Decreased amygdala CRF-binding protein mRNA in post-mortem tissue from male but not female bipolar and schizophrenic subjects.

Stressful life events are commonly associated with the onset and maintenance of psychopathology and much research has focused on the role of the corticotropin-releasing factor (CRF) system in mediating psychopathology. Since CRF serves to integrate the stress response, it is possible that the CRF system plays a role as a neurochemical linkage between stress and psychopathology. CRF-binding protein (CRF-BP) is thought to modulate CRF activity by decreasing its actions. Therefore, in some psychopathological states, alterations in CRF-BP function may contribute to dysregulation of the CRF system. Since the amygdala CRF system mediates stress- and anxiety-related behaviors and alterations in amygdala function are associated with psychopathology, we examined amygdala CRF-BP gene expression in post-mortem brains from subjects with major depression, bipolar disorder, and schizophrenia as well as in controls. In addition to characterizing the anatomic distribution of CRF-BP mRNA in the human amygdala and medial temporal lobe region, we found a significant decrease in CRF-BP mRNA levels in the basolateral amygdala of male bipolar and male schizophrenic subjects and the lateral amygdala of male bipolar subjects. These results raise the possibility that men with decreased amygdala CRF-BP may be more vulnerable to the effects of stress exposure on the etiology or maintenance of bipolar disorder or schizophrenia.     

Does exposure to infectious diseases in infancy affect old-age mortality? Evidence from a pre-industrial population

Many studies have shown that health conditions experienced in childhood play an important role on an individual's adult mortality. Recent research suggests that past reductions in early life exposure to infectious diseases have been a major contributor to the historical decline in old-age mortality. Drawing on French-Canadian data from cohorts born in the 17th and 18th centuries, we test whether a progressive deterioration in early life conditions (as revealed by an increasing infant mortality rate) translates into a decrease in survival prospects in late life. We use traditional demographic measures such as the age-specific probability of death, and a series of proportional hazard models to control for familial and environmental conditions. Results point toward little evidence of any early life effects. The trend of increasing infant mortality does not correlate with a general increase of mortality in older ages within the same cohorts. Period changes affecting survival at older ages (war, epidemics) as well as demographic and biological characteristics shared within families have a much larger role in old-age mortality than early life characteristics shared within the same cohorts.     

Prevalence of autoimmune diseases in islet transplant candidates with severe hypoglycaemia and glycaemic lability: previously undiagnosed coeliac and autoimmune thyroid disease is identified by screening.

AIMS: Autoimmune diseases such as Addison's or coeliac disease can contribute to hypoglycaemia or malabsorption and are more common in Type 1 diabetes (T1DM). This brief report describes the prevalence of known and newly detected autoimmune disease in clinical islet transplant candidates with longstanding T1DM and severe hypoglycaemia and/or glycaemic lability who are routinely screened for coexisting autoimmune disease. METHODS: One hundred and twenty-four C-peptide negative T1DM subjects [77 (62%) female, mean age 44 +/- 9 years, diabetes duration 28 +/- 11 years, body mass index 24.9 +/- 3.5 kg/m(2)] with indications for clinical islet transplantation at the University of Alberta were screened for autoimmune disease by history and measurement of anti-transglutaminase antibodies (positive > 10 U/ml), 09.00 h cortisol (followed by adrenocorticotrophic hormone-stimulation if < 495 nmol/l) and thyroid-stimulating hormone to determine the prevalence of coeliac disease, Addison's disease and autoimmune thyroid disease, respectively. RESULTS: Forty per cent of subjects had one or more coexisting autoimmune disease. The prevalence of autoimmune disease was 35%, coeliac disease 8% and Addison's disease 1.6%. In 11 individuals (9%), one or more autoimmune disease were newly detected (seven coeliac disease and five thyroid disease). Seven of 10 cases of coeliac disease were newly detected. A gluten-free diet in individuals with newly diagnosed coeliac disease reduced gastrointestinal symptoms, but indications for clinical islet cell transplantation persisted. CONCLUSIONS: Coexisting autoimmune disease is common in candidates for clinical islet cell transplantation. Screening in this group identified a substantial number of previously unrecognized cases. Clinicians should consider the presence of autoimmune disease even in the absence of classical symptoms.     

Online access to NDT for developing countries

As editors we want as many people to have access to NDT as possible.The last 18 months have seen a number of experimental initiativesto test the technical and logistical     

Patterns of cognitive change over time and relationship to age following successful treatment of Cushing's disease.

Chronically elevated levels of cortisol have been associated with changes in cognitive functioning and brain morphology. Using Cushing's disease as a model to assess the effects of high levels of cortisol on cognitive functioning, 27 patients with Cushing's disease were examined at baseline and three successive follow-up periods up to 18 months after successful surgical treatment. At all follow-up periods, patients were administered cognitive tests as well as measures of plasma and urinary free cortisol. Structural MRIs and a depression measure were taken at baseline and one-year follow-up. Results showed that there is a specific pattern of significant cognitive and morphological improvement following successful treatment. Verbal fluency and recall showed recovery, although brief attention did not. Age of participants was a significant factor as to when recovery of function occurred; younger patients regained and sustained their improvement in cognitive functioning more quickly than older participants. Improvement in verbal recall also was associated with a decrease in cortisol levels as well as an increase in hippocampal formation volume one year after treatment. Overall, these findings suggest that at least some of the deleterious effects of prolonged hypercortisolemia on cognitive functioning are potentially reversible, up to at least 18 months post treatment.     

Transforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro

To determine if transforming growth factor alpha (TGFα) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10⁻³M) exposure either with or without growth factor pretreatment. After TGFα (500ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGFα in organ of Corti explants.