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Biomedical subjects

P H Andersen

Publications and source records attributed to P H Andersen.

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

Noninvasive computerized analysis of skin chromophores in vivo by reflectance spectroscopy.

Reflectance spectroscopy in an objective and accurate method for determining skin colour and has been widely used for measuring physiological variations in skin colour and for monitoring dermatological treatment modalities. Previous studies have used pigment indexes to describe changes in skin colour. Using a multiple regression method to calculate reflectance spectroscopic data, it has been possible to calculate the relative amounts of the different chromophores present in the skin. The technique was found reliable in in vitro tests and in experimentally induced variations in pigment content caused by venous congestion or ultraviolet (UV) light irradiation. In developing UV-induced erythema, the primary events seem to be venous dilatation followed by an increase in blood flow.

Adult↗
PubMed1990

Phosphoinositide metabolism in adipocytes from fed and fasted rats.

Phosphoinositide turnover was investigated in adipocytes from fed and 48 hour fasted rats. Insulin stimulated phosphoinositide synthesis both in adipocytes from fed and fasted rats. Fasting enhanced this effect of insulin 2-fold. Hydrolysis of phosphoinositides to inositol phosphates was not activated by insulin, neither transient after 2 minutes nor after 60 minutes stimulation. Under similar conditions, alpha 1-adrenergic receptor stimulation induced a pronounced inositol phosphate production. Thus, it is suggested that phosphoinositide hydrolysis is not involved in insulin action. The alpha 1-adrenergic effect was similar in adipocytes from fed and fasting rats.

Adipose Tissue↗
PubMed1990

Spectral reflectance of human skin in vivo.

A newly developed skin reflectance spectrophotometer was evaluated for measurements of both melanin pigmentation and erythema. Physiological changes in blood flow and blood content in normal humans were induced by compression with an arm cuff during recording of skin reflectance spectra. Reflectance spectra of UV-induced erythema were also recorded and compared with laser-Doppler flow measurements. Spectral reflectance measurements were found to be highly sensitive in determining minimal erythema, which was not clinically detectable. The measurements of erythema using reflectance spectroscopy and UV irradiation were very highly correlated (r = 0.996). It was possible to calculate the in vivo absorbance of oxygenized haemoglobin. The melanin pigmentation following UV irradiation was quantified by reflectance spectroscopy and correlates highly with the dose of UV irradiation (r = 0.995). Furthermore, regional variations in skin melanin and haemoglobin were analysed for fair Caucasian skin.

Adult↗
PubMed1989

The dopamine inhibitor GBR 12909: selectivity and molecular mechanism of action.

The neurochemical profile of GBR 12909 (1-(2-bis(4-fluorphenyl)-methoxy)-ethyl)-4-(3-phenyl-propyl)pipera zine) was investigated. GBR 12909 was a potent and selective inhibitor of synaptosomal dopamine uptake (KI = 1 nM), with a 20-fold lower affinity for the histamine H1-receptor and a more than 100-fold affinity for the noradrenaline and 5-HT uptake carriers, the dopamine D-1, D-2, 5-HT2, 5-HT1A and alpha 1-receptors and voltage-dependent sodium channels. GBR 12909 (3 microM) was without effect on muscarinic, alpha 2, beta 1 + 2, gamma-aminobutyric acid (GABA) and benzodiazepine receptors, and on choline and GABA uptake carriers. The selective dopamine uptake inhibitory profile of GBR 12909 was confirmed by ex vivo uptake experiments. GBR 12909 inhibited uptake in vitro in a competitive manner as did cocaine and methylphenidate. [3H]GBR 12935 binding was competitively inhibited by GBR 12909 as well as by dopamine, cocaine and methylphenidate. Off-rate analysis of the [3H]GBR 12935 binding excluded the presence of allosteric binding sites on the dopamine carrier complex. Instead, the data favored the notion that GBR 12909 inhibits dopamine uptake by binding to the dopamine binding site on the carrier protein itself, thereby blocking the carrier process. In conclusion, GBR 12909 is a highly selective inhibitor of dopamine uptake, both in vivo and in vitro. At the moment GBR 12909 is the only compound with this neurochemical profile. The selective effect of GBR 12909 on this neuronal system makes it an interesting experimental tool and a potential antidepressant agent.

Animals↗
PubMed1989

Amphetamine discrimination: effects of dopamine receptor agonists.

Dopamine (DA) D-1 and D-2 receptor agonists and antagonists were characterized in receptor binding and adenylate cyclase assays with respect to affinity, selectivity and efficacy. The ability of the ligands to interact with the discriminative stimulus effects of d-amphetamine (AMPH) was then assessed. The D-2 agonists, quinpirole, pergolide and CH 29-717, substituted completely for AMPH while neither partial (SKF 38393 and SKF 75670) nor full D-1 receptor agonists (SKF 89626 and SKF 81297) substituted. On the other hand, the selective D-1 and D-2 antagonists all blocked AMPH. The substitution for AMPH by pergolide was blocked by raclopride but not by SCH 23390, indicating D-2 mediation. In contrast, the motor effects of pergolide were blocked by both raclopride and SCH 23390, indicating mixed D-1/D-2 receptor involvement. These results suggest that D-1 and D-2 are equally involved in the expression of functional effects in the DAergic motor systems. Conversely, D-2 receptors may play a primary role in the DA systems involved in the AMPH cue; furthermore, the D-1 and D-2 receptors in the systems are relatively uncoupled.

Adenylyl Cyclases↗
PubMed1989

15-hydroxyeicosatetraenoic acid (15-HETE) specifically inhibits the LTB4-induced skin response.

15-Hydroxyeicosatetraenoic acid (15-HETE), a 15-lipoxygenase product of arachidonic acid, inhibits leukotriene B4 (LTB4)-induced chemotaxis of polymorphonuclear leukocytes (PMNs) in vitro. In this study the effects of intradermal injections of LTB4 were determined in the absence or presence of 15-HETE. For comparison intradermal injections of purified human complement split product C5a were performed in the absence or presence of 15-HETE. The skin response was evaluated by measuring the diameter of the wheal, the area of the flare and by intensity of the erythema (erythema index). LTB4 and C5a were injected at the concentration of 200 ng/ml. At this concentration the maximal skin response of LTB4 and C5a were equivalent. In contrast to C5a reaction, which resolved within 1 h, LTB4-induced skin response lasted up to 18 h. In all subjects the skin response was significantly decreased when LTB4 was injected together with 300 ng of 15-HETE. The decrease of wheal, flare, and erythema index averaged 81.9%, 56.6%, 53.6%, respectively, when all parameters were obtained at the maximal skin response. In contrast, the C5a-induced skin response was not affected by addition of 15-HETE, even when the final dose of 15-HETE was increased 10 times to 3 micrograms. The LTB4-induced reaction could last up to 18 h after injection. After the addition of 300 ng of 15-HETE the skin response resolved after 1 h. The present results demonstrate that 15-HETE is a specific inhibitor of the LTB4-induced skin response and brings additional evidence in support of the ability of 15-HETE to regulate the proinflammatory effects of LTB4 in vivo.

Adult↗
PubMed1989

Vascular response of human skin after analgesia with EMLA cream.

We investigated vascular responses after cutaneous application of EMLA cream (a eutectic mixture of lignocaine and prilocaine) by skin reflectance spectroscopy and laser Doppler blood flowmetry. In healthy subjects, EMLA cream produced a biphasic vascular response with an initial vasoconstriction, maximal after 1.5 h of application. After prolonged application (greater than 3 h, vasodilatation occurred, presumably because of a smooth muscle relaxant effect of the analgesics. Vasoconstriction was also observed initially with two non-EMLA creams applied under occlusion, whereas the occlusive plastic film alone did not alter the vascular state. Thus late vasodilatation was unique to EMLA cream.

Adult↗
PubMed1989

Metformin improves peripheral but not hepatic insulin action in obese patients with type II diabetes.

UNLABELLED: Nine obese patients with Type II diabetes mellitus were examined in a double-blind cross-over study. Metformin 0.5 g trice daily or placebo were given for 4 weeks. At the end of each period fasting and day-time postprandial values of plasma glucose, insulin, C-peptide and lactate were determined, and in vivo insulin action was assessed using the euglycemic clamp in combination with [3-3H]glucose tracer technique. Metformin treatment significantly reduced mean day-time plasma glucose levels (10.2 +/- 1.2 vs 11.4 +/- 1.2 mmol/l, P less than 0.01) without enhancing mean day-time plasma insulin (43 +/- 4 vs 50 +/- 7 mU/l, NS) or C-peptide levels (1.26 +/- 0.12 vs 1.38 +/- 0.18 nmol/l, NS). Fasting plasma lactate was unchanged (1.57 +/- 0.16 vs 1.44 +/- 0.11 mmol/l, NS), whereas mean day-time plasma lactate concentrations were slightly increased (1.78 +/- 0.11 vs 1.38 +/- 0.11 mmol/l, P less than 0.01). The clamp study revealed that metformin treatment was associated with an enhanced insulin-mediated glucose utilization (370 +/- 38 vs 313 +/- 33 mg.m-2.min-1, P less than 0.01), whereas insulin-mediated suppression of hepatic glucose production was unchanged. Also basal glucose clearance was improved (61.0 +/- 5.8 vs 50.6 +/- 2.8 ml.m-2.min-1, P less than 0.05), whereas basal hepatic glucose production was unchanged (81 +/- 6 vs 77 +/- 4 mg.m-2.min-1, NS). CONCLUSIONS: 1) Metformin treatment in obese Type II diabetic patients reduces hyperglycemia without changing the insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1989

Two classes of [3H]spiperone binding sites in bovine neurohypophysis: D-2 receptors and putative 5-HT2 receptors.

Binding of [3H]spiperone was studied in membranes obtained from bovine neurohypophyses devoid of intermediate lobe tissue. Non-linear Scatchard plot suggested the presence of more than a single class of binding sites. Competition experiments using ketanserin, a ligand selective for 5-HT2 receptors, were carried out to ascertain whether serotonergic, in addition to dopaminergic receptors, might be responsible for the heterogeneity of [3H]spiperone binding. Computer-assisted modeling suggested the presence of two classes of binding sites for ketanserin (Kd = 1.6 +/- 0.2 and 366.7 +/- 20.5 nM, respectively). The Kd value for ketanserin binding to the high-affinity sites, as well as the Kd of [3H]spiperone for these sites suggested by the 2 sites model indicate that they represent serotonin 5-HT2 receptors. The [3H]spiperone Kd at the ketanserin low-affinity sites (65 +/- 7 pM) and the rank order of inhibitory potencies for several antagonists show that the low-affinity sites represent dopamine D-2 receptors.

Animals↗
PubMed1988

Differential effects of EEDQ on the dopamine D-1 receptor in vivo and in vitro.

As measured in vitro by means of [3H]SCH 23390 saturation analysis, 5 and 10 mg/kg (i.p., 24 h) of EEDQ caused a 70% reduction and 20 mg/kg and 80% reduction in the numbers of D-1 receptors. In vivo, also measured by [3H]SCH 23390 saturation analysis, 5 mg/kg of EEDQ caused no significant reduction in the D-1 receptor number whereas 10 and 20 mg/kg caused a 40 and 70% reduction, respectively. This difference in sensitivity to EEDQ in vivo as compared to in vitro suggests that EEDQ only destabilizes the D-1 receptor, whereas the inactivation occurs during preparation of the tissue for in vitro binding. Thus, caution should be exercised when animals depleted of D-1 receptors by EEDQ are used for behavioral studies.

Adrenergic alpha-Antagonists↗
PubMed1988

Evidence that phorbol ester-activated pathways are not directly involved in the action of insulin in rat adipocytes.

The effects of 12-phorbol 13-myristate acetate (PMA) on glucose transport, glucose metabolism and lipolysis in rat adipocytes were examined. Alone, PMA (100 ng/ml) stimulated 2-deoxyglucose transport, glucose oxidation and lipogenesis by an amount corresponding to about 30-50% of the maximal insulin effect. The effect of PMA on the insulin-stimulated processes was additive at all insulin concentrations. Adenosine deaminase-stimulated lipolysis was enhanced by about 50% by PMA (100 ng/ml). Thus, in contrast to insulin, PMA had a lipolytic effect. The antilipolytic effect of insulin was unaffected by the presence of PMA, both ED50 and maximal inhibition of insulin were unchanged. In conclusion, it is suggested that phorbol esters may activate pathways other than those activated by insulin in rat adipocytes.

Adipose Tissue↗
PubMed1988

Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding to dopamine receptors in vivo in mouse brain.

In vivo binding of the benzamide derivative [3H]raclopride was studied in mouse brain. The binding was saturable, reversible and stereospecific. Non-specific binding was 5-15% of the total binding. Pharmacological characterization of the binding indicated labelling of dopamine D2 receptors since the binding was potently inhibited by compounds with high affinity for this receptor in vitro. On the other hand, compounds with low affinity in vitro i.e., dopamine D1-selective compounds were weak or inactive as inhibitors of [3H]raclopride binding. A comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding in vivo indicated that compounds with selectivity in vitro retained this selectivity in vivo. Thus, spiroperidol, haloperidol, 1-sulpiride, clebopride, LY 171555 and (-)-NPA ((-)-N-propyl-norapomorphine) were D2 selective while SCH 23390, SKF 38393 and SKF 75670 were D1 selective. Clozapine, tilozepine, cis-flupentixol, chlorpromazine and butaclamol were non-selective both in vitro and in vivo. However, a few compounds changed profile in vivo compared to in vitro. Thus, fluperlapine and fluphenazine had a dual D1-D2 receptor profile in vitro but were D1- or D2-selective in vivo, respectively. Pergolide and molindone which were D2-selective in vitro both had a dual D1-D2 receptor profile in vivo. In conclusion, [3H]raclopride, in vivo, selectively labels the dopamine D2 receptor. Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding in vivo supported the that the dopamine D1 receptor is an important target for a variety of neuroleptics, especially of the clozapine type. This may indicate that blockade of the dopamine D1 receptor conveys antipsychotic action.

Animals↗
PubMed1988

A mixed meal potentiates the insulin sensitivity of glucose transport and metabolism in adipocytes from patients with type 2 diabetes mellitus.

Post-glucose enhancement of insulin action may represent a physiological mechanism for the acute regulation of insulin sensitivity of target tissues. To clarify whether a similar mechanism is operative in the insulin-resistant diabetic state we have investigated the effects of a mixed meal on adipocyte insulin action in eight patients with Type 2 diabetes mellitus. Ninety minutes after ingestion of breakfast insulin binding to fat cells increased by 21% (p less than 0.05). In the fasting state 6 patients had a significant response of glucose transport and lipogenesis to insulin whereas two exhibited non-responsiveness. In the 6 responders insulin sensitivity, as estimated by the insulin concentration at which half-maximal effect was achieved, increased for glucose transport (before, 260 +/- 46 pmoll-1; after, 105 +/- 21 pmol l-1; p less than 0.05) and for lipogenesis (before, 36 +/- 9 pmol l-1; after, 9 +/- 2 pmol l-1; p less than 0.05). No significant changes occurred in basal or maximal glucose transport or lipogenesis. In the two primary non-responders intake of the meal was associated with average increase in maximal insulin responsiveness of 52% for glucose transport and 28% for lipogenesis. Intake of a mixed meal is associated with a slight increase of insulin binding to adipocytes from patients with Type 2 diabetes mellitus but a marked increase of adipocyte insulin sensitivity at the post-binding levels of glucose transport and metabolism.

Adipose Tissue↗
PubMed1988

Teratogenicity and in vitro mutagenicity studies on nonoxynol-9 and -30.

Polyoxyethylene alkylphenols (PA) are a group of non-ionic surfactants with a widespread use. As part of the safety evaluation of PA a teratology study with nonoxynol-9 and -30 (NP-9 and NP-30) administered perorally and epicutaneously to rats was performed. In addition the mutagenicity of NP-9 was tested in the Ames test. Treatment of pregnant rats with NP-30 (up to 1 g/kg b.wt./day, orally) did not reveal any signs of adverse effects. Pregnant rats given 250 mg or 500 mg NP-9/kg b.wt./day orally exhibited a statistically significant decrease in weight gain. A concomitant effect in these dams on reproduction, and an increase in the incidence of extra ribs and dilated pelvic cavity in their foetuses was interpreted as a consequence of a toxic effect of high doses of NP-9. No clear cut effect was observed when pregnant rats were dosed epicutaneously with up to 500 mg of NP-9/kg b.wt./day. A slight but persistent response in one tester strain in the Ames test was not interpreted as a clear mutagenic effect of NP-9.

Animals↗
PubMed1988

In vivo action of glibenclamide in obese subjects with mild type 2 (non-insulin dependent) diabetes.

In order to evaluate whether the hypoglycaemic action of glibenclamide during chronic treatment of obese subjects with NIDDM is primarily due to changes in the daytime insulin level, in insulin secretion or to changes in tissue sensitivity to insulin, we studied eight NIDD's (age 43 +/- 3 years, body mass index 31.4 +/- 2.6 kg/m2) inappropriately controlled by dietary treatment alone. Before and after three months of glibenclamide treatment, plasma glucose, insulin and C-peptide were measured hourly (0800 to 1600 hours) and in vivo insulin sensitivity was evaluated using the sequential euglycaemic clamp (insulin infusion: 0, 0.8, 3.2 mU/kg/min) in combination with 3-3H-glucose tracer technique. During glibenclamide treatment the mean daytime glucose level was reduced (11.2 +/- 0.5 versus 7.1 +/- 0.4 mmol/l, p less than 0.001) but not to normal (5.2 +/- 0.2 mmol/l, p less than 0.001). Before treatment the mean daytime insulin level was higher than normal (38 +/- 58 versus 24 +/- 2 microU/ml, p less than 0.05) and was increased by 79% (67 +/- 8 microU/ml, p less than 0.001) after three months of treatment. In contrast the mean C-peptide level was unchanged (1.40 +/- 0.13 versus 1.30 +/- 0.17 nmol/l, p = NS), although it was higher than normal on both occasions (0.84 +/- 0.09 nmol/l, p less than 0.05). The basal hepatic glucose production rate was normal before treatment (86 +/- 4 versus 82 +/- 3 mg.m-2.min-1 in normals, p = NS), and unchanged after glibenclamide treatment (80 +/- 3 mg.m-2.min-1, p = NS versus pretreatment level).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Irradiation inactivation studies of the dopamine D1 receptor and dopamine-stimulated adenylate cyclase in rat striatum.

In frozen rat striatal tissue, exposed to 10 MeV electrons from a linear accelerator, the sizes of the dopamine (DA) D1 receptor and the DA-sensitive adenylate cyclase complex were determined using target size analysis. The number of D1 receptors (labelled by [3H]SCH 23390) declined monoexponentially with increasing radiation intensity, yielding a molecular weight (mol.wt.) of 80 kDa. Also the activity of the catalytic unit (C) of the adenylate cyclase (as measured by forskolin stimulation), decreased monoexponentially, however with a mol.wt. of 145 kDa. Both basal, DA- and fluoride (F-)-stimulated activity declined in a concave-downward fashion with a limiting mol.wt. of 134, 138 and 228 kDa, respectively. It was estimated that the basal and DA-stimulated activity originated from an enzyme complex with a mol.wt. of 325 kDa, a value close to the combined size of RGs and C. These data suggest that F- stimulation of the adenylate cyclase, which occurs by a Gs activation, does not cause dissociation of Gs into the alpha s and beta gamma subunits. Further, the DA-regulated adenylate cyclase apparently exists as a complex consisting of RGs and C; the mechanism of hormonal activation is a dissociation of C from this complex.

Adenylyl Cyclases↗
PubMed1987

[3H]GBR 12935 binding in vivo in mouse brain: labelling of a piperazine acceptor site.

The binding of the selective dopamine uptake inhibitor [3H]GBR 12935 was studied in vivo in mouse brain. The binding was reversible with t1/2 = 80 min. The localisation of [3H]GBR 12935 binding and of dopaminergic receptors did not overlap. The binding of [3H]GBR 12935 was distributed almost uniformly throughout the brain. Also, the in vitro inhibition of dopamine uptake and the inhibition of in vivo [3H]GBR 12935 binding did not correlate when a series of relevant reference compounds was used. The potencies of various dopamine uptake inhibitors to induce stereotyped behavior did not correspond to the inhibitory potencies in the [3H]GBR 12935 binding assay. In conclusion, [3H]GBR 12935 labels in vivo a site which is different from the dopamine uptake complex. We have recently obtained results for the in vitro binding of [3H]GBR 12935 that indicate that this site could be a piperazine acceptor site.

Animals↗