Addiction Rehab: Peroxisome Proliferator Activated Receptor-?/Hypoxia Inducible Factor-1? Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells.
Peroxisome Proliferator Activated Receptor-?/Hypoxia Inducible Factor-1? Interplay Sustains Carbonic Anhydrase IX and Apoliprotein E Expression in Breast Cancer Stem Cells.
Filed under: Addiction Rehab
PLoS One. 2013; 8(1): e54968
Papi A, Storci G, Guarnieri T, De Carolis S, Bertoni S, Avenia N, Sanguinetti A, Sidoni A, Santini D, Ceccarelli C, Taffurelli M, Orlandi M, Bonafé M
AIMS: Cancer stem cell biology is tightly connected to the regulation of the pro-inflammatory cytokine network. The concept of cancer stem cells “inflammatory addiction” leads to envisage the potential role of anti-inflammatory molecules as new anti-cancer targets. Here we report on the relationship between nuclear receptors activity and the modulation of the pro-inflammatory phenotype in breast cancer stem cells. METHODS: Breast cancer stem cells were expanded as mammospheres from normal and tumor human breast tissues and from tumorigenic (MCF7) and non tumorigenic (MCF10) human breast cell lines. Mammospheres were exposed to the supernatant of breast tumor and normal mammary gland tissue fibroblasts. RESULTS: In mammospheres exposed to the breast tumor fibroblasts supernatant, autocrine tumor necrosis factor-? signalling engenders the functional interplay between peroxisome proliferator activated receptor-? and hypoxia inducible factor-1? (PPAR?/HIF1?). The two proteins promote mammospheres formation and enhance each other expression via miRNA130b/miRNA17-5p-dependent mechanism which is antagonized by PPAR?. Further, the PPAR?/HIF1? interplay regulates the expression of the pro-inflammatory cytokine interleukin-6, the hypoxia survival factor carbonic anhydrase IX and the plasma lipid carrier apolipoprotein E. CONCLUSION: Our data demonstrate the importance of exploring the role of nuclear receptors (PPAR?/PPAR?) in the regulation of pro-inflammatory pathways, with the aim to thwart breast cancer stem cells functioning.
HubMed – addiction
Opioid overdose rates and implementation of overdose education and nasal naloxone distribution in Massachusetts: interrupted time series analysis.
Filed under: Addiction Rehab
BMJ. 2013; 346: f174
Walley AY, Xuan Z, Hackman HH, Quinn E, Doe-Simkins M, Sorensen-Alawad A, Ruiz S, Ozonoff A
OBJECTIVE: To evaluate the impact of state supported overdose education and nasal naloxone distribution (OEND) programs on rates of opioid related death from overdose and acute care utilization in Massachusetts. DESIGN: Interrupted time series analysis of opioid related overdose death and acute care utilization rates from 2002 to 2009 comparing community-year strata with high and low rates of OEND implementation to those with no implementation. SETTING: 19 Massachusetts communities (geographically distinct cities and towns) with at least five fatal opioid overdoses in each of the years 2004 to 2006. PARTICIPANTS: OEND was implemented among opioid users at risk for overdose, social service agency staff, family, and friends of opioid users. INTERVENTION: OEND programs equipped people at risk for overdose and bystanders with nasal naloxone rescue kits and trained them how to prevent, recognize, and respond to an overdose by engaging emergency medical services, providing rescue breathing, and delivering naloxone. MAIN OUTCOME MEASURES: Adjusted rate ratios for annual deaths related to opioid overdose and utilization of acute care hospitals. RESULTS: Among these communities, OEND programs trained 2912 potential bystanders who reported 327 rescues. Both community-year strata with 1-100 enrollments per 100?000 population (adjusted rate ratio 0.73, 95% confidence interval 0.57 to 0.91) and community-year strata with greater than 100 enrollments per 100?000 population (0.54, 0.39 to 0.76) had significantly reduced adjusted rate ratios compared with communities with no implementation. Differences in rates of acute care hospital utilization were not significant. CONCLUSIONS: Opioid overdose death rates were reduced in communities where OEND was implemented. This study provides observational evidence that by training potential bystanders to prevent, recognize, and respond to opioid overdoses, OEND is an effective intervention.
HubMed – addiction
Abstinence from repeated amphetamine treatment induces depressive-like behaviors and oxidative damage in rat brain.
Filed under: Addiction Rehab
Psychopharmacology (Berl). 2013 Feb 1;
Che Y, Cui YH, Tan H, Andreazza AC, Young LT, Wang JF
RATIONALE: Amphetamine has a significant potential for abuse and addiction. Among prolonged abusers, amphetamine withdrawal-induced depressive symptoms are common; however, their pathophysiological mechanism is not fully understood. Previously, we found that repeated treatment with amphetamine for 2 weeks induced oxidative stress in rat brain. OBJECTIVES: The purpose of the current study is to analyze whether abstinence from repeated amphetamine treatment in rats induces depressive-like behaviors and if oxidative damage in the brain continues during abstinence. METHODS: Rats were given repeated treatment with amphetamine once daily at 1, 2, or 4 mg/kg for 14 days. From 10 to 14 days after final amphetamine treatment, behavioral changes were monitored using open field test, novel object recognition test, and forced swim test. Oxidative damage in the medial frontal cortex and hippocampus was analyzed by immunohistochemistry. RESULTS: We found that drug abstinence after repeated amphetamine stimulation decreased locomotor activity and exploratory behavior in the open field test, increased immobility in the forced swim test, and had no significant effect on the recognition index in the novel object recognition test. We also found that amphetamine abstinence increased levels of 4-hydroxynonenal-protein adducts and 8-hydroxyguanosine in rat medial frontal cortex and in CA3 and dentate gyrus regions of the hippocampus. CONCLUSIONS: These results suggest that amphetamine abstinence displays depressive-like behaviors in rats and induces oxidative damage to lipids and RNA in rat brain. Our findings indicate that the process of oxidative stress may play a role in pathophysiological changes during drug abstinence from repeated amphetamine stimulation.
HubMed – addiction
Effect of wheel-running during abstinence on subsequent nicotine-seeking in rats.
Filed under: Addiction Rehab
Psychopharmacology (Berl). 2013 Jan 31;
Sanchez V, Moore CF, Brunzell DH, Lynch WJ
RATIONALE: Exercise appears to be a promising non-pharmacological treatment for nicotine addiction that may be useful for the vulnerable adolescent population. OBJECTIVES: The aim of this study is to determine if wheel-running, an animal model of aerobic exercise, during an abstinence period would decrease subsequent nicotine-seeking in rats that had extended access to nicotine self-administration during adolescence. METHODS: Male adolescent rats (n?=?55) were trained to self-administer saline or nicotine infusions (5 or 10 ?g/kg) under a fixed ratio 1 schedule with a maximum of 20 infusions/day beginning on postnatal day 30. After 5 days, access was extended to 23 h/day with unlimited infusions for a total of 10 days. After the last self-administration session, rats were moved to polycarbonate cages for a 10-day abstinence period where they either had access to a locked or unlocked running wheel for 2 h/day. Nicotine-seeking was examined following the 10th day of abstinence under a within-session extinction/cue-induced reinstatement paradigm. RESULTS: Intake was higher at the 10 ?g/kg dose as compared to the 5 ?g/kg dose; however, intake did not differ within doses prior to wheel assignment. Compared to saline controls, rats that self-administered nicotine at either dose showed a significant increase in drug-seeking during extinction, and consistent with our hypothesis, exercise during abstinence attenuated this effect. Nicotine led to modest but significant levels of cue-induced reinstatement; however, in this adolescent-onset model, levels were variable and not affected by exercise. CONCLUSIONS: Exercise may effectively reduce relapse vulnerability for adolescent-onset nicotine addiction.
HubMed – addiction
Functional Mapping of the Neuronal Substrates for Drug Tolerance in Drosophila.
Filed under: Addiction Rehab
Behav Genet. 2013 Feb 1;
Ghezzi A, Al-Hasan YM, Krishnan HR, Wang Y, Atkinson NS
Physical dependence on alcohol and anesthetics stems from neuroadaptive changes that act to counter the effects of sedation in the brain. In Drosophila, exposure to either alcohol or solvent anesthetics have been shown to induce changes in expression of the BK-type Ca(2+)-activated K(+) channel gene slo. An increase in slo expression produces an adaptive modulation of neural activity that generates resistance to sedation and promotes drug tolerance and dependence. Increased BK channel activity counteracts the sedative effects of these drugs by reducing the neuronal refractory period and enhancing the capacity of neurons for repetitive firing. However, the brain regions or neuronal populations capable of producing inducible resistance or tolerance remain unknown. Here we map the neuronal substrates relevant for the slo-dependent modulation of drug sensitivity. Using spatially-controlled induction of slo expression we identify the mushroom bodies, the ellipsoid body and a subset of the circadian clock neurons as pivotal regions for the control of recovery from sedation.
HubMed – addiction
Chocolate Addiction, Season 1- Episode 2 – Meet Tommie, hes 16, and hes addicted to chocolate. He has a serious chocolate addiction and wants to be chocolate free. He previously was a 3 weeks sober but has a relapse.
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