Quetiapine in refractory hyperactive and mixed intensive care delirium: a case series

Introduction  

Delirium affects up to 80% of patients admitted to intensive care units (ICUs) and contributes to increased morbidity and mortality. Haloperidol is the gold standard for treatment, although quetiapine has been successfully used in the management of delirium.     

SARS-CoV nucleocapsid protein interacts with cellular pyruvate kinase protein and inhibits its activity

The pathogenesis of SARS-CoV remains largely unknown. To study the function of the SARS-CoV nucleocapsid protein, we have conducted a yeast two-hybrid screening experiment to identify cellular proteins that may interact with the SARS-CoV nucleocapsid protein. Pyruvate kinase (liver) was found to interact with SARS-CoV nucleocapsid protein in this experiment. The binding domains of these two proteins were also determined using the yeast two-hybrid system. The physical interaction between the SARS-CoV nucleocapsid and cellular pyruvate kinase (liver) proteins was further confirmed by GST pull-down assay, co-immunoprecipitation assay and confocal microscopy. Cellular pyruvate kinase activity in hepatoma cells was repressed by SARS-CoV nucleocapsid protein in either transiently transfected or stably transfected cells. PK deficiency in red blood cells is known to result in human hereditary non-spherocytic hemolytic anemia. It is reasonable to assume that an inhibition of PKL activity due to interaction with SARS-CoV N protein is likely to cause the death of the hepatocytes, which results in the elevation of serum alanine aminotransferase and liver dysfunction noted in most SARS patients. Thus, our results suggest that SARS-CoV could reduce pyruvate kinase activity via its nucleocapsid protein, and this may in turn cause disease.     

Magnetic resonance imaging study of mouse islet allotransplantation

Although only 10% of islet transplant recipients maintain insulin independence, 80% of them are C-peptide positive at 5 years. To better understand the fate of transplanted islets, a magnetic resonance imaging (MRI) technique has been used to detect superparamagnetic iron oxide (SPIO)–labeled transplanted islets. Recently, we successfully used a novel MRI contrast agent, chitosan-coated SPIO (CSPIO) nanoparticles, to monitor mouse islet isografts for 18 weeks after transplantation. In the present study, we tested whether CSPIO could be applied to monitor islet allografts, which are supposedly rejected without immune interventions. Male C57BL/6 and Balb/c mice were used as donors and recipients of islet transplantation, respectively. After overnight incubation with or without CSPIO (10 μg/mL), 300 C57BL/6 islets were transplanted under the left kidney capsule of each Balb/c mouse. Starting from day 10 after transplantation, 3.0-Tesla MRI of the recipients was performed weekly. Four mice were followed for ≥38 days. At 38 and 45 days, 1 islet graft was removed for insulin and Prussian blue staining, respectively. From days 10 to 45 after transplantation, CSPIO-labeled islet grafts were visualized on MRI scans as sustained distinct hypointense spots homogeneously located at the upper pole of left kidney, the site of transplantation. At days 38 and 45, the histology of CSPIO-labeled islet grafts revealed insulin and iron staining colocalized in the same areas. Our results in a mouse allotransplantation model indicated that CSPIO-labeled islets survived as long as 45 days with positive MRI.     

Postpartum mood disorders may be related to a decreased insulin level after delivery

Postpartum mood disorders are very frequent complications of delivery. The prevalence of postpartum blue syndrome is around 25% and that of postpartum depression is around 10%. These disorders greatly affect the well-being of these newly delivering mothers. Currently, the etiology of postpartum mood disorders is still unknown. Although many hormones have been investigated for their possible roles in postpartum mood disorders, the results are still inconclusive. Several studies have shown that insulin increases gradually during pregnancy. The level of insulin secretion may double by the third trimester. Insulin level reaches a maximum before delivery and returns to the level before pregnancy after delivery. The drop in the insulin level during the postpartum period appears to be more sudden and abrupt than the rise of insulin level during pregnancy. Recent studies have showed that insulin affects the secretion of serotonin in the brain. While serotonergic nervous system is well known for its important role in the development of mood disorders, decreased insulin level may induce mood disorders through the mechanism of affecting serotonin secretion in the brain. In the current paper, we propose that the rapid decrease in insulin level during the postpartum period may be one of the causes of postpartum mood disorders. If the hypothesis is valid, clinicians may be able to prevent postpartum mood disorders by carbohydrate-rich food during the postpartum period to stimulate the secretion of insulin. A carbohydrate-rich diet may also become an adjunctive therapy in the treatment of postpartum mood disorders according to the present hypothesis.     

WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells

Oxidative stress-responsive kinase (OSR) 1 and sterile20-related, proline-, alanine-rich kinase (SPAK) are Ste20p-related protein kinases that bind to the sodium, potassium, two chloride cotransporter, NKCC. Here we present evidence that the protein kinase with no lysine [K] (WNK) 1 regulates OSR1, SPAK, and NKCC activities. OSR1 exists in a complex with WNK1 in cells, is activated by recombinant WNK1 in vitro, and is phosphorylated in a WNK1-dependent manner in cells. Depletion of WNK1 from HeLa cells by using small interfering RNA reduces OSR1 kinase activity. In addition, depletion of either WNK1 or OSR1 reduces NKCC activity, indicating that WNK1 and OSR1 are both required for NKCC function. OSR1 and SPAK are likely links between WNK1 and NKCC in a pathway that contributes to volume regulation and blood pressure homeostasis in mammals.     

High strain-rate response of injectable PAA hydrogel

Hydrogel materials have been widely considered as potential soft tissue replacements because of their high permeability, hydrophilicity, and biocompatibility, as well as their low coefficient of friction. Injectable (thermo-responsive) hydrogels can provide support and cushioning at irregularly shaped disease sites, and are thus suitable for use in treating osteoarthritis or degenerative disc disease. However, while some injectable hydrogels have been proven to sustain human body weight during daily activities, their mechanical properties under harsh dynamic conditions have not been well documented. A specified injectable polyacrylic acid (PAA) hydrogel was prepared for this study. To simulate sudden impacts or unexpected shocks to the PAA hydrogel, the split Hopkinson pressure bar technique was utilized. The dynamic responses of various hydrogels at confined high strain rates (100–2590 s^?1) were presented. Hydrogel specimens with 3.37, 6.75, and 13.5% acrylic acid (AAc) concentrations were tested in the following three different material conditions: raw, phosphate-buffered saline (PBS) swollen, and PBS swollen with elevated temperature (37 °C). The dynamic bulk moduli of the hydrogels varied from 1.55 to 47.8 MPa depending on the given hydrogel’s AAc concentration and swollen condition.