Attention-Deficit/Hyperactivity Disorder and antidepressants and prescription medications: A pilot study

Background. Attention Deficit-Hyperactivity Disorder (AD/HD) diagnosis in children and adolescents has been on the rise over the last couple of decades and a multitude of studies have been conducted in an aim to better understand the disease. Literature has explored the role of several factors suspected of contributing to development of the disease, including: prenatal smoking exposures, environmental exposures, and low-birth weight. However, there is very limited reporting of fetal/infant exposure to antidepressants and prescription medications and the long-term behavioral outcomes, namely development of AD/HD. The purpose of this study was to evaluate the relationship between mother's exposure to prescription medications and/or antidepressants around the time of conception, during pregnancy, or while breastfeeding and the development of Attention-Deficit/Hyperactivity Disorder in offspring. Methods. Secondary analysis of data from a case-control study was performed. Exposure histories were collected for the mother and offspring. Data were collected using a secure, confidential, self-report, online survey to evaluate the relationship between antidepressant and/or prescription medication exposure and the development of AD/HD. The period of exposure to these drugs was defined as: around the time of conception, during pregnancy, or while breastfeeding. Cases were defined as a child who had been diagnosed with AD/HD. Controls were defined as a child who had not been diagnosed with AD/HD. Results. Prescription medication and antidepressant medication exposures around the time of conception, during pregnancy, or while breastfeeding were not associated with development of AD/HD. However, traumatic brain injury (OR=2.77 (1.61–4.77)) and preterm birth (OR=1.48 (1.04–2.12)) were identified as potential risk factors. These results support existing literature on AD/HD, but future work must be undertaken to better evaluate fetal/infant medication exposures and long-term behavioral outcomes.^

Theory for normal and impaired experience-dependent plasticity in neocortex of adult rats

We model experience-dependent plasticity in the cortical representation of whiskers (the barrel cortex) in normal adult rats, and in adult rats that were prenatally exposed to alcohol. Prenatal exposure to alcohol (PAE) caused marked deficits in experience-dependent plasticity in a cortical barrel-column. Cortical plasticity was induced by trimming all whiskers on one side of the face except two. This manipulation produces high activity from the intact whiskers that contrasts with low activity from the cut whiskers while avoiding any nerve damage. By a computational model, we show that the evolution of neuronal responses in a single barrel-column after this sensory bias is consistent with the synaptic modifications that follow the rules of the Bienenstock, Cooper, and Munro (BCM) theory. The BCM theory postulates that a neuron possesses a moving synaptic modification threshold, θM, that dictates whether the neuron's activity at any given instant will lead to strengthening or weakening of its input synapses. The current value of θM changes proportionally to the square of the neuron's activity averaged over some recent past. In the model of alcohol impaired cortex, the effective θM has been set to a level unattainable by the depressed levels of cortical activity leading to “impaired” synaptic plasticity that is consistent with experimental findings. Based on experimental and computational results, we discuss how elevated θM may be related to (i) reduced levels of neurotransmitters modulating plasticity, (ii) abnormally low expression of N-methyl-d-aspartate receptors (NMDARs), and (iii) the membrane translocation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in adult rat cortex subjected to prenatal alcohol exposure.

For your baby's sake, don't drink.

Originally prepared by: Fetal Alcohol Syndrome Work Group, sponsored by Division of Alcoholism, Illinois Dept. of Mental Health and Developmental Disabilities on behalf of Governor's Citizens Advisory Council on Alcoholism.

Drinking and pregnancy.

Mode of access: Internet.

Gene expression in profiling in individual cases reveals consistent transcriptional changes in alcoholic human brain

Chronic alcohol exposure induces lasting behavioral changes, tolerance, and dependence. This results, at least partially, from neural adaptations at a cellular level. Previous genome-wide gene expression studies using pooled human brain samples showed that alcohol abuse causes widespread changes in the pattern of gene expression in the frontal and motor cortices of human brain. Because these studies used pooled samples, they could not determine variability between different individuals. In the present study, we profiled gene expression levels of 14 postmortem human brains (seven controls and seven alcoholic cases) using cDNA microarrays (46 448 clones per array). Both frontal cortex and motor cortex brain regions were studied. The list of genes differentially expressed confirms and extends previous studies of alcohol responsive genes. Genes identified as differentially expressed in two brain regions fell generally into similar functional groups, including metabolism, immune response, cell survival, cell communication, signal transduction and energy production. Importantly, hierarchical clustering of differentially expressed genes accurately distinguished between control and alcoholic cases, particularly in the frontal cortex.

Genetic study of alcoholism and novel gene expression in the alcoholic brain

Alcohol dependence may result from neuroadaptation involving alteration of gene expression after long-term alcohol exposure. The systematic study of gene expression profiles of the human alcoholic brain was initiated using the method of polymerase chain reaction (PCR)-differential display and was followed by DNA microarray. To date, more than 100 alcohol-responsive genes have been identified from the frontal cortex, motor cortex and nucleus accumbens of the human brain. These genes have a wide range of functions in the brain and indicate diverse actions of alcohol on neuronal function. This review discusses the current information on the genetic basis of alcoholism and the induction and characterization of these alcohol-responsive genes.

Protein adduct species in muscle and liver of rats following acute ethanol administration

Aims: Previous immunohistochemical studies have shown that the post-translational formation of aldehyde-protein adducts may be an important process in the aetiology of alcohol-induced muscle disease. However, other studies have shown that in a variety of tissues, alcohol induces the formation of various other adduct species, including hybrid acetaldehyde-malondialdehyde-protein adducts and adducts with free radicals themselves, e.g. hydroxyethyl radical (HER)-protein adducts. Furthermore, acetaldehyde-protein adducts may be formed in reducing or non-reducing environments resulting in distinct molecular entities, each with unique features of stability and immunogenicity. Some in vitro studies have also suggested that unreduced adducts may be converted to reduced adducts in situ. Our objective was to test the hypothesis that in muscle a variety of different adduct species are formed after acute alcohol exposure and that unreduced adducts predominate. Methods: Rabbit polyclonal antibodies were raised against unreduced and reduced aldehydes and the HER-protein adducts. These were used to assay different adduct species in soleus (type I fibre-predominant) and plantaris (type II fibre-predominant) muscles and liver in four groups of rats administered acutely with either [A] saline (control); [B] cyanamide (an aldehyde dehydrogenase inhibitor); [C] ethanol; [D] cyanamide+ethanol. Results: Amounts of unreduced acetaldehyde and malondialdehyde adducts were increased in both muscles of alcohol-dosed rats. However there was no increase in the amounts of reduced acetaldehyde adducts, as detected by both the rabbit polyclonal antibody and the RT1.1 mouse monoclonal antibody. Furthermore, there was no detectable increase in malondialdehyde-acetaldehyde and HER-protein adducts. Similar results were obtained in the liver. Conclusions: Adducts formed in skeletal muscle and liver of rats exposed acutely to ethanol are mainly unreduced acetaldehyde and malondialdehyde species.

Endocrine-disrupting compounds: A review of their challenge to sustainable and safe water supply and water reuse

The relevance of endocrine-disrupting compounds as potential contaminants of drinking water is reviewed, particularly in the reuse of wastewater. Growing populations and increasing intensification of land and water use for industry and agriculture have increased the need to reclaim wastewater for reuse, including to supplement the drinking water supply. The variety of anthropogenic chemicals that have been identified as potential endocrine disruptors in the environment and the problems arising from their use as human and livestock pharmaceuticals, as agricultural chemicals and in industry are discussed. The potentially adverse impact of these chemicals on human health and the ecology of the natural environment are reviewed. Data for the removal of estrogenic compounds from wastewater treatment are presented, together with the comparative potencies of estrogenic compounds. The relative exposure to estrogens of women on oral contraceptives, hormone replacement therapy, and through food consumption is estimated. A brief overview of some methods available or under development for the assessment of estrogenic activity in environmental samples is provided. The review concludes with a discussion of the directions for further investigation, which include human epidemiology, methodology development, and wastewater monitoring. (C) 2006 Wiley Periodicals, Inc.

Ethanol intake of paediatric intensive care patients

Background - Limiting the amount of alcohol in children's medicines is advisable but as alcohol is the second most common solvent used in liquid preparations, paediatric patients with increased medication intake may be exposed to a considerable alcohol intake. Few medicines are specifically designed for children in Paediatric Intensive Care (PICU), and therefore adult formulations are frequently administered, with high medication use further exposing a PICU patient to undesired alcohol intake. Aims - This small pilot study aimed to examiine the intake of a sample of PICU patients, highlight common medicines used on PICU containing alcohol, provide alternatives where possible and where alternatives are not possible, provide the prescriber with a list of the higher alcohol containing medicines. Method - A retrospective medication chart review was undertaken as a two point snap shot. Data collected included age, weight, medications prescribed and the formulations used at time of the study. The patients' sedation score was recorded. The electronic medicine compendium (EMC) was consulted for any ethanol content for the commercially available products. The manufacturer was contacted for ethanol content of all ‘specials’ and any commercial products found to contain ethanol from the EMC. The PICU patient's daily intake of ethanol was calculated. The calculation was converted to an adult equivalent alcohol unit intake and although this method of conversion is crude and does not take physiological differences of adult and children into account, it was done in order to provide the clinician with commonly used terminology in deciding the risk to the patient. Results - Twenty-eight patients were prescribed a range of 69 different medications. Of the 69 medicines, 12 products were found to contain ethanol. Patient ages ranged from a 26 week premature infant to 15 years old, weights ranges from 0.7 kg to 45 kg. Only 2 out of the 28 patients did not receive ethanol containing medications, and most patients were prescribed at least two medicines containing ethanol. Daily ethanol intake uncorrected for weight ranged from 0.006 ml to 2.18 ml (median 0.26 ml). Converting this to adult units per week, alcohol intake ranged from 0.07 to 15.2 units (median 1.4 units). The two patients receiving above 15 units/week adult equivalent were prescribed an oral morphine weaning regimen, therefore the high alcohol exposure was short term. The most common drugs prescribed containing alcohol were found to be nystatin, ranitidine, furosemide and morphine. No commercially available alcohol-free oral liquid preparations were found for ranitidine, furosemide or morphine at the time of the study. Correlation of the sedation score against ethanol intake was difficult to analyse as most patients were actively sedated. Conclusions - Polypharmacy in PICU patients increases the exposure to alcohol. Some commercially available medicines provide excessive ethanol intake, providing the clinician with ethical, potentially economical dilemmas of prescribing an unlicensed medicine to minimise ethanol exposure. Further research is required to evaluate the scope of the problem, effects of exposure and provision of alcohol free formulations.

Preschoolers’ Executive Control and Diurnal Cortisol as Mediators of the Relations of Prenatal Stress to Child Adjustment

Thesis (Ph.D.)--University of Washington, 2016-08

Anti-apoptotic effects of phyllanthin against alcoholinduced liver cell death

Purpose: To evaluate the anti-apoptotic effect of phyllanthin on alcohol-induced liver cell death in HepG2 cells alone and in co-culture with human monocytic (THP-1) differentiated macrophage cells. Methods: Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The cells were pretreated with 1, 5 and 10 μM phyllanthin for 24 h followed by 1300 mM alcohol for HepG2 cells and 2000 mM alcohol for the co-cultured cells. Thereafter, intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP) changes, apoptotic cell death and caspase-3/7 activities were assessed. Results: Alcohol exposure significantly increased intracellular ROS generation (p < 0.001), decreased MMP changes (p < 0.001), increased the number of apoptotic and necrotic cells (p < 0.001) and also induced higher caspase-3/7 activity (p < 0.001) in the co-culture with THP-1 differentiated macrophage cells than in HepG2 cells alone. Pretreatment of HepG2 cells and co-cultured cells with phyllanthin for 24 h prior to alcohol exposure significantly decreased intracellular production of ROS (p < 0.001) and also increased the change in MMP (p < 0.001) as well as caused a decrease in the number of apoptotic and necrotic cells (p < 0.001), but inhibited caspase-3/7 activity (p < 0.001). Conclusion: The results indicate that phyllanthin treatment may have a significant therapeutic effect on alcohol-related liver diseases.