Role of antioxidants in the neurobiology of drug addiction: An update.

Relationships between protective enzymatic and non-enzymatic pro-antioxidant mechanisms and addictive substances use disorders (SUDs) are analyzed here, based on the results of previous research, as well as on the basis of our current own studies. This review introduces new aspects of comparative analysis of associations of pro-antixidant and neurobiological effects in patients taking psychoactive substances and complements very limited knowledge about relationships with SUDs from different regions, mainly Europe. In view of the few studies on relations between antioxidants and neurobiological processes acting in patients taking psychoactive substances, this review is important from the point of view of showing the state of knowledge, directions of diagnosis and treatment, and further research needed explanation. We found significant correlations between chemical elements, pro-antioxidative mechanisms, and lipoperoxidation in the development of disorders associated with use of addictive substances, therefore elements that show most relations (Pr, Na, Mn, Y, Sc, La, Cr, Al, Ca, Sb, Cd, Pb, As, Hg, Ni) may be significant factors shaping SUDs. The action of pro-antioxidant defense and lipid peroxidation depends on the pro-antioxidative activity of ions. We explain the strongest correlations between Mg and Sb, and lipoperoxidation in addicts, which proves their stimulating effect on lipoperoxidation and on the induction of oxidative stress. We discussed which mechanisms and neurobiological processes change susceptibility to SUDs. The innovation of this review is to show that addicted people have lower activity of dismutases and peroxidases than healthy ones, which indicates disorders of antioxidant system and depletion of enzymes after long-term tolerance of stressors. We explain higher level of catalases, reductases, ceruloplasmin, bilirubin, retinol, α-tocopherol and uric acid of addicts. In view of poorly understood factors affecting addiction, analysis of interactions allows for more effective understanding of pathogenetic mechanisms leading to formation of addiction and development the initiation of directed, more effective treatment (pharmacological, hormonal) and may be helpful in the diagnosis of psychoactive changes.

Psychometric validation and cross-cultural adaptation of the Integrated Palliative care Outcome Scale in Polish (IPOS-Pol).

OBJECTIVE: The study aimed to assess the reliability and validity of the IPOS-Pol for patient self-reporting. METHOD: Patients (>18 years of age) with advanced cancer admitted to three palliative care centers (inpatient units and home-based) were recruited to a multicenter, cross-sectional, observational, prospective study. Participants provided responses to the IPOS-Pol Patient version and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire - Core 15 - Palliative Care (EORTC QLQ-C15-PAL) Polish version at baseline (T1) and four to seven days later (T2). We assessed test-retest reliability, internal consistency, and construct validity of the tool. RESULTS: One hundred and eighty patients were included. Test-retest reliability demonstrated no statistically significant differences in the average outcomes of the IPOS-Pol between T1 and T2 (27.2 ± 9.2 vs. 26.5 ± 8.7; p > 0.05). The intra-class correlation coefficient between T1 and T2 was r = 0.83 (p < 0.0001), the intra-class correlation coefficient for test-retest reliability of the IPOS-Pol items ranged from 0.63 to 0.84 (p < 0.0001), and the Cronbach's α coefficient for internal consistency was 0.773. The correlation coefficient between the IPOS-Pol and EORTC QLQ-C15-PAL total score was 0.79 (p < 0.001). SIGNIFICANCE OF RESULTS: The patient version of the Polish adaptation of IPOS is a valid and reliable outcome measure for assessing symptoms and concerns of individuals receiving palliative care, as well as the quality of care provided.

Achieving universal genetic assessment for women with ovarian cancer: Are we there yet? A systematic review and meta-analysis.

PURPOSE: Several professional organizations recommend universal genetic assessment for people with ovarian cancer as identifying pathogenic variants can affect treatment, prognosis, and all-cause mortality for patients and relatives. We sought to evaluate the literature on genetic assessment for women with ovarian cancer and determine if any interventions or patient characteristics drive utilization of services. METHODS: We searched key electronic databases to identify trials that evaluated genetic assessment for people with ovarian cancer. Trials with the primary aim to evaluate utilization of genetic assessment with or without interventions were included. Eligible trials were subjected to meta-analysis and the moderating influence of health interventions on rates of genetic assessment were examined. RESULTS: A total of 35 studies were included (19 report on utilization of genetic services without an intervention, 7 with an intervention, and 9 with both scenarios). Without an intervention, pooled estimates for referral to genetic counseling and completion of genetic testing were 39% [CI 27-53%] and 30% [CI 19-44%]. Clinician-facilitated interventions included: mainstreaming of genetic services (99% [CI 86-100%]), telemedicine (75% [CI 43-93%]), clinic-embedded genetic counselor (76% [CI 32-95%]), reflex tumor somatic genetic assessment (64% [CI 17-94%]), universal testing (57% [28-82%]), and referral forms (26% [CI 10-53%]). Random-effects pooled proportions demonstrated that Black vs. White race was associated with a lower rate of genetic testing (26%[CI 17-38%] vs. 40% [CI 25-57%]) as was being un-insured vs. insured (23% [CI 18-28%] vs. 38% [CI 26-53%]). CONCLUSIONS: Reported rates of genetic testing for people with ovarian cancer remain well below the goal of universal testing. Interventions such as mainstreaming can improve testing uptake. Strategies aimed at improving utilization of genetic services should consider existing disparities in race and insurance status.

Improvement of saccadic functions after dosing with methadone in opioid addicted individuals.

In the current experiment, we used the saccadometric test to study the effect of a single therapeutic dose of methadone on the integrity of cortico-subcortical brain functioning. In this prospective study, we used the Saccadometer System (Advanced Clinical Instrumentation, Cambridge, UK). The saccadometric test was performed before and 1.5 hours after methadone dosing. We analyzed the following saccadic parameters: latency, duration, amplitude, average and peak velocity, and processing performance (promptness) as well as a number of different types of saccades (like correct/incorrect, under/overshoot, and left-sided/right-sided). The sample consists of 40 subjects with an average 18 years of opioid addiction. The mean age is 35.3 ± 7 (80% males and 20% females). The mean period of heroin dependence is 15.3 ± 6.3 years. The mean daily dose of methadone in substitution therapy is 90 ± 26.5 mg. After administration of a single therapeutic dose of methadone, there were statistically significant differences in the values of saccade duration and latency when compared to the values before the drug administration. Average duration of saccade was significantly longer [51.40 ± 8.75 ms versus 48.93 ± 6.91 ms, z = 2.53, p = .01] and average latency was significantly longer [198.85 ± 52.57 ms versus 183.05 ± 30.95 ms, z = 2.09 p < .03]. This is the first study to test the therapeutic effect of daily methadone dosing on the integrity of the cortico-subcortical brain functions as measured by the saccadometry. More research is needed to explore the effect of illicit opioid use on the integrity of brain structures and functions, and the protective effect of opioid agonist therapy on reversing the damaging effects of illicit opioid use.

Oculomotor disturbances in HIV-positive individuals treated with methadone.

INTRODUCTION: Methadone substitution is claimed to be the most effective way of pharmacological management of human immunodeficiency virus (HIV) positive patients addicted to opioids. Possible and clinically the most relevant drug interactions are those between methadone and antiretroviral agents [13,18,25,32]. HIV causes cognitive impairment by infiltrating the central nervous system (CNS) in the initial phase of infection. The consequence of this is damage to the hippocampus, caudate nucleus, and basal ganglia [2,26]. METHODS: Eighty-six patients from the substitution program group were examined. The trial was conducted twice: before and about 1.5 hours after the administration of a therapeutic dose of methadone. The antisaccades task (AT) and latency task (LT) were performed using a saccadometer diagnostic system. RESULTS: The statistical analysis showed that the mean duration of latency measured by AT in HIV(-) and HIV(+) subjects after the administration of a therapeutic dose of methadone was significantly increased (p=0.03 HIV(-); p=0.04 HIV(+)). There was a statistically significant increase in the mean latency after the administration of methadone in HIV(+) subjects when compared to the control group measured by LT (p=0.03). CONCLUSION: The statistical analysis confirms the change in the saccadic refixation parameters in patients addicted to opioids. Methadone influences saccadic dynamic parameters less in HIV(+) than in HIV(-) drug users. Oculomotor disturbances are probably related to the neurotropic effects of HIV leading to damage of the striatum, which plays an important role in psychomotor functions.

Risk behavior in opioid-dependent individuals after the administration of a therapeutic dose of methadone.

BACKGROUND AND OBJECTIVES: Evidence suggests that methadone may play a protective role in the faulty decision-making in heroin-addicted individuals. This may reduce craving for opioids and the risky decisions associated with active opioid use. METHODS: We tested the effect of a daily therapeutic dose of methadone on faulty decision-making in eighty (n = 80) individuals with a history of opioid addiction. We used the Iowa Gambling Task (IGT) and compared the score and response time before and after the daily methadone dosing. RESULTS: The mean net IGT score before methadone dose was 10 (±22) and 22 (±23) after methadone dose (t = 4.23, p = .00006). These results reflect statistically significant improvement in faulty decisions after the administration of the daily methadone dose. The mean response time for the reward cards before methadone dose were 1,856 ms (±871) and 1,465 ms (±851) after methadone dose (t = 2.55, p = .012). The mean response time for the punishment cards before methadone dose were 1,688 ms (±911) and 1,399 ms (±827) after methadone dose (t = 1.86, p = .065). These results reflect statistically significant improvement in response time to a rewarding healthy decisions after the administration of the daily methadone dose. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: This is the first study to report the effect of a therapeutic dose of methadone on improving faulty decisions for individuals with a long history of opioids addiction. This study demonstrated that the time to making a healthy decision was significantly shorter as a result of administration of methadone.