scholarly journals The Impact of Zinc Supplementation on Oxidative Stress and Inflammatory Biomarkers in Opioid Addicts-Withdrawal Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Author(s):  
Amir Keshavarzi ◽  
Ali Hassanalizade ◽  
Akram Ranjbar ◽  
Ali Ghaleiha ◽  
Seyed Yaser Vafaei ◽  
...  

Abstract Background Opioid withdrawal can induce oxidative stress in opioid addicts. This interventional study aimed to investigate the effect of zinc supplementation on the oxidative profile of patients with an opioid withdrawal syndrome. Methods In the current study, 40 patients aged 18 to 65 years with opioid withdrawal syndrome were randomly assigned to intervention and control groups, each with 20 subjects. In addition to standard treatment, the intervention group received 30 mg of zinc daily, while the control group was given a placebo for one month. They were evaluated using Beck Depression Inventory (BDI), Clinical Opiate Withdrawal Scale (COWS), and Young Mania Rating Scale (YMRS) for withdrawal symptoms. Moreover, other parameters included catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and levels of total antioxidant capacity (TAC), total thiol groups (TTG), tumor necrosis factor-α (TNF-α), and malondialdehyde (MDA). Results The rate of withdrawal symptoms (COWS) was statistically significantly lower in the treated group in comparison to the control group (P < 0.05). In the treatment group, the levels of TAC, CAT, SOD, and GPx increased significantly compared to the control group (P < 0.05). In the treatment group compared to the control group, there was a statistically significant decrease in hs-CRP, MDA, and TNFα (P < 0.05). Conclusions The results revealed that zinc supplementation could effectively reduce withdrawal symptoms by increasing antioxidant activity and reducing the lipid peroxidation index.

2021 ◽  
pp. 1-3
Author(s):  
Mayumi Ishida ◽  
Mie Hiraoka ◽  
Ayako Yaguchi ◽  
Koji Sugano ◽  
Nasako Adachi ◽  
...  

Abstract Objective Naldemedine, an oral peripheral μ-opioid receptor antagonist, was developed for the treatment of constipation, a side effect of opioid use. Naldemedine is not generally recognized as causing opioid withdrawal in which associated symptoms affecting the central nervous system. Method From the series of cancer patients undergoing symptom management, we report a case treated with naldemedine for constipation in relation to the use of opioids for cancer pain and who displayed severe psychological symptoms associated with withdrawal immediately after the use of naldemedine. Results The patient was a 36-year-old woman diagnosed with cervical cancer Stage IIB, PS3. When the patient, who was using oxycodone hydrochloride hydrate (80 mg/day) for ileal pain, was started on naldemedine for constipation, she complained of sweating after just 5 min and hallucinations after 1 h. The patient also displayed physical/behavioral abnormalities such as diarrhea and hyperactivity, and psychological abnormalities such as aggression toward staff. Despite the psychiatric symptoms worsening over time, there were no abnormalities in terms of blood biochemical data, and no brain metastasis was observed on MRI. Based on the Clinical Opiate Withdrawal Scale, these symptoms were judged to indicate opioid withdrawal. Naldemedine was discontinued due to naldemedine-related opioid withdrawal syndrome and, thereafter, the psychiatric symptoms diminished, with no recurrence of similar symptoms observed to date. Significance of results If mental and behavioral abnormalities occur in patients receiving naldemedine, it is necessary to consider the possibility of opioid withdrawal syndrome as a differential diagnosis.


1991 ◽  
Vol 6 (2) ◽  
pp. 89-92 ◽  
Author(s):  
JC Perez de los Cobos ◽  
JJ Lopez-Ibor ◽  
P Sopelana ◽  
M Castañeda

SummaryThe present study was carried out in 2 successive phases. In the first, 91 inpatients admitted for opioid dependence were evaluated. All were treated with α2-agonists during the withdrawal period. Shortly after admission, a urine sample was taken and analyzed (EMIT and GC/MS). The presence of the cocaine metabolite benzoilecgonine in urine was a predictor of dropout probability during hospitalization (P < 0.01). A second study on a sample of 612 inpatients later admitted for similar reasons was carried out according to a simpler protocol (using only EMIT) in order to replicate the previous results. Again, the presence of benzoilecgonine in urine indicated dropout probability (P = 0.00004). Thus, the use of cocaine prior to admission for a treatment of opiate withdrawal syndrome with α2-agonists seems to predict therapeutic failure.


Author(s):  
Abdollah Farhadi Nasab ◽  
Safoura Raoufi ◽  
Naghmeh Bahrami

Introduction: Today, drug addiction is an important healthcare issue. Any helps to drug withdrawal may decrease its prevalence in the society. Ascorbic acid is a component, which can affect neurotransmitter systems as a regulator along with its cofactor role. Noradrenergic and dopaminergic systems are two important neurotransmitter systems in the opiate withdrawal syndrome. It seems that ascorbic acid can decrease the symptoms of opiate withdrawal through regulating the related systems. In this regard, the current study aimed to evaluate the effect of ascorbic acid on the symptoms of morphine withdrawal in Syrian mice. Materials and Methods: Male Syrian mice in eight experimental groups received incremental doses of morphine as 10, 20, 30 and 40 mg/kg within the first, second, third, and fourth days of the experiment, respectively, through intraperitoneal injection, twice a day, and the control group received and equal amount of saline. On the fifth day, six groups of morphine addicts received ascorbic acid with six doses of 10, 50, 100, 200,400 and 800 mg/kg through intraperitoneal injection. Then, naloxone 2 mg/kg was injected to all groups including morphine alone and morphine with acute does of ascorbic acid. Then, withdrawal symptoms were evaluated for 30 minutes. Results: Administration of an acute dose of ascorbic acid reduced dose dependent withdrawal symptoms in such a way that 10, 50, and 100 mg/kg doses of ascorbic acid reduced “writhing” symptom, 200 mg/kg reduced “jumping” symptom, and 400 and 800 mg/kg reduced “climbing, jumping, and standing” symptoms. Conclusion: It seems that ascorbic acid administration can improve the symptoms of opiate withdrawal syndrome. More studies on human population can also indicate the therapeutic effect of ascorbic acid on drug withdrawal.


2017 ◽  
Vol 36 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Srdjan Mijatović ◽  
Tamara Alempijević ◽  
Branislava Stefanović ◽  
Vasilije Jeremić ◽  
Slobodan Krstić ◽  
...  

Summary Background: Oxidative stress represents tissue damage caused by reactive forms of oxygen and nitrogen due to the inability of antioxidant mechanisms to reduce reactive forms into more stable ones. The aim of the study was to evaluate the influence of surgical trauma on nitric oxide (NO) and nitrotyrosine (NT) values in patients undergoing conventional and laparoscopic cholecystectomy. Methods: A prospective study included sixty patients from the Department of Emergency Surgery, Clinical Centre of Serbia who were operated for gallstone related chronic cholecystitis. All the patients enrolled in the study underwent cholecystectomy; the first group was operated conventionally (30 patients - control group), while the second group was operated laparoscopically (30 patients - treatment group). Results: There were no statistically significant differences in the values of NO and its postoperative changes in both groups, the conventionally operated group (p=0.943) and the laparoscopically operated group (p=0.393). We found an increase in NT values 24 hours postoperatively (p=0.000) in the conventionally operated patients, while in the group operated laparoscopically we didn’t find statistically significant changes in the values of NT (conventionally operated group (p=0.943) and laparoscopically operated group (p=0.393)). Conclusions: In our study, we found a significant increase in NT values 24 hours postoperatively in conventionally operated patients i.e. the control group, vs. the treatment group. Further randomized studies are needed for a better understanding of the impact of surgical trauma on oxidative stress response.


2021 ◽  
Author(s):  
Kristyn N. Borrelli ◽  
Emily J. Yao ◽  
Will W. Yen ◽  
Qiu T. Ruan ◽  
Melanie M. Chen ◽  
...  

ABSTRACTThe opioid epidemic led to an increase in the number of Neonatal Opioid Withdrawal Syndrome (NOWS) cases in infants born to opioid-dependent mothers. Hallmark features of NOWS include weight loss, severe irritability, respiratory problems, and sleep fragmentation. Mouse models provide an opportunity to identify brain mechanisms that contribute to NOWS. Neonatal outbred Swiss Webster Cartworth Farms White (CFW) mice were administered morphine (15mg/kg, s.c.) twice daily for postnatal days (P) 1-14, an approximate of the third trimester of human gestation. Male and female mice underwent behavioral testing on P7 and P14 to determine the impact of opioid exposure on anxiety and pain sensitivity. Ultrasonic vocalizations (USVs) and daily body weights were also recorded. Brainstems containing pons and medulla were collected during morphine withdrawal on P14 for RNA-sequencing. Morphine induced weight loss from P2-14, which persisted during adolescence (P21) and adulthood (P50). USVs markedly increased at P7 in females, emerging earlier than males. On P7 and P14, both morphine exposed female and male mice displayed hyperalgesia on the hot plate and tail flick assays, with females having greater hyperalgesia than males. Morphine-exposed mice exhibited increased anxiety-like behavior in the open-field arena at P21. Transcriptome analysis of the brainstem (medulla plus pons), an area implicated in opioid withdrawal and NOWS, identified pathways enriched for noradrenergic signaling in females and males. We also found sex-specific pathways related to mitochondrial function and neurodevelopment in females and circadian entrainment in males. Sex-specific transcriptomic neuroadaptations implicate unique neurobiological mechanisms underlying NOWS-like behaviors.SIGNIFICANCE STATEMENTNeonatal opioid withdrawal syndrome (NOWS) is a poorly understood condition that has both a genetic and environmental component and is thought to be mechanistically distinct from opioid withdrawal in adults. The development of murine models for measuring neurobehavioral responses is critical for informing the neurobiological adaptations underlying NOWS. Using outbred mice that more closely model human genetic variation, we discovered a surprising degree of sexual dimorphism in behavioral timing and severity of NOWS-model behaviors as well as transcriptomic adaptations in brain tissue that together suggest distinct mechanisms and sex-specific therapeutics for reversing withdrawal symptoms and restoring brain function.


Author(s):  
Florian Arendt

A test was done to see if reading a newspaper which consistently overrepresents foreigners as criminals strengthens the automatic association between foreign country and criminal in memory (i.e., implicit cultivation). Further, an investigation was done to find out if reading articles from the same newspaper produces a short-term effect on the same measure and if (1) emotionalization of the newspaper texts, (2) emotional reactions of the reader (indicated by arousal), and (3) attributed text credibility moderate the short-term treatment effect. Eighty-five participants were assigned to one of three experimental conditions. Participants in the control group received short factual crime texts, where the nationality of the offender was not mentioned. Participants in the factual treatment group received the same texts, but the foreign nationality was mentioned. Participants in the emotionalized treatment group received emotionalized articles (i.e., texts which are high in vividness and frequency) covering the same crimes, with the foreign nationality mentioned. Supporting empirical evidence for implicit cultivation and a short-term effect was found. However, only emotionalized articles produced a short-term effect on the strength of the automatic association, indicating that newspaper texts must have a minimum of stimulus intensity to overcome an effect threshold. There were no moderating effects of arousal or credibility pertaining to the impact on the implicit measure. However, credibility moderated the short-term effect on a first-order judgment (i.e., estimated frequency of foreigners of all criminals). This indicates that a newspaper’s effect on the strength of automatic associations is relatively independent from processes of propositional reasoning.


2021 ◽  
Vol 10 (5) ◽  
pp. 1148
Author(s):  
Makedonka Atanasovska Velkovska ◽  
Katja Goričar ◽  
Tanja Blagus ◽  
Vita Dolžan ◽  
Barbara Cvenkel

Oxidative stress and neuroinflammation are involved in the pathogenesis and progression of glaucoma. Our aim was to evaluate the impact of selected single-nucleotide polymorphisms in inflammation and oxidative stress genes on the risk of glaucoma, the patients’ clinical characteristics and the glaucoma phenotype. In total, 307 patients with primary open-angle glaucoma or ocular hypertension were enrolled. The control group included 339 healthy Slovenian blood donors. DNA was isolated from peripheral blood. Genotyping was performed for SOD2 rs4880, CAT rs1001179, GPX1 rs1050450, GSTP1 rs1695, GSTM1 gene deletion, GSTT1 gene deletion, IL1B rs1143623, IL1B rs16944, IL6 rs1800795 and TNF rs1800629. We found a nominally significant association of GSTM1 gene deletion with decreased risk of ocular hypertension and a protective role of IL1B rs16944 and IL6 rs1800629 in the risk of glaucoma. The CT and TT genotypes of GPX1 rs1050450 were significantly associated with advanced disease, lower intraocular pressure and a larger vertical cup–disc ratio. In conclusion, genetic variability in IL1B and IL6 may be associated with glaucoma risk, while GPX and TNF may be associated with the glaucoma phenotype. In the future, improved knowledge of these pathways has the potential for new strategies and personalised treatment of glaucoma.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3167
Author(s):  
Flavia Buonaurio ◽  
Maria Luisa Astolfi ◽  
Daniela Pigini ◽  
Giovanna Tranfo ◽  
Silvia Canepari ◽  
...  

Urinary concentrations of 16 different exposure biomarkers to metals were determined at the beginning and at the end of a working shift on a group of workers in the metal carpentry industry. Five different oxidative stress biomarkers were also measured, such as the oxidation products of RNA and DNA metabolized and excreted in the urine. The results of workers exposed to metals were compared to those of a control group. The metal concentrations found in these workers were well below the occupational exposure limit values and exceeded the mean concentrations of the same metals in the urine of the control group by a factor of four at maximum. Barium (Ba), mercury (Hg), lead (Pb) and strontium (Sr) were correlated with the RNA oxidative stress biomarker, 8-oxo-7, 8-dihydroguanosine (8-oxoGuo), which was found able to discriminate exposed workers from controls with a high level of specificity and sensitivity. The power of this early diagnostic technique was assessed by means of the ROC curve. Ba, rubidium (Rb), Sr, tellurium (Te), and vanadium (V) were correlated with the level of the protein oxidation biomarker 3-Nitrotyrosine (3-NO2Tyr), and Ba, beryllium (Be), copper (Cu), and Rb with 5-methylcytidine (5-MeCyt), an epigenetic marker of RNA damage. These effect biomarkers can help in identifying those workers that can be defined as “occupationally exposed” even at low exposure levels, and they can provide information about the impact that such doses have on their health.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Chacko ◽  
A Martinez-Naharro ◽  
T Kotecha ◽  
R Martone ◽  
D Hutt ◽  
...  

Abstract Background Cardiac involvement is the main driver of outcome in ATTR amyloidosis. Advances in therapeutics hold potential in transforming the course of the disease but the impact on cardiac amyloid load is unknown. The aim of this study was to evaluate the impact of patisiran, a new double stranded RNA based gene silencing therapy and a stabilizer, diflunisal, on cardiac amyloid load as measured by CMR and T1 mapping, in patients with ATTR amyloidosis. Methods and results Thirty-two patients with hereditary cardiac amyloidosis were studied. Sixteen patients received treatment with patisiran, and sixteen control subjects did not receive any disease modifying treatment. Patients were assessed with echocardiogram, CMR, NT-proBNP and six-minute walk time measurements at baseline and at 1 year (Mean interval 11.45±3.08 months in treatment group, mean interval 12.82±5.06 months in the control group). CMR analysis comprised LV volumes, T1 mapping to measure the extracellular volume (ECV) occupied by amyloid, T2 mapping and late gadolinium enhancement imaging. At 1-year follow-up, there was a substantial reduction in cardiac amyloid burden, in keeping with cardiac amyloid regression in 45% of patients on treatment. Overall the treatment group showed a reduction in ECV at 1 year follow up compared to an increase in ECV at 1 year in the control group (−1.37%, 95% CI: −3.43 to 0.68% versus 5.02%, 95% CI: 2.86% to 7.18% respectively, p&lt;0.001). The treatment group also showed an improvement in change in 6MWT at 1 year follow up compared to 6MWT at 1 year in the control group (−8.12 meters, 95% CI: −50.8 to 34.6 meters in the treatment group versus −132.27 meters, 95% CI: −216 to −48.6 meters in the control group, p=0.002). The treatment group showed a reduction in BNP at 1 year follow up compared to an increase in the control group (−567.87, 95% CI: −1288.90 to 153.15 in the treatment group versus 2004, 95% CI: 12.82 to 3995.45 in the control group, p&lt;0.001). There was no significant difference from baseline and 1-year data between the control and treatment groups for the difference in echocardiographic parameters, native T1, T2. There was a significant reduction in the percentage of injected dose by 99Tc-DPD scintigraphy in treated patients at 1 year compared to baseline. Conclusions These findings provide the first compelling evidence of substantial cardiac amyloid regression in ATTR amyloidosis, as well as the potential for CMR to be used to track response in treated patients with ATTR cardiac amyloidosis. Combination therapy with transthyretin knock down and stabilizing agents may well be synergistic given enhanced stoichiometry of stabilizers in the face of much reduced plasma transthyretin concentration. Funding Acknowledgement Type of funding source: None


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