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81.
Kerstin Kempf Martin Rhling Winfried Banzer Klaus Michael Braumann Martin Halle David McCarthy Hans Georg Predel Isabelle Schenkenberger Susanne Tan Hermann Toplak Aloys Berg Stephan Martin 《Nutrients》2021,13(5)
Lifestyle interventions, including meal replacement, are effective in the prevention and treatment of type-2-diabetes and obesity. Since insulin is the key weight regulator, we hypothesised that the addition of meal replacement to a lifestyle intervention reduces insulin levels more effectively than lifestyle intervention alone. In the international multicentre randomised controlled ACOORH (Almased Concept against Overweight and Obesity and Related Health Risk) trial, overweight or obese persons who meet the criteria for metabolic syndrome (n = 463) were randomised into two groups. Both groups received nutritional advice focusing on carbohydrate restriction and the use of telemonitoring devices. The intervention group substituted all three main meals per day in week 1, two meals per day in weeks 2–4, and one meal per day in weeks 5–26 with a protein-rich, low-glycaemic meal replacement. Data were collected at baseline and after 1, 3, 6 and 12 months. All datasets providing insulin data (n = 446) were included in this predefined subanalysis. Significantly higher reductions in insulin (−3.3 ± 8.7 µU/mL vs. −1.6 ± 9.8 µU/mL), weight (−6.1 ± 5.2 kg vs. −3.2 ± 4.6 kg), and inflammation markers were observed in the intervention group. Insulin reduction correlated with weight reduction and the highest amount of weight loss (−7.6 ± 4.9 kg) was observed in those participants with an insulin decrease > 2 µU/mL. These results underline the potential for meal replacement-based lifestyle interventions in diabetes prevention, and measurement of insulin levels may serve as an indicator for adherence to carbohydrate restriction. 相似文献
82.
83.
Carolin Lepa Sascha Hoppe Antje Stber Boris V. Skryabin Laura Katharina Sievers Barbara Heitplatz Giuliano Ciarimboli Ute Neugebauer Maja T. Lindenmeyer Clemens D. Cohen Hannes C.A. Drexler Peter Boor Thomas Weide Hermann Pavenstdt Britta George 《Journal of the American Society of Nephrology : JASN》2021,32(2):357
BackgroundInjury to kidney podocytes often results in chronic glomerular disease and consecutive nephron malfunction. For most glomerular diseases, targeted therapies are lacking. Thus, it is important to identify novel signaling pathways contributing to glomerular disease. Neurotrophic tyrosine kinase receptor 3 (TrkC) is expressed in podocytes and the protein transmits signals to the podocyte actin cytoskeleton.MethodsNephron-specific TrkC knockout (TrkC-KO) and nephron-specific TrkC-overexpressing (TrkC-OE) mice were generated to dissect the role of TrkC in nephron development and maintenance.ResultsBoth TrkC-KO and TrkC-OE mice exhibited enlarged glomeruli, mesangial proliferation, basement membrane thickening, albuminuria, podocyte loss, and aspects of FSGS during aging. Igf1 receptor (Igf1R)–associated gene expression was dysregulated in TrkC-KO mouse glomeruli. Phosphoproteins associated with insulin, erb-b2 receptor tyrosine kinase (Erbb), and Toll-like receptor signaling were enriched in lysates of podocytes treated with the TrkC ligand neurotrophin-3 (Nt-3). Activation of TrkC by Nt-3 resulted in phosphorylation of the Igf1R on activating tyrosine residues in podocytes. Igf1R phosphorylation was increased in TrkC-OE mouse kidneys while it was decreased in TrkC-KO kidneys. Furthermore, TrkC expression was elevated in glomerular tissue of patients with diabetic kidney disease compared with control glomerular tissue.ConclusionsOur results show that TrkC is essential for maintaining glomerular integrity. Furthermore, TrkC modulates Igf-related signaling in podocytes. 相似文献
84.
The Role of Growth Factors in the Control of Neurogenesis 总被引:2,自引:0,他引:2
Rohrer H 《The European journal of neuroscience》1990,2(12):1005-1015
85.
Susanne Danhauser-Riedl Edith Hausmann Hans-D. Schick Rita Bender Hermann Dietzfelbinger Johann Rastetter Axel-R. Hanauske 《Investigational new drugs》1993,11(2-3):187-195
Coupling of anthracyclines to high-molecular-weight carriers may alter drug disposition and improve antitumor effects. We have performed a clinical phase I trial of doxorubicin coupled to dextran (70000 m.w.). The drug was administered as single dose i.v. every 21–28 days. Thirteen patients have received a total of 24 courses (median 2; range 1–3). At the starting dose of 40 mg/m2 doxorubicin equivalent (DOXeq), WHO grade IV thrombocytopenia was noted in 2/2 patients. WHO grade IV hepatotoxicity and WHO grade III cardiotoxicity were noted in a patient with preexisting heart disease. Five patients were treated with 12.5 mg/m2 DOXeq. Maximal toxicity at this dose level was WHO grade III thrombocytopenia and local phlebitis (WHO grade II) in 1/5 patients, elevation of alkaline phosphatase (WHO grade III) and WHO grade III vomiting in another patient. Subsequently, five patients received 20 mg/m2 DOXeq. Hepatotoxicity was noted in 5/5 patients (1 × WHO grade IV, 1 × WHO grade III). Thrombocytopenia was noted in 3/5 patients (1 × WHO grade IV, 2 × WHO grade III). At 12.5 mg/m2 DOXeq, a patient diagnosed with a malignant fibrous histiocytoma had stable disease for 4 months. Pharmacokinetic analyses of total and free doxorubicin were performed in plasma and urine. The maximum peak plasma concentration (ppc) for total DOX was 12.3 g/ml at 40 mg/m2 DOXeq. The area under the plasma concentration time curve (AUC) ranged from 28.83–80.21 g/ml*h with dose-dependent elimination half lives (t1/2: 0.02–0.87 h;1/2: 2.69–11.58 h;1/2: 41.44–136.58 h). We conclude that the maximal tolerated dose (MTD) of AD-70 using this schedule is 40 mg/m2 DOXeq. The recommended dose for clinical phase II studies is 12.5 mg/m2 DOXeq.Abbreviations ALT
Alanine Aminotransferase
- AST
Aspartate Aminotransferase
- DOX
Doxorubicin
- DOXeq
Doxorubicin Equivalent
- ECG
Electrocardiogram
- HPLC
High Pressure Liquid Chromatography
- LD10
Lethal Dose for 10% of individuals
- MTD
Maximal Tolerated Dose
- ppc
Peak Plasma Concentration
- WHO
World Health Organisation 相似文献
86.
D. Steiner B. Hermann 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》1990,375(1):19-23
Zusammenfassung Die polarisationsoptische and histologische Untersuchung des oberen Bicepssehnenabschnittes an 26 Schultern bestätigt, daß die Sehne ihren Ursprung nicht nur, wie allgemein angenommen, am Tuberculum supraglenoidale hat, sondern außerdem -förmig im Labrum glenoidale. Dieser Befund kann phylogenetisch erklärt werden. Im weiteren Verlauf der Sehne können neue Befunde im Bereich des Sulcus bicipitalis erhoben werden. Hier ist regelmäßig ein Mesotenonium nachweisbar, das durch einen bindegewebigen Ausläufer an Sulcusdach oder -grund befestigt ist. Darüberhinaus wird gezeigt, daß das Sulcusdach nicht als Ligament (Ligamentum transversum humeri) anzusprechen ist, es handelt sich vielmehr um Ausläufer der Kollagenfasern von Subscapularis- bzw. Kapselansatz am Tuberculum minus.
Topography of the upper biceps tendon
Summary 26 shoulders are studied by polariscopic and histologic examination. It can be confirmed that the origin of the long biceps tendon is not only at the supraglenoid tubercle, but also -shaped in the glenoid labrum. This finding can be explained by phylogenetic means. Further details are found during the course of the tendon through the bicipital groove. A mesotenonium is seen regularly. This is fixed either to the roof or the ground of the sulcus by a band of connective tissue. It is shown also, that the roof of the groove is not a ligament (ligamentum transversum. humeri) but consists of collagen fibers continuing from the subscapularis and capsular attachment at the lesser tubercle.相似文献
87.
Walther Seiler Hermann Wetzel Andreas Hillert Günter Schöllnhammer Michael Langer Uwe Barlage Christoph Hiemke 《Psychopharmacology》1994,116(4):457-463
Pharmacokinetics and bioavailability of benperidol were determined in 13 schizophrenic patients after acute administration of 6 mg benperidol as an intravenous (i.v.) bolus injection, orally as liquid, and orally as tablets using a partially randomized cross-over design. Drug plasma levels were determined by high performance liquid chromatography with electrochemical detection and subjected to model independent pharmacokinetic analyses. After i.v. dosing the geometric means (mean-g) were 3.2 min for the distribution half-life, 5.80 h for the elimination half-life (t
1/2), 4.21 l/kg for the distribution volume, 7.50 h for the mean residence time (MRT), and 0.50 l/(h*kg) for the clearance. After oral administration as liquid and as tablet mean-g data for the time lag until the first appearance of measurable plasma concentrations were 0.33 and 1.1 h, mean-g
t
1/2 values were 5.5 and 4.7 h, respectively, mean-g t
max data were 1.0 h and 2.7 h, mean-g MRT values were 8.44 and 8.84 h, and mean-g C
max
maxvalues were 10.2 and 7.3 ng/ml. Differences between liquid and tablet administration were statistically significant for time lag,t
max, andC
max. Mean-g absolute bioavailabilities were computed as 48.6% after liquid and 40.2% after tablet administration respectively. All parameters studied exhibited large intersubject variation. The plasma concentrations of the presumed metabolite reduced benperidol were found to be very low. 相似文献
88.
89.
The effects of the phenylalkylamines verapamil, gallopamil, and devapamil on L-type calcium currents (ICa) were studied in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. In particular, the question was addressed, whether the pharmacological binding sites for these drugs were located at the inner and/or at the outer surface of the cell membrane. Therefore, tertiary verapamil, gallopamil, and devapamil and their corresponding quaternary derivatives were applied either from the outside or the inside of the cell membrane. Extracellular application of verapamil, gallopamil and devapamil (each at 3 M) reduced Ica to 16.1 ±8.6%, 11 ± 8.9 %, and 9.3 ± 6 % of control, respectively. Intracellular application of the same substances, via the patch pipette filled with 30 M of either verapamil, gallopamil, or devapamil, failed to depress ICa. The quaternary derivatives of the phenylalkylamines (30 M) were ineffective both when applied extracellularly or intracellularly. It is suggested that phenylalkylamines block ICa in ventricular myocytes by acting on a binding site of the calcium channel molecule located at the outer surface of the cell membrane. 相似文献
90.
Comparison of transarterial and multiple nerve stimulation techniques for axillary block using a high dose of mepivacaine with adrenaline 总被引:2,自引:0,他引:2
Koscielniak-Nielsen ZJ Nielsen PR Nielsen SL Gardi T Hermann C 《Acta anaesthesiologica Scandinavica》1999,43(4):398-404
BACKGROUND: High-dose transarterial (TA) technique results in high effectiveness of the axillary block. The technique is fast and simple, but does not produce a satisfactory success rate when using the manufacturer's recommended dose of mepivacaine. The multiple nerve stimulation (MNS) technique requires more time and experience. This double-blind study compared effectiveness, safety and the time used to obtain an effective analgesia in 101 patients, having an axillary block by either TA or MNS techniques. METHODS: Mepivacaine with adrenaline (MEPA), 850 mg, was used for the initial block. Five millilitres of 1% solution was injected subcutaneously. In the TA group, 20 mL of 2% solution was injected deep to, and 20 mL superficial to the axillary artery. In the MNS group, four terminal motor nerves were electrolocated in the axilla, and injected with 10 mL each. Analgesia was assessed every 10 min and, when needed, supplemented after 30 min. The block was effective when analgesia was present in all sensory nerve areas distal to the elbow. RESULTS: The MNS group required median 11 min for block performance compared with 8 min for the TA group (P < 0.001). Latency of the initial block was shorter and the frequency of supplemental analgesia lower in the MNS group (median 10 min and 6%) than in the TA group (30 min and 36%, respectively), P < 0.001. All incomplete blocks were successfully supplemented. However, the total time to obtain an effective block was shorter in the MNS group (23 min) than in the TA group (37 min), P < 0.001. Two patients in each group had signs and symptoms of systemic toxicity, the most serious being atrial fibrillation and temporary loss of consciousness in a cardiovascularly medicated patient. The local adverse effects (intravascular injections and haematomas) were fewer in the MNS group, P < 0.001. CONCLUSION: The MNS technique of axillary block by four injections of 10 mL of 2% MEPA produces faster and more extensive block than the TA technique by two injections of 20 mL. Therefore, the MNS technique requires fewer supplementary blocks and results in faster patient readiness for surgery. However, high doses of MEPA may result in dangerous systemic toxic reactions. 相似文献