Abstinence Time Research Articles

Impact of Environmental Enrichment on Perineuronal Nets in the Prefrontal Cortex following Early and Late Abstinence from Sucrose Self-Administration in Rats.

Perineuronal nets (PNNs) are aggregates of extracellular matrix that form structures surrounding a subset of GABAergic interneurons. The staining intensity of PNNs appears to be related to plasticity. Environmental enrichment (EE) influences plasticity during adulthood: EE decreases the rewarding effects of drugs of abuse and diminishes both drug- and sucrose-seeking behavior. We determined the impact of EE on PNN intensity in the medial prefrontal cortex (mPFC) in rats trained to self-administer sucrose. We examined the number and intensity of PNNs within the prelimbic (PL), infralimbic (IL), and orbitofrontal (OF) regions of the mPFC of adult Long-Evans rats that were trained for sucrose self-administration followed by acute or chronic EE during abstinence and a cue-induced reinstatement test. Rats exposed to EE prior to a cue-induced reinstatement of sucrose seeking had an increase in PNN staining compared with rats in standard housing. Conversely, naïve rats given 1 day of EE had a decrease in PNN intensity in the PL, no change in the IL, and an increase in the OF. Our findings demonstrate that EE increases PNN intensity in the mPFC after sucrose training, suggesting that training enhances the ability of EE to increase PNN intensity. We further demonstrate an interaction between time of abstinence, duration of EE exposure, and cue-induced reinstatement. Our results suggest that increased PNN intensity after EE may alter the excitatory/inhibitory balance of mPFC neurons such that rats are less responsive to a sucrose cue.

Bleeding Complications following Image-Guided Percutaneous Biopsies in Patients Taking Clopidogrel—A Retrospective Review

PurposeTo report incidence of bleeding after image-guided percutaneous core needle biopsy performed in patients taking clopidogrel within 5 days. Materials and MethodsThis was a retrospective review of image-guided percutaneous core needle biopsies performed in patients with clopidogrel use within 5 days of the procedure between January 2002 and November 2014. Data including biopsy site, needle size, number of samples, and serum coagulation studies were collected. Routine follow-up of patients was performed 24–72 hours after biopsy. Major bleeding complications were defined as grade 3 or greater using Common Terminology Criteria for Adverse Events. There were 63 deep biopsies performed in 63 patients with recent use of clopidogrel. Mean time of clopidogrel abstinence before biopsy was 2.9 days ± 1.9 (median 3 days). Clopidogrel had been taken within 24 hours of the biopsy by 12 patients. There were 48 patients (76%) who also took aspirin within 5 days of the procedure. The most common procedure was liver biopsy (21/63; 33%), followed by lung (12/63; 19%), abdominal/pelvic/retroperitoneal mass (12/63; 19%), and renal (11/63; 17%) biopsies. ResultsA major bleeding complication (1/63; 1.6%) occurred after injury to an intercostal artery during lung biopsy, which was successfully treated with coil embolization. No minor bleeding complications were identified. ConclusionsIn this study comprising a small number of patients undergoing various biopsy procedures, recent clopidogrel use was associated with a very low incidence of major bleeding.

A crossover–crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality in men with inflammatory bowel disease

BackgroundPhthalates are widely used chemicals with ubiquitous exposure. Dibutyl-phthalate (DBP), a male reproductive toxicant in animals, is understudied in humans. Some mesalamine medications used to treat inflammatory bowel disease (IBD) have DBP in their coating, whereas other mesalamine formulations do not. ObjectivesTaking advantage of differences in mesalamine formulations, we investigated whether high-DBP exposure from mesalamine medications was associated with decreased semen parameters. Methods73 men with IBD taking mesalamine participated in a crossover-crossback prospective study. Men taking non-DBP containing mesalamine at baseline i.e., background exposure, crossed-over for four months to high-DBP mesalamine and then crossed-back for four months to their non-DBP mesalamine (B1HB2-arm;Background1-High-Background2) and vice versa for men taking high-DBP mesalamine at baseline (H1BH2-arm;High1-Background-High2). Men provided up to six semen samples (2: baseline, 2: crossover and 2: crossback). ResultsWe estimated crossover, crossback and carryover effects using linear mixed models adjusted for abstinence time, age, season and duration on high-DBP mesalamine at baseline. Semen parameters in B1HB2-arm (26 men, 133 samples) decreased after high-DBP mesalamine exposure (crossover versus baseline), especially motility parameters, and continued to decrease further even after crossback to non-DBP mesalamine (crossback versus crossover). The cumulative carryover effect of high-DBP (crossback versus baseline) was a decrease of % total sperm motility by 7.61(CI:−13.1, −2.15), % progressive sperm motility by 4.23(CI:−8.05, −0.4) and motile sperm count by 26.0% (CI:−46.2%, 1.7%). However, H1BH2-arm (47 men, 199 samples) had no significant change during crossover or crossback. ConclusionsMen newly exposed to high-DBP mesalamine for four months had a cumulative reduction in several semen parameters, primarily sperm motility, that was more pronounced and statistically significant even after exposure ended for four months.

A crossover–crossback prospective study of dibutyl-phthalate exposure from mesalamine medications and semen quality

Introduction: Phthalates are widely used chemicals with ubiquitous exposure. Dibutyl phthalate (DBP), a testicular toxicant in animals, is understudied in humans. Certain medications like Asacol®-mesalamine used to treat inflammatory bowel disease (IBD), contains DBP in its coating, whereas other mesalamine formulations do not. Taking advantage of this difference, we investigated whether high-DBP exposure from mesalamine medications was associated with poorer semen quality. Methods: We conducted a crossover-crossback prospective study in adult men with IBD. Men taking non-DBP containing mesalamine at baseline crossed over for 4 months to high-DBP mesalamine then crossed back for 4 months to their non-DBP mesalamine (LHL arm; Low-High-Low) and vice versa for men taking high-DBP mesalamine at baseline (HLH arm; High-Low-High). Men provided up to 6 semen samples (2 baseline, 2 crossover and 2 crossback). We estimated crossover, crossback and carryover effects using linear mixed models adjusted for abstinence time, age, season, and duration on high-DBP mesalamine at baseline. Results: Participants included 73 men (median age 31.6 years). Semen parameters in LHL arm (26 men, 133 samples) decreased after exposure to high-DBP mesalamine; %total sperm motility decreased (%TSM) by 4.2 (p=0.10), %progressive sperm motility (%PSM) by 1.8 (p=0.33), and motile sperm count (MSC) by 13.7% (p=0.32). Even after crossback to non-DBP mesalamine, %TSM further decreased by 3.4 (p=0.20), %PSM by 2.5 (p=0.19), and MSC by 14.3% (p=0.32). The cumulative carryover effect of high-DBP exposure for 4 months, was a decrease of %TSM by 7.6 (p=0.007), %PSM by 4.2 (p=0.03) and MSC by 26.0% (p=0.06). However, in HLH arm (47 men, 199 samples) there was no change in semen parameters during crossover or crossback. Conclusions: Men newly exposed to high-DBP mesalamine for 4 months had a cumulative reduction in semen quality that persisted for 4 months even after exposure ended.

Use of varenicline for more than 12 months for smoking cessation in heavy chronic obstructive pulmonary disease smokers unmotivated to quit: a pilot study.

Introduction:Use of varenicline for as long as necessary to achieve abstinence has not been studied. The aim of this study was to test whether smokers with mild-to-moderate chronic obstructive pulmonary disease (COPD) are able to quit if they use varenicline for a sufficient length of time.Methods:A total of 30 heavy smokers with COPD took varenicline for sufficiently long enough for smoking cessation. Smokers were allowed to smoke without a fixed quit date. The main endpoints were the time of voluntary abstinence (VA) and the continuous abstinence rate (CAR) at 12 and 18 months.Results:Of 28 subjects, eight subjects continued to smoke and 20 subjects stopped smoking, demonstrating a CAR up to 18 months (71%). Median time of treatment was 6 (range 3–24) and 2 (range 1–8) months for abstainers and non-abstainers, respectively, and the median time of VA for abstainers was 4 (range 1–21) months.Conclusions:Use of varenicline for more than the traditional 12 recommended weeks may be a good strategy to increase the cessation rate in heavy smokers with mild COPD.

Motivational factors and negative affectivity as predictors of alcohol craving

Craving is thought to play an important role in alcohol use disorders. The recent inclusion of “craving” as a formal diagnostic symptom calls for further investigation of this subjective phenomenon with multiple dimensions. Considering that alcohol-dependent patients compensate negative physical/emotional states with alcohol, the aim of this study is to investigate alcohol craving and its correlation with drinking measures and affective personality dimensions. A sample of 135 alcohol-dependent patients (104 males and 31 females) was collected from a clinical setting. Subjects self-rated their cravings (Penn Alcohol Craving Scale) and the stage of change. Several personality scales were also administered. Craving was related to drinking status, abstinence time, age, and taking steps. After controlling for these conditions, psychological characteristics related to low self-concept, neuroticism, cyclothymic affective temperament, depression, and hostility were found to be predictors of craving in sober alcohol-dependent patients. Our results support craving as a component of the phenomenology of alcohol dependence and highlight the presence of unpleasant feelings as predictors of craving in sober alcohol-dependent patients without co-occurring psychiatric conditions. The predisposition to experience negative emotions may induce a stronger craving response and increase the likelihood of a first drink and a subsequent loss of control.

Anti-Müllerian hormone in seminal plasma and serum: association with sperm count and sperm motility.

Is anti-Müllerian hormone (AMH) in seminal plasma and serum associated with sperm count and sperm motility? AMH in seminal plasma is positively associated with sperm concentration, total sperm count, and progressive sperm motility, while no association was found between serum AMH levels and semen characteristics. AMH is secreted by the Sertoli cells and is detectable in both serum and seminal plasma in adult men. It has been suggested as a marker of spermatogenesis, however, its function in the adult male is largely unknown. Participants were recruited in between 2008 and 2013, from the general population (n = 94) and from couples with female factor infertility in a fertility clinic (n = 32). AMH data were available for 126 participants. Mean age of the participants was 36 years, and BMI was between 19 and 39 kg/m(2). Semen quality was evaluated by semen analysis according to the World Health Organization, and AMH levels were measured in seminal plasma. Blood samples were analyzed for AMH, total testosterone, FSH, LH, and inhibin B. AMH analysis was performed using the improved Beckman Coulter method. The central 95% intervals of AMH concentrations were 2-2812 pmol/l in seminal plasma and 15-134 pmol/l in serum. Total AMH (pmol/ejaculate) in seminal plasma was positively associated with sperm concentration (B = 0.177, P< 0.001) and total sperm count (B = 0.212, P< 0.001) when adjusted for age, BMI, time of abstinence, and positively associated with progressive sperm motility (B = 6.762, P = 0.001) when adjusted for age, BMI, time of abstinence, and site of sample collection. No association was found between serum AMH and semen characteristics. Serum levels of inhibin B were positively correlated with total AMH in seminal plasma (B = 18.52, P< 0.001) and concentration of AMH in serum (B = 0.507, P< 0.001). Participants were recruited both from the general population and from a fertility clinic. This may limit the applicability to men in the general population. The AMH levels found in this study show large inter-individual variation, especially in seminal plasma. AMH in seminal plasma may serve as a marker of sperm production, however, in the lower range the predictive value is low. All funding for this study was received from Oslo and Akershus University College of Applied Sciences. The authors have no conflicts of interest to declare.

Clinicians' Views of Hepatitis C Virus Treatment Candidacy With Direct-Acting Antiviral Regimens for People Who Inject Drugs

ABSTRACTBackground: Direct-acting antivirals (DAAs) are curative in most persons with chronic hepatitis C virus (HCV) infection. However, high cost and concerns about adherence and reinfection may present continued barriers to treatment, particularly for people who inject drugs (PWID). Objective: To understand changes in assessments of treatment candidacy, given advances in treatment. Methods: Clinicians attending the Liver Meeting® in 2014 who reported prescribing HCV treatment in the past three years were invited to complete a survey regarding HCV treatment decisions. Participants assessed their likelihood to treat HCV in PWID in association with time of abstinence from injection drug use and what impacts their decision to provide treatment using interferon and DAAs. Results: 108 clinicians completed the survey; 10% were willing to treat an active PWID (last injection within 30 days) using interferon-containing regimens, and 15% with all-oral regimens. For each increasing time interval of injection abstinence, there was an increase in the odds of a clinician reporting willingness to treat with DAAs (Odds Ratio (OR) 2.57, 95% CI 2.18, 3.03) and with interferon-based treatment (OR 2.22 (95% CI 1.90, 2.61), Reinfection and medication cost were cited as most important concerns when determining candidacy. Conclusions: A cure is now the norm in HCV treatment, and there is an increasing need to address the barriers to treating PWID, the population with the highest burden of infection. Understanding treatment candidacy assessments is essential to improving uptake. This study provides insight into how clinicians view treatment candidacy in this era of DAAs and can help identify supportive treatment environments and concurrent programs.

Abstinence Time and Its Impact on Basic and Advanced Semen Parameters

To assess the effect of ejaculatory abstinence (EA) periods on routine and advanced sperm tests. Men with normozoospermia provided semen samples after 1, 2, 5, 7, 9, and 11 days of abstinence. A standard semen analysis was performed on all samples. Each specimen was assessed for levels of reactive oxygen species (ROS) and sperm DNA fragmentation. Comparison was also made by grouping EA periods into short (1 day), recommended by World Health Organization (WHO) (2-7 days), and long (9-11 days). Semen volume (P < .001), sperm concentration (P < .001), and total sperm count (P < .001) increased significantly with abstinence length. Sperm DNA fragmentation was associated with the length of EA (P < .001). Both 1 and 2 days of EA had the least amount of DNA fragmentation (P < .001). Significant increase was seen in volume, pH, viscosity, total count, total motile sperm, and DNA fragmentation between short and recommended EA (P < .05), and between recommended and long EA (P < .05). Short EA had no detrimental impact on semen characteristics according to the 2010 WHO thresholds. Shortening of EA time is not detrimental to sperm quality in men with normozoospermia and is proposed as a method for reducing sperm DNA fragmentation. This strategy could help optimize sperm quality and the chances of natural and assisted conception. Accurate abstinence time should be considered when managing men with infertility problems with semen analyses even when it is within the recommended range.

Semen leukocytes and oxidative-dependent DNA damage of spermatozoa in male partners of subfertile couples with no symptoms of genital tract infection.

The influence of seminal leukocytes on generation of oxidative damage to sperm DNA was here investigated on male partners of subfertile couples asymptomatic for a genital tract infection. The study included 111 ejaculates from men attending the Andrology Centre at University of L'Aquila. Semen leukocytes subset included round cells expressing pan-leukocyte CD45 antigen, monocyte/macrophage lineage antigen CD14, and activated macrophages HLA-DR antigen. The 8-hydroxy-2'-deoxyguanosine (8-OHdG) expression identified spermatozoa with DNA oxidative adducts while terminal deoxynucleotidyl transferase (TdT)-mediated fluorescein-dUTP nick end labeling (TUNEL) assay detected spermatozoa with DNA fragmentation. Flow cytometry and immunocytochemistry was used for determinations. Main outcome measure was the association of semen leukocyte subpopulations with spermatozoa showing oxidative-related DNA damage and with routine semen parameters. Leukocyte subpopulations were strictly correlated (p<0.0001), but no association was found between the concentration of leukocytes, semen parameters, the percentage of TUNEL-positive and of 8-OHdG-positive spermatozoa. The percentage of 8-OHdG-positive spermatozoa was positively correlated with the percentage of TUNEL-positive spermatozoa (r=0.48; p<0.0001) and negatively correlated with sperm concentration (r=-0.44; p<0.0001). Sperm concentration and the percentage of TUNEL-positive spermatozoa independently contributed (β=-0.25, p=0.008; β=0.23, p=0.05, respectively) to the variation in percentage of 8-OHdG-positive spermatozoa after adjusting for age, abstinence time, and smoking. In conclusion, oxidative-dependent DNA damage in spermatozoa was associated to poor semen quality but not to different leukocyte subpopulations in ejaculates of men asymptomatic for a genital tract infection.

Knockout of p11 attenuates the acquisition and reinstatement of cocaine conditioned place preference in male but not in female mice.

Cocaine's enhancement of dopamine signaling is crucial for its rewarding effects but its serotonergic effects are also relevant. Here we examined the role of the protein p11, which recruits serotonin 5HT1B and 5HT4 receptors to the cell surface, in cocaine reward. For this purpose we tested wild-type (WT) and p11 knockout (KO) male and female mice for cocaine conditioned place preference (CPP) and its cocaine-induced reinstatement at different abstinence times, after 8 days of extinction and 28 days of being home-caged. All mice showed significant cocaine CPP. Among males, p11KO showed lower CPP than WT; this difference was also evident after 28 days of home-cage abstinence. In contrast, in females there were no CPP differences between p11KO and WT mice at any time point tested. Cocaine priming after the 28-day home-cage abstinence period also resulted in lower cocaine conditioned motor activity in both male and female p11KO mice. These results suggest that cocaine CPP and its persistence during extinction and reinstatement are modulated in a sex-differentiated manner by p11. The lack of protein p11 confers protection from CPP on male, but not female mice, immediately after cocaine conditioning as well as after prolonged abstinence, but not after short-term withdrawal. Synapse 70:293-301, 2016. © 2016 Wiley Periodicals, Inc.

Weighing the Evidence: A Systematic Review on Long-Term Neurocognitive Effects of Cannabis Use in Abstinent Adolescents and Adults.

Findings on neurocognitive effects of sustained cannabis use are heterogeneous. Previous work has rarely taken time of abstinence into account. In this review, we focus on understanding sustained effects of cannabis, which begin when clinical symptoms of the drug have worn off after at least 14days. We conducted a search between 2004 and 2015 and found 38 studies with such a prolonged abstinence phase. Study-design quality in terms of evidence-based medicine is similar among studies. Studies found some attention or concentration deficits in cannabis users (CU). There is evidence that chronic CU might experience sustained deficits in memory function. Findings are mixed regarding impairments in inhibition, impulsivity and decision making for CU, but there is a trend towards worse performance. Three out of four studies found evidence that motor function remains impaired even after a time of abstinence, while no impairments in visual spatial functioning can be concluded. Functional imaging demonstrates clear differences in activation patterns between CU and controls especially in hippocampal, prefrontal and cerebellar areas. Structural differences are found in cortical areas, especially the orbitofrontal region and the hippocampus. Twenty studies (57%) reported data on outcome effects, leading to an overall effect size of r mean = .378 (CI 95% = [.342; .453]). Heavy use is found to be more consistently associated with effects in diverse domains than early age of onset. Questions of causality-in view of scarce longitudinal studies, especially those targeting co-occurring psychiatric disorders-are discussed.

Pulmonary function and functional capacity of illicit drug users in detoxification process

Importance of the problem: The use of psychoactive substances represents a public health problem, causing complications that go beyond the social. Aim: Investigate the pulmonary function and functional capacity of drug addicts admitted to a rehabilitation center. Methods: Case reports with 13 men (24 ± 2.9 years), drug users and abstinence time of up to nine months, perform a protocol consisting of sociodemographic interview, spirometry and six minute walk test. Results: In the six-minute walk test, traveled on average 129% of the scheduled distance and pulmonary function showed no impairment. The majority began substance use in adolescence; in addition, presented the combined substance use and family history of consumption of psychoactive substances and alcohol. Comments: The findings suggest that the use of illegal drugs for less in twenty years does not alter pulmonary function and functional capacity

Associations of bisphenol A and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic

BackgroundIn the testis, steroid hormones play an important role in spermatogenesis, the production of semen, and the maintenance of secondary sex characteristics and libido. They may also play a role as a target for substances called endocrine disruptors (EDs). As yet, however, no complex study has been conducted evaluating the relationships between EDs and the steroid spectrum in the plasma and seminal plasma. ObjectivesTo shed more light into mechanisms of EDs and the effects of bisphenol A (BPA) and polychlorinated biphenyls (PCBs) on human spermatogenesis and steroidogenesis. MethodsWe determined BPA and 11 steroids in the plasma and seminal plasma of 191 men with different degrees of fertility, using a newly developed liquid-chromatography mass spectrometry method. Concurrently, plasma levels of 6 congeners of PCBs, gonadotropins, selenium, zinc and homocysteine were measured. Partial correlations adjusted for age, BMI and abstinence time were performed to evaluate relationships between these analytes. ResultsSeminal BPA, but not plasma BPA, was negatively associated with sperm concentration (r=−0.198; p=0.009), sperm count (r=−0.178; p=0.018) and morphology (r=−0.160; p=0.044). Divergent and sometimes opposing associations of steroids and BPA were found in both body fluids. The sum of PCB congeners was negatively associated with testosterone, free testosterone, the free androgen index and dihydrotestosterone in plasma. ConclusionBPA may negatively contribute to the final state of sperm quality. Moreover, our data indicate that BPA influences human gonadal and adrenal steroidogenesis at various steps. Environmental levels of PCBs negatively correlated with androgen levels, but surprisingly without negative effects on sperm quality.

Abnormal resting‐state functional connectivity of the nucleus accumbens in multi‐year abstinent heroin addicts

Functional neuroimaging studies suggest that abnormal brain functional connectivity may be the neural underpinning of addiction to illicit drugs and of relapse after successful cessation therapy. Aberrant brain networks have been demonstrated in addicted patients and in newly abstinent addicts. However, it is not known whether abnormal brain connectivity patterns persist after prolonged abstinence. In this cross-sectional study, whole-brain resting-state functional magnetic resonance images (8 min) were collected from 30 heroin-addicted individuals after a long period of abstinence (more than 3 years) and from 30 healthy controls. We first examined the group differences in the resting-state functional connectivity of the nucleus accumbens (NAc), a brain region implicated in relapse-related processes, including craving and reactivity to stress following acute and protracted withdrawal from heroin. We then examined the relation between the duration of abstinence and the altered NAc functional connectivity in the heroin group. We found that, compared with controls, heroin-dependent participants exhibited significantly greater functional connectivity between the right ventromedial prefrontal cortex and the NAc and weaker functional connectivity between the NAc and the left putamen, left precuneus, and supplementary motor area. However, with longer abstinence time, the strength of NAc functional connectivity with the left putamen increased. These results indicate that dysfunction of the NAc functional network is still present in long-term-abstinent heroin-dependent individuals.

P129. Deficits of early information processing in patients with alcohol dependence: On the way to optimized mismatch-negativity

Introduction The mismatch negativity (MMN) represents one of the major paradigms in cognitive neurophysiology. The attenuation of this subtraction wave of auditory event-related potentials (being a marker of discrimination of rare deviant stimuli among a series of standard stimuli) is well established in schizophrenia research. Moreover, first MMN results in patients with alcohol dependence mostly indicated an enhanced MMN though heterogeneously. In contrast to this “traditional” oddball MMN an optimized MMN including a higher number of deviants but within the same time interval was deficient in schizophrenia patients as shown by our group. Interestingly, the two clinical entities (schizophrenia, alcohol dependence) are in a close connection to glutamate neurotransmitter system underlying the generation of MMN. Methods 25 inpatients with alcohol dependence received a multichannel EEG with auditory MMN in i) oddball (20% deviants) as well as optimized MMN (50% standards, five deviants with 10% each). 25 healthy subjects without harmful use of alcohol served as controls. Results Following alcohol withdrawal patients showed decreased MMN amplitudes in the fronto-central region and increased latencies as compared to controls. Especially when taking the optimized MMN, the amplitudes of the cortico-central region significantly correlated positively (deviants: duration, intensity, localization: 0.001 > p’s) with length of time of alcohol abstinence. Conclusion Attenuation of optimized MMN might indicate down-regulation of glutamatergic systems after withdrawal. Further, this study confirms the alteration of latencies representing delay of early auditory information processing in alcohol patients. Efficient neurospychobiological monitoring could improve diagnostic evaluation and potentially prediction of effects of psychotropic agents in patients with substance dependence.

Effects of acute or chronic environmental enrichment on regional Fos protein expression following sucrose cue-reactivity testing in rats

Exposure to environmental enrichment (EE) reduces sucrose seeking by rats with a history of sucrose self-administration. The present experiment examined whether acute or chronic EE also reduces brain Fos levels, a protein marker indicative of neuronal activation. Fos levels were also examined after either 1 or 30days of forced abstinence to examine whether Fos levels vary with the incubation of sucrose craving. Fos expression was examined in 18 regions and was identified in brain slices using immunohistochemistry. Fos levels were higher in most regions after 30 days of forced abstinence and were decreased in most regions by either acute or chronic EE. Eleven regions had some statistically significant effect and/or interaction of EE or incubation on Fos; the most salient of these are listed here. In the prelimbic cortex, there was an incubation of Fos and EE reduced Fos at both forced abstinence time points. In contrast, in the orbitofrontal cortex, there was no Fos incubation but EE reduced Fos at both forced abstinence time points. An interaction of EE and incubation was observed in the anterior cingulate cortex and nucleus accumbens core and shell where Fos incubated but EE only decreased Fos at the day 30 forced abstinence time point. In contrast, in the dorsolateral striatum Fos incubated, but EE robustly decreased Fos expression at both forced abstinence time points. These differential expression patterns provide rationale for more detailed, site-specific molecular functional studies in how they relate to the ability of EE to reduce sucrose seeking.

Factores asociados a la variabilidad de la calidad seminal: un estudio de seguimiento

ObjectiveThe aim of this study is to analyze whether abstinence time or the frequency of ejaculation and selected lifestyles could be related to variability of semen quality. Material and methodsThis is a prospective, follow-up study over 1year evaluating several semen samples from 19 healthy male volunteers. Semen samples were obtained approximately every 4-6weeks. Besides, follow-up epidemiological questionnaires on lifestyles were filled out by the participants. Intra- (%CVi) and inter-individual (%CVe) coefficients of variation were calculated. ResultsThe highest CVi was 74.5% for sperm count and 65.6% for sperm concentration, followed by 41.2% form sperm morphology and 30.1% for volume. The lowest CVi was 14.6% for sperm motility. The CVe were higher and presented a similar pattern. With regard to lifestyles, comparable results were obtained. Generally, CVi and CVe were lower in subjects practicing regular, light or moderate exercise, and having irregular intake of wine, beer or coffee. ConclusionsThe recommendation of analyzing only one semen sample could lead to a mistaken diagnosis of the men's fertility potential. However, the results of a single semen analysis could be more reliable or consistent if some lifestyles are present.

No association between body mass index and sperm DNA integrity.

Is overweight associated with impaired sperm DNA integrity? High body mass index (BMI) is not associated with impaired sperm DNA integrity as assessed by the DNA Fragmentation Index (DFI). Previous studies, based on fewer subjects and including mainly subfertile men, have shown conflicting results regarding the influence of overweight and obesity on sperm DNA integrity. This cross-sectional study was based on semen samples from 1503 men from the general population. We included two cohorts (cohort A and B) of military recruits (n = 275, n = 304, respectively), one group (cohort C) of fertile men and men without known fertility problems (n = 724), and one group (cohort D) of men between 19 and 40 years without known fertility problems (n = 200). In all cohorts, data were available on BMI, DFI as measured by the sperm chromatin structure assay (SCSA), standard semen characteristics, and potential confounders (age, abstinence time, smoking habits). The subjects were categorized according to BMI into four groups: underweight (<18.5 kg/m(2)), normal weight (18.5-24.9 kg/m(2)), overweight (25.0-29.9 kg/m(2)) and obese (≥30.0 kg/m(2)). Using a linear regression model, the inter-group differences in DFI were calculated. Furthermore with the normal-weight group as the reference, the odds ratios (ORs) for DFI > 20% and DFI > 30%, were calculated for the other groups. Calculations were made for the material as a whole and after exclusion of cohort C which included proven fertile men. We found that normal-weight men had significantly higher DFI than overweight men, with a mean difference of 1.13% (95% CI: 1.05-1.22%); P = 0.001). Overweight men had a reduced risk of having DFI ≥ 20% and DFI ≥ 30%, compared with normal-weight men; adjusted odds ratio (OR) = 0.61 (95% CI: 0.42-0.88; P < 0.01) and adjusted OR = 0.48 (95% CI: 0.28-0.84; P < 0.01), respectively. When excluding cohort C, the statistical significance was lost. Regarding standard semen parameters, we found that obese men had a higher percentage of progressive motile spermatozoa than normal-weight men; mean difference 1.15% (95% CI: 1.02-1.30%, P < 0.05) but the significance was lost when excluding cohort C. All other standard semen parameters were unaffected by BMI. A main limitation might be the cross-sectional nature of the data. Furthermore our study included a significant proportion of men with proven fertility (75% of cohort C, n = 550), and could therefore be biased toward fertility. Our study indicates that overweight per se is not associated with a higher level of sperm DNA damage. This research has been given grants from the following: EU 5th and 7th framework program (Inuendo and Clear projects, [Contracts no. QLK4-CT-2001-00202 and FP7-ENV-2008-1-226217)]), the Swedish Research Council (Grants No. 2007-2590, 521-2004-6072 and 521-2002-3907); the Swedish Governmental Funding for Clinical Research, Skåne county council's research and development foundation, MAS Funds, University Hospital MAS Foundation in Malmö, Crafoordska Fund, Ove Tulefjords Fund, Foundation for Urological Research, Fundacion Federico SA, and Gunnar Nilssons Cancer Fund. The authors declare that there are no conflicts of interest.

SUPORTE SOCIAL EM CUIDADORES INFORMAIS DE DEPENDENTES DE SUBSTÂNCIAS

Informal caregivers must cope with situations that may induce stress and burden. A sample with 120 addicts’ caregivers, living in Portugal, completed a survey that included BDI (Beck, et al., 1961; McIntyre & Araujo-Soares, 1999), BSI (Canavarro, 1999; Derogatis, 1975, 1993), CRA (Given, et al., 1992), WHOQOL ‐ Bref (Fleck, 2000; Vaz Serra, et al., 2006) and IESSS (Ensel & Woelfel, 1986; Faria, 1999). Afterwards, the participants were assigned to one of three groups (G1, G2 and G3), based on the abstinence time of the family member whom they cared. This study explored the relationship among clinical variables, psychological variables and social support in those caregivers. The results revealed that living with the patient, distress, quality of life (social relations and psychological) and burden predict social support, explaining 48% of the observed variance. The mediation model demonstrated the social support was a partial mediator of the relationship between distress and burden, explaining 60% of the observed variance. Thus, the study emphasizes the importance of promoting social support in order to lessen the impact of distress and burden on informal caregivers.