Hepatic artery resistance in alcoholic liver disease.

Patency and direction of flow in portal veins and their branches are generally assessed by duplex Doppler ultrasonography (DDUS), whereas few data are available on hepatic arterial hemodynamics. In this study, resistive (RI) and pulsatility indexes (PI) were calculated at DDUS in 21 controls, 22 chronic alcoholic patients without evidence of liver damage, 19 patients with acute alcoholic hepatitis (AAH), 30 patients with chronic viral hepatitis (CVH), 23 patients with alcoholic cirrhosis, and 22 patients with viral-related cirrhosis. Diagnosis was based on clinical and histological findings. Mean +/- SD RI was similar in controls and CVH patients (0.64 +/- 0. 02 and 0.66 +/- 0.04, respectively), significantly decreased in alcoholic patients without liver damage and AAH patients (0.61 +/- 0. 07 and 0.60 +/- 0.07) (P < .05), and significantly increased in patients with alcoholic (0.72 +/- 0.04) and viral-related cirrhosis (0.74 +/- 0.04) (P < .05). It was <0.60 in 9 of the 19 AAH patients (47%) and 11 of the 22 alcoholic patients without liver damage (50%), and >0.70 in 39 of the 45 cirrhotic patients (87%) and 12 of the 71 noncirrhotic patients pooled together (17%). A significant correlation was observed between RI and PI (r = .83; P < .05). The coefficients of variation for intraobserver variability were 6.3% +/- 5.1% for RI and 10.1% +/- 6.2% for PI, and the corresponding figures for interobserver variability were 5.2% +/- 3.5% and 9.3% +/- 4.6%. These findings support the existence of ethanol-related hepatic arterial vasodilation in AAH and alcoholic patients without liver damage. Progression of liver damage from AAH to cirrhosis profoundly impairs the hepatic responsiveness as a consequence of fibrosis with vascular distortion.

Purification and characterization of N-acetylmuramoyl-L-alanine amidase from human serum.

Purification to homogeneity of the N-acetylmuramoyl-L-alanine amidase (mucopeptide amidohydrolase, EC 3.5.1.28) from human serum has been achieved with a high yield. By molecular sieving chromatography, a molecular weight of 120,000-130,000 has been found for the native enzyme. Polyacrylamide gel electrophoresis under native conditions gave a unique band of Mr = 125,000. The same technique performed under denaturing conditions revealed that the protein is a dimer composed of one subunit of Mr = 57,000 and another of Mr = 70,000. In isoelectrofocalization assays, the amidase behaved as an acidic protein. Ethylenediaminetetraacetate inhibited the enzyme activity; the Mg2+ requirement was confirmed. The simultaneous presence of sulfhydryl groups and disulfide bonds in the protein was evidenced by the inhibitions produced by different thiol-blocking reagents and by several thiol-bearing substances. Direct measurements established the presence of two accessible thiol groups and the occurrence of nine disulfide bonds per protein molecule. Studies of substrate hydrolyzing capacities showed a marked preference for the muramoyl tripeptide derived from the Escherichia coli or Bacillus cereus mureins, the disaccharide tetrapeptide and the bis disaccharide tetra-tetrapeptide from E. coli were also good substrates. Activities on small muropeptides of other composition are also reported. Whole (insoluble) peptidoglycans representing the main bacterial chemotypes were submitted to the enzyme action; although with weak specific activities, the human amidase was nevertheless able to release soluble peptides from some of them. A bacteriolytic capacity on some microorganisms cannot be excluded. Results are discussed and the human enzyme is compared to presently known microbial muramoyl amidases.