Biomedical subjects

M Pohl

Publications and source records attributed to M Pohl.

At least 73 records · Page 4Linked to original sources

PubMed1994

[Mechanical hemolysis caused by artificial organs--comparison of in vitro hemolysis studies and their application to in vivo conditions].

Changes of plasma concentration are often used for in vitro characterisation of the hemolytic potency of artificial organs and apparatus. Different indices of hemolysis are derived from Hb concentration, which, in general, depend on experimental conditions and cannot be compared quantitatively or used to describe the in vivo damage. In this paper we propose a similarity number called "lysis number" that is independent of experimental conditions. It describes the probability for a single blood cell to be completely destroyed in a single pass through the corresponding artificial assist system. The concept is based on the steps: 1. Definition of "lysis number" as an index of hemolytic performance of artificial organs or implants. 2. Description of more complex hemolytic damaging processes (different hemolytic steps) that may be in series or parallel and definition of an effective lysis number. 3. Experimental in vitro estimation of each of the processes in consecutive steps. 4. Calculation of total hemolysis of the complex system using the linkage rules. 5. Application to in vivo by an appropriate differential equation in RBC mas taking into account mechanically-induced hemolysis rate, survival time of normal RBC and erythropoetic generation rate.

Erythrocyte Aging↗

PubMed1994

[Testing the hydrodynamic properties of heart valve prostheses with a new test apparatus].

A new test apparatus for the testing of artificial heart valves makes it possible to realize both physiological flow through the valve during the flow period, and physiological pressure differences across the artificial valve during the closing phase, both for aortic and mitral valve positions, with freely selectable stroke volume and heart frequency. The major hydraulic parameters of the valve are measured directly (pressure drop, closing volume and closing time, leakage volume) or are calculated (e. g. energy loss). In association with the demonstration of the suitability of the HKP+ test apparatus for the measurement of hydraulic parameters in accordance with ISO 5840, the hydraulic properties of various types and sizes of valve with respect to pressure drop (resistance), together with their closing behaviour and leakage flow, are described for different fluids, and the correlations shown.

Aortic Valve↗

PubMed1994

[Long-functioning beta-D-glucose and L-lactate biosensors for continuous flow-through measurements for "fouling"-resistant and selectivity-optimized serum- and hemoanalysis].

Bioelectrochemical membrane-electrodes for O2-sensitive enzymatic flow-through analysis of beta-D-glucose and L-lactate are described. The enzyme-membranes of the biosensors consist of glucose-oxidase or lactate-oxidase molecules cross-linked with glutardialdehyde between two dialysis membranes. The accuracy of the biosensors is demonstrated by electroanalysis of diluted control serum and compared with redox-mediator-free H2O2 detection and photometric methods. Continuous haemoanalysis of uncoagulated blood was carried out, using an intermediate carrier stream with additive systems. Tangential streaming to the miniaturized dialysis chamber with a circular channel minimizes blockage of the pores of the dialysis membrane by erythrocytes, leukocytes or protein. An oxygenator pump for the exchange of gases between the buffered solution of the intermediate carrier and the surrounding atmosphere guarantees a constant oxygen partial pressure within the carrier stream. The pulsations produced by the oxygenator pump are dampened by a miniature pressure balance chamber with an unsignificant dead space volume for protecting the enzyme membrane of the sensor. Glutardialdehyde inhibits growth of microorganisms and any resulting oxygen consumption, so that even in protein-containing measuring solutions enzyme electrodes can be used without interference from microbial contamination. The bioelectrochemical measuring system can therefore also be employed for the electroanalysis of fermentation solutions. For continuous flow-through measurements, it is necessary to change the glucose-oxidase membranes after 100-150 days, and the lactate-oxidase membranes after 3-6 weeks.

Biosensing Techniques↗

PubMed1994

Is the site of action of ethosuximide in the hindbrain?

The action of ethosuximide, valproate and clonazepam against pentylenetetrazol-induced epileptic EEG phenomena was studied in acute experiments in rats with intercollicular brainstem transection. Ethosuximide lost its action against both rhythmic metrazol activity (model of human absences) and EEG seizures. On the contrary, the action of valproate and clonazepam in cerveau isolé rats was the same as in intact animals. The site of anticonvulsant action of ethosuximide may be localized in hindbrain structures, whereas the actions of both valproate and clonazepam may be demonstrated even if hindbrain structures had been eliminated.

Animals↗

PubMed1994

Influence of flunarizine on hippocampal epileptic afterdischarges in the rat.

Epileptic afterdischarges elicited by electrical stimulation of the dorsal hippocampus in freely moving rats were not significantly changed by flunarizine administration in comparison with control sessions in which the animals received the solvent only. On the other hand, flunarizine significantly reduced the number of wet dog shakes, the main automatisms accompanying limbic afterdischarges.

Animals↗

PubMed1993

Opioid control of the release of calcitonin gene-related peptide-like material from the rat spinal cord in vivo.

The possible control by opioids of the spinal release of calcitonin gene-related peptide-like material (CGRPLM) was investigated in halothane-anaesthetized rats whose intrathecal space was perfused with an artificial cerebrospinal fluid. Morphine (20 mg/kg i.v.; or at 10-100 microM added to the perfusing fluid), the mu selective agonist DAGO (10 microM) and the kappa selective agonist U 50488 H (10 microM) did not affect the spontaneous outflow of the CGRPLM. In contrast, the selective delta agonist DTLET (10 microM) significantly increased CGRPLM release. The latter effect could be prevented by the selective delta antagonist naltrindole (10 microM) as expected from the involvement of this class of opioid receptors. However, the addition of naltrindole alone to the perfusing fluid did not modify CGRPLM outflow, indicating that endogenous opioids do not exert a tonic control of CGRP-containing fibers through the stimulation of delta receptors. In contrast, intrathecal perfusion with naloxone (10 microM) or nor-binaltorphimine (10 microM), a selective antagonist of kappa receptors, produced a marked increase in spinal CGRPLM release, suggesting that endogenous opioids acting at mu and kappa receptors, respectively, exert a tonic inhibitory control of CGRP-containing fibers. Indeed, a significant decrease in the spinal release of CGRPLM release could be evoked by the combined addition of U 50488 H (10 microM) plus DAGO (10 microM) to the perfusing medium, indicating that the simultaneous stimulation of both kappa and mu receptors is required for this negative control to occur. This could notably be achieved with morphine (10 microM) in the presence of naltrindole (10 microM) which also produced a significant reduction in the spinal release of CGRPLM. In conclusion, morphine per se did not change CGRPLM release because this drug triggers opposite positive (through the stimulation of delta receptors) and negative (through the concomitant stimulation of both kappa and mu receptors) control mechanisms within the rat spinal cord.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Determination of the autonomously functioning volume of the thyroid.

The aim of this work was to determine the autonomously functioning volume in euthyroid and hyperthyroid goitres for prognostic and therapeutic purposes. To this end, various groups of patients were selected: individuals without evidence of thyroid disease, euthyroid patients with diffuse goitre of normal structure and function, euthyroid patients with evidence of autonomy and patients with hyperthyroidism due to autonomy. In all of them the thyroid uptake of technetium-99m was determined under exogenous suppression (TcUs) in the euthyroid state and under endogenous suppression (TcU) in the hyperthyroid state. It was demonstrated that: 1. In patients with unifocal autonomy the TcUs and TcU correlated linearly with the autonomous volume delineated and measured by sonography. 2. A nearly identical result was obtained if the mean autonomous volume in individuals without thyroid disease of 2.2 +/- 1.1 ml calculated by TcUs/TcU x total thyroid volume was used as a basis. 3. The critical autonomous volume, i.e. the volume at which hyperthyroidism will occur, was found to be 16 ml at a cumulated sensitivity and specificity of > 0.9. The method can be used to select patients for definitive treatment before hyperthyroidism occurs and to measure the autonomously functioning volume independent of its distribution within the thyroid for treatment with radioiodine. The method is easy to perform and is also an example of how a relative parameter of a function can be converted into an absolute parameter of a functioning volume.

Goiter↗

PubMed1993

Monoaminergic control of the release of calcitonin gene-related peptide- and substance P-like materials from rat spinal cord slices.

The possible control by monoamines of the spinal release of substance P- and calcitonin gene-related peptide-like materials (SPLM and CGRPLM, respectively) was investigated in vitro, using slices of the dorsal half of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Whereas the spontaneous outflow of SPLM and CGRPLM was changed by none of the agonists/antagonists of monoamine receptors tested, the overflow of both peptide-like materials due to 30 mM K+ was differentially affected by alpha 2-adrenoreceptor and dopamine D-1 receptor ligands. Noradrenaline (10 microM to 0.1 mM) and clonidine (0.1 mM) significantly reduced the K(+)-evoked overflow of SPLM, and both effects could be prevented by idazoxan (10 microM) and prazosin (10 microM) as expected from their mediation through the stimulation of alpha 2B-adrenoreceptors. In contrast, CGRPLM overflow remained unaffected by alpha 2-adrenoreceptor ligands. Dopamine D-1 receptor stimulation by SKF 82958 (10-100 nM) significantly increased the K(+)-evoked overflow of both SPLM and CGRPLM, and this effect could be prevented by the selective D-1 antagonist SCH 39166 (1 microM). Further studies with selective ligands of other monoamine receptors indicated that neither alpha 1- and beta-adrenergic receptors, dopamine D-2, nor serotonin 5-HT1A and 5-HT3 receptors are apparently involved in some control of the spinal release of CGRPLM and SPLM. These data are discussed in line with the postulated presynaptic control by monoamines of primary afferent fibres conveying nociceptive messages within the dorsal horn of the spinal cord.

Animals↗

PubMed1993

Increased in vivo release of calcitonin gene-related peptide-like material from the spinal cord in arthritic rats.

Possible alterations in spinal systems containing calcitonin gene-related peptide (CGRP) due to polyarthritis were assessed in rats 3-4 weeks after an intradermal injection of Freund's adjuvant in the low back. The tissue levels of CGRP-like material (CGRPLM) were approximately 50% higher in the dorsal zone of the spinal cord and dorsal root ganglia at both the cervical and lumbar (but not thoracic) segments in polyarthritic rats than in age-paired control animals. In addition the rate of the spinal release of CGRPLM determined through an intrathecal perfusion procedure in halothane-anaesthetized animals was approximately 15-fold higher in polyarthritic rats than in controls. The blockade of mu-opioid receptors by intrathecal perfusion with 10 microM naloxone produced a larger increase in the spontaneous CGRPLM outflow in polyarthritic rats than in age-paired controls. Furthermore, the stimulation of mu-opioid receptors by intrathecal perfusion with 10 microM DAGO significantly inhibited the spinal outflow of CGRPLM only in polyarthritic rats. These data indicate that CGRP-containing primary afferent fibres are markedly activated in chronic suffering polyarthritic rats. This activation occurs in spite of an increased tonic inhibitory control by endogenous opioids acting at mu receptors.

Analgesics↗

PubMed1993

Paired-pulse and frequency potentiation of cortical responses in developing rats.

The postnatal development of paired-pulse and frequency potentiations of the first positive and negative components (P1N1) of the cortical interhemispheric response (IHR) was studied in urethane anesthetized rats aged from 7 to 90 days. The paired-pulse potentiation appeared in the rat sensorimotor cortex starting from the age of 15 days. The magnitude of potentiation increased with age. The interpulse interval inducing maximum potentiation shortened from 125 ms in 15-day-old rats to 70 ms in adult rats. Similar results concerning the paired-pulse responses were found for visual cortex but the maturation was somewhat delayed--potentiation first appeared at postnatal day (PND) 18. The frequency potentiation reached adult properties in the sensorimotor cortex by PND 25. There is no time coincidence in the development of the two potentiation phenomena studied, paired pulse potentiation appeared earlier than frequency potentiation.

Animals↗

PubMed1993

Cyclic disulfide analogues of the complement component C3a. Synthesis and conformational investigations.

The flexible C-terminal region of the anaphylatoxic peptide C3a was reported to contain the receptor binding site. To elucidate the receptor binding conformation of the C-terminus, as well as to examine a synthetic approach to potential C3a-antagonists, 26 cyclic disulfide bridged C3a analogues were synthesized. Solid phase peptide synthesis was performed on different polymeric supports by individual peptide synthesis, with Fmoc strategy, and simultaneous multiple peptide synthesis, using Boc and Fmoc strategies. Both strategies gave open-chain peptides in comparable yields. Syntheses using the Boc strategy employed the HF-labile 4(methoxy)benzyl group (Mob) for beta-thiol protection of cysteine; in contrast, the TFA-stable protecting groups, acetamidomethyl (Acm) and trityl (Trt), were chosen for syntheses employing Fmoc strategy. Ring closure reactions by iodine oxidation were carried out starting from protected (Acm/Acm, Trt/Acm) or unprotected dithiols. The resulting cyclic C3a analogues were characterized by HPLC, amino acid analysis, and FAB-MS. Conformational investigations using CD spectroscopy and theoretical structural investigations by means of molecular dynamics calculations revealed that slight variations in sequence result in pronounced conformational consequences. The potential of cyclic C3a analogues to activate or to desensitize guinea pig platelets, a standard test system for biological activities of anaphylatoxic peptides like C3a, revealed relatively low activities for cyclic peptides (< 0.1% C3a activity). N-terminal acylation with cationic, arginine-rich sequences like YRRGR- led to amplified biological effects. Three of the synthesized peptides, namely CAALCLAR (P1), YRRGRCGGLCLAR (P5) and YRRGRAhxCGGLCLAR (P8), point in the direction of C3a antagonists.

Amino Acid Sequence↗

PubMed1993

[Immunogenic and non-immunogenic hyperthyroidism--a comparison].

In a retrospective study 161 hyperthyroid patients without treatment were divided into 74 with immunogenic hyperthyroidism (IMH) and 87 with non-immunogenic hyperthyroidism (NIMH). The frequency of complaints and the mean hormone concentrations were significantly higher in IMH and the median thyroid volume was significantly smaller. Diffusely reduced sonographic echoes were observed in only 50% of patients with IMH compared to 5% of those with NIMH. Homogeneous distribution of 99mTc in the thyroid was observed scintigraphically in 95% of patients with IMH and in only 3% of those with NIMH. Although the median of global thyroid uptake of 99mTc was significantly higher in IMH there was a broad overlap between the two groups. The mean hormone production is higher in IMH than in NIMH. In order to separate IMH and NIMH, several criteria have to be employed which differ concerning their diagnostic significance.

Humans↗

PubMed1992

Synthetic peptides as antagonists of the anaphylatoxin C3a.

Peptide compounds resembling the receptor-binding C-terminal domain of the anaphylatoxic peptide C3a were synthesized to examine two kinds of C3a antagonism: (a) specific desensitization of C3a-sensitive cells and (b) competitive binding to the C3a receptor. We used guinea-pig platelets, which express a C3a receptor and specifically release ATP upon stimulation, to evaluate the actions of the C3a analogues. The ATP liberation can be inhibited by pretreatment (i.e. desensitization) of the guinea-pig platelets with substimulatory concentrations of C3a or its analogues. Compared to C3a, several peptides were found with at least a tenfold greater difference between the required concentrations for C3a-specific half-maximal desensitization (DD50) and half-maximal platelet activation (ED50). The most potent compounds were YAAALKLAR and Fmoc-EAALKLAR (Fmoc: 9-fluorenylmethoxycarbonyl) with an ED50/DD50 of 140 +/- 28 and 80 +/- 17, respectively (mean +/- standard deviation). The ED50/DD50 of human C3a was found to be only 6 +/- 2. Some C3a derivatives were also tested in competitive binding studies for their ability to compete with C3a for receptor sites on guinea-pig platelets. Three of them were considered partial antagonists [YRRGRCGGLCLAR, YRRGRXCGGLCLAR and YRRGRXCGALCLAR (X = 6-aminohexanoyl)] because their Ki were smaller than their ED50 (Ki/ED50 = 0.6 +/- 0.3, 0.5 +/- 0.1 and 0.4 +/- 0.2, respectively). Interestingly, the last two compounds also had ED50/DD50 values greater than 60. Common to all three peptides are N-terminal arginine-rich sequences and intramolecular disulfide bridges which introduce conformational constraint.

Amino Acid Sequence↗

PubMed1992

GABA, acting at both GABAA and GABAB receptors, inhibits the release of cholecystokinin-like material from the rat spinal cord in vitro.

Superfusion of slices of the dorsal zone of the lumbar enlargement of the rat spinal cord with an artificial cerebrospinal fluid allowed the collection of cholecystokinin-like material (CCKLM) whose Ca(2+)-dependent release could be evoked by tissue depolarization with 30 mM K+. Studies on the possible influence of GABA and related agonists on this process showed that the amino acid, the GABAA agonist, muscimol, and the GABAB agonist, baclofen, inhibited the K(+)-evoked release of CCKLM from the rat spinal cord in a concentration-dependent manner. Maximal inhibition did not exceed -40% with either agonist. Furthermore, the effects of GABAA and GABAB receptor stimulation were not additive. Whereas the effects of muscimol (10 microM) and baclofen (1 microM) could be completely antagonized by bicuculline (1 microM) and phaclofen (10 microM), respectively, complete blockade of the inhibition by GABA (1 microM) could only be achieved in the presence of both antagonists. These data indicate that both GABAA and GABAB receptors are involved in the negative influence of GABA onto CCK-containing neurones within the dorsal horn of the rat spinal cord. Apparently, these receptors are not located on CCK-containing neurones themselves, since the inhibitory effect of GABA on the K(+)-evoked release of CCKLM could be completely prevented by tetrodotoxin (1 microM). As CCK acts centrally as an endogenous opioid antagonist, such a GABA-inhibitory control of spinal CCK-containing neurones might participate in the analgesic action of the amino acid via the intrathecal route.

Animals↗

PubMed1992

gamma-Aminobutyric acid, through GABAA receptors, inhibits the potassium-stimulated release of calcitonin gene-related peptide- but not that of substance P-like material from rat spinal cord slices.

Superfusion of slices of the dorsal zone of the lumbar enlargement with an artificial cerebrospinal fluid was used to investigate the possible modulation by GABA receptor ligands of the in vitro release of calcitonin gene-related peptide- and substance P-like materials (CGRPLM and SPLM) from the rat spinal cord. Whereas the spontaneous outflow of both peptides remained unaffected, the K+ (30 mM)-evoked overflow of CGRPLM could be partially inhibited (approx. -30%) by GABA (1 microM-0.1 mM) and muscimol (10 microM-0.1 mM) but not by baclofen (1-10 microM). Bicuculline methiodide (1 microM) completely prevented the inhibition by GABA (1 microM) and muscimol (10 microM) as expected from an action through GABAA receptors. By contrast, the K(+)-evoked SPLM overflow was altered neither by GABA nor muscimol and baclofen. These data further support that GABA exerts a presynaptic inhibitory control of (CGRP-containing) primary afferent fibres within the rat dorsal horn.

Animals↗

PubMed1992

Low magnesium-induced epileptiform discharges in guinea pig hippocampal slices: depression by the organic calcium antagonist verapamil.

The antiepileptic effects of the organic calcium channel blocker verapamil were tested in non-drug-induced epileptiform activities. Low Mg2+ epileptic field potentials (EFP) were elicited in hippocampal slices of guinea pigs. Verapamil reduced frequency of occurrence and amplitude of EFP until EFP failed. The EFP reappeared if verapamil was withdrawn from low Mg2+ solution. Elevating the KCl concentration from 4 to 8 mM resulted in shortening of the latency of EFP abolition by verapamil and prolongation of the depressive effects of verapamil following its withdrawal. The findings indicate that transmembraneous calcium fluxes play also an essential role in low Mg(2+)-induced epileptiform activities.

Animals↗

PubMed1992

Pentylenetetrazol-induced seizures in rats: an ontogenetic study.

A quantitative description of motor seizures induced by pentylenetetrazol (PTZ, metrazol) was performed. Seizures were induced by PTZ in doses from 40 to 120 mg/kg s.c. in 477 male albino rats of the Wistar strain 7 to 90 days old. Two patterns of seizures were elicited: minimal, i.e. predominantly clonic seizures of facial and forelimb muscles with preserved righting ability, and major, i.e. generalized tonic-clonic seizures with a loss of righting reflex. Minimal seizures could be reliably elicited since the age of 18 days; the CD50 for these seizures did not significantly differ with age. Major seizures were elicited regularly at all developmental stages studied. Their CD50 did not significantly differ among 7-, 12- and 25-day-old rat pups but the value for 18-day-old rats was smaller and for adult animals larger than these three age groups.

Aging↗

PubMed1992

Increased calcitonin gene-related peptide- and cholecystokinin-like immunoreactivities in spinal motoneurones after dorsal rhizotomy.

Possible changes in neuropeptides within the ventral horn of the spinal cord were investigated after unilateral dorsal rhizotomy at the lumbar level (L1-L6) in adult rats. Ten days after the surgery, immunohistochemical observations and radioimmunological determinations confirmed a marked loss of calcitonin gene-related peptide (CGRP)- and substance P (SP)-like immunoreactivities within the superficial layers of the deafferented dorsal horn, as expected from the degeneration of primary afferent fibres containing these peptides. A concomitant increase in immunohistochemical staining and levels of CGRP (+296%) and CCK (+71%)-like immunoreactivities was observed in the ipsilateral ventral horn where both peptides are located in motoneurones. In contrast, substance P-like immunoreactivity that is confined to fibres and terminals within the ventral horn, was not altered by dorsal rhizotomy. These data indicate that the expression of neuropeptides in spinal motoneurones can be influenced by primary afferent inputs.

Animals↗