Serum paraoxonase 1 activity status in patients with liver disorders

Paraoxonase 1 [PON1] is an esterase, exclusively synthesized by liver. The present study has two objectives: to determine the PON1 activity status in various disorders associated with hepatocellular damage and to correlate the changes of PON1 activity with the standard liver function and fasting lipid profile tests in these disorders. The study groups consisted of 95 patients with liver diseases including acute viral hepatitis [14], cirrhosis with portal hypertension [33], leptospirosis [14], sepsis and multi organ failure [15], left ventricular failure [9], and falciparum malaria [10]; and 53 healthy controls. Serum PON1 activity was measured manually using spectrophotometer. Liver function test parameters and fasting lipid profile were performed in clinical chemistry auto analyzer [HITACHI 912]. The serum PON1 activity in patients with acute viral hepatitis and sepsis decreased significantly [P<0.001] and moderately in falciparum malaria [P<0.05]. However, in patients with cirrhosis, leptospirosis and left ventricular patients, its activity did not change significantly. On applying Pearson correlation, serum PON1 activity correlated positively with high-density lipoprotein-cholesterol [HDL-C] in patients with sepsis [r=0.633, P<0.05], left ventricular failure patients [r=0.814, P<0.05] and negatively with acute viral hepatitis patients [r=-0.528, P<0.05]. PON1 activity has decreased significantly in acute viral hepatitis, sepsis with multi organ failure and falciparum malaria patients. Determination of PON1 activity may serve as a useful additional test in assessing these conditions

Purine nucleotides reduce superoxide production by nitric oxide synthase in a murine sepsis model

Sepsis involves a systemic inflammatory response of multiple endogenous mediators, resulting in many of the injurious and sometimes fatal physiological symptoms of the disease. This systemic activation leads to a compromised vascular response and endothelial dysfunction. Purine nucleotides interact with purinoceptors and initiate a variety of physiological processes that play an important role in maintaining cardiovascular function. The purpose of the present study was to investigate the effects of ATP on vascular function in a lipopolysaccharide (LPS) model of sepsis. LPS induced a significant increase in aortic superoxide production 16 h after injection. Addition of ATP to the organ bath incubation solution reduced superoxide production by the aortas of endotoxemic animals. Reactive Blue, an antagonist of the P2Y receptor, blocked the effect of ATP on superoxide production, and the nonselective P2Y agonist MeSATP inhibited superoxide production. Nitric oxide synthase (NOS) inhibition by L-NAME blocked vascular relaxation and reduced superoxide production in LPS-treated animals. In the presence of L-NAME there was no ATP effect on superoxide production. A vascular reactivity study showed that ATP increased maximal relaxation in LPS-treated animals compared to controls. The presence of ATP induced increases in Akt and endothelial NOS phosphorylated proteins in the aorta of septic animals. ATP reduces superoxide release resulting in an improved vasorelaxant response. Sepsis may uncouple NOS to produce superoxide. We showed that ATP through Akt pathway phosphorylated endothelial NOS and “re-couples” NOS function.

Coagulase negative Staphylococci from blood cultures: contaminants or pathogens? / Estafilococos Coagulasa-Negativos de Cultivos de Sangre: ¿Contaminantes o Patógenos?

Detailed clinical data, underlying conditions, inflammatory indices and microbiological parameters in 60 patients who had pure growth of coagulase negative staphylococci from their blood culture specimens at the University Hospital of the West Indies, Jamaica, were analyzed and the clinical significance of the isolates ascertained using standard criteria. This study was undertaken between April and September 2003. The isolates were true pathogens of bloodstream infections in only 5 of the 60 patients (8.4). In the vast majority ie 44 of 60 (73.3) they were mere blood culture contaminants and in 11 (18.3), the clinical significance could not be ascertained Fifteen of the 44 patients (34) with contaminating coagulase negative staphylococci were treated with specific anti-staphylococcal antibiotics; 5 (11.4) with vancomycin. Although there has been a relative increase of coagulase negative staphylococcal infections including bloodstream infections in recent years, the organisms still remain the most common contaminants in blood cultures. Over 70of isolates were contaminants in this study which is similar to that in a number of such studies in other parts of the world The findings underline the need for careful evaluation of coagulase negative staphylococci isolated from blood cultures before instituting therapy to avoid unnecessary use of antibiotics, especially vancomycin, and the consequent increase of antibiotic resistance in hospitals.

Los datos clínicos detallados, las condiciones subyacentes, los índices inflamatorios así como los parámetros microbiológicos de 60 pacientes que presentaron crecimiento puro de estafilococos coagu-lasa-negativos de sus cultivos de sangre en el Hospital Universitario de West Indies, Jamaica, fueron sometidos a análisis. De este modo, se pudo determinar la significación clínica de los aislados, usando criterios estándar. En sólo 5 de los 60 pacientes (8.4%), los aislados resultaron ser realmente pató-genos de infecciones del torrente sanguíneo. En la gran mayoría, a saber 44 de 60 (73.3%), se trataba tan sólo de contaminantes en el cultivo de la sangre, y en 11 (18.3%) no pudo determinarse la impor-tancia clínica. Quince de los 44 pacientes (34%) con estafilococos coagulasa-negativos contaminantes, fueron tratados con antibióticos antiestafilocócicos específicos, y 5 (11.4%) con vancomicina. Aunque en años recientes ha habido un aumento relativo de infecciones por estafilococos coagulasa-negativos – incluyendo infecciones del torrente sanguíneo – los organismos siguen siendo todavía los contamin-antes más comunes en los cultivos de sangre. Más del 70% de los aislados resultaron ser contaminantes en este estudio: un resultado similar al obtenido en una serie de estudios de este tipo realizado en otras partes del mundo. Los hallazgos apuntan a la necesidad de realizar una evaluación cuidadosa de los estreptococos coagulasa-negativos aislados en los cultivos de sangre antes de proceder a instituir la terapia, a fin de evitar el uso innecesario de antibióticos – en especial la vancomicina – y el consiguiente aumento de la resistencia antibiótica en los hospitales.