Alpha-1 antitrypsin deficiency: A conformational disease associated with lung and liver manifestations

Alpha-1 antitrypsin (A1AT) is a serine anti-protease produced chiefly by the liver. A1AT deficiency is a genetic disorder characterized by serum levels of less than 11 μmol/L and is associated with liver and lung manifestations. The liver disease, which occurs in up to 15% of A1AT-deficient individuals, is a result of toxic gain-of-function mutations in the A1AT gene, which cause the A1AT protein to fold aberrantly and accumulate in the endoplasmic reticulum of hepatocytes. The lung disease is associated with loss-of-function, specifically decreased anti-protease protection on the airway epithelial surface. The so-called 'Z' mutation in A1AT deficiency encodes a glutamic acid-to-lysine substitution at position 342 in A1AT and is the most common A1AT allele associated with disease. Here we review the current understanding of the molecular pathogenesis of A1AT deficiency and the best clinical management protocols. © Springer Science+Business Media B.V. 2008.

Maternal mental health and non-organic failure to thrive.

This study reports on the first phase of a large-scale, longitudinal, multidisciplinary community study examining the growth, learning and development of young children with a particular focus on failure to thrive without organic cause. However, the group identified in this study may be better described as weight faltering. This paper examines the psychological data collected using the Parenting Stress Index, Rosenberg Self-Esteem and the General Health Questionnaire in relation to child growth. There were no significant differences between the mothers of the weight faltering and control children in terms of parenting stress, maternal depression, maternal perceptions of their parenting competence or maternal self-esteem. Maternal sensitivity to comments about child size, regardless of direction, had a negative impact on mood.

An Examination of the Use of Coercion by Assertive Outreach and Community Mental Health Teams in Northern Ireland.

In mental health services over recent decades, the positive move away from hospital-based care to community-based services has entailed that people with higher levels of need are being supported by community mental health services. This paper begins by reviewing the literature on coercion in the field of community-based mental health care and treatment. It is argued that the lack of a critical understanding of the concept and how it is used by practitioners and agencies can have serious repercussions for the rights of service users. Using a quasi-experimental, longitudinal design, the authors then seek to test some of the ideas about coercion by comparing the activities of assertive outreach and community mental health teams in Northern Ireland, particularly the key ideas of perceived coercion, workers’ strategies and engagement with services. Key findings were that assertive outreach appeared to be more successful at reducing perceived coercion, minimizing the need for coercive strategies, engaging high-risk clients and reducing inpatient bed use. These findings are compared with other studies in this area. The authors also argue that there is a need for greater transparency in the way that practitioners use coercive measures and more explicit guidance is required in this crucial area of mental health practice.

Severe Vitamin E deficiency modulates airway allergic inflammatory responses in the murine asthma model

Allergic asthma is a complex immunologically mediated disease associated with increased oxidative stress and altered antioxidant defenses. It was hypothesized that a-tocopherol (a-T) decreases oxidative stress and therefore its absence may influence allergic inflammatory process, a pathobiology known to be accompanied by oxidative stress. Therefore, selected parameters of allergic asthma sensitization and inflammation were evaluated following ovalbumin sensitization and re-challenge of a-T transfer protein (TTP) knock-out mice (TTP-/-) that have greatly reduced lung a-T levels (e.g.

Mice lacking alpha-tocopherol transfer protein gene have severe alpha-tocopherol deficiency in multiple regions of the central nervous system

Ataxia with vitamin E deficiency is caused by mutations in a-tocopherol transfer protein (a-TTP) gene and it can be experimentally generated in mice by a-TTP gene inactivation (a-TTP-KO). This study compared a-tocopherol (a-T) concentrations of five brain regions and of four peripheral organs from 5 months old, male and female, wild-type (WT) and a-TTP-KO mice. All brain regions of female WT mice contained significantly higher a-T than those from WT males. a-T concentration in the cerebellum was significantly lower than that in other brain regions of WT mice. These sex and regional differences in brain a-T concentrations do not appear to be determined by a-TTP expression which was undetectable in all brain regions. All the brain regions of a-TTP-KO mice were severely depleted in a-T. The concentration of another endogenous antioxidant, total glutathione, was unaffected by gender but was decreased slightly but significantly in most brain regions of a-TTP-KO mice. The results show that both gender and the hepatic a-TTP, but not brain a-TTP gene expression are important in determining a-T concentrations within the brain. Interestingly, functional abnormality (ataxia) develops only very late in a-TTP-KO mice in spite of the severe a-tocopherol deficiency in the brain starting at an early age.

'An aid to mental health': natural history, alienists and therapeutics in Victorian Scotland

In the nineteenth century natural history was widely regarded as a rational and ‘distracting’ pursuit that countered the ill-effects, physical and mental, of urban life. This familiar argument was not only made by members of naturalists’ societies but was also borrowed and adapted by alienists concerned with the moral treatment of the insane. This paper examines the work of five long-serving superintendents in Victorian Scotland and uncovers the connections made between an interest in natural history and the management of mental disease. In addition to recovering a significant influence on the conduct of several alienists the paper explores arguments made outside the asylum walls in favour of natural history as an aid to mental health. Investigating the promotion of natural history as a therapeutic recreation in Scotland and elsewhere reveals more fully the moral and cultural significance attached to natural history pursuits in the nineteenth century.