., sulfenic acids, disulfides, etc.), whose roles in cell signaling are strongly indicated. The recent finding of Cys-SSH biosynthesis and translational incorporation into proteins is an unequivocal indication of its fundamental importance and necessitates a more profound look into the physiology of RSSH. In this Review, we discuss the currently reported chemical biology of RSSH (and related species) as a prelude to discussing their possible physiological roles., (© 2018 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

In addition to their role as oxygen transporters, red blood cells (RBCs) contribute to cardiovascular homeostasis by regulating nitric oxide (NO) metabolism via interaction of hemoglobin (Hb) with nitrite and NO itself. RBCs were proposed to also participate in sulfide metabolism. Although Hb is known to react with sulfide, sulfide metabolism by intact RBCs has not been characterized so far. Therefore we explored the role of Hb in sulfide metabolism in intact human RBCs. We find that upon exposure of washed RBCs to sulfide, no changes in oxy/deoxyhemoglobin (oxy/deoxyHb) are observed by UV-vis and EPR spectroscopy. However, sulfide reacts with methemoglobin (metHb), forming a methemoglobin-sulfide (metHb-SH) complex. Moreover, while metHb-SH is stable in cell-free systems even in the presence of biologically relevant thiols, it gradually decomposes to produce oxyHb, inorganic polysulfides and thiosulfate in intact cells, as detected by EPR and mass spectrometry. Taken together, our results demonstrate that under physiological conditions RBCs are able to metabolize sulfide via intermediate formation of a metHb-SH complex, which subsequently decomposes to oxyHb. We speculate that decomposition of metHb-SH is preceded by an inner-sphere electron transfer, forming reduced Hb (which binds oxygen to form oxyHb) and thiyl radical (a process we here define as "reductive sulfhydration"), which upon release, gives rise to the oxidized products, thiosulfate and polysulfides. Thus, not only is metHb an efficient scavenger and regulator of sulfide in blood, intracellular sulfide itself may play a role in keeping Hb in the reduced oxygen-binding form and, therefore, be involved in RBC physiology and function., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Significance: Oxidative stress is thought to account for aberrant redox homeostasis and contribute to aging and disease. However, more often than not, administration of antioxidants is ineffective, suggesting that our current understanding of the underlying regulatory processes is incomplete. Recent Advances: Similar to reactive oxygen species and reactive nitrogen species, reactive sulfur species are now emerging as important signaling molecules, targeting regulatory cysteine redox switches in proteins, affecting gene regulation, ion transport, intermediary metabolism, and mitochondrial function. To rationalize the complexity of chemical interactions of reactive species with themselves and their targets and help define their role in systemic metabolic control, we here introduce a novel integrative concept defined as the reactive species interactome (RSI). The RSI is a primeval multilevel redox regulatory system whose architecture, together with the physicochemical characteristics of its constituents, allows efficient sensing and rapid adaptation to environmental changes and various other stressors to enhance fitness and resilience at the local and whole-organism level., Critical Issues: To better characterize the RSI-related processes that determine fluxes through specific pathways and enable integration, it is necessary to disentangle the chemical biology and activity of reactive species (including precursors and reaction products), their targets, communication systems, and effects on cellular, organ, and whole-organism bioenergetics using system-level/network analyses., Future Directions: Understanding the mechanisms through which the RSI operates will enable a better appreciation of the possibilities to modulate the entire biological system; moreover, unveiling molecular signatures that characterize specific environmental challenges or other forms of stress will provide new prevention/intervention opportunities for personalized medicine. Antioxid. Redox Signal. 00, 000-000.

Significance: For >20 years, physiological signaling associated with the endogenous generation of hydrogen sulfide (H 2 S) has been of significant interest. Despite its presumed importance, the biochemical mechanisms associated with its actions have not been elucidated. Recent Advances: Recently it has been found that H 2 S-related or derived species are highly prevalent in mammalian systems and that these species may be responsible for some, if not the majority, of the biological actions attributed to H 2 S. One of the most prevalent and intriguing species are hydropersulfides (RSSH), which can be present at significant levels. Indeed, it appears that H 2 S and RSSH are intimately linked in biological systems and likely to be mutually inclusive., Critical Issues: The fact that H 2 S and polysulfides such as RSSH are present simultaneously means that the biological actions previously assigned to H 2 S can be instead because of the presence of RSSH (or other polysulfides). Thus, it remains possible that hydropersulfides are the biological effectors, and H 2 S serves, to a certain extent, as a marker for persulfides and polysulfides. Addressing this possibility will to a large extent be based on the chemistry of these species., Future Directions: Currently, it is known that persulfides possess unique and novel chemical properties that may explain their biological prevalence. However, significantly more work will be required to establish the possible physiological roles of these species. Moreover, an understanding of the regulation of their biosynthesis and degradation will become important topics in piecing together their biology. Antioxid. Redox Signal. 00, 000-000.

Nitroxyl (HNO) is a simple molecule with significant potential as a pharmacological agent. For example, its use in the possible treatment of heart failure has received recent attention due to its unique therapeutic properties. Recent progress has been made on the elucidation of the mechanisms associated with its biological signaling. Importantly, the biochemical mechanisms described for HNO bioactivity are consistent with its unique and novel chemical properties/reactivity. To date, much of the biology of HNO can be associated with interactions and modification of important regulatory thiol proteins. Herein will be provided a description of HNO chemistry and how this chemistry translates to some of its reported biological effects., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The recent finding that hydropersulfides (RSSH) are biologically prevalent in mammalian systems has prompted further investigation of their chemical properties in order to provide a basis for understanding their potential functions, if any. Hydropersulfides have been touted as hyper-reactive thiol-like species that possess increased nucleophilicity and reducing capabilities compared to their thiol counterparts. Herein, using persulfide generating model systems, the ability of RSSH species to act as one-electron reductants has been examined. Not unexpectedly, RSSH is relatively easily oxidized, compared to thiols, by weak oxidants to generate the perthiyl radical (RSS·). Somewhat surprisingly, however, RSS· was found to be stable in the presence of both O 2 and NO and only appears to dimerize. Thus, the RSSH/RSS· redox couple is readily accessible under biological conditions and since dimerization of RSS· may be a rare event due to low concentrations and/or sequestration within a protein, it is speculated that the general lack of reactivity of individual RSS· species may allow this couple to be utilized as a redox component in biological systems., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The discovery of nitric oxide (NO) as an endogenously generated signaling species in mammalian cells has spawned a vast interest in the study of the chemical biology of nitrogen oxides. Of these, nitroxyl (azanone, HNO) has gained much attention for its potential role as a therapeutic for cardiovascular disease. Known targets of HNO include hemes/heme proteins and thiols/thiol-containing proteins. Recently, due to their roles in redox signaling and cellular defense, selenols and selenoproteins have also been speculated to be additional potential targets of HNO. Indeed, as determined in the current work, selenols are targeted by HNO. Such reactions appear to result only in formation of diselenide products, which can be easily reverted back to the free selenol. This characteristic is distinct from the reaction of HNO with thiols/thiolproteins. These findings suggest that, unlike thiolproteins, selenoproteins are resistant to irreversible oxidative modification, support that Nature may have chosen to use selenium instead of sulfur in certain biological systems for its enhanced resistance to electrophilic and oxidative modification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The recent discovery of significant hydropersulfide (RSSH) levels in mammalian tissues, fluids and cells has led to numerous questions regarding their possible physiological function. Cysteine hydropersulfides have been found in free cysteine, small molecule peptides as well as in proteins. Based on their chemical properties and likely cellular conditions associated with their biosynthesis, it has been proposed that they can serve a protective function. That is, hydropersulfide formation on critical thiols may protect them from irreversible oxidative or electrophilic inactivation. As a prelude to understanding the possible roles and functions of hydropersulfides in biological systems, this study utilizes primarily chemical experiments to delineate the possible mechanistic chemistry associated with cellular protection. Thus, the ability of hydropersulfides to protect against irreversible electrophilic and oxidative modification was examined. The results herein indicate that hydropersulfides are very reactive towards oxidants and electrophiles and are modified readily. However, reduction of these oxidized/modified species is facile generating the corresponding thiol, consistent with the idea that hydropersulfides can serve a protective function for thiol proteins., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Recent reports indicate the ubiquitous prevalence of hydropersulfides (RSSH) in mammalian systems. The biological utility of these and related species is currently a matter of significant speculation. The function, lifetime and fate of hydropersulfides will be assuredly based on their chemical properties and reactivity. Thus, to serve as the basis for further mechanistic studies regarding hydropersulfide biology, some of the basic chemical properties/reactivity of hydropersulfides was studied. The nucleophilicity, electrophilicity and redox properties of hydropersulfides were examined under biological conditions. These studies indicate that hydropersulfides can be nucleophilic or electrophilic, depending on the pH (i.e. the protonation state) and can act as good one- and two-electron reductants. These diverse chemical properties in a single species make hydropersulfides chemically distinct from other, well-known sulfur containing biological species, giving them unique and potentially important biological function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Membrane proteins are made soluble in aqueous buffers by the addition of various surfactants (detergents) to form so-called protein-detergent complexes (PDCs). Properties of membrane proteins are commonly assessed by unfolding the protein in the presence of surfactant in a buffer solution by adding urea. The stability of the protein under these conditions is then monitored by biophysical methods such as fluorescence or circular dichroism spectroscopy. Often overlooked in these experiments is the effect of urea on the phase behavior and micellar microstructure of the different surfactants used to form the PDCs. Here the effect of urea on five polyoxyethylene surfactants - n-octylytetraoxyethylene (C(8)E(4)), n-octylpentaoxyethylene (C(8)E(5)), n-decylhexaoxyethylene (C(10)E(6)), n-dodecylhexaoxyethylene (C(12)E(6)) and n-dodecyloctaoxylethylene (C(12)E(8)) - is explored. The presence of urea increases the critical micelle concentration (CMC) of all surfactants studied, indicating that the concentration of both the surfactant and urea should be considered in membrane protein folding studies. The cloud point temperature of all surfactants studied also increases with increasing urea concentration. Small-angle neutron scattering shows a urea-induced transition from an elongated to a globular shape for micelles of C(8)E(4) and C(12)E(6). In contrast, C(8)E(5) and C(12)E(8) form more globular micelles at room temperature and the micelles remain globular as the urea concentration is increased. The effects of increasing urea concentration on micelle structure are analogous to those of decreasing the temperature. The large changes in micelle structure observed here could also affect membrane protein unfolding studies by changing the structure of the PDC.

Nitroxyl (HNO) has become a nitrogen oxide of significant interest due to its reported biological activity. The actions of HNO in the cardiovascular system appear to make it a good candidate for therapeutic applications for cardiovascular disorders and other potentially important effects have been noted as well. Although the chemistry associated with this activity has not been firmly established, the propensity for HNO to react with thiols and metals are likely mechanisms. Herein, are described the biological activity of HNO and some of the chemistry of HNO that may be responsible for its biological effects.

In vitro and in vivo clinical and experimental data have suggested that leukotrienes play a key role in inflammatory reactions of the skin. Antileukotriene drugs, ie, leukotriene receptor antagonists and synthesis inhibitors, are a class of anti-inflammatory drugs that have shown clinical efficacy in the management of asthma and in rhinitis with asthma. We searched MEDLINE database and carried out a manual search on journals specializing in allergy and dermatology for the use of antileukotriene drugs in urticaria. Montelukast might be effective in chronic urticaria associated with aspirin (ASA) or food additive hypersensitivity or with autoreactivity to intradermal serum injection (ASST) when taken with an antihistamine but not in mild or moderate chronic idiopathic urticaria [urticaria without any possible secondary causes (ie, food additive or ASA and other NSAID hypersensitivity, or ASST)]. Evidence for the effectiveness of zafirlukast and the 5-lipoxygenase inhibitor, zileuton, in chronic urticaria is mainly anecdotal. In addition, there is anecdotal evidence of effectiveness of antileukotrienes in primary cold urticaria, delayed pressure urticaria and dermographism. No evidence exists for other physical urticarias, including cholinergic, solar and aquagenic urticarias, vibratory angioedema, and exercise-induced anaphylaxis.