Reduced Neuronal Size and Glial Cell Density in Area 9 of the Dorsolateral Prefrontal Cortex in Subjects with Major Depressive Disorder

Cerebral Cortex (New York, N.Y. : 1991). Apr, 2002  |  Pubmed ID: 11884354

Reductions in glial cell density and neuronal size have been described recently in major depressive disorder (MDD). Considering the important trophic influence of glia on neurons, we hypothesized that this glial cell deficit is more prominent close to neurons. In this investigation we have characterized neuronal and glia cytoarchitecture in prefrontal area 9 using spatial point pattern techniques and two-dimensional measures of cell size and density. In post-mortem brain tissue of subjects with MDD, schizophrenia, bipolar disorder (BPD), and normal controls (15 subjects per group), we examined the laminar location and size of all neurons and glial nuclei in a 500 microm wide strip of cortex extending from the pia to the grey-white matter border. In MDD, we observed reductions in glial cell density (30%; P = 0.007) in layer 5 and neuronal size (20%; P = 0.003) in layer 6. We also found that glial cell density (34%; P = 0.003) was reduced in layer 5 in schizophrenia, while neuronal size was reduced in layers 5 (14%) (P = 0.006) and 6 (18%; P = 0.007) in BPD. The spatial pattern investigation of neurons and glia demonstrated no alteration in the clustering of glia about neurons between control and patient groups. These findings confirm that glial cell loss and neuronal size reductions occur in the deeper cortical layers in MDD, but provide no support for the hypothesis that an altered spatial distribution of glia about neurons plays a role in the development of these changes.

Stereochemical and Kinetic Comparisons of Mono- and Diepoxide Formation in the in Vitro Metabolism of Isoprene by Liver Microsomes from Rats, Mice, and Humans

Chemical Research in Toxicology. Jul, 2003  |  Pubmed ID: 12870896

Isoprene (2-methylbuta-1,3-diene) is a large scale petrochemical used principally in the manufacture of synthetic rubbers. It is also produced by plants and trees and is formed endogenously in mammals as a major endogenous hydrocarbon. Mammalian metabolism of isoprene involves cytochrome P450-dependent monooxygenases to give the regioisomeric monoepoxides, prop-2-enyloxirane and 2-ethenyl-2-methyloxirane. The isoprene monoepoxides are further oxidized to the mutagenic diepoxides, 2-methyl-2,2'-bioxiranes. The present studies have investigated the stereochemistry and comparative rates of the metabolic epoxidation in vitro of isoprene to mono- and diepoxides by liver microsomes from rat, mouse, and human in order to identify stereochemical and kinetic differences between species in the formation of these epoxide metabolites, which are key to understanding the toxicology of isoprene. The assignments of stereochemistry were based on comparisons with synthetic standards, the syntheses for which are described. Comparative enzyme kinetic parameters (apparent K(m) and apparent V(max) values) for the in vitro formation of all of the monoepoxide and diepoxide stereoisomers have been obtained. The rates of formation of both mono- and diepoxides were greater in the rodent systems as compared with the human in vitro system. The results provide comparative kinetic data that have potential for modeling and assessing the relevance of the animal carcinogenicity data for man. The possibility of human interindividual variation was also investigated with liver preparations from several individual humans, but significant differences between individuals were not observed in the formation of the monoepoxides from isoprene.

Cell Density and Cortical Thickness in Heschl's Gyrus in Schizophrenia, Major Depression and Bipolar Disorder

The British Journal of Psychiatry : the Journal of Mental Science. Sep, 2004  |  Pubmed ID: 15339832

There is evidence that the superior temporal gyrus and Heschl's gyrus within it are implicated in schizophrenia. We investigated neuronal and glial cell density and cortical thickness within Heschl's gyrus, using the optical disector to estimate cell density within cortical layers 3 and 5 in tissue derived postmortem from people with diagnoses of major depressive disorder, schizophrenia and bipolar disorder, compared with normal controls (n=15 per group). No significant difference in neuronal or glial cell density or in cortical thickness was observed between the groups; our findings therefore provide no support for the presence of cellular pathology within Heschl's gyrus in schizophrenia.

School Students As Drosophila Experimenters

PLoS Biology. Jul, 2005  |  Pubmed ID: 16000022

Over-expression of Tau Results in Defective Synaptic Transmission in Drosophila Neuromuscular Junctions

Neurobiology of Disease. Dec, 2005  |  Pubmed ID: 16023860

We have shown that over-expression of human tau (0N3R) in Drosophila larval motor neurons causes significant morphological and functional disruption to the neuromuscular junctions (NMJs). Tau-expressing NMJs are reduced in size with irregular and abnormal bouton structure. Immunocytochemical analysis shows that the abnormal NMJs still retain synaptotagmin expression and form active zones. Functionally, the NMJs exhibit abnormal endo/exocytosis as revealed by incorporation of the styryl dye FM1-43. Electrophysiological studies showed that with low frequency stimulation (1 Hz), evoked synaptic potentials produced from tau over-expressing motor neurons were indistinguishable from wild type, however, following high frequency stimulation (50 Hz), evoked synaptic potentials were significantly decreased. Analysis of the number and distribution of mitochondria showed that motor neurons over-expressing tau had a significant reduction in functional mitochondria in the presynaptic terminal. Collapsing the mitochondrial membrane potential in wild type larvae phenocopied the effects of tau over-expression on synaptic transmission. Our results demonstrate that tau over-expression in vivo cause a synaptic dysfunction, which may be caused by a reduced complement of functional mitochondria.

Deprivation and Volunteering by General Practices: Cross Sectional Analysis of a National Primary Care System

BMJ (Clinical Research Ed.). Dec, 2005  |  Pubmed ID: 16356981

Practice Size and Quality Attainment Under the New GMS Contract: a Cross-sectional Analysis

The British Journal of General Practice : the Journal of the Royal College of General Practitioners. Nov, 2006  |  Pubmed ID: 17132349

The Quality and Outcomes Framework (QOF) of the new General Medical Services contract, for the first time, incentivises certain areas of general practice workload over others. The ability of practices to deliver high quality care may be related to the size of the practice itself.

Low Serum Cortisol Predicts Early Death After Acute Myocardial Infarction

Critical Care Medicine. Mar, 2010  |  Pubmed ID: 20081532

To determine whether low serum cortisol concentrations are associated with adverse prognosis in patients with acute myocardial infarction. Low serum cortisol concentrations have been associated with adverse prognosis in critical illness of diverse etiology.

Gestational Age at Delivery and Special Educational Need: Retrospective Cohort Study of 407,503 Schoolchildren

PLoS Medicine. Jun, 2010  |  Pubmed ID: 20543995

Previous studies have demonstrated an association between preterm delivery and increased risk of special educational need (SEN). The aim of our study was to examine the risk of SEN across the full range of gestation.

Smoke-free Legislation and Hospitalizations for Childhood Asthma

The New England Journal of Medicine. Sep, 2010  |  Pubmed ID: 20843248

Previous studies have shown that after the adoption of comprehensive smoke-free legislation, there is a reduction in respiratory symptoms among workers in bars. However, it is not known whether respiratory disease is also reduced among people who do not have occupational exposure to environmental tobacco smoke. The aim of our study was to determine whether the ban on smoking in public places in Scotland, which was initiated in March 2006, influenced the rate of hospital admissions for childhood asthma.

Maternal Risk of Ischaemic Heart Disease Following Elective and Spontaneous Pre-term Delivery: Retrospective Cohort Study of 750 350 Singleton Pregnancies

International Journal of Epidemiology. Aug, 2011  |  Pubmed ID: 21278195

Previous studies have demonstrated an overall association between pre-term delivery and maternal risk of subsequent ischaemic heart disease (IHD). The underlying mechanism is unknown. We explored whether the association was specific to spontaneous or elective pre-term delivery.

Association Between Preterm Delivery and Subsequent C-reactive Protein: a Retrospective Cohort Study

American Journal of Obstetrics and Gynecology. Dec, 2011  |  Pubmed ID: 21890096

We sought to determine whether giving birth preterm is associated with raised maternal C-reactive protein (CRP) in later life and whether the association is specific to indicated or spontaneous delivery.

Impact of Scottish Smoke-free Legislation on Smoking Quit Attempts and Prevalence

PloS One. 2011  |  Pubmed ID: 22110585

In Scotland, legislation was implemented in March 2006 prohibiting smoking in all wholly or partially enclosed public spaces. We investigated the impact on attempts to quit smoking and smoking prevalence.

Clinical Outcomes Following Radial Versus Femoral Artery Access in Primary or Rescue Percutaneous Coronary Intervention in Scotland: Retrospective Cohort Study of 4534 Patients

Heart (British Cardiac Society). Feb, 2012  |  Pubmed ID: 22337951

ObjectiveTo assess short-term and medium-term outcomes following radial and femoral artery access for primary or rescue percutaneous coronary intervention (PCI).DesignRetrospective cohort study.SettingScotland-wide.PatientsAll 4534 patients undergoing primary or rescue PCI in Scotland between April 2000 and March 2009 using the Scottish Coronary Revascularisation Register.InterventionPrimary or rescue PCI.Main outcome measuresProcedural success; peri-procedural complications; 30-day and 1-year mortality, myocardial infarction or stroke and long-term mortality.ResultsUse of the radial approach increased from no cases in 2000 to 924 (80.5%) in 2009 (p<0.001). Patients in whom the radial approach was used were more likely to be male (p=0.041) and to have multiple comorbidities (p<0.001), including hypertension (p<0.001) and left ventricular dysfunction (p<0.001). They were less likely to have renal impairment (p=0.017), multi-vessel coronary disease (p=0.001) and cardiogenic shock (p<0.001). In multivariable analyses, use of radial artery access was associated with greater procedural success (adjusted OR 1.89, 95% CI 1.26 - 2.82, p=0.002) and a lower risk of any complications (adjusted OR 0.67, 95% CI 0.51 - 0.87, p=0.001) or access site bleeding complications (adjusted OR 0.21, 0.08 - 0.56, p=0.002), as well as a lower risk of myocardial infarction (adjusted OR 0.66, 95% CI 0.51-0.87, p=0.003) or death within 30 days (adjusted OR 0.51, 95% CI 0.04 - 0.52, p<0.001). The differences in myocardial infarction and death remained significant up to 9 years of follow-up.ConclusionUse of the radial artery for primary or rescue PCI is associated with improved clinical outcomes.