The use of PET imaging in studying cognition, genetics and pharmacotherapeutic interventions in schizophrenia

Positron emission tomography (PET) offers a strategic imaging platform to provide a map of functional neural correlates associated with the underlying cognitive deficits in schizophrenia. It enables regional cerebral glucose metabolism and dopaminergic and serotonergic receptor function to be studied. PET neuroimaging can therefore be used in drug development and to study putative treatments. Recent PET studies of the first-generation antipsychotics flupentixol and haloperidol, and of the second-generation antipsychotics risperidone, aripiprazole, quetiapine, sertindole, ziprasidone, paliperidone and olanzapine, have been carried out; modulation of limbic circuitry has been found to be a predictor of treatment response. PET can also be used to predict and monitor likely extrapyramidal side effects from antipsychotic treatment. PET and neuropsychological testing can together also allow the study of putative molecular genetic changes associated with schizophrenia. Advances in the imaging, cognition and molecular genetics are likely to lead to the development of future diagnostics, treatments and novel pharmacological agents.     

Myalgic encephalomyelitis or chronic fatigue syndrome: how could the illness develop?

Metabolic Brain Disease - A model of the development and progression of chronic fatigue syndrome (myalgic encephalomyelitis), the aetiology of which is currently unknown, is put forward, starting...     

Development of a sensitive size exclusion HPLC method with fluorescence detection for the quantitation of recombinant human erythropoietin (r-HuEPO) aggregates

Human erythropoietin produced by recombinant DNA technology, is now marketed worldwide for the treatment of anemias associated with chronic renal failure and chemotherapy. No sensitive methods, which can determine r-HuEPO dimer or oligomer aggregate content in formulated products, have been published to date. This report describes the development and validation of a sensitive size exclusion high performance liquid chromatography (HPLC) method for the quantitation of r-HuEPO aggregates in formulations containing 0.03% polysorbate 80. A Waters Alliance 2690 HPLC system connected to a TosoHaas TSKgel G3000 SWxl (7.8 mm x 30 cm, 250 A pore size, 5 microm particle size) column and a Waters 474 fluorescence detector was used. The mobile phase for the SEC-HPLC method consists of isopropyl alcohol-potassium phosphate (0.1 M)/potassium chloride buffer (pH 6.8+/-0.1, 0.2 M) (25:75, v/v). The flow rate was 0.3 mL/min and the method run time was 60 min. The SEC-HPLC method presented here was shown to be specific for r-HuEPO total aggregates (dimer and oligomers) and allows for their quantitation at 80 ng/mL or 4 ngs/injection, in the presence of r-HuEPO monomer and the pharmaceutical excipients, glycine (5 mg/mL), sodium chloride (4.3 mg/mL), and 0.03% polysorbate 80. The finalized method is stability-indicating and is suitable for determining r-HuEPO aggregates between 0.2 and 0.5% levels in the formulated product of r-HuEPO. This method offers a robust way to measure total aggregates on a routine basis with a high sensitivity for use in product quality control.     

Evidence for an Association between Brain-Derived Neurotrophic Factor Val66Met Gene Polymorphism and General Intellectual Ability in Early-Onset Schizophrenia

Background: Brain-derived neurotrophic factor (BDNF) plays a crucial role in the survival, development and maintenance of neuronal systems, and the Val66Met polymorphism has been implicated in memory functions. Method: We examined the association of BDNF with general intellectual ability in 161 individuals including 53 early-onset patients with schizophrenia (EOS), 91 healthy biological relatives, and 17 relatives with major depressive disorder (MDD), using the Wechsler Intelligence Scales (WISC). Results: Regardless of diagnosis, individuals with the Met66 allele had a significantly higher performance score than those homozygous for Val66 on vocabulary, block design and object assembly subtests of the WISC. EOS probands showed poor performance on all IQ subtests compared with relatives with and without MDD. Limitations: Relatively smaller sample size of individual genotypes. Conclusions: BDNF genotype may play a role in specific cognitive functions and dimensions of intelligence. The Met allele appears to be associated with superior performance in IQ compared with relatives Val/Val genotype.     

Burkholderia cenocepacia O polysaccharide chain contributes to caspase-1-dependent IL-1beta production in macrophages

Burkholderia cenocepacia infections in CF patients involve heightened inflammation, fatal sepsis, and high antibiotic resistance. Proinflammatory IL-1β secretion is important in airway inflammation and tissue damage. However, little is known about this pathway in macrophages upon B. cenocepacia infection. We report here that murine macrophages infected with B. cenocepacia K56-2 produce proinflammatory cytokine IL-1β in a TLR4 and caspase-1-mediated manner. We also determined that the OPS (O antigen) of B. cenocepacia LPS contributes to IL-1β production and pyroptotic cell death. Furthermore, we showed that the malfunction of the CFTR channel augmented IL-1β production upon B. cenocepacia infection of murine macrophages. Taken together, we identified eukaryotic and bacterial factors that contribute to inflammation during B. cenocepacia infection, which may aid in the design of novel approaches to control pulmonary inflammation.     

Potential therapeutic interventions based on the role of the endoplasmic reticulum stress response in progressive neurodegenerative diseases

正In 1945,Porter et al.published an electon microscopy study of cultured chick fibroblasts in which they observed:‘a granular background and details of a darker lacelike reticulum which in places appears to be made up of chains ofvesicles’(Porter et al.,1945).This constituted the first published observation of the endoplasmic reticulum(ER)and,while it was not evident at that time,this     

A case of postpartum chronic subdural hematoma

Headache is a common presentation during postpartum period. Anesthesiologist, obstetrician, and neurosurgeon should be aware of the possibility of subdural hematoma in patient complaining of headache following spinal anesthesia.