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Biomedical subjects

D Demuth

Publications and source records attributed to D Demuth.

16 recordsLinked to original sources
PubMed2004

[Computer-based information system (CliniTox) for the management of poisoning in small animals].

Because cases of poisoning are observed rarely, veterinary practitioners have only limited knowledge of clinical toxicology and may face considerable problems in handling toxicological emergencies. In this report, we describe a novel decision support system for the management of poisonings in companion animals that provides rapid access to the current knowledge of clinical toxicology. For that purpose, relevant reports from the peer-reviewed literature were evaluated and organised according to the requirements of a structured database. The information provided for each toxic substance includes a summary of its chemical and physical properties, sources, commercial uses or natural occurrences, toxicokinetic data, mechanisms of action, threshold doses, clinical symptoms with brief case reports, sampling and analytical results, post-mortem findings, differential diagnoses, therapeutic guidelines and references to the literature. This decision support system has been programmed with two user-friendly search functions: a search tool that allows to choose clinical symptoms, and another function that serves to find a substance using its chemical name, the class of compounds to wich it belongs, a possible source or one of its main applications. CliniTox can be accessed directly via our webserver (http://www.clinitox.ch).

Animals↗
PubMed2004

Pharmacokinetics of recombinant hirudin in healthy horses.

REASONS FOR PERFORMING STUDY: Recombinant (r)-hirudin is a specific inhibitor of thrombin that is independent of the activity of antithrombin. OBJECTIVES: To evaluate pharmacokinetic properties and coagulatory changes of r-hirudin in healthy horses. METHODS: Two clinically healthy horses received a single i.v. bolus of 0.4 mg/kg bwt r-hirudin and 6 clinically healthy horses received the same dose subcutaneously (subcut.) q. 12 h for 3 days. Coagulation times and r-hirudin plasma concentration were determined over 720 mins and 3 days after i.v. and subcut. administration, respectively. RESULTS: In all horses, treatment with r-hirudin was not associated with systemic or local side effects. After i.v. injection, the 2 horses showed an elimination half-life of 58 and 80 mins, respectively. After subcut. administration, maximum plasma concentration of r-hirudin occurred at 128 +/- 55 mins and declined with a terminal half-life of 561 +/- 364 mins. Maximum response of activated partial thromboplastin time (aPTT) occurred 1.5 h after administration of r-hirudin. A prolongation of 1.9 +/- 0.2 times the pretreatment value was noted. CONCLUSIONS: Pharmacokinetics of r-hirudin in healthy horses were similar to those in man and other animal species. POTENTIAL RELEVANCE: The results of this study indicate that r-hirudin can be used in horses, but further studies should be performed in order to prove its effectiveness in diseased horses.

Animals↗
PubMed2004

[CliniTox: the computer-based information system for poisoning in farm animals].

Poisonings can cause reduced performance and severe economic loss in farm animals. A swift and targeted action is required from veterinarians. We have established a computer-based decision support system for poisonings in ruminants and pigs. The system offers access to the most recent information available in clinical toxicology of farm animals. Towards this goal, relevant reports from the peer-reviewed literature were evaluated and organised according to the requirements of a structured database. The information provided for each toxic substance includes a summary of its chemical and physical properties, sources, commercial uses or natural occurrences, toxicokinetic data, mechanisms of action, threshold doses, clinical symptoms with brief case reports, sampling and analytical results, post-mortem abnormalities, differential diagnoses, therapeutic guidelines and references to the literature. This decision support system has been programmed with two user-friendly search functions: a search tool that allows the choice of clinical and pathological findings, and another function that serves to find a substance using its chemical name, the class of compounds to wich it belongs, a possible source or one of its main applications. CliniTox can be accessed directly via our webserver (http://www.clinitox.ch).

Animals↗
PubMed2003

Pharmacokinetics and sedative effects of intramuscular medetomidine in domestic sheep.

Intramuscular (i.m.) administration of medetomidine (MED) may avoid the severe pressor effects caused by peripheral actions of MED associated with intravenous (i.v.) dosing. The purpose of this study was to determine the pharmacokinetics, the time course of sedation and occurence of hypoxaemia after i.m. administration of MED in domestic sheep. The MED was injected i.m. at a dose of 30 micro g/kg in nine domestic sheep. Blood was sampled at 0, 5, 10, 20, 30, 40, 60, 120, 180, 240, 360 and 600 min after MED. Sedation was assessed and arterial blood samples were taken before and 35 min after MED application. Mean (SD) pharmacokinetic parameters of i.m. MED were: absorption half-life: 13.2 (7.5) min; terminal half-life: 32.7 (14.9) min; time to peak concentration: 29.2 (8.9) min; peak concentration: 4.98 (1.89) ng/mL; volume of distribution: 3.9 (2.4) l/kg; total body clearance: 81.0 (21.5) mL/(min kg). Peak sedation occurred between 30 and 40 min after injection of MED. The degree of sedation correlated with individual plasma concentrations (rS: 0.926). One animal became hypoxaemic (PaO2 = 54.1 mmHg).

Adrenergic alpha-Agonists↗
PubMed2001

A PDZ domain protein interacts with the C-terminal tail of the insulin-like growth factor-1 receptor but not with the insulin receptor.

In this study, we report on the isolation of a PDZ domain protein, here designated as IIP-1, insulin-like growth factor-1 (IGF-1) receptor-interacting protein-1, which binds to the IGF-1 receptor, but not to the related insulin receptor, and which is involved in the regulation of cell motility. The interaction between the IGF-1 receptor and IIP-1 as well as a splice variant IIP-1/p26 was demonstrated in the yeast two-hybrid system. Using co-precipitation experiments, we confirmed the interaction in transfected cells as well as in vitro. Analysis of deletion mutants indicates that the PDZ domain of IIP-1 mediates interaction with the C-terminal tail of the IGF-1 receptor (serine-threonine-cysteine). This finding demonstrates that the C terminus of the IGF-1 receptor acts as novel PDZ domain binding site. Immunofluorescence analysis revealed an overlapping localization of IIP-1 and the IGF-1 receptor in the breast cancer cell line MCF-7. A functional connection between IIP-1 and the IGF-1 receptor is further supported by the finding that the level of expression of IIP-1 and the IGF-1 receptor strongly correlates in different normal and cancer cells. Furthermore, overexpression of IIP-1 resulted in an attenuation of migration of MCF-7 cells, which is one of the biological activities mediated by the IGF-1 signaling system.

3T3 Cells↗
PubMed2000

Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol (Disoprivan) in comparison to propofol solved in polysorbate 80 in goats.

The aim of this study was to determine whether any pharmacokinetic or pharmacodynamic differences exist in goats between propofol in its currently licensed form (Disoprivan) and a new 1% solution of propofol (NSP) containing polysorbate 80. Nine goats received, on two different occasions in a randomized double-blinded order, 4 mg/kg propofol intravenously (i.v.; Disoprivan or NSP). To detect differences in cardiopulmonary effects and pharmacokinetics, the Wilcoxon signed rank test for paired data was used. In the NSP group the duration of initial apnoea was significantly longer, and 6 and 12 min after drug application PaO2 levels were significantly lower than in the Disoprivan group. Mean cardiovascular parameters did not differ significantly between the groups but in the NSP group in six goats marked changes in blood pressure occurred: systolic arterial pressures fell to a minimum of 40-60 mmHg within the first 10 min. This was followed by a marked increase in blood pressure, with maxima exceeding 300 mmHg. In the NSP group the half-life of propofol was significantly longer, the clearance rate was smaller and the areas under the drug concentration-time curves were larger than in the Disoprivan group. The cardiopulmonary side-effects of NSP suggest that propofol dissolved in polysorbate 80 is not a suitable alternative to the current formulation of propofol.

Anesthetics, Intravenous↗
PubMed2000

[Computer-supported poisonous plant information system for veterinary medicine].

Animals poisoned by plants are the subject of an increasing number of inquiries made to poison control centres. The most frequent questions are concerned with the identification of potentially toxic species and the choice of adequate therapeutic strategies. To meet this growing demand for information, we generated a database on poisonous plants to be used by veterinary practitioners. Relevant data were selected from the scientific literature and organised according to the requirements of a structured database. As a result, we now introduce a user-friendly decision support system that is equipped with several search functions for fast and efficient retrieval of data. The information provided for each plant includes the degree of toxicity, major toxic constituents, their mechanism of action, pathological findings, clinical symptoms with brief case reports, therapeutic guidelines and references. In addition, each species is accompanied by a botanical description with photographic illustrations. This information tool on poisonous plants is available via the internet (http:www.vetpharm.unizh.ch) or compact disc, and can be accessed on Macintosh, Windows or UNIX using a browser that supports HTML 3.

Animals↗
PubMed1999

Actinobacillus actinomycetemcomitans immunosuppressive protein is a member of the family of cytolethal distending toxins capable of causing a G2 arrest in human T cells.

We have previously shown that Actinobacillus actinomycetecomitans produces an immunosuppressive factor (ISF) capable of impairing human lymphocyte function by perturbing cell cycle progression. We now report that ISF is the product of the cdtB gene, one of three genes encoding the family of cytolethal distending toxins (Cdt). The ISF polypeptide exhibits >/=95% identity with Hemophilus ducreyi CdtB protein and </=60% homology with Escherichia coli or Campylobacter jejuni CdtB. Pretreatment of PHA-activated lymphocytes with 5-25 ng ISF results in G2 arrest of CD4+ and CD8+ T cells. Similarly, treatment of HeLa cells results in G2 arrest and cell elongation and distension. However, lymphocytes are at least 5 times more sensitive to ISF than HeLa cells and do not undergo the elongation and distension that characterizes interactions of Cdts with cell lines. ISF-treated lymphocytes express normal cyclin A and B1 levels, but contain reduced levels of cell cycle-dependent kinase-1 (Cdk1). Additionally, the majority of Cdk1 is in the hyperphosphorylated, inactive, form. In contrast, PHA-induced G2 cells contain elevated levels of the hypophosphorylated, active Cdk1. Failure of ISF-treated cells to dephosphorylate Cdk1 is not associated with decreased availability of Cdc25. These studies suggest that the CdtB protein alone is capable of inducing G2 arrest in lymphocytes and cell cycle arrest, elongation, and distension of HeLa cells. Our studies also suggest that lymphocytes may be primary targets for A. actinomycetemcomitans CdtB (ISF) and possibly for other Cdt family members as well. Thus, Cdts may function to impair host immunity and contribute to the pathogenesis of disease associated with Cdt-producing organisms.

Aggregatibacter actinomycetemcomitans↗
PubMed1999

Pharmacokinetics of medetomidine in ponies and elaboration of a medetomidine infusion regime which provides a constant level of sedation.

The pharmacokinetics of intravenous (i.v.) medetomidine (7 mcg kg(-1)) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h,(-1)t(1/2alpha)7. 6 (0.91) minutes and t(1/2beta)51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4. 2 l kg h(-1)and t(1/2)was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml(-1)) within 4 hours. Medetomidine 5 mcg kg(-1)i.v. followed by an infusion of 3.5 mcg kg h(-1)for two hours provided a constant level of sedation reaching steady state plasma medetomidine levels of 1-1.5 ng ml(-1)within 30 minutes. Sedation was reversed effectively by atipamezole (60 mcg kg(-1)) i.v. The pharmacokinetics of medetomidine make it suitable for prolonged use by infusion, such as is required as part of a total intravenous anaesthetic technique in horses.

Animals↗
PubMed1998

Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions.

Binding proteins for insulin-like growth factors (IGFs) IGF-I and IGF-II, known as IGFBPs, control the distribution, function and activity of IGFs in various cell tissues and body fluids. Insulin-like growth factor-binding protein-5 (IGFBP-5) is known to modulate the stimulatory effects of IGFs and is the major IGF-binding protein in bone tissue. We have expressed two N-terminal fragments of IGFBP-5 in Escherichia coli; the first encodes the N-terminal domain of the protein (residues 1-104) and the second, mini-IGFBP-5, comprises residues Ala40 to Ile92. We show that the entire IGFBP-5 protein contains only one high-affinity binding site for IGFs, located in mini-IGFBP-5. The solution structure of mini-IGFBP-5, determined by nuclear magnetic resonance spectroscopy, discloses a rigid, globular structure that consists of a centrally located three-stranded anti-parallel beta-sheet. Its scaffold is stabilized further by two inside packed disulfide bridges. The binding to IGFs, which is in the nanomolar range, involves conserved Leu and Val residues localized in a hydrophobic patch on the surface of the IGFBP-5 protein. Remarkably, the IGF-I receptor binding assays of IGFBP-5 showed that IGFBP-5 inhibits the binding of IGFs to the IGF-I receptor, resulting in reduction of receptor stimulation and autophosphorylation. Compared with the full-length IGFBP-5, the smaller N-terminal fragments were less efficient inhibitors of the IGF-I receptor binding of IGFs.

3T3 Cells↗
PubMed1997

[Veterinary services on the Internet].

The world wide web (www) on the internet is already a rich source of veterinary informations and offers several world wide discussion fora for problems of veterinary practice. With this article, we provide practical tips for first-time users of the www and encourage exploration of this new information technology for continuing education. The Swiss Drug Compendium is now accessible on www and-in the near future-the exchange and interpretation of laboratory results and diagnostic images via internet seems feasible.

Animals↗
PubMed1996

NMR Studies of Single-File Diffusion in Unidimensional Channel Zeolites

Single-file diffusion is the restricted propagation of particles that cannot pass each other. The occurrence of this phenomenon should be reflected by a change in the time dependence of the mean particle displacement in comparison with ordinary diffusion. Although this process is considered to be the rate-controlling mechanism in a large variety of processes, so far no direct evidence of this phenomenon has been provided. Diffusion measurements made with pulsed field gradient nuclear magnetic resonance (NMR) in unidimensional pore systems (zeolites AlPO4-5 and Theta-1) reflect the expected time dependence of single-file diffusion.

Journal Article↗
PubMed1994

[Adverse effects of veterinary drugs].

We report cases of adverse reactions, some of which serious, of four frequently used therapeutic substances in several animal species. In order to avoid similar cases we discuss special measures or alternative therapies.

Animals↗
PubMed1986

Chromosomal localization of a human band 3-like gene to region 7q35----7q36.

Band 3, the major transmembrane protein of erythrocytes, mediates the exchange of anions across the membrane and anchors the erythroid membrane skeleton. Proteins immunologically related to Band 3 have been detected in a variety of nonerythroid cells. We have isolated a human cDNA clone that encodes a protein related to but distinct from the erythroid form of Band 3, based on the comparison of the amino acid sequence for the two proteins. The presence of the gene for the Band 3-like protein in a panel of mouse-human somatic cell hybrids containing subsets of human chromosomes correlated with the presence of human chromosome 7. In situ hybridization analysis using the c-DNA for this nonerythroid Band 3 gene further localized the gene to region 7q35----7q36 of human metaphase chromosomes.

Animals↗
PubMed1983

The nucleotide sequence and derived amino acid sequence of cDNA coding for mouse carbonic anhydrase II.

The nucleotide sequence of a clone containing mouse carbonic anhydrase (CA) cDNA in pBR322 has been determined. The cloned cDNA contains all of the coding region except for nucleotides specifying the first eight amino acids, and all of the 3' noncoding region, which consists of 700 nucleotides. A cDNA clone was identified which contains an additional 54 bp at the 5' end, so that the complete amino acid sequence of mouse CA could be deduced. This sequence showed a 73-81% homology with other mammalian CA form II isozymes, 56-63% with form I isozymes, and 52-56% with form III isozymes. By examination of the amino acids which are unique and invariant for each isozyme, the mouse amino acid sequence was found to contain 16 of the 23 residues that are unique and invariant to mammalian CA form II isozymes, but only one or no residue for forms I and III, respectively.

Amino Acid Sequence↗