Component 3 Levels Research Articles

Gender differences in postprandial ketone bodies in normolipidemic subjects and in untreated patients with familial combined hyperlipidemia.

An increased hepatic flow of free fatty acids (FFAs) is associated with impaired peripheral FFA trapping by malfunctioning of the complement component 3 (C3)/acylation-stimulating protein system and overproduction of VLDL in familial combined hyperlipidemia (FCHL). Postprandial ketone bodies reflect FFA oxidation in the liver, but the postprandial changes in male and female patients separately have not been determined yet. Gender differences in postprandial ketone bodies and C3 changes were investigated in normolipidemic patients and patients with untreated FCHL. Thirty-two normolipidemic patients (16 female and 16 male) and 19 patients with untreated normolipidemia (9 female and 10 male) underwent an oral fat-loading test. Total and incremental areas under the curves (AUC and dAUC, respectively) after the oral fat load were calculated. Triglyceride AUC was similar between genders in each group. Normolipidemic female subjects showed a higher levels of dAUC-hydroxybutyric acid than male subjects (1.37+/-0.49 and 0.98+/-0.43 mmol x h/L). In FCHL, a similar trend was observed in female (1.92+/-0.38) compared with male (1.55+/-0.87) subjects. In contrast to normolipidemia, FCHL did not show a postprandial increase in C3, although C3 was higher in FCHL. Women have higher postprandial ketone bodies than men, probably reflecting enhanced postprandial hepatic FFA oxidation. In FCHL, both genders have higher postprandial ketone bodies and therefore higher hepatic FFA delivery. The higher fasting and postprandial C3 levels in FCHL may reflect resistance of the C3/acylation-stimulating protein system to promote peripheral fatty acid trapping.

Delayed and exaggerated postprandial complement component 3 response in familial combined hyperlipidemia.

Very low density lipoprotein overproduction is the major metabolic characteristic in familial combined hyperlipidemia (FCHL). Peripheral handling of free fatty acids (FFAs) in vitro may be impaired in FCHL by decreased action of acylation-stimulating protein (ASP), which is identical to the immunologically inactive complement component 3a (C3adesArg). Because decreased FFA uptake by impaired complement component 3 (C3) response (as the precursor for ASP) may result in enhanced FFA flux to the liver in FCHL, we have evaluated postprandial C3 changes in vivo in FCHL patients. Accordingly, 10 untreated FCHL patients and 10 matched control subjects underwent an oral fat loading test. Fasting plasma C3 and ASP levels were higher in FCHL patients (1.33+/-0.09 g/L and 70.53+/-4.37 mmol/L, respectively) than in control subjects (0.91+/-0.03 g/L and 43.21+/-8.96 mmol/L, respectively; P=0.01 and P<0.05). In control subjects, C3 concentrations increased significantly after 4 hours (to 1.03+/-0.04 g/L). In FCHL, plasma C3 was unchanged after 4 hours. The earliest postprandial C3 rise in FCHL patients occurred after 8 hours (1.64+/-0.12 g/L). The maximal apolipoprotein B-48 concentration was reached after 6 hours in FCHL patients and control subjects. Postprandial FFA and hydroxybutyric acid (as a marker of hepatic FFA oxidation) were significantly higher in FCHL patients than in control subjects, and the early postprandial C3 rise was negatively correlated with the postprandial FFA and hydroxybutyric acid concentrations. The present data suggest an impaired postprandial plasma C3 response in FCHL patients, most likely as a result of a delayed response by C3, as the precursor for the biologically active ASP, acting on FFA metabolism. Therefore, an impaired postprandial C3 response may be associated with impaired peripheral postprandial FFA uptake and, consequently, lead to increased hepatic FFA flux and very low density lipoprotein overproduction.

Subcutaneous injected chitosan induces systemic activation in dogs

Systemic activation by subcutaneous administration of chitin, chitosan, and chitosan oligomer was investigated in dogs by determining the chemiluminescence (CL) response of circulating polymorphonuclear cells (PMN). Chitin (10 and 100mg/kg), chitosan oligomer (10mg/kg), latex beads (10mg/kg) and physiological saline (10ml) did not cause activation of PMN. However, chitosan caused systemic activation of PMN in a dose-dependent manner. The peak CL response of PMN was significantly increased in the 1 and 10mg/kg chitosan groups at 3 days after administration. In addition, chitosan (10mg/kg) prevented a decrease of the CL response in dogs given dexamethasone. Serum obtained from the 10mg/kg chitosan group significantly activated PMN from normal dogs. At 3 days after chitosan administration, the serum level of complement component 3 (C3) was increased about 1.6 times that of the prechitosan C3 level. In conclusion, subcutaneous administration of chitosan induces systemic activation of both PMN and serum.

Inflammatory Alterations in Muscle Contraction Headache

To investigate the pathophysiology of muscle contraction headache (MCH), several parameters of inflammation were evaluated in 48 patients suffering from MCH, and compared with 50 healthy control subjects: erythrocyte sedimentation rate; C-reactive protein; white blood cell count; immunoglobulin (Ig) G, A, M; and complement component 3(C3) and C4. Serum C3 and C4 levels were significantly elevated in MCH as compared to control subjects, but the other parameters did not differ significantly. This suggests that the inflammatory process may be involved in the production of MCH.

Activation of Classical Pathway Complement in Chronic Inflammation

Split products of complement component 3 (C3) and complement component 4 (C4) derived from activation of the alternative and classical complement pathways were measured in untreated outpatients, 20 with Crohn's disease and 19 with rheumatoid arthritis. Elevated levels of the d split product of C4 (C4d) were observed in 12 of 19 patients with rheumatoid arthritis and in 9 of 20 patients with Crohn's disease. Levels of the d split product of C3 (C3d) were increased in 14 of 19 patients with rheumatoid arthritis and in 6 of 20 Crohn's disease patients. The median values of C4d and C3d were significantly increased in both groups of patients. C3d concentrations correlated positively with C4d levels (rs = 0.51-0.56, p less than 0.005). The complement activation was not reflected in reduced plasma levels of native C3 and C4. The data indicate activation of the classical complement pathway in both rheumatoid arthritis and Crohn's disease.