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Biomedical subjects

C Nordin

Publications and source records attributed to C Nordin.

107 records · Page 6Linked to original sources
PubMed1985

CSF and plasma levels of nortriptyline and its 10-hydroxy metabolite.

After 3 weeks' nortriptyline (NT) treatment the mean plasma concentration of its 10-hydroxy metabolite (10-OH-NT) (599 +/- 207 nmol l-1) was higher than that of the parent drug (433 +/- 199 nmol l-1) in 25 depressed patients. Also in the cerebrospinal fluid (CSF) the mean level of 10-OH-NT (67 +/- 20 nmol l-1) was higher than that of NT (39 +/- 23 nmol l-1). There was a strong correlation (P less than 0.001) between the CSF and plasma concentration of both NT (r = 0.92) and 10-OH-NT (r = 0.77). The interindividual variation in the CSF/plasma ratio of both compounds was small, compared to the variation in plasma levels. These results show that 10-OH-NT passes the blood-brain barrier as it is present in concentrations higher than those of NT in the CSF. 10-OH-NT has previously been shown to be a potent blocker of noradrenaline uptake and to have much less affinity for muscarinic receptors than NT itself. This active metabolite might therefore be a potential antidepressant with less disturbing anticholinergic side-effects.

Aged↗
PubMed1985

Delayed afterdepolarizations and triggered activity in ventricular muscle from rats with streptozotocin-induced diabetes.

Previous studies have shown that myocardium of the diabetic rat has impaired myoplasmic calcium metabolism. Delayed afterdepolarizations and triggered activity are potentiated by conditions believed to increase intracellular calcium concentration therefore, we performed this study to investigate the possibility that myocardium of the diabetic rat is more susceptible than normal tissue to develop afterdepolarizations and triggered activity. We used standard microelectrode techniques to record the electrical activity of papillary muscles from hearts of control rats and rats made diabetic with streptozotocin. We compared the response of control and diabetic preparations to conditions presumed to create progressively more severe degrees of myoplasmic calcium loading, viz. perfusion with solutions containing ouabain (5 X 10(-5) M) and increasing concentrations of calcium (2.4, 4.8, 7.2, and 9.6 mM). Our results showed the following. Ventricular muscle from diabetic rats was more prone than normal myocardium to develop delayed afterdepolarizations and triggered activity under conditions believed to cause myoplasmic calcium overload. The external calcium concentration correlated with the incidence but not the magnitude or coupling interval of the delayed afterdepolarizations in fibers of diabetic rats. The action potentials in fibers of diabetic rats decreased markedly in duration after exposure to ouabain, whereas normal action potentials were not affected significantly; as external calcium was increased with ouabain still present, the action potential duration in diabetic fibers decreased slightly more, whereas the action potential duration in normal fibers did not change significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Desmethylimipramine overdose: nonlinear kinetics in a slow hydroxylator.

A case of desmethylimipramine (DMI) overdose is described. The analysis of DMI and its main metabolite, 2-hydroxydesmethylimipramine (2-OH-DMI), in plasma was performed by high performance liquid chromatography with fluorescence detection. Characterization of the elimination kinetics of DMI by using the SAAM 25 computer program indicated Michaelis-Menten kinetics. The patient was phenotyped with respect to debrisoquine hydroxylation and classified as a slow hydroxylator. Both nonlinear kinetics and slow hydroxylation might have contributed to the marked difference between the concentration of DMI and 2-OH-DMI in plasma in this patient.

Desipramine↗
PubMed1984

Combined renovascular hypertension and diabetes in rats: a new preparation of congestive cardiomyopathy.

Myocardial function, electrophysiologic characteristics, and structure were studied in rats with both renovascular hypertension and streptozotocin-induced diabetes (HD). Ventricular papillary muscles from untreated rats with HD showed a marked slowing of isometric and isotonic contractions. Peak developed tension and peak shortening were preserved, except in one animal with findings of congestive heart failure. Transmembrane action potentials increased fivefold in duration. Myocardial interstitial fibrosis was frequently observed. Physiologic parameters of rats with HD treated by left nephrectomy, captopril, and insulin were very similar to those of age-matched controls. The mortality rate of rats with HD was 43% over 5 to 6 months in the first study. In a second study, spontaneously dying rats with HD were compared with those deliberately killed. A 55% mortality was observed over 7 months. Myocardial structural damage and histologic evidence of congestive heart failure were more frequent in spontaneously dying rats with HD. Combined renovascular hypertension and diabetes in rats appears to be a new preparation of congestive cardiomyopathy.

Action Potentials↗
PubMed1983

The effect of estrogen dose on postmenopausal bone loss.

In order to establish whether the favorable effect of estrogen therapy on postmenopausal bone loss was dose related, we measured sequential changes in the cortical diameters of the metacarpals by radiographic morphometry in 120 normal postmenopausal women who were being treated with ethinyl estradiol in doses ranging from 5 to 50 micrograms daily. There was a net loss of bone at doses below 15 micrograms per day and a net gain at doses of 25 micrograms per day and above. At doses between 15 and 25 micrograms daily, bone was neither gained nor lost. The loss of bone with the low doses was due to expansion of the medullary cavity that was unaccompanied by any change in total bone width. There was no change in bone volume with the intermediate doses because endosteal resorption of bone was offset by periosteal apposition. The net gain of bone with the higher doses occurred because endosteal resorption was totally inhibited but periosteal bone apposition continued. Thus, in postmenopausal women the reduction in the rate of cortical bone loss in response to estrogen therapy depends on the dose administered.

Adult↗
PubMed1983

Altered myocardial response to ouabain in diabetic rats: mechanics and electrophysiology.

Diabetes induced by streptozotocin in rats is associated with changes in the mechanical function of isolated ventricular papillary muscle. Relaxation is slowed and shortening velocity is depressed. The effects of ouabain (10(-7) to 2 x 10(-4)M) and changes in extracellular calcium ([Ca2+]0 = 0.6 to 12 mM) on the mechanical and electrical properties of normal and diabetic papillary muscles were studied. High doses of ouabain caused a rise in resting tension and a fall in developed tension in both diabetic and control muscles. However, these changes were strikingly greater in diabetic muscles which developed partial contractures at 10(-4)M. The altered response to ouabain was observed in chronically (5 to 7 weeks or 3 months) but not acutely (less than 1 week) diabetic animals. Similarly, the response to ouabain was restored to normal after chronic (5 weeks) therapy with insulin but not after acute (4 days) therapy. In both normal and diabetic muscles, the mechanical effects of increasing [Ca2+]0 from 2.4 to 12.0 mM were qualitatively similar to those seen with ouabain at 10(-5) to 10(-4)M. Electrophysiologic studies showed that under control conditions action potentials of diabetic muscles were significantly longer than those of normal muscles. Treatment with progressively higher concentrations of ouabain (10(-7) to 10(-4)M) and [Ca2+]0 (2.4 to 12.0 mM) caused shortening of both normal and diabetic action potentials, but the effects of these interventions were much greater in the diabetics. These results suggest that the response of diabetic muscles to ouabain is markedly different from normal and that this altered response may be due to impaired regulation of intracellular Ca2+ levels in diabetic myocardium.

Action Potentials↗
PubMed1981

Bromocriptine treatment of depressive disorders. Clinical and biochemical effects.

Fifteen depressed patients were treated with increasing doses of bromocriptine in an open study. Twelve were treated for 5 weeks (final dose 20-60 mg daily) and nine of these recovered almost completely. As expected from a dopamine agonist, bromocriptine decreased the level of homovanillic acid (HVA) in cerebrospinal fluid (CSF) by 15% (P less than 0.05) and 23% (P less than 0.01) after 2 and 5 weeks of treatment, respectively. After 2 but not after 5 weeks of treatment there was also a small but significant decrease (13%; P less than 0.001) of the noradrenaline metabolite HMPG in CSF. Although there was no mean effect on 5-HIAA in CSF, there was a significant relationship between the HVA and 5-HIAA levels (as % of pretreatment level) both after 2 and 5 weeks of treatment (r = 0.96 and r = 0.62, respectively). This may indicate that the drug has an effect on the serotonin system secondary to the dopamine receptor stimulation. The amelioration of depression was not related to HVA, but did correlate to HMPG in CSF (r = 0.65; P less than 0.05) both metabolites measured before treatment. These results indicate that bromocriptine may have antidepressant effects possibly mediated through the noradrenergic system rather than the dopaminergic system.

Adult↗
PubMedDate not supplied

Gradients of CSF monoamine metabolites: a comparison between male and female volunteers.

Lumbar puncture at the L4-5 level was performed on 12 healthy male and 12 healthy female volunteers. Confirming previous results, we found pronounced gradients in cerebrospinal fluid (CSF) 5-HIAA and HVA (5-hydroxyindoleacetic acid and homovanillic acid). We also found a gradient in 4-hydroxy-3-methoxyphenylglycol (HMPG), but only in the male volunteers. We also found that tapping-time was significantly longer in females than in males. One reason for this discrepancy may be that an estimate of the spinal distance was greater in males, which might indicate that a hydrodynamic factor plays a role. On taking tapping-time into consideration, the 5-HIAA and HMPG concentrations were significantly higher in males than in females.

Adult↗
PubMedDate not supplied

Influence of tapping-time and atmospheric pressure on concentrations of monoamine metabolites in the cerebrospinal fluid: a prospective study in female volunteers.

Lumbar puncture was performed on 12 healthy female volunteers at the L4-5 level. CSF concentrations of 5-HIAA, HVA and HMPG were included in turn as dependent variables in repeated analyses of covariance with age, height, tapping-time, atmospheric pressure and the distance on the spine in the lying position as regressors. Use or non-use of oral contraceptives was included as a nominal variable. Results obtained were confirmed by nonparametric statistics. We found significant relationships between 5-HIAA and HVA, respectively, and height when the concentrations per minute of tapping-time (nM/min) were used as dependent variables. Hypothetically, the tapping-time mirrors the transport of concentrated CSF from the cranial to the caudal region when sitting up. We also found significant influences of atmospheric pressure and the use or non-use of oral contraceptives on HMPG. The role of atmospheric pressure is not clear but it might contribute to the transport of HMPG from the periphery to the CSF or affect the outflow of HMPG from the lumbar CSF compartment. The contribution of oral contraceptives might reflect interactions in the cerebral catecholamine metabolism.

Adult↗
PubMedDate not supplied

Acid monoamine metabolites in the CSF of healthy controls punctured without preceding strict bedrest: a retrospective study.

Data were obtained from 46 healthy volunteers, 16 males and 30 females, lumbar punctured at the L4-5 level without strict bedrest prior to puncture. 18 ml of CSF was collected at the puncture, which was performed with a 0.9 mm diameter needle. Contradictory to previous reports, body height did not influence CSF 5-hydroxyindoleacetic acid (5-HIAA) or homovanillic acid (HVA). Age influenced HVA (but not 5-HIAA) in a curvilinear manner in male volunteers and the HVA/5-HIAA ratio in females. In contrast to previously reported correlations between 5-HIAA and HVA, a weak correlation was found, but only in females. In males, body weight related to 5-HIAA and atmospheric pressure to HVA, both in a positive direction. Our findings are largely contradictory to previous reports, a fact that might, hypothetically, be due to the absence of strict bedrest before puncture. The use of a comparatively wide needle (0.9 mm in diameter) and the amount of 18 ml CSF drawn might, taken together, make at least some contribution to an explanation.

Adolescent↗
PubMedDate not supplied

Monoamine precursors, transmitters and metabolites in cerebrospinal fluid: a prospective study in healthy male subjects.

In order to elucidate methodological aspects of CSF investigations, 14 healthy male subjects were lumbar-punctured at the L4-5 level following a standardised procedure. CSF concentrations of precursors, transmitters and transmitter metabolites were used as dependent variables, while age, height, body weight, atmospheric pressure and some other factors served as independent variables. 5-HIAA and HVA (but not HMPG) have pronounced concentration gradients. We also found CSF gradients for the precursors tryptophan and tyrosine, as well as for serotonin, dopamine and the dopamine metabolite DOPAC. Dopamine and atmospheric pressure showed a positive intercorrelation. Age correlated curvilinearly (convex upward) with tryptophan but showed a negatively directed linear correlation with serotonin. Serotonin and 5-HIAA showed no intercorrelation. Our results suggest an age-dependent disposition of tryptophan in the CSF. The absence of a correlation between serotonin and 5-HIAA might be inconsistent with the notion that 5-HIAA is a marker of central serotonin turnover. The comparatively high body weight of our volunteers might explain the lack of a gradient for HMPG.

3,4-Dihydroxyphenylacetic Acid↗