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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 67 (1989), S. 253-259 
    ISSN: 1432-1440
    Keywords: Platelet volume ; Thrombopoiesis ; Megakaryocytes ; Glycoprotein IB ; Flow-Cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Increased functional properties of diabetic platelets might be already conditionated during thrombopoiesis in the stem cell system. This hypothesis was studied by recording the distribution characteristics of the peripheral platelet pool in 218 diabetic patients versus 51 controls. Furthermore, platelet membrane coating with the stem cell marker glycoprotein IB was analyzed in 41 diabetic subjects and compared to 23 healthy volunteers. A consistant, significant shift of the volume distribution to larger platelets was found in diabetics: Mean platelet volume (MPV) — 7.9±0.9 versus 7.2±0.8 [fl]; Megathrombocyte index (MTI) — 20.4±2.8 versus 18.1±2.5 [fl]. These deviations were present in all patient subsets, however did not correlate to parameters of glucose metabolism. Whole blood platelet count was increased in the patient group: 195.0±59.5 versus 184.0±37.5×103 plts/ul. Coating with glycoprotein IB receptors correlated significantly to platelet size in platelets of both controls and diabetics (r normal=0.52±0.07;r diabetic=0.46±0.1). The quantitativ expression of glycoprotein IB was significantly enhanced in the diabetic group: 54500×1.28±1 versus 39100×1.3±1 molecules per platelet. In conclusion, these findings strongly support the assumption of diabetic stem cell dysfunction of the megakaryocytic series and progenitor cells resulting in platelets with primarily increased potency to adhere and aggregate in diabetes mellitus.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1440
    Keywords: Glycoproteins ; Prethrombotic State ; Monoclonal Antibodies ; Flow-Cytometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Formation of a hemostatic plug is trigered by platelets. Platelet function (e.g. adhesion, aggregation) depends essentially on membrane bound receptorproteins. Conventional chromatografic analysis of these glycoprotein macromolecules is difficult and not appropriate for diagnostic routine. In combination of cytoflowmetric single cell analysis with monoclonal staining we developed a bio-assay for qualitative and semi-quantitative analysis of glycoprotein IB and IIB/IIIA on vital fixed platelets. The expression of these molecules was evaluated in 20 healthy volunteers. The assay offers for the first time the possibility of screening the expression of receptor proteins on platelet membranes, which are related to indicate either a functional lack in bleeding disorders or a prethrombotic state due to an enhanced functional potential in high risk patients.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Type 1 diabetes ; Hypoglycemia ; Glucose counterregulation ; Insulin pumps
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We were interested in studying whether impaired hypoglycemic awareness after intensified insulin treatment with insulin pumps is associated with impaired glucose counterregulation. Glucose counterregulatory hormones were measured in 7 type I diabetic patients with altered symptoms after 6 months of continuous subcutaneous insulin infusion (CSII) (group 1) and in 9 patients with unchanged symptoms of hypoglycemia under CSII (group 2). The groups did not differ in diabetic control, duration of diabetes, or prevalence of neuropathy. Counterregulatory hormone response to an insulin-induced episode of hypoglycemia was measured before (first test) and after 6 months (second test) of CSII. Glucose nadirs and glucose recovery were similar in both groups and both tests. The mean plasma glucagon values demonstrate a lack of glucagon response in both groups and both tests. Growth hormone and cortisol increased in both groups and both tests without any difference between the groups or first and second tests. Epinephrine response was similar in both tests of group 2 (first test: 50±5 to 416±73; second test; 45±5 to 456 pg/ml), while in group 1 the response was not increased significantly in the second test [first test: 32± 6 to 346± 63; second test: 44± 7 to 575± 91 pg/ml; areas under curve (AUC) 11977 and 16345 pg×ml−1×90 min−1 (p= 0.36)]. There was a norepinephrine response in both groups and both tests, with nonsignificantly higher plasma levels during the second test [AUC in pg×ml−1×90 min−1; group 1, first test: 20954, second test: 26675 (p=0.394); group 2, first test: 20745, second test: 27089 (p=0.302)]. The results demonstrate that impaired awareness of hypoglycemic symptoms after intensified insulin therapy is not associated with impaired glucose recovery of hypoglycemia or impaired response of glucose counterregulatory hormones. Further-more, we found that the frequency of glucopenic symptoms reported by the patients during everyday life increased after CSII, while adrenergic symptoms were less frequent.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1440
    Keywords: Type 1 diabetes ; Recent onset ; Glycemic control ; Nerve conduction ; Autonomic function ; Cutaneous sensation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Motor and sensory nerve conduction velocities (MNCV, SNCV), beat-to-beat variation (BBV) at rest, speed of pupillary dilation (SPD), and pupillary latency time (PLT) were measured in 32 patients aged 12–36 years after 19±2 (mean±SEM) days and again after 3, 12, and 24 months of insulin treatment. Moreover, BBV under deep respiration was determined after 12 and 24 months, and thermal discrimination thresholds (TDT) as well as pain and vibration perception thresholds (PPT, VPT) were evaluated after 24 months. Mean HbA1 levels during months 3–24 within the normal range (7.2±0.2%; mean±SEM) were observed in 20 patients (group 1), while in 12 patients (group 2) mean HbA1 of months 3–24 was elevated (10.1±0.4%). There were no significant differences between both groups with regard to the nerve function tests at baseline and after 3 months. After 12 months mean median MNCV and median, ulnar, and sural SNCV were significantly lower in group 2 than in group 1 (p〈0.05). After 24 months mean median MNCV, peroneal MNCV, median SNCV, and sural SNCV as well as both BBV tests and PLT were significantly impaired in group 2 as compared to group 1 (p〈0.05). In addition, mean malleolar VPT and PPT to heat and cold stimuli on the thenar and the foot were significantly elevated in group 2 as compared to group 1 (p〈0.05). These findings suggest that early deterioration of somatic nerve function after one year and of autonomic function after 2 years of diabetes may be prevented by effective glycemic control initiated immediately after diagnosis of the disease.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Spontaneous diabetes ; mutationobob ; NZO mice ; diabetes in mice ; obesity in mice ; hereditary obesity ; insulin ; Beta-cells of pancreatic islets ; adipose tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé En étudiant le développement du syndrome obésité-hyperglycémic des sourisobob et NZO, des différences prononcées ont été trouvées entre ces deux souches. — Chez la souris NZO, la tolérance au glucose décroît progressivement avec l'augmentation du poids et de l'âge. — Chez la sourisobob, on distingue un développement du syndrome en 3 phases. Dans un premier temps dynamique, la tolérance au glucose diminue alors que la sécrétion d'insuline et le poids corporel augmentent. La phase intermédiaire ou transitoire — lorsque les animaux pèsent environ 55 g — est caractérisée par un changement rapide de l'allure des courbes de tolérance, c'est à dire qu'une mauvaise tolérance au glucose avec insulinémie élevée est suivie d'une amélioration de la tolérance au glucose et d'une diminution de l'insulinémie. Dans un troisième temps, statique, les taux de glucose sanguin et d'insuline circulante sont voisins de ceux des souris normales de même âge. Le poids corporel diminue lentement. Les modifications de la tolérance au glucose et l'insulinémie vont de pair avec des modifications morphologiques des cellules des îlots pancréatiques. La gluconéogénèse est accrue dans les phases dynamique et transitoire, mais diminuée dans la phase statique.
    Abstract: Zusammenfassung Ein Vergleich der altersbedingten Veränderungen der Glucosetoleranz beiobob- undNZO- Mäusen ergab folgende Unterschiede: Die Glucosetoleranz der NZO-Mäuse nimmt mit zunehmendem Alter und Körpergewicht progressiv ab. Beiobob-Mäusen lassen sich eine dynamische (I), eine intermediäre (II) und eine statische (III) Phase unterscheiden. Im Verlauf der Phase I nimmt die Glucosetoleranz ab, die Seruminsulinkonzentrationen und das Körpergewicht nehmen zu. Zu Beginn der Phase II (Körpergewicht ca. 55 g) ist die Glucosetoleranz sehr schlecht, die Seruminsulinkonzentrationen liegen sehr hoch; später verbessert sich die Glucosetoleranz etwas und die Insulinkonzentrationen sinken ab. Während der Phase III kehren Blutzucker und Seruminsulinkonzentrationen beinahe in den Bereich der bei Normaltieren des gleichen Wurfes gemessenen Werte zurück. Das Körpergewicht zeigt eine langsame Reduktion. Die Langerhans'schen Inseln zeigen während der Phasen I und II eine deutliche Hyperplasie, die sich im Verlaufe der Phase III weitgehend zurückbildet. Während der Phasen I und II sind die Aktivitäten gluconeogenetischer Enzyme deutlich erhöht.
    Notes: Summary Marked differences were shown in the development of the obese-hyperglycemic syndrome in NZO andobob mice. — In NZO mice glucose tolerance decreases continuously with increasing age and body weight. — Inobob mice three phases in the development of the obese-hyperglycemic syndrome are differentiated. In the first, dynamic phase glucose tolerance decreases and insulin secretion increases as does body weight. The intermediary or transitional phase, when the animals weigh about 55 g, is characterised by rapidly changing glucose patterns, i. e. an extremely poor glucose tolerance and extremely high serum insulin level is followed by improving glucose tolerance and decreasing insulin levels. In the third, static phase blood sugar values and serum insulin levels have nearly returned to those of the lean littermates. Body weight slowly decreases. The changes in glucose tolerance and serum insulin are parallelled by changes in islet cell morphology. The gluconeogenic capacity is increased during the dynamic and transitional phases, it declines during the static phase.
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  • 6
    ISSN: 1432-0428
    Keywords: Spontaneous diabetes ; mutationobob ; NZO mice ; diabetes in mice ; obesity in mice ; hereditary obesity ; adipose tissue ; lipolysis ; lipogenesis ; size of fat cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Résumé Chez la souris NZO, il existe une étroite corrélation entre la dimension de la cellule adipeuse et l'augmentation du poids corporel. Chez ces animaux, la libération des AGL et du glycérol à partir du tissu adipeux augmente en fonction du poids et de la dimension des cellules adipeuses, que ce soit dans les conditions de base ou après stimulation par la noradrénaline, l'ACTH, le DB-AMP cyclique et la théophylline. La réponse aux agents lipolytiques est la même chez la souris NZO normopondérale et les souris normales provenant de la même nichée que les sourisobob. Chez ces dernières, la dimension de la cellule adipeuse et le poids corporel sont en corrélation jusqu'à un poids corporel d'environ 60 g. Chez des sourisobob plus âgées, une diminution de la dimension de la cellule est observée lorsque le poids augmente. Aucune corrélation ne peut être établie entre la stimulation de la lipolyse et la dimension de la cellule adipeuse. Il existe une corrélation inverse entre l'insulinémie et la stimulation de lipolyse dans le tissu adipeux. — Il est conclu de ces expériences que les souris NZO pourraient être atteintes d'un type d'obésité hypértrophiqué et les souris obob d'un type d'obésité hyperplasique, dont la distinction semble pouvoir se faire par l'examen morphologique de la cellule adipeuse et par la sensibilité du tissu adipeux aux agents lipolytiques.
    Abstract: Zusammenfassung BeiNZO-Mäusen besteht eine enge Korrelation zwischen Zunahme des Körpergewichtes und Vergrößerung der Einzelfettzelle. Unter Basalbedingungen sowie nach Stimulierung mit Noradrenalin, ACTH, DB-cyclo AMP und Theophyllin nimmt die Freisetzung von Glycerin und freien Fettsäuren aus dem Fettgewebe beiNZO-Mäusen mit steigendem Körpergewicht und Vergrößerung der Fettzelle zu. — Junge, nicht fettsüchtigeNZO-Mäuse und nicht fettsüchtige Wurfgeschwister hyperglykämischerobob-Mäuse reagieren in ähnlicher Weise auf lipolytische Stimuli. — Beiobob-Mäusen besteht zwischen der Fettzellgröße und dem Körpergewicht eine Korrelation, bis die Tiere ein Gewicht von ungefähr 60 g erreicht haben. Bei älterenobob-Mäusen tritt trotz einer weiteren Zunahme des Körpergewichtes eine Abnahme der Fettzellgröße auf. Es besteht keine Korrelation zwischen stimulierter Lipolyse und Fettzellgröße. Die Höhe des Seruminsulinspiegels und die stimulierte Lipolyse des Fettgewebes verhalten sich bei diesen Tieren umgekehrt proportional. — Es wird geschlossen, daßNZO-Mäuse den Typ einer hypertrophischen Fettsucht undobob-Mäuse den Typ einer hyperplastischen Fettsucht verkörpern, die sich hinsichtlich der Fettzellmorphologie und der Empfindlichkeit des Fettgewebes auf lipolytische Agenzien voneinander unterscheiden.
    Notes: Summary In NZO mice fat cell size is strongly correlated to increasing body weight; FFA and glycerol release from adipose tissue under basal conditions and after stimulation with norepinephrine, ACTH, DB-cyclic AMP and theophylline increase with body weight and fat cell size. Normal weight NZO mice and lean littermates ofobob mice respond similarly to lipolytic agents. — Inobob mice cell size and body weight are correlated until a body weight of about 60 g is reached. Olderobob mice show a decrease in cell size with increasing body weight. There is no correlation between stimulated lipolysis and fat cell size. In these animals an inverse relationship between serum insulin and stimulated lipolysis in adipose tissue was observed. — It is concluded that NZO mice exhibit a type of hypertrophic obesity andobob mice a type of hyperplastic obesity, which may be differentiated by fat cell morphology and the sensitivity of adipose tissue to lipolytic agents.
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