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Biomedical subjects

P H Andersen

Publications and source records attributed to P H Andersen.

At least 55 records · Page 3Linked to original sources
PubMed1994

Effects of glipizide on glucose metabolism and muscle content of the insulin-regulatable glucose transporter (GLUT 4) and glycogen synthase activity during hyperglycaemia in type 2 diabetic patients.

To examine whether sulphonylureas influence hyperglycaemia-induced glucose disposal and suppression of hepatic glucose production (HGP) in type 2 diabetes mellitus, a 150-min hyperglycaemic (plasma glucose 14 mmol/l) clamp with concomitant somatostatin infusion was used in eight type 2 diabetic patients before and after 6 weeks of glipizide (GZ) therapy. During the clamp a small replacement dose of insulin was given (0.15 mU/kg per min). Isotopically determined glucose-induced glucose uptake was similar before and after GZ administration which led to improved glycaemic control (basal plasma glucose 12.2 +/- 1.3 vs 8.9 +/- 0.7 mmol/l; P < 0.01). Glucose-induced suppression of HGP was, however, more pronounced during GZ treatment (0.96 +/- 0.14 vs 1.44 +/- 0.20 mg/kg per min; P < 0.02). Following GZ treatment hyperglycaemia failed to stimulate glycogen synthase activity. Moreover, GZ resulted in a significant increase in the immunoreactive abundance of the insulin-regulatable glucose transport protein (GLUT 4) (P < 0.02). In conclusion, these results suggest that GZ therapy in type 2 diabetic patients enhances hepatic sensitivity to hyperglycaemia, while glucose-induced glucose uptake remains unaffected. In addition, GZ tends to normalize the activity of glycogen synthase and increases the content of GLUT 4 protein in skeletal muscle.

Adult↗
PubMed1994

Plasma concentrations of betamethasone after topical application of betamethasone 17-valerate: comparison with oral administration.

Plasma concentrations of betamethasone were measured by r.i.a. after oral administration of 0.6 mg betamethasone and topical application of betamethasone 17-valerate in the same five healthy subjects. Betamethasone 17-valerate was prepared as a suspension in medical grade pressure sensitive adhesive and applied to a 100 cm2 area on the back for 28 h. Mean maximum plasma concentrations were 5.0 and 0.24 ng ml-1 and mean AUC values were 75.4 and 7.74 ng ml-1 h after oral and topical administrations, respectively. The mean plasma elimination half-life of betamethasone after the removal of topical betamethasone 17-valerate was 16.6 h which was twice that after oral administration, 8.1 h. Betamethasone 17-valerate may require application to the skin more than twice daily.

Administration, Oral↗
PubMed1994

Faecal enzymes: in vivo human skin irritation.

Digestive enzymes in faeces have been reported to possess skin irritation potential. The present study was designed to investigate the in vivo irritant potentials of faecal concentrations of proteolytic and lipolytic digestive enzymes in bile salt mixtures. In a 21-day cumulative irritation assay, clinical evaluation and noninvasive bioengineering techniques were used. 5 days occlusive exposure to phosphate buffer (pH = 8) caused no visual skin damage but reflectance spectroscopy demonstrated significant vasodilation (p < 0.01) and increases in transepidermal water loss (TEWL) and skin pH were also observed (p < 0.01). These increases were still present at days 12 and 19. Occlusive exposure to physiologic concentrations of faecal enzymes resulted in significant visual and objective scores at day 5, 12, and 19, with increased readings as a function of exposure time (p < 0.01). The enzyme mixture containing lipase caused delayed onset of skin erythema and epidermal barrier disruption compared to elastase and chymotrypsin containing solutions. Prolonged occlusive exposure to digestive enzymes in faecal concentrations caused severe skin erythema and epidermal barrier disruption in a human model, suggesting a possible etiologic role of digestive enzymes in perianal, circumstomal or diaper dermatitis.

Adult↗
PubMed1994

Pre- and posttranslational upregulation of muscle-specific glycogen synthase in athletes.

Expression of muscle-specific glycogen synthase (GS) and phosphofructokinase (PFK) was analyzed in seven athletes and eight control subjects who were characterized using the euglycemic, hyperinsulinemic (2 mU.kg-1.min-1) clamp technique in combination with indirect calorimetry and biopsy sampling of vastus lateralis muscle. In the basal state, total GS activity and half-maximal GS activation by glucose 6-phosphate (G-6-P) were respectively 34% (P < 0.03) and 50% (P < 0.005) higher in athletes than in control subjects. In parallel, GS mRNA/microgram total RNA in athletes was 40% (P < 0.005) higher. No difference in GS immunoreactive protein abundance was found between the groups. PFK activity and protein levels were respectively 15% (P < 0.05) and 20% (P < 0.02) lower in athletes, whereas no differences was found in the level of PFK mRNA. After 4 h of hyperinsulinemia, total glucose disposal rate (P < 0.005) and both nonoxidative (P < 0.02) and oxidative (P < 0.03) glucose metabolism were significantly higher in athletes. In parallel, after hyperinsulinemia, the relative activation of GS by G-6-P was significantly higher in athletes, whereas total activity and gene expression of both GS and PFK were unaffected by insulin. We conclude that athletes have increased whole body insulin-stimulated nonoxidative glucose metabolism associated with both pretranslational (mRNA) and posttranslational (enzyme activity) upregulation of GS. However, the immunoreactive mass of GS is normal, emphasizing that posttranslational regulation of the GS protein activity is important for the increased glycogen synthesis rate of muscle in endurance-trained individuals.

Adult↗
PubMed1994

Effect of feeding regimen on concentration of free endotoxin in ruminal fluid of cattle.

The influence of concentrate diets on endotoxin concentration in sterile filtrate of ruminal fluid was assessed in ruminally fistulated Jersey cows. Three cows underwent a change in diet from hay to a diet containing 3.0 kg and 14 d later 6.0 kg of a 12% CP concentrate. The cows had free access to water and a mineral-stone. A modified Limulus Amoebocyte Lysate technique was used for the endotoxin analyses. The endotoxin concentration in the ruminal fluid of cows fed on hay were 148 +/- 84 and 118 +/- 50 endotoxin units (EU)/mL (mean +/- SD) on two separate days and increased from the 2nd d of supplementation with 3.0 kg of concentrate to 408 +/- 198 EU/mL on d 5. When the cows were fed 6.0 kg of concentrate, the endotoxin concentrations increased to 1,599 +/- 944 EU/mL. To assess the influence on the ruminal endotoxin concentration of an adaptation of the ruminal environment to concentrate before hyperalimentation, four ruminally fistulated Jersey cows previously fed either hay or a high-concentrate diet for 1 mo were hyperalimented with 60 to 70 g of barley per kilogram BW. A relative increase in ruminal endotoxin concentration was determined only in the two cows previously fed concentrates. The results show that high-concentrate diets do not consistently relate to increases of ruminal endotoxin concentrations.

Adaptation, Physiological↗
PubMed1994

Endotoxin and arachidonic acid metabolites in portal, hepatic and arterial blood of cattle with acute ruminal acidosis.

Ruminal acidosis was induced experimentally with 70 g barley/kg body weight in 2 rumen fistulated cows with chronic indwelling catheters in the portal vein, in a hepatic vein and the carotid artery. The cows were followed for 24 and 20h after the overfeeding and evaluated clinically and by clinical chemistry. The 2 cows exerted different responses to the treatment. Both cows showed signs of severe ruminal acidosis. Both cows had endotoxin in portal and hepatic vein blood, but only 1 of the cows convincingly developed a systemic endotoxaemia. A pre-hepatic release of the stable prostacyclin and thromboxane metabolites, 6-ketoprostaglandin F1 alpha and thromboxane B2 was demonstrated in this cow. The results of the present study show that endotoxin and arachidonic acid metabolites of pre-hepatic origin may be factors involved in the pathogenesis of ruminal acidosis, and that investigation of the factors affecting translocation of ruminal endotoxin and subsequent clearing in the liver, will be of importance.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

[A study of skin and mucosal irritation and incidence of allergy among office staff exposed to self-copying paper].

At a public office with a staff of 129, twenty people work for short periods with large amounts of self-copying paper. A controlled study has shown a significantly higher incidence of pruritus and nasal congestion amongst staff exposed to large amounts of self-copying paper or its components, no drying of the skin after working with the paper and no increased degree of irritation of the skin were found in the study group at dermatological examination. No differences were found between the study group and the control group with respect to allergy or skin status or working conditions apart from the contact with self-copying paper. The study confirms that contact with fresh self-copying paper may result in pruritus and skin irritation, but allergy to the paper or microcapsule contents could not be demonstrated in this study.

Adult↗
PubMed1993

cis-1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles: synthesis and in vitro binding affinity at dopamine D1 and D2 receptors.

cis-1,2,3a,4,5,9b-Hexahydro-3H-benz[e]indoles were synthesized and evaluated for in vitro dopamine D1 and D2 receptor binding affinity. The target compounds 21-25 were readily prepared by reduction of the air-sensitive tricyclic enamines 10-14. Reduction of 10-14 with sodium borohydride, sodium cyanoborohydride, palladium on carbon in ethanol, and platinum oxide in ethanol or acetic acid gave only the cis (3a,9b) 1,2,3a,4,5,9b-hexahydro-3H-benz[e]indoles. The stereochemistry was confirmed by single-crystal X-ray analysis. In the 6-hydroxy series, the binding affinity at D1 and D2 receptors was of the order 22 (N-n-butyl) > 21 (N-n-propyl) > 23 (N-H). The compounds demonstrated greater binding affinity at D2 receptors than at D1 binding sites. In contrast, 8-OH derivatives exhibited affinity only for D2 receptors, with 25 (N-n-butyl) having slightly greater affinity than 24 (N-n-propyl).

Animals↗
PubMed1993

A corticosteroid, a non-steroidal anti-inflammatory drug and an antihistamine modulate in vivo vascular reactions before and during post-occlusive hyperaemia.

Post-occlusive reactive hyperaemia is the temporary increase of blood flow in a tissue following transient vascular obstruction, and has recently been proposed as an in vivo method for ranking topical corticosteroid potency. We investigated in vivo vascular reactions before and during post-occlusive hyperaemia using laser-Doppler flowmetry and reflectance spectroscopy (RS). RS enables resolution of in vivo erythema into deoxygenated (venous) [DOH] and oxygenated (arterial) haemoglobin (OH) components (expressed in arbitrary units, AU). Using a randomized 24-h occlusive exposure in 10 healthy volunteers the effects of a corticosteroid (betamethasone-17-valerate), a non-steroidal anti-inflammatory drug (NSAID) [indomethacin], an antihistamine (diphenhydramine), or vehicle, were studied before and during post-occlusive hyperaemia. The 24-h vehicle exposure decreased total haemoglobin (composed of a small increase in OH [P < 0.001] and a greater decrease in DOH [P < 0.005], [OH, 0.23 +/- 0.18 AU; DOH, 0.28 +/- 0.12 AU]). The blood flow increased 7.1% to 28 +/- 8 AU (P > 0.05). Betamethasone-17-valerate exposure decreased total haemoglobin further (OH, 0.10 +/- 0.09 AU [P < 0.005]; DOH, 0.18 +/- 0.08 AU [P < 0.05]), which corresponded to a 15% blood flow decrease (P < 0.05). Indomethacin reduced OH to 0.18 +/- 0.12 AU (P < 0.02) and increased DOH slightly, with a trend towards decreased blood flow (P > 0.05). Diphenhydramine caused no significant changes in RS or laser-Doppler flowmetry readings before post-occlusive hyperaemia. Post-occlusive hyperaemia increased total haemoglobin maximally at the first observation time (OH, 0.63 +/- 0.13 AU; DOH, 0.31 +/- 0.11 AU [P < 0.001]).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

The effect of intensive insulin therapy on the insulin-regulatable glucose transporter (GLUT4) expression in skeletal muscle in type 1 diabetes.

Studies in normal man and rodents have demonstrated that the expression of the dominant glucose transporter in skeletal muscle, GLUT4, is regulated by insulin at supraphysiological circulating levels. The present study was designed to determine whether intensified insulin replacement therapy for 24 h given to patients with Type 1 diabetes in poor metabolic control was associated with an adaptive regulation of GLUT4 mRNA and protein levels in vastus lateralis muscle. Nine Type 1 diabetic patients with a mean HbA1c of 10.3% were included in the protocol. After intensified treatment with soluble insulin for 24 h the fasting plasma glucose concentration decreased from 20.8 +/- 2.3 (SD) to 8.7 +/- 2.3 mmol 1-1, whereas the fasting serum insulin level increased from 0.06 +/- 0.02 to 0.17 +/- 0.09 nmol 1-1. However, despite a 2.8-fold increase in serum insulin levels and more than a halving of the plasma glucose concentration for at least 15 h no significant alterations occurred in the amount of GLUT4 protein (0.138 +/- 0.056, poor control vs 0.113 +/- 0.026 arb. units, improved control, p = 0.16) or GLUT4 mRNA (96432 +/- 44985, poor control vs 81395 +/- 25461 arb. units, improved control, p = 0.54). These results suggest, that in spite of evidence that high insulin levels affect GLUT4 expression in muscle, changes in serum insulin within the physiological range do not play a major role in the short-term regulation of GLUT4 expression in Type 1 diabetic patients.

Adult↗
PubMed1993

Increased insulin-stimulated glucose uptake in athletes: the importance of GLUT4 mRNA, GLUT4 protein and fibre type composition of skeletal muscle.

In the present study the expression of GLUT4 and fibre type composition were examined in biopsies from skeletal muscle in seven male athletes and eight male sedentary subjects. Estimated maximal oxygen uptake was increased in the trained group when compared with the sedentary group (74.0 +/- 3.9 vs. 42.9 +/- 5.1 ml kg-1 min-1; P < 0.01). A biopsy of vastus lateralis muscle was taken in the fasting state, 36 h after the last bout of exercise. A second muscle biopsy was obtained following 4 h of a hyperinsulinaemic (2 mU kg-1 min-1), euglycaemic clamp. The rate of insulin-stimulated glucose uptake was increased in the trained subjects (17.34 +/- 0.53 vs. 13.53 +/- 0.79 mg kg-1 min-1, P < 0.01). In parallel, the steady state levels of GLUT4 protein and mRNA per DNA were higher in muscle biopsies obtained in the basal state from athletes than in sedentary controls, 21 and 71% respectively (P < 0.05). In the total group of participants, GLUT4 protein per DNA in the basal state and insulin-stimulated glucose uptake rate correlated positively, (r = 0.51, P = 0.05). In the insulin-stimulated state we did not find any significant correlation between GLUT4 protein per DNA and glucose uptake rate (r = 0.13, n.s.). No significant relationships between GLUT4 protein abundance per DNA and muscle fibre type distribution were observed. A significantly negative correlation was found between type 2B fibre area and insulin-stimulated glucose uptake (r = -0.63, P < 0.05). In conclusion, the abundance of GLUT4 protein and mRNA, respectively, is increased in skeletal muscle from endurance trained subjects compared to sedentary subjects. However, factors other than GLUT4 immunoreactive protein abundance seem to be determinant for the increased insulin-stimulated whole body glucose uptake in endurance trained subjects.

Adult↗
PubMed1993

Interstitial hyperthermia of colorectal liver metastases with a US-guided Nd-YAG laser with a diffuser tip: a pilot clinical study.

Ultrasound (US)-guided interstitial hyperthermia performed with the neodymium yttrium aluminum garnet laser with a diffuser tip involves placement of a laser fiber in solid tissue followed by irradiation from within the center of the tumor to be treated. The authors previously described the development of a US-guided technique that permits simultaneous interstitial laser irradiation and temperature measurements, with real-time US monitoring. With the use of a dedicated diffuser tip modification of the bare laser fiber, it has proved possible to produce spherical coagulations with a diameter comparable to that of liver metastases of clinical relevance. This technique was used in 11 patients with 16 colorectal liver metastases, 12 of which were radically ablated. Real-time US and interstitial temperature monitoring during treatment had a positive predictive value of 86% and negative predictive value of 100% in judging the final result. The technique is feasible, effective, and safe, but the effect on patient survival must be tested in future randomized clinical studies.

Adult↗
PubMed1993

Effect of physical training on glucose transporter protein and mRNA levels in rat adipocytes.

Physical training increases insulin-stimulated glucose transport and the number of glucose transporters in adipocytes measured by cytochalasin B binding. In the present study we used immunoblotting to measure the abundance of two glucose transporters (GLUT-4, GLUT-1) in white adipocytes from trained rats. Furthermore, the abundance of the mRNAs for these proteins and glucose transport was measured. Rats were swim-trained for 10 wk, and adipocytes were isolated from epididymal fat pads. The amount of GLUT-4/adipocyte volume unit was significantly higher in trained animals compared with both age- and cell size-matched animals. The amount of GLUT-4 mRNA was also increased by training and it decreased with increasing age. Furthermore, young age as well as training was accompanied by relatively low GLUT-4 protein/mRNA and relatively high overall GLUT-4 efficiency (recruitability and/or intrinsic activity). GLUT-1 protein and mRNA levels/adipocyte volume did not change with age or training.

3-O-Methylglucose↗
PubMed1993

GLUT-4 content in plasma membrane of muscle from patients with non-insulin-dependent diabetes mellitus.

The abundance of GLUT-4 protein in both total crude membrane and plasma membrane fractions of vastus lateralis muscle from 13 obese non-insulin-dependent diabetes mellitus (NIDDM) patients and 14 healthy subjects were examined in the fasting state and after supraphysiological hyperinsulinemia. In the basal state the immunoreactive mass of GLUT-4 protein both in the crude membrane preparation and in the plasma membrane fraction was similar in NIDDM patients and control subjects. Moreover, in vivo insulin exposure neither for 30 min nor for 4 h had any impact on the content of GLUT-4 protein in plasma membranes. With the use of the same methodology, antibody, and achieving the same degree of plasma membrane purification and recovery, we found, however, that intraperitoneal administration of insulin to 7-wk-old rats within 30 min increased the content of GLUT-4 protein more than twofold (P < 0.01) in the plasma membrane from red gastrocnemius and soleus muscle. In conclusion, when the subcellular fractionation method was applied to human muscle biopsies taken in the basal state, no difference could be found in the plasma membrane content of immunoreactive GLUT-4 protein between NIDDM patients and normal subjects. With this technique, we were unable to show evidence for a regulatory effect of insulin on the plasma membrane level of GLUT-4 protein in human muscle.

4-Nitrophenylphosphatase↗
PubMed1993

Expression of the major insulin regulatable glucose transporter (GLUT4) in skeletal muscle of noninsulin-dependent diabetic patients and healthy subjects before and after insulin infusion.

In a cross-sectional study we have examined the regulatory effect of insulin in vivo on the major insulin regulatable glucose transporter (GLUT4) in vastus lateralis muscle from 12 noninsulin-dependent diabetes mellitus (NIDDM) patients and 8 healthy control subjects. Insulin-stimulated glucose uptake rate in peripheral tissue was decreased by 41% (P < 0.01) in NIDDM patients compared to healthy subjects, whereas no significant differences could be shown in the abundance of total GLUT4 protein per DNA or GLUT4 messenger RNA (mRNA) per DNA among the 2 groups in muscle biopsies obtained in the basal state. In healthy subjects, 4 h of insulin infusion (2 mU/kg/min) induced a 31% reduction (P < 0.05) in the total GLUT4 protein content per DNA and a 35% increase (P < 0.05) in GLUT4 mRNA per DNA, whereas the GLUT4 mRNA and protein responses to insulin were heterogenous and statistically unaltered in the NIDDM patients. The GLUT4 protein per DNA of muscle obtained in the basal state correlated positively with the in vivo insulin-stimulated glucose uptake rate in the control group (r = 0.82, P < 0.05), whereas there was no comparable correlation in the NIDDM group (r = 0.05, P = 0.88). Furthermore, GLUT4 protein content in skeletal muscle after 4 h of insulin infusion did not correlate with insulin-stimulated glucose uptake in any of the groups. In conclusion, 4 h of insulin infusion causing supraphysiological serum insulin levels modulates the expression of GLUT4 in skeletal muscle from healthy subjects, with divergent effects at protein and mRNA levels. The physiological significance of these observations will have to be elucidated in future studies. Factors other than total GLUT4 protein content of muscle play a role in determining insulin-stimulated glucose uptake in human skeletal muscle.

Actins↗
PubMed1993

Influence of short-term dexfenfluramine therapy on glucose and lipid metabolism in obese non-diabetic patients.

In a short-term (eight days) double-blind crossover study involving 10 obese patients, the effects of dexfenfluramine on glucose and lipid metabolism were examined. The protocol comprised whole body in vivo measurements (hyperinsulinemic euglycemic clamp in combination with indirect calorimetry) and in vitro studies of isolated adipocytes (lipolysis and glucose transport). All study participants were weight stable during the study period (103.1 +/- 3.2, placebo vs 103.3 +/- 3.1 kg, dexfenfluramine, NS). The following parameters were significantly reduced after dexfenfluramine treatment: fasting levels of plasma glucose (6.2 +/- 0.2 vs 5.7 +/- 0.2 mmol/l, p < 0.01), serum insulin (168.0 +/- 14.5 vs 138.9 +/- 7.9 pmol/l, p < 0.05), serum C-peptide (0.68 +/- 0.03 vs 0.58 +/- 0.02 nmol/l, p < 0.05) and total serum cholesterol (6.07 +/- 0.41 vs 5.48 +/- 0.38 mmol/l, p < 0.01). In the basal state glucose oxidation rate was significantly reduced by 36% (p < 0.001), whereas non-oxidative glucose disposal was significantly increased by 41% (p < 0.01), following dexfenfluramine treatment. Insulin-stimulated (2 mU.kg-1 x min-1) glucose disposal rate tended to be increased (18%, p = 0.10) after dexfenfluramine. In conclusion, dexfenfluramine possesses beneficial regulatory effects on glucose and lipid metabolism in non-diabetic obese patients, independently of weight loss.

Adipose Tissue↗