Developmental Hippocampal Neuroplasticity in a Model of Nicotine Replacement Therapy during Pregnancy and Breastfeeding

The influence of developmental nicotine exposure on the brain represents an important health topic in light of the popularity of nicotine replacement therapy (NRT) as a smoking cessation method during pregnancy.In this study, we used a model of NRT during pregnancy and breastfeeding to explore the consequences of chronic developmental nicotine exposure on cerebral neuroplasticity in the offspring. We focused on two dynamic lifelong phenomena in the dentate gyrus (DG) of the hippocampus that are highly sensitive to the environment: granule cell neurogenesis and long-term potentiation (LTP).Pregnant rats were implanted with osmotic mini-pumps delivering either nicotine or saline solutions. Plasma nicotine and metabolite levels were measured in dams and offspring. Corticosterone levels, DG neurogenesis (cell proliferation, survival and differentiation) and glutamatergic electrophysiological activity were measured in pups.Juvenile (P15) and adolescent (P41) offspring exposed to nicotine throughout prenatal and postnatal development displayed no significant alteration in DG neurogenesis compared to control offspring. However, NRT-like nicotine exposure significantly increased LTP in the DG of juvenile offspring as measured in vitro from hippocampal slices, suggesting that the mechanisms underlying nicotine-induced LTP enhancement previously described in adult rats are already functional in pups.These results indicate that synaptic plasticity is disrupted in offspring breastfed by dams passively exposed to nicotine in an NRT-like fashion

Design, baseline characteristics, and retention of African American light smokers into a randomized trial involving biological data

<p>Abstract</p> <p>Background</p> <p>African Americans experience significant tobacco-related health disparities despite the fact that over half of African American smokers are light smokers (use ≤10 cigarettes per day). African Americans have been under-represented in smoking cessation research, and few studies have evaluated treatment for light smokers. This paper describes the study design, measures, and baseline characteristics from <it>Kick It at Swope III </it>(KIS-III), the first treatment study of bupropion for African American light smokers.</p> <p>Methods</p> <p>Five hundred forty African American light smokers were randomly assigned to receive bupropion (150mg bid) (n = 270) or placebo (n = 270) for 7 weeks. All participants received written materials and health education counseling. Participants responded to survey items and provided blood samples for evaluation of phenotype and genotype of CYP2A6 and CYP2B6 enzymes involved in nicotine and bupropion metabolism. Primary outcome was cotinine-verified 7-day point prevalence smoking abstinence at Week 26 follow-up.</p> <p>Results</p> <p>Of 2,628 individuals screened, 540 were eligible, consented, and randomized to treatment. Participants had a mean age of 46.5 years and 66.1% were women. Participants smoked an average of 8.0 cigarettes per day, had a mean exhaled carbon monoxide of 16.4ppm (range 1-55) and a mean serum cotinine of 275.8ng/ml. The mean Fagerström Test for Nicotine Dependence was 3.2, and 72.2% of participants smoked within 30 minutes of waking. The average number of quit attempts in the past year was 3.7 and 24.2% reported using pharmacotherapy in their most recent quit attempt. Motivation and confidence to quit were high.</p> <p>Conclusion</p> <p>KIS-III is the first study designed to examine both nicotine and bupropion metabolism, evaluating CYP2A6 and CYP2B6 phenotype and genotype in conjunction with psychosocial factors, in the context of treatment of African American light smokers. Of 1629 smokers screened for study participation, only 18 (1.1%) were ineligible to participate in the study because they refused blood draws, demonstrating the feasibility of recruiting and enrolling African American light smokers into a clinical treatment trial involving biological data collection and genetic analyses. Future evaluation of individual factors associated with treatment outcome will contribute to advancing tailored tobacco use treatment with the goal of enhancing treatment and reducing health disparities for African American light smokers.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="URL">NCT00666978</a></p

Direct Effective Dose Calculations in Pediatric Fluoroscopy-Guided Abdominal Interventions with Rando-Alderson Phantoms – Optimization of Preset Parameter Settings

The aim of the study was to calculate the effective dose during fluoroscopy-guided pediatric interventional procedures of the liver in a phantom model before and after adjustment of preset parameters.Organ doses were measured in three anthropomorphic Rando-Alderson phantoms representing children at various age and body weight (newborn 3.5kg, toddler 10kg, child 19kg). Collimation was performed focusing on the upper abdomen representing mock interventional radiology procedures such as percutaneous transhepatic cholangiography and drainage placement (PTCD). Fluoroscopy and digital subtraction angiography (DSA) acquisitions were performed in a posterior-anterior geometry using a state of the art flat-panel detector. Effective dose was directly measured from multiple incorporated thermoluminescent dosimeters (TLDs) using two different parameter settings.Effective dose values for each pediatric phantom were below 0.1mSv per minute fluoroscopy, and below 1mSv for a 1 minute DSA acquisition with a frame rate of 2 f/s. Lowering the values for the detector entrance dose enabled a reduction of the applied effective dose from 12 to 27% for fluoroscopy and 22 to 63% for DSA acquisitions. Similarly, organ doses of radiosensitive organs could be reduced by over 50%, especially when close to the primary x-ray beam.Modification of preset parameter settings enabled to decrease the effective dose for pediatric interventional procedures, as determined by effective dose calculations using dedicated pediatric Rando-Alderson phantoms

A influência da genética na dependência tabágica e o papel da farmacogenética no tratamento do tabagismo The influence of genetics on nicotine dependence and the role of pharmacogenetics in treating the smoking habit

Mesmo com os esforços intensivos para o controle do tabagismo nas últimas décadas, uma proporção substancial de pessoas inicia a fumar ou mantém-se fumando apesar do pleno conhecimento dos malefícios do hábito. Os estudos têm focado atualmente as bases genéticas da adição nicotínica. O tabagismo tem sido associado a vários polimorfismos genéticos, mas os fatores ambientais também devem ser enfatizados. Esta revisão apresenta alguns dos principais dados disponíveis dos estudos genéticos sobre o comportamento tabágico. Esta linha de pesquisa poderá, no futuro, ajudar os clínicos a individualizar o tipo, a dosagem e a duração do tratamento da dependência tabágica, conforme o genótipo de cada fumante, maximizando a eficácia do esquema proposto.<br>Despite the considerable efforts made in the fight against smoking in the last decades, there are still substantial numbers of people who, in full knowledge of the health hazards, begin smoking or continue smoking. Recent studies have focused on the genetic bases of the nicotine addiction. Various genetic polymorphisms have been associated with smoking. However, environmental factors have also been shown to play a role. In this review, we present some of the principal data collected in genetic studies of smoking behavior. The results obtained through this line of research will eventually aid clinicians in individualizing the type, dosage and duration of treatment for patients with nicotine dependence in accordance with the genotype of each smoker, thereby maximizing the efficacy of the proposed treatment regimen