The minimum substrate of cyclic AMP-stimulated protein kinase, as studied by synthetic peptides representing the phosphorylatable site of pyruvate kinase (type L) of rat liver.
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Animals↗
Biomedical subjects
L Berglund
Publications and source records attributed to L Berglund.
Non-dependence on native structure of pig liver pyruvate kinase when used as a substrate for cyclic 3',5'-AMP-stimulated protein kinase.
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Animals↗
Cyclic 3',5'-AMP-stimulated and non-stimulated phosphorylation of protein fractions from rat-liver cell sap on incubation with (gamma-32P)ATP.
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Adenosine Triphosphate↗
Sn-protoporphyrin lowers serum bilirubin levels, decreases biliary bilirubin output, enhances biliary heme excretion and potently inhibits hepatic heme oxygenase activity in normal human subjects.
Sn-protoporphyrin, a potent competitive inhibitor of heme oxygenase, the rate-limiting enzyme in the degradation of heme to bile pigment, was administered to 10 normal volunteers: 8 males and 2 females. A significant decrease in the levels of serum (mean decrease; 38%) and biliary bilirubin (mean decrease: 47%) was demonstrated in all 10 subjects. The decrease in these parameters lasted for a minimum of 4 days after administration of the metalloporphyrin. Sn-protoporphyrin also facilitated the excretion of endogenous heme in bile during the 24- to 48-hr period following administration of the compound. The metalloporphyrin was rapidly cleared from plasma with a half-life of 3.4 hr. A small amount (3 to 6%) of Sn-protoporphyrin was excreted in both urine and bile. The activity of microsomal heme oxygenase was measured in five human liver samples freshly obtained at the time of cholecystectomy and varied from approximately 2 to 4 nmoles bilirubin formed per mg protein per hour. The addition of Sn-protoporphyrin to microsomal heme oxygenase isolated from these liver samples resulted in a dose-dependent decrease in the activity of this enzyme at concentrations of the metalloporphyrin in the range of 10(-7) to 10(-9) M. The findings reported here provide strong evidence that the suppression of biliary and serum bilirubin levels and the enhancement of heme excretion in the bile of the normal volunteers examined in this study were due to inhibition of physiological rates of heme oxidation activity by the synthetic heme analog, Sn-protoporphyrin.
Adult↗
Placental transfer of methionine during protein restriction in the rhesus monkey studied by position emission tomography.
Four pregnant Rhesus monkeys were given a 1 week protein restricted diet with the objective to monitor possible effects on transplacental transfer of [11CH3]-L-methionine with positron emission tomography (PET). The weight was reduced in all monkeys, two of which later had an intrauterine fetal death. The mean venous serum concentrations of free methionine in the mothers were not significantly changed during the study period, although a tendency towards lower values during protein restriction was noted like in the majority of the amino acids. The uptake of trace amount of [11CH3]-L-methionine in the fetus was studied with PET before the reduced diet, after 1 week on the reduced diet and after the return to a habitual diet. Our results indicate an increase in the uptake of radioactivity in the amniotic cavity after protein restriction. The PET-technique in its present form seems to be a useful method in the investigation of transplacental transfer of several natural amino acids as well as of other compounds labelled with 11C.
Animals↗
Residual C-peptide excretion is associated with a better long-term glycemic control and slower progress of retinopathy in type I (insulin-dependent) diabetes mellitus.
We evaluated the progression of microangiopathic lesions in 22 type I diabetic patients with residual C-peptide excretion and in 22 type I diabetic patients matched for age at onset and disease duration without residual C-peptide excretion. We also wished to elucidate whether certain HLA-DR phenotypes were associated with preserved insulin secretory activity and/or microvascular lesions. The two groups of patients were investigated in 1984 and 1985. In the previous report, we observed less frequent signs of early microangiopathic lesions in association with a lower HbA1c in the group with a detectable urinary C-peptide excretion. The HbA1c level has been measured regularly (7-12 times) since the initial investigation; the mean value was lower in the patient group with residual C-peptide excretion than in the non-C-peptide group (p = 0.01). Nine of the patients in the group without urinary C-peptide excretion had increased severity of retinopathy, but only two in the group with urinary C-peptide excretion (p = 0.04) had progression of retinopathy. Incipient and/or manifest albuminuria was observed in six of the nonexcretor group and one of the C-peptide excretors. Four of the patients were receiving antihypertensive treatment and three others had a diastolic blood pressure greater than or equal to 90 mmHg in the non-C-peptide excretor group as compared with one with a pressure greater than or equal to 90 mmHg in the C-peptide excretor group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Structural properties of interlocking nails, canine femora, and femur-interlocking nail constructs.
Using standard material testing techniques (bending stiffness, torsional stiffness, and maximum torque to failure or yield torque), the structural properties of interlocking nails (IN), canine femora, and IN/femur constructs were determined. Specimens that were tested included: 6 and 8 mm diameter IN with 5 to 10 screw holes (n = 18), and intact canine femora (n = 10), which also, with an IN inserted, formed the intact construct (IC) group, (n = 10). Specimens in the IC group were first tested with an 8 mm diameter IN with zero screws, followed by one and two screws (4.5 mm diameter) in the proximal and distal femur. A fracture model construct (FMC), (n = 14), consisting of a transverse femoral osteotomy with a 3 mm gap, was used with either 6 mm or 8 mm IN. In the 6 mm FMC, one and two 3.5 mm screws were used sequentially in the proximal and distal femoral segment. In the 8 mm FMC, one and two 3.5 mm screws and one and two 4.5 diameter screws were used similarly. When bending forces were applied parallel to IN screw holes, mean IN stiffness was 20% less than with forces perpendicular to the holes (n = 18), (P < .05). Eight-millimeter IN were 220% stiffer in torsion and 270% stiffer in bending than 6 mm IN (P < .05). Six-millimeter IN had approximately 32% of the bending stiffness and torsional stiffness of intact femurs (P < .05). Eight-millimeter IN had 93% and 79% of the bending stiffness and torsional stiffness, respectively, of intact femurs. Intact femur constructs (8 mm IN with four, 4.5 mm screws) had 147% of the bending stiffness (P < .05), and similar torsional stiffness and maximum torque, as intact femora (P > .05). The mean values of 6 mm FMC with four screws (3.5 mm) were 21% and 33% in torsional stiffness and bending stiffness, respectively, of intact femora values. When tested in torsion, 8 mm FMC failed by bone fracture; 6 mm FMC, in contrast, underwent plastic deformation. In comparing FMC stabilized with an 8 mm IN with two screws (4.5 mm diameter) in each bone segment, to intact femurs, the maximum torque was similar, FMC torsional stiffness was 40% (P < .05), and FMC bending stiffness was 65% (P < .05). These 8 mm FMC percentages are comparable to human IN fracture model construct values, indicating that the 8 mm IN/four screw construct should provide adequate stabilization for many canine diaphyseal femoral fractures.
Animals↗
The antioxidant butylated hydroxytoluene protects against atherosclerosis.
Rabbits fed a 1% cholesterol diet with or without the antioxidant butylated hydroxytoluene (BHT) developed typical atherosclerotic lesions. The addition of BHT gave higher levels of total cholesterol (+40%), triglycerides (+250%), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) in plasma. Despite the lower plasma lipid levels, the degree of atherosclerosis of the aortic surface was considerably higher in rabbits fed cholesterol than in the group treated with cholesterol and BHT. The mean atherosclerotic involvement was 18.6 +/- 4.4% in the former group and 5.9 +/- 1.7% in the latter group (p = 0.02). In all animals, there was a high correlation between the area of the arterial lesion and cholesterol content (r = 0.96). Serum levels of cholesterol autooxidation products (7-ketocholesterol and cholesterol 5 alpha,6 alpha-epoxide) were lower in the group of rabbits treated with BHT (p less than 0.005). Serum levels of vitamin E were slightly higher in the BHT group. There was no significant difference in the clearance of beta-VLDL between the two treatment groups after using either beta-VLDL from cholesterol-fed animals or beta-VLDL from BHT-fed animals. The results are in accord with the contention that oxidative modification of lipoproteins is important for the development of atherosclerosis and that antioxidants may have a protective effect. At present, however, other explanations cannot be completely excluded, for example, effects of antioxidants on immunologic factors or monocyte adhesion.
Animals↗
Metabolism of lipoprotein remnants in humans. Studies during intestinal infusion of fat and cholesterol in subjects with varying expression of the low density lipoprotein receptor.
To study the possible importance of the low density lipoprotein (LDL) receptor in regulating the degree of postprandial lipemia, a cholesterol-rich fat emulsion was infused into the duodenum of subjects who were divided into four groups based on the expected variation in the expression of the LDL receptor: young men (n = 11), elderly men (n = 7), male patients on estrogen therapy (n = 5), and patients with familial hypercholesterolemia (n = 9). In familial hypercholesterolemia, fasting plasma levels of lipoproteins of d less than 1.006 g/ml, intermediate density lipoproteins, and LDLs were increased. During the fat infusion, the cholesterol and triglyceride contents in the d less than 1.006 g/ml fraction increased to a similar extent in all groups, whereas a concomitant reduction of LDL cholesterol levels was observed. The degree of the decrease in LDL cholesterol was positively correlated with the observed increase in triglycerides in the d less than 1.006 g/ml fraction. There were no signs of accumulation of intermediate density lipoproteins during infusion in any of the groups studied. The results indicate that the capacity for clearance of chylomicrons and chylomicron remnants is not affected by variation in LDL receptor expression.
Adult↗
Safety and efficacy of Omacor in severe hypertriglyceridemia.
BACKGROUND: Severe hypertriglyceridemia is a risk factor for acute pancreatitis, therefore decreasing serum triglyceride concentrations is an important component of risk management. Omega-3 fatty acids are well known hypotriglyceridemic agents, but their efficacy in severe forms of the disorder is not well documented. Our objective was to examine the effects of Omacor, a drug composed of 85% omega-3 fatty acid ethyl esters. METHODS: Forty-two patients with triglyceride concentrations between 5.65 and 22.60 mmol/l (500 and 2000 mg/dl) were studied in a prospective, double-blind, placebo-controlled trial of Omacor (4 g/day for 4 months). RESULTS: Compared with baseline values, Omacor significantly reduced mean triglyceride concentrations by 45% (P<0.00001), cholesterol by 15% (P< 0.001), very-low-density lipoprotein cholesterol by 32% (P< 0.0001) and cholesterol:high density lipoprotein (HDL) cholesterol ratio by 20% (P=0.0013), and increased HDL cholesterol by 13% (P=0.014) and low-density lipoprotein cholesterol by 31% (P=0.0014). The placebo had no effect on these parameters. Omacor was well tolerated and no patient discontinued medication because of side effects. CONCLUSIONS: Four capsules of Omacor per day markedly decreased triglyceride concentrations in patients with severe hypertriglyceridemia. The availability of a potent and safe omega-3 fatty acid preparation for this patient population should diminish the risk for acute pancreatitis, and may also reduce the long-term risk for cardiovascular disease.
Cholesterol↗