Search PubMed⌕ Search

Biomedical subjects

J J Larsen

Publications and source records attributed to J J Larsen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Insulin-stimulated muscle glucose clearance in patients with NIDDM. Effects of one-legged physical training.

Physical training increases insulin action in skeletal muscle in healthy men. In non-insulin-dependent diabetes mellitus (NIDDM), only minor improvements in whole-body insulin action are seen. We studied the effect of training on insulin-mediated glucose clearance rates (GCRs) in the whole body and in leg muscle in seven patients with NIDDM and in eight healthy control subjects. One-legged training was performed for 10 weeks. GCR in whole body and in both legs were measured before, the day after, and 6 days after training by hyperinsulinemic (28, 88, and 480 mU x min(-1) x m(-2)), isoglycemic clamps combined with the leg balance technique. On the 5th day of detraining, one bout of exercise was performed with the nontraining leg. Muscle biopsies were obtained before and after training. Whole-body GCRs were always lower (P < 0.05) in NIDDM patients compared with control subjects and increased (P < 0.05) in response to training. In untrained muscle, GCR was lower (P < 0.05) in NIDDM patients (13 +/- 4, 91 +/- 9, and 148 +/- 12 ml/min) compared with control subjects (56 +/- 12, 126 +/- 14, and 180 +/- 14 ml/min). It Increased (P < 0.05) in both groups in response to training (43 +/- 10, 144 +/- 17, and 205 +/- 24 [NIDDM patients] and 84 +/- 10, 212 +/- 20, and 249 +/- 16 ml/min [control subjects]). Acute exercise did not increase leg GCR. In NIDDM patients, the effect of training was lost after 6 days, while the effect lasted longer in control subjects. Training increased (P < 0.05) muscle lactate production and glucose storage as well as glycogen synthase (GS) mRNA in both groups. We conclude that training increases insulin action in skeletal muscle in control subjects and NIDDM patients, and in NIDDM patients normal values may be obtained. The increase in trained muscle cannot fully account for the increase in whole-body GCR. Improvements in GCR involve enhancement of insulin-mediated increase in muscle blood flow and the ability to extract glucose. They are accompanied by enhanced nonoxidative glucose disposal and increases in GS mRNA. The improvements in insulin action are short-lived.

Analysis of Variance↗
PubMed1994

Physical training increases muscle GLUT4 protein and mRNA in patients with NIDDM.

Patients with non-insulin-dependent diabetes mellitus (NIDDM) exhibit insulin resistance and decreased glucose transport in skeletal muscle. Total content of muscle GLUT4 protein is not affected by NIDDM, whereas GLUT4 mRNA content is reported, variously, to be unaffected or increased. Physical training is recommended in the treatment of NIDDM, but the effect of training on muscle GLUT4 protein and mRNA content is unknown. To clarify the effect of training in NIDDM, seven men with NIDDM (58 +/- 2 years of age [mean +/- SE]) and eight healthy men (59 +/- 1 years of age) (control group) performed one-legged ergometer bicycle training for 9 weeks, 6 days/week, 30 min/day. Biopsies were obtained from the vastus lateralis leg muscle before and after training. GLUT4 protein analyses was performed along with analyses of muscle biopsies from five young (23 +/- 1 years of age) (young group), healthy subjects who participated in a previously published identical study. In response to training, maximal oxygen uptake increased (delta 3.3 +/- 1.8 in NIDDM subjects and 4.5 +/- 1.2 ml.min-1.kg-1 in control subjects [both P < 0.05]). Before training, GLUT4 protein content was similar in NIDDM, control, and young subjects (0.35 +/- 0.02, 0.34 +/- 0.03, and 0.41 +/- 0.03 arbitrary units, respectively), and it increased (P < 0.05) in all groups during training (to 0.43 +/- 0.03, 0.40 +/- 0.03, and 0.57 +/- 0.08 arbitrary units, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Food intake increases the relative oral bioavailability of vanoxerine.

Each of 12 healthy male subjects received single oral doses of 100 mg vanoxerine (GBR 12909), a dopamine reuptake inhibitor with potential antidepressant activity, on three different occasions (fasting, after a low-fat meal and after a high-fat meal) according to a randomized, cross-over design. The mean tmax value increased from 0.82 h after fasting to 1.44 h after a low-fat meal and to 2.46 h after a high-fat meal. Only modest food effects were seen on mean Cmax values (55 nM, 52 nM and 84 nM, after fasting, after the low-fat meal and after the high-fat meal, respectively) but values of AUC up to the last measurable concentration (AUC(0,t)) increased by 76% (from 110 to 194 nM h) after the low-fat meal and by 255% (from 110 to 391 nM h) after the high-fat meal compared with fasting. All of these effects were statistically significant except for the differences in tmax and Cmax between fasting and the low-fat meal. The mechanism of these changes is unclear, but it seems likely that food may lower the first-pass metabolism of vanoxerine, as has been shown for other lipophilic basic drugs.

Administration, Oral↗
PubMed1992

Educational outcome of neonatal intensive care graduates.

Studies of developmental outcome of neonatal intensive care unit graduates have generally been limited to the first 2 to 3 years of life, with outcome determined by psychometric tests. This study followed neonatal intensive care unit graduates born 1975 through 1983 (n = 457) into the public school system and compared their educational outcomes with those of newborn nursery graduates (n = 656). Outcomes were evaluated by placement in four academic categories: regular classroom, academic problems, speech/language impairment, and major impairment. Educational outcomes for children of both groups were essentially the same. Their placement in the four academic categories were equally affected by nonmedical variables, primarily income (below/above poverty level), race, and sex. Seventy percent of poverty-level children were in one of the three problem categories, compared with 40% of children above poverty level. Neither neonatal intensive care unit treatment nor low birth weight were major predictors of educational outcome. The only clear-cut neonatal intensive care unit effect occurred among children born with sensory or physical impairments. Therefore, in order to reduce poor educational outcomes, follow-up and intervention programs should be targeted primarily to children with diagnosable handicaps and from minority, low-income families.

Child↗
PubMed1991

Infertility in rats induced by 2,5-hexanedione in combination with acetone.

The morphological changes as well as the functional consequences for the reproduction of the testis-injuring effect of 2,5-hexanedione (2,5-HD) were evaluated in rats. The potentiation by acetone and the reversibility of the effects was also studied. Male rats were dosed for 6 weeks with 0, 0.13%, 0.25% or 0.50% 2,5-HD alone or in combination with 0.50% acetone in the drinking water. During the last week of treatment the fertility of half of the treated males was studied by introducing each of them to a non-treated female rat, after which the number of matings, pregnancies and foetuses was examined. In order to evaluate the degree of reversibility of the effect on testis the same examination was made in the other half of the males after a 10 weeks dose-free period. The weight and morphology of testis from all the males was studied. The weight of testis, testis tubuli diameter and fertility was reduced by 2,5-HD and further reduced in groups dosed with 2,5-HD, 0.25% and 0.50% plus acetone 0.50%. Combined administration of acetone and 2,5-HD caused a potentiation comparable to the effect of the double dose of 2,5-HD. Minor changes were reversible within the 10 weeks dose-free period, whereas infertility and other severe changes in the highest combined group were non-reversible within this period. The number of matings was unaffected. It is concluded that 2,5-HD has a testis-injuring effect, which in high doses and combined with acetone causes non-reversible infertility and that testis is more sensitive than the nerve tissue to 2,5-HD.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetone↗
PubMed1991

Irreversible effects in rats of toluene (inhalation) exposure for six months.

The irreversible CNS effects of six months' exposure to toluene (0, 500, and 1500 p.p.m.) in rats was studied applying a multi-disciplinary approach. After an exposure-free period, neurobehavioural, morphometric, pathological, and biochemical examinations were performed. No neurobehavioural or gross pathological changes were found. Morphometric measurements did not show loss of neurones. At 500 p.p.m. the mean nuclear volume and mean perikaryonal volume and the variation of the values of these parameters was increased in the exposed groups compared to the controls. Noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) levels were significantly changed in various brain regions. It is concluded that this investigation failed to reveal overt toluene-induced CNS-neurotoxicity, however, certain irreversible effects were found which further add to the accumulating evidence of the chronic CNS-neurotoxicity of toluene.

Administration, Inhalation↗
PubMed1990

Effect of toluene on ethanol preference in rats.

The effect of toluene on the preference of ethanol was studied in rats. Toluene was administered orally by stomac tube in doses of 200, 400 or 800 mg/kg daily for 5 weeks or by inhalation at a concentration of 2000 p.p.m. 6 or 8 hr daily for 5 or 6 days per week for 2 weeks in rats of different age. During toluene inhalation exposure the rats had access to either tap water or ethanol-containing water (6 or 10%). After the exposure and during oral administration the rats had access to both ethanol-free and ethanol-containing water. Toluene inhibited the body weight gain in the highest oral dose group and in rats exposed to toluene and forced to drink ethanol in the inhalation experiments. In these experiments, the intake of fluid was reduced in the exposure period in rats forced to drink ethanol-containing water and further reduced in rats exposed to both ethanol and toluene. Exposure to toluene alone increased the fluid consumption. The preference of ethanol defined as consumed ethanol-containing water in per cent of the total water intake was not influenced by oral administration of toluene. It was, however, reduced by toluene given by inhalation to rats forced to drink ethanol-containing water during the exposure period. Toluene exposure alone or forced ethanol intake alone caused in these experiments a short-lasting reduction of the ethanol preference. It is concluded that toluene decreases the preference of ethanol in rats forced to drink ethanol during exposure to toluene.

Administration, Inhalation↗
PubMed1988

SCH 23390--a selective dopamine D-1 receptor antagonist with putative 5-HT1 receptor agonistic activity.

The selective dopamine D-1 receptor antagonist SCH 23390 has been tested in vitro in the rat fundus model and in vivo in the electrically stimulated flexor reflex model. In the fundus model, SCH 23390 showed a potent agonistic activity compared to that of different 5-HT receptor agonists. Pindolol, 1-propranolol and pirenperone showed no or only weak inhibition of the SCH 23390-induced contractions in the fundus strip whereas methysergide was a potent inhibitor. The 5-HT3 receptor antagonist ICS 205-930 did not induce an inhibitory effect. In the electrically stimulated flexor reflex model in pithed rats, SCH 23390 induced a marked increase of the reflex. This increase was slightly inhibited by a mixed dopamine (DA) D-1/D-2 antagonist cis(Z)-flupentixol and by a specific DA D-2 antagonist YM 09151-2. Different reference antagonists: bicuculline (GABAergic), propranolol (beta-adrenergic), scopolamine (muscarinic), yohimbine (alpha 2-adrenergic), prazosin (alpha 1-adrenergic) were all without an antagonist effect on the SCH 23390-induced increase of the flexor reflex. Ketanserin, a selective 5-HT2 receptor antagonist, showed a weak and short-lasting inhibition of the SCH 23390 effect in high doses, whereas ritanserin showed only 35% inhibition of the SCH 23390-induced flexor reflex at a dose of 1.3 mumol/kg i.v. The mixed 5-HT1/5-HT2 antagonists methiothepin and metergoline showed a marked inhibitory effect at 2.6 mumol/kg i.v. and 3.1 mumol/kg i.v., respectively (1.3 mg/kg i.v.). These findings suggest that SCH 23390 might possess 5-HT1 receptor agonist activity.

Animals↗
PubMed1986

Pharmacological profile of a novel class of muscarinic acetylcholine receptor agonists.

Some in vivo pharmacological effects of a number of muscarinic acetylcholine receptor agonists containing the bicyclic 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO) skeleton were studied in rats and mice. The key compounds O,N-dimethyl-THPO (2) and O-methyl-THPO (4) are bioisosteres of arecoline and norarecoline, respectively. The vasodepressor effects of arecoline and the title compounds in anaesthetized rats gave parallel log dose-response curves. The order of potency of the compounds in this test system was identical with that measured earlier using a guinea-pig ileum preparation, arecoline and 2 being the most active compounds. This order of potency was different from those for the antinociceptive and anticonvulsant effects of the compounds using grid shock and isoniazid antagonism tests, respectively, where O-propargyl-THPO (3) proved to be the most active. The pA2 values for the atropine or scopolamine antagonism of these effects of arecoline and 4 were calculated. The partition coefficients (log P values) of the compounds were measured and shown to conform with their ability to penetrate the blood-brain barrier.

Analgesics↗
PubMed1986

Neurotransmitter-role of VIP in non-adrenergic relaxation of feline myometrium.

The feline myometrium is heavily innervated by VIP-containing nerve fibres. Transmural electrical stimulation (10 Hz, 2 msec, 150 mA) of muscle strips from feline myometrium in the presence of adrenoreceptor blocking agents caused a muscle relaxation. The smooth muscle relaxation was accompanied by a significant increase in immunoreactive VIP in the superfusate. Both the VIP release and the relaxation were completely annulled by tetrodotoxin, a selective blocker of axonal conduction. Furthermore, passive immunoneutralization with antiserum against VIP markedly reduced the smooth muscle relaxation induced by electrical stimulation. In the light of the previously demonstrated smooth muscle relaxant effect of VIP, the present findings indicate that the peptides may participate as neurotransmitter in non-adrenergic relaxation of the feline myometrium.

Animals↗
PubMed1986

A novel class of conformationally restricted heterocyclic muscarinic agonists.

A series of conformationally restricted compounds containing the 4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridin-3-ol (THPO) skeleton, including O-methyl-THPO (10a) and O,5-dimethyl-THPO (11a), were synthesized. The compounds were designed by bioisosteric replacement of the methyl ester groups of the muscarinic cholinergic agonists norarecoline and arecoline by the 3-methoxyisoxazole group, and their interactions with central and peripheral muscarinic receptors were tested in vitro. The compounds 10a, 11a, O-ethyl-THPO (10b), O-propargyl-THPO (10j), and O-ethyl-5-methyl-THPO (11b) were inhibitors of the binding of the muscarinic mustard [3H]PrBCM to rat brain membranes with an increasing order of potency. There was, however, a very low degree of correlation between these binding data and the effects of the compounds on peripheral (ileal) muscarinic receptors, where 11a, 10j, 11b, and 10a were agonists with a decreasing order of potency, whereas O-isopropyl-THPO (10e) showed antagonistic effects. The relatively low pKa values of the compounds (7.5-7.7 for compounds with secondary and 6.1-7.0 for compounds with tertiary amino groups) are likely to allow the compounds to penetrate the blood-brain barrier.

Animals↗
PubMed1986

Microscopic epidural lesions in goats given repeated epidural injections of morphine: use of a modified autopsy procedure.

Epidural catheterization was performed in six goats. Five days later either saline or 20 mg (5 mg/ml) preservative free morphine was injected epidurally once daily for 8 days. The goats were sacrificed 4, 24 or 48 hours after the last injection. The lumbar part of columna was removed in toto for microscopic examination of the spinal cord and the entire epidural space after decalcification and transverse sectioning. After saline, minimal changes including a fibrous membrane surrounding the catheter, scattered fat cell necrosis, scattered small focal cell infiltrations and occasionally focal haemorrhages were seen. After morphine the changes were considerably more severe including diffuse cellular inflammatory reaction in the epidural space, fat cell necrosis, occasionally focal exudative inflammation and chronic inflammatory reaction in the vicinity of the fibrous membrane demarcating position of the catheter. It is concluded that the present modified autopsy procedure permits microscopic examination of the epidural space. It has been shown that repeated administration of morphine caused tissue damage in the epidural space of goats. The human predictability of the results obtained is unknown. However, the results are encouraging for investigations with similar procedure in humans.

Animals↗
PubMed1986

The Knowledge of Child Development Inventory.

The need for an instrument that measures knowledge of child development and is comprehensible to lay populations and young adolescents has led to the development of the Knowledge of Child Development Inventory (KCDI). The KCDI is a 56-item multiple-choice test of knowledge of child development from birth to age three in the areas of emotional, cognitive, physical, and social development. Normative data were obtained on the KCDI from a sample population of 434 adolescent and adult females from varying racial backgrounds. The instrument has a reading level of 8.0 (Fry Reading Index), a minimum of technical terminology, reliability of .93 (Cronback's alpha coefficient of internal consistency), and criterion validity of .83. The KCDI would be relevant in educational settings where pre- and post-assessment of knowledge of child development is desired, i.e., high school courses in child development, prenatal classes, Head Start parent-training programs, and early childhood/special education parent-training programs. In addition, the KCDI would be relevant in clinical settings where the assessment of a person's concepts of child development are of importance i.e., adoption agencies, abuse centers, and teenage pregnancy centers.

Adolescent↗
PubMed1985

Receptor-binding profiles of neuroleptics.

Dopamine-receptor blockade seems to be a prominent effect of neuroleptics. Blockade of other receptors might, however, contribute to the therapeutic effect. A series of neuroleptics have been tested for affinity to DA D-1 and D-2 receptors, serotonin receptors (S2), alpha-adrenoceptors (alpha 1), histamine receptors (H1), and muscarinic cholinergic receptors. According to the affinity to DA D-1 and D-2 receptors, neuroleptics can be divided into different groups. Thioxanthenes have affinity for both D-1 and D-2 receptors; phenothiazines have affinity for D-2 receptors and considerably lower affinity for D-1 receptors; and butyrophenones, diphenylbutylpiperidines, and benzamides have affinity only for D-2 receptors. Concerning affinity to other receptors the only consistent finding is affinity for S2 receptors. The clinical significance of these findings is speculative. In several behavioral tests the D-1/D-2 classification is also observed, and it is suggested that D-1-receptor activation is responsible for dyskinesia, and that thioxanthenes - due to their D-1 receptor blocking effect-induce less dyskinesia than other neuroleptics.

Antipsychotic Agents↗
PubMed1985

Influence of pregnancy and sex steroids on concentration, motor effect and receptor binding of VIP in the rabbit female genital tract.

The influence of sex steroid and pregnancy on the tissue concentration, uterine motor effect and receptor binding of VIP has been studied in the female genital tract of pregnant rabbits and oophorectomized rabbits during progesterone and/or oestrogen substitution. The concentration of immunoreactive VIP was high in the vagina and cervix, and lower in the uterine body of both pregnant and non-pregnant rabbits. A significant decrease in the VIP concentration (pmol/g wet weight) of the uterine body was observed toward term of pregnancy. The total uterine content of VIP, however, seems unchanged. Treatment of oophorectomized rabbits with ovarian steroids had no effect on the VIP concentration. The sensitivity for and potency of VIP on the relaxation of uterine muscle was significantly higher in oophorectomized rabbits treated with a combination of progesterone and oestrogen than in control rabbits. No difference was observed between non-pregnant and pregnant rabbits. The degradation and binding affinity for 125I-labelled VIP was highest in oophorectomized rabbits substituted with both oestrogen and progesterone. In the pregnant rabbits, the amount of receptors was decreased near term. In conclusion, sex steroids are able to influence the motor effect of VIP at the receptor level, but have no effect on the VIP concentration in the female genital tract.

Animals↗
PubMed1985

5-HT-uptake inhibition potentiates antinociception induced by morphine, pethidine, methadone and ketobemidone in rats.

The effect of the specific 5-HT-uptake inhibitor citalopram on the antinociception induced by morphine, pethidine, methadone and ketobemidone was examined in rats by means of the hot plate test. Further the 5-HT-uptake-inhibiting potency of these opioid-receptor stimulants was examined in vitro in rat brain synaptosomes. In doses devoid of antinociceptive activity, citalopram in a dose-dependent manner potentiated the antinociception induced by the four opioid analgesics. The potentiation of the ketobemidone-induced antinociception was not influenced by the spasmolytic agent A 29 (N,N-dimethyl-3,3-diphenyl-1-methylallylamine) which together with ketobemidone constitutes the active substances in Ketogan. The 5-HT-uptake-inhibiting potencies of the opioid receptor stimulants were from 21 to more than 56000 times lower than that of citalopram, the order of potency being methadone greater than pethidine greater than ketobemidone greater than morphine. The results support the suggested role of 5-HT in morphine-induced antinociception and indicate a similar role in the antinociceptive effect induced by other opioid-receptor stimulants.

Analgesics↗
PubMed1985

Neurochemical profile of Lu 19-005, a potent inhibitor of uptake of dopamine, noradrenaline, and serotonin.

The neurochemical profile of a new compound, Lu 19-005 [(+/-)trans-3-(3,4-dichlorophenyl)-N-methyl-1-indanamine hydrochloride], has been investigated. Lu 19-005 is a potent inhibitor of the synaptosomal uptake of 3,4-dihydroxyphenylethylamine (dopamine, DA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT, serotonin). In this respect it resembles diclofensine, whereas compounds such as GBR 13.069 and bupropion are more selective DA-uptake inhibitors. Although Lu 19-005 releases DA in in higher concentrations it must be considered as an uptake inhibitor, as the accumulation of DA is inhibited in much lower concentrations. Lu 19-005 attenuates the DA and NA depletion caused by 6-hydroxydopamine in mouse brain. These properties confirm the DA- and NA-uptake-inhibitory properties of the compound. In receptor-binding models and functional in vitro tests Lu 19-005 is devoid of dopaminergic-, serotonergic-, noradrenergic-, histaminergic-, and cholinergic-inhibiting properties. Since DA, NA, and 5-HT seem to be involved in depression, the profile of Lu 19-005--with equally potent activity on the three neuronal systems--makes it an interesting experimental tool and a potential new antidepressant agent.

Animals↗