Preliminary assessment of glycine conjugation of para-aminobenzoic acid as a quantitative test of liver function.

OBJECTIVES: Our hypothesis is that because of its hepatic metabolism paraaminobenzoic acid (PABA) could be a test of liver function. DESIGN AND METHODS: PABA is well absorbed by the gastrointestinal tract and acetylated and conjugated in the liver to glycine before being excreted. Its three major metabolites include para-acetoamidobenzoic acid (PAABA), paraaminohippuric acid (PAHA), and paraacetamidohippuric acid (PAAHA). In this study, we measured the metabolism of lidocaine to monoethylglycinexylidide (MEGX) and PABA to PAHA+PAAHA/PABA+PAABA+PAHA+PAAHA (hippurate ratio) in 14 patients with liver disease and 12 control subjects. RESULTS: Comparison of the total bilirubin with the hippurate ratio (at 30 min) and the conventional MEGX test (at 15 min) was assessed. The 30 min hippurate ratio correlated well with the 15 min MEGX results (r = 0.69). CONCLUSIONS: While these results are preliminary the PABA test appears to be equally sensitive to MEGX and has the distinct advantage over the MEGX test of being administered orally versus the intravenous administration of lidocaine which is often associated with unwanted side-effects such as hypotension, drowsiness and paresthesias.

Evidence for hydroxyl radical involvement in group B streptococcus-induced pulmonary hypertension and arterial hypoxemia in young piglets.

Early onset neonatal GBS infection is associated with pulmonary hypertension, pulmonary edema, and arterial hypoxemia. Although the mechanisms underlying these cardiopulmonary disturbances are not completely understood, multiple lines of evidence suggest that inflammatory mediators may be involved. This study examined the actions of dimethylthiourea (DMTU), a relatively selective scavenger of hydroxyl radical, on GBS-induced pulmonary hypertension, arterial hypoxemia, and pulmonary edema formation in young piglets. Relative to control animals, intravenous infusion of GBS (10(8) organisms/kg/min for 60 min) provoked sustained increases in pulmonary arterial pressure (Ppa: +88%) and total pulmonary resistance (TPR: 128%). GBS infusion also was associated with profound decreases in arterial PO2 (-58%). Pulmonary edema was present in GBS-treated animals as evidenced by an 8.4% increase in the lung wet-to-dry weight ratio. After pretreatment with DMTU (0.75 g/kg administered intravenously over 30 min), GBS increased Ppa by 33% and TPR by only 16%. Similarly, after DMTU pretreatment GBS decreased arterial oxygen tension by only 12%. DMTU also limited the GBS-induced increase in lung wet-to-dry weight ratio to 2.6%. These findings demonstrate that DMTU attenuates GBS-induced pulmonary hypertension, pulmonary edema, and arterial hypoxemia and suggest that hydroxyl radicals play an important role in these cardiopulmonary disturbances.

In vitro cytocidal effect of novel lytic peptides on Plasmodium falciparum and Trypanosoma cruzi.

Plasmodium falciparum and Trypanosoma cruzi were killed by two novel lytic peptides (SB-37 and Shiva-1) in vitro. Human erythrocytes infected with P. falciparum, and Vero cells infected with T. cruzi, were exposed to these peptides. The result, in both cases, was a significant decrease in the level of parasite infection. Furthermore, the peptides had a marked cytocidal effect on trypomastigote stages of T. cruzi in media, whereas host eukaryotic cells were unaffected by the treatments. In view of the worldwide prevalence of these protozoan diseases and the lack of completely suitable treatments, lytic peptides may provide new and unique chemotherapeutic agents for the treatment of these infections.