Mild oxidation of human serum low-density lipoprotein (LDL) converts the apoprotein from a nearly homogeneous component of high apparent molecular weight to a mixture of apparently lower mo ecular weight polypeptide components, as characterized by sodium dodecyl sulfate/ polyacrylamide gel electrophoresis. This protein alteration, which correlates temporally with increases in the formation of lipid oxidation products and in the fluorescence of the apoprotein, is markedly reduced when oxygen is excluded or when EDTA or the free-radical-scavenging antioxidants, butylated hydroxytoluene or propyl gallate, are added. The conversion thus appears to be due to a reaction between the protein moiety and auto-oxidizing lipid. The presence of the antibacterial agent sodium azide markedly accelerates the oxidation, suggesting that it should only be used with caution in lipid-containing solutions. Structural and functional characterization of serum lipoproteins has received attention because molecular or metabolic abnormalities associated with this class of molecules might be significant in the development of atherosclerosis (1). The lowdensity lipoprotein fraction (LDL) has been of particular interest because of its apparent role in atherogenesis. Such a role is indicated by a correlation between high serum levels of LDL and clinical atherosclerosis (2), as well as the accelerated atherosclerosis in patients who have an inherited abnormality in LDL catabolism (familial hypercholesterolemia) (3). LDL is catabolized after it is bound through its protein moiety (apo-B or apo-LDL) to a cell-surface receptor (4).Although characterization of the apoprotein of LDL has been difficult (5), studies on the lipid moiety appear to be less controversial. LDL contains a large proportion of unsaturated lipids (somewhat variable on diet) (6) and is unique among the serum lipoproteins in its susceptibility for undergoing auto-oxidation in vitro (7-9). This finding has led some authors to speculate that such auto-oxidation plays a role in atherogenesis (7,10,11). Although structural (7-13), spectrophotometric (9,13,14), and lipid compositional (8, 11) changes in LDL have been observed upon oxidation, its polypeptide chain has not been characterized. Model studies with lipid-protein mixtures have shown that oxidized lipid can lead to major modification of protein components; such modifications include crosslinking (15), polypeptide scission (16), and loss of amino acids (17, 18). It thus seems possible that some of the difficulties encountered in characterizing apo-B are associated with partial oxidation of LDL during purification and/or storage. The observation that plasma lipids from human subjects contain significant diene conjugation (an early manifestation of lipid auto-oxidation) suggests that oxidation of LDL can be initiated in vivo (19).We show here that mild oxidation of LDL in vitro results in altering the sodium dodecyl sulfate (NaDodSO4)-apoprotein electrophoretic pattern from a single major band of low mobility into nume...

The results presented in this communication will form part of the dissertation of Gordon F. Fairclough, Jr., in partial fulfillment of the requirements for the Ph.D. degree from Yale University.

Among hypertensive and diabetic patients undergoing elective noncardiac surgery, preoperative status and intraoperative changes in mean arterial pressure (MAP) were evaluated as predictors of postoperative ischemic complications. Of 254 patients evaluated before operation and monitored during operation, 30 (12%) had postoperative cardiac death, ischemia, or infarction. Twenty-four per cent of patients with a previous myocardial infarction or cardiomegaly had an ischemic postoperative cardiac complication. Only 7% of those without either of these conditions sustained an ischemic complication. No other preoperative characteristics, including the presence of angina, predicted ischemic cardiac risk. Nineteen per cent of patients who had 20 mm Hg or more intraoperative decreases in MAP lasting 60 minutes or more had ischemic cardiac complications. Patients who had more than 20 mm Hg decreases in MAP lasting 5 to 59 minutes and more than 20 mm Hg increases lasting 15 minutes or more also had increased complications (p less than 0.03). Changes in pulse were not independent predictors of complications and the use of the rate-pressure product did not improve prediction based on MAP alone. In conclusion patients with a previous infarction or radiographic cardiomegaly are at high risk for postoperative ischemic complications. Prolonged intraoperative increases or decreases of 20 mm or more in MAP also resulted in a significant increase in these potentially life-threatening surgical complications.

No abstract

The synthesis and structural characterisation (Fourier transform infrared, FTIR spectrometry, scanning electron microscopy, SEM and energy-dispersive X-ray, EDX) of amino-modified silicates (unloaded L1, and aspirin-loaded, L2) are reported. The optimal conditions for the extraction of aspirin from water by the modified silicate material were determined as a function of the mass of the extracting agent and the pH of the aqueous solution. The optimum mass was found to be 0.08–0.10 g with 99.9% removal of aspirin. Maximum extraction of aspirin by the material was observed at pH 4. The kinetics, the removal capacity of the material, as well as its recycling, were investigated. The results indicate that (i) the process is fast and (ii) the removal capacity for the drug is greater than that of previously reported materials and (iii)the modified silicate can be easily recycled. These data along with the low cost involved in the production of the material led to the conclusion that the modified silicate has the required potential for industrial use. Molecular simulation calculations suggest that one unit of aspirin interacts with one unit of the modified silicate L1 through hydrogen bond formation between the amine functional group of the silicate and the oxygen donor atoms of aspirin. Final conclusions are given.