Biomedical subjects
P Forster
Publications and source records attributed to P Forster.
Selective inactivation of viruses in the presence of human platelets: UV sensitization with psoralen derivatives.
Inactivation of viruses in blood products requires that the method employed display selectivity in its action for viral elements while not affecting the biological entity of interest. Several methods have been developed for the treatment of human plasma or products derived from human plasma. An effective technique for the treatment of the cellular components of blood has been lacking, in part due to the inability to develop agents capable of selectively targeting viral agents in the milieu of cellular material. In this paper, we examine the behavior of a group of viral sensitizers designed to be added to cellular samples and be activated upon exposure to UVA light. Upon activation, these agents are capable of disrupting nucleic acids of the virus in a manner that renders them inactive for proliferation. The selectivity observed in this inactivation is determined by the chemical structure of the sensitizer, which can be varied to increase viral killing capacity while diminishing collateral damage to cellular and protein constituents.
Fluoxetine for premature ejaculation.
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Definitive treatment of patients with serious mental disorders in an emergency service, Part II.
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Definitive treatment of patients with serious mental disorders in an emergency service, Part I.
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An optimized electroporation protocol applicable to a wide range of cell lines.
A number of transfection methods for mammalian cells are available; however, many cell lines may appear resistant to efficient transfection, or at best, necessitate lengthy optimization procedures in recommended protocols. We describe here an electroporation protocol that yields highly efficient gene transfer (20%-100% of surviving cells) in all 19 cell lines tested so far, including lymphoid, myeloid, glial, fibroblast and COS cells. Unlike earlier electroporation protocols, adaptation of this protocol to a cell line of interest only requires the optimization of a single parameter, i.e., the voltage, and can be performed within a day. Furthermore, it is also superior to transfection protocols for other methods (calcium phosphate precipitation, lipofection, DEAE-dextran transfection and transferrinfection) in terms of reproducibility, economy and average transfection efficiency for a wide variety of cell lines.
Medicine in Europe. Equal opportunities: progress so far.
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Actions of capsaicin on peripheral nociceptors of the neonatal rat spinal cord-tail in vitro: dependence of extracellular ions and independence of second messengers.
1. We have tested the hypothesis that capsaicin-induced activation, desensitization and impairment of peripheral nociceptor function is mediated by separate mechanisms. This was investigated by use of an in vitro preparation of the neonatal rat spinal cord with the functionally attached tail in which the cord and tail were separately superfused with physiological solution. Activation of peripheral fibres by noxious (capsaicin, bradykinin, 5-hydroxytrptamine, heat, pinch) and innocuous (light brush) stimuli was assessed by recording the depolarization of a spinal ventral root (L3-L5). 2. Brief administration of capsaicin produced dose-related depolarizing responses (EC50 = 280 nM). These responses could be reproduced for many hours following the repeated application of capsaicin at a submaximal concentration. Prolonged application of 0.5-2.0 microM capsaicin induced a selective desensitization to subsequent brief administrations of capsaicin. Prolonged administration at 20-50 microM produced an additional non-selective reduction in responses to all noxious stimuli without changing innocuous brush responses. 3. Removal of extracellular calcium from the tail superfusate did not reduce the response to capsaicin or prevent capsaicin-induced desensitization. However, high concentrations of capsaicin no longer induced a non-specific reduction of responses to other noxious stimuli. The response to a brief administration of capsaicin was unaffected by calcium channel blocking drugs including nifedipine, cadmium or omega-conotoxin. On the other hand high extracellular calcium increased the incidence of the non-selective reduction of responses to all noxious stimuli produced by high concentrations of capsaicin. 4. Replacement of extracellular sodium with choline blocked peripheral nerve conduction but did not prevent the desensitization produced by capsaicin. In addition, high concentrations of capsaicin were less effective in reducing the responsiveness to other noxious stimuli. 5. Neither capsaicin-evoked responses nor capsaicin-induced desensitization were affected by the administration of forskolin, dibutyryl cyclic AMP, nitroprusside, dibutyryl cyclic GMP, beta-12,13 phorbol dibutyrate, trifluoperazine, indomethacin, staurosporine or mepacrine, in the tail superfusate. 6. These data suggest that capsaicin-induced activation, desensitization and impairment of peripheral nociceptors may be separable phenomena. Extracellular calcium is not required for capsaicin-induced activation or desensitization but calcium as well as sodium are important for capsaicin-induced impairment of nociceptive responses. Desensitization may occur independently of peripheral fibre activation and cannot be attributed to a central mechanism. Finally neither capsaicin-induced activation nor desensitization require the participation of a second messenger.
Resiniferatoxin, a potent capsaicin-like stimulator of peripheral nociceptors in the neonatal rat tail in vitro.
1. A spinal ventral root response was measured following the activation of peripheral fibres by noxious (heat at 48 degrees C, capsaicin, bradykinin) and innocuous (brush) stimuli in a preparation of the neonatal rat spinal cord-tail maintained in vitro. 2. Following superfusion of the tail with 0.1-1.0 nM of the potent irritant, resiniferatoxin (RTX), brief, irregular depolarization and a selective loss of capsaicin sensitivity was produced. RTX 10-100 nM evoked a tonic response, initiated transient irregular depolarizations and densitization to further applications of RTX and capsaicin but not to other stimuli. Following RTX 1 microM a prolonged loss of sensitivity to all noxious stimuli was produced. 3. When a selective densitization to capsaicin was produced by a long application of capsaicin, RTX was also ineffective. 4. Superfusion of the tail with 4 beta-phorbol, 12, 13-dibutyrate (PDBu), a protein kinase C activator, stimulated capsaicin-sensitive peripheral fibres. Prolonged administration of PDBu attenuated or abolished further responses to PDBu and bradykinin but responses to RTX and capsaicin were unchanged. The protein kinase C inhibitor staurosporine (50-200 nM), attenuated the effects of PDBu and bradykinin but not those of RTX or capsaicin. 5. The present data suggest that neither RTX nor capsaicin act on peripheral nociceptors via a phorbol ester-like stimulation of protein kinase C. Rather, RTX acts on nociceptors by a similar mechanism to capsaicin. These effects may be the basis for the irritant properties of RTX and may further relate to the antinociceptive actions observed in vivo. RTX is therefore a potent new tool with which to investigate the properties of nociceptive neurones and provides a prototype for further development of antinociceptive agents.
In defence of casualty departments.
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Capsaicin desensitization of peripheral nociceptive fibres does not impair sensitivity to other noxious stimuli.
Capsaicin was tested on peripheral fibres in vitro to determine whether evoked depolarization or desensitization were likely to explain the antinociception observed after acute systemic capsaicin in vivo. The activation of peripheral fibres by noxious (capsaicin, bradykinin, heat) and innocuous (light brush) stimuli was recorded as a depolarization of a spinal ventral root (L3-L5) in the neonatal rat spinal cord with attached tail. Prolonged superfusion of the tail with low doses (0.2-2 microM) of capsaicin produced a short lasting depolarization followed by a complete loss of sensitivity to capsaicin without changes in sensitivity to other noxious or innocuous stimuli. Partial recovery from this selective desensitization could be observed 3-5 h later. In most preparations superfusion of the tail with 20 microM capsaicin produced a prolonged and non-selective impairment of sensitivity to all noxious stimuli. These data suggest that neither depolarization by capsaicin nor the selective desensitization of peripheral fibres to capsaicin are likely to account for the acute antinociceptive effect of systemic capsaicin. On the other hand the non-selective reduction in sensitivity to noxious stimuli induced by capsaicin may contribute to its antinociceptive action.
Bradykinin-induced stimulation of afferent fibres is mediated through protein kinase C.
In an in vitro preparation of the neonatal spinal cord with the tail attached, brief administration of bradykinin or capsaicin in the tail superfusate containing a normal calcium concentration, activated peripheral fibres and produced a depolarization recorded at a spinal ventral root (L3-L5). Perfusion with a phorbol ester (4 beta-phorbol 12,13-dibutyrate, PDBu) produced a small and inconsistent activation of peripheral fibres. In subsequent experiments calcium was omitted from the tail superfusate since under this condition responses to bradykinin and capsaicin were unchanged but PDBu evoked reproducible depolarization when applied at intervals of 60 min or more. Prolonged desensitization followed repeated administration at shorter intervals. Pretreatment of the tail with capsaicin, to impair transmission in C-fibres, abolished the effect of each agonist. Inactivation of protein kinase C with the inhibitor staurosporine (10-100 nM) attenuated the effect of bradykinin and PDBu but not that of capsaicin. Pretreatment with PDBu also attenuated the effect of bradykinin. These data suggest that a phorbol ester and bradykinin stimulate capsaicin-sensitive C-fibres by a mechanism which involves the activation of protein kinase C.
Activation of a bradykinin receptor in peripheral nerve and spinal cord in the neonatal rat in vitro.
In an in vitro preparation of the neonatal rat spinal cord with attached tail, administration of bradykinin (Bk) to the spinal cord or to the tail produced depolarization of a ventral root (L3-L5). The effect of Bk at each site was selectively and reversibly antagonized by D-Arg [Hyp2, Thi5,8 D-Phe7]-Bk but could not be mimicked or antagonized by the B1-receptor ligands [des-Arg9]-Bk or Leu8[des-Arg9]-Bk, respectively. Peripherally evoked noxious responses produced by capsaicin or heat, were unaffected by either antagonist administered to the spinal cord. These data suggest that Bk-evoked responses in the spinal cord and at peripheral nociceptors were mediated via a receptor which by definition is of the B2-type. Additionally Bk is unlikely to be a physiological mediator of acute nociception in the spinal cord.
Purine effects on (3H)-clonidine binding to rat brain.
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Reproducibility of individual response to exposure to high altitude.
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Peak expiratory flow rate at high altitude.
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Methazolamide in acute mountain sickness.
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