Evaluation of dynorphin and kappa-opioid receptor level in the human blood lymphocytes and plasma: Possible role as a biomarker in severe opioid use disorder.

BACKGROUND: The dynorphin (DYN)/kappa opioid receptor (KOR) system plays an important role in the development of addiction, and dysregulation of this system could lead to abnormal activity in the reward pathway. It has been reported that the expression state of the neurotransmitters and their receptors in the brain is reflected in peripheral blood lymphocytes (PBLs). METHODS: We have evaluated the PBLs and plasma samples of four groups: 1) subjects with severe opioid use disorder (SOD), 2) methadone-maintenance treated (MMT) individuals, 3) long-term abstinent subjects having former SOD, and 4) healthy control subjects (n = 20 in each group). The mRNA expression level of preprodynorphin (pPDYN) and KOR in PBLs has been evaluated by real-time PCR. Peptide expression of PDYN in PBLs has been studied by western blot, and DYN concentration in plasma has been measured by ELISA. RESULTS: The relative expression level of the pPDYN mRNA and PDYN peptide in PBLs were significantly up-regulated in SOD, MMT, and abstinent groups compared to control subjects. No significant difference was found in the plasma DYN concentration between study groups. The expression level of the KOR mRNA in PBLs was significantly decreased in all three study groups compared to the control subjects. CONCLUSION: the expression changes in the DYN/KOR system after chronic exposure to opioids, including methadone, seems to be stable and does not return to normal levels even after 12 months abstinence. These long-time and permanent changes in PBLs may serve as a biomarker and footprint of SOD development in the periphery.

The Effect of Self-Care Education on the Quality of Life in Children with Allergic Asthma.

Asthma is a condition where the airways become tiny and swollen producing extra mucus. This can cause breathing difficulty and wheezing, coughing, and shortness of breath. Self-care education affects the quality of life of children. This study examined the effect of self-care education on quality of life for children between 8 and 11 years with allergic asthma. This study was a randomized controlled trial. Study sample included 70 children between 8 and 11 years with asthma allergy referred to Children's Hospital Clinic of Khorramabad, Lorestan Province in 2015; they were selected by possible non-consecutive sampling method. Children were divided by random sampling of blocks, and classified into two groups of 35 patients each in the experimental and control groups. Both groups were matched for age and sex of children's and parents' educational level and initial quality of life scores were analyzed (using covariance analysis). At the beginning, quality of life was calculated by the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) for each of the group. The intervention was carried out in four sessions of 45 minutes of self-care education for children in the case group. No intervention was done in the control group. Eight weeks later quality of life was measured in each of the group. There was a significant difference between increase values of PAQLQ in the intervention group and control group (p < 0.001). These results show that self-care education enhances the quality of life in asthmatic children.

The protective potential of metformin against acetaminophen-induced hepatotoxicity in BALB/C mice.

CONTEXT: Acetaminophen overdose is regarded to a common cause of acute liver failure. The hepatotoxicity leads to mitochondrial oxidative stress and subsequent necrotic hepatocellular death. OBJECTIVE: This study examines the protective effect of metformin on acetaminophen-induced oxidative stress, inflammation and subsequent hepatotoxicity in mice. MATERIALS AND METHODS: Male BALB/c mice were orally administered to acetaminophen (250 mg/kg/d) for a 7-day period. The mice received metformin (100 and 200 mg/kg/d, p.o.) for 21 days. To evaluate acetaminophen-induced oxidative stress, liver tissue level of malodialdehyde (MDA), end product of membrane lipid peroxidation, and activities of superoxide dismutase (SOD) and glutathione (GSH) were measured. Histological analysis and measurement of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were performed. Moreover, tissue concentrations of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), along with, C-reactive protein (CRP) were assessed. RESULTS: Acetaminophen caused focal hepatocyte necrosis, inflammation and fatty degeneration, as well as increased tissue levels of AST, ALT, ALP and MDA, and also decreased GSH and SOD activities. Moreover, IL-6, TNF-α and CRP levels were increased following acetaminophen hepatotoxicity. Metformin (200 mg/kg/d) significantly normalized MDA, SOD and GSH levels (p < 0.001), and exerted a hepatoprotective effect by significant decreasing ALT, AST and ALP concentrations (p < 0.001). The tissue levels of IL-6, TNF-α and CRP were markedly decreased by 21-day treatment with metformin (200 mg/kg/d) (p < 0.001). DISCUSSION: The results suggest metformin protects hepatocytes against acute acetaminophen toxicity. Metformin is indicated to diminish oxidative stress, proinflammatory cytokines, and hepatocyte necrosis.