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Biomedical subjects

O C Ingebretsen

Publications and source records attributed to O C Ingebretsen.

At least 19 recordsLinked to original sources

The progression of chronic kidney disease: a 10-year population-based study of the effects of gender and age.

The increase in demand for renal replacement therapy makes it important to investigate the prognosis of the earlier stages of chronic kidney disease (CKD). We examined the change in glomerular filtration rate (GFR), and patient and renal survival in CKD stage 3 in the municipality of Tromsø, a well-defined European community with a population of 58,000. All patients with estimated GFR between 30 and 59 ml/min/1.73 m(2) for more than 3 months during a 10-year study period were identified from a complete database of all 248 560 measurements of serum creatinine made in the community in the study period. Change in GFR was estimated for each patient using a multilevel model. A complete follow-up with respect to patient and renal survival was obtained from hospital databases. A total of 3047 patients was included. The median number of measurements of creatinine for each patient was 9, and the median observation time was 44 months. Mean estimated change in GFR was--1.03 ml/min/1.73 m(2)/year. Seventy-three percent of the patients experienced a decline in GFR. The 10-year cumulative incidence of renal failure was 0.04 (95% CI 0.03-0.06) and mortality 0.51 (95% CI 0.48-0.55). Female gender was associated with slower decline in GFR and better patient and renal survival. In this population-based study, the decline in GFR in CKD was slower than in previously studied selected patient groups. A high mortality pre-empted the development of renal failure in many patients. The prognosis of CKD depended strongly on gender.

Adult↗

Combination of recombinant human growth hormone and glutamine-enriched total parenteral nutrition to surgical patients: effects on circulating amino acids.

BACKGROUND & AIMS: Both recombinant human growth hormone (rhGH) and glutamine (GLN) may have beneficial anabolic actions on amino acid metabolism. The aim of this study was to evaluate the additive effects of rhGH and GLN on plasma amino acids postoperatively. METHODS: 31 females undergoing laparoscopic cholecystectomy were randomized to three groups: Group I (n=10) received 13 IU/m(2) of rhGH the morning of surgery and the following three postoperative days, together with glutamine-free TPN for the first two postoperative days. Group II (n=11) received rhGH as the first group, together with glutamine-enriched (7 g GLN/m(2)/day) TPN. Group III (n=10) received glutamine-enriched TPN as the second group, but rhGH was replaced by placebo. Daily plasma amino acid concentrations and nitrogen balance were determined. RESULTS: In the GH treated groups, the plasma concentrations of several amino acids were decreased on the third postoperative day, compared to preoperatively. This was not observed in Group III. The changes were more pronounced in Group II. In Group II the negative AV-differences of amino acids tended to be attenuated, while the patients in Group III had increased negative AV-differences. The cumulative nitrogen balance was significantly improved in the GH groups, compared with Group III. CONCLUSION: The combined treatment of growth hormone and glutamine has additive effects on AV-balances of amino acids postoperatively, whereas nitrogen balance is not further improved when adding glutamine to rhGH treatment.

Adult↗

Cimetidine reduces weight and improves metabolic control in overweight patients with type 2 diabetes.

OBJECTIVE: To investigate the weight-reducing effect of cimetidine in overweight patients with Type 2 diabetes. DESIGN: A 12-week clinical intervention study of 400 mg cimetidine prescribed three times daily in a randomised, double-blind, placebo-controlled design. SUBJECTS: Forty-three overweight patients with Type 2 diabetes (age 18-65 y, body mass index (BMI) 27.2-48.2 kg/m2). MEASUREMENTS: Body weight, BMI, body fat, waist and hip circumference, waist/hip ratio, blood pressure, fasting blood glucose, HbA1c, plasma concentrations of insulin, insulin/glucose ratio and lipids at the start and after 12 weeks, and daily recordings of appetite. RESULTS: Subjects given cimetidine (n = 19) and placebo (n = 24) lost 5.0 +/- 2.2 kg (mean +/- s.d.) and 1.3 +/- 1.1 kg, respectively. Significant reductions were observed in appetite, body fat (29.9 +/- 6.6% to 25.3 +/- 7.4%), waist circumference (111.5 +/- 10.3 cm to 107.4 +/- 10.6 cm), waist/hip ratio (0.96 +/- 0.08 to 0.94 +/- 0.08), and systolic and diastolic blood pressure (reductions of 6.9 +/- 11.4 mm Hg and 6.0 +/- 6.6 mm Hg, respectively) in cimetidine group only. Significant decreases in fasting concentrations of blood glucose, HbA1c, plasma insulin, insulin/glucose ratio, plasma triglycerides and a significant increase in plasma high-density lipoprotein cholesterol were observed in the cimetidine group only. CONCLUSIONS: Cimetidine reduces appetite and body weight, and improves metabolic control in overweight subjects with Type 2 diabetes.

Adolescent↗

Effects of Simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia.

OBJECTIVES: Patients with combined hyperlipidemia are at increased risk for development of coronary heart disease. The purpose of this study was to evaluate the efficiency and the safety of treatment with Simvastatin and omega-3 fatty acids in patients with this lipid disorder. DESIGN: A double-blind placebo controlled, randomized study evaluating the effects of Simvastatin separately and in combination with omega-3 fatty acids in 41 healthy patients with defined hyperlipidemia. After a 16 weeks dietary run-in period the patients were treated in periods of 5 weeks. RESULTS: As expected Simvastatin (20 mg day[-1]) reduced serum total cholesterol, triacylglycerols, apolipoproteins B and E and increased HDL-cholesterol and apolipoprotein A1. Addition of omega-3 fatty acids (4 g day[-1]) further decreased serum triacylglycerols (P = 0.007), total cholesterol (P = 0.052) and apolipoprotein E (P = 0.035). No significant changes attributable to supplementation of polyunsaturated fatty acids on the content of lipid peroxides in plasma and in the various lipoprotein fractions were observed. CONCLUSIONS: The combined treatment of Simvastatin and omega-3 fatty acids seems to be an efficient and safe alternative for patients with combined hyperlipidemia.

Adult↗

Gender differences in the relationships between plasma plasminogen activator inhibitor-1 activity and factors linked to the insulin resistance syndrome in essential hypertension.

Impaired fibrinolysis due to elevated levels of plasma plasminogen activator inhibitor type 1 (PAI-1) is a risk factor for thromboembolic disease. Hypertension, obesity, derangements in lipid and glucose homeostasis, and elevated levels of PAI-1 are features of the insulin resistance syndrome. The interrelationships between PAI-1 and the metabolic disturbances seen in this condition are unsettled. We investigated the associations between PAI-1 activity and components of the insulin resistance syndrome in 53 men and 31 women with untreated hypertension. In men, PAI-1 activity correlated significantly with plasma glucose (r = .41, P = .002), insulin sensitivity (r = -.35, P = .01), and insulin-induced suppression of nonesterified fatty acid (NEFA) (r = -.43, P = .007). Plasma glucose and NEFA suppression were independently associated with PAI-1 activity in a multivariate analysis. In women, PAI-1 activity correlated with body mass index (r = .62, P = .0005), waist-to-hip ratio (r = .75, P = .0001), plasma glucose (r = .50, P = .007), insulin (r = .49, P = .009), proinsulin (r = .57, P = .002), C-peptide (r = .60, P = .0009), insulin sensitivity (r = -.74, P = .0001), NEFA suppression (r = -.64, P = .003), and triglycerides (r = .58, P = .001). In multivariate analyses, insulin sensitivity and NEFA suppression were independently associated with PAI-1 if waist-to-hip ratio was not included in the model. After introduction of waist-to-hip ratio into the model, waist-to-hip ratio was the only independent predictor of PAI-1 activity. We conclude that in women, waist-to-hip ratio, body mass index, and insulin-induced NEFA suppression are determinants for PAI-1 activity. In men, insulin-induced NEFA suppression and plasma glucose are independently associated with PAI-1 activity.

Adult↗

Fibrinolytic function after dietary supplementation with omega3 polyunsaturated fatty acids.

Hypertension is associated with derangements in glucose and lipid metabolism. Increased levels of plasminogen activator inhibitor type 1 (PAI-1) are thought to potentiate the development of coronary events in this condition. Fish oil (omega3 polyunsaturated fatty acids [PUFAs]) have lipid-lowering effects, but the cardioprotective potential has been questioned because fish oil has been found to increase PAI-1 activity. This study was performed to determine the effects of omega3 PUFAs on the fibrinolytic function in hypertension. Seventy-eight persons with untreated hypertension were included in a 16-week, double-blind, randomized, controlled intervention study with 4 g/d of eicosapentaenoic and docosahexaenoic acids or corn oil placebo. Plasma PAI-1 activity, tissue plasminogen activator (tPA) activity, levels of fibrinogen and factor VII(c), and platelet count were measured before and after intervention (mean+/-SE). PAI-1 activity changed similarly in the fish oil and corn oil groups (1.8+/-1.0 U/mL versus 3.5+/-1.2 U/mL, P=.25), as did tPA (-0.02+/-0.02 IU/mL versus -0.13+/-0.03 IU/mL, P=.28), levels of factor VII(c) (6+/-5% versus 5+/-4%, P>.3), and platelet count (2+/-7x10(9)/L versus 3+/-5x10(9)/L, P>.3). None of these variables changed from pretreatment levels during fish oil intake. Fibrinogen levels increased significantly both during fish oil (0.6+/-0.1 g/L, P=.0001) and corn oil (0.4+/-0.1 g/L, P=.002) intake. There was no between-group difference (P>.3). In conclusion, a daily intake of 4 g omega3 PUFAs does not affect PAI-1 and tPA activity in persons with hypertension. A modest increase in fibrinogen levels was observed after both fish oil and corn oil intake.

Adult↗

Effects of n-3 polyunsaturated fatty acids on glucose homeostasis and blood pressure in essential hypertension. A randomized, controlled trial.

OBJECTIVE: To determine whether dietary supplementation with fish oil adversely affects glycemic control in patients with hypertension. DESIGN: Randomized, double-blind, placebo-controlled study. PATIENTS: 78 persons with untreated hypertension recruited from a population survey. INTERVENTION: Participants were randomly assigned to receive eicosapentaenoic and docosahexaenoic acids, 4 g/d, or corn oil placebo, 4 g/d, for 16 weeks. MEASUREMENTS: An oral glucose tolerance test; assessments of insulin release, glucose disposal, and insulin sensitivity done using the hyperglycemic clamp technique to keep plasma glucose levels at 10 mmol/L for 180 minutes; assessment of insulin sensitivity done using a euglycemic hyperinsulinemic clamp technique (infusing insulin and glucose to keep plasma glucose levels at 5 mmol/L); assessments of lipid levels and blood pressure. Measurements were done before and after intervention. RESULTS: Changes in integrated glucose and insulin response after the oral glucose challenge did not differ between the fish oil and corn oil groups after intervention (-0.6 +/- 0.7 compared with -1.0 +/- 0.6 mmol/L [P > 0.3] for integrated glucose and 143 +/- 76 compared with 169 +/- 84 pmol/L [P > 0.3] for insulin response). Changes in first-phase insulin release (34 +/- 72 pmol/L in the fish oil group compared with 191 +/- 112 pmol/L in the corn oil group [P > 0.3]), second-phase insulin release (179 +/- 66 pmol/L compared with 257 +/- 122 pmol/L [P > 0.3]), and insulin sensitivity index (-0.03 +/- 0.01 compared with -0.01 +/- 0.01 [mumol/kg.min divided by pmol/L]; P > 0.3) were also similar in both groups after treatment. Fish oil lowered systolic blood pressure by 3.8 mm Hg more than control (P = 0.04) and lowered diastolic blood pressure by 2.0 mm Hg more than control (P = 0.10). After fish oil treatment, triglyceride levels decreased by 0.28 +/- 0.08 mmol/L more than control (P = 0.01), and very-low-density lipoprotein cholesterol levels decreased by 0.13 +/- 0.04 mmol/L more than control (P = 0.01). CONCLUSION: Fish oil, in doses that reduce blood pressure and lipid levels in hypertensive persons, does not adversely affect glucose metabolism.

Adult↗

The level of gamma-glutamyltransferase in serum, effect of carbohydrate heterogeneity on clearance rate.

The measurement of serum gamma-glutamyltransferase (GT) is a frequently used parameter of liver diseases. The serum enzyme originates from liver and is cleared from the circulation by the galactose receptor in liver. The rate of uptake will thus vary with the amount of terminal galactose residues on the enzymes' carbohydrate moiety. Using an experimental rat model we have studied the relative clearance rates of variant forms of GT with different carbohydrate composition. GT purified from pancreas and kidney contains less sialic acid and showed considerably higher clearance rates than the enzyme from liver. The rapid uptake of the kidney and pancreas enzymes indicates that these enzymes may not reach detectable levels if released from these organs to the circulation. On the other hand, GT in serum of alcoholics contains increased amount of sialic acid and this enzyme variant showed a slightly decreased clearance rate compared to the normal liver enzyme. Increased sialylation of GT may thus contribute to the increased level of the enzyme in serum after alcohol abuse.

Alcoholism↗

Influence of a concentrated ethylester compound of n-3 fatty acids on lipids, platelets and coagulation in patients undergoing coronary bypass surgery.

Twenty patients accepted for coronary bypass surgery were randomized to receive either a concentrated ethylester compound of n-3 fatty acids, with a daily dose of 3.15 g of eicosapentaenoic acid (EPA) and 1.89 g of docosahexaenoic acid (DHA), or corn oil (controls) in a double blind study, to evaluate the effect on lipids, platelets and coagulation during the pre- and postoperative phase. Only patients with fasting triglyceride (TG) levels greater than or equal to 1.6 mmol/l at recruitment were eligible. The study was continued for 5 to 6 months. Surgery was usually performed at mid-intervention. Blood samples were collected during morning hours in fasting subjects, just prior to intervention, preoperatively and at final postoperative follow-up. Moreover, blood loss was accurately accounted for postoperatively. A threefold increase (p = 0.0001) of EPA was noted at pre- and postoperative follow-up. TG-levels were reduced 20 and 39%, respectively, in patients on n-3 fatty acids, reaching statistical significance at end of intervention (p = 0.034). TG-levels in controls remained largely unchanged. In patients on n-3 fatty acids, there was a statistically significant increase in serum total cholesterol preoperatively, but this change was no longer present at completion of the study. No significant changes were noted in platelet function, as judged by bleeding time, collagen induced platelet aggregation and release of TxB2 during aggregation. Parameters of extrinsic coagulation, including phospholipase C-sensitive factor VII (PLC-VII) and extrinsic pathway inhibitor (EPI), also remained essentially unchanged in both groups of patients. However, fibrinogen was significantly reduced in controls (p less than 0.05) at end of intervention.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Depressed metabolism and low protein catabolism in fasting grey seal pups.

Grey seal pups (Halichoerus grypus) were collected at the time of weaning (mid-October) and fasted for 52 days at thermoneutrality in separate cages. Body weight decreased exponentially, while metabolic rate dropped 45% from an average of 2.95 +/- 0.15 (SEM) W kg-1 at day 2 of fasting to a stable level of 1.62 +/- 0.06 (SEM) W kg-1 from day 10 to day 47 of fasting. Respiratory quotient was low, indicating extensive catabolism of triglycerides, while plasma cortisol was fairly stable at 110 +/- 8 (SEM) nmol l-1 throughout the fasting period. Daily urinary output decreased from 236 +/- 20 (SEM) ml day-1 at day 2 to a stable value of 87 +/- 6 (SEM) ml day-1 between days 8 and 50 of fasting. The urine was analysed for urea, uric acid, creatinine, ammonia, total nitrogen and osmolality. Urea was always the principal excretory end-product, amounting to between 70 and 80% of the total excreted nitrogen. The urine was moderately concentrated (range 770-1300 mosmol kg-1). Total excreted urinary nitrogen decreased by 68% from 3.7 +/- 0.7 (SEM) g day-1 to 1.2 +/- 0.4 (SEM) g day-1 between days 2 and 50. The urinary nitrogen was used to calculate the daily amount of protein being oxidized and its energy content was compared with the measured basal metabolic rate of individual animals. Approximately 6% of the energy expended by grey seal pups during the post-weaning fast is derived from oxidation of protein. It is concluded that a rapid depression of basal metabolic rate and extensive blubber catabolism enable grey seal pups to endure prolonged periods of fasting without any apparent signs of discomfort or stress.

Animals↗

Phospholipase C-sensitive factor VIII activity in normal pregnancy.

We have previously reported the existence of a phospholipase C-sensitive form of factor VII-probably a factor VII-phospholipid complex in normal pregnancy. By bivariate regression analysis, the level of this complex shows highly significant positive correlations with serum triglycerides (r = 0.90, p less than 0.0001) and blood platelet count (r = 0.067, p = 0.0004). This high degree of correlation was verified by stepwise multiple regression analysis. It is presently not known how this factor VII complex formes.

Adult↗

Liquid chromatography of serotonin and adenine nucleotides in blood platelets, illustrated by evaluation of functional integrity of platelet preparations.

In this relatively rapid liquid-chromatographic procedure the endogenous serotonin in blood platelets is quantified by fluorometry. We used this experimental procedure to estimate the platelet-release reaction as an indicator of the functional integrity of stored platelets. a decrease in the platelet-release reaction more sensitively indicates platelet changes during storage than do alterations in total ATP concentration or adenylate energy charge. The described method for quantifying serotonin is convenient enough for routine use in blood banks.

Adenine Nucleotides↗

Relationship between myocardial adenine nucleotide catabolism and tissue blood flow rate in experimental ischaemia.

A method was developed for tissue preservation and evaluation of the adenine nucleotide metabolism in small samples of myocardium after 45 min of ischaemia. Ischaemia was produced by coronary artery occlusion in anaesthetized cats. Adenine nucleotides and their metabolites were measured by isocratic liquid chromatographic systems which allow quantitative analysis of the nucleotides and their metabolites inosine, hypoxanthine and xanthine in biopsies of 5-20 mg tissue. Regional myocardial blood flow was measured in the tissue surrounding the biopsies by the distribution of 15 micron radiolabelled microspheres. In central ischaemic regions the ATP level was approximately 1 mumol/g wet weight, whereas in normally perfused myocardium the ATP level was approximately 5 mumol/g tissue. In tissue with intermediate flow values, intermediate ATP levels were found. Energy charge, which summarizes all adenine nucleotide concentrations, was reduced from 0.88 to 0.50, and the molar concentrations of inosine, hypoxanthine and xanthine increased in ischaemic tissue. We conclude that this method provides reliable characterization of the local cellular energy status in cat hearts with ischaemic regions.

Adenine Nucleotides↗

The content of coenzyme A, acetyl-CoA and long-chain acyl-CoA in human blood platelets.

The amounts of coenzyme A (CoASH) and acetyl-CoA in the acid-soluble extract of human blood platelets were quantitated by an isocratic reversed-phase liquid-chromatographic system. The analytical column was Supelcosil LC-18, and the solvent was 220 mmol/l potassium phosphate, pH 4.0, and 120 ml/l methanol. Long-chain acyl-CoA was estimated by the released coenzyme A after an alkaline hydrolysis of the acid-insoluble material of the blood platelets. The median values in platelets from fourteen healthy persons were 30 pmol CoASH/mg platelet protein, 45 pmol acetyl-CoA/mg platelet protein, and 34 pmol long-chain acyl-CoA/mg platelet protein.

Acetyl Coenzyme A↗

Determination of adenine nucleotides and inosine in human myocard by ion-pair reversed-phase high-performance liquid chromatography.

An isocratic high-performance liquid chromatographic system for the quantitation of AMP, ADP and ATP is presented. The separations were achieved at room temperature by reversed-phase chromatography (Supelcosil LC-18). The standard solvent was 220 mM potassium phosphate, pH 6.9, 1% (v/v) methanol and 0.3 mM tetrabutylammonium hydrogen sulphate. A selective retention of the adenine nucleotides as a group relative to the mono-, di- and triphosphates of guanosine, uridine and cytidine was observed under these experimental conditions. The adopted procedure was applied to the separation of adenine nucleotides in biological extracts, i.e., human myocard. The adenine nucleotides in an extract of myocard were quantitated in less than 20 min. Only 5-10 mg (wet weight) of myocard were needed in order to determine the energy charge of a myocardial sample. Also inosine was easily quantitated in this liquid chromatographic system.

Adenine Nucleotides↗

Transport of ascorbate into guinea pig liver mitochondria.

The amount of ascorbate associated with guinea pig liver mitochondria was estimated by high-performance liquid chromatography. Incubation of mitochondria with ascorbate revealed a time-dependent and temperature-dependent accumulation of the vitamin. A steady-state level of ascorbate was obtained in the mitochondria after about 20 min of incubation at 37 degrees C, whereas no accumulation was observed at 0 degrees C. The matrix concentration of ascorbate was highly correlated to the concentration of ascorbate in the incubation medium. The initial rate of accumulation (about 7 pmol/mg protein per min at 10 degrees C) was three orders of magnitude less than for compounds that are transported across the mitochondrial inner membrane by specific carriers. Experiments with the enzyme ascorbate oxidase demonstrated that the mitochondrial membrane is also permeable to dehydroascorbate, and that the accumulated dehydroascorbate is stable in the mitochondria. There was no effect of the energy state of the mitochondrial membrane of the initial transport rate of ascorbate. Electrostatic binding of ascorbate to the membrane was excluded from experiments performed in isosmotic potassium chloride medium. Diffusion of ascorbate across the mitochondrial inner membrane accounts for the experimental findings.

Animals↗

Uric acid determinations: reversed-phase liquid chromatography with ultraviolet detection compared with kinetic and equilibrium adaptations of the uricase method.

A reversed-phase liquid-chromatographic procedure is presented for quantitation or uric acid in human serum, with absorbance measured at 292 nm. The mobile phase was sodium acetate (35 mmol/L, pH 5.0)/acetonitrile (9/1 by vol). Complete precipitation of serum proteins was obtained by mixing serum (50-500 microL) with an equal volume of acetonitrile, and the precipitate was removed by centrifugation. Aliquots (20 microL) of the supernate were injected directly into the liquid chromatograph, which was adjusted so that the absorbance reading of the uric acid peak was as high as possible. Routinely, a full-scale deflection of 1.28 absorbance units was used. The within-run precision (CV) was 0.6% for a serum uric acid concentration of 227 mumol/L and day-to-day precision over a 15-day period was 0.8% for uric acid of 345 mumol/L. No interferences from related compounds were observed. We compared results by this method with those by kinetic (aca, Du Pont) and equilibrium adaptations (Ames kit; Nyco-test, Nyegaard; and Monotest, Boehringer Mannheim) of uricase methods. The method we report is simple, and can be used in a fully automatic liquid-chromatographic system.

Chromatography, High Pressure Liquid↗