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Biomedical subjects

J Mulligan

Publications and source records attributed to J Mulligan.

45 records · Page 3Linked to original sources

Oral nicotine induces an atherogenic lipoprotein profile.

Male squirrel monkeys were used to evaluate the effect of chronic oral nicotine intake on lipoprotein composition and metabolism. Eighteen yearling monkeys were divided into two groups: 1) Controls fed isocaloric liquid diet; and 2) Nicotine primates given liquid diet supplemented with nicotine at 6 mg/kg body wt/day. Animals were weighed biweekly, plasma lipid, glucose, and lipoprotein parameters were measured monthly, and detailed lipoprotein composition, along with postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activity, was assessed after 24 months of treatment. Although nicotine had no effect on plasma triglyceride or high density lipoproteins (HDL), the alkaloid caused a significant increase in plasma glucose, cholesterol, and low density lipoprotein (LDL) cholesterol plus protein while simultaneously reducing the HDL cholesterol/plasma cholesterol ratio and animal body weight. Levels of LDL precursors, very low density (VLDL) and intermediate density (IDL) lipoproteins, were also lower in nicotine-treated primates while total postheparin lipase (LPL + HTGL) activity was significantly elevated. Our data indicate that long-term consumption of oral nicotine induces an atherogenic lipoprotein profile (increases LDL, decreases HDL/total cholesterol ratio) by enhancing lipolytic conversion of VLDL to LDL. These results have important health implications for humans who use smokeless tobacco products or chew nicotine gum for prolonged periods.

Administration, Oral↗

Oral nicotine impairs clearance of plasma low density lipoproteins.

The effect of chronic oral nicotine intake on plasma low density lipoprotein (LDL) clearance, lipid transfer protein, and lecithin:cholesterol acyltransferase (LCAT) was examined in male atherosclerosis susceptible squirrel monkeys. Eighteen yearling primates were divided into two groups: 1) Controls fed isocaloric liquid diet; and 2) Nicotine monkeys given liquid diet supplemented with nicotine at 6 mg/kg body wt/day for a two-year period. Averaged over 24 months of treatment, animals in the Nicotine group had significantly higher levels of plasma and LDL cholesterol compared to Controls while plasma LCAT activity was similar for both groups. Following simultaneous injection of 3H LDL and 14C high density lipoprotein (HDL) cholesteryl ester (CE), removal of the latter was not altered by oral nicotine while plasma clearance of 3H LDL was dramatically delayed in Nicotine monkeys. Transfer of 14C HDL CE to very low density lipoprotein (VLDL)-LDL particles was greatly accelerated in the Nicotine group vs Controls while the reciprocal movement of 3H LDL CE to HDL was only higher in experimental animals at two time points following injection of the isotopes. Results from this study provide evidence that one major detrimental effect of long-term oral nicotine use is an increase in the circulating pool of atherogenic LDL which is due to: 1) accelerated transfer of lipid from HDL; and 2) impaired clearance of LDL from the plasma compartment. Diminished removal of LDL is of particular importance because an extended residence time of these particles in circulation would increase the likelihood of their deposition in the arterial wall.

Administration, Oral↗

Sensitivity to shearing and compressive motion in random dots.

The sensitivity of the visual system to motion of differentially moving random dots was measured. Two kinds of one-dimensional motion were compared: standing-wave patterns where dot movement amplitude varied as a sinusoidal function of position along the axis of dot movement (longitudinal or compressional waves) and patterns of motion where dot movement amplitude varied as a sinusoidal function orthogonal to the axis of motion (transverse or shearing waves). Spatial frequency, temporal frequency, and orientation of the motion were varied. The major finding was a much larger threshold rise for shear than for compression when motion spatial frequency increased beyond 1 cycle deg-1. Control experiments ruled out the extraneous cues of local luminance or local dot density. No conspicuous low spatial-frequency rise in thresholds for any type of differential motion was seen at the lowest spatial frequencies tested, and no difference was seen between horizontal and vertical motion. The results suggest that at the motion threshold spatial integration is greatest in a direction orthogonal to the direction of motion, a view consistent with elongated receptive fields most sensitive to motion orthogonal to their major axis.

Humans↗

Ethanol induced alterations in low and high density lipoproteins.

Male squirrel monkeys fed ethanol (ETOH) at variable doses were used to determine whether alcohol modifies levels of plasma low density lipoproteins (LDL) in addition to increasing high density lipoproteins (HDL). Because we earlier showed that high alcohol consumption enhances lipoprotein cholesterol synthesis, experiments were also performed to further assess whether ETOH alters lipoprotein clearance and plasma transfer processes in vivo. Monkeys were divided into three groups: Controls fed isocaloric liquid diet; and Low and High ETOH animals fed liquid diet with vodka substituted isocalorically for carbohydrate at 12 and 24 of the calories, respectively. High ETOH primates had significantly more LDL lipid and protein while serum glutamate oxaloacetate transaminase was similar for the three groups. Although removal of 3H LDL cholesteryl ester (CE) from the plasma compartment was not affected by dietary ETOH, transfer of LDL CE to HDL was impaired in the High ETOH group suggesting a mechanism for the enlarged circulating pool of LDL. Transfer of 14C HDL CE to lower density lipoproteins was similar for the three groups. However, ETOH at both doses delayed clearance of radiolabeled HDL CE from circulation. Thus besides enhancing synthesis of lipoproteins, ETOH at a moderately high dose (24% of calories) influences lipoprotein levels in primates by modifying lipid transfer processes (LDL) as well as by altering clearance (HDL) without adversely affecting liver function.

Animals↗

Comparison of labetalol, hydrallazine, and propranolol in the therapy of moderate hypertension.

The efficacy of labetalol, an alpha and beta adrenoceptor blocking drug, has been compared with that of placebo, of propranolol alone, of hydrallazine alone, and of hydrallazine plus propranolol in combination in a randomized double-blind, fixed-dose crossover trial. Labetalol (300 mg twice a day) was equally effective with propranolol (80 mg twice a day), and more effective than hydrallazine (50 mg twice a day) alone. The effect of labetalol was comparable with that of hydrallazine plus propranolol when the patient was standing, but less potent with the patient in the supine position. Side effects were few.

Antihypertensive Agents↗

Sleep disorders in children after burn injury.

Eighty-two children and adolescents between the ages of 30 months and 20 years (mean, 11.8 years) who were admitted to one of two pediatric burn units with a mean initial burn injury of 43.8% total body surface area and a mean age at time of injury of 4.2 years were studied 1 year or more after burn injury (mean, 7.3 years). Subjects were found to have profound at-home sleep disorders, which were manifested as nightmares in 30 subjects (37%), bed-wetting in 20 (24%), and sleep-walking in 6 (18%). Dream content related to normal childhood topics in 45 patients (55%), burn injury in 6 (7%), and burn treatment in 5 (6%). No relationship exists between age at time of burn, length of time after burn injury, cause of burn injury, family history of nightmares, or patient history of bed-wetting and the incidence of nightmares. Daytime naps were reported in 50 subjects (63%), although 46 (mean age, 11.7 years) were well beyond the normal age for napping.

Adolescent↗