Correlates of extramedical use of OxyContin versus other analgesic opioids among the US general population

BackgroundThere has been substantial public and media attention regarding extramedical use of OxyContin^®, but few studies focus on the characteristics of extramedical OxyContin^® users and whether they differ from extramedical other opioid users.MethodsWe used data from 8218 respondents who were past-year extramedical opioid analgesic users in the 2005 and 2006 National Survey of Drug Use and Health (NSDUH). We investigated differences in socio-demographic and psychiatric characteristics associated with past-year extramedical OxyContin^® use (n = 1144) versus extramedical other opioid analgesics use (n = 7074). Data on opioid sources was compared among past-month users. We also compared extramedical opioid users (n = 8218) versus other drug users (n = 16,214), and individuals with an analgesic disorder who had past-year extramedical OxyContin^® use (n = 339) versus those with other opioid use (n = 820).ResultsPast-year opioid users were more likely than users of other illegal drugs to be more educated and have a past-year major depressive episode. Past-year OxyContin^® users were more likely than other opioid users to be 18–25 years old (aOR = 1.9[1.1,3.2]), and have mental health and deviant behavior problems. Those with past-year analgesic disorder who used OxyContin^® were more likely to be younger, sell illegal drugs (aOR = 2.5[1.5,4.2]), and use illegal drugs than those who used other opioids. Past-month OxyContin^® users were more likely than past-month other opioid users to buy analgesics from drug dealers/other strangers and obtain opioid analgesics from multiple sources.ConclusionOur findings point out differences between OxyContin^® and other opioid users that might help prevention specialists and assist efforts to curb opioid analgesics diversion.     

Effect of the nutritional supplement ALAnerv® on the serum PON1 activity in post-acute stroke patients

BackgroundParaoxonase-1 (PON1) is one of the HDL-associated proteins which contributes to the antioxidant properties of these lipoproteins. The aim of this pilot study was to evaluate the effect of the nutritional supplement ALAnerv^® on serum PON1 activity in post-acute stroke patients undergoing rehabilitation.MethodsWe enrolled 28 post-acute stroke patients and randomly divided them into (–) ALAor (+) ALAstudy groups. All the patients underwent the same rehabilitation program and received comparable standard medications. Moreover, (+) ALA patients received ALAnerv^® for two weeks (2 pills/day). The serum PON1 activity was assessed on blood samples taken at the admission and at the discharge moments, respectively. We used paraoxon (paraoxonase activity, PONA), phenyl acetate (arylesterase activity, ARYLA) and dihydrocoumarin (lactonase activity, LACTA) as substrates, the latter activity being regarded as physiologically relevant. A control group of 14 apparently healthy subjects was also created.ResultsIn the (+) ALAgroup, LACTAsignificantly increased during the study period (17.6 ± 3.2 vs. 27.6 ± 3.5, p = 0.002). Moreover, the percentage of LACTAvariation between (–) ALAand (+) ALAgroups during the study was also statistically different (–11.7 ± 6.9% vs. +95.1 ± 29.7%, p < 0.0001).ConclusionsThese preliminary results suggest that ALAnerv^® could contribute to the improvement of the physiologically relevant LACTAof PON1 in post-acute stroke patients, enabling this enzyme to contribute to the redox correction. Also, this study raises the question about the effect of a longer treatment period over the other enzymatic activities of serum PON1.     

Case–control association analysis of polymorphisms in the delta-opioid receptor,OPRD1, with cocaine and opioid addicted populations

BackgroundAddiction susceptibility and treatment responsiveness are greatly influenced by genetic factors. Sequence variation in genes involved in the mechanisms of drug action have the potential to influence addiction risk and treatment outcome. The opioid receptor system is involved in mediating the rewarding effects of cocaine and opioids. The μ-opioid receptor (MOR) has traditionally been considered the primary target for opioid addiction. The MOR, however, interacts with and is regulated by many known MOR interacting proteins (MORIPs), including the δ-opioid receptor (DOR).MethodsThe present study evaluated the contribution of OPRD1, the gene encoding the DOR, to the risk of addiction to opioids and cocaine. The association of OPRD1 polymorphisms with both opioid addiction (OA) and cocaine addiction (CA) was analyzed in African American (OA n = 336, CA n = 503) and European American (OA n = 1007, CA n = 336) populations.ResultsThe primary finding of this study is an association of rs678849 with cocaine addiction in African Americans (allelic p = 0.0086). For replication purposes, this SNP was analyzed in a larger independent population of cocaine addicted African Americans and controls and the association was confirmed (allelic p = 4.53 × 10^?5; n = 993). By performing a meta-analysis on the expanded populations, the statistical evidence for an association was substantially increased (allelic p = 8.5 × 10^?7) (p-values non-FDR corrected).ConclusionThe present study suggests that polymorphisms in OPRD1 are relevant for cocaine addiction in the African American population and provides additional support for a broad role for OPRD1 variants in drug dependence.     

Test of association between GABRA2 (SNP rs279871) and adolescent conduct/alcohol use disorders utilizing a sample of clinic referred youth with serious substance and conduct problems,controls and available first degree relatives

Recent findings have linked the GABRA2 gene with antisocial personality disorder and alcohol dependence (AD) in adults and conduct disorder (CD), but not AD symptoms, in children and adolescents. We sought to replicate previous findings and test for an association between a single nucleotide polymorphism (SNP) in the GABRA2 gene (rs279871) and CD among adolescents.MethodsAdolescent patients (n = 371), 13–18 years old, were recruited from a university substance abuse treatment program. Patient siblings (n = 245), parents of patients (n = 355), adolescent controls (n = 185), siblings of controls (n = 163) and parents of controls (n = 263) were included in these analyses (total sample n = 1582). Case-control (using only Caucasian and Hispanic probands) and family-based association tests were completed to test for association between rs279871 and several a priori CD and AD phenotypes.ResultsFor case-control association tests, rs279871 was significantly associated with CD (p = 0.02) but not AD phenotypes; the result did not survive strict correction for multiple testing. All family-based association tests were non-significant (CD p = 0.48; CD symptom count age corrected within sex p = 0.91; AD p = 0.84; alcohol use disorder p = 0.52).ConclusionsConsistent with previous findings, the results do not support the association between GABRA2 SNP rs279871 and AD in adolescents. Our results also do not support an association between rs279871 and CD; the study limitations are reviewed.     

Binding of new aminopropan-2-ol compounds to bovine serum albumin, α1 acid glycoprotein and rat serum using equilibrium dialysis and LC/MS/MS

BackgroundThe binding of three new aminopropan-2-ol compounds briefly called 2F109, ANBL and TWo8 with potential cardiovascular activity to bovine serum albumin (BSA), α₁-acid glycoprotein (AGP) and to rat serum was studied. The chemical structures of these compounds are related to carvedilol. They possess an antiarrhythmic and hypotensive activity, and β- and α-adrenolytic mechanism of action. All analogues are weak bases with pKa values 8.65,8.85 and 8.26 for 2F109, ANBL and TWo8, respectively, and they possess lipophilic character (log P > 1.9584).MethodsThe extent of protein binding was determined using equilibrium dialysis in the range 2.5 – 900 μM, and 2.5 – 300 μM for binding of investigated compounds to BSA and AGP, respectively, and the quantitative measurement was done by LC/ESI-MS/MS assay.ResultsThe studied compounds bound to a single class of binding sites on BSA which was characterized by low affinity (K_d for 2F109 = 8.49 × 10^–5 M, for ANBL = 1.92 × 10^–5 M, and for TWo8 = 1.71 × 10^–5 M) and low capacity(n = 0.53 for 2F109,0.132 for ANBL and 0.13 for TWo8). The binding of 2F109, ANBL and TWo8 to AGP revealed one class of binding sites, with moderate affinity (K_d for 2F109 = 4.67 × 10^–6 M, for ANBL = 3.48 × 10^–5 M, and for TWo8 = 1.13 × 10^–5 M) and higher capacity (n = 2.21 for 2F109, 2.76 for ANBL and 2.28 for TWo8).ConclusionThe obtained data indicate that 2F109, ANBL and TWo8 moderately bind to BSA (34.2 – 71.2%) with low capacity (K_a = 6.21 × 10³–7.61 × 10³ M^–1)and strongly bind to AGP(71.5–85.5%)with moderate affinity (K_a = 7.94 × 104⁴.73 ×10⁵ M^–1).     

Characterization of fasted human gastric fluid for relevant rheological parameters and gastric lipase activities

PurposeTo characterize human gastric fluid with regard to rheological properties and gastric lipase activity. In addition, traditional physicochemical properties were determined.MethodsFasted HGA were collected from 19 healthy volunteers during a gastroscopic examination. Rheological characterization of the aspirates was conducted on a TA AR-G2 rheometer, using cone and plate geometry. Lipase activity was measured by continuous titration of released free fatty acid from tributyrate. Further, pH, osmolality, buffer capacity, and surface tension were measured and the total protein content and bile salt level were determined using assay kits.ResultsRheological examination of HGA showed non-Newtonian shear-thinning behavior with predominant elastic behavior in the linear range. The apparent viscosity was measured to be in the range of 1.7–9.3 mPa s at a shear rate of 50 s⁻¹. The FaSSGF and HCl pH 1.2 have no shear-thinning properties and showed lower viscosity (1.1 mPa s at 50 s⁻¹). The observed viscosity of the HGA will decrease the intrinsic dissolution rate of drugs. The activity of the gastric lipase was 7.4 ± 4.0 U/mL (N = 6, n = 3) and 99.0 ± 45.3 U/mL (N = 19, n = 3) at pH 2.8 and 5.4, respectively. pH, surface tension, buffer capacity, bile salt concentration, and osmolality were measured and compared with literature data.ConclusionThe rheological behavior and the mean apparent viscosity of HGA are significantly different from that of water and should therefore be considered important during development of gastric simulated media. Further, the activity of the HGL is active even under fasted gastric conditions and might contribute to the digestion and emulsification of lipid-based drug delivery systems in the entire gastrointestinal tract. HGL should therefore be considered in gastric evaluation of lipid-based drug delivery systems.     

Clinical and immunological consequences of total glucosides of paeony treatment in Sjögren's syndrome: A randomized controlled pilot trial

BackgroundThe total glucosides of paeony (TGP) can inhibit inflammation and alleviate symptoms in autoimmune diseases. This study investigated the clinical and immunological consequences of TGP treatment in patients with primary Sjögren's syndrome (SS).MethodsWe conducted a randomized, double-blinded, placebo-controlled clinical trial in 45 patients with primary SS. Patients were randomized at 2:1 ratio to either TGP group (n = 29) or placebo group (n = 16) and followed up for 24 weeks. The primary outocme was the European League Against Rheumatism Sjögren's Syndrome Patient Reported Index (ESSPRI). The secondary outcomes were stimulated and unstimulated salivary flow rate, Schirmer's test and erythrocyte sedimentation rate (ESR), immuneglobulin (Ig), anti-nuclear antibody (ANA), anti-SSA, and anti-SSB. The proportions of B cells in peripheral blood and the levels of serum inerleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and B cell activating factor belonging to the TNF family (BAFF) were measured at baseline and at the end of follow up of 24 weeks.ResultsThe average score of ESSPRI in both groups had no statistical significance at 24th week. The mean of ESSPRI in the dry-mouth part of questionnaire in patients who scored 3 to 6 points was significantly reduced in the TGP group changed from (4.81 ± 0.60) at baseline to (4.20 ± 1.46) (P = 0.027) at week 24. Stimulated salivary flow rate increased at week 24 from (1.80 ± 0.39) to (2.01 ± 0.51) (P = 0.031) and unstimulated salivary flow rate increased from (0.65 ± 0.46) to (0.78 ± 0.45) (P = 0.011) in the TGP group, but the placebo group showed no significant difference. Erythrocyte sedimentation rate (ESR) was decreased significantly compared to the placebo group at 12- and 24-week from (40.9 ± 18.0) to (29.4 ± 12.2) (P = 0.003) and (30.4 ± 17.3) (P = 0.024). The percentage of naive B cells decreased at week 24 in the TGP group from (77.34 ± 12.20) to (64.59 ± 15.60) (P = 0.005) while memory B cells increased from (21.79 ± 11.97) to (34.21 ± 15.48) (P = 0.006) respectively. The concentrations of TNF-α and IFN-γ decreased in the TGP group at week 24 from (32.51 ± 26.67) to (24.22 ± 13.56) (P = 0.017) and (10.71 ± 8.94) to (6.55 ± 4.88) (P = 0.022), respectively. No significant difference in ANA titer, anti-SSA antibodies, anti-SSB antibodies, C3 concentration or C4 concentration was observed between the two groups.ConclusionTGP appears to improve the glandular secreting function and decrease the level of inflammatory cytokines.     

Effects of cigarette smoke on Holter ECG recordings in patients with arterial hypertension. Part 2: Parameters of heart rate turbulence

The studies aimed at evaluation of cigarette smoke effect on heart rate turbulence (HRT) in patients with arterial hypertension (AH). 223 consecutive individuals were qualified to the studies. The following groups of patients not suffering from other disease which may affect HRT were distinguished: 1 – patients with AH (n = 145); 2 – patients without AH (n = 48). In group 1 the following patient subgroups were studied: A – active smokers (n = 42), B – non-smokers exposed to cigarette smoke (n = 30), C – non-smokers not exposed to tobacco smoke (n = 34), D – former smokers who had quit smoking (n = 26). In every participant HRT analysis was conducted. Subgroup A manifested significantly higher values of TO and lower values of TS as compared to analogous values obtained in subgroups B–D. Subgroups B and D were characterized also by significantly higher values of TO and lower values of TS as compared to subgroup C. Active and passive cigarette smoking were found to represent independent risk factors for an abnormal HRT.ConclusionBoth active and passive exposure to tobacco smoke induces causes abnormal HRT in patients with arterial hypertension.     

The effect of FT500 Plus® on ovarian stimulation in PCOS women

Both oxidative stress and polycystic ovary syndrome have been involved in several aspects of female reproduction. In this retrospective observational study, the outcome of controlled ovarian stimulation and follicular microenvironment of twenty-five women affected by PCOS (Group A) have been explored, evaluating the effects of myo-inositol in association with antioxidant activities (FT500 Plus^®). Twenty-five untreated-PCOS women (Group B) with similar characteristics served as control group. Although there was no difference in ovarian volume at time zero, this parameter was significantly smaller at the 5-month follow-up in the Group A (11.1 ± 0.9 versus 13.5 ± 1; P = 0.0001). Group A showed a significant increase in the number of MII oocytes (6.3 ± 2.5 versus 4.5 ± 2; P = 0.03) and glutathione peroxidase activity in follicular fluid (15.4 ± 6.2 versus 11 ± 2.2; P = 0.04). FT500 Plus^® may be considered in PCOS patient for improving oocyte quality.     

Neurocognitive,psychiatric, and substance use characteristics in opioid dependent adults

AimsTo describe neurocognitive function among opioid-dependent adults seeking buprenorphine treatment and to explore the impact of lifetime psychiatric conditions on neurocognitive function. To explore the additive interaction of patient-based characteristics that may help to inform treatment.DesignCross-sectional assessment of neurocognitive function, substance use, and psychiatric characteristics of adults seeking buprenorphine treatment within substance use treatment centers in New York City.ParticipantsThirty-eight opioid-dependent adults seeking buprenorphine treatment.MeasurementsA comprehensive battery, which included measures of executive functioning, learning, memory, verbal fluency, attention, processing speed, and motor functioning were administered. The Wide Range Achievement Test-Third Edition, the Composite International Diagnostic Interview, and an audio computer assisted structured interview were also completed. Correlations and independent sample t-tests were used to ascertain group differences.FindingsThirty-nine percent of participants were impaired in global neurocognitive function (n = 15). Over one third were impaired in either: learning (n = 28), memory (n = 26), executive functioning (n = 17), motor functioning (n = 17), attention/working memory (n = 14) or verbal fluency (n = 12). Lifetime history of alcohol dependence was associated with impairment in global neurocognitive, executive functioning, and motor functioning. Lifetime history of cocaine dependence was associated with impairment in executive functioning and motor functioning (all p's < 0.05). Major depressive disorder history was not associated with neurocognitive impairment.ConclusionsAmong this sample of opioid-dependent adults, there were high rates of global and domain-specific neurocognitive impairment, with severe impairment in learning and memory. Lifetime alcohol and cocaine dependence were associated with greater neurocognitive impairment, particularly in executive functioning. Because executive functioning is critical for decision-making and learning/memory dysfunction may interfere with information encoding, these findings suggest that opioid-dependent adults may require enhanced support for medical decision-making.     

Panic attacks and smoking cessation among cancer patients receiving smoking cessation treatment

ObjectiveLittle is known about factors associated with smoking cessation in cancer patients. This study examined the impact of panic attacks on smoking abstinence likelihood among cancer patients receiving tobacco cessation treatment.MethodThe relationship of panic attacks to 7-day point-prevalence abstinence at mid-treatment, end of treatment, and 6-month post-end of treatment were examined among cancer patients (N = 2255 patients; 50.1% female; M_age = 54.9, SD = 11.0) who received counseling and pharmacotherapy for smoking cessation. Panic attack history indexed by two questions from the Patient Health Questionnaire (PHQ). Point-prevalence abstinence was assessed via the Timeline Follow-Back.ResultsCancer patients with a history of panic attacks, (n = 493, 21.9%) relative to those without, were less likely to be abstinent at mid-treatment (OR = 0.79, CI_95% = 0.64–0.98) and end of treatment (OR = 0.72, CI_95% = 0.58–0.89). After adjusting for significant covariates, panic attack history remained predictive of decreased abstinence likelihood at end of treatment (OR = 0.78, CI_95% = 0.62–0.99).ConclusionsPanic attacks may be related to poorer cessation outcome during smoking treatment among cancer patients, and may be usefully assessed and targeted for intervention.     

P-glycoprotein function in peripheral T lymphocyte subsets of myasthenia gravis patients: Clinical implications and influence of glucocorticoid administration

Myasthenia gravis (MG) is an autoimmune neuromuscular disorder with a chronic clinical course that requires long-term glucocorticoid (GC) therapy. A drug efflux pump, P-glycoprotein (P-gp), actively transports GC out of target cells, thereby reducing its efficacy. We evaluated the P-gp function of peripheral-blood mononuclear cells in 59 MG patients. P-gp function was estimated from a decrease in fluorescent P-gp substrate Rhodamine 123 and its inhibition by the conformation-sensitive UIC2 monoclonal antibody. P-gp function on CD8⁺ T cells in 21 MG patients having experienced GC therapy was higher than that in 19 MG patients having no history of GC therapy (p = 0.026). There was a significant correlation between P-gp function in CD3⁺ (r = 0.55, p = 0.014) or CD4⁺ (r = 0.48, p = 0.034) T cells and the total dose of prednisolone for treatment. P-gp function on CD4⁺ T cells in MG patients who showed low responses to prednisolone therapy (n = 8) was higher than that in patients who showed relatively high responses to prednisolone therapy (n = 10) (p = 0.045). These results suggest that higher P-glycoprotein activity on CD3⁺ or CD4⁺ cells necessitated treatment with higher steroid doses in order to achieve a clinical response. The measurement of P-gp function on CD4⁺ T cells is useful in the assessment of clinical response to GC therapy.     

Effects of alcohol on disinhibition towards alcohol-related cues

BackgroundWe investigated (1) the effects of acute alcohol on inhibition of alcohol-related versus neutral cues, (2) the effects of drinking status on inhibition of alcohol-related versus neutral cues, and (3) the similarity of any effects of alcohol or drinking status across two different cue types (lexical versus pictorial).MethodsParticipants received 0.0 g/kg, 0.4 g/kg or 0.6 g/kg of alcohol in a between-subjects design. Healthy, heavy and light social alcohol users (n = 96) completed both lexical and pictorial cue versions of an alcohol-shifting task. Participants were instructed to respond to target stimuli by pressing the spacebar, but to ignore distracter stimuli. Errors towards distracter stimuli were analysed using a series of mixed-model ANOVAs, with between-subjects factors of challenge and drinking status and within-subjects factors of distracter type (alcohol, neutral) and block (shift, non-shift).ResultsLexical commission error data indicated a main effect of distracter (F [1,90] = 43.25, p < 0.001, η² = 0.33), which was qualified by a marginal interaction with challenge condition (F [2,90] = 2.77, p = 0.068, η² = 0.06). Following an acute high dose of alcohol participants made more errors towards alcohol distracters. Pictorial commission error data indicated a significant main effect of distracter (F [1,90] = 67.40, p < 0.001, η² = 0.43), such that all participants made more errors towards neutral image distracters versus alcohol distracter images.ConclusionsOur results reveal acute alcohol's impairment of inhibitory control may be enhanced when a response towards alcohol-related lexical stimuli is required to be withheld.     

Perceived unmet need for alcohol and drug use treatments and future use of services: Results from a longitudinal study

BackgroundThis study assessed the association of perceived need for and perceived barriers to treatments for substance use disorder (SUD) with subsequent use of these treatments in community settings.MethodsDrawing on data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), we examined the association of perceived need and barriers to SUD treatments in waves 1 of NESARC (2001–2002; n = 43,093) with the subsequent use of these treatments in the follow-up wave 2 (2004–2005; n = 34,625).ResultsOnly 8.5% (n = 195) of the 2333 NESARC participants with an untreated 12-month SUD in wave 1 perceived a need for SUD treatment. Participants who reported a perceived need were more likely to use these services in follow-up than those who did not report such a need (14.8% vs. 4.9%, adjusted odds ratio [aOR] = 3.16, 95% confidence intervals [CI] = 1.70–5.90, P < 0.001). Among participants who perceived a need, those who reported pessimistic attitudes towards treatments as a barrier were less likely than others to use services in follow-up (aOR = 0.08, 95% CI = 0.01–0.73, P = 0.027). Other barriers, including financial barriers and stigma were not significantly associated with treatment seeking.ConclusionsThe findings suggest the need for a two-pronged approach to improving treatment seeking for SUD in community settings: one focusing on enhancing recognition of these disorders, the other focusing on educating potential consumers regarding the benefits of SUD treatments.     

Gabapentin-induced changes of plasma cortisol level and immune status in hysterectomized women

AimWe have examined the effects of gabapentin (GBP) on stress-related changes of cortisol and catecholamines in patients who underwent hysterectomy because of uterine fibrinoids. Additionally, we have observed the effect of GBP on the immune status in the acute stress response to surgery.MethodsSixty patients scheduled for an abdominal hysterectomy were randomly assigned to the GBP administration 1 h before surgery (n = 30 pts), or to the placebo group (n = 30 pts). Blood samples were collected before and 24 h after the surgery. The intensity of pain was assessed by a visual analogue scale (VAS) every 8 h at rest. Immunomodulatory effects of GBP were determined by flow cytometry. We followed the total proportion of CD3⁺ lymphocytes, CD3⁺CD4⁺, CD3⁺CD8⁺, CD19⁺ B lymphocytes, CD16⁺CD56⁺CD3⁻NK cells and CD16⁺CD56⁺CD3⁺ NKT cells before and 24 h after hysterectomy. The plasma cortisol and catecholamines concentration was used to estimate the level of the stress response.ResultsVAS pain score at rest was significantly lower in the GBP group than in the placebo group (P = 0.003). Application of GBP significantly decreased the plasma cortisol level 24 h after the operation in comparison to the placebo group (P < 0,001). We found significant positive correlation between the VAS pain score and concentration of cortisol in all patients (P = 0.025). GBP reduced the concentration of catecholamines (p < 0.05). The proportion of CD3⁺ (P = 0.027) and CD3⁺CD4⁺cells (P = 0.006) was significantly lower in the GBP group 24 h after operation, while the contribution of CD19⁺ (P = 0.033) was significantly higher.ConclusionPreoperative administration of GBP reduced the pain scores at rest in patients at 0, 16 and 24 h after abdominal hysterectomy. Additionally, GBP reduced the stress response and changed immune parameters in the reaction to surgery.     

Toxicity of natural insecticides on the larvae of wheat head armyworm,Dargida diffusa (Lepidoptera: Noctuidae)

The wheat head armyworm, Dargida (previously Faronta) diffusa (Walker) (Lepidoptera: Noctuidae), is widely distributed in North American grasslands and is most common on the Great Plains, where it is often a serious pest of corn and cereal crops. Six commercially available botanical or microbial insecticides used against D. diffusa were tested in the laboratory: Entrust^® WP (spinosad 80%), Mycotrol^® ESO (Beauveria bassiana GHA), Aza-Direct^® (azadirachtin), Met52^® EC (Metarhizium brunneum F52), Xpectro^® OD (Beauveria bassiana GHA + pyrethrins), and Xpulse^® OD (Beauveria bassiana GHA + azadirachtin). Concentrations of 0.1, 0.5, 1.0 and 2.0 fold the lowest labelled rates of formulated products were tested for all products, while for Entrust WP additional concentrations of 0.001 and 0.01 fold the label rates were also assessed. Survival rates were determined from larval mortality at 1–9 days post treatment application. We found that among the tested chemicals, Entrust^® (spinosad) was the most effective, causing 83–100% mortality (0–17% survival rate) at day 3 across all concentrations. The others, in order of efficacy from most to least, were Xpectro^® (B. bassiana GHA + pyrethrins), Xpulse^®OD (B. bassiana GHA + azadirachtin), Aza-Direct^® (azadirachtin), Met52^® EC (M. brunneum F52), and Mycotrol^® ESO (B. bassiana GHA). These products and entomopathogenic fungi caused 70–100% mortality (0–30% survivability) from days 7 to 9. The tested products and entomopathogenic fungi can be used in management of D. diffusa.     

Associations between PTSD and intimate partner and non-partner aggression among substance using veterans in specialty mental health

BackgroundRisk factors of violence perpetration in veterans include substance use and posttraumatic stress disorder (PTSD); however, it is unknown whether these factors are associated with greater risk for partner or non-partner violence. This study investigated the associations between probable PTSD, heavy drinking, marijuana use, cocaine use, and partner and non-partner violence perpetration.MethodsSelf-report questionnaires assessing past-year partner and non-partner aggression (CTS2) as well as past-month substance use (SAOM), probable PTSD (PCL-C), and probable depression (PHQ-9) were administered to 810 substance using veterans entering VA mental health treatment.ResultsIn bivariate analyses, probable PTSD in substance using veterans was associated with violence perpetration (partner physical, χ² = 11.46, p = 0.001, φ = 0.12; non-partner physical, χ² = 50.64, p < 0.001, φ = 0.25; partner injury, χ² = 6.41, p = 0.011, φ = 0.09; non-partner injury, χ² = 42.71, p < 0.001, φ = 0.23). In multiple logistic regression analyses that adjusted for sociodemographic characteristics, probable PTSD was independently associated with non-partner physical (odds ratio [OR], 2.82; 95% confidence interval [CI], 1.97–4.05) and injury aggression (OR, 3.96; CI, 2.56–6.13). Cocaine and heavy drinking were independently associated with non-partner physical and injury aggression and non-partner injury aggression respectively.ConclusionsThe results provide evidence that probable PTSD, heavy drinking, and cocaine use are associated with increased risk of non-partner violence perpetration in substance using veterans. These results underscore the importance of screening for PTSD symptoms and violence perpetration towards non-partners in substance using veterans presenting for treatment.     

Comparative evaluation of two dye probes in the rat everted gut sac model for unambiguous classification of P-gp substrate and inhibitor

IntroductionP-glycoprotein (P-gp) plays a crucial role in beta-amyloid efflux from the blood–brain barrier thus becoming a promising pharmacological target in the treatment of Alzheimer's disease (AD). The increase of P-glycoprotein expression and activity by a P-gp inducer could be an effective pharmacological strategy in slowing or halting the progression of AD. Commonly used in vitro methods to classify a P-gp interacting molecule as substrate, inhibitor, modulator or inducer are not always confirmed by in vivo experiments. Here we validate the new dye-probe beta-amyloid (1–40) HiLyte Fluor? TR-labeled (Ab-HiLyte) (Anaspec) P-gp mediated transport in the ex vivo rat everted gut sac assay by using MC18 or MC266, a fully characterized P-gp inhibitor and substrate, respectively, and compare it with the commonly used dye rhodamine.MethodsMale Wistar rats' everted intestines were divided into sacs, each sac was filled with 10 μM Ab-HiLyte with or without 50 μM of MC18 or MC266. Ab-HiLyte concentrations in mucosal fluid were measured spectrophotometrically at 594 nm at each appropriate time.ResultsThe Ab-HiLyte P-gp mediated efflux had a K = 1.00 × 10^? 2 min^? 1 and t_1/2 = 68.74 min, while in the presence of MC18, the Ab-HiLyte efflux turned out to be reduced by an order of magnitude (K = 1.65 × 10^? 3 min^? 1) and the half life is extremely increased (t_1/2 = 419 min). A P-gp substrate, like MC266, determines no change in the efflux of Ab: the kinetic constant and the half life turned out to be unmodified (K = 1.81 × 10^? 2 min^? 1 and t_1/2 = 38.28 min).DiscussionThe results demonstrate that the new dye probe, Ab-HiLyte, could be a probe of choice to unequivocally distinguish between a P-gp substrate and an inhibitor. This is particularly important as different groups obtain a controversial classification of the same compound.     

Sulfur mustard causes oxidants/antioxidants imbalance through the overexpression of free radical producing-related genes in human mustard lungs

The aim of this study is to analyze oxidative stress (OS) and changes in expression of reactive oxygen species (ROS) producing-related genes in mustard lungs. Human lung biopsies provided from controls (n = 5) and sulfur mustard (SM)-exposed patients (n = 6). Changes in expression of dual oxidases (DUOXs), aldehyde oxidase 1 (AOX1), thyroid peroxidase (TPO), myeloperoxidase (MPO) and eosinophil Peroxidase (EPO) were measured using RT² Profiler™ PCR Array. OS was evaluated by determining bronchoalveolar lavage fluids (BALF) levels of total antioxidant capacity (TAC) and malondialdehyde (MDA). Higher TAC value was observed in BALF of controls compared with patients (0.138 ± 0.02683 μmol/l vs 0.0942 ± 0.01793 μmol/l), whereas a significant increase in MDA concentration was found in patients (0.486 ± 0.04615 nmol/l vs 0.6467 ± 0.05922 nmol/l). All ROS producing-related genes were overexpressed in the order AOX1> MPO> DUOX2> DUOX1> TPO> EPO. Upregulation of these genes may be a reason for overproduction of ROS, oxidants/antioxidants imbalance, OS and respiratory failures in mustard lungs.