Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.1 (ERK)
 95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A system of animal models potentially useful for the discovery and evaluation of new effective antiatherosclerotic agents is described. The models consist of a series of lipoprotein and atherosclerosis assays in rats, SEA Japanese quail and cynomolgus monkeys. SEA quail are particularly useful for detecting compounds that inhibit arterial cholesterol deposition. The use of this integrated system of models is illustrated with data on clofibrate, adamantyloxyaniline (a hypobetalipoproteinemic agent), and o,p'-DDD. Male SEA quail appear to be a quite satisfactory model for testing the effects of large numbers of compounds on atherosclerosis and are available in limited numbers to all qualified investigators in the field of atherosclerosis research for evaluation in their laboratories.
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PMID:Animal models for an integrated approach to the pharmacologic control of atherosclerosis. 12 Jan 68

Male SEA quail were fed a 0.5% cholesterol supplemented diet, to which was added 0%, 1%, and 2% beta-sitosterol, for a period of seven days. Dietarily administered beta-sitosterol reduced total serum cholesterol levels by 62% and 72% at the 1% and 2% treatment doses, respectively. This hypocholesterolemic activity of sitosterol in cholesterol fed SEA quail was anticipated on the basis of the numerous earlier studies demonstrating similar activity in cholesterol fed chickens. Beta-sitosterol was tested in SEA quail to experimentally confirm its expected serum cholesterol lowering effects and to expand further the utility of the SEA quail model in cholesterol and atherosclerosis research.
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PMID:Hypocholesterolemic activity of beta-sitosterol in cholesterol fed sea quail. 206 17

Young, male, SEA (Susceptible to Experimental Atherosclerosis) Japanese quail (Coturnix coturnix japonica) were fed an atherogenic diet consisting of yellow corn meal and soybean meal supplemented with 2% cholesterol and 1% cholic acid. A control group of ten animals was fed the atherogenic diet for eight weeks, and another group was fed the same diet containing 2% colestipol hydrochloride for the same length of time. At the end of the treatment period serum and arterial total cholesterols were measured and extent of macroscopic atherosclerotic lesions assessed. Colestipol hydrochloride treatment significantly reduced both serum and arterial total cholesterol levels by 50 and 59%, respectively. Grossly visible atherosclerosis was significantly reduced by 64%. These data further demonstrate that male SEA quail are an appropriate and relevant small animal model for examining the cardiovascular effects of bile acid sequestrants.
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PMID:Anti-atherosclerotic activity of colestipol hydrochloride in SEA quail. 233 84

The pharmacopolymer bile acid sequestrants cholestyramine and colestipol hydrochloride were mixed with a diet supplemented with 0.5% cholesterol at levels of 0.25%, 0.5%, and 1.0% for cholestyramine and 0.5% and 1.0% for colestipol and fed to young, male, SEA (Susceptible to Experimental Atherosclerosis) Japanese quail (Coturnix coturnix japonica) for a period of seven days. After treatment blood was obtained by venipuncture from non-fasted animals and analyzed for serum total cholesterol concentration. Cholestyramine significantly reduced total cholesterol concentrations at all doses in a dose dependent manner. Colestipol significantly reduced total cholesterol only at the 1.0% dose. Based on these observations, cholestyramine is significantly more potent for reducing serum cholesterol in hypercholesterolemic male SEA quail than is colestipol hydrochloride.
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PMID:Comparison of hypocholesterolemic activities of the bile acid sequestrants cholestyramine and colestipol hydrochloride in cholesterol fed SEA quail. 239 2

Male SEA (Susceptible to Experimental Atherosclerosis) quail were fed a semi-purified diet containing 0.5% cholesterol for a period of one week. Colestipol hydrochloride was mixed with the diet at levels of 0.5% and 1.0%. In control animals total serum cholesterol increased from a basal level of 241 mg/dl to 820 mg/dl after one week on the cholesterol supplemented diet. At 0.5% colestipol hydrochloride treated animals experienced a change in serum cholesterol from 223 mg/dl to 528 mg/dl after one week of cholesterol feeding. Colestipol hydrochloride at 1.0% in the diet completely prevented any increase in serum cholesterol in response to the hypercholesterolemic diet. Total serum cholesterols in this treatment group were 258 and 222 mg/dl initially and after the one week treatment, respectively. These data demonstrate that the bile acid sequestrant colestipol hydrochloride clearly prevents the hypercholesterolemia produced by feeding male SEA quail a cholesterol supplemented diet. Based on this activity cholesterol fed SEA quail may be a convenient and practical model for the preclinical evaluation of new cholesterol lowering drugs which act via a mechanism of bile acid sequestration.
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PMID:Hypocholesterolemic activity of colestipol hydrochloride in SEA quail. 258 93

Receptors for insulin, low-density lipoprotein, and colony stimulating factor 1 are associated with diabetes, atherosclerosis, and cancer in man. Complementary DNA clones for Insr, Ldlr, and Csfmr were used to chromosomally assign the three genes in mouse. In contrast to their close linkage on the short arm of human Chromosome 19, Insr and Ldlr are asyntenic, residing on mouse Chromosomes 8 and 9, respectively. The genes for CSF1R, CSF1, CSF2, IL-3, and IL-5 form a cluster on the long arm of human Chromosome 5. In mouse, Csfm, Csfgm, and IL-3 are syntenic on Chromosome 11. The Csfmr gene was assigned to mouse Chromosome 18 and is thus unlinked to other members of this gene cluster. These gene assignments provide additional topographical information on conservation of linkage groups in man and mouse and provide a genetic framework for evaluating the possible roles for the three receptor genes in genetic diseases in mouse.
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PMID:Chromosome assignment of mouse insulin, colony stimulating factor 1, and low-density lipoprotein receptors. 306 42

Timefurone was evaluated in several animal models for cholesterol-lowering and anti-atherosclerotic activity. In normal male rats, a dose-response study with timefurone (3, 10, 30, 50 and 100 mg/kg/day) was conducted for 7 days. Significant activity was observed only at 50 and 100 mg/kg/day, where very low and low density lipoprotein cholesterol [(VLDL + LDL)-C] and total-C levels were reduced (mean 27 and 20%). High density lipoprotein cholesterol (HDL-C) was lowered 24% by the high timefurone dose. Timefurone (10, 20, 50 and 100 mg/kg/day in the diet) was then examined in normocholesterolemic SEA japanese quail. beta-lipoprotein cholesterol (VLDL + LDL)-C was reduced at all doses (mean 58%), while alpha-lipoprotein cholesterol (HDL-C) was elevated by all doses of timefurone (mean 45%). Male weanling rats made moderately hypercholesterolemic represented a 3rd phase of timefurone (2.5, 5, 10, 20, 50, 100 mg/kg/day) testing. After 4 days of drug treatment, marked hypocholesterolemic activity was observed for (VLDL + LDL)-C (mean decrease 49%) and total-C (mean 33%). HDL-C levels were increased with 10 and 100 mg/kg/day doses. Timefurone (25 and 100 mg/kg/day in the diet) also caused a significant reduction in atherosclerotic development in hypercholesterolemic SEA japanese quail. Atherosclerotic involvement (determined by visual assessment of plaque), arterial weight, and arterial cholesterol (total and mg/g artery) were clearly lowered by both doses of timefurone. There was no evidence of significant drug toxicity in any of these experiments. On the basis of these data, timefurone has excellent therapeutic potential and additional study of the drug's hypocholesterolemic and anti-atherosclerotic properties appears warranted.
Atherosclerosis 1985 Sep
PMID:Evaluation of timefurone, a new anti-atherosclerotic drug, for its effects on lipoprotein cholesterol in male SEA Japanese quail and rats. 386 23

To assess the relation between the physical order of a membrane and its sensitivity to ethanol, we enriched biomembranes with cholesterol, both in vivo and in vitro. Japanese quail of the SEA line (selectively bred for susceptibility to experimental atherosclerosis) were treated for 9 to 16 weeks with a diet that contained 2% cholesterol. This regimen increased the cholesterol content of serum and erythrocytes. The cholesterol content of brain synaptosomal plasma membranes (SPM) was unaffected by the high cholesterol diet. In other experiments, isolated mouse synaptosomal plasma membranes were incubated with cholesterol/phospholipid (C/P) vesicles; different amounts of cholesterol were transferred according to the sterol content of the donor vesicles. Membrane order was determined in both types of membranes by a sensitive electron paramagnetic resonance (EPR) technique. The order parameter with 5- and 12-doxylstearic acid increased along with the cholesterol content. As expected, ethanol disordered membranes (decreased the order parameter) in a concentration-related manner. The slope of the concentration response curve was less steep in high cholesterol than low cholesterol membranes, indicating that cholesterol enrichment partially blocks the membrane action of ethanol in both types of membranes.
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PMID:Cholesterol blocks the disordering effects of ethanol in biomembranes. 652 12

Male Japanese quail (strain SEA) rapidly develop atherosclerotic lesions in the aorta and brachiocephalic arteries when fed an atherogenic diet containing 1.0% cholesterol and 0.5% cholic acid. The present study was conducted to determine the parameters of the atherosclerotic response. Groups of 20 quail fed the atherogenic diet were killed at 0 days, 1 day, 3 days, or weekly from 1 to 12 weeks. Quail fed the atherogenic diet for 1 day showed a significant increase in serum cholesterol; a plateau was reached by 2 weeks. A significant increase in arterial cholesterol was seen after 2 weeks on the atherogenic diet, and arterial cholesterol showed a linear increase with time from 2 to 12 weeks. Increased incorporation of tritiated thymidine into the DNA of arterial cells was first seen at 2 weeks; thymidine incorporation increased to a maximum value at 9 weeks, then declined to 50-60% of the 9-week value at weeks 11 and 12. Grossly visible atherosclerotic lesions were first seen at 3 weeks, and 90% of birds showed gross atherosclerotic lesions by 8 weeks. Atherosclerosis induced in Japanese quail by feeding cholesterol and cholic acid is characterized initially by lipid deposition in the arterial wall, followed by increased incorporation of tritiated thymidine and the appearance of gross lesions.
Atherosclerosis 1982 Mar
PMID:Temporal association between arterial cholesterol deposition, thymidine incorporation into DNA, and atherosclerosis in Japanese quail fed an atherogenic diet. 708 12

Eleven healthy young women (age range 20-28 years) were given three different oral contraceptives (OCs) in random order, each contraceptive for 3 months. Smoking, eating, drinking and habits of physical activity were similar throughout the study period. The combinations were: ethinyl-estradiol/noretisterone (EE/NET) 35 micrograms/0.5 mg, 35 micrograms/1 mg and 50 micrograms/1 mg. The 35/0.5 and the 50/1 EE/NET combinations led to significant weight increases of 2.4 and 1.7 kg, respectively. All EE/NET combinations produced LDL-TG increases, from a pretreatment value of 0.28 +/- 0.04 (SD) mmol/l to 0.34 +/- 0.07, 0.35 +/- 0.06 and 0.42 +/- 0.13 mmol/l (P less than 0.01 for all). LDL-cholesterol increased from 2.99 +/- 0.63 mmol/l to 3.35 +/- 0.62 (P less than 0.01) after 35/1 treatment and to 3.43 +/- 0.62 mmol/l (P less than 0.001) after 50/1 treatment. These two EE/NET combinations also caused significant reductions of HDL-cholesterol, in both cases from a pretreatment value of 1.75 +/- 0.16 mmol/l to 1.64 +/- 0.24 mmol/l (P less than 0.05). Since all values after EE/NET treatment remained well within normal ranges, these low-dose OCs probably have little effect on the development of atherosclerosis due to serum lipoprotein abnormalities. However, our findings suggest that OCs may interfere with the cholesterol ester/TG exchange between LDL and HDL.
Atherosclerosis 1982 Dec
PMID:Effects of ethinyl-estradiol/noretisterone combinations on serum lipoproteins. 715 2


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