Contingency management with community reinforcement approach or twelve-step facilitation drug counseling for cocaine dependent pregnant women or women with young children

Background

Cocaine abuse among women of child-bearing years is a significant public health problem. This study evaluated the efficacy of contingency management (CM), the community reinforcement approach (CRA), and twelve-step facilitation (TSF) for cocaine-dependent pregnant women or women with young children.

Methods

Using a 2 × 2 study design, 145 cocaine dependent women were randomized to 24 weeks of CRA or TSF and to monetary vouchers provided contingent on cocaine-negative urine tests (CM) or non-contingently but yoked in value (voucher control, VC). Primary outcome measures included the longest consecutive period of documented abstinence, proportion of cocaine-negative urine tests (obtained twice-weekly), and percent days using cocaine (PDC) during treatment. Documented cocaine abstinence at baseline and 3, 6, 9 and 12 months following randomization was a secondary outcome.

Findings

CM was associated with significantly greater duration of cocaine abstinence (p < .01), higher proportion of cocaine-negative urine tests (p < 0.01), and higher proportion of documented abstinence across the 3-, 6-, 9- and 12-month assessments (p < 0.05), compared to VC. The differences between CRA and TSF were not significant for any of these measures (all p values ≥0.75). PDC decreased significantly from baseline during treatment in all four groups (p < 0.001) but did not differ significantly between CM and VC (p = 0.10) or between TSF and CRA (p = 0.23).

Interpretation

The study findings support the efficacy of CM for cocaine dependent pregnant women and women with young children but do not support greater efficacy of CRA compared to TSF or differential efficacy of CM when paired with either CRA or TSF.     

Contingency management is efficacious and improves outcomes in cocaine patients with pretreatment marijuana use

Background

Marijuana use is common in patients seeking treatment for cocaine use. Nevertheless, few studies have examined effects of marijuana use on treatment outcomes in general, and even fewer with respect to contingency management (CM) treatment, which has been criticized for potentially increasing non-reinforced drug use.

Methods

Data from three randomized clinical trials of CM versus standard treatment (ST) in cocaine-abusing patients were examined ( [Petry et al., 2004], [Petry et al., 2005a] and [Petry et al., 2006a]; N = 393) to assess effects of pretreatment marijuana use on outcomes. Patients were divided into two groups: (1) no self-reported marijuana use (No Pre-M; n = 315) and (2) any self-reported marijuana use (Pre-M; n = 78) in the 30 days pretreatment.

Results

CM was especially efficacious in enhancing retention in Pre-M patients such that retention nearly doubled among Pre-M patients assigned to CM versus those assigned to ST. In contrast, CM exerted only modest benefits on retention in No Pre-M patients. Pretreatment marijuana use was not related to during-treatment abstinence from cocaine, opioids, and alcohol, or abstinence at a Month 9 follow-up. However, CM treatment and longest duration of abstinence achieved during treatment were significant predictors of Month 9 abstinence. Pre-M patients also evidenced more improvements in drug problems over time when randomized to CM.

Conclusions

CM was especially efficacious in facilitating retention and improving severity of drug-related problems in those who used marijuana in the month before initiating treatment.     

Abstinence and psychological distress in co-morbid smokers using various pharmacotherapies

Background

Existing trials of varenicline have typically excluded smokers with concurrent medical and psychiatric illnesses and no data exist comparing effectiveness of varenicline with combination pharmacotherapy. This study evaluated abstinence and psychiatric outcomes of various tobacco dependence medications, including varenicline.

Methods

Retrospective cohort of 723 smokers, most with significant medical and psychiatric comorbidity, was evaluated at the UMDNJ-Tobacco Dependence Clinic from 2006 to 2008. Demographics, measures of tobacco dependence and co-morbidities, and a validated instrument measuring psychological distress (Kessler-6) were obtained. Primary outcome was 7-day point abstinence at 6 months after target quit date.

Results

Cessation medications used included combination pharmacotherapy (39%), single nicotine replacement therapy (NRT) or bupropion (29%), and varenicline (23%), with 9% using no medications. Overall, 23% of patients were abstinent at 6 months. In an adjusted regression model, smokers using varenicline or combination medications were more likely abstinent at 6 months than those using no medications (adjusted odds ratio = 2.99; 95% confidence interval = 1.20-7.47 and 2.80; 1.15-6.82, respectively), but not statistically higher than those using single medications (AOR = 1.70). Age, gender, education, marital status, cigarettes per day, time to first cigarette, night smoking, and menthol smoking were not significantly related to abstinence. Varenicline or combination medications did not significantly increase serious psychological distress over the treatment period compared to other medication options.

Conclusions

Both varenicline and combination pharmacotherapy were effective and did not increase psychological distress for up to 6 months in smokers with co-morbidities treated at a specialty clinic.     

Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: A randomized trial

Background

Fear of weight gain is a significant obstacle to smoking cessation, preventing some smokers from attempting to quit. Several previous studies of naltrexone yielded promising results for minimization of post-quit weight gain. Given these encouraging findings, we endeavored to test whether minimization of weight gain might translate to better quit outcomes for a population that is particularly concerned about gaining weight upon quitting.

Methods

Smokers (N = 172) in this investigation were prospectively randomized to receive either 25 mg naltrexone or placebo for 27 weeks (1 week pre-, 26 weeks post-quit) for minimization of post-quit weight gain and smoking cessation. All participants received open label therapy with the nicotine patch for the first 8 weeks post-quit and behavioral counseling over the 27-week treatment. The 2 pre-specified primary outcomes were change in weight for continuously abstinent participants and biologically verified end-of-treatment 7-day point-prevalence abstinence at 26 weeks after the quit date.

Results

The difference in weight at 26 weeks post-quit between the naltrexone and placebo groups (naltrexone: 6.8 lbs ± 8.94 vs placebo: 9.7 lbs ± 9.19, p = 0.45) was not statistically different. Seven-day point-prevalence smoking abstinence rates at 26 weeks post-quit was not significantly different between the 2 groups (naltrexone: 22% vs placebo: 27%, p = 0.43).

Conclusions

For smokers high in weight concern, the relatively small reduction in weight gain with low-dose naltrexone is not worth the potential for somewhat lower rates of smoking abstinence.     

Psychosocial treatments for cocaine dependence: the role of depressive symptoms

Background

The association between cocaine use and depression has been frequently observed. However, less is known about the significance of depression in the treatment of cocaine use disorders. This study examined possible interrelations between drug use and depression severity among cocaine-dependent patients in psychosocial treatments for cocaine dependence.

Methods

Monthly assessed drug use and depression severity scores of N = 487 patients during 6-month psychosocial treatments for cocaine dependence were analyzed using hybrid latent growth models.

Results

Results indicated a moderate but statistically significant (z = 3.13, p < .01) influence of depression severity on increased drug use in the upcoming month, whereas drug use did not affect future depression severity.

Conclusions

Findings suggest that depression symptoms are an important predictor of drug use outcomes during psychosocial treatments for cocaine dependence and, hence, underline the importance of adequately addressing depression symptoms to improve treatment outcomes.     

Percutaneous penetration of 5-methoxypsoralen in rhesus monkeys

Objective and design

5-methoxypsoralen (bergapten) has been used in the treatment of psoriasis and vitiligo, and as a sun tanning accelerator. While low plasma concentrations have previously been detected, there is no data on its dermatopharmacokinetics.

Materials and methods

Three rhesus monkeys were used as a model for human skin. [14C]-5-methoxypsoralen, as a parenteral excretion control, was injected in propylene glycol with an activity of 1.12 uCi/ml at a concentration of 80 mcg/ml and urine was collected at 4, 8, 12, 24 h, and then daily for a total of 6 days. [14C]-5-methoxypsoralen was then applied topically in acetone with a dose of 1.19 mc (72 mcg) and urine was collected at 4 and 24 h and then daily for a total of 7 days. The amount excreted was corrected for the previously determined parenteral excretion kinetics.

Results

Intramuscular [14C]-5-methoxypsoralen had an average of 71.87 ± 7.77% of excretion and percutaneously applied [14C]-5-methoxypsoralen had an average of 58.4 ± 11.8% of excretion.

Conclusion

A high percentage of the administered 5-methoxypsoralen was absorbed. This provides a foundation of methodology to evaluate the efficacy of other delivery vehicles for 5-methoxypsoralen and serves as part of its dermatotoxic profile.     

Cigarette, marijuana, and alcohol use and prior drug treatment among newly homeless young adults in New York City: Relationship to a history of foster care

Background

This study examined whether a history of foster care was associated with the risk for substance use among newly homeless young adults, controlling for demographics and other risk factors.

Methods

Multiple logistic regression analyses, adjusted for controls, among consecutive admissions of 424 newly homeless young adults (18-21 years), determined the association between foster care and substance use.

Results

A history of foster care was reported by 35% of the sample. Alcohol, marijuana, and cigarettes were the most frequently used substances. After adjusting for demographics, childhood emotional, physical, and sexual abuse, prior arrest, unemployment, lack of high school diploma, and family drug use, homeless young adults with histories of foster care were: three times as likely to smoke cigarettes (AOR = 3.09); more than three times as likely to use marijuana (AOR = 3.30); and almost nine times as likely to have been in drug treatment (AOR = 8.81) than those without such histories.

Conclusions

It is important to screen homeless young adults who exited foster care for substance use, particularly cigarettes and marijuana. Risk reduction interventions should be targeted and tailored to their substance prevention needs.     

Chronic treatment with curcumin enhances methamphetamine locomotor sensitization and cue-induced reinstatement of methamphetamine self-administration

Objectives

Curcumin, a major active component of Curcuma longa, possesses antidepressant effects that are mediated by the 5-HT system. However, little is known about the effect of curcumin on the behavioral consequences of methamphetamine (METH).

Methods

The subjects were male, adult Sprague-Dawley rats. In Experiment 1, the effects of 20 and 40 mg/kg curcumin (i.p.) on response rates and breakpoints of 0.06 mg/kg/infusion METH were evaluated. In Experiment 2, rats were self-administering METH for 10 days followed by a 14-day abstinence period. During the abstinence period, the animals were treated with DMSO, 20 or 40 mg/kg curcumin. All rats were then tested for extinction responding and cue-induced reinstatement. In Experiment 3, rats were treated with DMSO, 20, or 40 mg/kg curcumin15 min before a METH-induced locomotor activity test for 14 consecutive days. In Experiment 4, rats were pretreated with DMSO or curcumin (20 mg/kg or 40 mg/kg) for 13 days and were subsequently tested for METH-induced locomotor activity on the 14th day. In Experiment 5, three groups were tested for locomotor activity after an injection of DMSO, 20, or 40 mg/kg curcumin. The test was repeated for 14 days.

Results

Curcumin produced little effect on response rates and breakpoints maintained by METH. Chronic treatment of only 40 mg/kg curcumin during the abstinence phase enhanced cue-induced reinstatement of METH self-administration. Chronic administration of curcumin increased METH-induced sensitization of locomotor activity at the lower (20 mg/kg) but not higher (40 mg/kg) dose. However pretreatment of curcumin alone showed no significant effect on acute locomotor responses to METH and locomotor responses per se.

Conclusions

Curcumin enhanced, rather than inhibited the behavioral effects of METH.     

5-HT induces temporomandibular joint nociception in rats through the local release of inflammatory mediators and activation of local β adrenoceptors

Objectives

The present studies assessed the effects of adolescent and adult ethanol exposure on the rewarding effects of cocaine as measured with the conditioned place preference procedure.

Methods

Male rats were exposed to intraperitoneal (IP) injections of ethanol or vehicle for 10 days [postnatal days (PNDs) 30-39 or PNDs 70-79; 2 mg/kg]. Place preference conditioning began on PND 65 or PND 105, respectively, and consisted of a baseline test followed by four conditioning cycles with either 0, 5, 10 or 20 mg/kg cocaine. Following the fourth conditioning cycle a final preference test was performed. Changes in time on the drug-paired side between the baseline and final test were analyzed.

Results

Animals exposed to vehicle (during adolescence or adulthood) showed a significant place preference at 20 mg/kg cocaine. Animals exposed to ethanol (during adolescence or adulthood) showed a significant place preference at 10 mg/kg cocaine.

Conclusions

Exposure to ethanol (adolescents or adults) sensitized the rewarding effects of cocaine. This may indicate an increase in the abuse liability of cocaine following a history of ethanol exposure.     

Risky decision-making predicts short-term outcome of community but not residential treatment for opiate addiction. Implications for case management

Background

Opiate addiction is associated with decision-making deficits and we previously showed that the extent of these impairments predicts aspects of treatment outcome. Here we aimed to establish whether measures of decision-making performance might be used to inform placement matching.

Methods

Two groups of opiate dependent individuals, one receiving treatment in a community setting (n = 48) and one in a residential setting (n = 32) were administered computerised tests of decision-making, impulsivity and planning shortly after the beginning of treatment, to be followed up three months into each programme.

Results

In the community sample, performance on the decision-making tasks at initial assessment predicted abstinence from illicit drugs at follow-up. In contrast, in the residential sample there was no relationship between decision-making and clinical outcome.

Conclusions

Intact decision-making processes appear to be necessary for upholding a resolve to avoid taking drugs in a community setting, but the importance of these mechanisms may be attenuated in a residential treatment setting. The results support the placement matching hypothesis, suggesting that individuals with more prominent decision-making deficits may particularly benefit from treatment in a residential setting and from the inclusion of aspects of cognitive rehabilitation in their treatment programme.     

Sleep disturbance and the effects of extended-release zolpidem during cannabis withdrawal

Background

Sleep difficulty is a common symptom of cannabis withdrawal, but little research has objectively measured sleep or explored the effects of hypnotic medication on sleep during cannabis withdrawal.

Methods

Twenty daily cannabis users completed a within-subject crossover study. Participants alternated between periods of ad libitum cannabis use and short-term cannabis abstinence (3 days). Placebo was administered at bedtime during one abstinence period (withdrawal test) and extended-release zolpidem, a non-benzodiazepine GABA_A receptor agonist, was administered during the other. Polysomnographic (PSG) sleep architecture measures, subjective ratings, and cognitive performance effects were assessed each day.

Results

During the placebo-abstinence period, participants had decreased sleep efficiency, total sleep time, percent time spent in Stage 1 and Stage 2 sleep, REM latency and subjective sleep quality, as well as increased sleep latency and time spent in REM sleep compared with when they were using cannabis. Zolpidem attenuated the effects of abstinence on sleep architecture and normalized sleep efficiency scores, but had no effect on sleep latency. Zolpidem was not associated with any significant side effects or next-day cognitive performance impairments.

Conclusions

These data extend prior research that indicates abrupt abstinence from cannabis can lead to clinically significant sleep disruption in daily users. The findings also indicate that sleep disruption associated with cannabis withdrawal can be attenuated by zolpidem, suggesting that hypnotic medications might be useful adjunct pharmacotherapies in the treatment of cannabis use disorders.     

Comparison between the antiproliferative effect and intracellular glutathione depletion induced by Casiopeína IIgly and cisplatin in murine melanoma B16 cells

Background

Casiopeína IIgly (Cas IIgly) [Cu(4,7-dimethyl-1,10-phenanthroline)(glycinate)]NO₃ induce oxidative damage in different human tumour cell strains, as the known anticancer agent cisplatin (CDDP) does.

Purpose

To compare glutathione (GSH) depletion induced by Cas IIgly and CDDP in murine melanoma B16 cells and its relationship with their antiproliferative effect.

Materials and methods

Cell growth was determined according to the sulforhodamine B assay. Intracellular GSH levels were measured by the reduction of Ellman’s reagent (DTNB).

Results

Cas IIgly IC50 in B16 cells was 54.5 μM (24.21 μg/mL), which depleted GSH from 1092 to 585 ng per million cells in a 30 min incubation period. In the other hand, CDDP was less toxic at the same conditions with an IC50 equal to 197.76 μM (59.33 μg/mL), and depleted GSH to 50% of the normal only after a longer exposure period (4 h). The addition of 1.8 mM ascorbic acid (Asc) or 1 mM buthionine sulfoximine (BSO) enhanced Cas IIgly toxicity, whereas it was prevented by 100 U/mL catalase. BSO sensitised B16 cells to CDDP, but neither Asc or catalase modified CDDP effects.

Conclusions

The antiproliferative effect of both drugs correlated to intracellular GSH levels. Unlike CDDP, GSH depletion induced by Cas IIgly occurs earlier, it is enhanced by ascorbic acid and preventable by catalase. Redox cycles, feasible only with Cas IIgly, may be an important difference in their mode of action.     

Adolescent nicotine exposure sensitizes cue-induced reinstatement of cocaine seeking in rats bred for high and low saccharin intake

Background

Quit attempts may have different outcomes based on menstrual cycle phase on quit day. This is the first preliminary study examining whether smoking cessation outcomes vary by menstrual cycle phase of quit date in women receiving a 6-week open trial of sustained release (SR) bupropion.

Methods

Thirty-three treatment-seeking premenopausal women were studied. Abstinence outcomes were compared for women quitting during the luteal versus follicular phase.

Results

Women receiving bupropion SR whose self-selected quit date occurred in the luteal phase had significantly higher rates of point prevalence abstinence during the final week of a 6-week post-quit treatment period than women quitting in the follicular phase (62.5% versus 29.4%; p < 0.05). A similar, but non-significant, pattern of findings was demonstrated for continuous abstinence during the treatment phase and for point prevalence abstinence at 3-month follow-up.

Conclusions

Women receiving bupropion SR were significantly more likely to be abstinent at treatment completion if quitting occurred during the luteal phase. This is consistent with recent findings of outcome related to cycle phase at quit date in the absence of pharmacotherapy, and differs from findings utilizing nicotine replacement. Results add to emerging data suggesting that smoking cessation interventions with varying mechanisms of action may result in different outcomes for premenopausal women based on gonadal hormones at quit date.     

The needle and the damage done: clinical and behavioural markers of severe femoral vein damage among groin injectors

Aim

To identify factors associated with severe femoral vein (FV) damage among groin injectors (GIs) on oral opioid substitution treatment.

Design

A cohort study.

Setting

Drug treatment centres in South East England.

Participants

GIs attending an ultrasound ‘health-check’ clinic.

Measures

Femoral ultrasonography and clinical grading of venous disease in each leg.

Method

Comparison of 67 GIs with severely damaged FV and 86 GIs with minimal/moderate damage.

Findings

The majority were men (69.3%) and the mean age was 36.2 years with mean duration of injecting drug use (IDU) of 13.3 years. There were no significant between-group differences in age, gender or duration of IDU. Severe FV damage was associated with longer duration of groin injecting (GI; P < 0.005), use of thick needles (blue-hub, 23G; or green-hub, 21G; P < 0.001), benzodiazepine injection (P < 0.005), history of deep vein thrombosis (DVT, P < 0.001) and recurrent DVT (P < 0.001), presence of depressed groin scar (P < 0.001) and chronic venous disease (CVD, P < 0.001). Logistic regression analysis revealed needle size (β 1.2, Wald 4.9, P < 0.05) and DVT (β 3.3, Wald 38.5, P < 0.001) as the main predictors of severe FV damage.

Conclusion

Needle and syringe exchange services should consider only supplying appropriate lengths of orange-hub needle (25G) on request from GIs. Early cessation of GI, avoidance of benzodiazepine injection and prompt diagnosis and treatment of DVT might also reduce the prevalence of severe FV damage among GIs and the associated healthcare burden. Routine examination of injecting sites among these patients should include an assessment of severity of venous disease in each leg.     

A systematic review of the impact of alcohol use disorders on HIV treatment outcomes, adherence to antiretroviral therapy and health care utilization

Background

Alcohol use disorders (AUDs) are highly prevalent and associated with non-adherence to antiretroviral therapy, decreased health care utilization and poor HIV treatment outcomes among HIV-infected individuals.

Objectives

To systematically review studies assessing the impact of AUDs on: (1) medication adherence, (2) health care utilization and (3) biological treatment outcomes among people living with HIV/AIDS (PLWHA).

Data sources

Six electronic databases and Google Scholar were queried for articles published in English, French and Spanish from 1988 to 2010. Selected references from primary articles were also examined.

Review methods

Selection criteria included: (1) AUD and adherence (N = 20); (2) AUD and health services utilization (N = 11); or (3) AUD with CD4 count or HIV-1 RNA treatment outcomes (N = 10). Reviews, animal studies, non-peer reviewed documents and ongoing studies with unpublished data were excluded. Studies that did not differentiate HIV+ from HIV− status and those that did not distinguish between drug and alcohol use were also excluded. Data were extracted, appraised and summarized.

Data synthesis and conclusions

Our findings consistently support an association between AUDs and decreased adherence to antiretroviral therapy and poor HIV treatment outcomes among HIV-infected individuals. Their effect on health care utilization, however, was variable.     

Prenatal cocaine exposure and small-for-gestational-age status: effects on growth at 6 years of age

Objective

To evaluate the impact of prenatal cocaine exposure and small-for-gestational-age (SGA) status on childhood growth.

Study design

Cocaine exposure was defined by history or meconium metabolites. Hierarchical linear modeling was used to examine cocaine exposure and SGA status on growth, while controlling for exposure to other drugs and alcohol use.

Results

At birth cocaine-exposed infants (n = 364) had significantly lower growth parameters compared to non-exposed children (n = 771). At 6 years, weight was similar between exposed and unexposed children. SGA infants continued to be growth impaired. There was a significant interaction between prenatal cocaine exposure and SGA status at 6 years. The negative effects of cocaine on weight and height were greater among non-SGA than SGA children (432 vs. 280 gm, and 0.7 and 0.5 cm, respectively) while negative effects of SGA status on weight and height were larger in non-cocaine exposed compared to the exposed children (2.3 kg vs.1.6 kg and 2.2 and 1.0 cm).

Conclusions

Children exposed to prenatal cocaine were similar in weight to non-exposed children at 6 years of age. Cocaine had an unexplained greater detrimental effect on non-SGA than SGA children. SGA status at birth has an independent detrimental effect on childhood growth.     

Cigarette smoking status in pathological gamblers: association with impulsivity and cognitive flexibility

Background

While the majority of pathological gamblers are current cigarette smokers (CS), some have quit smoking (former smokers, FS) while others never smoked (never smokers, NS). The reasons for elevated smoking rates in pathological gambling are not known, but gamblers may use nicotine as a putative cognitive enhancer. This study evaluated impulsivity and cognitive flexibility in a sample of pathological gamblers with differing smoking status.

Methods

Fifty-five subjects with pathological gambling (CS, n = 34; FS, n = 10; NS, n = 11) underwent cognitive assessments using the Stop-Signal (SST) and Intradimensional/Extra-dimensional (ID/ED) set-shift tasks.

Results

CS reported less severe gambling problems than either FS or NS on the Yale Brown Obsessive Compulsive Scale modified for Pathological Gambling, and CS was associated with significantly fewer directional errors on the SST task, compared to NS. In addition, in CS, higher daily cigarette consumption was associated with fewer total errors on the ID/ED task.

Conclusions

The potential role of nicotine as a cognitive enhancer was supported by objective tests of impulsivity and cognitive flexibility. Human laboratory studies using nicotine challenges in pathological gambling will shed further light on this relationship.     

Changed preference for sweet taste in adulthood induced by perinatal exposure to bisphenol A-A probable link to overweight and obesity

Background

The preference of obesity has risen dramatically worldwide over the past decades. Some latest reports showed significant increase of obesity in men compared to women. Implication of environmental endocrine disruptors has been focused more and more. Numerous studies in vitro and vivo implied metabolic actions of bisphenol A (BPA), however much less consideration is given to the possibility of BPA exposure-induced change in gender-specific behaviors which result in obesity and overweight.

Objectives

To examine whether perinatal exposure to BPA at relative dose to environmental levels can influence sweet preference of male and female rats and consequently lead to alteration in bodyweight.

Methods

Rats perinatally exposed to BPA at doses of 0.01, 0.1 and 1.0 mg/L were tested sweet preference for 0.25%, 0.5% saccharin and 15% sucrose by two-bottle choice (water vs. saccharin/sucrose). The food intake, liquid consumption and bodyweight of each rat were monitored daily. At the end of the test, the fat percentage and tail blood pressure were measured.

Results

Significant sex difference of preference for 0.25% and 0.5% saccharin was shown in control and all BPA-treated groups (p < 0.001, female vs. male). 0.1 and 1.0 mg/L BPA treatment induced the increase of preference for 0.25% saccharin solution in males, but not in females. 0.1 mg/L BPA treatment increased sucrose preference in males at postnatal day (PND) 70 and 140 (p < 0.05 and p < 0.001, compared to control respectively) but decreased sucrose preference in females at PND 140 (p < 0.05, compared to control). The males treated by BPA showed overweight (p < 0.001), high fat percentage (p < 0.001) and tail blood pressure (p < 0.05) than control at PND 140.

Conclusion

Perinatal exposure to a low dose of BPA could increase sweet preference of male rats. Calorie intake may be programmed during early life, leading to changes of body weight depending on the gender. Although further researches concerning the mechanism are required, the results of the present study are particularly important with regards to the more significant increasing prevalence of obesity in men and the environmental endocrine disruptors.     

Ex vivo study of bevacizumab transport through porcine nasal mucosa

Introduction

Hereditary hemorrhagic telangiectasia (HHT) is a genetic disorder associated with abnormal angiogenesis and disabling epistaxis, for which bevacizumab is reported to be a new therapeutic option. In the present study, bevacizumab transport in porcine nasal mucosa was investigated to determine antibody bioavailability.

Material and methods

Transmucosal absorption of bevacizumab was examined by using nasal mucosa specimens mounted onto static vertical diffusion cells then treated with bevacizumab solution (25 mg mL⁻¹, 500 μg) for 2.5 h. Bevacizumab concentrations were measured by enzyme-linked immunosorbent assays. Mucosal integrity was examined by histological examination of treated mucosa.

Results

Transmucosal transport of bevacizumab followed a Fickian diffusion process (permeability coefficient: [0.63 ± 22] × 10⁻⁶ cm s⁻¹; and steady-state flux: 56.4 ± 19.6 μg cm⁻² h⁻¹). Total recovery of bevacizumab throughout the 2.5 h experiment was 83% of the initial dose distributed (i) at the mucosal surface (263 ± 73 μg; ∼53%) and (ii) into (95 ± 14 μg; ∼19%) and through (56 ± 26 μg; ∼11%) the mucosa. There was no evidence of any noticeable histological effects, confirming the harmlessness of nasal bevacizumab delivery.

Conclusion

In the present study, absorption of bevacizumab into nasal mucosa was demonstrated, providing new fundamentals that are mandatory for further clinical trials in HHT patients.     

Associations among types of impulsivity, substance use problems and neurexin-3 polymorphisms

Background

Some of the genetic vulnerability for addiction may be mediated by impulsivity. This study investigated relationships among impulsivity, substance use problems and six neurexin-3 (NRXN3) polymorphisms. Neurexins (NRXNs) are presynaptic transmembrane proteins that play a role in the development and function of synapses.

Methods

Impulsivity was assessed with the Barratt Impulsiveness Scale Version 11 (BIS-11), the Boredom Proneness Scale (BPS) and the TIME paradigm; alcohol problems with the Michigan Alcoholism Screening Test (MAST); drug problems with the Drug Abuse Screening Test (DAST-20); and regular tobacco use with a single question. Participants (n = 439 Caucasians, 64.7% female) donated buccal cells for genotyping. Six NRXN3 polymorphisms were genotyped: rs983795, rs11624704, rs917906, rs1004212, rs10146997 and rs8019381. A dual luciferase assay was conducted to determine whether allelic variation at rs917906 regulated gene expression.

Results

In general, impulsivity was significantly higher in those who regularly used tobacco and/or had alcohol or drug problems. In men, there were modest associations between rs11624704 and attentional impulsivity (p = 0.005) and between rs1004212 and alcohol problems (p = 0.009). In women, there were weak associations between rs10146997 and TIME estimation (p = 0.03); and between rs1004212 and drug problems (p = 0.03). The dual luciferase assay indicated that C and T alleles of rs917906 did not differentially regulate gene expression in vitro.

Conclusions

Associations between impulsivity, substance use problems and polymorphisms in NRXN3 may be gender specific. Impulsivity is associated with substance use problems and may provide a useful intermediate phenotype for addiction.