Biomedical subjects

M S Christensen

Publications and source records attributed to M S Christensen.

At least 19 recordsLinked to original sources

PubMed2000

Bioequivalence between ready-to-use recombinant human growth hormone (rhGH) in liquid formulation and rhGH for reconstitution.

The bioequivalence of recombinant human growth hormone (rhGH) for reconstitution, at either 24 IU or 8 mg, and three strengths of liquid formulation of rhGH (5, 10 or 15 mg per 1.5 ml, hGH) was tested in two randomized, single-blind, four-period, crossover studies in healthy subjects. The study drugs were administered by subcutaneous injection at a dose of 2.5 mg rhGH/m(2)body surface area or as a fixed dose of 5 mg rhGH. Endogenous hGH release was suppressed by a continuous somatostatin infusion. The 90% confidence intervals for the estimated mean ratios of AUC(0-24 h)and C(max)(analysis of variance) between all products were within 80-125% in both studies. Also, no significant differences (P> 0.05; Wilcoxon signed rank test) were found between t(max)for the liquid formulations of rhGH. These data demonstrate that there is bioequivalence between rhGH for reconstitution and the liquid formulations of rhGH.

Adult↗

PubMed2000

Single-dose pharmacokinetics of repaglinide in subjects with chronic liver disease.

Repaglinide is a novel insulin secretagogue developed in response to the need for a fast-acting, oral prandial glucose regulator for the treatment of type 2 (non-insulin-dependent) diabetes mellitus. Repaglinide is metabolized mainly in the liver; its pharmacokinetics may therefore be altered by hepatic dysfunction. This open, parallel-group study compared the pharmacokinetics and tolerability of a single 4 mg dose of repaglinide in healthy subjects (n = 12) and patients with chronic liver disease (CLD) (n = 12). Values for AUC and Cmax were significantly higher in CLD patients compared with healthy subjects, and the MRT was prolonged in CLD patients. Values for tmax did not differ between the groups, but t1/2 was significantly prolonged in CLD patients compared with previously determined values in healthy subjects. AUC was inversely correlated with caffeine clearance in CLD patients but not in healthy subjects. Blood glucose profiles were similar in both groups. Adverse events (principally hypoglycemia) were similar in the two groups; none was serious. Repaglinide clearance is significantly reduced in patients with hepatic impairment; the agent should be used with caution in this group.

Adult↗

PubMed2000

Alpha-linolenic acid and heart rate variability.

BACKGROUND AND AIM: The marine long-chained n-3 polyunsaturated fatty acids seem to have antiarrhythmic effects in humans. Similar effect has also been postulated for alpha-linolenic acid, a plant-derived polyunsaturated fatty acid--from the n-3 family. The purpose of the study was to examine the relation between the content of alpha-linolenic acid in cell membranes and the risk of malignant arrhythmias as assessed by determination of heart rate variability (HRV). METHODS AND RESULTS: Patients at high risk of sudden cardiac death (52 with a previous myocardial infarction and 29 with chronic renal failure on dialysis) were enrolled as well as 64 healthy volunteers. The cell membrane content of alpha-linolenic acid was analyzed by gas chromatography and related to 24-hour HRV, which was measured in all subjects. No correlations were found between levels of alpha-linolenic acid and 24-hour HRV. CONCLUSION: The present study was unable to demonstrate a positive correlation between cell membrane levels of alpha-linolenic acid and HRV. Our results suggest that alpha-linolenic acid per se is devoid of an antiarrhythmic effect, though this effect could arise from its conversion to the longer chained n-3 PUFA, usually derived from fish.

Aged↗

PubMed1999

Assay for levormeloxifene, a selective estrogen receptor modulator, in human and monkey plasma employing high-performance liquid chromatography and solid-phase extraction.

Assays for levormeloxifene, a new selective estrogen receptor modulator, and its 7-desmethyl metabolite in human and cynomolgus monkey plasma are described. Plasma was extracted on mixed-mode bonded sorbent material (C8/SCX) and the extracts were analysed by high-performance liquid chromatography with fluorescence detection. Recoveries of levormeloxifene and the metabolite exceeded 70%. Within and total assay precision calculated as a coefficient of variation (C.V.) were <8% for both compounds at all concentration levels, except at the limit of quantitation (LOQ) where the C.V. was 15%. Within and total-assay accuracy calculated as a percentage of the nominal value were between 90 and 114% for both analytes. The LOQ was for levormeloxifene and 7-desmethyllevormeloxifene, respectively, 1.5 and 2.5 ng/ml (man) and 5.2 and 6.9 ng/ml (monkey). In the monkey plasma assay, human plasma could substitute monkey plasma as blank plasma.

Animals↗

PubMed1999

1-(1,2,5-Thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2,6)]heptanes as new potent muscarinic M1 agonists: structure-activity relationship for 3-aryl-2-propyn-1-yloxy and 3-aryl-2-propyn-1-ylthio derivatives.

Two new series of 1-(1,2,5-thiadiazol-4-yl)-4-azatricyclo[2.2.1.0(2, 6)]heptanes were synthesized and evaluated for their in vitro activity in cell lines transfected with either the human M1 or M2 receptor. 3-Phenyl-2-propyn-1-yloxy and -1-ylthio analogues substituted with halogen in the meta position showed high functional potency, efficacy, and selectivity toward the M1 receptor subtype. A quite unique functional M1 receptor selectivity was observed for compounds 8b, 8d, 8f, 9b, 9d, and 9f. Bioavailability studies in rats indicated an oral bioavailability of about 20-30%, with the N-oxide as the only detected metabolite.

Animals↗

PubMed1999

Lipidemic effects of an interesterified mixture of butter, medium-chain triacylglycerol and safflower oils.

The objective of this study was to determine if the positional structure of dietary triacylglycerol affected lipidemic responses. Thirty healthy adults (16 men and 14 postmenopausal women) with low-density lipoprotein cholesterol (LDL-C) concentrations >3.37 mM (130 mg/dL) enrolled in a prospective, single-blind, cross-over outpatient clinical trial that consisted of two 5-wk dietary phases. After baseline screening, subjects were instructed to follow individualized meal plans (weight maintenance diets with 36% of total energy from fat, half of which was from a test oil) and randomized to receive either butter (B) or an interesterified mixture (IM) of butter, medium-chain triacylglycerol (MCT), and safflower oils. Blood drawn during weeks 5 and 10 of feeding was analyzed for total cholesterol (TC), high density lipoprotein cholesterol (HDL-C),LDL-C, and triacylglycerols (TAG). Mean plasma levels of TC (B, 6.98+/-1.06 mM; IM, 7.09+/-1.20 mM), HDL-C (B,1.30+/-0.35 mM; IM, 1.29+/-0.34 mM), and LDL-C (B, 4.91+/-0.95 mM; IM, 4.92+/-1.10 mM) were not significantly different between the two dietary treatments. Mean TAG levels were higher for the interesterified B-MCT mixture (B, 1.75+/-0.72 mM; IM, 1.96+/-0.86 mM, P < 0.05). We conclude that an IM of B, MCT, and safflower oils as compared to native B has no appreciable effect on plasma cholesterol concentrations but is associated with a modest rise in plasma TAG.

Adipose Tissue↗

PubMed1999

Heart rate variability and plasma lipids in men with and without ischaemic heart disease.

Decreased 24-h heart rate variability (HRV) is associated with increased coronary mortality. The objective of this study was to examine the relation between plasma lipids and HRV (1) in men with a previous myocardial infarction (MI) and left ventricular dysfunction and (2) in healthy men. Forty seven men (mean age 63 years) with a previous MI and a left ventricular ejection fraction < or = 0.40 and 38 healthy men (mean age 37 years) were included. A 24-h Holter recording and fasting blood samples were performed in all the subjects. Plasma total-cholesterol and low-density-lipoprotein (LDL)-cholesterol were inversely correlated with 24-h HRV in both groups. Plasma cholesterol remained significantly inversely correlated to the 24-h HRV in a stepwise multiple regression analysis. The men were dichotomized according to the mean plasma cholesterol in the study population which was 6.2 mmol/l in patients with a previous M1, and 5.2 mmol/l in the group of healthy men. In both groups, men with plasma cholesterol levels above the mean had the lowest HRV. In conclusion, the data suggest, that hypercholesterolaemia is associated with a decreased 24-h HRV in men with and without ischaemic heart disease, suggesting an increased risk of sudden cardiac death.

Adult↗

PubMed1999

Heart rate variability and fatty acid content of blood cell membranes: a dose-response study with n-3 fatty acids.

BACKGROUND: Dietary intake of long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against sudden cardiac death, an event that may be predicted by measurement of heart rate variability (HRV). OBJECTIVE: The objectives of this study were to 1) examine the correlations between the content of fatty acids in blood cell membranes (platelets and granulocytes) and HRV in healthy subjects, and 2) assess the effect on HRV of dietary intervention with n-3 PUFA in different doses. DESIGN: Sixty healthy volunteers (25 women and 35 men) were randomly assigned to 3 treatment groups in a double-blind design. Subjects received a daily supplement of either 6.6 g n-3 PUFA, 2.0 g n-3 PUFA, or placebo (olive oil). A 24-h Holter recording was obtained for each subject before supplementation and after 12 wk of supplementation; the 24-h HRV was then related to the content of fatty acids in granulocytes and platelets. RESULTS: Before supplementation, positive correlations were observed in men between the content of docosahexaenoic acid in cell membranes and HRV indexes (r = 0.50, P < 0.01), whereas such correlations were not found in women. Dietary intervention revealed a dose-dependent effect of n-3 PUFA on HRV in men, whereas no effect was found in women. CONCLUSION: The study showed a beneficial effect of n-3 PUFA on HRV in healthy men, suggesting an antiarrhythmic effect of n-3 PUFA. No such effect was observed in healthy women.

Adult↗

PubMed1997

Essential fatty acid deficiency in patients with severe fat malabsorption.

Essential fatty acid deficiency is commonly described in patients receiving parenteral nutrition, but the occurrence in patients with severe fat malabsorption not receiving parenteral nutrition is uncertain. One hundred twelve patients were grouped according to their degree of fat malabsorption: group 1, < 10% (n = 52); group 2, 10-25% (n = 21); group 3, 25-50% (n = 24); and group 4, > 50% (n = 15). Fecal fat was measured by the method of Van de Kamer the last 2 of 5 d of a 75-g fat diet. Serum fatty acids in the phospholipid fraction were measured by gas-liquid chromatography after separation by thin-layer chromatography and expressed as a percentage of total fatty acids. The concentration of linoleic acid in groups 1, 2, 3, and 4 was 21.7%, 19.4%, 16.4%, and 13.4% respectively (P < 0.001). The concentration of linolenic acid in groups 1, 2, 3, and 4 was 0.4%, 0.4%, 0.3% and 0.3%, respectively (P = 0.017). Evidence of essential fatty acid deficiency, defined as a serum concentration of linoleic acid less than the lower limit if the 95% CI in patients without fat malabsorption (group 1), was 5% (1/21), 38% (9/24), and 67% (10/15) in groups 2, 3, and 4, respectively. A considerable proportion of patients with gastrointestinal diseases resulting in malabsorption of > 25-50% of dietary fat intake and not treated with parenteral nutrition have biochemical signs of essential fatty acid deficiency. The clinical effect of these changes are yet to be elucidated.

Adult↗

PubMed1997

n-3 fatty acids do not decrease plasma endothelin levels in healthy individuals.

The effect of three different doses of n-3 polyunsaturated fatty acids (PUFA) on endothelin-1 (ET-1) was studied. Study 1 included 40 healthy volunteers randomized to a single supplement of 20 g of n-3 or n-6 PUFA. Plasma ET-1 was measured 14 h after ingestion, and no changes in plasma ET-1 after intake of n-3 PUFA were observed, compared to baseline values. In study 2, 32 subjects had 0.65 g of n-3 PUFA or a fat mixture per day for 12 weeks. No changes in plasma ET-1 were found after the oil supplements. Finally, 22 persons had 4 g of n-3 PUFA for 6 weeks. A significant increase in plasma ET-1 was seen in this group after the supplement. Thus, n-3 PUFAs do not lower plasma levels of ET-1, the most potent vasoconstrictor known.

Adult↗

PubMed1996

Effects of dietary triacylglycerol structure on triacylglycerols of resultant chylomicrons from fish oil- and seal oil-fed rats.

We investigated the influence of the intramolecular fatty acid distribution of dietary triacyl-sn-glycerols (TAG) rich in n-3 polyunsaturated fatty acids (PUFA) on the structure of chylomicron TAG. Fish oil and seal oil, comparable in fatty acid compositions but with different contents of major n-3 PUFA esterified at the sn-2 position (20:5n-3, 46.6%, and 5.3%; 22:6n-3, 75.5%, and 3.8%, respectively), were fed to rats. Mesenteric lymph was collected and the chylomicrons were isolated by ultracentrifugation. The fatty acid composition of chylomicrons largely reflected the fatty acid composition of the oils administered. The intramolecular fatty acid distributions of the TAG fed were reflected in the chylomicron TAG as the fraction of the total contents observed in the sn-2 position of 20:5n-3 were 23.6 and 13.3%, and of 22:6n-3 were 30.6 and 5.4% for resultant chylomicrons following fish oil and seal oil administration, respectively. Thus, after seal oil administration, significant higher load of n-3 PUFA was esterified in the sn-1,3 positions of chylomicron TAG compared with fish oil administration (P < 0.05).

Animals↗

PubMed1995

Absorption of triglycerides with defined or random structure by rats with biliary and pancreatic diversion.

Fat absorption may be compromised by pancreatic or bile insufficiency, resulting in low uptake of essential fatty acid and energy. Using a rat model of malabsorption, we examined the absorption of defined triglycerides with medium-chain fatty acids (MCFA) in the sn-1,3 positions and essential fatty acids in the sn-2 position (MLM) compared to other fats. The thoracic duct was cannulated for collection of lymph, and the common bile and pancreatic duct was cannulated to divert both the pancreatic juice and bile. The rats were given a single bolus of triglyceride as a taurocholate emulsion. Fat absorption was measured from collected lymph samples. The triglycerides administered were a defined triglyceride, MLM [mainly (8:0/10:0)-(18:2n-6)-(8:0/10:0)], a similar triglyceride subjected to chemical randomization, a mixture of medium-chain triglycerides and soybean oil, and soybean oil, respectively. The first three triglycerides had approximately 36 wt% linoleic acid (18:2n-6) content. Administration of defined triglyceride was followed by significantly higher lymphatic level (wt%) of 18:2n-6 (P < 0.01) as well as a relative enhancement in mol% of 18:2n-6 (P < 0.05) compared to the other triglycerides. Lymphatic absorption of MCFA was similar in the three first groups but not as efficient as for long-chain fatty acids. Our results indicate that defined triglycerides thus may provide a means to increase absorption of essential fatty acids in fat malabsorption, such as that seen in cystic fibrosis, or for pre-term infants.

Absorption↗

PubMed1995

Intestinal absorption and lymphatic transport of eicosapentaenoic (EPA), docosahexaenoic (DHA), and decanoic acids: dependence on intramolecular triacylglycerol structure.

We compared the absorption of eicosapentaenoic (EPA, 20:5n-3), docosahexaenoic (DHA, 22:6n-3), and decanoic acids in mesenteric lymph duct-cannulated rats following intragastric administration of two oils with different intramolecular triacylglycerol structures. One oil had a specific triacylglycerol structure with EPA and DHA located in the sn-2 position and decanoic acid in the sn-1 and sn-3 positions (specific M-n3-M) whereas the other oil had a random fatty acid distribution (random M-n3-M). The mol% (mol/100 mol total fatty acids) of fatty acids in the two oils was similar, with approximately 66 mol% of decanoic acid and 22 mol% of EPA and DHA. The lymphatic transport (microgram/min) of EPA and DHA as well as the mol% in the total lymph lipids were significantly (both P < 0.01) increased following intragastric administration of specific M-n3-M compared with random M-n3-M. The mol% of decanoic acid in the total lymph lipids was significantly (P < 0.01) higher after random M-n3-M compared with specific M-n3-M but the transport (microgram/min) of decanoic acid was not significantly different. We conclude that under our experimental conditions specific M-n3-M with EPA and DHA predominantly in the sn-2 position of the triacylglycerols was a more readily absorbed source of EPA and DHA and in this context should be investigated further for the potential use in clinical nutrition.

Animals↗

PubMed1994

Lymphatic absorption of n - 3 polyunsaturated fatty acids from marine oils with different intramolecular fatty acid distributions.

Male Wistar rats were given 0.5 ml of either fish oil or seal oil intragastrically. The intramolecular fatty acid distributions of the triacylglycerols administered were determined by non-specific Grignard degradation followed by isolation and analysis of the 2-monoacylglycerols. The n - 3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acid (20:5(n - 3)) and docosahexaenoic acid (22:6(n - 3)), were located in outer positions (sn-1/3) in the seal oil triacylglycerols whereas the sn-2 position of fish oil triacylglycerols was enriched in 20:5(n - 3) and 22:6(n - 3). The mesenteric lymph was collected over the following 24 h and the absorption patterns of n-3 PUFAs were determined. In the lymph, the n - 3 fatty acids characteristic of the marine oils rapidly increased both with regard to mole percentage and transport (micrograms/min). There were, however, no overall significant differences in the absorption patterns over a 24 h period. The ratio between mole percentage in the oil and mole percentage in the lymph calculated at the steady-state period was significantly greater for both 20:5(n - 3) and 22:6(n - 3) following fish oil administration compared with seal oil. Initially, the recovery of n - 3 PUFAs as a percentage of the total amount transported over the experimental period was higher following injection of fish oil than seal oil but seal oil resulted in greater recovery in the last two fractions at 8 and 24 h post injection, respectively. This indicated that n - 3 PUFAs from fish oil may have been better absorbed in the initial period of digestion but overall the structure of dietary triacylglycerols had negligible effects on the assimilation of n - 3 PUFAs when these were administered as native marine oils.

Animals↗

PubMed1994

Effects of eltanolone on cerebral blood flow and metabolism in healthy volunteers.

BACKGROUND: Eltanolone is a new steroid anesthetic agent that may prove to be useful in clinical practice. The aim of the present study was to evaluate the effects of eltanolone on cerebral blood flow (CBF) and metabolism in healthy volunteers. METHODS: In a randomized cross-over study, eight subjects received intravenous eltanolone 0.6 mg/kg or its vehicle. CBF was measured with the intravenous xenon 133 technique before and 2 and 30 min after administration of eltanolone or vehicle. Cerebral metabolic rate for oxygen (CMRO2) was calculated as the product of the measured cerebral arteriovenous oxygen content difference and the blood flow. RESULTS: CBF decreased from a baseline value of 64 +/- 4 (mean +/- SD) to 42 +/- 6 ml.100 g-1.min-1 at 2 min after administration of eltanolone and only 4% after vehicle. Cerebral oxygen consumption was 4.1 +/- 0.4 ml.100 g-1.min-1 at baseline and decreased to 2.7 +/- 0.6 at 2 min after eltanolone, whereas metabolism did not change significantly after administration of vehicle. At 30 min CBF and Cerebral metabolic rate for oxygen were 16 and 10% less than baseline values, respectively. Coupling between CBF and Cerebral metabolic rate for oxygen was preserved at all measurements. After administration of eltanolone a significant decrease in mean arterial blood pressure of 6 mmHg and a period of hypoventilation were observed. This did not occur after injection of vehicle. CONCLUSIONS: Eltanolone was shown to reduce cerebral oxygen consumption and blood flow in healthy volunteers. Coupling between metabolism and flow was preserved.

Adult↗

PubMed1994

Intestinal absorption of octanoic, decanoic, and linoleic acids: effect of triglyceride structure.

The influence of triglyceride structure on the intestinal absorption of specific triglycerides was investigated. A bolus of either a structured or a randomized oil was given to lymph-cannulated rats. The structured oil contained medium-chain fatty acids (MCFA) in the sn-1 and sn-3 position of the triglyceride, and linoleic acid (C18:2 n-6) in the sn-2 position, whereas in the randomized oil the same fatty acids were distributed randomly between the three positions. The absorption of MCFA was highest from the randomized oil, where approximately 33% of the MCFA were located in the sn-2 position. The absorption of C18:2 n-6 was highest from the structured oil, where C18:2 n-6 is located in the sn-2 position, indicating that the intestinal absorption is influenced by triglyceride structure, and that the absorption is enhanced for fatty acids located in the sn-2 position. Prior to lymph collection, the rats were fed either a fish oil or a vegetable oil diet. The absorption of C18:2 n-6 was highest in the rats previously fed the fish oil diet. The incorporation of the highly unsaturated fatty acids from the fish oil into the membrane phospholipids may thus influence the absorption of fat.

Animals↗

PubMed1991

[Costs and prices of laboratory services].

Cost accounting is performed in private and public laboratories. Guidelines for these activities are required and with this objective in mind, the Board of the Danish Society of Clinical Chemistry commissioned a working group to produce a position paper which is presented now in this report. The report discusses the objectives, the principles and the general requirements for cost accounting. The significance of information on costs for the clinicians' rational use of the laboratory is also illustrated. The working group points out that prerequisites for lucid and appropriate costing guidelines are clarification of which purposes information on costs are meant to serve, identification of the relevant cost centers and quality assurance of laboratory services to a defined extent. It is common practice to express laboratory costs as costs per test. The report advocates calculation of the cost per patient contact, i.e. the overall costs for laboratory service in a given investigative situation.

Accounting↗

PubMed1990

Epidermal growth factor reactivity in rat milk.

The concentration of EGF immunoreactivity in rat whey increases from 0.3 pmol/ml at lactation day 1 to 2.0 pmol/ml at lactation day 19. The concentration of EGF is not influenced when the rats undergo sialoadenectomy prior to mating. On S-200 gel chromatography, almost all EGF-reactivity in rat whey elutes as a broad peak corresponding to a Stokes radius of 4.0 nm (an approximate molecular weight of 80 kDa). Almost no 6 kDa EGF is present. Judged by gel filtration of whey pre-incubated with 125I-EGF (6 kDa), no binding protein for EGF is present in rat whey. When rat milk is incubated overnight at 37 degrees C, the 80 kDa EGF is degraded and elutes as a peak with a Stokes radius of 2.7 nm, corresponding to a molecular weight of approximately 35 kDa EGF and as a peak corresponding to 6 kDa EGF. Also, after partial purification by immuno-affinity chromatography, the EGF-reactive material in rat whey behaves as a peptide with a Stokes radius of 2.7 nm, corresponding to a molecular weight of approximately 35 kDa at gel filtration. Comparative binding studies between EGF purified from the submandibular glands and the EGF purified from rat whey confirm differences in the binding to antibodies raised against submandibular EGF, but not in binding to the EGF-receptor. Our results make it unlikely that EGF in rat whey is derived from the submandibular glands.

Animals↗