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Biomedical subjects

M Pohl

Publications and source records attributed to M Pohl.

At least 91 records · Page 5Linked to original sources

Cholecystokinin (CCK)-like material and CCK mRNA levels in the rat brain and spinal cord after acute or repeated morphine treatment.

The effects of a single or repeated administrations of morphine on the tissue levels of cholecystokinin-like material (CCKLM) and pre pro cholecystokinin mRNA (CCK mRNA) were examined in various brain and spinal cord regions (cerebral cortex, cerebellum, hippocampus, septum, substantia nigra, lumbar enlargement) in adult rats using a specific radioimmunoassay and 'Northern blot' analysis, respectively. Although a clear parallelism existed between the regional distribution of CCKLM (septum greater than cerebral cortex greater than or equal to hippocampus much greater than lumbar enlargement, dorsal zone greater than substantia nigra greater than lumbar enlargement, ventral zone much much greater than cerebellum) and that of CCK mRNA, some mismatch was found notably in the septum where CCK mRNA levels were less than in other regions except the cerebellum. Neither CCKLM nor CCK mRNA levels were altered one hour after an acute administration of morphine (5 mg/kg i.p.). Similarly, morphine addiction after a four-day treatment with this drug was not associated with any change in the tissue levels of CCKLM and CCK mRNA. These data indicate that the previously reported modulatory action of opioids on central CCKergic systems could occur without affecting the preproCCK gene transcription and the tissue peptide concentrations.

Animals↗

In vivo release of calcitonin gene-related peptide-like material from the cervicotrigeminal area in the rat. Effects of electrical and noxious stimulations of the muzzle.

The continuous perfusion with an artificial cerebrospinal fluid of the cervicotrigeminal area of the spinal cord in halothane-anaesthetized rats allowed the collection of calcitonin gene-related peptide-like material with the same immunological and chromatographic characteristics as authentic rat alpha-calcitonin gene-related peptide. The spinal release of calcitonin gene-related peptide-like material could be significantly increased by the local application of 60 mM K+ (approximately +100%), high-intensity percutaneous electrical stimulation (approximately +200%) and noxious heat (by immersion in water at 52 degrees C; approximately +150%) applied to the muzzle. By contrast, noxious mechanical (pinches) and chemical (subcutaneous formalin injection) stimulations and deep cooling (by immersion in water at 0 degrees C) of the muzzle did not alter the spinal release of calcitonin gene-related peptide-like material. In addition, low-intensity electrical stimulation, recruiting only the A alpha/beta primary afferent fibres, significantly reduced (approximately -30%) the release of calcitonin gene-related peptide-like material from the cervicotrigeminal area. These data suggest that among the various types of natural noxious stimuli, noxious heat may selectively excite calcitonin gene-related peptide-containing A delta and C primary afferent fibres projecting within the dorsal horn of the spinal cord, and that activation of A alpha/beta fibres reduces spontaneous calcitonin gene-related peptide-like material release possibly through an inhibitory presynaptic control of calcitonin gene-related peptide-containing A delta/C fibres.

Animals↗

Influence of phenytoin and valproate on thalamocortical evoked potentials and their paired-pulse potentiation.

The action of phenytoin and valproate on thalamocortical responses was studied in adult rats. Single responses were not influenced by either drug. Paired-pulse potentiation of the initial components (first positive and first negative) observed with intervals from 50 to 200 ms under control conditions was abolished by phenytoin (60 mg/kg i.p.) but only moderately influenced by valproate (400 mg/kg i.p.). Paired-pulse potentiation of thalamocortical phenomena cannot be put into connection with the generation of the spike-and-wave rhythm.

Action Potentials↗

In vitro hemolysis by mechanical heart valve prostheses with tilting disc.

Hemolytic and subhemolytic blood damage by mechanical heart valve prostheses have been observed in both clinical and in vitro investigations. A direct comparison between these studies is not possible. Nevertheless the transfer of some in vitro results to the behaviour of the valve in situ may be performed considering the similarity principle. This requires the use of dimensionless similarity numbers such as the plasma's hemoglobin concentration (PHb) or others, instead of dimensioned parameters. To evaluate the in vitro hemolysis of valve prosthesis a test chamber filled with human banked blood was used. An artificial ventricle ensuring an oscillatory flow through the valve was also used. The rise of PHb was evaluated in terms of a similarity number, called the lysis number. This number describes the probability of destroying a single red blood cell participating once in the hemolytic process under consideration. The lysis number, a Björk-Shiley valve (TAD 29), was found to be in the order of 2 x 10(-4). From this, the survival time of erythrocytes in patients with an artificial heart valve was estimated. It was found to be in the order of 20 d of T50 Cr in agreement with clinical results.

Erythrocyte Aging↗

Staphylococcus aureus alpha-toxin. Dual mechanism of binding to target cells.

Staphylococcal alpha-toxin was radiolabeled to high specific radioactivity (1,500-3,000 Ci/mmol) under retention of its hemolytic activity. Binding studies with susceptible rabbit erythrocytes and highly resistant human erythrocytes revealed that binding of alpha-toxin to target cells can occur via two different mechanisms. Binding of alpha-toxin to rabbit erythrocytes initially involves specific binding sites and occurs at low concentrations, with half-maximal binding at 1-2 nM. In contrast, toxin binding to human erythrocytes is absorptive and nonspecific, in this case, significant binding as well as hemolysis occur only at alpha-toxin concentrations exceeding 1 microM. Autoradiographic analyses of membrane-associated alpha-toxin from either cell species proved that hemolysis was inevitably associated with the formation of toxin hexamers. Our data indicate that the high susceptibility of certain target cells toward alpha-toxin is caused by the presence of specific binding sites. However, membrane damage of both susceptible and nonsusceptible target cells occurs via a common mechanism involving toxin oligomerization and pore formation.

Animals↗

Opioid control of the release of Met-enkephalin-like material from the rat spinal cord.

The possible control by opioids of the release of Met-enkephalin-like material (MELM) from the rat spinal cord was investigated in vitro and in vivo. Superfusion of slices of the dorsal zone of the lumbar enlargement with the mu selective agonists DAGO or PL 017 or the delta selective agonist DTLET produced a significant reduction in the K(+)-evoked MELM release from these tissues. These effects persisted in the presence ot tetrodotoxin, as expected from their mediation through presynaptically located opioid autoreceptors. Furthermore, the inhibitory effect of DAGO and PL 017, but not that of DTLET, was prevented by the preferential mu antagonist naloxone. Conversely, the effect of DTLET was prevented by the delta antagonist naltrindole but not by naloxone. In vivo experiments performed in halothane-anaesthetized rats have shown that the intrathecal perfusion of DAGO and DTLET significantly depressed the spontaneous MELM outflow from the whole spinal cord. In contrast to these mu and delta agonists, the kappa selective agonist U 50488 H did not affect the in vivo- and only slightly reduced (at a very high concentration: 50 microM) the in vitro-release of MELM from the rat spinal cord. These data indicate that both mu and delta opioid autoreceptors are involved in a local presynaptic autoinhibitory control of MELM release in the rat dorsal horn.

Animals↗

Leakage of mechanical heart valve prostheses of Björk-Shiley type: in vitro investigations using Newtonian fluids.

The leakage of mechanical heart valve prostheses with tilting disc occluders was investigated. A U tube apparatus and a quasi-stationary method were used for measuring the backflow pressure characteristics. The method has several advantages over pulsatile or oscillatory techniques described in the literature. We have attempted to interpret the results of our measurements in terms of laminar and turbulent losses of energy. This leads to dimensionless loss numbers for valve leakage which are independent of arbitrary experimental conditions.

Biomechanical Phenomena↗

[Hydrodynamic in vitro comparison of a new artificial heart valve with the Björk-Shiley valve (standard)].

Measurements performed to compare a newly developed tilting disc valve with the Björk-Shiley valve included velocity profiles downstream of the heart valves, valve-induced flow turbulence and pressure drop across the opened valves. The velocity profiles measured with pulsed Doppler ultrasound are similar, although they do not permit a quantitative comparison of the valves. The interpretation of the 90 degrees-component of Doppler signals as a measure of the turbulence permits a quantitative comparison without the need for extensive measurements. However, only large vortices are recorded, so that our turbulent shear stresses are lower than these reported in the literature. The pressure drop across the opened valve is a measure of the energy loss, and important parameters for the valve can be derived from it. The pressure drop is dependent on the test conditions, and is therefore not a characteristic constant of the valve. The transformation of the power law Q = C delta P beta into a relation between Re- and Eu-number gives a nondimensional similarity number that is characteristic for tilting disc valves. Its verification requires more investigations, involving variation of valve size and the viscosity of the test fluid.

Blood Flow Velocity↗

Functional similarity between the haemolysins of Escherichia coli and Morganella morganii.

Haemolysin produced by a clinical isolate of Morganella morganii was examined for antigenic relatedness to the haemolysin of Escherichia coli and for similarities in mode of action. The M. morganii haemolysin migrated in SDS-PAGE as a single protein band with a slightly higher molecular weight than that of E. coli haemolysin. Several murine monoclonal antibodies against E. coli haemolysin cross-reacted with the M. morganii haemolysin in Western blots. Diminished haemolysis in the presence of osmotically-stabilising solutes indicated the formation of a pore by M. morganii haemolysin with an effective diameter of 1.5-3 nm. Results from dose-response experiments indicated that a single "hit" was sufficient for lysis of an erythrocyte. Detergent solubilisation of toxin-treated membranes led to recovery of bound toxin exclusively in monomeric form. M. morganii haemolysin was a potent leucocidin, that caused rapid leakage of ATP and death of human polymorphonuclear leucocytes. Under in-vitro conditions M. morganii haemolysin displayed similar leucocidal and haemolytic efficiency. The data demonstrate that M. morganii haemolysin shows functional properties virtually identical with those of E. coli haemolysin.

Adenosine Triphosphate↗

Regional distribution of calcitonin gene-related peptide-, substance P-, cholecystokinin-, Met5-enkephalin-, and dynorphin A (1-8)-like materials in the spinal cord and dorsal root ganglia of adult rats: effects of dorsal rhizotomy and neonatal capsaicin.

Biochemical mapping of five different peptide-like materials--calcitonin gene-related peptide (CGRP), substance P (SP), Met5-enkephalin (ME), cholecystokinin (CCK), and dynorphin A (1-8) (DYN)--was conducted in the dorsal and ventral zones of the spinal cord at the cervical, thoracic, and lumbar levels in 3-month-old rats 10 days after unilateral dorsal rhizotomy at the cervical level (C4-T2) or after neonatal administration of capsaicin (50 mg/kg s.c.). In control rats, all peptide-like materials were more abundant in the dorsal than in the ventral zone all along the spinal cord. However, in both zones, absolute concentrations of CGRP, SP, ME, and CCK were significantly higher at the lumbar than at the cervical level. Rhizotomy-induced CGRP depletion (-85%) within the ipsilateral dorsal zone of the cervical cord was more pronounced than that due to neonatal capsaicin (-60%), a finding suggesting that this peptide is contained in both capsaicin-sensitive (mostly unmyelinated) and -insensitive (myelinated) primary afferent fibers. In contrast, similar depletions of SP (-50%) were observed after dorsal rhizotomy and neonatal capsaicin treatment, as expected from the presence of SP only in the capsaicin-sensitive small-diameter primary afferent fibers. Although the other three peptides remained unaffected all along the cord by either intervention, evidence for the existence of capsaicin-insensitive CCKergic primary afferent fibers could be inferred from the increased accumulation of CCK (together with SP and CGRP) in dorsal root ganglia ipsilateral to dorsal root sections.

Afferent Pathways↗

Localisation of the origin of self-sustained after-discharges (SSADs) in the rat: the serrated wave (SerW) type of SSAD.

The self-sustained after-discharges (SSADs) characterised by the EEG pattern of serrated waves (SerW) were induced by rhythmic low frequency electrical stimulation of thalamic nuclei and the hippocampus of Wistar albino male rats in acute experiments. We used spreading depression to eliminate functionally the cortex and the hippocampus. Suction ablation of the cortical somatosensory projection area was also used to test its involvement in the SerW SSAD induction. The hippocampal spreading depression but not the cortical one abolished the SerW SSAD induced by the stimulation of the thalamic nuclei. The animals with the suction ablation of the somatosensory projection area also produced SerW SSADs when the stimulation electrodes were placed in the thalamic ventrobasal complex (in intact animals this stimulation induces spike-and-wave SSADs but not SerW-SSAD). The crucial importance of the hippocampus in the SerW SSAD generation and its possible use as a model of partial seizures with complex symptomatology is discussed.

Animals↗

[Time of extraction and cavity position in in-vitro tests of dentin adhesives].

Cylindrical cavities were prepared in different tooth segments (coronal, cervical and radicular) and at different times (1 hour, 1 day, 1 week and 1 month) after extraction into face-ground dentin surfaces of extracted teeth. The cavities were filled with composite resin materials using different dentin adhesives. Before and after thermocycling (TC) the marginal adaptation was evaluated using defined criteria. The statistical evaluation did not show any significant differences (p greater than 0.01) after TC within the different groups of dentin adhesives. For in vitro tests of dentin adhesives neither the position nor the time of extraction decisively influences the process.

Composite Resins↗

Neonatal capsaicin treatment abolishes the modulations by opioids of substance P release from rat spinal cord slices.

The possible modulation by opioids of substance P (SP) release at the spinal level was studied using slices of the dorsal half of the rat lumbar enlargement superfused with an artificial cerebrospinal fluid. Capsaicin (0.5 microM) selectively evoked a Ca2+-dependent overflow of SP-like material (SPLI) from primary afferent fibers which was enhanced in the presence of mu-opioid agonists (DAGO, FK 33824, sufentanyl, morphine), reduced by the delta-opioid agonist DTLET, and unaltered by the kappa-opioid agonist U 50488 H. Selective antagonists (naloxone, ICI 154129) prevented the effects of mu- and delta-opioid agonists. Neonatal capsaicin (50 mg/kg) abolished the stimulatory effect of in vitro capsaicin (0.5 microM) but not that of 30 mM K+ on SPLI outflow. This K+-induced SPLI release was unaffected by opioids. Presynaptic inhibitory control of SPLI release from capsaicin-sensitive primary afferent fibers might account for the analgesic effect of delta- but not mu- and kappa-opioid agonists at the spinal level.

Animals↗

Opioid control of the in vitro release of calcitonin gene-related peptide from primary afferent fibres projecting in the rat cervical cord.

In vitro superfusion of slices from the dorsal half of the rat cervical enlargement allowed the measurement of spontaneous, K+ (30 mM)- and capsaicin (0.5 microM)-evoked release of calcitonin gene-related peptide-like immunoreactive material (CGRPLI). The greater part of this immunoreactive material originated in primary afferent fibres since dorsal rhizotomy from C4 to Th2 (8 days before sacrifice) resulted in a 85-90% decrease in CGRPLI release. CGRPLI outflow which persisted after dorsal rhizotomy could still be enhanced by K+-induced depolarization but was no longer sensitive to the stimulatory effect of 0.5 microM capsaicin. Both delta (DTLET, D-Pen2-D-Pen5-enkephalin) and mu (DAGO, PL 017) opioid receptor agonists reduced the K+ evoked release of CGRPLI from the dorsal half of the cervical enlargement. Morphine was also inhibitory but the selective K opioid agonist U 69593 was inactive. As expected from the involvement of delta and mu receptors, the selective opioid antagonist ICI 174864 and naloxone prevented the inhibitory effects of DTLET and DAGO, respectively. These data suggest that opioid-induced presynaptic inhibiton of CGRP-containing primary afferent fibres may be involved in the analgesic effect of intrathecally injected delta and mu opioid agonists in rats.

Afferent Pathways↗

Direct stimulatory effect of calcitonin on [3H]5-hydroxytryptamine release from the rat spinal cord.

The in vitro effects of porcine, salmon and human calcitonin on the K+-evoked overflow of [Met5]enkephalin, substance P and [3H]5-HT (previously taken up) were investigated in superfusion experiments with spinal cord slices. Porcine and salmon calcitonin did not affect the release of [Met5]enkephalin and substance P but enhanced that of [3H]5-HT. In contrast, human calcitonin was inactive. The stimulatory effect of porcine and salmon calcitonin on K+-evoked [3H]5-HT overflow was found with slices from the dorsal or the ventral half of the lumbar enlargement but not with hippocampal or hypothalamic slices. The calcitonin effect on [3H]5-HT outflow persisted in the absence of extracellular Ca2+ but was totally suppressed by 5-HT uptake inhibitors such as citalopram and chlorimipramine and by the 5-HT-releasing agent, p-chloroamphetamine. Direct investigation of the possible action of porcine calcitonin on [3H]5-HT uptake and release demonstrated that the enhanced [3H]5-HT overflow resulted from a p-chloramphetamine-like 5-HT-releasing effect of the hormone at the spinal level. This action might be involved in the potent analgesic effect of intrathecal calcitonin.

Animals↗