Biomedical subjects

F Andreasen

Publications and source records attributed to F Andreasen.

At least 55 records · Page 3Linked to original sources

PubMed1990

Mechanisms behind the relaxing effect of furosemide on the isolated rabbit ear artery.

The effect of furosemide on isometric contraction and 86Rb uptake were studied in the isolated rabbit central ear artery (CEA). A concentration-dependent relaxing effect of furosemide (0.06 mM-1.0 mM) was found in vessel segments with intact endothelium. The maximal relaxation was 28.6 +/- 3.9% (10). The effect was not diminished in segments deprived of endothelium, and removal of endothelium itself caused no change of the force development to electrical field stimulation. The relaxing effect was time-dependent and stimulation-dependent and was not significantly affected by membrane depolarization induced by increasing external [K+] from 10 to 120 mM. The 86Rb uptake was inhibited by both furosemide and ouabain (8.0 +/- 0.5(8) and 5.3 +/- 0.5(8) versus 12.8 +/- 0.9(16) nmol (K+).mm-1.(10 min.)-1 in the furosemide (1.0 mM), ouabain (1.0 mM) and control groups, respectively) without interaction between the two drugs. The 86Rb uptake was not further inhibited by increasing the furosemide concentration from 0.12 mM to 1.0 mM. Our results suggest: firstly, the direct relaxing effect of furosemide on isolated vessel segments is endothelium-independent and secondly, the inhibition of the Na(+)-K(+)-Cl- cotransport and a possible consequent hyperpolarization of the membrane is unlikely to be the sole mechanism responsible for the vasorelaxant effect of furosemide. The demonstrated direct effect on vascular tone may be of clinical importance in situations with very high plasma concentrations of the drug or very low concentrations of serum albumin.

Animals↗

PubMed1989

Influence of a very low calorie diet on the clearance of oxazepam and antipyrine in man.

A very low calorie diet (Prodi) was administered to eleven otherwise healthy obese subjects for fourteen days. The daily intake of protein was 52.7 g and carbohydrate 25.7 g, corresponding to 360 kcal. The clearance of oxazepam and antipyrine was investigated before and after the diet period. Total oxazepam clearance was 1.04 ml.min-1.kg-1 and it decreased 0.88-fold after the diet. The mean clearance of unbound oxazepam was correspondingly reduced 0.88-fold. The elimination half-life increased to 1.22-times the control value, 7.9 h. No significant change was found in the volume of distribution or protein binding of oxazepam. Antipyrine clearance, estimated by the one-sample technique, was 52.4 and 51.8 ml.min-1, before and after the diet, respectively. It appears that a very low calorie diet with a sufficient protein and a very low carbohydrate content decreases the metabolism of oxazepam by glucuro-conjugation, whereas no effect was seen on the oxidative metabolism of antipyrine.

Adult↗

PubMed1989

Rhizomucor miehei triglyceride lipase is processed and secreted from transformed Aspergillus oryzae.

The cDNA encoding the precursor of the Rhizomucor miehei triglyceride lipase was inserted in an Aspergillus oryzae expression vector. In this vector the expression of the lipase cDNA is under control of the Aspergillus oryzae alpha-amylase gene promoter and the Aspergillus niger glucoamylase gene terminator. The recombinant plasmid was introduced into Aspergillus oryzae, and transformed colonies were selected and screened for lipase expression. Lipase-positive transformants were grown in a small fermentor, and recombinant triglyceride lipase was purified from the culture broth. The purified enzymatically active recombinant lipase (rRML) secreted from A. oryzae was shown to have the same characteristics with respect to mobility on reducing SDS-gels and amino acid composition as the native enzyme. N-terminal amino acid sequencing indicated that approximately 70% of the secreted rRML had the same N-terminal sequence as the native Rhizomucor miehei enzyme, whereas 30% of the secreted rRML was one amino acid residue shorter in the N-terminal. The recombinant lipase precursor, which has a 70 amino acid propeptide, is thus processed in and secreted from Aspergillus oryzae. We have hereby demonstrated the utility of this organism as a host for the production of recombinant triglyceride lipases.

Amino Acids↗

PubMed1989

Effects of general anaesthesia with halothane on antroduodenal motility, pH and gastric emptying rate in man.

Antroduodenal motility, pH and gastric emptying rate were measured in 11 patients undergoing orthopaedic or plastic surgery with general anaesthesia. Motility was measured by manometry and gastric emptying rate by the rate of paracetamol absorption. During anaesthesia, gastric emptying was delayed in eight patients. General anaesthesia with halothane reduced the duration of the interdigestive motility complex (P less than 0.01), mainly by a shortening of phase II (P less than 0.01) which correlated with the inhaled concentrations of halothane (P less than 0.01). Anaesthesia impeded the occurrence of antral contractions during phase II (P less than 0.01); the frequency of contractions was unchanged during anaesthesia, but decreased during the recovery period (P less than 0.01). The amplitudes of antral contractions diminished with anaesthesia (P less than 0.01), but increased after operation. The frequency of contractions in the duodenum was unchanged during phase II and reduced during phase III (P less than 0.01). Gastric pH increased during and after operation (P less than 0.01). General anaesthesia with halothane affects gastroduodenal motility especially during phase II, increases gastric pH and delays gastric emptying rate.

Adult↗

PubMed1989

Antroduodenal motility, pH and gastric emptying during balanced anaesthesia: comparison of pethidine and fentanyl.

In a randomized study of 22 patients, antroduodenal motility, pH and gastric emptying rate were measured during barbiturate anaesthesia with pethidine or fentanyl. Motility was measured by manometry and gastric emptying rate by the paracetamol absorption test. Anaesthesia reduced the duration of the interdigestive motility complexes with both analgesics (P less than 0.001), mainly by a shortening of phase II (P less than 0.01). The duration of phase II and III were shorter with pethidine, and pethidine reduced both the frequency and amplitudes of antral contractions during phase II (P less than 0.01). Fentanyl affected only the amplitudes. The phase III variables assessed were unchanged, apart from a decrease in the velocity of propagation of the motility complexes with pethidine (P less than 0.01). The gastric pH increased in both groups during and after operation (P less than 0.01). Gastric emptying rate was normal in 82% with fentanyl and in 60% with pethidine. Motility in the recovery period approached, but did not reach, preoperative values. Balanced anaesthesia with pethidine and fentanyl seem to have minor influence on gastroduodenal motility and gastric emptying rate.

Anesthesia↗

PubMed1989

Rat heart thyroxine 5'-deiodinase is sensitively depressed by amiodarone.

Thyroxine 5'-deiodinase activity (5'-D) is depressed in rat liver by amiodarone. To investigate the possible tardive effect of amiodarone on 5'-D in different tissues, rats were fed amiodarone according to a short-term (group A, 50 mg amiodarone/kg/day for 10 days, total dose 150 mg, n = 16) and long-term regimen (group B, 25 mg amiodarone/kg/day for 20 days, n = 16) (control group, n = 12). Serum, heart, and other tissues were collected for 10 days after drug cessation. Thyroxine (T4), triiodothyronine (T3), amiodarone, and its active metabolite desethylamiodarone (DEA) were determined in serum, and 5'-D was determined in tissues. In group A, amiodarone concentrations in the heart at the time of drug cessation were two times higher than in group B. Higher amiodarone concentrations were also found in other tissues, and DEA was immeasurable in nearly all tissues at all times. In all tissues the amiodarone content declined rapidly. 5'-D was depressed to about 50% of controls (p less than 0.05) in heart throughout the 10-day observation period, despite unmeasureable drug levels (less than 0.03 microgram/g tissue). In contrast, liver and kidney 5'-D normalized after the first day in both treated groups, while muscle 5'-D did not differ from controls at any time. In conclusion, heart 5'-D seems to be more sensitively depressed by amiodarone than other tissues. Inhibition of thyroid hormone effect in the heart may contribute to the antiarrhythmic properties of amiodarone; however, it cannot be concluded that amiodarone is responsible for the tardive drug effect.

Amiodarone↗

PubMed1989

Antroduodenal motility and gastric emptying. Gastroduodenal motility and pH following ingestion of paracetamol.

The influence of paracetamol on antroduodenal motility and gastric pH was studied in 11 healthy subjects and the relationship between gastroduodenal motility and gastric emptying rate time, tmax, to peak concentration of serum paracetamol, Cmax, was evaluated. The incidence of antral phase III activity and the duration of phase III was diminished with paracetamol (P less than 0.05). The other motility parameters assessed were unchanged. Three patterns of motility and absorption were observed. One group (n = 5) were fast absorbers with a tmax of 1 h and a motility pattern characterized by antral activity, a high motility index and a short duration of phase II (33-60 min); the phase IIIs were complete except in one case. The second group (n = 4) had tmax at 1.5 h and their phase II motility was characterized by a longer duration (80-133 min) (P less than 0.05), by antral activity, and by a high motility index; their phase IIIs were all incomplete. The last group (n = 2) were slow absorbers: Cmax was not reached in the investigation period, no antral contractions were seen, and the motility index was low. The area under the serum-concentration curve of paracetamol differed between the groups at 90 and 180 min (P less than 0.01).

Acetaminophen↗

PubMed1989

Dose dependency of furosemide-induced sodium excretion.

Intravenous furosemide doses ranging from 5 to 120 mg were given to healthy young volunteers with and without individualized active rehydration with a sodium chloride solution. Sodium excretion rates and fractional sodium excretions (FENa) percentages were correlated significantly with dose and with urinary excretion rates of furosemide. The ED50 was below 5 mg and no additional natriuretic effect was seen above 40 mg. The efficiency (FENa percentage per microgram of furosemide excreted per minute during a certain clearance period) was dependent on hydration and on time. For the period 15 to 30 min a significant linear relationship between furosemide dose and the reciprocal of the efficiency indicated a higher efficiency for lower doses and a theoretical maximal value of FENa of 0.4% per micrograms of furosemide excreted per minute. A relative value for a dose-dependent efficiency reduction was calculated for each dose. The ED50 for dose-dependent efficiency reduction was about 12 mg i.v. Simultaneous measurements of lithium clearance indicated a proximal site of action for furosemide which was saturated at furosemide excretion rates above 50 micrograms/minute. For the major, distal, site of action no maximal value was demonstrated. It is concluded that a wanted balance between a strong natriuretic effect and weak sodium retaining mechanism not necessarily is achieved by a high dose and that information concerning that problem must be obtained from studies in relevant patient groups.

Adult↗

PubMed1989

Effects of general anaesthesia with enflurane on antroduodenal motility, pH and gastric emptying rate in man.

Antroduodenal motility, pH and gastric emptying rate were investigated before, during and after general anaesthesia with enflurane in 11 patients undergoing elective surgery not involving the abdomen. Motility was measured by manometry and the gastric emptying rate by the rate of paracetamol absorption. During anaesthesia gastric emptying rate was delayed in nine patients. General anaesthesia with enflurane nearly abolished the motility in the antrum. The duration of successive interdigestive motor complexes was reduced (P less than 0.001) mainly be a reduction in Phase II (P less than 0.01). The frequency of contractions was unchanged in the duodenum during Phase II and decreased during Phase III (P less than 0.01). The amplitudes of contractions were unchanged in the proximal part of the duodenum and decreased in the distal part (P less than 0.01). General anaesthesia with enflurane increased the gastric pH per- and post-operatively (P less than 0.01). Motility in the antrum was rapidly regained in the recovery period. General anaesthesia with enflurane seems to delay gastric emptying rate by affecting the motility in the gastric antrum. The acidity of the stomach contents is reduced.

Adult↗

PubMed1988

Bioavailability and pharmacokinetics of oxazepam.

Six healthy volunteers received oxazepam 15 mg i.v. and orally at an interval of at least one week. The kinetic variables of i.v. oxazepam were: elimination half-life (t1/2 beta) 6.7 h, total clearance (CL) 1.07 ml.min-1.kg-1, volume of distribution (Vc) 0.27 l.kg-1 (0.21-0.49) and volume of distribution at steady-state (Vss) 0.59 l.kg-1. The intravenous disposition of unbound oxazepam was characterized by a clearance of 22.5 ml.min-1.kg-1 and a distribution volume of 12.3 l.kg-1. After oral oxazepam the peak plasma level was reached in 1.7 to 2.8 h. The plasma t1/2 beta at 5.8 h was not significantly different from the i.v. value. Absorption was almost complete, with a bioavailability of 92.8%. Urinary recovery was 80.0 and 71.4% of the dose after intravenous and oral administration, respectively. Renal clearance (CLR) of the glucuronide metabolite was 1.10 ml.min-1.kg-1 (0.98-1.52). Oxazepam was extensively bound to plasma protein with a free fraction of 4.5%.

Administration, Oral↗

PubMed1988

Gastrointestinal motility and gastric pH and emptying following ingestion of diazepam.

The effects of diazepam on antroduodenal motility, gastric pH and gastric emptying rate were investigated in 10 volunteers. Gastric emptying was assessed using paracetamol absorption and antroduodenal motility and pH by means of a perfused multilumen tube. On the first study day, the volunteers received paracetamol in phase I after the occurrence of one complete interdigestive motility complex (IDMC). Diazepam was given on the second study day at the beginning of the first phase I and paracetamol was given one IDMC later. The rate of absorption correlated with motility (P less than 0.03). Some volunteers were fast absorbers on the first study day and slow on the second, indicating that absorption rate is not constant, but dependent on gastroduodenal motility. Diazepam tended to increase the gastric emptying rate and enhanced the amplitude of contractions and the motility index during phase II (P less than 0.02). Gastric pH increased after ingestion of diazepam (P less than 0.05).

Adult↗

PubMed1988

The effect of furosemide on vascular smooth muscle is influenced by plasma protein.

The effect of furosemide on vascular smooth muscle was studied on segments of rabbit blood vessels. Furosemide (20 micrograms/ml) induced small (3-4%) decreases in resting tension whereas nitroglycerin (0.5 micrograms/ml) induced decreases from 8 to 13%. The addition of albumin (45 g/l) abolished the furosemide response whereas the nitroglycerin response was unaffected. Similarly the pronounced effect of nitroglycerin on electrically evoked contractions was unaffected by the presence of albumin whereas the furosemide effect was weakened by albumin. The biologically determined free fraction of furosemide increased with increasing drug concentrations from 13% at 16 micrograms/ml to 35% at 256 micrograms/ml.

Animals↗

PubMed1988

Steady state pharmacokinetics of naproxen in elderly rheumatics compared with young volunteers.

The elderly rheumatic patients and 7 healthy young persons received naproxen (Naprosyn, Syntex) 500 mg orally twice a day for 4 weeks. The serum concentrations were determined using mass fragmentography. After an initial 1,000-mg dose, no significant differences were found between the two groups in peak serum concentration, time to peak serum concentration, area below the serum concentration-time curve, volume of distribution, elimination half-life, or total body clearance of naproxen. At steady state, the median total through naproxen concentration was 50.5 mg/l in the elderly and 62.7 in the young (p = 0.08); the unbound concentration was 58 micrograms/l and 44 micrograms/l, respectively (p = 0.06). There was a significant inverse correlation between serum albumin and the free fraction of naproxen (R = -0.58, p = 0.01). The hepatic extraction ratio of naproxen is relatively low and it is suggested that the reduced protein binding in the elderly may conceal the age-related reduction in cellular activity. An estimated value of intrinsic clearance was reduced by 37% in the elderly patients. It is suggested to start naproxen at the lower end of its dose range in the elderly.

Adult↗

PubMed1988

Amiodarone during pregnancy.

A case study is presented in which amiodarone (A) was given during the whole of pregnancy and during the breast feeding period. An intensive observation of thyroid tests, serum concentrations of A and its metabolite, desethylamiodarone (DEA) was undertaken. The child was observed in the same way from birth until 2 months of age. The milk was analyzed for A and DEA. As reported in other published cases, transplacental passage was found and there was a relatively high concentration of amiodarone in the milk. Our child like the other children was healthy at birth, being euthyroid and with no goiter or corneal deposits. No effect was observed of the medication on growth, thyroid tests or cornea. It is concluded that amiodarone can be given during pregnancy but it is advisable to use as low doses as possible and control the serum concentrations at regular intervals. Breast feeding need not be forbidden.

Adolescent↗

PubMed1987

A method of oxygen supply to a low volume tissue bath containing a protein solution.

A method that makes it possible to follow the in vitro activity of a ring of the rabbit ear artery submerged in a protein solution for hours is described. The necessary oxygen and carbon dioxide are supplied to the tissue bath through a semipermeable membrane from a pressure chamber. By this procedure, disturbing foam formation is avoided. The tissue bath has a volume of 5 ml. For the rabbit ear artery, it is demonstrated that the response to electrical field stimulation is influenced by the addition of albumin.

Animals↗

PubMed1987

Effects of thiopentone or chlormethiazole on human placental stem villous arteries.

Small placental stem villous arteries were micro dissected from specimens obtained at normal term vaginal delivery (n = 25). Ring preparations of the vessels were mounted in organ baths and isometric tension was measured. Prostaglandin F2 alpha (PGF2 alpha) 10(-7)-10(-4) mol litre-1 produced concentration-dependent contractile responses that were inhibited by thiopentone 10(-4)-10(-3) mol litre-1 and by chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1. Thiopentone 10(-4)-10(-3) mol litre-1 and chlormethiazole 3 x 10(-4)-3 x 10(-3) mol litre-1 decreased the tension in vessels previously treated with PGF2 alpha 10(-5) mol litre-1. Chlormethiazole 3 x 10(-3) mol litre-1 inhibited, and thiopentone 10(-4)-10(-3) mol litre-1 abolished contractile responses to 5-hydroxytryptamine. Contractions induced by angiotensin II were inhibited by thiopentone 10(-3) mol litre-1 and chlormethiazole 3 x 10(-3) mol litre-1. The concentrations of the two drugs needed to affect contractile activation of isolated human stem villous arteries exceeded the free plasma concentrations reached during anaesthesia induced by the agents during Caesarean section, and the present results do not suggest any major effects of thiopentone or chlormethiazole on fetal placental vascular resistance during the clinical use of these drugs.

Angiotensin II↗

PubMed1987

Amiodarone for refractory supraventricular tachycardias.

Amiodarone was administered to 53 patients with otherwise drug-refractory supraventricular tachycardias. Therapy was effective in 35 patients and partially effective in nine patients for a median duration of 35 months. The median maintenance dose was 200 mg/day in both groups, whereas the median serum amiodarone concentrations were 1.1 mg/l and 0.7 mg/l, respectively. Amiodarone was ineffective in nine patients despite higher dosage (median 400 mg/day) and insignificantly higher serum concentrations (median 2.0 mg/l). Neither the age of the patients, the duration or type of arrhythmia, the cardio-thoracic index, nor the type of underlying heart disease were predictive of the efficacy of amiodarone. Side-effects occurred in 28 patients, leading to withdrawal of therapy in 12 patients. Side-effects were not associated with higher serum amiodarone concentrations. Despite its efficacy, amiodarone should be reserved for otherwise drug-resistant supraventricular tachyarrhythmias.

Adolescent↗

PubMed1987

Dose dependence of proximal and distal tubular effects of furosemide in conscious rats.

The dose-response relationship for the diuretic effect of furosemide, given as i.v. bolus injections (0.1-480 mg/kg) was investigated by clearance technique in conscious rats. By measuring the renal Li clearance, the effects on proximal and distal nephron segments were separated, and peak responses were correlated to the maximal excretion rate of furosemide in the urine. At the highest dose of furosemide, fractional Na excretion was increased from 1 to 19%, due to inhibition of fractional proximal Na reabsorption from 65 to 40% and fractional distal Na reabsorption from 97 to 57%. Furosemide inhibition of fractional proximal Na reabsorption showed a maximum at intermediate doses (7.5 mg/kg), whereas there was no maximum for the inhibition of distal fractional Na reabsorption. The natriuretic response was shorter than expected from the decline in furosemide excretion due to an abrupt fall in glomerular filtration rate and a rapid normalization of proximal fractional Na reabsorption. It is suggested that the maintenance of a normal delivery of tubular fluid to the distal nephron during furosemide-induced volume contraction may be due to inhibition of proximal tubular reabsorption.

Animals↗