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  • 1
    ISSN: 1432-0428
    Keywords: Diabetes mellitus ; counter-regulatory hormones ; glucagon ; cortisol ; growth hormone ; adrenaline ; insulin ; non-esterified fatty acids ; ketone bodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To evaluate the relative role of “diabetogenic” hormones as insulin antagonists in severe derangements of diabetic control, glucagon, cortisol, growth hormone and adrenaline were administered by continuous intravenous infusion, separately and in combination, to ketosis-prone insulin-dependent diabetics (n=11). The amount of insulin required for the assimilation of a 50 g glucose load during the various hormone infusions was determined by means of an automated glucose-controlled insulin infusion system and used as an index of insulin effectiveness. Raising plasma hormone concentrations acutely into the range seen in severe diabetic states (glucagon 517±70 pg/ml; cortisol 32±3 μg/dl; growth hormone 14±3 ng/ml) did not alter significantly blood glucose profile and insulin requirement (control 11.3±1.1 U; glucagon 11.6±2.0 U; cortisol 11.1±0.4 U; growth hormone 12.9±1.4U), except for adrenaline (plasma level 550±192 pg/ml), which caused a marked rise in blood glucose levels and a threefold increase in insulin demand (31.1±3.7 U). Combined infusion of all hormones did not potentiate significantly the latter effect (38.3±4.7 U). The effectiveness of metabolic control by insulin was assessed by a marked decrease in plasma non-esterified free fatty acids and ketone bodies upon its administration after glucose ingestion in all groups studied. It is concluded that from the hormones investigated within this study adrenaline exerts the strongest diabetogenic action during its short term administration followed by that of growth hormone. Whereas it may well be that over-insulinization of the patients by the glucose controlled insulin infusion system has overcome and disguised the smaller diabetogenic effects of cortisol and glucagon.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Trestatin ; Ro 9-0154 ; Type2 diabetes ; α-amylase inhibitor ; starch digestion ; starch meal ; blood glucose ; plasma insulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Trestatin (Ro 9-0154), a new specific α-amylase inhibitor of microbial origin, was tested in six normal subjects and seven Type 2 (non-insulin-dependent) diabetic patients. In normal subjects the maximal increases in blood glucose following a 115-g starch meal were 2.19±0.57 mmol/l (mean±SEM) with placebo, but 1.32±0.39 mmol/l with 10 mg, 1.06±0.26 mmol/l with 20 mg, 0.43±0.07 mmol/l with 50 mg (p〈0.05) and 0.26±0.14 mmol/l with 100 mg (p〈0.05) Trestatin. The corresponding increases in plasma insulin were 116.5±19.6mU/l; 74.8±17.5 mU/l; 50.7±8.3 mU/l; 28.7±6.9 mU/l (p〈0.05) and 16.5±3.2 mU/l (p〈0.05). In the diabetic patients the maximal increases in blood glucose following a 50-g starch meal were 6.09±0.02 mmol/l with placebo, but 3.17±0.59 mmol/ (p〈0.05) with 10 mg and 1.69±0.41 mmol/l (p〈0.05) with 30 mg Trestatin. The corresponding insulin increases were: 58.8±12.7 mU/l, 31.5±9.7mU/l (p〈0.05) and 23.4±4.8 mU/l (p〈0.05). Trestatin fully retained this pharmacological activity during treatment for 4 weeks in the diabetic patients. Trestatin did not influence glucose and insulin profiles after oral glucose and sucrose. These results are consistent with a specific inhibition of α-amylase in man.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Obesity ; Type 2 diabetes ; hyperinsulinaemia ; insulin production rate ; splanchnic insulin retention ; splanchnic glucose output ; insulin resistance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary To differentiate peripheral and hepatic insulin resistance in hyperinsulinaemic overweight Type 2 (non-insulin-dependent) diabetic patients (n = 17; 143±4% ideal body weight; mean±SEM) arterial concentrations and splanchnic exchange of glucose, pyruvate, lactate, non-esterified fatty acids, β-hydroxybutyrate and acetoacetate, as well as the insulin production rate, were determined before and during oral glucose loads of 25 g or 100 g. Insulin production rate, hepatic insulin retention and splanchnic exchange of glucose and metabolites were estimated by means of the hepatic venous catheter technique. In the basal state insulin production rate was greater in overweight Type 2 diabetic patients (2.57±0.28 pmol.kg-1. min-1) than in healthy control subjects (1.68±0.17 pmol.kg-1. min-1; p〈0.01). After ingestion of 25 g glucose, the cumulative insulin production rate exceeded normal values (p 〈 0.05), but was below normal with 100 g glucose (p 〈 0.01). Relative insulin trapping by the splanchnic bed in the diabetic patients was 54±3%, not different from normal. Following a 100 g glucose load, splanchnic insulin retention fell by 20% in the patients, and less consistently so in healthy controls. Splanchnic glucose output was normal in the diabetic patients both in the basal state and after glucose ingestion although the induced arterial blood glucose levels were greater in the diabetic patients than in control subjects (p 〈 0.005). Splanchnic output of pyruvate (p 〈 0.025), lactate (p 〈 0.01), and β-hydroxybutyrate (p 〈 0.005) were greater in the basal state in the diabetic patients than in healthy subjects. However, no difference in splanchnic exchange was seen between the two groups in their metabolites' respective response to glucose ingestion. These data suggest that obese hyperinsulinaemic Type 2 diabetic patients may represent a subgroup of diabetic patients with predominantly peripheral, but compensated hepatic, insulin resistance being associated with an increased basal insulin production rate which only exhausts after ingestion of a large glucose load.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Insulin production rate ; splanchnic C-peptide output ; hepatic insulin retention ; splanchnic metabolism ; man ; glucose
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Insulin production rate has been estimated in healthy male volunteers (n = 16), and evaluated with respect to splanchnic glucose exchange. Insulin production rate was calculated from splanchnic immunoreactive C-peptide output. C-peptide secretion was estimated by the hepatic venous catheter technique both in the basal state and for 2h following ingestion of various glucose loads (0, 12.5, 25, 50, 75, and 100 g). The results demonstrate a basal insulin production rate of 0.017±0.002 U/min (mean±SEM) or 2.04 U/2 h. Values rose in a dose dependent manner from 2.6±1.1 U/2 h after ingestion of 12.5 g of glucose to 10.8±1.1 U/2 h following a glucose load of 100 g. Insulin retention by the liver was estimated at 0.012±0.001 U/min in the basal state, and ranged from 47–85% (70±2%) of production following an oral glucose load. It was also demonstrated 1) that the relative splanchnic glucose output was inversely related to the amount of ingested glucose, and reached a minimum when glucose in excess of 50 g was ingested; and 2) that hepatic glucose retention was directly proportional to insulin production rate (r=0.83; p〈0.001; n= 15). It is suggested that the adaptive capacity of the splanchnic bed to retain glucose depending on the amount of ingested glucose guarantees that splanchnic glucose output fluctuates in healthy man only within a narrow range.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Acta neuropathologica 55 (1981), S. 307-318 
    ISSN: 1432-0533
    Keywords: Diphtheritic polyneuropathy ; Muscle biopsy ; Intramuscular nerves ; Electron microscopy ; Histochemistry ; Diphtherie-Polyneuropathie ; Muskelbiopsie ; intramuskuläre Nerven ; Elektronenmikroskopie ; Histochemie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Biopsien aus Extremitätenmuskeln von vier Kranken mit schwerer tetraplegischer Form der Diphtherie-Polyneuropathie konnten nahe dem Höhepunkt der Erkrankung gewonnen und mit modernen Methoden einschließlich Histochemie, Elektronenmikroskopie und morphometrischer Verfahren untersucht werden. Vergleichbare Studien wurden bisher nicht veröffentlicht. Die Muskulatur bot vorwiegend neurogene Veränderungen mit disseminierten angulierten Fasern, eine besonders die Typ-2B-Fasern betreffende, mehr generaliierte Atrophie sowie Targetoidherde oder „Cores” in Typ-1-Fasern. Darüber hinaus fanden sich eindeutige myogene Veränderungen mit unterschiedlichen Degenerationsphänomenen bis zur totalen Nekrose, offenbar — wie am Herzmuskel —toxischer Herkunft. Das neurogen-myogene Mischbild entsprach den elektromyographischen Befunden. Die intramuskulären Gefäße waren unauffällig bis auf vereinzelte perivaskuläre, vorwiegend mononukleäre Zellinfiltrate mit reichlich zerebriformen lymphoiden Zellen, wahrscheinlich T-Lymphozyten. An 11 intramuskulären Nerven und zwei motorischen Endplatten waren eindeutig auf die Diphtherie zu beziehende Veränderungen nicht aufzudecken. Dies kann als Hinweis auf eine vorwiegend proximale Entmarkung bei der Diphtherie-Polyneuropathie des Menschen gedeutet werden, die damit eher der experimentellen Form des Kaninchens als der des Meerschweinchens entspricht.
    Notes: Summary Mucle biopsies from the lower extremities of four patients with severe tetraplegic form of diphtheritic polyneuropathy were examined by modern techniques including histochemistry, electron microscopy and morphometric procedures. Until now comparable studies have not been published. The biopsies were removed during the acute stage of the polyneuropathy. We found scattered small angulated muscle fibers beside a more generalized slight atrophy predominantly of type 2B fibers and targetoid-phenomenons or cores in type 1 fibers. Beside this neurogenic pattern there also were, corresponding with the results of electromyography, primary myogenic alterations with different degenerative phenomenons, suspicious of toxic origin as in cardiac muscle. The intramuscular vessels showed no abnormalities except some perivascular predominantly mononuclear cellular reactions with a remarkable number of cerebriform lymphoid cells, probably T-lymphocytes. No specific pathological alterations could be detected in 11 intramuscular nerves and two motor endplates. This may reflect the more proximal demyelination of human peripheral neurons by the diphtheria toxin as found in experimental diphtheria of the rabbit in contrast to the more distal type of the guinea pig.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 60 (1982), S. 823-828 
    ISSN: 1432-1440
    Keywords: Diabetes mellitus ; Plasma norepinephrine ; Blood pressure regulation ; Diabetes mellitus ; Plasmanoradrenalin ; Blutdruckregulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Das Verhalten von Blutdruck, Plus und Plasmanoradrenalin während verschiedener Stimulationsmanöver sympathisch nervöser Aktivität sowie das vaskuläre Reaktionsvermögen auf infundiertes Noradrenalin (50, 100 und 200 ng/kg−1/min−1,t=15 min) wurde bei 17 Diabetikern und 6 gesunden Probanden untersucht. Unterschieden wurden Diabetiker 1) ohne Zeichen autonomer Dysfunktion und ohne periphere Neuropathie (n=6), 2) ohne Zeichen autonomer Dysfunktion jedoch mit schwerer peripherer Neuropathie (n=6) und 3) mit autonomer Dysfunktion, mit (n=3) und ohne (n=2) peripherer Neuropathie. Während eines „Cold pressor tests“ (2 min), mechanischer Hautirritation (10 min) und Orthostase (10 min) zeigten Diabetiker ohne klinische Zeichen autonomer Dysfunktion ein den gesunden Kontrollpersonen vergleichbares Verhalten von Blutdruck, Plus und Plasmanoradrenalin, während Diabetiker mit autonomer Dysfunktion unabhängig vom Bestehen einer peripheren Neuropathie während der Orthostase, nicht jedoch während des „Cold pressor tests“ und mechanischer Hautirritation eine deutlich herabgesetzte Noradrenalinfreisetzung (P〈0.05) aufwiesen. Normalpersonen und Diabetiker ohne autonome Dysfunktion unterschieden sich bezüglich ihres Blutdruckverhaltens während Noradrenalininfusion nicht, während Diabetiker mit autonomer Dysfunktion auf die Verabreichung von exogenem Noradrenalin (200 ng/kg/min) mit einem gegenüber Normalpersonen verstärkten (P〈0.05) Blutdruckanstieg reagierten. Störungen der Noradrenalinfreisetzung und der adrenergen Blutdruckregulation scheinen somit, unabhängig vom Bestehen einer peripheren Neuropathie, nur bei Diabetikern mit klinischen Zeichen autonomer Dysfunktion aufzutreten. Der Nachweis derartiger Störungen gelingt jedoch nur bei Anwendung von Stimuli größerer Intensität wie Orthostase oder Infusion einer hohen Noradrenalindosis.
    Notes: Summary Changes in blood pressure (BP) and plasma norepinephrine (NE) following various stimuli of the sympathetic nervous system were studied in six healthy subjects and in 17 diabetic patients. The latter were subdivided in three groups: (1) six patients with neither peripheral neuropathy nor autonomic dysregulation, (2) six patients with severe peripheral neuropathy without autonomic dysregulation, and (3) five patients with autonomic dysregulation, three of whom suffered also from peripheral neuropathy. The following procedures were performed: (1) cold pressor test (2 min), (2) mechanical irritation of the skin by suction (0.75 kg/cm2, 10 min), (3) orthostasis (10 min), and (4) i.v. infusion of NE (50, 100, 200 ng kg−1 min−1 for 15 min each). Both the stimulated endogenous plasma NE levels and BP response to exogenous NE were the same in normal subjects, in diabetic controls and in diabetics with peripheral neuropathy without autonomic dysregulation. In contrast, diabetics with postural hypotension showed a less pronounced release of NE to standing (P〈0.05), but not to cold pressor test and mechanical skin irritation. Furthermore, they showed increased vasoreactivity to the highest dose (P〈0.05), but not to the lower doses of exogenous NE. Thus NE release and adrenergic BP regulation seem to be altered only in diabetics with clinical signs of autonomic dysregulation. These alterations can only be evaluated when patients are exposed to stimuli of higher intensity, such as orthostasis or infusion of a high NE dose.
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  • 7
    ISSN: 1432-1440
    Keywords: Plasma catecholamines ; Dopamine ; Norepinephrine ; Epinephrine ; Sulfoconjugation ; Infants ; Children
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Plasma concentrations of free and sulfoconjugated catecholamines were measured in healthy infants and children under resting conditions. Free norepinephrine and epinephrine levels were up to three times higher in healthy children under 2 years than in adults, even under true resting conditions. In contrast, free dopamine concentrations of all age groups fell within the normal range for adults. The levels of sulfoconjugation were in the adult range.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naturwissenschaften 1 (1913), S. 1084-1087 
    ISSN: 1432-1904
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology , Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Biological cybernetics 10 (1972), S. 64-77 
    ISSN: 1432-0770
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Computer Science , Physics
    Notes: Abstract The preprocessing of optical information in the visual system takes place in the two-dimensional homogeneous nervous nets of the retina and the geniculate body. These networks can be considered as band-pass filters for space-dependent oscillations if the input stimuli are independent of time. If the synapses of the neurons have timefrequency dependent properties the performance of the system in the space domain, which is important for pattern recognition, is determined by the time dependence of input signal. For a description of these networks in this investigation the space spectrum for various values of the time frequency ω is used. The answers of real nervous nets can be interpreted by the model when the two-dimensional input signals are switched, flickered or moved. For this reason these dynamic stimuli are necessary for an analysis of the cortex. The theoretical combination of space- and time-dependent filtering is essential for an understanding of cortical transformations.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 42 (1992), S. 227-229 
    ISSN: 1432-1041
    Keywords: Tenoxicam ; Warfarin ; drug interaction ; pharmacokinetics ; anticoagulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The influence of tenoxicam on plasma warfarin concentrations and on its anticoagulant effect has been studied in healthy volunteers. Tenoxicam did not alter the plasma warfarin concentration versus time profile. Treatment with it for 14 days had no effect on the average dose of warfarin required to maintain the prothrombin time within a specified range. The coumarin dose index, an indicator of warfarin sensitivity, remained unchanged during tenoxicam administration. The results demonstrate the lack of a clinically relevant effect of tenoxicam on warfarin-induced anticoagulation.
    Type of Medium: Electronic Resource
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