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Biomedical subjects

U Schroeder

Publications and source records attributed to U Schroeder.

At least 37 records · Page 2Linked to original sources
PubMed1998

Small drug sample fabrication of controlled release polymers using the microextrusion method.

Ethylene vinylacetate polymer (EVA) has been used for many years to fabricate controlled-release polymeric implant devices with which drugs of high or low molecular weight compounds could be delivered with zero-order kinetics. However, because the known fabrication methods such as solvent evaporation, casting and possible shrinkage are not sufficiently controllable we have now developed the microextrusion method with which even small amount of clinically important and expensive drugs can be incorporated into EVA with high reproducibility. We show here that devices produced by the microextrusion method allows for a controlled delivery of several neurotoxic and neurotherapeutic compounds such as alpha-methyl-p-tyrosine, diazepam, quinolinic acid, and phencyclidine. Each substance is slowly released from the polymer, as evidenced by spectrophotometric data, for up to 120 days at daily rates varying from 18.4 microg of phencyclidine to 97.6 microg/day of diazepam. Thus, microextrusion is a valuable method for fabricating controlled-release polymers in which small amounts of scarce drugs can be incorporated. Another advantage of the current procedure is that polymers can be fabricated with very little amount of solvent.

Delayed-Action Preparations↗
PubMed1998

Simulation of psychosis by continuous delivery of phencyclidine from controlled-release polymer implants.

To simulate psychosis in rats we have developed a method for the continuous delivery of phencyclidine (PCP) using implantable controlled-release polymers. PCP polymer implants produced deficits in latent inhibition which do not occur after repeated bolus injections. PCP implanted rats were also devoid of any anxiogenic signs, motoric hyperactivity and learning acquisition which can be seen in rats receiving daily bolus injections of a comparable PCP dose. This behavioral double-dissociation of the two modes of PCP application was accompanied by respective neurochemical changes. PCP binding sites were reduced in both striatum and hippocampus, but in the hippocampus, loss of PCP binding sites was more severe following pulsatile PCP administration. Morphological assessment revealed a significant shrinkage of the CA3 region in hippocampus in both groups. Pharmacokinetic analysis showed that the maximum PCP concentration in the brain after bolus injections was 10-fold above the PCP implants.

Animals↗
PubMed1998

Efficacy of oral dalargin-loaded nanoparticle delivery across the blood-brain barrier.

The Leu-enkephalin dalargin normally does not penetrate the blood-brain barrier (BBB) when given intravenously. To transport dalargin across the blood-brain barrier, the peptide was adsorbed onto the surface of poly(butyl)cyanoacrylate nanoparticles and coated with polysorbate 80. After systemic administration the central analgesia was measured by hot plate test. Furthermore, nanoparticles were fabricated with different stabilizers. After the adsorption of the peptide on polysorbate 85 stabilized nanoparticles analgesia was observable after intravenously and oral application even when nanoparticles were not coated. Thus, our data support the usefulness of nanoparticles as a method to deliver drugs to the brain.

Administration, Oral↗
PubMed1998

Nanoparticle technology for delivery of drugs across the blood-brain barrier.

The Leu-enkephalin dalargin and the Met-enkephalin kyotorphin normally do not cross the blood-brain barrier (BBB) when given systemically. To transport these neuropeptides across the BBB they were adsorbed onto the surface of poly(butylcyanoacrylate) nanoparticles (NPs) and the NPs were coated with polysorbate 80. Central analgesia was measured by the hot plate test in mice. The antidepressant amitriptyline, which normally penetrates the BBB, was used to examine the versatility of the NP method. The concentration of amitriptyline in serum and brain of mice was determined by a gas chromatographic method. Furthermore, NPs were fabricated with different stabilizers. After the adsorption of the peptides on polysorbate 85-stabilized NPs, analgesia was noted after intravenous application when NPs were not coated. The amitriptyline level was significantly enhanced in brain when the substance was adsorbed onto the NP and coated or when the particles were stabilized with polysorbate 85.

Amitriptyline↗
PubMed1997

Amphetamine induces hypermotility in MPTP-lesioned mice.

Two strains of mice (NMRI and C57B1/ 6) were treated with MPTP (within 8 h 4 x 30 mg/kg MPTP, IP) and motility was monitored 10 days later. An acute administration of amphetamine (2.5 mg/kg or 10.0 mg/kg) or apomorphine (0.5 mg/kg or 5.0 mg/kg) led to hypermotility and a dose-dependent increase of stereotyped behavior. Immunocytochemical investigations indicated a substantial loss of tyrosine-hydroxylase immunoreactivity in the basal ganglia which was accompanied by a 15% increase of 3H-spiroperidol binding to a striatal membrane preparation. No difference was found in biochemical and behavioral measures between both mice strains. Thus, MPTP-induced lesions in mice are probably followed by a denervation-like supersensitivity of the dopaminergic system, which might account for the finding that despite a severe degeneration of dopaminergic terminals amphetamine induces hypermotility.

Animals↗
PubMed1997

The role of striatal glutamatergic system in haloperidol-induced dopamine receptor supersensitivity and effects of monosialoganglioside GM1.

The mechanism underlying the action of ganglioside GM1 on the increase of haloperidol-induced dopamine receptor supersensitivity was studied using the method of chemically stimulated (3H)-D-aspartate release in rat striatal slices. After a 3-week chronic haloperidol treatment the transmitter release was reduced by about 30%, with a further reduction to 40% when GM1 was applied chronically as well. This suggests that the downregulation of the glutamatergic system by chronic haloperidol treatment is potentiated by gangliosides. The acute effect of gangliosides on the stimulated (3H)-D-aspartate release from striatal slices was tested by adding GM1 to the superfusion medium. When given at a concentration of 10(-4) M, GM1 did not alter the amino acid release itself. GM1 did, however, reduce the haloperidol-enhanced (3H)-D-aspartate release to control levels and elevated the glutamate-stimulated (3H)-D-aspartate release. Binding experiments indicate that gangliosides do not directly interact with glutamate or dopamine receptors. The data are discussed in view of earlier findings that GM1 potentiates the behavioral supersensitivity following chronic haloperidol treatment without directly altering dopamine receptor supersensitivity.

Animals↗
PubMed1994

Peptidase D of Escherichia coli K-12, a metallopeptidase of low substrate specificity.

Peptidase D of Escherichia coli was overproduced from a multicopy plasmid and purified to electrophoretic homogeneity. The pure enzyme was stable at 4 degrees C or -20 degrees C and had a pH optimum at pH 9, and a pI of 4.7; the temperature optimum was at 37 degrees C. As the enzyme was activated by Co2+ and Zn2+, and deactivated by metal chelators, it appears to be a metallopeptidase. By activity staining of native gels, 11 dipeptides which are preferentially cleaved by peptidase D were identified. Peptidase D activity required dipeptide substrates with an unblocked amino terminus and the amino group in the alpha or beta position. Non-protein amino acids and proline were not accepted in the C-terminal position, whereas some dipeptide amides and formyl amino acids were hydrolyzed. Km values of 2 to 5 mM indicate a relatively poor interaction of the enzyme with its substrates.

Dipeptidases↗
PubMed1993

dcp gene of Escherichia coli: cloning, sequencing, transcript mapping, and characterization of the gene product.

Dipeptidyl carboxypeptidase is a C-terminal exopeptidase of Escherichia coli. We have isolated the respective gene, dcp, from a low-copy-number plasmid library by its ability to complement a dcp mutation preventing the utilization of the unique substrate N-benzoyl-L-glycyl-L-histidyl-L-leucine. Sequence analysis of a 2.9-kb DNA fragment revealed an open reading frame of 2,043 nucleotides which was assigned to the dcp gene by N-terminal amino acid sequencing and electrophoretic molecular mass determination of the purified dcp product. Transcript mapping by primer extension and S1 protection experiments verified the physiological significance of potential initiation and termination signals for dcp transcription and allowed the identification of a single species of monocistronic dcp mRNA. The codon usage pattern and the effects of elevated gene copy number indicated a relatively low level of dcp expression. The predicted amino acid sequence of dipeptidyl carboxypeptidase, containing a potential zinc-binding site, is highly homologous (78.8%) to the corresponding enzyme from Salmonella typhimurium. It also displays significant homology to the products of the S. typhimurium opdA and the E. coli prlC genes and to some metalloproteases from rats and Saccharomyces cerevisiae. No potential export signals could be inferred from the amino acid sequence. Dipeptidyl carboxypeptidase was enriched 80-fold from crude extracts of E. coli and used to investigate some of its biochemical and biophysical properties.

Amino Acid Sequence↗
PubMed1993

[Routine postoperative epidural analgesia. X-ray control of epidural catheter position and prevention of the spread of epidural contrast media].

In the last few years epidural analgesia with bupivacaine and/or opioids has become an important technique in the therapy of postoperative pain. Using bupivacaine only 2-20% of the patients are treated without sufficient success. To ascertain and evaluate the underlying reasons for this, we prospectively investigated 51 patients routinely, and 6 patients with an insufficient analgetic effect from a group of 212 patients, by means of epidurography. All patients were treated mainly with bupivacaine. The observed and documented radiographic data were compared with the individual analgetic results. METHODS. All investigations were performed within 24 h after placing the catheters. The contrast agent was injected under radiographic guidance in two different positions, and the end of the distribution was documented in the anterior-posterior ray path. In group I (n = 26) the catheter position and the distribution of the contrast medium with 3.0 ml iopamidol were documented. In group II (n = 25) the catheter position was documented in the same way, but the distribution was documented for the stepwise-injected contrast medium (3.0 ml + 2.0 ml + 3.0 ml). As a result of these findings we changed our epidural catheter placement concept in the following patients (group III, n = 212), and performed radiographic examinations in patients with a therapy failure only (group IIIa, n = 6). Instead of placing the catheter postoperatively mostly lumbal in a lateral position, we now placed them preoperatively, in the sitting position, as near as possible to the centre of the segments to be treated. RESULTS. Only 27 patients demonstrated an ideal catheter position and a typical contrast medium distribution. Three of these patients still could not be treated successfully. In 12 patients the spread of the contrast medium was inhomogeneous, and in 5 patients the contrast medium was found on one side of the epidural space only. Half of these 17 patients (n = 9) needed supplementary therapy. Surprisingly, 4 of 8 patients with a paraepidural catheter position were treated with success. DISCUSSION. Effective bupivacaine therapy by epidural catheter injections constitutes no striking evidence for a correct epidural catheter position. If the catheter lies in the epidural space, the actual therapeutic effect of bupivacaine therapy is determined mainly by the distribution of the substance. The epidural position of the catheter--central or lateral in the epidural space--seems, however, not to be particularly important. If high-quality analgesia is to be achieved with bupivacaine alone, or in combination with an opioid, the catheter should usually be placed near to, or better into the centre of the segments to be treated. The results demonstrate that in the case of failure of epidural catheter therapy, epidurographic examinations are very helpful in ascertaining and evaluating the underlying reasons for this failure and in coming to a logical decision for changing the concept.

Adolescent↗
PubMed1989

Accurate mapping of the Escherichia coli pepD gene by sequence analysis of its 5' flanking region.

A cloned DNA fragment, carrying the gene for peptidase D (pepD) of Escherichia coli, was partially sequenced. By purification of peptidase D and sequence determination of an amino-terminal oligopeptide the reading frame of the pepD gene, starting with a GTG initiator codon, was unambiguously identified. An overlap of the established nucleotide sequence with the previously sequenced 5' flanking region of the gpt gene allowed the exact distance between pepD and gpt to be calculated. The two genes are pointing towards each other and are separated by 260 bp. A search for open reading frames (ORFs) and the analysis of possible codon usage in the intercistronic region indicate the absence of an additional gene (lpcA) between pepD and gpt.

Amino Acid Sequence↗
PubMed1989

Efficacy and benefit of mediastinal computed tomography as a selection method for mediastinoscopy.

In 95 consecutive patients with proven or suspected bronchial carcinoma, computed tomographic evaluation of the upper mediastinum for N2 disease was performed prospectively. Patients with positive results underwent mediastinoscopy. Patients with perinodal N2 or N3 disease at mediastinoscopy were not considered candidates for operation. The mediastinum was declared negative only when intraoperative mediastinal lymph node dissection showed tumor-free nodes. Of the 95 patients, 12 had benign lesions, 14 were excluded from further evaluation because the lymph node status of the mediastinum was not proven intraoperatively, and 6 others were excluded from the final evaluation because of violation of the protocol. Twenty-two of the 75 remaining patients had a positive computed tomographic scan and underwent mediastinoscopy. Fourteen patients with positive results were considered to have inoperable disease. Fifty-three patients (70.7%) did not undergo mediastinoscopy. We performed seven probably incomplete resections, two for palliative reasons, and two thoracotomies without resection in patients with N2 disease. A policy of routine mediastinoscopy would have prevented only 5% of the thoracotomies performed in patients with lung cancer.

Aged↗
PubMed1988

Investigation of the nutritional state of children in a Congolese village. I. Anthropometrical data, plasma prealbumin, albumin, immunoglobulins, ferritin, C-reactive protein, circulating immune complexes.

The nutritional status of an unselected group of 111 children from the village of Bouansa, People's Republic of the Congo, was studied. Comprehensive clinical examinations, anthropometrical measurements and analysis of albumin, prealbumin, ferritin, C-reactive protein (CRP), IgA, IgG, IgM, IgE, IgG- and IgM-circulating immune complexes (CIC) were carried out. The results show, by anthropometrical classification, a high prevalence of moderate malnutrition. Low levels of plasma proteins and high levels of immunoglobulins and CIC were found. No correlation between anthropometrical classification and plasma proteins was established. Children with increased levels of CRP showed low prealbumin values and increased levels of ferritin. Patterns of immunoglobulins and CIC were close to those found in other studies in tropical countries. To evaluate the anthropometrical and biochemical findings it is necessary to take into consideration the apparently healthy appearance of the children, which shows the degree of adaptation to the limited availability of food and the high rate of acute and chronic infections.

Adolescent↗