Effect of chlordiazepoxide on conditioned and unconditioned fear in rats.
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Biomedical subjects
Publications and source records attributed to M D Morris.
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We estimated the effects of age, sex, saturated and polyunsaturated dietary fat, and two levels of dietary cholesterol intake on cholesterol absorption in juvenile baboons between 15 and 51 months of age. We compared the reproducibility of methods of measuring cholesterol absorption within animals, and also compared estimates of percentage cholesterol absorption by three different methods. Cholesterol absorption was significantly greater in all diet groups at 27 and 39 months of age than it was at 15 or 51 months (P < 0.001). Cholesterol absorption (%) was significantly greater in animals fed low cholesterol diets than it was in animals fed high cholesterol diets. However, cholesterol absorption was not affected by type of fat (saturated or unsaturated) in the diet or by sex. The range of reproducibility (within-animal standard deviation) of percentage cholesterol absorption for different diet groups was 3.35 to 3.90% for the Borgström method (1969. J. Lipid Res. 10: 331--337), 4.67 to 7.30% for the Sodhi method (1971. Proc. Soc. Exp. Biol. Med. 137: 277-279), and 3.69 to 7.15% by a combined isotopic chromatographic method (Method I). Percentage absorption measured by either the Sodhi method or Method I was significantly greater than that measured by the Borgström method.
The accuracy and reliability of noninvasive measurement of blood pressure in the forearms of baboons by means of an automated oscillometric method were evaluated. Comparisons of 255 oscillometric determinations of systolic, diastolic and mean arterial pressure in eight anesthetized animals with simultaneously taken direct radial artery pressure measurements revealed average differences and standard deviations of +0.14 (+/- 9.05), +4.34 (+/- 6.75), and -1.01 (+/- 5.84) Torr, respectively. Computation of statistical error bounds indicated that any single oscillometric reading could be expected to fall within 9.6%, 11.0% nd 7.4% of directly measured systolic, diastolic, and mean blood pressure with a probability of 0.90. The oscillometric determinations accurately tracked rapid changes in pressure caused by intravenous infusion of pressor and depressor drugs. The method provided fast, reliable readings of arterial pressure without the use of microphones or other transducers that require precise placement and low-noise environments.
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The interaction between chlordiazepoxide (CDP) and forebrain noradrenaline (NA) was investigated in rats with bilateral radiofrequency lesions of the noradrenergic dorsal tegmental bundle (DTB). Forebrain NA was reduced to 35% of control by the DTB lesions; hypothalamic NA and dopamine were unchanged. Rats were trained on a straight alley runway task for food reward. During extinction of the runway task, CDP significantly increased extinction responding in sham lesion animals but not in DTB lesion animals. Thus, CDP was ineffective in increasing resistance to extinction responding in the runway task in animals with significant depletion of forebrain NA.
Rats were trained on an appetitive discretetrial discriminated-punishment task in which they learned to suppress responding when an intense flashing light predicting punishment was present and to respond rapidly on trials when the flashing light was absent. Once animals were performing discriminatively, 0.75, 3.0, or 6.0 mg/kg of morphine (base) was administered and a fear extinction session consisting of 60 nonshocked presentations of the flashing light was given. Two saline control groups, one that received fear extinction and one that did not, were also included in the experiment. On the day following fear extinction, all rats were tested in the undrugged state on the discriminated punishment problem, but without shock. The rats receiving 3.0 and 6.0 mg/kg of morphine before the fear extinction session were suppressed by the flashing light more than the saline extinction group or the 0.75 mg/kg morphine treatment group. Moreover, the two higher dose morphine groups were suppressed as readily as the saline group that received no fear extinction. These results are attributed to the antiemotionality effects of morphine.
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Blood was collected from the umbilical cord of infants with a 1-min Apgar score of 9 to 10. Total cord serum lipoproteins were isolated by ultracentrifugation, at a density of 1.220 g/ml. The isolated serum lopoproteins were then separated by gel filtration chromatography on 6% agarose. The overall recovery of the separated lipoprotein cholesterol was 90% or greater. In cord serum, four lipoprotein peaks were found, whereas three peaks were present in adult lipoproteins. The major lipoproteins of cord serum correspond to low density lipoprotein (LDL) and high density lipoprotein (HDL). Very low density lipoproteins (VLDL) were heterogeneous in cord serum. After gel filtration chromatography, the distribution of cord serum cholesterol is about 5% in peak 1, 10% in peak 2, 40% in peak 3 (LDL), and 45% in peak 4 (HDL). An additional difference between the lipoproteins isolated from cord serum and those from adult serum was the slower electrophoretic mobility of cord serum VLDL in agarose gel.
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A case of nonrhegmatogenous retinal detachment with choroidal detachment was seen 3 weeks after onset and was evaluated clinically with emphasis on the fluid contents from one eye. The right eye showed slight subretinal fluid and minimal RPE pigmentary mottling. The left eye was severely involved with a near flat anterior chamber, a 360 degrees peripheral serous retinal detachment with shifting fluid and 360 degrees choroidal separations. Fluorescein showed mottled retinal pigment epithelium changes in each eye. Cell free samples of the subretinal fluid were high in protein (16.5 gm/100 ml) with a near absence of the alpha-2 fraction. Epichoroidal fluid from the choroidal detachments exhibited a protein content and makeup similar to that of normal plasma. The concentration of protein in the cerebrospinal fluid was elevated (0.096 gm/100 ml) without evidence of inflammatory changes. Ultrastructural examinations of sclera revealed a normal structure. There was no indication of the cause of the elevated protein content of the subretinal and spinal fluids. Following subretinal and epichoroidal fluid evacuation, the patient was treated with systemic steroids. The retinal and choroidal separations subsided slowly over several months, leaving multiple retinal pigment epithelial pigmentary clumps with drusen-like centers. A more appropriate name for this entity is idiopathic chorioretinal effusion.
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Marked hypertriglyceridemia and hypercholesterolemia accompanied by angina and a left cerebral thrombosis occurred in a long-term hemodialysis patient following 5 1/2 weeks of oral treatment with oxymetholone, 100 mg/day, a synthetic androgen. After androgen therapy was discontinued, over a three-month period, plasma lipid values progressively decreased below pretreatment values, and clinical symptoms disappeared. During rechallenge with oxymetholone, serum lipid values increased substantially, and the lipoprotein pattern changed from a type IV to a type V. Detailed lipid studies showed subnormal postheparin lipolytic activity and a fast-migrating pre-beta-lipoprotein in a very-low-density lipoproteins (VLDL) fraction. Because of the data linking lipid abnormalities to atherosclerosis and the acceleration of atherosclerosis in long-term hemodialysis patients, great caution should be exercised in administering androgenic steroids to these patients.
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