Biomedical subjects

F Andreasen

Publications and source records attributed to F Andreasen.

At least 37 records · Page 2Linked to original sources

PubMed1997

The effect of NaO Li Su on memory functions and blood chemistry in elderly people.

In traditional Chinese medicine a mixture of bee pollen, radix polygoni multiflore, semen ziziphi spinosae, radix salviae multiorhizae, fructus schisandrae and fructus ligustris lucidae, known as NaO Li Su, has a reputation as a remedy against declining memory functions. In the present study the effect of the preparation on failing memory was assessed in 100 elderly Danish volunteers who complained of a deteriorating memory. The study was a double-blind placebo controlled cross-over trial. The effect was evaluated after treatment periods of 3 months' duration by a battery of psychological and biochemical tests. No desirable effects on memory functions were achieved by the active treatment. Increases in the number of red blood cells and in the serum creatinine levels were seen after active treatment. In the subgroup initially showing a number of red blood cells below the median a significant positive correlation was found between changes in the number of red blood cells and changes in the Wechsler Memory Scale scores.

Aged↗

PubMed1997

Functional and structural changes in the thick ascending limb of Henle's loop in rats with liver cirrhosis.

Five weeks after common bile duct ligation (CBL), Wistar rats had histologically verified liver cirrhosis with sodium retention but without ascites. Plasma concentrations of vasopressin and aldosterone were normal. Glomerular filtration rate was unchanged, although renal plasma flow was increased. A test dose of furosemide (7.5 mg/kg body wt iv) produced significantly greater diuretic (+59%) and natriuretic (+66%) responses in Wistar CBL rats than in sham-operated controls. Stereological examination of kidneys demonstrated a 47% increase in the volume of the inner stripe of the outer medulla, with a 55% increase in the volume of thick ascending limb of Henle's loop (TALH) epithelium in cirrhotic Wistar rats relative to controls. CBL produced a similar degree of liver cirrhosis in vasopressin-deficient Brattleboro rats. However, both functional and structural renal changes observed in cirrhotic Wistar rats were absent in vasopressin-deficient cirrhotic Brattleboro rats. These results suggest a permissive action of vasopressin for the adaptive changes in TALH in rats with experimental liver cirrhosis. Our results are consistent with the hypothesis that increased sodium chloride reabsorption in the TALH may contribute to the early sodium retention that precedes ascites formation in rats with secondary biliary liver cirrhosis.

Animals↗

PubMed1996

Effects of brain death and glucose infusion on hepatic glycogen and blood hormones in the pig.

We wished to study the effects of intravenous glucose/ insulin infusion to brain-dead pigs on the hepatic glycogen content. Four groups of 40-kg pigs were studied: brain-dead and control pigs given isotonic saline or glucose/insulin (7.5 mg glucose/kg/min, 1.25 mU insulin/kg/ min) (n = 5 to 10 in each group). Brain death was induced by inflating a balloon placed in the epidural space. In brain-dead pigs given saline, liver glycogen decreased from 45 +/- 11 mmol/g DNA (mean +/- SEM) to 7 +/- 3 mmol/ g DNA after 6 hours. Thereafter, it increased to 28 +/- 9 mmol/g DNA after 9 hours (P = .05 compared with the 6-hour measurement). These changes were accompanied by transient increases in plasma adrenaline, glucose, free fatty acids (FFA), and glucagon. Following glucose/ insulin infusion, hepatic glycogen increased steadily and was approximately double after 12 hours (P < .01) in both brain-dead and in non-brain-dead pigs. In brain-dead pigs, the increases in the aforementioned blood measurements were smaller following glucose/insulin infusion than following saline infusion. However, studies of longer duration will be needed to examine these effects on a time scale that is relevant to human organ donors. In conclusion, the decrease in hepatic glycogen content after brain death could be prevented by intravenous glucose/insulin infusion probably because of a reduction of the adrenaline response to the induction of brain death.

Animals↗

PubMed1996

Inhibition of muscle glycogen synthase activity and non-oxidative glucose disposal during hypoglycaemia in normal man.

The purpose of the present study was to evaluate the role of muscle glycogen synthase activity in the reduction of glucose uptake during hypoglycaemia. Six healthy young men were examined twice; during 120 min of hyperinsulinaemic (1.5 mU.kg-1. min-1) euglycaemia followed by: 1)240 min of graded hypoglycaemia (plasma glucose nadir 2.8 mmol/l) or 2) 240 min of euglycaemia. At 350-360 min a muscle biopsy was taken and indirect calorimetry was performed at 210-240 and 330-350 min. Hypoglycaemia was associated with markedly increased levels of adrenaline, growth hormone and glucagon and also with less hyperinsulinaemia. During hypoglycaemia the fractional velocity for glycogen synthase was markedly reduced; from 29.8 +/- 2.3 to 6.4 +/- 0.9%, p < 0.05. Total glucose disposal was decreased during hypoglycaemia (5.58 +/- 0.55 vs 11.01 +/- 0.75 mg.kg-1. min-1 (euglycaemia); p < 0.05); this was primarily due to a reduction of non-oxidative glucose disposal (2.43 +/- 0.41 vs 7.15 +/- 0.7 mg.kg-1 .min-1 (euglycaemia); p < 0.05), whereas oxidative glucose disposal was only suppressed to a minor degree. In conclusion hypoglycaemia virtually abolishes the effect of insulin on muscle glycogen synthase activity. This is in keeping with the finding of a marked reduction of non-oxidative glucose metabolism.

Adult↗

PubMed1995

Role of extracellular and intracellular acidosis for hypercapnia-induced inhibition of tension of isolated rat cerebral arteries.

The importance of smooth muscle cell pHi and pHo for the hypercapnic vasodilation of rat cerebral arteries was evaluated in vitro. Vessel segments were mounted in a myograph for isometric tension recording; pHi was measured by loading the smooth muscle cells with the fluorescent dye BCECF, and pHo was measured with a glass electrode. In all studies, Ca(2+)-dependent basal tension (in the absence of any agonist) and tension in the presence of arginine vasopressin were investigated. Control solution was physiological saline bubbled with 5% CO2 and containing 25 mmol/L HCO3- (pH 7.45 to 7.50). Induction of hypercapnic acidosis (10% CO2) or normocapnic acidosis (15 mmol/L HCO3-) caused significant inhibition of smooth muscle tension, and both conditions reduced pHi as well as pHo. N-Nitro-L-arginine significantly inhibited the relaxation to hypercapnic acidosis but had no significant effect on relaxation to normocapnic acidosis. Predominant extracellular acidosis, induced by reducing [HCO3-] from 25 to 9 mmol/L and CO2 from 5% to 2.5%, also caused inhibition of tension in steady state. By contrast, predominant intracellular acidosis, induced by increasing [HCO3-] from 25 to 65 mmol/L and CO2 from 5% to 15%, induced a small increase of basal tension and a small decrease of tension in the presence of arginine vasopressin. The responses to predominant intracellular or extracellular acidosis were qualitatively similar in the presence and absence of endothelium and in the presence and absence of N-nitro-L-arginine. It is concluded that the extracellular acidosis and not smooth muscle intracellular acidosis is responsible for the relaxation to hypercapnic acidosis.

Acidosis↗

PubMed1995

Supra-additive natriuretic synergism between bendroflumethiazide and furosemide in rats.

To examine the diuretic and natriuretic synergism between bendroflumethiazide (BFTZ) and furosemide (FUR), the acute diuretic and natriuretic response to BFTZ was compared when given alone, during acute and during chronic FUR infusion. Responses to diuretics were assessed in conscious, chronically instrumented rats and, to avoid confounding influences of diuretic-induced volume contraction, extracellular fluid volume was kept constant by a computer-driven servo-control technique. Two groups were pretreated with osmotic minipumps chronically infusing either FUR (0.25 mg/hr; group CF; n = 9) or vehicle (8% ethanolamine; group CV; n = 8) i.p. for 7 days before the experiment. During the experiment, two other groups received either acute infusion with FUR (0.25 mg/hr; group AF; n = 16) or acute infusion with vehicle (150 mM glucose; group AV; n = 11). After a 60-min control period, BFTZ (0.083 mg; 0.25 mg/hr) was administered for 90 min to all four groups. Whereas the diuretic and natriuretic response to BFTZ was similar in groups AF, AV and CV, a supra-additive response was observed in the CF group (vs. group CV: delta urine flow rate: +78%; delta urinary Na excretion: +69%). BFTZ had no effect on the fractional excretion of Li, which suggests that the supra-additive effect was due to inhibition of an enhanced distal tubular Na reabsorption induced by chronic FUR administration. Because before BFTZ administration urinary Na excretion was 3-fold higher during acute than during chronic FUR infusion, an increased delivery of NaCl to the thiazide segment cannot by itself explain the exaggerated BFTZ response during chronic FUR treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗

PubMed1994

ACE inhibitor premedication attenuates sympathetic responses during surgery.

We studied cardiovascular and catecholamine responses for 3 days in three groups of patients undergoing abdominal hysterectomy. The night before surgery and again 2 h before induction of anaesthesia, patients received the ACE inhibitor, ramipril, the beta 1 blocker, metoprolol, or placebo. In the actively treated groups, mean diastolic pressure was reduced during surgery and increases in heart rate and arterial pressure after surgical incision were attenuated. During operation, stroke volume (SV) and cardiac output (CO) were significantly higher in the ramipril group. In contrast, beta 1, adrenergic block caused no significant changes in SV or CO. The concentration of noradrenaline in plasma and urine indicated that ACE inhibition caused attenuated release of noradrenaline. The results support the concept that angiotensin II facilitates release of noradrenaline from sympathetic nerves and that ACE inhibition inhibits this release.

Adult↗

PubMed1994

Effect of needle biopsy from the vastus lateralis muscle on insulin-stimulated glucose metabolism in humans.

To examine the cellular mechanisms behind conditions characterized by insulin resistance, the clamp technique is often combined with muscle biopsies. To test whether the trauma of a needle biopsy from the vastus lateralis muscle per se may influence insulin-stimulated glucose uptake, eight healthy subjects underwent two randomly sequenced hyperinsulinemic (insulin infusion rate: 0.6 mU.kg-1.min-1 for 150 min) euglycemic clamps with an interval of 4-6 wk. In one study (study B) a muscle biopsy (approximately 250 mg, i.e., larger than normal standard) was taken in the basal state just before the clamp procedure, whereas the other was a control study (study C). Insulin-stimulated glucose uptake was significantly reduced in study B (5.36 +/- 0.96 mg.kg-1.min-1) compared with study C (6.06 +/- 0.68 mg.kg-1.min-1; P < 0.05). Nonoxidative glucose disposal (indirect calorimetry) was decreased (2.81 +/- 1.08 vs. 3.64 +/- 1.34 mg.kg-1.min-1; P < 0.05), whereas glucose oxidation was unaltered. Likewise, endogenous glucose output ([3-3H]glucose) was identically suppressed during hyperinsulinemia. Circulating levels of epinephrine, glucagon, and growth hormone did not differ significantly in studies B and C. In contrast, plasma norepinephrine, serum cortisol, and free fatty acid rose after biopsy (P < 0.05). In conclusion, performance of a muscle biopsy may diminish insulin sensitivity by affecting nonoxidative glucose metabolism. This should be considered when assessing whole body insulin sensitivity after a percutaneous needle muscle biopsy.

Adult↗

PubMed1994

The glycaemic index of spaghetti and gastric emptying in non-insulin-dependent diabetic patients.

OBJECTIVE: In the dietary treatment of non-insulin-dependent diabetes mellitus (NIDDM) great interest has been focused on foods with low glycaemic indices. Spaghetti has a low glycaemic index, but in NIDDM the underlying mechanism has not been elucidated. We investigated whether the low glycaemic index in spaghetti was the result of a retarded gastric emptying. DESIGN: Randomized study. SETTING: Department of Endocrinology & Metabolism, Aarhus County Hospital. SUBJECTS: Eight NIDDM in-patients participated without drop-outs. INTERVENTIONS: Paracetamol was used as a marker of the gastric emptying. On three different occasions the patients ingested 40 g of carbohydrate as: (1) spaghetti without paracetamol, (2) spaghetti containing 1.5 g paracetamol, and (3) mashed potatoes with 1.5 g paracetamol added. During the 4 h observation periods blood samples were drawn frequently. The spaghettis were industrially manufactured. RESULTS: The spaghetti meals induced similar glucose and insulin responses. The potato meal induced significantly higher glucose and paracetamol areas [607 +/- 108 vs 284 +/- 54 mmol/l*240 min (P = 0.02), and 18,668 +/- 999 vs 4979 +/- 369 mumol/l*240 min (P < 0.02)] as well as lower emptying index (time(peak)/peak concentration ratio of paracetamol) [2.1 +/- 0.3 vs 0.4 +/- 0.1 (P = 0.001)], as compared with the spaghetti meal. CONCLUSIONS: This study shows that the ingestion of spaghetti was associated with a slower gastrointestinal accessibility of the carbohydrates, which accounts for the low glycaemic index of spaghetti in NIDDM subjects.

Acetaminophen↗

PubMed1993

Contractile function of right ventricular papillary muscle after left ventricular infarction in rats: effects of early and late inhibition of angiotensin converting enzyme.

Alterations in the right ventricular function may or may not contribute to progressive cardiac dysfunction after left ventricular infarction. Ligation of the left coronary artery (LCAL) was lethal within 24 h for 25% of 100 rats, whereas none of 21 sham-operated rats died. No rats died during the following 4 weeks, after which the ischaemic area of the left ventricular wall appeared fibrotic and weighed 0.041% of the body weight. Simultaneously, the weight of the right ventricle increased from 0.037 to 0.072% of the body weight. The hypertrophied right papillary muscle had a depressed force of contraction and prolonged contraction and relaxation phases. Angiotensin converting enzyme inhibition (ACEI) started early (24 h) prevented hypertrophy and normalized the contractile pattern under basic conditions. However, isoprenaline stimulation revealed that the relaxation phase was still prolonged. Concentration-effect curves for Ca2+ indicated that the pathological relaxation observed in the hypertrophied muscles and during isoprenaline stimulation of myocardium in ACEI treated animals could be due to insufficient re-uptake of cytosolic Ca2+ by the sarcoplasmic reticulum. The results support the idea that the development of right ventricular hypertrophy may contribute to pathophysiological consequences of an infarct in the left ventricle. ACEI started after 24 h prevented hypertrophy, whereas ACEI started after 14 days did not. ACEI was unable to normalize completely the balance between energy demand and energy delivery.

Angiotensin II↗

PubMed1993

A comparison of three diuretic regimens in heart failure.

Eight patients with mild heart failure were treated in random order for 1 week with 2 mg bumethanide at 0800 and 1200 (treatment 1) h, 1 mg bumethanide at 0800, 1200, 1800, 2200 (treatment 2) and 5 mg bendroflumethiazide at 0800 and 1800 (treatment 3) h. The 'quality of life' did not differ significantly between the three treatment periods. At the presumed trough of the diuretic effect the circulating blood volume was largest during treatment 1; it was 6.3% smaller during treatment 2 (P < 0.02) and 6.7% lower during treatment 3 (P < 0.05). In comparison with treatment 1, the maximal increase in rate-pressure product during physical exercise was 24.6% higher in treatment 3. Compared with treatment 1 the area under the curve (AUC) for plasma lactate during physical exercise was 14% lower during treatment 2 (P < 0.05) and 18% lower during treatment 3 (P < 0.01). These findings suggest that the type of program for diuretic therapy influences the magnitude of inevitable diurnal fluctuations in body fluids, the ability of the heart to work and the ability of the body to adjust to the oxygen demand.

Aged↗

PubMed1992

[Angiotensin I converting inhibitors in connection with anesthesia and surgery].

The renin angiotensin system is activated during anaesthesia and operation, and the degree to which this activation takes place depends on the hydration and circulation of the patient. The anaesthetic agent used is also important for the activation. Treatment with ACE-inhibitors blunts or abolishes the sympathetic response to anaesthesia/operation. ACEI treatment reduces the need for other hypotensive agents in controlled hypotensive anaesthesia. Some studies suggest that ACEI-treatment should be continued peroperatively on account of its stabilising effect on the circulation to avoid sudden fluctuations in blood pressure and organ perfusion. On the other hand measurements of the cerebral blood flow under anaesthesia in patients treated with ACEI have shown low values in a few patients and this led the authors to recommend discontinuation before anaesthesia. We conclude that controlled clinical trials to evaluate the haemodynamic and neurohumoral consequences of the interaction between ACEI and anaesthetics are required.

Anesthetics↗

PubMed1991

Furosemide kinetics and dynamics in rats and humans.

1. Increasing doses of furosemide (F) were given intravenously to rats and humans and initial pharmacokinetics and pharmacodynamics were compared. 2. Weight-related initial renal excretion rate of F was twice as high in rats and serum concentration at 30 min was twice as high in humans (P less than 0.01). 3. Volume of distribution for F was 44% larger in rats (P less than 0.01). 4. Maximal weight-related diuretic and natriuretic responses were, like the theoretical maximal efficiency, 5-6 times higher in the rat. The potency was 230 times lower in the rats. 5. On a molecular basis species differences in kinetics disappeared when standardization was based on ERPF and species differences in dynamics disappeared when standardization was based on GFR.

Animals↗

PubMed1991

Functional properties in vitro of systemic small arteries from rabbits fed a cholesterol-rich diet for 12 weeks.

1. Recent evidence has suggested that the impairment of endothelium-dependent cholinergic relaxation in vitro, which is seen in atherosclerotic large arteries of animals and man, could be part of a general deleterious effect to the endothelium of hypercholesterolaemia. 2. This possibility has been investigated in vitro by measuring the response to acetylcholine, sodium nitroprusside, 5-hydroxytryptamine and noradrenaline in segments of aorta and of femoral, mesenteric and cerebral small arteries (internal diameter approximately 200 microns) from control rabbits (n = 12) and from rabbits fed a 1% (w/w) cholesterol and 3% (w/w) coconut oil diet (n = 12) for 12 weeks. 3. Thoracic aorta segments from the control rabbits exhibited a maximal relaxation in response to acetylcholine of 64 +/- 11% compared with 10 +/- 5% (P less than 0.01) for thoracic segments from cholesterol-fed animals. Cerebral, femoral and mesenteric small arteries exposed to acetylcholine (10(-9)-10(-4) mol/l) relaxed to the same degree as arteries from control rabbits. The responses to sodium nitroprusside and bradykinin of the small arteries from the cholesterol-fed rabbits remained unaffected. 5-Hydroxytryptamine evoked comparable contractions in the small arteries, while the sensitivity to noradrenaline of the femoral small arteries was significantly decreased and the response of cerebral small arteries to noradrenaline in cholesterol-fed rabbits slightly increased compared with control rabbits. 4. Aorta from the cholesterol-fed rabbits had extensive atheromatous lesions. Morphological measurements and histological examination showed unchanged thickness and light microscopic appearance of intima and media of small arteries from cholesterol-fed animals compared with control animals. 5. The present study indicates that hypercholesterolaemia in this rabbit model is followed by atherosclerotic lesions and changed function of large arteries, but that both function and structure of systemic small arteries are largely unaffected.

Animals↗

PubMed1991

Single dose pharmacokinetics and pharmacodynamics of oral oxazepam in very elderly institutionalised subjects.

The effect of extreme old age on the pharmacokinetics and pharmacodynamics of orally administered oxazepam 15 mg was studied in 10 healthy elderly (age 80-94 years) institutionalised subjects and 10 healthy young controls (age 26-42 years). The total oxazepam clearance was 1.24 (0.91-1.80) ml min-1 kg-1 (median and range) and 1.44 (0.88-2.13) ml min-1 kg-1 in the elderly and young, respectively (NS), and the elimination half-lives were 8.1 (5.5-10.8) h and 5.7 (4.9-6.2) h. respectively (P less than 0.01). The percent of unbound oxazepam was greater in the elderly; 9.8 (8.1-13.3)% as opposed to 5.1 (3.7-5.9)% in the young (P less than 0.0001). Clearance of unbound oxazepam was lower in the elderly, median values being 13.8 (7.1-21.1) ml min-1 kg-1 compared with 30.3 (18.3-41.5) ml min-1 kg-1 in the young (P less than 0.0001). A single 15 mg dose oxazepam decreased the ability of the elderly to perform a finger tapping test at 3 h but not 8 h after drug administration, whereas placebo had no effect at either times. No effect was observed in the young subjects.

Administration, Oral↗

PubMed1990

Glucuronidation of oxazepam is not spared in patients with hepatic encephalopathy.

The disposition of oral oxazepam was investigated in seven patients with decompensated cirrhosis and encephalopathy and in nine healthy individuals to further examine the hypothesis of preservation of glucuronidation in liver disease. The patients showed a severe reduction in the quantitative liver function as assessed by estimation of the clearance of antipyrine; the median value was 9 ml.min-1 and the range was 6 to 12 ml.min-1. Apparent clearance of oxazepam in cirrhotic patients was 0.55 ml.min-1.kg-1, with a range of 0.46 to 1.24 ml.min-1.kg-1, compared with 1.19 ml.min-1.kg-1 and a range of 0.80 to 1.66 ml.min-1.kg-1 in the controls (p less than 0.05). The unbound clearance of oxazepam in patients was 4.1 ml.min-1.kg-1, with a range of 3.4 to 5.5 ml.min-1.kg-1, compared with 25.4 ml.min-1.kg-1, and a range of 16.7 to 43.7 ml.min-1.kg-1, p less than 0.001, in the controls. In patients with liver disease, the unbound clearance of oxazepam correlated significantly with antipyrine clearance (r = 0.88; p less than 0.05). The results suggest a reduced capacity for glucuronidation in patients with decompensated liver disease and severe hepatic failure that corresponds to the general reduction in the quantitative liver function.

Absorption↗

PubMed1990

Effect of amiodarone on 3H-ouabain binding sites in human skeletal muscle.

Na,K-ATPase, or the Na,K-pump, is essential for the excitability and contractility of muscle tissue. Hypothyroidism in associated with a marked decrease in the Na,K-pump concentration in skeletal muscle and myocardium. In 7 patients on long-term amiodarone treatment there was a 36% reduction in the concentration of 3H-ouabain binding sites in skeletal muscle biopsies compared to 7 healthy subjects. This decrease during long-term amiodarone treatment may represent an equivalent reduction in the concentration of the functional Na,K-pump and it may be important in the adverse effect of amiodarone on muscle.

Adult↗

PubMed1990

Pharmacokinetics and pharmacodynamics of oxazepam and metabolism of paracetamol in severe hypothyroidism.

1. The effect of severe hypothyroidism on the pharmacokinetics and pharmacodynamics of oxazepam 15 mg given orally (n = 10) and the metabolism of paracetamol 750 mg given intravenously (n = 8) was investigated before and after treatment with levothyroxine. 2. The median total and unbound clearance of oxazepam increased significantly during the study period from 0.78 ml min-1 kg-1 (0.40-1.25) to 1.22 ml min-1 kg-1 (0.66-1.94) and from 9.3 ml min-1 kg-1 (5.2-14.2) to 15.9 ml min-1 kg-1 (7.8-21.8), respectively (P less than 0.01). 3. The elimination half-life of oxazepam was prolonged by hypothyroidism to a median (range) value of 9.3 h (5.4-21.9) compared with 7.5 h (4.8-10.5) in the euthyroid state (P less than 0.05). 4. Hypothyroidism did not affect the protein binding of oxazepam; median values of the free percentage being 8.2% as compared with 7.7% when euthyroid. 5. The median (range) clearance of paracetamol under hypothyroid conditions was 3.12 ml min-1 kg-1 (1.64-4.40) and 4.70 ml min-1 kg-1 (3.18-5.70) following replacement therapy (P less than 0.01). This increase was associated with a comparable increase in the partial clearance to the glucuronide metabolite: 1.86 ml min-1 kg-1 to 2.70 ml min-1 kg-1. 6. Hypothyroidism was associated with decreased performance in a finger tapping test that was exacerbated by oxazepam. When the patients were euthyroid oxazepam did not produce any effect.

Acetaminophen↗