D W Kimberlin — Page 2

PubMed1995

Modulation of expression of genes involved in the inflammatory response by lipopolysaccharide and temperature in cultured human astroglial cells.

In bacterial sepsis and meningitis, large concentrations of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) correlate directly with morbidity and mortality. This laboratory has reported previously that elevated temperature in the physiologic range is associated with down regulation of IL-1 beta and TNF alpha expression in cultured astroglia after lipopolysaccharide (LPS) stimulation. To further investigate the role of elevated temperature in the CNS inflammatory response, the effects of LPS and elevated temperature on the expression of genes that participate in the inflammatory response were determined in cultured transformed human fetal astrocytes and in an astrocytoma cell line. The effect of physiologic temperature elevation on cytokine concentrations in cerebrospinal fluid (CSF) was also investigated in a rabbit meningitis model. The findings indicate that astrocytes express a wide variety of cytokines, growth factors, growth factor receptors, and other genes that could play important roles in CNS inflammation. Furthermore, temperature elevation in the febrile range can lead to alterations in the patterns of expression of many genes involved in the inflammatory response of these cells.

Animals↗

PubMedDate not supplied

Advances in the treatment of neonatal herpes simplex infections.

Neonatal HSV disease is a potentially devastating illness with significant mortality and morbidity. Collaborative research efforts over the past 25 years have provided therapeutic options that were beyond hope just a generation ago. The use of high-dose acyclovir for the treatment of acute neonatal HSV disease has reduced mortality rates to their lowest level ever. Application of PCR to clinical specimens from neonates suspected of having neonatal HSV infection largely has eliminated the need to perform invasive brain biopsies, while at the same time providing a new tool with which to re-define the natural history of neonatal HSV disease. A limitation of PCR is the lack of standardisation in methodologies from laboratory to laboratory, which can impede a clinician's ability to interpret the PCR results. As such, all test results, including those from PCR, must be evaluated in the context of the patient's medical condition. Areas for continued research for further means of improvement in disease outcome include raising awareness of neonatal HSV disease so that the time between disease onset and the initiation of antiviral therapy can be shortened, as well as the evaluation of monoclonal antibodies as adjunctive therapy to high-dose acyclovir. Utilisation of suppressive oral acyclovir following acute neonatal disease is another therapeutic option under clinical investigation with the potential to improve morbidity outcomes of neonatal HSV disease survivors.

Acute Disease↗