Effects of ethanol and transforming growth factor beta (TGF beta) on neuronal proliferation and nCAM expression

BACKGROUND Developmental events targeted by ethanol are cell proliferation, neuronal migration, and neurite outgrowth; the latter processes being mediated by neural cell adhesion molecule (nCAM). TGFbeta1 affects all three of these events. Therefore, the effects of ethanol on transforming growth factor (TGF) beta1 mediated activities in neocortical neurons in vitro were examined.METHODS Primary cultures of cortical neurons were obtained from 16-day-old fetuses and were treated with TGFbeta1 (0 or 10 ng/ml) and ethanol (0 or 400 mg/dl) for 48 hr. The effects of these substances on cell numbers, [ H]thymidine incorporation, and the expression of nCAM were determined.RESULTS Both cell growth (the change in cell numbers over time) and cell proliferation were inhibited by TGFbeta1 and ethanol. The action of these two anti-mitogenic factors was additive. In contrast, TGFbeta1 also promoted the expression of three isoforms of nCAM. Likewise, ethanol also up-regulated nCAM expression. On the other hand, ethanol blocked TGFbeta1-mediated nCAM expression, particularly of the 120 and 180 kDa isoforms.CONCLUSIONS TGFbeta ligands inhibit neuronal proliferation and stimulate the expression of cell adhesion proteins that promote the movement of postmitotic neurons and process outgrowth. Ethanol alters these phenomena as well. Thus, in neurons, as in astrocytes, TGFbeta1 and ethanol may interact.     

Treating Individuals and Families for Alcohol/Other Drug Problems in an Intensive Outpatient Setting

ABSTRACT

This article presents a family program set in an intensive outpatient setting for treating alcohol/other drug problems. The program stems from concern that families are not provided enough attention and/or services as residential settings have provided in the past. In addition, the collaborative process in developing the program between professionals from two different disciplines will be illuminated.     

Prevalence of fetal alcohol spectrum disorder in Greater Manchester,UK: An active case ascertainment study

Background

Despite high levels of prenatal alcohol exposure in the UK, evidence on the prevalence of fetal alcohol spectrum disorders (FASD) is lacking. This paper reports on FASD prevalence in a small sample of children in primary school.

Methods

A 2-phase active case ascertainment study was conducted in 3 mainstream primary schools in Greater Manchester, UK. Schools were located in areas that ranged from relatively deprived to relatively affluent. Initial screening of children aged 8–9 years used prespecified criteria for elevated FASD risk (small for age; special educational needs; currently/previously in care; significant social/emotional/mental health symptoms). Screen-positive children were invited for detailed ascertainment of FASD using gold standard measures that included medical history, facial dysmorphology, neurological impairment, executive function, and behavioral difficulties.

Results

Of 220 eligible children, 50 (23%) screened positive and 12% (26/220) proceeded to Phase 2 assessment. Twenty had a developmental disorder, of whom 4 had FASD and 4 were assessed as possible FASD. The crude prevalence rate of FASD in these schools was 1.8% (95% CI: 1.0%, 3.4%) and when including possible cases was 3.6% (2.1%, 6.3%). None of these children had previously been identified with a developmental diagnosis.

Conclusions

FASD was found to be common in these schools and most of these children's needs had not previously been identified. A larger, more definitive study that uses a random sampling technique stratified by deprivation level to select schools is needed to make inferences regarding the population prevalence of FASD.

     

Intensive Case Management for Homeless People with Alcohol and Other Drug Proplems

An intensive casc management program designed to be ellcclive with homeless persons affected by alcohol and other drug problems was implemented and rigorously evaluated The service demonstration site for the Denver project was Arapahoe House, Colorado's largest and most comprehensive substance abuse treatment center. The evaluation research efforts was conducted by the University of Denver. This project implemented an innovative model of case management, in which case managers operated in dyads and with a small caseload of clients. This model was oonceived as an optimal strategy to bind clients to the continuum of substance abuse s e m within Arapahoe How and to link clients to other needed services and benefits in the community.     

Chronic prenatal ethanol exposure increases adiposity and disrupts pancreatic morphology in adult guinea pig offspring

Background:

Ethanol consumption during pregnancy can lead to a range of adverse developmental outcomes in children, termed fetal alcohol spectrum disorder (FASD). Central nervous system injury is a debilitating and widely studied manifestation of chronic prenatal ethanol exposure (CPEE). However, CPEE can also cause structural and functional deficits in metabolic pathways in offspring.

Objectives and Methods:

This study tested the hypothesis that CPEE increases whole-body adiposity and disrupts pancreatic structure in guinea pig offspring. Pregnant guinea pigs received ethanol (4 g kg⁻¹ maternal body weight per day) or isocaloric-sucrose/pair-feeding (control) for 5 days per week throughout gestation.

Results:

Male and female CPEE offspring demonstrated growth restriction at birth, followed by a rapid period of catch-up growth before weaning (postnatal day (PD) 1–7). Whole-body magnetic resonance imaging (MRI) in young adult offspring (PD100–140) revealed increased visceral and subcutaneous adiposity produced by CPEE. At the time of killing (PD150–200), CPEE offspring also had increased pancreatic adipocyte area and decreased β-cell insulin-like immunopositive area, suggesting reduced insulin production and/or secretion from pancreatic islets.

Conclusion:

CPEE causes increased adiposity and pancreatic dysmorphology in offspring, which may signify increased risk for the development of metabolic syndrome and type 2 diabetes mellitus.     

Inhibitory control in young adult women with fetal alcohol syndrome: Findings from a pilot functional magnetic resonance imaging study

Background

Executive dysfunction, especially impaired inhibitory control, is a common finding in individuals with fetal alcohol syndrome (FAS). Previous research has mostly focused on neural correlates of inhibitory deficits in children and adolescents. We investigated inhibitory functions and underlying cerebral activation patterns in young adult women with FAS.

Methods

Task performance and functional magnetic resonance imaging (fMRI) data were acquired during a Go/NoGo (GNG) inhibition task in 19 young adult women with FAS and 19 healthy female control subjects. Whole-brain activation and task performance analyses were supplemented by region of interest (ROI) analyses of fMRI data within a predefined cognitive control network (CCN).

Results

Task performance did not differ significantly between groups on errors of commission, associated with inhibitory control. Similarly, overall activation within the preselected ROIs did not differ significantly between groups for the main inhibitory contrast NoGo > Go. However, whole-brain analyses revealed activation differences in the FAS group when compared to controls under inhibitory conditions. This included hyperactivations in the left inferior frontal, superior temporal, and supramarginal gyri in the FAS group. Likewise, lateralization tendencies toward right-hemispheric ROIs were weaker in FAS subjects. In contrast to comparable inhibitory performance, attention-related errors of omission were significantly higher in the FAS group. Correspondingly, FAS subjects had lower activity in attention-related temporal and parietal areas.

Conclusions

The known alterations of inhibitory functions associated with prenatal alcohol exposure in children and adolescents were not seen in this adult sample. However, differential brain activity was observed, reflecting potential compensatory mechanisms. Secondary results suggest that there is impaired attentional control in young adult women with FAS.     

慢性心功能不全患者围术期处理的进展

目前围术期医师面对着越来越多慢性心功能不全患者,慢性心功能不全治疗给围术期处理带来诸多问题。现对围术期慢性心功能不全药物治疗中的问题及慢性心功能不全急性发作的处理等作简要综述。     

Management of Noncardiac Comorbidities in Chronic Heart Failure

Prevalence of heart failure is increasing, especially in the elderly population. Noncardiac comorbidities complicate heart failure care and are increasingly common in elderly patients with reduced or preserved ejection fraction heart failure, owing to prolongation of patient's lives by advances in chronic heart failure (CHF) management. Common comorbidities include respiratory disease, renal dysfunction, anemia, arthritis, obesity, diabetes mellitus, cognitive dysfunction, and depression. These conditions contribute to the progression of the disease and may alter the response to treatment, partly as polypharmacy is inevitable in these patients. Cardiologists and other physicians caring for patients with CHF need to be vigilant to comorbid conditions that complicate the care of these patients. There is now more guidance on management of noncardiac comorbidities in heart failure, and this article contains a comprehensive review of the most recent updates on management of noncardiac comorbidities in CHF.     

Validation of the FASD-Tree as a screening tool for fetal alcohol spectrum disorders

Background

As many as 80% of individuals with fetal alcohol spectrum disorders (FASD) are misdiagnosed or not diagnosed. This study tests the accuracy and validity of a web-based screening tool (the FASD-Tree) for identifying children and adolescents with FASD.

Methods

Children with histories of prenatal alcohol exposure (PAE) and controls (N = 302, including 224 with PAE and 78 controls) were examined for physical signs of fetal alcohol syndrome (FAS), and parents completed behavioral questionnaires. Data were entered into the FASD-Tree, a web-based decision tree application. The FASD-Tree provided two outcomes: a dichotomous indicator (yes/no) and a numeric risk score (0 to 5), which have been shown separately to identify children with PAE and neurobehavioral impairment and to correlate with neurobehavioral outcomes. Overall accuracy (ACC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the decision tree, risk score, and their combination. Misclassified cases were examined for systematic bias.

Results

The FASD-Tree was successful in accurately identifying youth with histories of PAE and the subgroup of individuals with FASD, indicating its validity as an FASD screening tool. Overall accuracy rates for FASD-Tree components ranged from 75.0% to 84.1%, and both the decision tree outcome and risk score, and their combination, resulted in fair to good discrimination (area under the curve = 0.722 to 0.862) of youth with histories of PAE or FASD. While most participants were correctly classified, those who were misclassified differed in IQ and attention. Race, ethnicity, and sex did not affect the results.

Conclusion

The FASD-Tree is not a biomarker of PAE and does not provide definitive evidence of prenatal alcohol exposure. Rather it is an accurate and valid screening tool for FASD and can be used by clinicians who suspect that a patient has a history of PAE, even if the exposure is unknown.