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Biomedical subjects

K Hermansen

Publications and source records attributed to K Hermansen.

At least 91 records · Page 5Linked to original sources
PubMed1990

The isolated mouse atria as a new model for testing cardioactive drugs with special reference to doxorubicin (Adriamycin).

Spontaneously beating isolated atria from mice were used as a new in vitro model to characterize the mechanism of the cardiotoxic action of the anthracycline cytostatic doxorubicin (Adriamycin). After stabilization at 28 degrees the atria showed a contractile rate and--force of 284 +/- 31 (S.D.) beats/min. and 49 +/- 6.5 mg. Doxorubicin (Dox) (10(-6)-10(-5) M) had a positive chronotropic action per se and decreased the pD2 for the chronotropic action of isoprenaline in a dose-dependent way. However only the effect of the higher concentration proved statistically significant, a concentration which also caused a marked decrease (63%) of the Emax. Pretreatment with Dox 15 mg/kg intraperitoneally 72 hr previously did not influence the pD2 but caused a significant increase in the Emax of the isoprenaline concentration response curve. The results indicate that Dox in vitro interferes with the beta-adrenoceptor function of isolated mouse atria in an unspecific way and that the subacute cardiotoxicity of Dox in mice is probably not due to interference with the beta-adrenoceptor system. Further it is concluded that isolated atria from mice may be a useful model for testing cardioactive drugs.

Animals↗
PubMed1990

Gastrin releasing peptide stimulates the secretion of insulin, but not that of glucagon or somatostatin, from the isolated perfused dog pancreas.

Gastrin releasing peptide (GRP) is an intrapancreatic peptide, but its physiological function is unknown. Previously, the peptide has been shown to increase plasma levels of insulin and glucagon in vivo in dogs, but no studies on the possible direct actions on islet hormone secretion from the dog pancreas have been undertaken. Therefore, we examined the effects of a 10-min perfusion of synthetic porcine GRP at four different dose rates over a wide range (0.1-50 nmol l-1) on the islet hormone release from the isolated dog pancreas (n = 5-6 in each group) at 5.5 mM glucose. We found that, at all four concentrations tested, GRP rapidly and markedly stimulated insulin secretion. The stimulation was, however, transient: the increased insulin secretion returned to basal levels within 7-8 min despite the ongoing GRP perfusion for 10 min. In contrast, GRP did not affect the pancreatic secretion of glucagon or somatostatin. We conclude that GRP stimulates insulin secretion by a direct pancreatic action without affecting the secretion of glucagon or somatostatin.

Animals↗
PubMed1989

[Knowledge of AIDS and of transmission risks of HIV infection in a group of homosexual people. A questionnaire study].

A questionnaire investigation among 430 homosexual persons all of whom were members of an organization for homosexuals was completed by 144 (33%). These replies showed that they knew about HIV infection, risk behaviour and "safe sex". Their knowledge about the signs of HIV infection and AIDS was, however, more limited. The replies were compared with an age-matched group of the male population. The results of the investigation provide reasons to suppose that the information campaigns have been of value but information to prevent spread of infection is still necessary. In addition, further information is necessary about the subjective signs of HIV-infection so that persons in whom these signs develop may be offered the best possible treatment as early as possible.

Acquired Immunodeficiency Syndrome↗
PubMed1989

[A group of homosexuals change their sex habits after information about AIDS. A questionnaire survey].

A questionnaire investigation to which 144 homosexual persons replied anonomously revealed alterations in the sexual habits after information about AIDS. Significant reduction in the annual number of partners and significantly fewer employ the more dangerous sexual practices which now occur particularly in more permanent partnerships are among the alterations started. An unchanged number still employ active anal and orogenital coitus. Employment of condoms has increased significantly, particularly in anal coitus and "casual" partners (from 3% to 82%). The majority accept the use of condoms and state that they employ more "safe sex" than prior to information about AIDS. 12% stated that they had sex with both sexes and the possibility of spread of infection from homosexual to heterosexual groups is present. The intensive informative work from the homosexuals own organisation and from public health authorities appear to have had some effect but further information and influencing are necessary if the spread of HIV infection is to be stopped.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Cardiotoxic effects and the influence on the beta-adrenoceptor function of doxorubicin (Adriamycin) in the rat.

The possible relationship between the effect of the anthracycline-cytostatic doxorubicin (Dox) on the cardiac beta-adrenoceptor function in vitro and the development of delayed cardiotoxicity in vivo has been investigated in the rat. Dox (10(-5)-10(-4) M) blocked the chronotropic effect of isoprenaline on isolated atria in a competitive manner. Treatment with a single dose of Dox 5 mg/kg intravenously caused marked ECG changes manifested by progressive prologations of the Q alpha T and S alpha T-intervals, which amounted to 37% and 58% respectivity 5 weeks after the medication. At this time no beta-blocking action was detectable when tested on the isolated atria in the same rats. The results indicate that the delayed cardiotoxicity induced by Dox is not mediated by an interference with the cardiac beta-adrenoceptor function.

Animals↗
PubMed1989

On the nature of the galanin action on the endocrine pancreas: studies with six galanin fragments in the perfused dog pancreas.

Galanin, a 29 amino acid peptide, inhibits insulin and somatostatin secretion from the isolated, perfused dog pancreas. To assess the nature of the influences of galanin on the endocrine pancreas, we examined the effects of porcine galanin and six different galanin analogues at the equimolar concentration of 1 nmol/l on the hormone release from the isolated, perfused dog pancreas. It was found that galanin2-29 (by 75 +/- 4%), like the native galanin1-29 (by 90 +/- 3%) potently inhibited insulin secretion (p less than 0.001). In contrast, galanin3-29 did not significantly affect insulin secretion. This indicates that removal of the two N-terminal amino acids markedly reduces the potency of galanin. Also, the replacement of the amino acid number 2 (Trp) by Tyr or Phe was followed by a loss of the insulin lowering effect of galanin at this dose level. Likewise, galanin10-29 had no significant effect on insulin secretion. In contrast, the C-terminally deleted galanin1-15 significantly inhibited insulin secretion (by 24 +/- 5%; p less than 0.01), though with a lower potency than did native galanin (p less than 0.05). Consequently, the C-terminal end of galanin is also of importance for the effect. Somatostatin secretion was inhibited by galanin (p less than 0.001), but not by any of the other investigated peptides. Glucagon secretion was not affected by galanin. It is concluded that the two N-terminal amino acids of galanin are essential for the inhibitory action on the insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1989

Effect of pump versus pen treatment on glycaemic control and kidney function in long-term uncomplicated insulin-dependent diabetes mellitus (IDDM).

Glycaemic control on pump versus pen treatment was evaluated and the effects of optimised metabolic control on kidney function was studied in very long-term uncomplicated insulin-dependent diabetes mellitus (IDDM). Ten otherwise healthy patients participated, age: 36.5 yr +/- 7.9, diabetes duration: 23.7 yr +/- 2.9, urinary albumin excretion (UAE): 5.8 micrograms/min x/ divided by 2.2, se-creatinine and blood pressure were normal and only background retinopathy was present. A 2 x 6 months randomised cross-over study was performed using continuous subcutaneous insulin infusion (CSII) and multiple injection technique (MIT). Glycaemic control was evaluated by a six point profile every two weeks and by measuring HbA1c monthly. At 0, 6 and 12 months, glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the constant infusion technique, and UAE by radioimmunoassay. Glycaemic control was significantly better on CSII as compared to MIT (p = 0.01) or pre-study conventional treatment (CT), p = 0.03, whereas there was no difference between MIT and CT. There was no change in kidney function during either treatment. Thus, in these very long-term uncomplicated patients, glycaemic control was significantly improved during CSII. In spite of this, no change was found in GFR, which might suggest that in long-standing diabetes, kidney function is unaltered by changes in metabolic control.

Adult↗
PubMed1988

Glucagon responses to intravenous arginine and oral glucose in insulin-dependent diabetic patients during six months conventional or continuous subcutaneous insulin infusion.

To elucidate the impact of subcutaneous insulin infusion (CSII) treatment on the glucagon response to intravenous (IV) arginine and to oral glucose a 6-month prospective randomized study in insulin-dependent diabetics was carried out. The effects were investigated of CSII (7-patients) and conventional insulin treatment (UCT) (9 patients) on the changes in glucagon, growth hormone, glucose, lactate, glycerol, 3-hydroxybutyrate, and alanine to IV arginine and to oral glucose in insulin-dependent diabetics who were made euglycemic and isoinsulinemic using the artificial pancreas (Biostator, Miles, Elkhart, IN). HbA1c was significantly lower in the group treated by CSII. Despite the improved glycemic control no significant change in the responses of A-cell secretion to arginine or glucose challenges was found. In addition, there were no significant differences in hormone or metabolite values between the two groups at entry to the study or after 6 months of either therapy. Thus, normalization of the A-cell sensitivity to glucose in insulin-dependent diabetic subjects requires further amelioration of the intermediary metabolism than can be achieved with insulin pump treatment.

Administration, Oral↗
PubMed1988

Insulin treatment of the insulin-dependent diabetic patient undergoing minor surgery. Continuous intravenous infusion compared with subcutaneous administration.

In a prospective randomised study in 20 insulin-dependent diabetics who had minor surgery under general anaesthesia we compared the metabolic responses to intravenous glucose-insulin-potassium infusion with those who had conventional subcutaneous insulin administration. The former treatment resulted in lower blood glucose levels both during the infusion period (p less than 0.05) as well as the entire observation period (operative, first and second postoperative days; p less than 0.01). More blood glucose values were within the intended range of 5 to 10 mmol/litre in the glucose-insulin-potassium as compared to the conventional group (48% versus 24%; p less than 0.01). The levels of lactate, 3-hydroxybutyrate, glycerol, alanine, glucagon, insulin and growth hormone did not differ between the two groups. The infusion regimen resulted in better glycaemic control both peri-and postoperatively than the conventional subcutaneous insulin regimen in insulin-dependent diabetic patients who have minor surgery.

Adult↗
PubMed1988

Marked impairment of the effect of hyperglycaemia on glucose uptake and glucose production in insulin-dependent diabetes.

The effect of hyperglycaemia per se on glucose utilization and glucose production was evaluated in 12 patients with insulin-dependent diabetes and in 9 non-diabetic control subjects. In diabetic patients normoglycaemia was maintained during the night preceding the study by a variable intravenous insulin infusion. During the study endogenous insulin secretion was suppressed by somatostatin (300 micrograms h-1) and replaced by infusion of insulin (0.2 mU kg-1 min-1). Glucose utilization and hepatic glucose production rates were quantified at two plasma glucose concentrations (6.7 and 16.7 mmol l-1) using the two-step sequential hyperglycaemic clamp technique in combination with 3-3H-glucose tracer infusion. Duration of each step was 120 min. In diabetic patients glucose utilization, at a glucose concentration of 6.7 mmol l-1, was not different from normal (mean +/- SE: 2.9 +/- 0.2 vs 3.6 +/- 0.3 mg kg-1 min-1, 0.05 less than p less than 0.10), but the response to marked hyperglycaemia was significantly reduced (5.4 +/- 0.5 vs 9.4 +/- 1.0 mg kg-1 min-1, p less than 0.01). Hepatic glucose production was also normal at 6.7 mmol l-1 (1.4 +/- 0.1 vs 1.4 +/- 0.1 mg kg-1 min-1, NS), but whereas in control subjects glucose production was suppressed during hyperglycaemia of 16.7 mmol l-1 (0.3 +/- 0.4 mg kg-1 min-1, p less than 0.01), a slight increase was observed in diabetic patients (2.0 +/- 0.2 mg kg-1 min-1, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Effects of galanin on the release of insulin, glucagon and somatostatin from the isolated, perfused dog pancreas.

Galanin is a 29 amino acid peptide which has been found in intrapancreatic nerves. The effects of galanin, adrenergic and cholinergic blockade as well as somatostatin on the hormone release from the isolated perfused dog pancreas were studied. It was found that galanin dose-dependently inhibited insulin (P less than 0.001) and somatostatin (P less than 0.001) but not glucagon secretion at normal glucose levels. The lowest galanin concentration that caused a significant suppression of insulin and somatostatin secretion was 10(-11) and 10(-10) mol/l, respectively. Similar effects were evident during stimulation with 2.5 mmol/l arginine. Galanin (10(-9) mol/l) caused a more pronounced inhibition of insulin and somatostatin secretion at high (10 mmol/l) and normal (5 mmol/l) than at low glucose (1.3 mmol/l). In contrast, suppression of the glucagon secretion was only seen at low glucose (1.3 mmol/l). Perfusion of 10(-6) mol/l of atropine, phentolamine and propranolol had no effect on the galanin-mediated (10(-10) mol/l) inhibition of insulin and somatostatin secretion. Galanin (10(-12)-10(-10) mol/l) and somatostatin (10(-12)-10(-10) mol/l) were equipotent in inhibiting insulin secretion whereas only somatostatin exerted a suppression of the glucagon secretion at normal glucose. Thus, galanin exerts a differential effect on islet hormone secretion and may participate in the hormonal control of insulin, glucagon and somatostatin secretion.

Adrenergic alpha-Antagonists↗
PubMed1988

Autonomic and somatosensory nerve function after 2 years of continuous subcutaneous insulin infusion in type I diabetes.

Autonomic and somatosensory nerve function was studied in 24 insulin-dependent diabetic subjects (aged 29 +/- 7 yrs, diabetes duration 8 +/- 4 yr) randomly allocated to either continuous subcutaneous insulin infusion (CSII; n = 12) or unchanged conventional insulin therapy (CIT; n = 12). Measures of glycemic control and somatosensory and autonomic nerve function were comparable in the two groups at the start. Glycemic control was significantly improved in the CSII group throughout study, whereas it remained unchanged in the CIT group. In the CIT group, vibratory perception threshold (VPT) of the great toe and the medial malleolus deteriorated, as did heart rate variation (HRV) at rest, at deep breathing (.05 less than P less than .06), and at standing. In contrast, CSII patients retained their VPT and HRV. Comparison of nerve function alterations during the 2-yr trial showed better preservation in CSII than in CIT patients of VPT in the great toe (0.8 +/- 1.7 vs. -1.4 +/- 1.9 V, P less than .01) and the medial malleolus (1.5 +/- 2.9 vs. -1.4 +/- 1.8 V, P less than .05) and of HRV at rest (10 +/- 24 vs. -13 +/- 22 ms, P less than .05) and at standing (-0.01 +/- 0.13 vs. -0.15 +/- 0.16 ms, P less than .05). We conclude that intensified glycemic control can favorably influence parasympathetic and somatosensory nerve function in insulin-dependent diabetes mellitus.

Adult↗
PubMed1988

Comparison of blood glucose and insulin responses in non-insulin dependent diabetic patients. Studies with spaghetti and potato taken alone and as part of a mixed meal.

Recently, we demonstrated that spaghetti caused significantly lower glycaemic response than rice and potato in insulin-dependent diabetic (IDDM) subjects and that this difference was also present when spaghetti and potato were taken as part of a mixed meal. We have now compared the blood glucose and insulin responses to 50 g of carbohydrate in the form of white bread, potato and white spaghetti in 6 non-insulin-dependent diabetic (NIDDM) patients. The blood glucose response after white spaghetti observed over a 3-h period was only 60 +/- 10 per cent (P less than 0.02) of that seen in response to potato (395 +/- 116 mmol/l x 180 min vs 641 +/- 108 mmol/l x 180 min) and 47 +/- 9 per cent (P less than 0.01) of that seen in response to white bread (395 +/- 116 mmol/l x 180 min vs 805 +/- 93 mmol/l x 180 min). Insulin responses showed an identical pattern reflecting the glycaemic responses. To see if the difference in the glucose responses in NIDDM patients is preserved if these carbohydrate-rich foods are taken as part of a mixed meal we looked at the blood glucose and insulin responses to 50 g of carbohydrate in the form of potato and white spaghetti when ingested together with bolognese sauce (167 g) in 7 NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

Clinical outcome of using insulin at 40 IU/ml and 100 IU/ml in pump treatment. Results of a controlled multi-center trial.

In three different diabetes centers the use of insulin at a strength of 40 IU/ml (U40) and 100 IU/ml (U100) in continuous subcutaneous insulin infusion (CSII) treatment of insulin dependent (Type I) diabetic patients was compared in a randomized cross-over design. Forty-six Type I diabetic patients, all previously treated with CSII for at least one year, completed consecutively two 13-week periods of treatment with U40 and U100. Body weight and insulin requirements were identical at the end of the two periods. Slightly higher levels of glycemia were recorded during U40 when compared to U100 treatment: mean blood glucose was 142 +/- 34 (SD) vs. 133 +/- 34 mg/dl (2 p less than 0.01). The same tendency was observed in the mean glycosylated hemoglobin value (6.84 +/- 1.35 vs. 6.65 +/- 1.13%, 2 p greater than 0.1). There were no significant differences between U40 and U100 in the number of catheters used and the number of catheter blockages reported, while the development of subcutaneous nodules at the insertion sites was significantly more frequent during U40 treatment. It is concluded that the implementation of insulin in the strength of 100 IU/ml is as effective as the use of insulin in the strength of 40 IU/ml for CSII therapy, and might even be associated with slightly improved glycemic control and less subcutaneous side-effects.

Adult↗
PubMed1987

Greater in vivo than in vitro pulsatility of insulin secretion with synchronized insulin and somatostatin secretory pulses.

To examine the control of pulsatile insulin secretion by an intrapancreatic pacemaker, samples at minute intervals were taken from the portal vein in dogs in vivo and from an isolated perfused pancreas preparation in vitro. Anesthetized dogs had high amplitude pulsatile insulin secretion which was not consistently regular. Fourier transform analysis showed dominant 20- and 10-min periods of spectral power (P less than 0.01). After vagotomy, the relative oscillatory power was reduced from 83% to 42%, about a lower mean concentration with abolition of the 20-min oscillations. The isolated perfused dog pancreas also had oscillatory insulin secretion with oscillatory power of 12%. Autocorrelation showed regularity of in vitro insulin secretion with a period of 10-11 min (P less than 0.0001). In addition, somatostatin was secreted from the in vitro pancreas in pulses in phase with insulin (cross-correlation P less than 0.0001). These data are in accord with the theory that the pancreas has an internal pacemaker which controls insulin secretion, and that the amplitude of the oscillations is modulated by vagal control. The pacing of the islets may be coordinated by a neural network, whereas coincident pulsatile somatostatin release may temporarily suppress islet secretion and help to synchronize hormonal oscillations.

Animals↗