Antibiotic Therapy, Endotoxin Concentration in Cerebrospinal Fluid, and Brain Edema in Experimental Escherichia coli Meningitis in Rabbits

We investigated the effect of cefotaxime and chloramphenicol on endotoxin concentrations in cerebrospinal fluid (CSF) and on the development of brain edema in rabbits with Escherichia coli meningitis. Both antibiotics were similarly effective in reducing bacterial titers. Cefotaxime, but not chloramphenicol, induced a marked increase of endotoxin in CSF, from log10 1.5 ± 0.8 to log10 2.8 ± 0.7 ng/ml (P < .01). This result was associated with an increase in brain water content (405 ± 12 g of water/100 g of dry weight compared with 389 ± 8 g in untreated controls; P < .01), whereas in animals treated with chloramphenicol, brain water content was identical to controls. The cefotaxime-induced increase in endotoxin concentration and brain edema were both neutralized by polymyxin B, which binds to the lipid A moiety of endotoxin, or by a monoclonal antibody to lipid A. These results indicate that treating gram-negative bacillary meningitis with selected antibiotics induces increased endotoxin concentrations in CSF that are associated with brain edem

Debt Maturity Choices, Multi-stage Investments and Financing Constraints

We develop a dynamic investment options framework with optimal capital structure and analyze the effect of debt maturity. We find that in the absence of financing constraints short-term debt maximizes firm value. In contrast with most literature results, in the absence of constraints, higher volatility may increase initial debt for firms with low initial revenues, issuing long term debt that expires after the investment option maturity. This effect, which is due to the option value of receiving the value of assets and remaining tax savings, does not hold for short term debt and firms with high profitability, where an increase in volatility reduces the firm value. The importance of short-term debt is reduced in the presence of non-negative equity net worth or debt financing constraints and firms behave more conservatively in the use of initial debt. With non-negative equity net worth, higher volatility has adverse effects on the firm value, while with debt financing constraints higher volatility may enhance firm value for firms with relatively low revenue that have out-of-the-money investment options

Phosphorylation of Ubc9 by Cdk1 Enhances SUMOylation Activity

Increasing evidence has pointed to an important role of SUMOylation in cell cycle regulation, especially for M phase. In the current studies, we have obtained evidence through in vitro studies that the master M phase regulator CDK1/cyclin B kinase phosphorylates the SUMOylation machinery component Ubc9, leading to its enhanced SUMOylation activity. First, we show that CDK1/cyclin B, but not many other cell cycle kinases such as CDK2/cyclin E, ERK1, ERK2, PKA and JNK2/SAPK1, specifically enhances SUMOylation activity. Second, CDK1/cyclin B phosphorylates the SUMOylation machinery component Ubc9, but not SAE1/SAE2 or SUMO1. Third, CDK1/cyclin B-phosphorylated Ubc9 exhibits increased SUMOylation activity and elevated accumulation of the Ubc9-SUMO1 thioester conjugate. Fourth, CDK1/cyclin B enhances SUMOylation activity through phosphorylation of Ubc9 at serine 71. These studies demonstrate for the first time that the cell cycle-specific kinase CDK1/cyclin B phosphorylates a SUMOylation machinery component to increase its overall SUMOylation activity, suggesting that SUMOylation is part of the cell cycle program orchestrated by CDK1 through Ubc9

Default risk, state ownership and the cross-section of stock returns: evidence from China

We apply a structural model to estimate firm-level default risk in China and investigate the stock return predictability of default risk and the moderating effects of state ownership for the sample period from 2003 to 2015. We show unique evidence that in China, default risk is positively associated with expected stock returns and state ownership matters considerably to the return predictability of default risk. We find investors of state-owned enterprises (SOEs) are not compensated appropriately in China despite of their higher default risk exposure. Our empirical evidence supports the conjecture on shareholder advantages and suggests that a strong bargaining power of equity holders would have a negative impact on stock returns

Medication errors and patient complications with continuous renal replacement therapy

Continuous renal replacement therapy (CRRT) is commonly used for renal support in the intensive care unit. While the risk of medication errors in the intensive care unit has been described, errors related specifically to CRRT are unknown. The purpose of this study is to characterize medication errors related to CRRT and compare medication errors that occur with manually compounded solutions versus commercially available solutions. We surveyed three separate internet-based, pediatric list serves that are commonly used for communications for programs utilizing CRRT. Data regarding CRRT practices and medication errors were recorded. Medication errors were graded for degree of severity and compared between programs using manually compounded dialysis solutions versus commercially available dialysis solutions. In a survey with 31 program responses, 18 reported medication errors. Two of the 18 were related to heparin compounding, while 16/18 were due to solution compounding errors. Half of the medication errors were classified as causing harm, two of which were fatal. All medication errors were reported by programs that manually compounded their dialysis solutions. Medication errors related to CRRT are associated with a high degree of severity, including death. Industry-based, commercially available solutions can decrease the occurrence of medication errors due to CRRT.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45869/1/467_2006_Article_49.pd