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Biomedical subjects

K Ziegler

Publications and source records attributed to K Ziegler.

At least 19 recordsLinked to original sources
PubMed2006

Reduced cellular toxicity of a new silver-containing antimicrobial dressing and clinical performance in non-healing wounds.

Bacterial colonisation of wounds may delay wound healing. Modern silver-containing dressings are antimicrobial, yet cellular toxicity is a serious side-effect. We provide data for a newly formulated silver-containing ointment dressing, Atrauman Ag, for antimicrobial activity and cytotoxicity. Atrauman Ag effectively killed a panel of commensal skin as well as pathogenic bacterial strains while cytotoxicity for HaCaT keratinocytes was only around 10%. With these favourable in vitro tests, Atrauman Ag was analysed in 86 patients with traumatic and non-healing wounds of different aetiologies. The wound state was evaluated for 3 subsequent dressing changes. The slough score was reduced from 59.2 to 35.8%, granulation tissue increased from 27 to 40% and epithelialisation went up from 12.1 to 24%. We conclude that Atrauman Ag has a superior profile of antimicrobial activity over cellular toxicity and the low silver ion release rate may prevent interference with wound-healing mechanisms.

Aged↗
PubMed2003

Impact of reflux disease on general and disease-related quality of life - evidence from a recent comparative methodological study in Germany.

BACKGROUND: The clinical and socioeconomic burden of gastro-esophageal reflux disease (GERD) is considerable. The primary symptom of GERD is heartburn, but it may also be associated with extraesophageal manifestations, such as asthma, chest pain and otolaryngologic disorders. AIM: To describe the impact of heartburn on patients' Health-Related Quality of Life (HRQL) in Germany, using validated generic and disease-specific instruments to measure patient-reported outcomes. METHOD: Patients with symptoms of heartburn completed the German versions of the Gastrointestinal Symptom Rating Scale (GSRS), the Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD), the Short Form-36 (SF-36) and the Hospital Anxiety and Depression (HAD) scale. Frequency and severity of heartburn during the previous 7 days were also recorded. RESULTS: 142 consecutive patients completed the assessments (mean age of 47.5 years, SD = 14.6; 55.6 % female). 70 % of patients had moderate symptoms. Over half (68 %) had symptoms on more than 4 days in the previous week. Patients were most bothered by symptoms of reflux with a mean GSRS score, (ranges from 1 [not bothered] to 7 [very bothered]), of 3.9, indigestion of 3.3 and abdominal pain of 3.0, respectively. As a result of their symptoms, patients experienced problems with food and drink. The mean QOLRAD score (ranges from 1 to 7; the lower the value the more severe the impact on quality of life) of daily functioning was 4.4, impaired vitality 4.6, emotional distress 5.0 and sleep disturbance 5.1, respectively. This led to impaired overall HRQL across all domains (mean SF-36 score of this heartburn population compared to a general population in Germany). Using HAD, 25 % of patients were anxious and 8 % were depressed. CONCLUSION: There is consistent evidence that heartburn substantially impairs all aspects of health-related quality of life.

Adult↗
PubMed2001

A mutant of the cyanobacterium Anabaena variabilis ATCC 29413 lacking cyanophycin synthetase: growth properties and ultrastructural aspects.

The gene cphA encoding cyanophycin synthetase was interrupted in Anabaena variabilis ATCC 29413 by insertional mutagenesis. The mutant lacked cyanophycin granules and the polar nodules of heterocysts. The mutant grew as fast as the wild-type irrespective of the nitrogen source at low light intensity whereas growth on N(2) was somewhat reduced in high light. It is concluded that cyanophycin metabolism and polar nodules are not essential for aerobic N(2) fixation.

Aerobiosis↗
PubMed2000

Details of disorder matter in 2D d-wave superconductors

Within numerically exact solutions of the Bogoliubov-de Gennes equations, we demonstrate that discrepancies between predicted low-energy quasiparticle properties in disordered 2D d-wave superconductors occur because of the unanticipated importance of disorder model details and normal state particle-hole symmetry. For the realistic case, which is best described by a binary alloy model without particle-hole symmetry, we predict density-of-state suppression below an energy scale which appears to be correlated with the corresponding single impurity resonance.

Journal Article↗
PubMed2000

Ochratoxin A from a toxicological perspective.

Ochratoxin A (OTA) is a widespread mycotoxin which is produced mainly by the mould fungi Aspergillus ochraceus and Penicillum verrucosum during the storage of cereals, cereal products and other plant-derived products such as herbs, spices, grapes, etc. By carry over from mouldy fodder, ochratoxin A is also found in pork meat, offal and sausages containing pork blood. When ingested as a food contaminant, OTA is very persistent in human beings with a blood half-life of 35 days after a single oral dosage due to unfavourable elimination toxicokinetics. This renders the toxin among the most frequent mycotoxin contaminants in human blood in the EU, the US, Canada, and elsewhere, where it has been investigated. OTA is neither stored nor deposited in the body, but heterogeneous body distribution may impose serious damage to the kidneys. The toxin was classified a 2B cancer compound, being possibly carcinogenic for humans. It was among the strongest carcinogenic compounds in rats and mice. As the toxicological profile also includes teratogenesis, nephrotoxicity, and immunotoxicity, legislation authorities are currently discussing maximal residue levels (MRL) for OTA in various foodstuffs. In the present article arguments are presented which suggest an acceptable daily intake (ADI) of 1.5 ng OTA/kg body weight and a much lower MRL than 5 microgram OTA/kg cereals and cereal products as has been postulated by the EU commission.

Animals↗
PubMed2000

Biosynthesis of the cyanobacterial reserve polymer multi-L-arginyl-poly-L-aspartic acid (cyanophycin): mechanism of the cyanophycin synthetase reaction studied with synthetic primers.

Biosynthesis of the cyanobacterial nitrogen reserve cyanophycin (multi-L-arginyl-poly-L-aspartic acid) is catalysed by cyanophycin synthetase, an enzyme that consists of a single kind of polypeptide. Efficient synthesis of the polymer requires ATP, the constituent amino acids aspartic acid and arginine, and a primer like cyanophycin. Using synthetic peptide primers, the course of the biosynthetic reaction was studied. The following results were obtained: (a) sequence analysis suggests that cyanophycin synthetase has two ATP-binding sites and hence probably two active sites; (b) the enzyme catalyses the formation of cyanophycin-like polymers of 25-30 kDa apparent molecular mass in vitro; (c) primers are elongated at their C-terminus; (d) the constituent amino acids are incorporated stepwise, in the order aspartic acid followed by arginine, into the growing polymer. A mechanism for the cyanophycin synthetase reaction is proposed; (e) the specificity of the enzyme for its amino-acid substrates was also studied. Glutamic acid cannot replace aspartic acid as the acidic amino acid, whereas lysine can replace arginine but is incorporated into cyanophycin at a much lower rate.

Adenosine Triphosphate↗
PubMed1999

Cyanophycinase, a peptidase degrading the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartic acid (cyanophycin): molecular cloning of the gene of Synechocystis sp. PCC 6803, expression in Escherichia coli, and biochemical characterization of the purified enzyme.

The branched polypeptide multi-L-arginyl-poly-L-aspartic acid, also called cyanophycin, is a water-insoluble reserve material of cyanobacteria. The polymer is degraded by a specific hydrolytic enzyme called cyanophycinase. By heterologous expression in Escherichia coli, a gene encoding cyanophycinase has been identified in the sequenced genome of Synechocystis sp. PCC 6803. The gene, designated cphB, codes for a protein of 29.4 kDa. The high level of expression of active cyanophycinase in E. coli from the Synechocystis gene allowed for its purification to electrophoretic homogeneity. The enzyme, which appears to be specific for cyanophycin, hydrolysed the polymer to a dipeptide consisting of aspartic acid and arginine. Based on inhibitor sensitivity and primary sequence, cyanophycinase appears to be a serine-type exopeptidase related to dipeptidase E [Conlin, C.A., Haakensson, K., Liljas, A. & Miller, C.G. (1994) J. Bacteriol. 176, 166-172].

Amino Acid Sequence↗
PubMed1999

Relative effectiveness and cost-effectiveness of methods of androgen suppression in the treatment of advanced prostate cancer.

OBJECTIVES: With 184,500 new cases and 39,200 deaths anticipated in 1998, prostate cancer is second only to lung cancer in cancer mortality for men. This report is a systematic review of the evidence from randomized controlled trials on the relative effectiveness of alternative strategies for androgen suppression as treatment of advanced prostate cancer. Three key issues are addressed: (1) the relative effectiveness of the available methods for monotherapy (orchiectomy, luteinizing hormone-releasing hormone [LHRH] agonists, and antiandrogens), (2) the effectiveness of combined androgen blockade compared to monotherapy, and (3) the effectiveness of immediate androgen suppression compared to androgen suppression deferred until clinical progression. Outcomes of interest are overall, cancer-specific, and progression-free survival; time to treatment failure; adverse effects; and quality of life. Two supplementary analyses were conducted for each key question: (1) meta-analysis of overall survival at 2 years (questions 1 and 2) and 5 years (questions 2 and 3), and (2) cost-effectiveness analysis. SEARCH STRATEGY: The MEDLINE, CANCERLIT, and EMBASE databases were searched from 1966 to March 1998, and Current Contents to August 24, 1998, for the terms: leuprolide (Lupron); goserelin (Zoladex); buserelin (Suprefact); flutamide (Eulexin); nilutamide (Anandron, Nilandron); bicalutamide (Casodex); cyproterone acetate (Androcur); diethylstilbestrol (DES); and orchiectomy (castration, orchidectomy). The search was then limited to human studies indexed under the MeSH term "prostatic neoplasms" and by the UK Cochrane Center search strategy for randomized controlled trials. Total yield was 1,477 references. SELECTION CRITERIA: We Reports of efficacy outcomes were limited to randomized controlled trials. Phase II studies that reported on withdrawals from therapy and all studies reporting on quality of life were also included. DATA COLLECTION AND ANALYSIS: The systematic review used a prospectively designed protocol conducted by two independent reviewers, with disagreements resolved by consensus. The meta-analysis combined data on overall survival using a random effects model. The cost-effectiveness analysis used a decision analysis model of advanced prostate cancer with health states and transitions derived from the literature and estimates of effectiveness derived from the meta-analysis. The cost-effectiveness analysis is conducted from a societal perspective, consistent with the guidelines of the U.S. Public Health Service Panel on Cost-Effectiveness in Health and Medicine. MAIN RESULTS: Survival after treatment with an LHRH agonist is equivalent to survival after orchiectomy. The available LHRH agonists are equally effective, and no LHRH agonist is superior to the other when adverse effects are considered. Survival may be somewhat lower with use of a nonsteroidal antiandrogen. There is no statistically significant difference in survival at 2 years between patients treated with combined androgen blockade or monotherapy. Meta-analysis of the limited data available shows a statistically significant difference in survival at 5 years that favors combined androgen blockade. However, the magnitude of this difference is of questionable clinical significance. For the subgroup of patients with good prognosis, there is no statistically significant difference in survival. Adverse effects leading to withdrawal from therapy occurred more often with combined androgen blockade. No evidence is yet available from randomized controlled trials of androgen suppression initiated at prostate-specific antigen (PSA) rise after definitive therapy for clinically localized disease. For patients who are newly diagnosed with locally advanced or asymptomatic metastatic disease, the evidence is insufficient to determine whether primary androgen suppression initiated at diagnosis improves outcomes. (ABSTRACT TRUNCATED)

Androgen Antagonists↗
PubMed1998

Molecular characterization of cyanophycin synthetase, the enzyme catalyzing the biosynthesis of the cyanobacterial reserve material multi-L-arginyl-poly-L-aspartate (cyanophycin).

Cyanophycin (multi-L-arginyl-poly-L-aspartate), a water-insoluble reserve polymer of cyanobacteria, is a product of nonribosomal peptide synthesis. The purification of cyanophycin synthetase of the cyanobacterium Anabaena variabilis is described. In sodium dodecylsulfate/polyacrylamide gel electrophoresis, the enzyme preparation shows one band with an apparent molecular mass of 100 kDa. The native enzyme has an apparent molecular mass of approximately 230 kDa, as determined by size-exclusion chromatography, suggesting that the active form is a homodimer. During catalysis, ATP is converted to ADP. The gene coding for cyanophycin synthetase has been identified in the sequenced genome of Synechocystis sp. PCC 6803. The C-terminal 60% of the deduced amino acid sequence of cyanophycin synthetase show sequence similarity to enzymes of the superfamily of ligases involved in the biosynthesis of murein and of folyl-poly(gamma-glutamate). Cells of Escherichia coli harbouring the gene on a plasmid express active synthetase and accumulate cyanophycin-like material. The results prove that a single enzyme catalyzes the de novo synthesis of cyanophycin.

Adenosine Triphosphate↗
PubMed1998

[Stages in coping after stroke].

People who suffer a stroke most often experience a major crisis in their lives. This leads to psychological problems which are likely to influence the patient's life satisfaction, long-term rehabilitation outcome, and quality of life as much as the physical consequences caused by the stroke, The patient's ability to accept the new reality created by a disability as a part of their future life is therefore essential. This necessitates an individual coping strategy in the center of which is a mourning process, which unfolds in the same way as other experiences of vital threat, e.g. confrontation with one's own dying. Different stages of mourning that can also be found in stroke patients are nonacceptance of the facts, erupting emotions, parting with the former and finding of a new self as well as new perspectives for one's future. Whether a coping process is successful does not depend on the type of the defense mechanisms or stages, but essentially on their persistence. It is the task of the therapeutical team to support this process by applying a basic therapeutic behavior, stage-consistent interventions and a positive feedback. A failed process of coping may be one of the causes of the high prevalence of psychological disorders like depression and anxiety disorders in patients having suffered a stroke.

Adaptation, Psychological↗
PubMed1997

Binding proteins for cyclic and linear oligopeptides in plasma membranes and the cytosol of rat hepatocytes.

Using a cyclolinopeptide A analogue, the hydrophobic cyclic peptide c(-Ala-Lys-Pro-Phe-Phe-Ala-Lys-Pro-Phe-Phe-), termed CDP (cyclodecapeptide), as ligand in affinity chromatography, hepatocellular peptide binding proteins were isolated from the integral part of plasma membranes and the cytosol. The sequence of the isolated protein with MW of 50 kDa from the integral part of the plasma membrane fraction was identical to cytochrome P450 II C13 and cytochrome P450 II C22, whereas the sequence of the 54 kDa protein was identical to 3-hydroxyandrogen-UDP-glucuronosyltransferase. These proteins have also been described as binding proteins for bile acids. As shown in earlier studies, bile acids and CDP also compete for uptake into hepatocytes. In the cytosol, a further known bile acid binding protein, the glutathione-S-transferase (G-S-T) subunit Yb1, was isolated and sequenced as binding protein for CDP and also for a further cyclopeptide, the somatostatin analogue OO8, and a linear peptide with renin-inhibiting activity, EMD 55068. As shown in uptake studies using isolated basolateral plasma membrane vesicles, G-S-T was able to increase the uptake of EMD 51921, a linear peptide with renin-inhibiting potency, into the vesicles when the latter were preloaded with G-S-T. The binding of the substrate to the outside of the preloaded vesicles was not different than binding to unloaded vesicles. The maximal transport rate of the carrier-mediated/facilitated diffusion and the rate of permeation, however, were doubled in the presence of G-S-T, pointing to the involvement of intracellular binding proteins such as G-S-T in the unloading of the carrier protein and in the reduction of the free substrate concentration.

Animals↗
PubMed1996

Solution and solid state structure of an aib-containing cyclodecapeptide inhibiting the cholate uptake in hepatocytes.

The conformational analysis of synthetic cyclodecapeptide c(Pro-Phe-phe-Aib-Leu)2 related to the cyclolinopeptide A, in the solid state and solution, has been carried out by x-ray diffraction and nmr spectroscopy. The structure of the monoclinic form obtained from methanol [a = 11.351 (5) A, b = 27.455 (2) A, c = 12.716 (8) A, beta = 99.65 (3) degrees; space group P2(1); Z = 2] shows the presence of six intramolecular NH...CO hydrogen bonds, with formation of four turns (three of type I and one of type III) and two C16 ring structures. All peptide units are trans. The solution structure, as found by nmr, indicates that, at room temperature, the peptide is conformationally homogeneous; the structure determined is perfectly symmetrical and topologically similar to that found in the solid state. The cyclodecapeptide exhibits similar biological activity to cyclolinopeptide A.

Animals↗
PubMed1996

Hepatobiliary elimination of certain peptide-mimicking drugs: linear hydrophobic and hydrophilic renin-inhibitors and hydrophobic cyclopeptides.

Kinetic investigations on the hepatocellular uptake of certain peptide-mimicking drugs revealed that in most cases carrier-mediated mechanisms are responsible for their rapid extraction from portal blood. The driving forces for uptake, however, are unknown. Uptake is not dependent on the presence of sodium ions. The membrane potential or other energy sources may drive their uphill transport. Efforts to isolate the transport proteins involved in hepatocellular uptake using the Xenopus laevis oocyte system failed due to high unspecific binding of the peptides. Intracellular cytosolic and membrane-associated binding proteins, however, were isolated and sequenced. Uptake of certain of the drugs investigated is related to the uptake of bile acids. The recently cloned bile acid transporters ntcp and oatp are not the related transport systems. The carrier protein for these peptide-mimicking drugs has yet to be cloned. At the canalicular pole of the cell, excretion of two linear renin-inhibitors EMD 51,921 and CGP 38,560 is due to ATP-dependent transport mechanisms. MDR gene products seem to be involved in the elimination of the renin-inhibitor CGP 38,560, whereas the endogenous ATP-dependent transport system for the renin-inhibitor EMD 51,921 has not been identified.

Animals↗