Excessive tryptophan catabolism along the kynurenine pathway precedes ongoing sepsis in critically ill patients.

It has recently been shown that an increased plasma level of the tryptophan catabolite kynurenine is an early indicator for the development of sepsis in major trauma patients. We examined the predictive value of kynurenine pathway activity for ongoing sepsis in patients being admitted to a surgical intensive care unit for different reasons. In addition, we asked whether an accumulation of kynurenines in patients' plasma depends on reduced renal clearance. We conducted a prospective observational study including 100 consecutive patients and monitored laboratory variables, physiological and adverse events, sepsis and outcome. Using tandem mass spectrometry, we quantified the five indoleamines tryptophan, serotonin (5-HT), kynurenine, quinolinic acid and kynurenic acid at baseline and twice a week during the intensive care unit stay. Among the patients enrolled, 50 did not develop sepsis in the intensive care unit (non-septic), 18 patients did not have sepsis at baseline but developed sepsis later on (pre-septic) and 32 patients already fulfilled the criteria of severe sepsis and septic shock at baseline (septic). In general, non-septic critically ill patients showed activation of the kynurenine pathway, but septic shock coincided with an exacerbation of kynurenine pathway activity even in the absence of renal failure. Importantly, plasma concentrations of quinolinic acid (area under the curve 0.832 [95% confidence interval 0.710 to 0.954]) and the Quin/Trp ratio (area under the curve 0.835 [95% confidence interval; 0.719 to 0.952]) showed the best discrimination between non-septic and pre-septic patients at baseline. These findings open new avenues for further investigations on the pathophysiology of sepsis.

A novel acute phase marker in cattle: lipopolysaccharide binding protein (LBP).

The host response to infection, the "acute phase response" is a highly conserved series of physiological reactions including marked changes in concentrations of plasma proteins. These proteins have been shown to participate in the immune response to infections. Several recent studies have elevated the role of acute phase proteins (APPs) as predictive markers in infection. APPs such as serum amyloid A and haptoglobin but not C-reactive protein (CRP) have been identified as markers of inflammation in cattle. In humans, lipopolysaccharide (LPS) binding protein (LBP) has certain biological functions in host defence and participates in acute phase reactions. We measured plasma levels of LBP in a group of 20 calves experimentally infected with Gram-negative Mannheimia haemolytica (Pasteurella) in comparison to haptoglobin, the most widely studied APP in cattle. In infected calves, LBP levels rose significantly 6 h after infection, reaching a maximum at 24 h. Haptoglobin concentrations significantly rose after 12 h, and peak responses were measured 48 h after infection. Thus, LBP may prove to be a diagnostic marker in cattle infection and is faster than haptoglobin in detecting sepsis.

Sindrome de Werner. (Presentacion de un caso y actualizacion del tema). / Werners syndrome. (Presentation of a case and subject updating)

Se estudia una paciente de 37 anos con las caracteristicas de un sindrome de Werner: cataratas, canicie precoz, esclerosis, hiperqueratosis y pigmentacion cutanea. Cambios de voz, osteoporosis, calcificaciones tendinosas, hipogenitalismo, alteracion del test de tolerancia a la glucosa, dislipoidosis, hiperreflexia profunda generalizada, baja estatura, facies y proporciones corporales propias del mismo. Se efectua una revision de hallazgos experimentales y posible explicacion patogenica del sindrome y otros caracterizados por senilidad precoz, cuyos diagnosticos diferenciales son resumidos

Sindrome de Werner. (Presentacion de un caso y actualizacion del tema). / Werner's syndrome. (Presentation of a case and subject updating)

Se estudia una paciente de 37 anos con las caracteristicas de un sindrome de Werner: cataratas, canicie precoz, esclerosis, hiperqueratosis y pigmentacion cutanea. Cambios de voz, osteoporosis, calcificaciones tendinosas, hipogenitalismo, alteracion del test de tolerancia a la glucosa, dislipoidosis, hiperreflexia profunda generalizada, baja estatura, facies y proporciones corporales propias del mismo. Se efectua una revision de hallazgos experimentales y posible explicacion patogenica del sindrome y otros caracterizados por senilidad precoz, cuyos diagnosticos diferenciales son resumidos