Iron and iron-responsive proteins in the cardiomyopathy of Friedreich’s ataxia

Hypertrophic cardiomyopathy is a common complication of Friedreich's ataxia (FRDA). Histological sections reveal abnormal cardiomyocytes, muscle fiber necrosis, reactive inflammation, and increased endomysial connective tissue. Scattered muscle fibers display perinuclear collections of minute iron-positive granules that lie in rows between myofibrils. Frataxin deficiency in FRDA causes mitochondrial iron dysmetabolism. We studied total iron and the iron-related proteins ferritin, mitochondrial ferritin, divalent metal transporter 1 (DMT1), and ferroportin in FRDA hearts by biochemical and histological techniques. Total iron in the left ventricular wall of FRDA patients (30.7+/-19.3 mg/100 g dry weight) was not significantly higher than normal (31.3+/-24.1 mg/100 g dry weight). Similarly, cytosolic holoferritin levels in FRDA hearts (230+/-172 microg/g wet weight) were not significantly elevated above normal (148+/-86 microg/g wet weight). The iron-positive granules exhibited immunoreactivity for cytosolic ferritin, mitochondrial ferritin, and ferroportin. Electron microscopy showed enhanced electron density of mitochondrial deposits after treatment with bismuth subnitrate supporting ferritin accumulation. The inflammatory cells in the endomysium were reactive for CD68, cytosolic ferritin, and the DMT1 isoform(s) translated from messenger ribonucleic acids containing iron-responsive elements (DMT1+). Progressive cardiomyopathy in FRDA is the likely result of iron-catalyzed mitochondrial damage followed by muscle fiber necrosis and a chronic reactive myocarditis.     

Elevated synaptophysin I in the prefrontal cortex of human chronic alcoholics

Convergent lines of evidence suggest potentiation of glutamatergic synapses after chronic ethanol exposure, and indicate that the presynaptic effect hereof is on modulators of synaptic strength rather than on executors of glutamate release. To address this hypothesis in the context of ethanol dependence in humans, we used semiquantitative immunoblotting to compare the immunoreactivities of synaptophysin I, syntaxin 1A, synaptosome-associated protein 25, and vesicle-associated membrane protein in the prefrontal and motor cortices between chronic alcoholics and control subjects. We found a region-specific elevation in synaptophysin I immunoreactivity in the prefrontal cortex of alcoholics, but detected no significant differences between the groups in the immunoreactivities of the other three proteins. Our findings are consistent with an effect of repeated ethanol exposure on modulators of synaptic strength but not on executors of glutamate release, and suggest a role for synaptophysin I in the enduring neuroplasticity in the prefrontal cortical glutamate circuitry that is associated with ethanol dependence.     

Changing trends in heroin-related deaths in Sydney,Australia-1995 to 1999

This 1997-1999 study replicates an earlier one (1995-1997) in which coronial cases were reviewed at the Department of Forensic Medicine in Australia. Ten percent of the 2945 cases were considered accidental illicit drug deaths, compared to 4% in the previous study. Heroin was associated with 90% of the deaths, but in only 17% of these cases as a single drug. Concomitant drug use, in particular alcohol, benzodiazepines, and antidepressants, has increased considerably. The combined effects of these substances might play a role in the disturbingly large increase in heroin (morphine) related deaths during this period.     

Stereological analysis of microvascular parameters in a double transgenic model of Alzheimer's disease

Morphological alterations in microvasculature occur as a common finding in the brains of non-demented aged persons and patients with Alzheimer's disease. Quantifying the extent of this vascular pathology, however, has been complicated by systematic error (bias) associated with the applications of assumption- and model-based morphometric techniques to human and animal tissues. The current study used novel assumption- and model-free stereological approaches to quantify capillary parameters in the corpus callosum of a double amyloid precursor protein/presenilin-1 transgenic murine model of Alzheimer's disease. The results revealed significant reductions in the total number of capillary segments in white matter of transgenic mice compared to non-transgenic littermates, with no differences in total capillary length. These findings support the view that the expression of mutant human genes for beta-amyloid peptides alters the normal architecture of cerebral capillary vessels in the white matter of mouse brain, which may model microvasculature changes reported in Alzheimer's disease.     

Scurvy: forgotten but not gone

Scurvy is still seen sporadically in the developed world. At a time when subclinical vitamin C deficiency in the general population is being recognized increasingly, the need for clinicians to be aware of this disease remains. We present the case of a 9-year-old boy admitted to hospital with musculoskeletal pain, weakness and changes in the skin and gums. After extensive investigation, he was found to have vitamin C deficiency resulting from a restricted eating pattern. Musculoskeletal complaints are a common mode of presentation of scurvy in children. Failure to appreciate this fact and the risk factors for poor vitamin C intake in the paediatric age group can result in unnecessary and invasive investigations for apparent 'multisystem' disease.     

An integrated model for adolescent inpatient group therapy

This paper proposes an integrated group therapy model to be utilized by psychiatric and mental health nurses; one innovatively designed to meet the therapeutic needs of adolescents admitted to inpatient psychiatric programs. The writers suggest a model of group therapy primarily comprised of interpersonal approaches within a feminist perspective. The proposed group focus is on active therapeutic engagement with adolescents to further interpersonal learning and to critically examine their contextualized lived experiences. Specific client and setting factors relevant to the selection of therapeutic techniques are reviewed. Selected theoretical models of group therapy are critiqued in relation to group therapy with adolescents. This integrated model of group therapy provides a safe and therapeutic forum that enriches clients' personal and interpersonal experiences as well as promotes healthy exploration, change, and empowerment.