Institute For Klinische Pharmakologie

Hannover, Germany

Institute For Klinische Pharmakologie

Hannover, Germany

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PubMed | Institute For Klinische Pharmakologie, Humanitas Clinical and Research Center, IRCCS Policlinico San Donato and University of Milan
Type: Journal Article | Journal: Philosophical transactions. Series A, Mathematical, physical, and engineering sciences | Year: 2014

We propose a symbolic analysis framework for the quantitative characterization of complex dynamical systems. It allows the description of the time course of a single variable, the assessment of joint interactions and an analysis triggered by a conditioning input. The framework was applied to spontaneous variability of heart period (HP), systolic arterial pressure (SAP) and integrated muscle sympathetic nerve activity (MSNA) with the aim of characterizing cardiovascular control and nonlinear influences of respiration at rest in supine position, during orthostatic challenge induced by 80 head-up tilt (TILT) and about 3 min before evoked pre-syncope signs (PRESY). The approach detected (i) the exaggerated sympathetic modulation and vagal withdrawal from HP variability and the increased presence of fast MSNA variability components during PRESY compared with TILT; (ii) the increase of the SAP-HP coordination occurring at slow temporal scales and a decrease of that occurring at faster time scales during PRESY compared with TILT; (iii) the reduction of the coordination between fast MSNA and SAP patterns during TILT and PRESY; (iv) the nonlinear influences of respiration leading to an increased likelihood to observe the abovementioned findings during expiration compared with inspiration one. The framework provided simple, quantitative indexes able to distinguish experimental conditions characterized by different states of the autonomic nervous system and to detect the early signs of a life threatening situation such as postural syncope.


Rogosch T.,University of Marburg | Sinning C.,Martin Luther University of Halle Wittenberg | Podlewski A.,University of Marburg | Watzer B.,University of Marburg | And 8 more authors.
Bioorganic and Medicinal Chemistry | Year: 2012

Dipyrone is a common antipyretic drug and the most popular non-opioid analgesic in many countries. In spite of its long and widespread use, molecular details of its fate in the body are not fully known. We administered dipyrone orally to mice. Two unknown metabolites were found, viz. the arachidonoyl amides of the known major dipyrone metabolites, 4-methylaminoantipyrine (2) and 4-aminoantipyrine (3). They were identified by ESI-LC-MS/MS after extraction from the CNS, and comparison with reference substances prepared synthetically. The arachidonoyl amides were positively tested for cannabis receptor binding (CB 1 and CB 2) and cyclooxygenase inhibition (COX-1 and COX-2 in tissues and as isolated enzymes), suggesting that the endogenous cannabinoid system may play a role in the effects of dipyrone against pain. © 2011 Elsevier Ltd. All rights reserved.


Schaefer J.R.,University of Marburg | Gitt A.K.,University of Heidelberg | Weizel A.,Vorsitzender der DGFF Lipid Liga e.V. Planegg | Jannowitz C.,MSD SHARP and DOHME GmbH | And 3 more authors.
Vascular Health and Risk Management | Year: 2013

Aims: We aimed to document the drug management of patients at high cardiovascular risk in daily practice, with the special focus on lipid-lowering treatment. Methods and results: In this prospective noninterventional study in 2387 outpatient centers throughout Germany, a total of 13,942 high-risk patients (mean age 65.7 years, 61.6% males) were treated with simvastatin 40 mg/day at entry as monotherapy. All patients were followed up for 12 months in terms of drug utilization, laboratory values, target attainment, and clinical events (including death, hospitalization, vascular events, and dialysis). Patients had coronary heart disease in 35.0%, diabetes mellitus in 24.4%, and the combination of coronary heart disease plus diabetes mellitus in 25.7%. In 21% of patients, a cholesterol absorption inhibitor was added to statin therapy at the entry visit, and in 23%, this was added at the follow up visit 6 months later. The target values for low-density lipoprotein-cholesterol (,2.6 mmol/L) were reached by 31.8% of patients at entry and by 50.0% at the end of this registry after 12 months. Mean blood pressure decreased (from 135.9/80.5 mmHg at baseline) by 3.1/1.9 mmHg after 12 months. In patients with documented diabetes, the targeted glycated hemoglobin (HbA1c,6.5%) was reached by 33.5% at baseline and by 40.0% after 12 months. Clinical events occurred in 11.7% of patients between baseline and month 6, and in 12.0% between months 6 and 12. Conclusion: In patients at high risk for cardiovascular events, comprehensive management under daily practice conditions leads to improvement of lipid, glucose, and blood pressure parameters. There is a need to improve secondary prevention among high-risk patients. © 2013 Schaefer et al, publisher and licensee Dove Medical Press Ltd.


Nollmann F.I.,Goethe University Frankfurt | Dowling A.,University of Exeter | Kaiser M.,Swiss Tropical and Public Health Institute | Deckmann K.,Institute For Klinische Pharmakologie | And 3 more authors.
Beilstein Journal of Organic Chemistry | Year: 2012

The synthesis of the recently characterized depsipeptide szentiamide (1), which is produced by the entomopathogenic bacterium Xenorhabdus szentirmaii, is described. Whereas no biological activity was previously identified for 1, the material derived from the efficient synthesis enabled additional bioactivity tests leading to the identification of a notable activity against insect cells and Plasmodium falciparum, the causative agent of malaria. © 2012 Nollmann et al.


PubMed | Praxiszentrum Rheumatologie, Institute For Klinische Pharmakologie, Bundesinstitut For Arzneimittel Und Medizinprodukte Bfarm and Abt. Rheumatologie
Type: Journal Article | Journal: Zeitschrift fur Rheumatologie | Year: 2016

NSAIDs exert their anti-inflammatory and analgesic effects by inhibition of COX2, a key enzyme for proinflammatory prostanoid synthesis. Therapy with NSAIDs is limited by their typical gastrointestinal, cardiovascular and renal side effects, which are caused by inhibition of COX1 (gastrointestinal toxicity), COX2 (cardiovascular side effects) or both COX-isoenzymes (renal side effects). Appropriate prevention strategies should be employed in patients at risk. If gastrointestinal risk factors are present, co-administration of a proton pump inhibitor or misoprostol is recommended; in patients with cardiovascular risk, coxibs, diclofenac and high-dose ibuprofen should be avoided. Furthermore, drug interactions and contraindications should be considered. In patients with renal impairment (GFR <30ml/min) all NSAIDs must be avoided. Ulcer anamnesis is a contraindication for traditional NSAIDs. Preexisting cardio- or cerebrovascular diseases are contraindications for coxibs. Treatment decisions should be individually based with a continuous monitoring of the risk - benefit ratio and exploitation of non-pharmacological treatment options.


Migeotte P.-F.,Royal Military Academy | Tank J.,Institute For Klinische Pharmakologie | Pattyn N.,Royal Military Academy | Funtova I.,Russian Academy of Sciences | And 4 more authors.
Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS | Year: 2011

Balistocardiography was recorded in 3-D on a free floating astronaut in space as well as on healthy volunteers participating to a dry immersion study in a terrestrial laboratory. We demonstrate a new technique suitable for the analysis of 3-D BCG. The spatial curve of the displacement vector is analyzed instead of the three components of acceleration. The technique presented is invariant from the axis of representation and provides important novel physiological information. © 2011 IEEE.


Jordan J.,Institute For Klinische Pharmakologie | Tank J.,Institute For Klinische Pharmakologie
Nervenheilkunde | Year: 2013

Treatment resistant arterial hypertension is diagnosed when concurrent use of three properly dosed antihypertensive medications including a diuretic is not sufficient to control blood pressure. Secondary causes have to be excluded. Electrical carotid sinus stimulation has been developed for high risk patients not responding to maximal antihypertensive therapy. In the brain, electrical baroreceptor stimulation is perceived as further blood pressure increase, which leads to reflex sympathetic inhibition. Indeed, electrical carotid sinus stimulation acutely reduces muscle sympathetic nerve activity and blood pressure in patients with treatment resistant hypertension. Moreover, venous renin concentration decreases suggesting that renal sympathetic activity is also attenuated. Physiological baroreflex control is not perturbed. Results from clinical trials suggest that electrical carotid sinus stimulation elicits a sustained blood pressure reduction in a subgroup of patients. However, data from controlled clinical trials are not yet sufficient to justify widespread clinical use. © Schattauer 2013.


In the year 2015, many questions regarding the pathophysiology of essential arterial hypertension remain unresolved. Substantial scientific progress has been made in various medical areas aided by novel molecular“omics” techniques. The findings could then be implemented in diagnostic and therapeutic procedures. In the field of hypertension research such methods have been applied in very large cohorts but have contributed less to pathophysiological understanding and clinical management than expected. The findings on the pathophysiological importance of baroreflex mechanisms, natriuretic peptides and osmotically inactive sodium storage discussed in this article all have something in common: all are based on small, carefully conducted human physiological investigations and often challenge current textbook knowledge. Nevertheless, these findings have opened up new research fields and are likely to affect clinical care. © 2015, Springer-Verlag Berlin Heidelberg.


Schroder J.,Institute For Klinische Pharmakologie
Deutsche Medizinische Wochenschrift | Year: 2013

Elderly patients often suffer from sleep disturbances. Disorders are mostly caused by medical neurological or psychiatric diseases and multimorbidity. The treatment of the underlying disease should therefore be prioritised. In the symptomatic treatment of insomnia cognitive-behavioural strategies are established. Drug therapy should be considered only if non-pharmacological treatments fail. Most hypnotics have a poor risk-benefit ratio in older patients. In acute severe sleep disturbances prescription of short-acting benzodiazepines and nonbenzodiazepine hypnotics in low doses over a short period of time is acceptable. In patients suffering from chronic insomnia a treatment with sedative antidepressants can be considered keeping in mind possible adverse effects. Studies analysing the current status of care for elderly insomnia patients in Germany are limited. Analyses of health insurance data suggest that especially nursing home patients often use hypnotics. The treatment of sleep disorders in elderly patients must therefore be optimized in practice © Georg Thieme Verlag KG Stuttgart New York.


PubMed | Institute For Klinische Pharmakologie
Type: Journal Article | Journal: Der Internist | Year: 2015

In the year 2015, many questions regarding the pathophysiology of essential arterial hypertension remain unresolved. Substantial scientific progress has been made in various medical areas aided by novel molecularomics techniques. The findings could then be implemented in diagnostic and therapeutic procedures. In the field of hypertension research such methods have been applied in very large cohorts but have contributed less to pathophysiological understanding and clinical management than expected. The findings on the pathophysiological importance of baroreflex mechanisms, natriuretic peptides and osmotically inactive sodium storage discussed in this article all have something in common: all are based on small, carefully conducted human physiological investigations and often challenge current textbook knowledge. Nevertheless, these findings have opened up new research fields and are likely to affect clinical care.

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