The regulation of leptin gene expression in the C6 glioblastoma cell line

The hormone leptin is implicated in the regulation of appetite and body weight in rodents, primates and humans. We reported that the leptin gene (ob) is expressed in the brain, but the factors which control ob expression in the central nervous system are not known. We previously showed that brain-derived rat C6 glioblastoma cells express ob mRNA and protein. In the present study we examined the regulation of ob expression in C6 cells. Leptin and leptin receptor immunoreactivity was detected in C6 cells, suggesting a possible autocrine role for leptin. The identity of the leptin immunoreactivity (OB-ir) in C6 cells was confirmed by immunoprecipitation and Western blotting using two leptin specific polyclonal antibodies. Using RT-PCR analysis a product of the expected size for the short, but not the long, leptin receptor isoform was detected in C6 cells. Cells were maintained in serum-free (SF) media for 0-24 h in the presence of various regulators of leptin expression. Leptin mRNA levels were significantly higher in cells treated with dbcAMP (1 mM), IGF 1 (100 ng/ml) or insulin (5 microg/ml) compared to SF controls. In contrast, corticosterone (10(-7)M) reduced leptin mRNA. In the presence of dbcAMP, C6 cells undergo a dramatic alteration in morphology which is coincident with an apparent increase in the number of leptin-ir nuclei and an increase in leptin immunoreactivity. In contrast to C6 cells, glucocorticoids are reported to increase leptin levels in adipocytes/adipose tissue, while increases in intracellular cAMP levels are reported to reduce leptin levels. Overall, our in vitro data suggest that the regulation of leptin gene expression in C6 glioblastoma cells is different from that in adipocytes.     

Chronic effects of cannabis on sensory gating

Chronic cannabis use has been associated with neurocognitive deficits, alterations in brain structure and function, and with psychosis. This study investigated the effects of chronic cannabis use on P50 sensory-gating in regular users, and explored the association between sensory gating, cannabis use history and the development of psychotic-like symptoms. Twenty controls and 21 regular cannabis users completed a P50 paired-click (S1 and S2) paradigm with an inter-pair interval of 9 s. The groups were compared on P50 amplitude to S1 and S2, P50 ratio (S2/S1) and P50 difference score (S1–S2). While cannabis users overall did not differ from controls on P50 measures, prolonged duration of regular use was associated with greater impairment in sensory gating as indexed by both P50 ratio and difference scores (including after controlling for tobacco use). Long-term cannabis users were found to have worse sensory gating ratios and difference scores compared to short-term users and controls. P50 metrics did not correlate significantly with any measure of psychotic-like symptoms in cannabis users. These results suggest that prolonged exposure to cannabis results in impaired P50 sensory-gating in long-term cannabis users. While it is possible that these deficits may have pre-dated cannabis use and reflect a vulnerability to cannabis use, their association with increasing years of cannabis use suggests that this is not the case. Impaired P50 sensory-gating ratios have also been reported in patients with schizophrenia and may indicate a similar underlying pathology.     

Neural time course of threat-related attentional bias and interference in panic and obsessive–compulsive disorders

Attentional biases to threat are considered central to anxiety disorders, however physiological evidence of their nature and time course is lacking. Event-related potentials (ERPs) characterized sensory and cognitive changes while 20 outpatients with panic disorder (PD), 20 with obsessive–compulsive disorder (OCD), and 20 healthy controls (HCs) responded to the color (emotional Stroop task) or meaning of threatening and neutral stimuli. ERPs indicated larger P1 amplitude and longer N1 latency in OCD, and shorter P1 latency in PD, to threatening (versus neutral) stimuli, across instructions to attend to, or ignore, threat content. Emotional Stroop interference correlated with phobic anxiety and was significant in PD. Participants with emotional Stroop interference had augmented P1 and P3 amplitudes to threat (versus neutral) stimuli when color-naming. The results suggest early attentional biases to threat in both disorders, with disorder-specific characteristics. ERPs supported preferential early attentional capture and cognitive elaboration hypotheses of emotional Stroop interference.     

Outcome of children requiring intensive care following haematopoietic SCT for primary immunodeficiency and other non-malignant disorders

Haematopoietic SCT (HSCT) is curative for many children with primary immunodeficiencies or other non-malignant conditions. Outcome for those admitted to intensive care following HSCT for oncology diagnoses has historically been very poor. There is no literature available specifically regarding the outcome for children with primary immunodeficiency requiring intensive care following HSCT. We reviewed our post-HSCT admission to intensive care over a 5-year period. A total of 111 children underwent HSCT. Median age at transplant was 1 year 4 months. The most common diagnosis was SCID. In all, 35% had at least one intensive care admission and 44% survived to be discharged from intensive care. Also, 73% of admission episodes requiring invasive ventilation but no inotropes or renal replacement therapy resulted in survival to discharge. Children undergoing HSCT for immunological diagnoses had a high rate of admission to intensive care. No factors were identified that could predict the need for admission. Invasive ventilation alone has a much better outcome than that in historical series. However, the need for multi-organ system support was still associated with a poor outcome. This information is useful when counselling families of children that have deteriorated and been admitted to intensive care during the HSCT procedure.     

Pan-canadian cardiovascular data definitions and quality indicators: a status update

After the 2009 publication of Building a Heart Healthy Canada, the Canadian Cardiovascular Society was commissioned to address a long-standing information gap related to the compatibility and comparability of data on the quality of cardiovascular care in Canada. Through collaboration between the Canadian Institute for Health Information, the Institute for Clinical Evaluative Sciences, the Public Health Agency of Canada, and 5 regional cardiovascular registries, 2 committees were tasked with developing standardized cardiovascular data definitions and quality indicators. The work culminated in national consensus on the definitions of 55 patient, disease, and therapeutic variables (core and optional) to facilitate cardiovascular care comparisons within and across Canada. Supplemental data definition chapters were then developed on acute coronary syndrome and coronary angiography/revascularization, with chapters on heart failure and atrial fibrillation electrophysiology to follow. This foundational work led to a critical appraisal of cardiac quality indicator development initiatives via the Appraisal of Guidelines for Research and Evaluation II (AGREE II) Quality Indicator tool, followed by the development of quality indicator catalogues on heart failure and atrial fibrillation. These indicators will be embedded within the clinical practice guidelines of the Canadian Cardiovascular Society, facilitating national comparisons across Canada on cardiovascular disease incidence, prevalence, patterns and quality of care, and clinical outcomes. This methodology-achieving national stakeholder consensus on a standardized process for the development and selection of cardiovascular quality indicators-illustrates the capacity to reach agreement by drawing on expertise and research across diverse organizational mandates and agendas, potentially contributing to improved cardiovascular care and outcomes for patients.