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  • 1
    Electronic Resource
    Electronic Resource
    Microdialysis measurement of the absolute glucose concentration in subcutaneous adipose tissue allowing glucose monitoring in diabetic patients (1992)
    Springer
    Diabetologia 35 (1992), S. 1177-1180 
    Details
    ISSN: 1432-0428
    Keywords: Microdialysis ; glucose monitoring ; subcutaneous ; adipose tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The possibility of continuously monitoring the absolute glucose concentration in subcutaneous adipose tissue, using microdialysis of the extracellular water space, was investigated in six Type 1 (insulin-dependent) diabetic patients. By using a large microdialysis probe (30×0.62 mm), and by perfusing with a low flow rate (0.5 μl/min), complete recovery of glucose was attained in vitro. In the patients the dialysis probe was implanted subcutaneously, perfused by a wearable microinfusion pump, and dialysate samples were collected in 60-min fractions over 10 h. The absolute glucose concentration in the tissue dialysate was the same or almost the same as the blood glucose concentration (range 87–101 % of the blood glucose value). The changes in blood glucose were closely paralleled by the variations in adipose tissue glucose (r=0.93, p〈0.01), and the recovery of glucose in the microdialysate remained constant during the 10-h study period. In conclusion, it is possible, using microdialysis, to directly determine the absolute glucose concentration in subcutaneous adipose tissue. Hence, this technique may be used for continuous glucose monitoring in diabetic patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401374
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  • 2
    Electronic Resource
    Electronic Resource
    Effect of insulin on human adipose tissue metabolism in situ. Interactions with beta-adrenoceptors (1992)
    Springer
    Diabetologia 35 (1992), S. 664-670 
    Details
    ISSN: 1432-0428
    Keywords: Microdialysis ; glucose ; glycerol ; lactate ; pyruvate ; isoproterenol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of insulin, and its interactions with catecholamines through beta-adrenoceptors, on human adipose tissue glucose utilization and lipolysis were investigated in vivo. Microdialysis of the extracellular compartment of abdominal subcutaneous adipose tissue was performed in healthy subjects of normal weight, before and during a 2-h hyperinsulinaemic (61±3 mU/l), euglycaemic clamp. The tissue was perfused with or without the beta-adrenergic agonist isoproterenol (10−mol/l), and the tissue dialysate concentrations of glucose, glycerol (lipolysis index) lactate and pyruvate were determined. During the insulin infusion, glucose in adipose tissue decreased by 20% (p〈0.001), despite arterial steady-state normoglycaemia. The concentrations of lactate and pyruvate increased gradually to a steadystate plateau of twice the basal level in adipose tissue and arterial blood. Insulin-induced suppression of glycerol (lipolysis index) was, if anything, more marked in adipose tissue than in plasma (65% vs 50% decrease from baseline levels, p〈0.05). In situ perfusion of adipose tissue with isoproterenol, starting either at the beginning of the study period or at 45 min after initiation of the insulin infusion, resulted in marked and rapid elevations of all the investigated metabolites in the adipose tissue extracellular compartment (p〈0.05–0.005).Itis concluded that insulin action on glucose uptake and lipolysis in human adipose tissue in vivo is counteracted by beta-adrenoceptor stimulation. In contrast, insulin and beta-adrenoceptors have synergistic effects on non-oxidative glucose metabolism in human adipose tissue in situ.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400260
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  • 3
    Electronic Resource
    Electronic Resource
    A circadian rhythm in lipid mobilization which is altered in IDDM (1997)
    Springer
    Diabetologia 40 (1997), S. 1070-1078 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Microdialysis ; glycerol ; non-esterified fatty acids ; circadian rhythm ; growth hormone.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It is not clear how circadian lipolysis and circulating concentrations of non-esterified fatty acids (NEFA) are altered in intensively treated insulin-dependent diabetic (IDDM) patients. Ten IDDM patients on an intensive insulin regimen and eight healthy control subjects were investigated under ordinary living conditions for 27 h by microdialysis of subcutaneous adipose tissue. The true tissue glycerol concentration and adipose blood flow changes were monitored as an index of lipolysis. A circadian pattern in adipose tissue lipolysis was observed in both groups, decreasing during the day and increasing during evening-night. The daytime decrease was normal, but the evening-night rise was elevated in IDDM (p = 0.03). Circulating NEFA decreased during the day and increased at night. The latter increase was enhanced threefold in IDDM (p = 0.003) and correlated with fasting glucose levels (r = 0.77). Nocturnal growth hormone (GH) was increased fivefold in IDDM and correlated to nocturnal lipolysis (r = 0.83). Adipose tissue blood flow increased during the night in a similar fashion in both groups. Near-normalization of glucose for 24 h in IDDM did not affect the nocturnal increases in NEFA, GH and lipolysis. In conclusion, a circadian rhythm in lipolysis was found. Increased lipolytic rates during evening-night may at least in part raise nocturnal circulating NEFA. Nocturnal NEFA and lipolysis are further enhanced in IDDM, maybe due to elevated GH, but not to insulinopenia or hyperglycaemia. [Diabetologia (1997) 40: 1070–1078]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050789
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  • 4
    Electronic Resource
    Electronic Resource
    Short-Term increase and long-term reversion of striatal cell activity after degeneration of the nigrostriatal dopamine system (1978)
    Springer
    Experimental brain research 33 (1978), S. 159-171 
    Details
    ISSN: 1432-1106
    Keywords: 6-OH dopamine ; Striatum ; Parkinsonism ; Plasticity ; Spontaneous activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The spontaneous activity of neurons in the head of the striatum was studied in rats 3 days and more than 1 year after a 6-hydroxydopamine-induced lesion of the nigrostriatal dopamine system in comparison to unlesioned animals. Cells were detected and tracked by stimulating the excitatory corticostriatal pathway. In unlesioned animals striatal cells discharged at very low frequencies, with a median of 0.04 impulses/second. The activity was increased to 0.28 impulses/second 3 days after the lesion. This increase was related to the degree of dopamine depletion. More than 1 year after the lesion, the frequency had decreased to a level indistinguishable from that measured in unlesioned animals, with a median of 0.03 impulses/second. Cells in 3-day lesioned animals discharged a higher number of bursts at shorter intervals as compared to unlesioned animals, while in long-term denervated animals the bursting pattern was similar to that in unlesioned animals. This demonstrates that removal of the dopaminergic input results in increased activity only during an initial phase and that adaptive processes subsequently occur. The data from this Parkinsonian model suggest that symptoms of this disease cannot simply be related to an increased striatal cellular activity. The fact that the initially increased spontaneous activity adapted indicates that functional effects of a lesion can only be evaluated when studying the resulting changes throughout a time course.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238057
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  • 5
    Electronic Resource
    Electronic Resource
    Striato-nigral dynorphin and substance P pathways in the rat (1986)
    Springer
    Experimental brain research 64 (1986), S. 169-192 
    Details
    ISSN: 1432-1106
    Keywords: Basal ganglia ; Transmitters ; Neuropeptides ; GABA ; Enkephalin ; Striato-nigral pathways
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of striatal ibotenic acid lesions on dynorphin-, substance P- and enkephalin-like immunoreactivities in the substantia nigra has been studied with immunohistochemistry as well as biochemistry. A comparison was made with the effects produced by intranigral ibotenic acid lesion and by 6-hydroxy-dopamine injection into the medial forebrain bundle. In addition, the effect of the striatal lesions on nigral glutamic acid decarboxylase (GAD)-positive structures was analysed with immunohistochemistry. The effect of the lesions was analysed functionally in the Ungerstedt rotational model, in order to obtain a preliminary evaluation of the extent of the lesions. The striatal lesions produced a parallel depletion of dynorphin and substance P levels in the substantia nigra, pars reticulata, ipsilateral to the treated side, which was dependent upon the extent and location of the lesion. Ibotenic acid lesions into the tail and the corpus of the striatum produced stronger nigral-peptide depletion than lesions in the head and the corpus of the striatum. Comparison of placement of lesions and localization of depleted area in the substantia nigra revealed a topographical relationship. Furthermore, the nigral depletion patterns of dynorphin and substance P were similar. The immunohistochemical analysis revealed that also GAD-positive fibers in the pars reticulata to a large extent disappeared after striatal lesions, in parallel to the dynorphin- and substance P-positive fibers. However, the depletion was less pronounced for GAD than for the peptides, probably related to presence of local GABA neurons in the zona reticulata of the substantia nigra. These results indicate that with the types of lesion used in this study it is not possible to provide evidence for a differential localization within the striatum of dynorphin-, substance P- and GABA-positive cell bodies projecting to the substantia nigra. The radioimmunoassay showed that (Leu)- but not (Met)-enkephalin was affected to the same extent as the dynorphin peptides, supporting the view that (Leu)-enkephalin in the pars reticulata of the substantia nigra is derived from proenkephalin B and not from proenkephalin A. In the immunohistochemical analysis (Met)-enkephalin-like immunoreactivity could only be detected in the pars compacta of the substantia nigra and did not seem to be affected by any of the lesions. The striatal lesions produced a behavioural asymmetry, which could be disclosed by stimulating the rats with apomorphine, which produced ipsilateral rotation. The total number and intensity of the rotation were closely correlated to the extent and location of the striatal lesion as well as to the amount of dynorphin and substance P depletion found in the substantia nigra of the treated side. The results provide further evidence for the presence of a dynorphin-containing system with fibers originating mainly in the corpus and tail of the striatum and terminating in the zona reticulata of the substantia nigra and may, similarly to the previously characterized substance P and GABA containing pathways, have a role in the control of motor behaviour.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238213
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  • 6
    Electronic Resource
    Electronic Resource
    Chronic implants of chromaffin tissue into the dopamine-denervated striatum. Effects of NGF on graft survival, fiber growth and rotational behavior (1985)
    Springer
    Experimental brain research 60 (1985), S. 335-349 
    Details
    ISSN: 1432-1106
    Keywords: Chromaffin grafts ; Dopamine denervation ; Experimental parkinsonism ; Nerve growth factor ; Rotational behavior ; Falck-Hillarp histochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Adult rat chromaffin tissue was transplanted into striatum of adult rat recipients whose nigrostriatal dopamine pathway had been lesioned on the grafted side by 6-hydroxydopamine. Long-term survival of the intrastriatal chromaffin grafts and the effects of treatment with nerve growth factor (NGF) was studied histochemically using Falck-Hillarp fluorescence histochemistry and functionally using rotational behavior induced by apomorphine. Small, cortex-free adrenal chromaffin tissue grafts survived permanently in striatum. The number of surviving cells was significantly increased by NGF. NGF treatment also caused transformation of many cells towards a more neuronal phenotype and greatly enhanced the adrenergic nerve fiber outgrowth into host brain tissue. NGF was either injected stereotaxically into the site of transplantation or infused continuously using implantable osmotic minipumps and a stereotaxically placed chronic indwelling dialysis fiber through striatum. The latter arrangement permitted continuous infusion of NGF for 14–28 days and caused a vigorous adrenergic nerve growth response by the grafts directed towards the source of NGF in the brain. There was a clearcut correlation between morphological signs of taking and rotational behavior. Grafts, and in particular grafts treated with NGF, were able to significantly and permanently counteract the rotational behavior induced by apomorphine. There seemed to be a dose relationship between NGF treatments and amount of reduction of asymmetric behavior. NGF treatment probably decreased the relative importance of diffuse release of catecholamines from chromaffin cells in the graft and increased the importance of adrenergic innervation of host striatum by cells in the graft. Immunofluorescence using antibodies against glial fibrillary acidic protein did not reveal any marked gliosis around the grafts nor were there any marked gliotic reactions around chronic indwelling dialysis fibers. We conclude that implantation of chromaffin tissue into striatum in conjunction with NGF treatments is an effective means of counteracting some of the symptoms of experimentally induced unilateral parkinsonism in rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00235929
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  • 7
    Electronic Resource
    Electronic Resource
    Striato-nigral dynorphin and substance P pathways in the rat (1986)
    Springer
    Experimental brain research 64 (1986), S. 193-207 
    Details
    ISSN: 1432-1106
    Keywords: Basal ganglia ; Dopamine ; Dynorphin ; Substance P ; 6-hydroxy-dopamine ; Ibotenic acid ; Rotational behaviour ; Intracerebral dialysis technique ; Feedback regulation ; Efferent pathways
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In the present study the functional role of the striato-nigral dynorphin and substance P pathways in rat brain has been studied using the rotational behavioural model and an intracerebral dialysis technique complemented with brain lesions and immunohistochemical analysis. Attempts were made to evaluate whether these striato-nigral neurons have a feed-back modulatory action on the dopaminergic nigro-striatal system, or whether they represent an outflow pathway conveying motor information from the striatum. Unilateral injection of dynorphin A into the substantia nigra reticulata of naive rats induced contralateral rotational behaviour. This effect was dose-dependent and mimicked by the kappa-opioid receptor agonist, U50,488H. Intranigral injection of substance P, as well as substance K, also produced dose-dependent contralateral rotational behaviour. Unilateral injections of ibotenic acid into various sites of the striatum were used to destroy the striato-nigral pathways. The lesions produced a depletion of dynorphin- and substance P-like immunoreactivity in the pars reticulata of the substantia nigra ipsilateral to the lesion and markedly affected the behavioural responses to intranigral peptide injections. Dynorphin A more potently induced contralateral rotation in the lesioned compared to naive non-lesioned rats, suggesting development of supersensitivity for this peptide. Substance P on the other hand, was markedly less potent in inducing rotation in lesioned animals. The rotational responses to both dynorphin A and substance P were potentiated by injection of amphetamine 1 h later, suggesting that both peptides act via nigro-striatal dopamine neurons. However, in rats with unilateral nigro-striatal dopamine denervation, produced with 6-hydroxy-dopamine, dynorphin A retained its potency to induce rotational behaviour; substance P was again much less potent. Thus, both the ibotenic acid and 6-hydroxy-dopamine lesions differently affect the action of dynorphin A and substance P in the zona reticulata of the substantia nigra. The data suggests that substance P requires an intact dopamine pathway to produce the rotational response, while dynorphin A does not. Direct evidence that behavioural activation produced by dynorphin A is not dependent upon dopamine stimulation was obtained by intrastriatal dialysis experiments in which changes in striatal dopamine release were measured following intranigral injection of dynorphin A or substance P. Intranigral dynorphin A in fact reduced, while substance P increased the release of dopamine. It is concluded that the dynorphin and substance P striatonigral pathways have different functions. Thus, substance P in the striato-nigral pathway may have a role in a positive feed-back loop regulating the firing of nigro-striatal dopamine neurons, while dynorphin might be important in negative feed-back control. The rotational behaviour produced by DYN A is probably due to direct stimulation of receptors located on nigro-thalamic and nigro-tectal pathways.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00238214
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  • 8
    Electronic Resource
    Electronic Resource
    Treatment of malignant glioma by a new therapeutic principle (1992)
    Springer
    Acta neurochirurgica 114 (1992), S. 8-11 
    Details
    ISSN: 0942-0940
    Keywords: Malignant glioma ; microdialysis ; L-2,4 diaminobutyric acid ; cytolysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary L- 2,4 diaminobutyric acid (DAB) is a non-physiological, cationic amino acid transported into cells by System A with potent antitumour activity in vitro against human glioma cells. This activity was the result of the pronounced concentrated uptake of DAB in glioma cells to the extent that a cellular lysis could occur due to osmotic reasons. We describe the treatment of 3 patients with inoperable malignant glioma by direct and continuous administration of DAB in tumour tissue employing a microdialysis technique. One to three microdialysis probes were implanted in the tumour tissue through small dural incisions in 3 patients with inoperable malignant glioma. Micropumps charged with 3 ml a day of a Trisbuffered 0.125 M DAB solution made isotonic at pH 7.55 were adapted to the input channel of the probe and a sampling tube to the output for continuous flowing into tumour tissue. The patients were treated in this way for a total of 14–21 days without side effects assignable to DAB. Massive tumour necrosis occurred as judged by comparison of computed tomography performed before and after DAB treatment. The yield of the dialysis procedure with regard to DAB was estimated to be 40–50%. The dialysate concentration of arginine (a cationic amino acid considered to be transported mainly by system A) was high and increased nearly 4-fold from day 3 to day 6 of treatment. DAB administered in this way into malignant brain tumour tissue was well tolerated and showed promising antitumour activity in the 3 patients with inoperable malignant glioma. High and increasing concentrations of arginine in the dialysate during treatment indicated a displacement of this amino acid from the intracellular space of malignant tumour cells most probably as a consequence of huge intracellular accumulation of DAB preceding cellular lysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01401106
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  • 9
    Electronic Resource
    Electronic Resource
    Neurometabolic monitoring of the ischaemic human brain using microdialysis (1990)
    Springer
    Acta neurochirurgica 102 (1990), S. 91-97 
    Details
    ISSN: 0942-0940
    Keywords: Brain ; ischaemia ; man ; microdialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent animal research has provided evidence that brain ischaemia is associated with a shift of energy related metabolites (lactate, adenosine, inosine, and hypoxanthine) and several transmitters from the intracellular to the extracellular fluid (ECF). These chemical changes of the ECF reflect the energy crisis of the ischaemic tissue. We have proposed that measurement of these metabolites in the ECF using microdialysis may be a useful technique for detection of secondary ischaemia in neurosurgical intensive care patients. As a first step in the evaluation of such a possible clinical application of microdialysis the aim of this study was to measure energy related metabolites and amino acid transmitters during cerebral ischaemia in man. Microdialysis probes were inserted in tumour-free cortical tissue in the frontal lobe in patients undergoing frontal lobe resection as a treatment for brain tumours. Dialysis samples were collected in 10 minutes fractions before and during frontal lobe resection, thus serving as a simulated ischaemia model. The resection procedure was associated with markedly elevated levels of the energy related metabolites as well as transmitter amino acids. The tissue surrounding the probes was examined histologically, and the degree of oedema was estimated from CT scans. In two of the patients the tissue hosting the probes was oedematous. These patients had markedly higher basal levels of lactate. The main conclusions were (1) that the results support the clinical potential of microdialysis, (2) that lactate may be a sensitive indicator of the metabolic disturbances associated with brain oedema, and (3) that frontal lobe resection may be a useful human brain ischaemia model.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01405420
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  • 10
    Electronic Resource
    Electronic Resource
    Tachykinins and Related Peptides in the Substantia Nigra and Neostriatum (1991)
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 632 (1991), S. 0 
    Details
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1749-6632.1991.tb33107.x
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