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Biomedical subjects

J Sieber

Publications and source records attributed to J Sieber.

9 recordsLinked to original sources
PubMed2006

NON-activated protein C as post-treatment after spinal cord compression injury in rats.

BACKGROUND: Neuroprotective effects of recombinant human activated Protein C (rhAPC) in models of Spinal Cord Injury (SCI) and ischemic stroke have been reported in rodents. To rule out immunogenicity of rhAPC and to possibly maintain the physiological PC/thrombin balance the use of zymogen PC in SCI might be preferable. Although activation of Protein C (PC) has been demonstrated in rats, the efficacy and drug safety of NON activated PC has not been previously tested in experimental SCI. METHODS: Twelve rats were subjected to 40 g compression of the spinal cord at TH11 for 20 minutes and randomly allocated to either the NON activated PC (25 IU/kg) or the Placebo group (saline).Results. 25 IU treatment yielded improved recovery from SCI compared to placebo and the triple fold dose of PC (75 IU/kg) was subsequently tested to detect treatment associated complications (TAC). Treatment was administered as a single shot via the right vena jugularis forty minutes after onset of compression. The observation period was 5 weeks in 25 IU treated and 1 week in the 75 IU treated rats. Improvement of motor function recovery was measured with behaviour tests and electrophysiology. FINDINGS: Single shot treatment with 25 IU/kg of NON activated PC led to improved recovery in terms of behaviour and electrophysiology. TACs neither occurred in the 25 IU nor in the 75 IU group within one week. CONCLUSION: NON activated PC is a potent and safe drug in experimental SCI and should be considered for treatment in neurotrauma.

Animals↗
PubMed2006

Immune mechanisms of allergen-specific sublingual immunotherapy.

Sublingual immunotherapy has been shown in some clinical studies to modulate allergen-specific antibody responses [with a decrease in the immunoglobulin E/immunoglobulin G4 (IgE/IgG4) ratio] and to reduce the recruitment and activation of proinflammatory cells in target mucosa. Whereas a central paradigm for successful immunotherapy has been to reorient the pattern of allergen-specific T-cell responses in atopic patients from a T helper (Th)2 to Th1 profile, there is currently a growing interest in eliciting regulatory T cells, capable of downregulating both Th1 and Th2 responses through the production of interleukin (IL)-10 and/or transforming growth factor (TGF)-beta. We discuss herein immune mechanisms involved during allergen-specific sublingual immunotherapy (SLIT), in comparison with subcutaneous immunotherapy. During SLIT, the allergen is captured within the oral mucosa by Langerhans-like dendritic cells expressing high-affinity IgE receptors, producing IL-10 and TGF-beta, and upregulating indoleamine dioxygenase (IDO), suggesting that such cells are prone to induce tolerance. The oral mucosa contains limited number of proinflammatory cells, such as mast cells, thereby explaining the well-established safety profile of SLIT. In this context, second-generation vaccines based on recombinant allergens in a native conformation formulated with adjuvants are designed to target Langerhans-like cells in the sublingual mucosa, with the aim to induce allergen-specific regulatory T cells. Importantly, such recombinant vaccines should facilitate the identification of biological markers of SLIT efficacy in humans.

Administration, Sublingual↗
PubMed2004

Nonlinear dynamics of semiconductor lasers with active optical feedback.

An in-depth theoretical as well as experimental analysis of the nonlinear dynamics in semiconductor lasers with active optical feedback is presented. Use of a monolithically integrated multisection device of submillimeter total length provides access to the short-cavity regime. By introducing an amplifier section as a special feature, phase and strength of the feedback can be separately tuned. In this way, the number of modes involved in the laser action can be adjusted. We predict and observe specific dynamical scenarios. Bifurcations mediate various transitions in the device output, from single-mode steadystate to self-pulsation and between different kinds of self-pulsations, reaching eventually chaotic behavior in the multimode limit.

Journal Article↗
PubMed2001

Single- and multiple-dose pharmacokinetics of repaglinide in patients with type 2 diabetes and renal impairment.

OBJECTIVE: The primary objective of this single-centre, open-label, parallel-group study was to evaluate the pharmacokinetics and safety profile of the prandial glucose regulator repaglinide, following single and multiple dosing, in patients with type 2 diabetes with and without varying degrees of renal impairment. METHODS: The study comprised three screening visits, followed by a 7-day inpatient period. Thirty-four patients, with normal renal function (n = 12), mild-to-moderate renal dysfunction (n = 12) or severe renal dysfunction (n = 10), received a single 2-mg dose of repaglinide on day 1, followed by preprandial 2-mg doses with main meals (breakfast, lunch and dinner) on each of days 2-4. A final 2-mg dose of repaglinide was administered on day 5. RESULTS: Patients with mild-to-moderate renal impairment showed no significant differences in the pharmacokinetics of repaglinide, compared with patients with normal renal function. In the group of patients with severe renal dysfunction, the main pharmacokinetic finding was a longer half-life after multiple dosing. Rates of minor hypoglycaemia were similar in patients with severe, mild-to-moderate and no renal dysfunction. No major hypoglycaemic episodes occurred. CONCLUSION: Patients with type 2 diabetes and mild or moderate impairment of renal function may be treated with repaglinide without special precautions. If repaglinide is used in patients with severely impaired renal function, dose adjustment may be necessary if indicated by blood glucose measurements.

Aged↗
PubMed1992

Patellar tendon rupture. Description of a simplified operative method for a current therapeutic problem.

A simple operative method for the treatment of patellar tendon rupture is introduced. The operative procedure is described and we present the short-term results of the first seven patellar tendon ruptures that have been treated accordingly at our clinic. The technique is easily reproducible and utilizes a minimum of foreign body implant. A secondary procedure for removal of suture material is rarely necessary.

Adult↗
PubMed1991

Repair of specific base pair mismatches formed during meiotic recombination in the yeast Saccharomyces cerevisiae.

Heteroduplexes formed between DNA strands derived from different homologous chromosomes are an intermediate in meiotic crossing over in the yeast Saccharomyces cerevisiae and other eucaryotes. A heteroduplex formed between wild-type and mutant genes will contain a base pair mismatch; failure to repair this mismatch will lead to postmeiotic segregation (PMS). By analyzing the frequency of PMS for various mutant alleles in the yeast HIS4 gene, we showed that C/C mismatches were inefficiently repaired relative to all other point mismatches. These other mismatches (G/G, G/A, T/T, A/A, T/C, C/A, A/A, and T/G) were repaired with approximately the same efficiency. We found that in spores with unrepaired mismatches in heteroduplexes, the nontranscribed strand of the HIS4 gene was more frequently donated than the transcribed strand. In addition, the direction of repair for certain mismatches was nonrandom.

Alleles↗
PubMed1983

Changes in contractility and oxygen metabolism of isolated canine heart following application of urapidil.

Changes of contractility and oxygen metabolism following the administration of urapidil (Ebrantil) are described. Investigations were carried out on isolated, metabolically supported canine hearts. Results show that this drug has a myocardial effect in addition to its known antihypertensive effect. Moreover, a dose-dependent negative inotropism is coupled with a reduction in myocardial oxygen consumption. Urapidil reduces the cardiac metabolic rate, decreases cardiac load due to a reduction in peripheral resistance, and has a negative inotropic action. These properties are usually found only in beta-blockers.

Animals↗
PubMed1981

[The effect of AR-L 115 BS on contractility dynamics of the isolated, metabolically supported dog heart (author's transl)].

In this study the contractility dynamics of the left ventricle are analysed independent of respiration, pre- and afterload, heart rate and perfusion pressure. These parameters alter varyingly following the administration of 2-[(2-methoxy-4-methylsufinyl)phenyl]-1H-imidazo[4,5-b]pyridine (AR-L 115 BS) so that the study plan selected must take these factors into account. The model employed consisted of a metabolically supported isolated pulsating dog's heart. The dose of AR-L 115 Bs used was 0.125 mg/kg body weight and it was infused over a period of 30 min. Altogether the study demonstrates that AR-L 115 BS has a marked positive inotropic effect on the isolated heart even under the conditions of infusion. The coronary resistance diminishes and the cardiac output increases.

Animals↗