Satisfaction with life and opioid dependence

<p>Abstract</p> <p>Background</p> <p>Serious substance misuse and dependence is widely seen as damaging to an individual and to society in general. Whereas the medical and society effects of substance misuse are widely described, some commentators suggest substance misuse may be an "alternative lifestyle".</p> <p>Aim</p> <p>To assess general life satisfaction amongst treatment-seeking people with substance dependence.</p> <p>Methods</p> <p>The Satisfaction With Life Scale (SWLS) was administered to a sample of opioid-dependent people receiving substitute medication.</p> <p>Results</p> <p>105 subjects and 105 age-sex matched subjects in a comparison group completed the questionnaire. The mean SWLS score was 7.12 (SD = 10.6; median = 6) for patients compared to 22.6 (SD = 6.8) in the comparison group. (Two sided p < 0.0001; Median difference = -13.5; Wilcoxon signed rank test.)</p> <p>Conclusion</p> <p>The study used a validated instrument and objective reports to confirm significantly higher rates of dissatisfaction with life among opioid dependent people in treatment when compared to members of the general population.</p

KAI407, a potent non-8-aminoquinoline compound that kills Plasmodium cynomolgi early dormant liver stage parasites in vitro.

Preventing relapses of Plasmodium vivax malaria through a radical cure depends on use of the 8-aminoquinoline primaquine, which is associated with safety and compliance issues. For future malaria eradication strategies, new, safer radical curative compounds that efficiently kill dormant liver stages (hypnozoites) will be essential. A new compound with potential radical cure activity was identified using a low-throughput assay of in vitro-cultured hypnozoite forms of Plasmodium cynomolgi (an excellent and accessible model for Plasmodium vivax). In this assay, primary rhesus hepatocytes are infected with P. cynomolgi sporozoites, and exoerythrocytic development is monitored in the presence of compounds. Liver stage cultures are fixed after 6 days and stained with anti-Hsp70 antibodies, and the relative proportions of small (hypnozoite) and large (schizont) forms relative to the untreated controls are determined. This assay was used to screen a series of 18 known antimalarials and 14 new non-8-aminoquinolines (preselected for blood and/or liver stage activity) in three-point 10-fold dilutions (0.1, 1, and 10 μM final concentrations). A novel compound, designated KAI407 showed an activity profile similar to that of primaquine (PQ), efficiently killing the earliest stages of the parasites that become either primary hepatic schizonts or hypnozoites (50% inhibitory concentration [IC50] for hypnozoites, KAI407, 0.69 μM, and PQ, 0.84 μM; for developing liver stages, KAI407, 0.64 μM, and PQ, 0.37 μM). When given as causal prophylaxis, a single oral dose of 100 mg/kg of body weight prevented blood stage parasitemia in mice. From these results, we conclude that KAI407 may represent a new compound class for P. vivax malaria prophylaxis and potentially a radical cure

Impulsivity and response inhibition in alcohol dependence and problem gambling.

Abstract Introduction Impulsivity is a central feature of drug addiction and may arise as a result of impaired inhibitory control. The extent to which inhibitory deficits arise as a consequence of drug exposure or relate to pre-existing addiction vulnerability is unknown. Materials and methods This study compared measures of impulsivity in outpatients with alcohol dependence (n=23) and problem gambling (n=21), a putative behavioural addiction where direct effects of drug exposure may be minimal. Healthy controls (n=27) were also tested, in a cross-sectional design. Subjects completed the stop-signal test as a neurocognitive probe of response inhibition, alongside self-report ratings of impulsivity, adult ADHD and OCD. Results On the stop-signal test, Go reaction time and stopsignal reaction time were significantly slower in the alcohol-dependent group, compared with healthy controls. Healthy controls slowed their responding after successful and failed stop trials. Slowing after failed stop trials was significantly attenuated in the alcohol-dependent subjects. Go reaction time and post-error slowing were correlated with chronicity and severity, respectively, in the alcoholdependent subjects. Problem gamblers did not differ significantly from controls on the stop-signal test, despite trait elevations in impulsivity ratings. Conclusion Inhibitory control is impaired in alcohol dependence but occurs in the context of psychomotor slowing. In addition, alcohol-dependent individuals failed to show behavioral adjustment following failed stops. These deficits may represent direct effects of chronic alcohol administration on fronto-striatal circuitry