Sepsis and multiple organ failure

Sepsis is a heterogeneous disease process. Individuals with severe sepsis frequently develop organ dysfunction and often require admission to critical care. The sepsis syndrome is generated by a complex interaction of pathogen and host inflammatory response. Progress has been made in recent years in understanding the highly complex nature of the host response in sepsis. Prompt recognition of the sepsis syndrome, aggressive resuscitation, source control and early antibiotic therapy are key steps in treating severe sepsis and ameliorating the multiple organ dysfunction which frequently complicates it.     

Fluorescent Cell Chip a new in vitro approach for immunotoxicity screening

The Fluorescent Cell Chip (FCC) has been developed specifically for immunotoxicity screening of chemical compounds. This in vitro test is based on a panel of genetically modified reporter cell lines that regulate the expression of fluorescent protein in the same way as they regulate expression of cytokines. Thus, changes in fluorescence intensity represent changes in cytokine expression. Consequently, this technique conforms to efficiency expected from high throughput screening assay. In a pre-validation effort we analyzed 46 compounds. The experimental protocol employed five reporter cell lines derived from murine EL-4 T cells. Reporter cells were exposed to tested chemicals on a 96 well plate and analyzed for EGFP-mediated fluorescence using automated flow cytometric assay. Tested compounds reproducibly generated compound-specific patterns of changes in fluorescence that allows for the hierarchical clustering of their expected activities based on pattern similarity analysis. Resultant classification revealed correlation with available in vivo immunotoxicity data. In conclusion, FCC is a new promising approach for in vitro screening of chemicals for their immunotoxicity.     

Increased frequency of multiradial chromosome structures in mouse embryonic fibroblasts lacking functional Werner syndrome protein and poly(ADP-ribose) polymerase-1

To determine whether the mouse Werner syndrome homologue (Wrn) and the poly (ADP-ribose) polymerase-1 (PARP-1) enzymes act in concert to prevent specific chromosomal rearrangements, mice with a mutation in the helicase domain of the Wrn gene (Wrn(Deltahel/Deltahel) mice) were crossed to PARP-1 null mice. Spectral karyotyping of the mouse metaphases was used in correlation with conventional G-banded karyotype analysis to precisely define the chromosomal aberrations in cells. Although there was no recurrent clonal chromosome aberration, PARP-1 null/Wrn(Deltahel/Deltahel) fibroblasts were distinguished by an increased frequency of chromatid breaks. Interestingly, multiradial structures were the only type of DNA rearrangement that was significantly higher in such PARP-1 null/Wrn(Deltahel/Deltahel) cells. These results indicate that Wrn and PARP-1 enzymes may be part of a protein complex involved in the processing of DNA breaks that can ultimately lead to multiradial structures when both enzymes are nonfunctional. Finally, regions of chromosomes known to be fragile sites in the mouse genome are not more prone to DNA rearrangements in the absence of both PARP-1 and functional Wrn proteins. Moreover, the low number of recurrent rearranged chromosome at any given site suggest a random mutagenesis process in PARP-1 null/Wrn(Deltahel/Deltahel) fibroblasts.     

Automatic identification and normalization of dosage forms in drug monographs

Background

In April 2010, with an endorsement from the Ministry of Health of the People's Republic of China, the Chinese Society of Nephrology launched the first nationwide, web-based prospective renal data registration platform, the Chinese Renal Data System (CNRDS), to collect structured demographic, clinical, and laboratory data for dialysis cases, as well as to establish a kidney disease database for researchers and policy makers.

Methods

The CNRDS program uses information technology to facilitate healthcare professionals to create a blood purification registry and to deliver an evidence-based care and education protocol tailored to chronic kidney disease, as well as online forum for communication between nephrologists. The online portal https://www.cnrds.net is implemented as a Java web application using an Apache Tomcat web server and a MySQL database. All data are stored in a central databank to establish a Chinese renal database for research and publication purposes.

Results

Currently, over 270,000 clinical cases, including general patient information, diagnostics, therapies, medications, and laboratory tests, have been registered in CNRDS by 3,669 healthcare institutions qualified for hemodialysis therapy. At the 2011 annual blood purification forum of the Chinese Society of Nephrology, the CNRDS 2010 annual report was reviewed and accepted by the society members and government representatives.

Conclusions

CNRDS is the first national, web-based application for collecting and managing electronic medical records of patients with dialysis in China. It provides both an easily accessible platform for nephrologists to store and organize their patient data and acts as a communication platform among participating doctors. Moreover, it is the largest database for treatment and patient care of end-stage renal disease (ESRD) patients in China, which will be beneficial for scientific research and epidemiological investigations aimed at improving the quality of life of such patients. Furthermore, it is a model nationwide disease registry, which could potentially be used for other diseases.