Burden, screening, and treatment of depressive and anxious symptoms among women referred to cardiac rehabilitation : a prospective study

Women with cardiovascular disease experience a significantly greater burden of psychosocial distress than men. Clinical practice guidelines promote screening in cardiac rehabilitation (CR). The objectives of this thesis were to describe the burden of psychosocial distress, screening, forms of treatment, awareness of elevated symptoms, and whether receipt of treatment was related to subsequent psychosocial distress symptom severity, within women referred to CR. This study presents a secondary analysis of a multi-centre trial of women outpatients randomized to 1 of 3 CR models. Consenting participants were asked to complete an initial and follow-up survey 6 months later, and clinical data were extracted from charts. Findings reiterate that despite clinical recommendations, few women reported being screened for psychological distress, and when screened, only approximately 1/5th were informed of their results. When treated, most women were prescribed anti-depressants by their family doctor. Unfortunately therapy was not related to improvements in symptoms

TNF-α and neuropathic pain - a review

Tumor necrosis factor alpha (TNF-α) was discovered more than a century ago, and its known roles have extended from within the immune system to include a neuro-inflammatory domain in the nervous system. Neuropathic pain is a recognized type of pathological pain where nociceptive responses persist beyond the resolution of damage to the nerve or its surrounding tissue. Very often, neuropathic pain is disproportionately enhanced in intensity (hyperalgesia) or altered in modality (hyperpathia or allodynia) in relation to the stimuli. At time of this writing, there is as yet no common consensus about the etiology of neuropathic pain - possible mechanisms can be categorized into peripheral sensitization and central sensitization of the nervous system in response to the nociceptive stimuli. Animal models of neuropathic pain based on various types of nerve injuries (peripheral versus spinal nerve, ligation versus chronic constrictive injury) have persistently implicated a pivotal role for TNF-α at both peripheral and central levels of sensitization. Despite a lack of success in clinical trials of anti-TNF-α therapy in alleviating the sciatic type of neuropathic pain, the intricate link of TNF-α with other neuro-inflammatory signaling systems (e.g., chemokines and p38 MAPK) has indeed inspired a systems approach perspective for future drug development in treating neuropathic pain

Fentanyl: Receptor pharmacology, abuse potential, and implications for treatment.

Opioid overdoses, many of which are attributed to use of illicit fentanyl, are currently one of the leading causes of death in the U.S. Although fentanyl has been used safely for decades in clinical settings, the widespread use of illicit fentanyl is a recent phenomenon. Starting in 2013, illicitly manufactured fentanyl and its analogs began to appear on the streets. These substances were added to or sold as heroin, often unbeknownst to the user. Because fentanyl is so potent, only small amounts are needed to produce pharmacological effects, but the margin between safe and toxic doses is narrow. Surprisingly little is known about the exact signaling mechanisms underlying fentanyl-related respiratory depression or the effectiveness of naloxone in reversing this effect. Similarly, little is known about the ability of treatment medications such as buprenorphine, methadone, or naltrexone to reduce illicit fentanyl use. The present article reviews the receptor, preclinical and clinical pharmacology of fentanyl, and how its pharmacology may predict the effectiveness of currently approved medications for treating illicit fentanyl use

Effect of cold plasma treatment on the antigenicity of peanut allergen Ara h 1

The objective of this study was to investigate the effects of cold atmospheric plasma on the antigenicity of protein Ara h 1. Dry, defatted peanut flour (DPF), whole peanut (WP) were subjected to cold atmospheric plasma at voltage of 80 kV for different treatment durations (0, 15, 30, 45 and 60 min). The allergen samples were analyzed using SDS-PAGE, immunoblot and competitive ELISA. Furthermore, the secondary structure was examined using circular dichroism. SDS-PAGE results revealed no change in the protein intensity bands corresponding to Ara h 1 for both DPF and WP. Competitive ELISA of samples showed a reduction in antigenicity up to 43% for DPF and 9.3% for WP. Circular dichroism studies revealed modifications in secondary structure induced by plasma reactive species. Industrial relevance Cold plasma has emerged as a novel processing technique. This study provides evidence for reduction of antigenicity of Ara h1 in peanuts using cold plasma. This study also demonstrated the plasma-induced changes in protein structure at high treatment duration. The work described in this research is relevant to the processing of cereal grains and legumes wherein allergenicity is a major concern. This results provide the basis for possible industrial implementation

Ultra-low dose naltrexone attenuates chronic morphine-induced gliosis in rats

BackgroundThe development of analgesic tolerance following chronic morphine administration can be a significant clinical problem. Preclinical studies demonstrate that chronic morphine administration induces spinal gliosis and that inhibition of gliosis prevents the development of analgesic tolerance to opioids. Many studies have also demonstrated that ultra-low doses of naltrexone inhibit the development of spinal morphine antinociceptive tolerance and clinical studies demonstrate that it has opioid sparing effects. In this study we demonstrate that ultra-low dose naltrexone attenuates glial activation, which may contribute to its effects on attenuating tolerance.ResultsSpinal cord sections from rats administered chronic morphine showed significantly increased immuno-labelling of astrocytes and microglia compared to saline controls, consistent with activation. 3-D images of astrocytes from animals administered chronic morphine had significantly larger volumes compared to saline controls. Co-injection of ultra-low dose naltrexone attenuated this increase in volume, but the mean volume differed from saline-treated and naltrexone-treated controls. Astrocyte and microglial immuno-labelling was attenuated in rats co-administered ultra-low dose naltrexone compared to morphine-treated rats and did not differ from controls. Glial activation, as characterized by immunohistochemical labelling and cell size, was positively correlated with the extent of tolerance developed. Morphine-induced glial activation was not due to cell proliferation as there was no difference observed in the total number of glial cells following chronic morphine treatment compared to controls. Furthermore, using 5-bromo-2-deoxyuridine, no increase in spinal cord cell proliferation was observed following chronic morphine administration.ConclusionTaken together, we demonstrate a positive correlation between the prevention of analgesic tolerance and the inhibition of spinal gliosis by treatment with ultra-low dose naltrexone. This research provides further validation for using ultra-low dose opioid receptor antagonists in the treatment of various pain syndromes

Dissociation between morphine-induced spinal gliosis and analgesic tolerance by ultra-low-dose α2-adrenergic and cannabinoid CB1-receptor antagonists.

Long-term use of opioid analgesics is limited by tolerance development and undesirable adverse effects. Paradoxically, spinal administration of ultra-low-dose (ULD) G-protein-coupled receptor antagonists attenuates analgesic tolerance. Here, we determined whether systemic ULD α2-adrenergic receptor (AR) antagonists attenuate the development of morphine tolerance, whether these effects extend to the cannabinoid (CB1) receptor system, and if behavioral effects are reflected in changes in opioid-induced spinal gliosis. Male rats were treated daily with morphine (5 mg/kg) alone or in combination with ULD α2-AR (atipamezole or efaroxan; 17 ng/kg) or CB1 (rimonabant; 5 ng/kg) antagonists; control groups received ULD injections only. Thermal tail flick latencies were assessed across 7 days, before and 30 min after the injection. On day 8, spinal cords were isolated, and changes in spinal gliosis were assessed through fluorescent immunohistochemistry. Both ULD α2-AR antagonists attenuated morphine tolerance, whereas the ULD CB1 antagonist did not. In contrast, both ULD atipamezole and ULD rimonabant attenuated morphine-induced microglial reactivity and astrogliosis in deep and superficial spinal dorsal horn. So, although paradoxical effects of ULD antagonists are common to several G-protein-coupled receptor systems, these may not involve similar mechanisms. Spinal glia alone may not be the main mechanism through which tolerance is modulated

Impact of Cold Plasma Processing on Major Peanut Allergens

Cold plasma is emerging as a novel food processing technology, with demonstrated efficacies for microbial inactivation and residual chemical dissipation of food products. Given the technology’s multimodal action it has the potential to reduce allergens in foods, however data on the efficacy and mechanisms of action are sparse. This study investigates the efficacy of cold plasma on major peanut allergens (Ara h 1 and Ara h 2). For this purpose, dry, whole peanut (WP) and defatted peanut flour (DPF) were subjected to an atmospheric air discharge using a pin to plate cold plasma reactor for different treatment durations. With increases in plasma exposure, SDS‑PAGE analysis revealed reduced protein solubility of the major peanut allergens. Alterations in allergenicity and structure of Ara h 1 and Ara h 2 were examined using ELISA and circular dichroism (CD) spectroscopy. Competitive ELISA with proteins purified from plasma treated WP or DPF revealed reduced antigenicity for both Ara h 1 and Ara h 2. The highest reduction in antigenicity was 65% for Ara h 1 and 66% Ara h 2 when purified from DPF. Results from CD spectroscopy analysis of purified proteins strongly suggests the reduction in antigenicity is due to modifications in the secondary structure of the allergens induced by plasma reactive species. Cold plasma is effective at reducing peanut protein solubility and causes changes in allergen structure leading to reduced antigenicity