A novel SNP in COMT is associated with alcohol dependence but not opiate or nicotine dependence: a case control study

Background It is well established that COMT is a strong candidate gene for substance use disorder and schizophrenia. Recently we identified two SNPs in COMT (rs4680 and rs165774) that are associated with schizophrenia in an Australian cohort. Individuals with schizophrenia were more than twice as likely to carry the GG genotype compared to the AA genotype for both the rs165774 and rs4680 SNPs. Association of both rs4680 and rs165774 with substance dependence, a common comorbidity of schizophrenia has not been investigated. Methods To determine whether COMT is important in substance dependence, rs165774 and rs4680 were genotyped and haplotyped in patients with nicotine, alcohol and opiate dependence. Results The rs165774 SNP was associated with alcohol dependence. However, it was not associated with nicotine or opiate dependence. Individuals with alcohol dependence were more than twice as likely to carry the GG or AG genotypes compared to the AA genotype, indicating a dominant mode of inheritance. The rs4680 SNP showed a weak association with alcohol dependence at the allele level that did not reach significance at the genotype level but it was not associated with nicotine or opiate dependence. Analysis of rs165774/rs4680 haplotypes also revealed association with alcohol dependence with the G/G haplotype being almost 1.5 times more common in alcohol-dependent cases. Conclusions Our study provides further support for the importance of the COMT in alcohol dependence in addition to schizophrenia. It is possible that the rs165774 SNP, in combination with rs4680, results in a common molecular variant of COMT that contributes to schizophrenia and alcohol dependence susceptibility. This is potentially important for future studies of comorbidity. As our participant numbers are limited our observations should be viewed with caution until they are independently replicated.

A DRD2 and ANKK1 haplotype is associated with nicotine dependence

To test the importance of the dopamine D2 receptor (DRD2) region in nicotine dependence, 150 smokers and 228 controls were genotyped for the DRD2 C957T, -141delC and ANKK1 TaqIA polymorphisms (rs6277, rs1799732 and rs1800497, respectively). The -141delC SNP did not show any association but both the C957T and TaqIA SNPs showed association at the allele, genotype, haplotype and combined genotype levels. The 957C/TaqI A1 haplotype was more than 3.5 times as likely to be associated with nicotine dependence compared with the 957T/TaqI A1 haplotype (P = 0.003). Analysis of the combined genotypes of both SNPs revealed that individuals who were homozygous for the 957C-allele (CC) and had either one or two copies of the TaqI A1-allele were 3.3 times as likely to have nicotine dependence compared to all other genotype combinations (P = 0.0003) and that these genotypes accounted for approximately 13% of the susceptibility to nicotine addiction in our population. Our findings suggest that the DRD2 C957T polymorphism and the ANKK1 TaqIA polymorphism are key contributors to the genetic susceptibility to nicotine dependence.

Improved treatment of nicotine addiction and emerging pulmonary drug delivery

Nicotine addiction remains the leading cause of death and disease in developed and developing nations and a major cause of mortality around the world. Currently, nicotine replacement therapies (NRTs), bupropion, and varenicline are approved by the regulatory agencies as first-line treatments for nicotine addiction. Emerging evidence indicates that varenicline and bupropion have some therapeutic limitations for treating nicotine addiction with oral route of administration. Thus, continued investigation of innovative drug delivery for nicotine addiction remains a critical priority. This review will discuss some novel strategies and future directions for pulmonary drug delivery, an emerging route of administration for smoking cessation. It is anticipated that the advancement of knowledge on pulmonary drug delivery will provide better management for nicotine addiction and other addictive disorders.

Neuronal nicotinic acetylcholine receptors : neuroplastic changes underlying alcohol and nicotine addictions

Addictive drugs can activate systems involved in normal reward-related learning, creating long-lasting memories of the drug's reinforcing effects and the environmental cues surrounding the experience. These memories significantly contribute to the maintenance of compulsive drug use as well as cue-induced relapse which can occur even after long periods of abstinence. Synaptic plasticity is thought to be a prominent molecular mechanism underlying drug-induced learning and memories. Ethanol and nicotine are both widely abused drugs that share a common molecular target in the brain, the neuronal nicotinic acetylcholine receptors (nAChRs). The nAChRs are ligand-gated ion channels that are vastly distributed throughout the brain and play a key role in synaptic neurotransmission. In this review, we will delineate the role of nAChRs in the development of ethanol and nicotine addiction. We will characterize both ethanol and nicotine's effects on nAChR-mediated synaptic transmission and plasticity in several key brain areas that are important for addiction. Finally, we will discuss some of the behavioral outcomes of drug-induced synaptic plasticity in animal models. An understanding of the molecular and cellular changes that occur following administration of ethanol and nicotine will lead to better therapeutic strategies.

Water-based exercise for patients with chronic arm lymphedema : a randomized controlled pilot trial

Objective: To evaluate the feasibility and effect of a water-based exercise (WBE) program on lymphedema status and shoulder range of motion (ROM) among women with breast cancer related lymphedema. Design: Single-blinded, randomized controlled pilot trial. Twenty-nine eligible breast cancer survivors (median 10 years after surgery) with arm lymphedema (median 21% inter limb difference) were included and randomized into intervention (n= 15) or control (n=14). Twenty-five participants completed the study. The intervention was at least twice weekly WBE for 8 weeks; supervised initially but performed independently during the study period. Outcomes of interest were feasibility as measured by retention and adherence, lymphedema status as measured by optoelectronic perometry, bioimpedance spectroscopy and tissue dielectric constant, and shoulder range of motion (ROM) as measured by goniometer. Results: Four participants were not measured at post-intervention and were not included in the analysis (retention). Four participants in the intervention group did not perform the minimum WBE criteria set (adherence). No effect was found on lymphedema status. Compared to the control group, median ROM change for flexion was 6 (1-10) degrees (p<0.001) and 6 (0-15.5) degrees (p=0,07) for external rotation. Clinically relevant increase in the intervention group was found for 36% in flexion (p≤0.05) and (57%) in external rotation (p≤0.05) compared to controls. Conclusions: This study shows WBE is feasible for breast cancer survivors with arm lymphedema and that shoulder ROM can be improved years after cancer treatment has been completed.

National Institute for Clinical Studies Report for Phase 1, Evidence Uptake Network : Best Practice Community Care for Clients with Chronic Venous Leg Ulcers

Chronic leg ulcers cause significant pain, cost, decreased quality of life and morbidity for a considerable segment of the older population (Graham et al., 2003a). At any given time the prevalence of patients with open leg ulcers receiving treatment is between 0.11% - 0.18% (Briggs & Closs 2003). Chronic leg ulcers occur in approximately 1 - 2% of the over 60 population in the US, UK, Europe and Australia (Baker & Stacey 1994; Johnson 1995; Lees & Lambert 1992; Margolis et al. 2002). Considerable research has been undertaken to determine the best treatment practices that will aid in the management and the healing of these ulcers, and practical and effective strategies and techniques for healing venous leg ulcers have been trialled to demonstrate their beneficial effects (Nelson et al. 2004; Cullum et al. 2001)...

Nutritional intervention incorporating expedited 10g protein counter (EP-10) to improve the albumin and transferrin of chronic hemodialysis patients

Objective: The expedited 10g protein counter (EP-10) is a quick and valid clinical tool for dietary protein quantification. This study aims to assess the clinical effectiveness of the EP-10 in improving serum albumin and transferrin in chronic hemodialysis patients. Methods: Forty-five patients with low serum albumin (< 38 g /L) were enrolled in this study. Parameters measured included dry weight, height, dietary intake, and levels of serum albumin, transferrin, potassium, phosphate and kinetic modeling (Kt/v). The nutritional intervention incorporated the EP-10 in two ways (1)lto quantify protein intake of patients and (2)ito educate patients to meet their protein requirements. Mean values of the nutritional parameters before and after intervention were compared using paired t-test. Results: Three months after nutritional intervention, mean albumin levels increased significantly from 32.2+4.8g/L to 37.0+3.2g/L (p<0.001). Thirty-eight (84%) patients showed an increase in albumin levels while two (4%) maintained their levels. Of the thirty-six (80%) patients with low transferrin levels (<200 mg/dL), 28 (78%) had an increase and two maintained their levels post-intervention. Mean transferrin levels increased significantly from 169.4+39.9mg/dL to 180.9+38.1mg/dL (p< 0.05). Conclusion: Nutritional intervention incorporating the EP-10 method is able to make significant improvements to albumin and transferrin levels of chronic hemodialysis patients.

Biochemical profiling of proteins and metabolites in wound exudate from chronic wound environments

The lack of fundamental knowledge on the biological processes associated with wound healing represents a significant challenge. Understanding the biochemical changes that occur within a chronic wound could provide insights into the wound environment and enable more effective wound management. We report on the stability of wound fluid samples under various conditions and describe a high-throughput approach to investigate the altered biochemical state within wound samples collected from various types of chronic, ulcerated wounds. Furthermore, we discuss the viability of this approach in the early stages of wound sample protein and metabolite profiling and subsequent biomarker discovery. This approach will facilitate the detection of factors that may correlate with wound severity and/or could be used to monitor the response to a particular treatment.

Associations exist between food insecurity, poor diet, chronic illness and obesity among an Australian population

Food insecurity is the limited availability of, or access to, sufficient amounts of nutritious, culturally-appropriate and safe foods, or the inability to access such foods by socially-acceptable means. Evidence from the United States and Canada suggests that food insecurity may be associated with poor dietary intakes, obesity, and chronic disease including depression and diabetes, thus constituting a significant public health issue. Currently, no existing studies have investigated the dietary and health factors associated with food insecurity among the general Australian population. The current study investigated the potential associations between food insecurity, diet and health among Australian adults (18 years and over) participating in the cross-sectional National Health Survey (n = 19,500). Data were analysed by logistic regression adjusting for sociodemographic covariates. Those from food insecure households were 50% less likely to consume the recommended number of servings of fruit, 60% more likely to report poor health and experienced a 6-fold increase in the risk of severe depressive disorders, compared to their food secure counterparts. Furthermore, food insecurity was associated with a 50% increase in the risk of being diagnosed with ‘high sugar levels’. Finally, women from food insecure households were 30% more likely to be obese compared to their food secure counterparts. These findings suggest that food insecurity may play an important role in preventing adherence with national dietary recommendations, and may increase the risk of obesity and chronic illness. This has important implications for both clinical practice, and the development of interventions and policy to address food insecurity.