Evidence for altered hepatic matrix degradation in genetic haemochromatosis.

BACKGROUND: Altered matrix degradation contributes to fibrosis in some liver diseases but the role of matrix degradation in fibrogenesis associated with genetic haemochromatosis has not previously been addressed. AIMS: To measure serum concentrations of tissue inhibitor of metalloproteinase 1 (TIMP-1) and matrix metalloproteinases (MMP), MMP-1, MMP-2, and MMP-3 in patients with haemochromatosis and control subjects. PATIENTS: Forty patients with haemochromatosis and 19 healthy control subjects. Ten of the 40 patients were studied before and after venesection therapy. METHODS: Serum levels of TIMP-1, MMP-1, MMP-2, and MMP-3 were measured by enzyme immunoassay and correlated to hepatic iron concentration and degree of histological fibrosis. RESULTS: Serum TIMP-1 was increased in patients with haemochromatosis compared with controls (163 (30) versus 123 (28) ng/ml, p < 0.0002). Mean serum TIMP-1 concentration of patients with haemochromatosis without fibrosis was significantly higher than in controls (153 (16) versus 123 (28) ng/ml, p = 0.03). Serum TIMP-1 concentration correlated with both hepatic iron concentration and hepatic iron index (r = 0.42, p < 0.01; r = 0.42, p < 0.01). Serum MMP-2 concentrations correlated with increasing degree of fibrosis in patients with haemochromatosis (r = 0.38, p = 0.01). The mean MMP-1: TIMP-1, MMP-2:TIMP-1 and age/sex matched MMP-3:TIMP-1 ratios were significantly lower in patients with haemochromatosis than controls (0.11 (0.06) versus 0.2 (0.14), p = 0.02; 3.32 (0.9) versus 3.91 (0.81), p = 0.05; and 0.26 (0.12) versus 0.47 (0.27), p = 0.007, respectively). Following venesection, MMP-2 and MMP-3 concentrations increased by 11% (p = 0.03) and 19% (p = 0.03), respectively. CONCLUSIONS: This study provides the first evidence of an alteration in matrix degradation in haemochromatosis that may be a contributing factor to hepatic fibrogenesis in this disease.

Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis.

BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease that occasionally progresses to cirrhosis but usually has a benign course. The aim of this study was to investigate the role of the hemochromatosis mutation Cys282Tyr in development of the mild hepatic iron overload found in some patients with NASH and its association with hepatic damage in these patients. METHODS: Fifty-one patients with NASH were studied. The presence of the Cys282Tyr mutation was tested in all patients, and the data were analyzed with respect to the histological grade of steatosis, inflammation, Perls' staining, hepatic iron concentration (HIC), and serum iron indices. RESULTS: Thirty-one percent of patients with NASH were either homozygous or heterozygous for the Cys282Tyr mutation. This mutation was significantly associated with Perls' stain grade (P < 0.005), HIC (P < 0.005), and transferrin saturation percentage (P < 0.005) but not with serum ferritin levels. Linear regression analysis showed that increased hepatic iron (Perls' stain or HIC) had the greatest association with the severity of fibrosis (P < 0.0001). CONCLUSIONS: The Cys282Tyr mutation is responsible for most of the mild iron overload found in NASH and thus has a significant association with hepatic damage in these patients. Heterozygosity for the hemochromatosis gene mutation therefore cannot always be considered benign.

Early expression of hereditary deep pectoral myopathy in turkeys due to forced wing exercise.

In a deep pectoral myopathy selected (DPMS) line, forced wing exercise (FWE) at 20 weeks of age resulted in the same level of expressed deep pectoral myopathy (DPM) as seen in unexercised DPMS turkey by 72 weeks of age. The FWE at 15 and 17 weeks of age in DPMS line females increased the incidence of DPM to 30 and 50% compared to 5% in unexercised controls. There is an apparent developmental age X exercise relationship in the expression of DPM. In varieties, lines, and crosses without a history of DPM, FWE does not induce the myopathy. Additional evidence confirms the modifier effect in the polygenic DPM defect. Body weight and breast width measurements in genetically susceptible turkeys were not closely or consistently associated with expression of the myopathy. The results suggest FWE of turkeys at 20 weeks of age or later as a method for detecting genetic carriers at prebreeding ages.

Acanthocephalan parasitism in the Western Bluebird (Sialia mexicana).

Acanthocephalan parasites of the species Plagiorhynchus (Prosthorhynchus) formosus Van Cleave, 1918, were recovered from the intestinal tracts of two male and two female wild Western Bluebirds (Sialia mexicana). Parasitism by P. formosus was considered to be a contributory cause of death of these breeding adult bluebirds. This is the first reported recovery of acanthocephalan parasites from Western Bluebirds.