Search PubMed⌕ Search

Biomedical subjects

S K Peng

Publications and source records attributed to S K Peng.

At least 55 records · Page 3Linked to original sources

Cholesterol oxidation derivatives and arterial endothelial damage.

Three groups of New Zealand male while rabbits were given either 2.5 mg/kg of 25-hydroxycholesterol, cholestane-3 beta, 5 alpha, 6 beta-triol or vehicle only, intravenously. 24 h after treatment, the luminal surfaces of aortae of rabbits receiving 25-hydroxycholesterol were examined by scanning electron microscopy (SEM) and showed numerous balloon-like protrusions and crater-like defects as well as circulating, formed elements adhering on the luminal surface. The luminal surface of aortae of rabbits given cholestane-3 beta, 5 alpha, 6 beta-triol had similar but more frequent lesions when compared with those of the 25-hydroxycholesterol group. Microthrombi were occasionally found. The aortae of the control group had significantly fewer lesions. Transmission electron-microscopic studies showed intracytoplasmic vacuoles and diffuse subendothelial edema in the aortae of the two groups receiving the oxidation derivatives of cholesterol. The balloon-like protrusions and crater-like defects observed by SEM appeared to represent the initial sterol-induced endothelial cell injury. Repeated episodes of arterial injury followed by thrombus formation could eventually lead to atherosclerosis.

Animals↗

Influence of cholesterol oxidation derivatives on membrane bound enzymes in cultured aortic smooth muscle cells.

Cholestane-3 beta, 5 alpha, 6 beta-triol and 25-hydroxycholesterol are two of the most cytotoxic and also relatively abundant of the autoxidation derivatives of cholesterol. Cultured aortic smooth muscle cells which were incubated with 10 micrograms/ml of either sterol for 24 to 48 hr showed a marked decrease of 5'-nucleotidase activity in isolated crude membranes. It was further demonstrated that 5'-nucleotidase activity was also markedly decreased in plasma membrane-enriched fractions when cells were incubated with cholestane-3 beta,5 alpha,6 beta-triol. Na+,K+-ATPase activity in crude membranes showed a significant decrease (32%) only in cells incubated with cholestane-3 beta,5 alpha,6 beta-triol for 48 hr. There was no effect on Na+,K+-ATPase activity in cells incubated for 24 hr with either sterol.

5'-Nucleotidase↗

Effects of oxygenated derivatives of cholesterol on cholesterol uptake by cultured aortic smooth muscle cells.

The cytotoxicity of oxygenated derivatives of cholesterol on the cultured cells may not only be due to their potent inhibition of cholesterol biosynthesis, but also could be related to their capability for inhibiting cholesterol uptake from exogenous sources, particularly in arterial cells, which synthesize cholesterol at a very slow rate. In cultured aortic smooth muscle cells, the most potent inhibitor of cholesterol uptake was cholestane-3 beta,5 alpha,6 beta triol, which at 100 micrograms/ml medium reduced uptake of cholesterol to 10% of the control. The next most potent inhibitors were 5 alpha,6 alpha- epoxycholesterol and 25-hydroxycholesterol, which reduced uptake of cholesterol to 60%. 7 alpha- and 7 beta-hydroxycholesterol and 7-ketocholesterol inhibited cholesterol uptake to 30-50%. A consequence of their inhibitory effects on cholesterol uptake could be a depletion of cell membrane cholesterol, resulting in alterations in membrane structure and function and eventually in cell death.

Animals↗

Effects of cholesterol autoxidation derivatives on hexose transport in cultured aortic smooth muscle cells.

Several cholesterol autoxidation derivatives known to be cytotoxic to arterial smooth muscle cells both in vivo and in vitro were shown to inhibit hexose transport in these cells in culture. Cholestane-3 beta, 5 alpha, 6 beta-triol was the most potent inhibitory sterol. The rapid onset of inhibition (15 min) and the reversibility of the effect upon removal of the sterol from the tissue culture medium suggests that the effect may be due to incorporation of the sterol into the plasma membrane. 25-Hydroxycholesterol, a potent inhibitor of sterol biosynthesis in cultured arterial smooth muscle cells, did not affect hexose transport up to 8 hr of incubation. The cytotoxic effect of 25-hydroxycholesterol, therefore, may be a consequence of the reduced sterol biosynthesis caused by this sterol.

Animals↗

Hydrophobic surfactant treatment prevents atherosclerosis in the rabbit.

The hypocholesterolemic effect of the hydrophobic surfactant, poloxalene 2930, was studied in the rabbit to determine whether this agent prevents experimentally produced atherosclerosis. Male rabbits were divided into four groups and fed a control diet (group A) or an atherogenic diet (groups B, C, and D) for 10 wk. Diets of groups C and D were supplemented with 0.5 and 1% poloxalene 2930, respectively. Animals in group B developed significantly greater levels of cholesterol in the serum and aorta compared with group A. Addition of poloxalene 2930 to the diets of groups C and D prevented significant elevations in cholesterol concentrations of both serum and aorta compared with group B with values for group D being essentially similar to those observed in group A. Groups C and D also had significant increases of fecal excretion of both neutral fat and neutral steroids as compared with either groups A or B. There were no atherosclerotic lesions of the aortas from group D. Aortas from rabbits in group B had numerous atheromatous plaques while one rabbit each from groups A and C had several very small atheromatous lesions. These results demonstrate that poloxalene 2930 reduces the rise of serum cholesterol in rabbits in response to an atherogenic diet and prevents the development of atherosclerosis. This hypocholesterolemic effect is likely mediated by the effect of this surfactant on the small intestine.

Animals↗

Distribution of 25-hydroxycholesterol in plasma lipoproteins and its role in atherogenesis. A study in squirrel monkeys.

Oxidation products of cholesterol have been shown to be potent inhibitors of cholesterol biosynthesis and also highly toxic to cultured aortic smooth muscle cells. In rabbit experiments, these compounds produced arterial injury resulting in arteriosclerosis. Purified cholesterol only minimally inhibited cholesterol biosynthesis and had no effect on cultured aortic smooth muscle cells. This raises the possibility that plasma lipoproteins containing beta-apoprotein (i.e. LDL and VLDL), which are considered to be atherogenic, may carry more oxidation products than HDL which is not atherogenic [3H]25-hydroxycholesterol and [14C]cholesterol were given only orally to 10 squirrel monkeys (Saimiri sciureus) and blood samples were collected via femoral puncture 24 h after administration. Lipoproteins were separated by ultracentrifugation and the radioactivity in each fraction was counted. Results show that the distribution of labeled cholesterol in VLDL, LDL, and HDL was almost identical to that of unlabeled cholesterol. Most of the radio-activity of 25-hydroxycholesterol was located in LDL & VLDL (55.1% and 34.7%, respectively), only 10.2% was present in HDL. If the radioactivity of 25-hydroxycholesterol were calculated on the basis of the apoprotein content of the lipoprotein micelle, the relative capacity of VLDL and LDL to carry 25-hydroxycholesterol was even greater and more significant than that of HDL (90 X and 42 X, respectively).

Animals↗

Central nervous system vasculitis in cytomegalovirus infection.

A 51-year-old man received cyclophosphamide, vincristine, procarbazine and prednisone in the treatment of a small-cell undifferentiated lymphoma. Two years later, he developed a rapidly progressive neurological syndrome characterized by a decline in alertness, deafness, blindness and paraplegia. Examination of his eyes revealed severe hemorrhagic chorioretinitis. Leg weakness was thought to be due to transverse myelopathy at a thoracic level. He had a grand mal convulsion and died from terminal bronchopneumonia. Autopsy examination of the eyes revealed sweeping destruction of the retina due to inclusion body chorioretinitis. The brain and spinal cord showed multiple small infarcts accounting for the deafness and paraplegia. The lesions were due to occlusive arteritis in gray and white matter. Veins were also involved. Tissue surrounding the foci of necrosis contained cells with intranuclear an intracytoplasmic inclusion bodies. Some of the Cowdry type A inclusion bodies were large, measuring 30 micrometer in diameter and were located in enlarged cells. Electron microscopy of retina and brain tissue disclosed virus particles compatible with cytomegalovirus. The subject of cerebral and ocular angiitis due to herpes virus infections is reviewed.

Brain↗

Cytotoxicity of oxidation derivatives of cholesterol on cultured aortic smooth muscle cells and their effect on cholesterol biosynthesis.

Aortic smooth muscle cell death is an important initial lesion of atherosclerosis. A number of autooxidation products of cholesterol which has been recognized recently has the capability of inducing rabbits' aortic smooth cell death in vitro. Twelve oxidation derivatives of cholesterol, available commercially, were dissolved in small amounts of ethanol, then added to the culture medium at levels not exceeding 0.8%. The medium contained 10% fetal calf's serum which served as an in situ vehicle for the sterols. The degrees of cytotoxicity were graded and measured as percentage of dying and dead cells in the cultures within 24 hr. 25-Hydroxycholesterol and cholesthan-3 beta, 5 alpha, 6 beta-triol, were the most toxic compounds among the sterols tested. When these oxidation derivatives of cholesterol were added to these cultured cells, they significantly depressed activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase, a regulatory enzyme of cholesterol biosynthesis (up to 83% inhibition by 25 hydroxycholesterol at a 3 microgram/ml concentration in culture medium) but the sequence of degree of inhibition was not exactly correlated with that of cytotoxicity. Various mechanisms are speculated. Purified cholesterol showed no cytotoxic effect and minimal inhibition of cholesterol biosynthesis.

Animals↗

Experimental arteriosclerosis in Rhesus monkeys induced by multiple risk factors: cholesterol, vitamin D, and nictotine.

Forty-four rhesus monkeys were given various regimens involving three vasotoxic factors: dietary hypercholesteremia, hypervitaminosis D2 and nicotinism for period ranging from 14 to 62 weeks. When administered singly, no or only early disease was observed. The combined three "risk factor" group demonstrated the most impressive arteriosclerosis. Major arteriosclerotic changes: fat, calcium and mensenchyme of thirty standardized segments of aorta, coronary and limb arteries of all monkeys were graded according to a standardized system. Statistical analysis revealed that the total arteriosclerotic scores of the three vasotoxic factor group was significantly greater than those of any other group and that this was the only group with significant coronary arteriosclerosis as well as complicated lesions such as thrombosis or occlusion of arterial luminae of the extremities. A lowering of the vitamin D2 dosage, resulting in a lengthening of the survival time of animals which should allow sufficient time for complicated disease to develop, is recommended for future studies.

Animals↗

Effect of auto-oxidation products from cholesterol on aortic smooth muscle cells: an in vitro study.

Purified cholesterol is quite unstable when stored in air at room temperature. Products of cholesterol auto-oxidation were concentrated from several lots of USP-grade cholesterol by recrystallizing cholesterol from the methanol extract, retaining the mother liquor, and evaporating the residuum to dryness under vacuum. By application of thin-layer chromatography and gas-liquid chromatography, major, individual, oxidation compounds were identified and quantitated. Biological activities of these oxidation compounds were studied by using cultured rabbits' aortic smooth muscle cells. The concentrate of the auto-oxidation products of cholesterol showed remarkable in vitro cytotoxic effects, whereas purified cholesterol at the same concentration produced no toxic effects. The concentrate was further separated into six thin-layer chromatographical fractions. The results showed that 25-hydroxycholesterol and cholestane-3beta, 5alpha, 6beta-triol were probably responsible for the biological toxicity of the concentrate

Aorta↗

MR imaging of Ho:YAG laser diskectomy with histologic correlation.

Twelve cadaveric vertebral specimens were imaged after holmium yttrium aluminum garnet (Ho:YAG) laser diskectomy to determine the usefulness of magnetic resonance (MR) imaging in evaluating treatment outcome. The Ho:YAG laser was operated at 1.0-2.0 J per pulse, 5 Hz, and 250-microseconds pulse width. The total energy varied between 600 and 2,700 J. Two distinct patterns emerged on MR images. Tissue ablation at higher power (1.5 and 2.0 J per pulse) produced discrete signal voids that correlated with areas of laser-induced ablation identified at gross inspection. More subtle changes, characterized by a high-signal-intensity ring, were seen in the specimens lased at 1.0 J per pulse. The latter appearance corresponded to incomplete vaporization of diskal tissue, a broader zone of minimal thermal injury, and sparing of adjacent vertebral endplates. Total mass loss did not appear to be affected by the choice of power setting (1.0 vs 1.5 J per pulse), with total laser energy held constant.

Adult↗