- • protective role of PARP inhibitors in septic shock is likely to be more complex than merely • protective role of PARP inhibitors in septic shock is likely to be more complex than merely the regulation of NF-kB/Rel-dependent gene expression.
- • of the PI3-kinase - Akt/protein kinase B cytoprotective pathway is likely to contribute • of the PI3-kinase - Akt/protein kinase B cytoprotective pathway is likely to contribute to the protective effects of PARP inhibitors in shock and inflammation.

## Carboxy-PTIO On Hemodynamic And Blood Gas Changes

- • of LPS caused a marked decrease in mean arterial pressure (MAP), metabolic acidosis, • of LPS caused a marked decrease in mean arterial pressure (MAP), metabolic acidosis, and hypoxia. These effects were reversed by co-administration of carboxy-PTIO, without affecting other hemodynamic parameters. In control animals, neither hemodynamic nor blood gas parameters changed with or without carboxy-PTIO.
- • results indicate that carboxy-PTIO attenuates LPS-induced hypotension, metabolic • results indicate that carboxy-PTIO attenuates LPS-induced hypotension, metabolic acidosis, and hypoxia by scavenging excess NO from the circulation without affecting NO synthase (NOS) activity. An NO scavenger, carboxy-PTIO, may be preferable to non-selective NOS inhibitors for the treatment of human septic shock.

## Asymmetrical Dimethyl Arginine Levels

Overwhelming infection with resultant multiple organ failure, which has been termed the 'sepsis syndrome' , is a devastating illness with an incidence of 3 per 1,000 population per annum. It has been characterised as a dysregulation of inflammation in response to infection attributable to a combination of excessive inflammation, disseminated coagulopathy and disruption of the integrity of microvascular endothelium.

- • dimethyl arginine (ADMA) is an endogenous non-selective inhibitor of nitric oxide • dimethyl arginine (ADMA) is an endogenous non-selective inhibitor of nitric oxide synthase that may influence the severity of organ failure and the occurrence of shock secondary to an infectious insult. Levels may be genetically determined by a promoter polymorphism in a regulatory gene encoding dimethylarginine dimethylaminohydrolase II (DDAH II)
- • prospective observational study was designed, and 47 intensive care unit (ICU) patients with • prospective observational study was designed, and 47 intensive care unit (ICU) patients with severe sepsis and 10 healthy controls were enrolled. Serum ADMAand IL-6 were assayed on admission to the ICU and seven days later. Allelic variation for a polymorphism at position -449 in the DDAH II gene was assessed in each patient.
- • and Sequential Organ Failure Assessment scores were directly associated on day • and Sequential Organ Failure Assessment scores were directly associated on day one (p = 0.0001) and day seven (p = 0.002). The degree of acidaemia and lactaemia was directly correlated with ADMAlevels at both time points (p < 0.01). On day seven, IL-6 was directly correlated with ADMAlevels (p = 0.006). The variant allele with G at position -449 in the DDAH II gene was associated with increased ADMAconcentrations at both time points (p < 0.05).
- • of organ failure, inflammation and presence of early shock in severe sepsis are • of organ failure, inflammation and presence of early shock in severe sepsis are associated with increased ADMAlevels. ADMAconcentrations may be influenced by a polymorphism in the DDAH II gene.