Clearance Of Alpha Research Articles

Faecal alpha-1-antitrypsin and excretion of 111indium granulocytes in assessment of disease activity in chronic inflammatory bowel diseases.

Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with eight patients with non-inflammatory bowel diseases, or 19 healthy volunteers. There was wide range of overlap between active and inactive inflammatory disease. Contrary to serum alpha 1-AT, faecal excretion and clearance of alpha 1-AT did not correlate with ESR, serum-albumin, orosomucoid, and two indices of disease activity. A comparison of alpha 1-AT faecal excretion and clearance with the faecal excretion of 111In labelled granulocytes in 27 patients with chronic inflammatory bowel diseases, showed no correlation between the intestinal protein loss and this highly specific marker of intestinal inflammation. Enteric protein loss expressed by faecal excretion and clearance of alpha 1-AT does not depend on mucosal inflammation only, but may be influenced by other factors.

Physiology of ileoanal anastomosis with ileal reservoir for ulcerative colitis and adenomatosis coli.

A physiologic and metabolic assessment was carried out on eight patients six months after total proctocolectomy with ileal reservoir for ulcerative colitis and familial adenomatosis coli. All patients were continent and able to defecate spontaneously, stool frequency ranging from two to five per 24 hours. Anal sphincter resting pressures (35 +/- 14 mmHg) and squeeze pressures (88 +/- 24.2 mmHg) were similar to those of a healthy population, with the exception of one patient's complaint of nocturnal mucous leakage per anus. Biopsies of the ileal mucosa of the reservoirs showed a mild inflammation in seven patients; in one a subtotal villous atrophy (plus glandular pattern) was found. Anthropometric measurements, lymphocyte counts, hemoglobin, albumin, transferrin, iron, B12, and folate were normal in all. In the majority of patients there was no evidence of bacterial overgrowth. Vitamin B12 absorption was reduced slightly in only one patient. Lipid absorption (as judged by the 14C-Triolein breath test) was abnormal in three patients. Fecal clearance of alpha 1 antitrypsin as protein losses index was abnormal in three patients. Bile acid malabsorption was the most important ileal dysfunction observed in the patients.

Increased Intestinal Clearance of $aP1-Antitrypsin in Patients with $aP1-Antitrypsin Deficiency

To evaluate the possible contribution of enteric losses of alpha 1-antitrypsin (alpha 1-AT) to the low serum levels of alpha 1-AT seen in patients with alpha 1-AT deficiency, we investigated intestinal clearance of alpha 1-AT (C-alpha 1-AT) in five of these patients (mean age 3.4 years) and compared it to that of 10 patients (mean age 3.7 years) with gastrointestinal disorders and normal serum albumin values who served as controls. C-alpha 1-AT was also determined in four patients (mean age 9 months) with noncirrhotic liver disease. The percent of daily alpha 1-AT turnover which could be attributed to stool losses was calculated in these groups of patients. alpha 1-AT was measured in stool and serum by radial immunodiffusion and the clearance calculated. The mean C-alpha 1-AT in the patients with alpha 1-AT deficiency was significantly (p less than 0.05) higher than that of the controls. The liver disease patients had values for C-alpha 1-AT in the range of the controls. Three of the alpha 1-AT deficiency patients had values for C-alpha 1-AT greater than the mean plus 3 SD of the control, but these were not in the range seen in patients with protein losing enteropathy. Mean percent contribution of stool losses to total daily alpha 1-AT turnover was similar in all three groups. We conclude that patients with alpha 1-AT deficiency have increased fecal clearance of alpha 1-AT seemingly unrelated to the liver disease, but that this is not a major cause of the low serum levels.

Clearance and binding of two electrophoretic “fast” forms of human alpha 2-macroglobulin.

These studies explore the role of conformational change and exposed carbohydrate residues in the clearance of alpha 2-macroglobulin-trypsin (alpha 2M-T) complexes in the mouse. Human alpha 2-macroglobulin (alpha 2M) was purified and demonstrated to be homogeneous in the electrophoretic "slow" form. Two conformationally altered derivatives, alpha 2M-T and alpha 2-macroglobulin-methylamine (alpha 2M-MeNH2), were prepared and demonstrated to exist in the electrophoretic "fast" form. Radiolabeled alpha 2M-T and alpha 2M-MeNH2 were cleared rapidly with a half-life of 2-4 min following injection into mice. Radiolabeled native alpha 2M, however, remained in the circulation with a half-life of several hours. Both alpha 2M-T and alpha 2M-MeNH2 bound specifically to mouse peritoneal macrophages at 4 degrees C and occupancy of receptor sites increased with increasing time and radioligand concentration. Excess amounts of unlabeled alpha 2M-T or alpha 2M-MeNH2 cross-completed with trace amounts of the other in both clearance studies and binding assays, indicating that both derivatives were removed by the same receptor pathway. The clearance and binding of alpha 2M-T and alpha 2M-MeNH2 were not inhibited by excess amounts of unlabeled asialoorosomucoid, fucosyl-bovine serum albumin, mannosyl-BSA, or N-acetylglucosaminyl-BSA. Our results indicate that the clearance pathway removing alpha 2M-T complexes from the circulation recognizes a fundamental conformational change in alpha 2M secondary to protease binding, which can also be induced by exposure to methylamine. Therefore, other chemical or physical alterations that occur in alpha 2M upon binding trypsin, apart from the conformational change also present in alpha 2M-MeNH2, do not seem necessary for the recognition of alpha 2M-T by cells in the clearance pathway. In addition, this pathway appears distinct from several systems already described mediating clearance of glycoproteins through recognition of terminal galactose, fucose, N-acetylglucosamine, or mannose on oligosaccharide side chains.