Correlation of sweat chloride concentration with genotypes in cystic fibrosis patients in Saguenay Lac-Saint-Jean, Quebec, Canada.
De Braekeleer M. Allard C. Leblanc JP. Aubin G. Simard F.
Departement des Sciences Humaines, Universite du Quebec a Chicoutimi, Canada.
OBJECTIVES: Saguenay Lac-Saint-Jean, a geographically isolated region of northeastern Quebec has a high incidence of cystic fibrosis (CF) and three mutations only account for 94% of the CF chromosomes. The objective of the present study was to determine whether different mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene had different effects upon the sweat chloride concentration. DESIGN AND METHODS: The sweat chloride concentration of 114 patients was measured by quantitative pilocarpine iontophoresis. RESULTS: CF patients carrying the A455E mutation, usually associated with pancreatic sufficiency, had lower sweat chloride concentrations than those carrying mutations associated with pancreatic insufficiency (delta F508 and 621 + 1G-->T). CONCLUSIONS: Our results confirm that mutations resulting in a reduction of the chloride current at the apical membrane of epithelial cells induce lower sweat chloride values. However, there are differences in the chloride current between genotypes, even if they are composed of mutations apparently having the same functional effect.
Effects of antihypertensive drugs on cholesterol metabolism of human mononuclear leukocytes and hepatoma cells.
Naegele H. Behnke B. Gebhardt A. Strohbeck M.
Abt. fur Herzchirurgie, Universitats-Krankenhaus Eppendorf, Hamburg, Germany.
OBJECTIVES: Primary prevention trials of antihypertensive therapy have shown conflicting results on coronary events. Potential interference of antihypertensive agents with cellular lipid metabolism may alter the atherosclerotic risk of individuals. DESIGN AND METHODS: The effects of the calcium antagonist's verapamil, diltiazem, and nifedipine and of the beta-blockers propranolol and metoprolol on low density lipoprotein (LDL) receptor activity, cholesterol esterification rate, oleate incorporation in triglycerides and sterol synthesis were studied in freshly isolated human leukocytes and HEP G2 cells. RESULTS: Up to a concentration of 3-10 mumol/L, verapamil, propranolol, and metoprolol led to an increased cellular content of 125I-LDL by an inhibition of degradation. In mononuclear cells verapamil stimulated accumulation and degradation. No effect on binding was observed. Diltiazem was only stimulatory on 125I-LDL processing in leukocytes. Beta blockers and verapamil significantly reduced the LDL mediated 14C-oleate incorporation in cholesterol esters. In the presence of 25-hydroxycholesterol the esterification was not diminished, which suggests that cholesterolacyltransferase (ACAT) was not affected per se. Whereas all the agents induced the synthesis of lanosterol, metoprolol inhibited cholesterol synthesis. None of the agents had a significant influence on 14C-oleate incorporation in triglycerides, suggesting a specific influence on cholesterol metabolism. CONCLUSIONS: Antihypertensive drugs affect the cholesterol metabolism on a cellular level. Mechanisms are an interference with degradation of LDL and consequent alterations of cholesterol esterification. Using leukocytes as peripheral cells and HEP G2 as a model of human liver, these results may have importance when antihypertensive long-term therapy is conducted for primary or secondary prevention of atherosclerotic complications.
Surgical trauma induces group II phospholipase A2 production by neutrophils at a local site after surgery.
Abe T. Sakamoto K. Mita S. Kamohara H. Hirano Y. Kuwahara N. Ogawa M.
Department of Surgery II, Kumamoto University School of Medicine, Japan.
OBJECTIVES: Group II phospholipase A2 (PLA2) regulates eicosanoids and platelet activating factor (PAF) production and plays an important role in regulating critical mediators in inflammatory diseases such as trauma, sepsis and multiple organ failure. To elucidate the local effect of surgical trauma, we investigated the production of group II PLA2 at a local site after surgery. DESIGN AND METHODS: We utilized a radioimmunoassay to measure group II PLA2 levels in peritoneal exudates from the operative field and blood in patients who underwent gastrectomy. We also investigated the production of group II PLA2 in cells from peritoneal exudates by Northern blotting and immunocytochemistry. RESULTS: Immunoreactive group II PLA2 levels were significantly increased from 3 h after surgery and peaked at 12 h peritoneal exudates. However, serum group II PLA2 levels peaked at 24-48 h and decreased gradually after surgery, findings similar to levels of postoperative serum C-reactive protein (CRP). There was no significant correlation between group II PLA2 levels in peritoneal exudates and those in blood. Group II PLA2 mRNA was expressed at high level in cells from peritoneal exudates, by Northern blot analysis, but not those from blood. The localization of group II PLA2 protein was intense in neutrophils, as determined by immunocytochemistry. No group II PLA2 expression was observed in corresponding peripheral blood cells. CONCLUSIONS: After surgery, group II PLA2 is increased in peritoneal exudates prior to elevation in the blood circulation and is produced by neutrophils recruited and activated at a local site. Group II PLA2 produced in peritoneal exudates by neutrophils has an important role in the physiological and pathological states at a local site, after surgery.
Increased retinol binding protein in the sera of patients with severe ischemic damage of the liver after transplantation.
Mastroianni A. Regalia E. Facchetti G. Longoni PD. Formelli F. Pulvirenti A. Mazzaferro V.
Division of Clinical Chemistry and Microbiology, National Cancer Institute, Milano, Italy.
OBJECTIVE: To study retinol binding protein variation in the serum of patients who have undergone liver transplantation. METHODS: Retinol binding protein was retrospectively determined by the immunonephelometric method on serum from 14 patients who had undergone orthotopic liver transplantation 2 weeks after the surgery and then once a month during the first year posttransplantation. The patients were divided into two groups on the basis of early (first 10 days) postoperative graft function: group I, 6 patients with severe ischemic damage; and II 8 patients with moderate-severe liver dysfunction. RESULTS: The men retinol binding protein level at one year of follow-up was persistently higher in group I than in group II (83.1 +/- 33.4 vs 44.6 +/- 20.7 mg/L, p < 0.001). Interestingly, retinol binding protein levels remained higher in patients of group I event when the other biochemical parameter of liver function returned to normal. The increase in retinol binding protein serum levels was independent of variation in other parameters of liver and kidney function, but was correlated with an increase in transthyretin and retinol levels. CONCLUSION: Our results show a close relationship between a permanent high retinol binding protein level and severe graft injury after liver transplantation. However, the mechanism underlying the increase remains to be defined.