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Biomedical subjects

A S Katocs

Publications and source records attributed to A S Katocs.

15 recordsLinked to original sources
PubMed1996

Hypercholesterolemia in the rabbit induced by feeding graded amounts of low-level cholesterol. Methodological considerations regarding individual variability in response to dietary cholesterol and development of lesion type.

While a number of studies have presented detailed examinations of lesion development in the cholesterol-fed rabbit, individual variability in response to cholesterol feeding and type of lesion produced relative to the degree of cholesterol exposure is not well defined. This study analyzed such critical parameters in an attempt to further characterize the model and establish a baseline for future testing of treatments targeted at limiting atherosclerosis. For these experiments, male New Zealand White rabbits were fed atherogenic diets consisting of 0.05%, 0.10%, 0.15%, 0.20%, or 0.25% cholesterol dissolved in 6% peanut oil for 31 to 32 weeks. Raising dietary cholesterol from 0.05% to 0.15% resulted in a less than twofold stepwise increase in total plasma cholesterol (TPC) exposure (area under plasma cholesterol versus time curve), whereas further increases in cholesterol intake resulted in an exponential four- to fivefold increase in TPC exposure. Regression analysis of TPC exposure with aortic sudanophilia demonstrated a threshold of approximately 5000 cholesterol weeks; below this limit lesions were minimal, and above this value the degree of plaque correlated with TPC exposure. Furthermore, a wide biological variability occurred among rabbits with respect to individual responsiveness to dietary cholesterol. In the aorta, various types of plaques, from fatty streaks to atheromatous lesions, were observed, depending on the degree of cholesterol intake. Diets consisting of < 0.15% cholesterol resulted in the development of fatty streak lesions, while transitional lesions and atheromatous plaques were mostly found with higher cholesterol feeding. Coronary artery atherosclerosis was present in > 50% of animals fed diets > or = 0.15% cholesterol. Despite the level of TPC exposure, coronary lesions in epicardial vessels were generally the fibrous type, whereas intramyocardial arteries demonstrated predominantly intimal foam cells. In conclusion, by adjusting dietary cholesterol intake and selecting rabbits with a similar responsiveness to cholesterol, the overall cholesterol exposure can be more closely controlled to minimize the inherent individual variability among animals in this model. The nature of the target lesion must also be carefully considered, because the efficacy of some treatments may depend on the type of atherosclerotic plaque.

Animals↗
PubMed1990

Platelet-activating factor or a platelet-activating factor antagonist decreases tumor necrosis factor-alpha in the plasma of mice treated with endotoxin.

When L-platelet-activating factor (PAF) or alprazolam (a PAF antagonist) was administered to lipopolysaccharide (LPS)-treated mice, the level of plasma tumor necrosis factor (TNF alpha) determined by either ELISA or a cytotoxic assay using WEHI cells was significantly lowered. The inactive stereoisomer, D-PAF, was not effective in lowering plasma TNF alpha levels in LPS-treated mice. The decrease in plasma TNF alpha induced by L-PAF or alprazolam was partly reversed by indomethacin. Despite a decrease in plasma TNF alpha, L-PAF or alprazolam caused an increase in the amount of TNF alpha mRNA present in the kidneys and the livers of LPS-treated mice, suggesting that a posttranscriptional event leading to the synthesis or release of TNF alpha was inhibited by these agents.

Alprazolam↗
PubMed1989

Potential antiatherosclerotic agents. 6. Hypocholesterolemic trisubstituted urea analogues.

The discovery that a series of N,N-dialkyl-N'-arylureas were inhibitors of the ACAT enzyme has led to a structure-activity study involving the systematic modification of three sites of the urea backbone. This study culminated in the selection of N'-(2,4-dimethylphenyl)-N-benzyl-N-n-butylurea (115) for more extensive biological evaluation. ACAT inhibitors are seen as potentially beneficial agents against hypercholesterolemia and atherosclerosis.

Adrenal Glands↗
PubMed1982

Antiatherogenic activity of cetaben sodium, sodium p-(hexadecylamino) benzoate, in the aortae of hypercholesteremic rabbits subjected to aortic endothelial cell desquamation.

The effects of sodium p-(hexadecylamino)benzoate [cetaben sodium] on plasma sterol concentrations, aortic sterol deposition and the incidence of atherosclerotic lesions in cholesterol-fed rabbits subjected to aortic deendothelialization with a balloon catheter have been studied. At a dose of 113 mg/kg/day, cetaben sodium decreased plasma cholesterol and the accumulation of aortic sterol and appeared to decrease the incidence of gross atherosclerotic lesions. At a dose of 27 mg/kg/day, no hypocholesteremic activity was observed, but cetaben sodium decreased both aortic sterol deposition and lesion development in the abdominal segment of the aorta. The decreases in total aortic sterol content observed in the drug-treated rabbits were shown to have resulted from a reduction in esterified rather than free sterol. When tested in vitro, cetaben sodium effectively inhibited (KI = 7.4 x 10(-5) M) the esterification of cholesterol catalyzed by a crude preparation of fatty acyl CoA:cholesterol acyl transferase isolated from cholesterol-fed rabbit aortae. These observations suggest that cetaben sodium possesses antiatherosclerotic activity and that this activity may result from direct actions on the aortic wall, in addition to vascular effects secondary to hypocholesteremic activity.

4-Aminobenzoic Acid↗
PubMed1981

Real-time B-mode ultrasonography of the femoral arteries: comparison to contrast arteriography.

Forty-five patients with symptomatic peripheral vascular disease were studied with a high-resolution, real-time B-mode echo imaging system for visualization of the femoral arteries. Common femoral and superficial femoral arteries were visualized in over 88 per cent of cases, whereas the profunda femoris artery was demonstrated in only about one-third of cases. Stenotic lesions (+ or - 20% of arteriographic assessment) were identified in two-thirds of cases. Prostheses and grafts in the proximal and medial cases. Prostheses and grafts in the proximal and medial thigh were well visualized. Anatomic information provided by B-mode imaging will complement functional assessments of lower extremity vascular insufficiency.

Aged↗
PubMed1980

Comparison of pulsed Doppler and real-time B-mode echo arteriography for noninvasive imaging of the extracranial carotid arteries.

Accuracy and clinical applications of noninvasive imaging of the extracranial carotid arteries were compared using pulsed Doppler and real-time B-mode ultrasonography. During the period December, 1977, to February, 1979, 530 ultrasonograms (265 patients) were performed. Angiographic correlations were available in 90 patients (172 arteries) using the pulsed Doppler technique, and both techniques were employed in 43 patients (84 arteries). Greatest accuracy with pulsed Doppler ultrasonography occurred in confirmation of normal vasculature (73%) and diagnosis of occluded internal carotid arteries (96%). Estimation of the percentage of stenosis was less accurate; however, this determination could be made somewhat more accurately by B-mode ultrasonography. Incidence of false positive and negative results for the pulsed Doppler technique was 11% and 14%, respectively, whereas for the corresponding incidence for B-mode imaging it was 11% and 59%. The higher incidence of false negative results with the B-mode technique related to its inaccuracy in diagnosis of occlusion (18%). Current clinical applications of carotid ultrasonography include confirmation of normalcy and diagnosis of occlusion, visualization of atheroslerotic plaques with characterization of their size and ultrasonic morphology, and an anticipated reduction in the requirements for contrast arteriography in selected patients.

Aged↗
PubMed1977

Perifused adipose cells, quantitation and kinetics of lipolysis.

The perifused fat cell system is a system with which lipolytic activity can be monitored on a minute-to-minute basis. Thus, the rate at which lipolysis changes following the addition and removal of hormones can be followed. Catecholamines and other lipolytic agents produced a time-dependent increase in lipolysis following addition of agents, and a time-dependent decrease in lipolysis occurred following removal of the agent. ACTH also produced an increase in lipolysis. However, on termination of ACTH infusion, the lipolytic rate did not return to basal level but remained elevated for at least an additional 30 min (persistent phase). The persistent phase could be terminated by removal of Ca2+. Readdition of Ca2+ in the absence of additional ACTH resulted in a rapid increase in glycerol release. No persistant phase occurred following ACTH if the adipocytes were perifused in a Ca2+-free buffer. However, if Ca2+ was added to the system 20 min after termination of ACTH infusion, lipolysis increased to a rate greater than that obtained initially by infusing ACTH in a Ca2+-free buffer. It is concluded that ACTH is bound to some component of the fat cell in a Ca2+ independent, tenacious manner, and the full manifestation of that binding is dependent on the presence of Ca2+.

Adipose Tissue↗