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Asthma is one of the most common chronic inflammatory airway diseases. Airway oxidative stress is defined as an imbalance between oxidative and antioxidative processes in the airways. ML385 There is evidence that chronic damage caused by oxidative stress may be involved in asthmatic inflammation and reduced lung function. Given their biological antioxidant function, the antioxidant genes in the glutathione S-transferase (GST) family are believed to be associated with development and progression of asthma. This review aims to summarize evidence on the relationship between GST gene polymorphisms and asthma and interactions with environmental exposures.

The current evidence on the association between GST genes and asthma is still weak or inconsistent. Failure to account for environmental exposures may explain the lack of consistency. It is highly likely that environmental exposures interact with GST genes involved in the antioxidant pathway. According to current knowledge, carriers of GSTM1(rs366631)/T1(rs17856199l exposures interact with GST genes involved in the antioxidant pathway. According to current knowledge, carriers of GSTM1(rs366631)/T1(rs17856199) null genotypes and GSTP1 Val105 (rs1695) genotypes are more susceptible to environmental oxidative exposures and have a higher risk of asthma. Some doubt remains regarding the presence or absence of interactions with different environmental exposures in different study scenarios. The GST-environment interaction may depend on exposure type, asthma phenotype or endotype, ethnics, and other complex gene-gene interaction. Future studies could be improved by defining precise asthma endotypes, involving multiple gene-gene interactions, and increasing sample size and power. Although there is evidence for an interaction between GST genes, and environmental exposures in relation to asthma, results are not concordant. Further investigations are needed to explore the reasons behind the inconsistency.

Hereditary alpha-tryptasemia (HαT) is an autosomal dominant genetic trait and a common cause of elevated basal serum tryptase in Western populations. It is a risk factor for severe anaphylaxis among individuals with venom allergy and an established modifier of anaphylaxis and mast cell mediator-associated symptoms among patients with systemic mastocytosis. Understanding the physiology of tryptases and how this may relate to the clinical features associated with HαT is the first step in identifying optimal medical management and targets for novel therapeutics.

HαT prevalence is increased in both clonal and non-clonal mast cell-associated disorders where it augments symptoms of immediate hypersensitivity, including anaphylaxis. The unique properties of naturally occurring α/β-tryptase heterotetramers may explain certain elements of phenotypes associated with HαT, though additional mechanisms are being evaluated. This review provides an overview of the clinical and translational studies that have identified HαT as a modifier of mast cell-associated disorders and anaphylaxis and discusses mechanisms that may potentially explain some of these clinical findings.

HαT prevalence is increased in both clonal and non-clonal mast cell-associated disorders where it augments symptoms of immediate hypersensitivity, including anaphylaxis. The unique properties of naturally occurring α/β-tryptase heterotetramers may explain certain elements of phenotypes associated with HαT, though additional mechanisms are being evaluated. This review provides an overview of the clinical and translational studies that have identified HαT as a modifier of mast cell-associated disorders and anaphylaxis and discusses mechanisms that may potentially explain some of these clinical findings.

To present a method enabling in vivo quantification of tissue membrane potential (ΔΨ

), a proxy of mitochondrial membrane potential (ΔΨ

), to review the origin and role of ΔΨ

, and to highlight potential applications of myocardial ΔΨ

imaging.

Radiolabelled lipophilic cations have been used for decades to measure ΔΨ

in vitro. Using similar compounds labeled with positron emitters and appropriate compartment modeling, this technique now allows in vivo quantification of ΔΨ

with positron emission tomography. Studies have confirmed the feasibility of measuring myocardial ΔΨ

in both animals and humans. In addition, ΔΨ

showed very low variability among healthy subjects, suggesting that this method could allow detection of relatively small pathological changes. In vivo assessment of myocardial ΔΨ

provides a new tool to study the pathophysiology of cardiovascular diseases and has the potential to serve as a new biomarker to assess disease stage, prognosis, and response to therapy.

Radiolabelled lipophilic cations have been used for decades to measure ΔΨm in vitro. Using similar compounds labeled with positron emitters and appropriate compartment modeling, this technique now allows in vivo quantification of ΔΨT with positron emission tomography. Studies have confirmed the feasibility of measuring myocardial ΔΨT in both animals and humans. In addition, ΔΨT showed very low variability among healthy subjects, suggesting that this method could allow detection of relatively small pathological changes. In vivo assessment of myocardial ΔΨT provides a new tool to study the pathophysiology of cardiovascular diseases and has the potential to serve as a new biomarker to assess disease stage, prognosis, and response to therapy.

Although opioids are excellent analgesics, they are associated with severe short- and long-term side effects that are especially concerning for the treatment of chronic pain. Peripherally acting opioid receptor agonists promise to mitigate the more serious centrally mediated side effects of opioids, and the goal of this paper is to identify and elaborate on recent advances in these peripheral opioid receptor therapeutics.

Peripheral opioid receptor agonists are effective analgesics that at the same time circumvent the problem of centrally mediated opioid side effects by (1) preferentially targeting peripheral opioid receptors that are often the source of the pain and (2) their markedly diminished permeability or activity across the blood-brain barrier. Recent novel bottom-up approaches have been notable for the design of therapeutics that are either active only at inflamed tissue, as in the case of fentanyl-derived pH-sensitive opioid ligands, or too bulky or hydrophilic to cross the blood-brain barrier, as in the case of morphine covalently bound to hyperbranched polyglycerols.