Hormone-induced calcium oscillations depend on cross-coupling with inositol 1,4,5-trisphosphate oscillations.

Receptor-mediated oscillations in cytosolic Ca(2+) concentration ([Ca(2+)]i) could originate either directly from an autonomous Ca(2+) feedback oscillator at the inositol 1,4,5-trisphosphate (IP3) receptor or as a secondary consequence of IP3 oscillations driven by Ca(2+) feedback on IP3 metabolism. It is challenging to discriminate these alternatives, because IP3 fluctuations could drive Ca(2+) oscillations or could just be a secondary response to the [Ca(2+)]i spikes. To investigate this problem, we constructed a recombinant IP3 buffer using type-I IP3 receptor ligand-binding domain fused to GFP (GFP-LBD), which buffers IP3 in the physiological range.

Low plasma leptin in cognitively impaired ADNI subjects: gender differences and diagnostic and therapeutic potential.

Analysis of data derived from the Alzheimer's Disease Neuroimaging Initiative (ADNI) program showed plasma leptin levels in individuals with Mild Cognitive Impairment (MCI) or Alzheimer's disease (AD) to be lower than those of subjects with normal cognition (NC). Approximately 70% of both men and women with MCI have plasma leptin levels lower than the median values of NC. Additionally, half of these subjects carry at least one apolipoprotein-E4 (APOE-ε4) allele.

Isotyping the human TOMM40 variable-length polymorphism by gene amplification and restriction digest.

Recent studies have shown that the translocase of outer mitochondrial membrane 40 homolog (TOMM40) contains a polymorphic poly-T variant, the long variant of which is associated with an increase in AD incidence among APOE 3 carriers. Current methods to isotype the poly-T region rely on long PCR, subcloning and sequencing to distinguish among the allelic variants. While such methods are extremely accurate as well as quantitative in determining the number of T residues in the poly-T region, the process can be cumbersome, time consuming and expensive to employ in routine laboratories.

Repositioning leptin as a therapy for Alzheimer's disease.

The data from the initial clinical trials utilizing recombinant human leptin as an obesity therapy were published in 1998. Since then, numerous studies have been described which address dosage, safety and efficacy of leptin replacement for a variety of disorders with diverse patient groups, including pediatric and adult subjects. We review the current clinical trial data, demonstrate that leptin administration is safe for long term use in humans, and summarize reported cognitive benefits.

Leptin boosts cellular metabolism by activating AMPK and the sirtuins to reduce tau phosphorylation and β-amyloid in neurons.

Leptin is a pleiotropic hormone primarily secreted by adipocytes. A high density of functional Leptin receptors has been reported to be expressed in the hippocampus and other cortical regions of the brain, the physiological significance of which has not been explored extensively. Alzheimer's disease (AD) is marked by impaired brain metabolism with decreased glucose utilization in those regions which often precede pathological changes.

Measurement of urinary metadrenaline and normetadrenaline by liquid chromatography tandem mass spectrometry for the diagnosis of phaeochromocytoma.

Background: Measurement of metadrenalines has been recommended in the investigation of phaeochromocytoma. Urinary assays remain the most common; however, drug interference is still one of the main challenges for analytical systems. We have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of total urinary normetadrenaline and total urinary metadrenaline, which does not require extraction procedures prior to analysis.

The needs of aging parents caring for an adult with acquired brain injury.

This study focused on issues of concern to and service needs of older parents caring for an adult son or daughter with an acquired brain injury (ABI) in Ontario. Three issues were identified as particularly challenging: diagnosis of the brain injury, parents' feelings about the cause of the brain injury, and planning for long-term accommodation for their family member with a brain injury. The most frequently cited services needed for the person with ABI were social and/or recreational activities, day programs, and residential placement.

Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer's disease.

We have previously reported anti-amyloidogenic effects of leptin using in vitro and in vivo models and, more recently, demonstrated the ability of leptin to reduce tau phosphorylation in neuronal cells. The present study examined the efficacy of leptin in ameliorating the Alzheimer's disease (AD)-like pathology in 6-month old CRND8 transgenic mice (TgCRND8) following 8 weeks of treatment. Leptin-treated transgenic mice showed significantly reduced levels of amyloid-beta (Abeta){1-40} in both brain extracts (52% reduction, p= 0.

Chronic Leptin Supplementation Ameliorates Pathology and Improves Cognitive Performance in a Transgenic Mouse Model of Alzheimer's Disease.

We have previously reported anti-amyloidogenic effects of leptin using in vitro and in vivo models and, more recently, demonstrated the ability of leptin to reduce tau phosphorylation in neuronal cells. The present study examined the efficacy of leptin in ameliorating the Alzheimer's disease (AD)-like pathology in 6-month old CRND8 transgenic mice (TgCRND8) following 8 weeks of treatment. Leptin-treated transgenic mice showed significantly reduced levels of amyloid-beta (Abeta){1-40} in both brain extracts (52% reduction, p= 0.

Leptin inhibits glycogen synthase kinase-3beta to prevent tau phosphorylation in neuronal cells.

We have previously demonstrated that Leptin reduces extracellular amyloid beta (Abeta) protein both in vitro and in vivo, and intracellular tau phosphorylation in vitro. Further, we have shown that these effects are dependent on activation of AMP-activated protein kinase (AMPK) in vitro. Herein, we investigated downstream effectors of AMPK signaling directly linked to tau phosphorylation.

Leptin: a novel therapeutic strategy for Alzheimer's disease.

Adipocyte-derived leptin appears to regulate a number of features defining Alzheimer's disease (AD) at the molecular and physiological level. Leptin has been shown to reduce the amount of extracellular amyloid beta, both in cell culture and animal models, as well as to reduce tau phosphorylation in neuronal cells. Importantly, chronic administration of leptin resulted in a significant improvement in the cognitive performance of transgenic animal models.

Leptin regulates tau phosphorylation and amyloid through AMPK in neuronal cells.

Leptin, which serves as a lipid-modulating hormone to control metabolic energy availability, is decreased in Alzheimer's disease (AD) patients, and serum levels are inversely correlated to severity of dementia. We have previously described the effects of leptin in reducing amyloid beta protein both in vitro and in vivo, and tau phosphorylation in vitro. Herein, we systematically investigated the signaling pathways activated by leptin, leading to these molecular endpoints, to better understand its mechanism of action.

Leptin reduces Alzheimer's disease-related tau phosphorylation in neuronal cells.

Leptin is a centrally acting hormone controlling metabolic pathways. Recently, it was shown that leptin can reduce amyloid beta levels both in vitro and in vivo. Herein, phosphorylation of tau was investigated following treatment of neuronal cells with leptin and insulin.

'Participate to learn': a promising practice for community ABI rehabilitation.

Objective: To identify best practices and promising practices to enhance participation in meaningful and productive activities.

Method: An electronic search of the ABI rehabilitation research literature since 1990 yielded 974 articles of which 30 focused on interventions that targeted participation and evaluated effectiveness using direct measures of participation. Three reviewers rated these articles according to the standards set out by the Centre for Reviews and Dissemination.

Calcium oscillations in type-1 astrocytes, the effect of a presenilin 1 (PS1) mutation.

Stimulation of type-1 astrocytes, by a number of agonists, has been shown to increase cytosolic Ca2+ concentrations in an oscillatory manner. However, it is unknown how these are driven or altered by aging, injury or disease. Therefore, we characterized the signaling properties of rat type-1 astrocytes in monolayer cultures.

Obesity-related leptin regulates Alzheimer's Abeta.

Abeta peptide is the major proteinateous component of the amyloid plaques found in the brains of Alzheimer's disease (AD) patients and is regarded by many as the culprit of the disorder. It is well documented that brain lipids are intricately involved in Abeta-related pathogenic pathways. An important modulator of lipid homeostasis is the pluripotent peptide leptin.

Stereotactic breast biopsy: an audit of 18 months at BreastScreen Auckland.

Stereotactic biopsy has become a widely used technique for marnmographically detected lesions that are clinically and sonographically occult. Vacuum-assisted (mammotome) biopsy on a dedicated prone stereotactic unit has further increased ease of biopsy and utility of the technique. Results of an 18-month audit in the national breast screening programme (BreastScreen Auckland and North) in the Auckland region demonstrates results comparable with those achieved elsewhere.

Community integration: a useful construct, but what does it really mean?

The primary objective of this paper is to contribute to a clearer understanding of the construct of community integration. Rehabilitation literature is discussed in relation to three measures of community integration: the AIMS Interview, Community Integration Measure and Community Integration Questionnaire. Results of a principal components analysis with varimax rotation indicated that the measures are independent and coherent.