The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
Stephan Schmidt - One of the best experts on this subject based on the ideXlab platform.
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development of a mechanism based pharmacokinetic pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice
Acta Pharmaceutica Sinica B, 2016Co-Authors: Xi Ling Jiang, Hong Wu Shen, Donald E. Mager, Stephan SchmidtAbstract:We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)-induced Hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. Harmaline-induced hypothermia and 5-MeO-DMT-elicited Hyperthermia were attributable to the loss of heat through the activation of 5-HT1A receptor and thermogenesis via the stimulation of 5-HT2A receptor, respectively. Thus serotonergic 5-MeO-DMT-induced Hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. This PK/PD model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-MeO-DMT and harmaline PK properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results revealed a 4-fold decrease of apparent SC50 value (1.88-0.496 µmol/L) for 5-MeO-DMT when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent MAOI harmaline on 5-MeO-DMT-induced Hyperthermia. In addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5-MeO-DMT, although the body temperature profiles were mispredicted by the model. The results indicate that current PK/PD model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation.
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Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice
Acta pharmaceutica Sinica. B, 2016Co-Authors: Xi Ling Jiang, Hong Wu Shen, Donald E. Mager, Stephan SchmidtAbstract:We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)-induced Hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. Harmaline-induced hypothermia and 5-MeO-DMT-elicited Hyperthermia were attributable to the loss of heat through the activation of 5-HT1A receptor and thermogenesis via the stimulation of 5-HT2A receptor, respectively. Thus serotonergic 5-MeO-DMT-induced Hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. This PK/PD model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-MeO-DMT and harmaline PK properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results revealed a 4-fold decrease of apparent SC50 value (1.88-0.496 µmol/L) for 5-MeO-DMT when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent MAOI harmaline on 5-MeO-DMT-induced Hyperthermia. In addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5-MeO-DMT, although the body temperature profiles were mispredicted by the model. The results indicate that current PK/PD model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation.
Peter Wust - One of the best experts on this subject based on the ideXlab platform.
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Hyperthermia related clinical trials on cancer treatment within the clinicaltrials gov registry
International Journal of Hyperthermia, 2015Co-Authors: Nikola Cihoric, Jacek Nadobny, Alexandros Tsikkinis, Gerard C Van Rhoon, Hans Crezee, Daniel M Aebersold, Stephan Bodis, Marcus Beck, Volker Budach, Peter WustAbstract:AbstractPurpose: Hyperthermia has been shown to improve the effectiveness of chemotherapy and radiotherapy in the treatment of cancer. This paper summarises all recent clinical trials registered in the ClinicalTrials.gov registry. Materials and methods: The records of 175,538 clinical trials registered at ClinicalTrials.gov were downloaded on 29 September 2014 and a database was established. We searched this database for Hyperthermia or equivalent words. Results: A total of 109 trials were identified in which Hyperthermia was part of the treatment regimen. Of these, 49 trials (45%) had hyperthermic intraperitoneal chemotherapy after cytoreductive surgery (HIPEC) as the primary intervention, and 14 other trials (13%) were also testing some form of intraperitoneal hyperthermic chemoperfusion. Seven trials (6%) were testing perfusion attempts to other locations (thoracic/pleural n = 4, limb n = 2, hepatic n = 1). Sixteen trials (15%) were testing regional Hyperthermia, 13 trials (12%) whole body Hyperthermia...
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Standards and perspectives in locoregional Hyperthermia
Wiener medizinische Wochenschrift (1946), 2004Co-Authors: Bert Hildebrandt, Beate Rau, Johanna Gellermann, Thoralf Kerner, Annett Nicolaou, Jens-uwe Blohmer, Ralf Ulrich Trappe, Hanno Riess, Peter WustAbstract:The term "Hyperthermia" summarises different procedures of raising the temperature of a tumour-loaded tissue to a temperature of 40-43 degrees C. In this context, locoregional procedures (radiative/capacitive local, interstitial and regional Hyperthermia; endoluminal Hyperthermia), hyperthermic perfusion techniques (hyperthermic peritoneal and isolated limb perfusion), and whole-body Hyperthermia differ with regard to their indication, expenditure of application, and evidence of efficacy. All Hyperthermia techniques have in common that they have no sufficient antineoplastic activity alone in the temperature range below 43-45 degrees C, but act in a synergistic way with radiotherapy and certain cytotoxic drugs. 14 out of 18 published randomised trials on Hyperthermia as an adjunct to standard radio- or chemotherapy refer to locoregional approaches. Particular progress has been made in regional radiofrequency Hyperthermia, where novel multiantenna-applicators and their integration into MR-applicators ("hybrid-systems") have recently been introduced into clinical practice. In addition, combinations of Hyperthermia with novel technologies (magnetic fluid Hyperthermia, thermosensitive liposomes, immunotherapy, gene targeting) are imminent. We here give a critical update on the proven indications of the different locoregional Hyperthermia approaches and on the current clinical and technological progress in this field.
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the cellular and molecular basis of Hyperthermia
Critical Reviews in Oncology Hematology, 2002Co-Authors: Bert Hildebrandt, Thoralf Kerner, Peter Wust, Olaf Ahlers, Annette Dieing, Geetha Sreenivasa, R Felix, Hanno RiessAbstract:Abstract In oncology, the term ‘Hyperthermia’ refers to the treatment of malignant diseases by administering heat in various ways. Hyperthermia is usually applied as an adjunct to an already established treatment modality (especially radiotherapy and chemotherapy), where tumor temperatures in the range of 40–43 °C are aspired. In several clinical phase-III trials, an improvement of both local control and survival rates have been demonstrated by adding local/regional Hyperthermia to radiotherapy in patients with locally advanced or recurrent superficial and pelvic tumors. In addition, interstitial Hyperthermia, hyperthermic chemoperfusion, and whole-body Hyperthermia (WBH) are under clinical investigation, and some positive comparative trials have already been completed. In parallel to clinical research, several aspects of heat action have been examined in numerous pre-clinical studies since the 1970s. However, an unequivocal identification of the mechanisms leading to favorable clinical results of Hyperthermia have not yet been identified for various reasons. This manuscript deals with discussions concerning the direct cytotoxic effect of heat, heat-induced alterations of the tumor microenvironment, synergism of heat in conjunction with radiation and drugs, as well as, the presumed cellular effects of Hyperthermia including the expression of heat-shock proteins (HSP), induction and regulation of apoptosis, signal transduction, and modulation of drug resistance by Hyperthermia.
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The cellular and molecular basis of Hyperthermia.
Critical reviews in oncology hematology, 2002Co-Authors: Bert Hildebrandt, Thoralf Kerner, Peter Wust, Olaf Ahlers, Annette Dieing, Geetha Sreenivasa, R Felix, Hanno RiessAbstract:In oncology, the term 'Hyperthermia' refers to the treatment of malignant diseases by administering heat in various ways. Hyperthermia is usually applied as an adjunct to an already established treatment modality (especially radiotherapy and chemotherapy), where tumor temperatures in the range of 40-43 degrees C are aspired. In several clinical phase-III trials, an improvement of both local control and survival rates have been demonstrated by adding local/regional Hyperthermia to radiotherapy in patients with locally advanced or recurrent superficial and pelvic tumors. In addition, interstitial Hyperthermia, hyperthermic chemoperfusion, and whole-body Hyperthermia (WBH) are under clinical investigation, and some positive comparative trials have already been completed. In parallel to clinical research, several aspects of heat action have been examined in numerous pre-clinical studies since the 1970s. However, an unequivocal identification of the mechanisms leading to favorable clinical results of Hyperthermia have not yet been identified for various reasons. This manuscript deals with discussions concerning the direct cytotoxic effect of heat, heat-induced alterations of the tumor microenvironment, synergism of heat in conjunction with radiation and drugs, as well as, the presumed cellular effects of Hyperthermia including the expression of heat-shock proteins (HSP), induction and regulation of apoptosis, signal transduction, and modulation of drug resistance by Hyperthermia.
E. Chojnacka-wójcik - One of the best experts on this subject based on the ideXlab platform.
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Hyperthermia induced bym-trifluoromethylphenylpiperazine (TFMPP) orm-chlorophenylpiperazine (m-CPP) in heat-adapted rats
Psychopharmacology, 1992Co-Authors: A. Kłodzińska, E. Chojnacka-wójcikAbstract:TFMPP and m -CPP, non-selective 5-HT agonists, administered in doses of 1–20 mg/kg evoked Hyperthermia in rats at a high ambient temperature (28°C). The hyperthermic effect of TFMPP (10 mg/kg) or m -CPP (10 mg/kg) was dose-dependently antagonized by the 5-HT_1c and 5-HT_2 receptor antagonists mesulergine (0.5–4 mg/kg), ketanserin (0.6–2.5 mg/kg) and ritanserin (0.5–2 mg/kg) and by the non-selective 5-HT antagonist metergoline (0.5–1 mg/kg), or was attenuated by the 5-HT_1A, 5-HT_2 and dopamine receptor antagonist spiperone (3 mg/kg, but not 0.3 or 1 mg/kg). On the other hand, the 5-HT_1A, 5-HT_1B and β adrenoceptor antagonists pindolol (2 mg/kg) and cyanopindolol (2 mg/kg), the 5-HT_1A receptor agonist/antagonist ipsapirone (10 and 35 mg/kg) and haloperidol (0.25 and 0.5 mg/kg) showed a tendency towards enhancing the TFMPP- or m -CPP-induced Hyperthermia. The 5-HT_1A and α_1-adrenoceptor antagonist NAN-190 (1–4 mg/kg), the 5-HT_3 antagonists tropisetron (0.01–1 mg/kg) and zacopride (0.5 and 1 mg/kg), the β -blockers betaxolol (8 mg/kg) and ICI 118, 551 (8 mg/kg), which have no affinity for 5-HT receptors and prazosin (1 mg/kg), did not affect the hyperthermic effect of TFMPP or m -CPP. The Hyperthermias studied were not modified, in animals with 5-HT lesion produced by p -chloroamphetamine (PCA) either. All the drugs used as putative receptor antagonists, as well as PCA, did not change or decreased (ipsapirone) the body temperature in heat-adapted rats. The obtained results suggest that the Hyperthermia induced by TFMPP or m -CPP is mediated by 5-HT_2, and maybe also by 5-HT_1c receptors — those which are located postsynaptically.
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Hyperthermia induced by m-trifluoromethylphenylpiperazine (TFMPP) or m-chlorophenylpiperazine (m-CPP) in heat-adapted rats.
Psychopharmacology, 1992Co-Authors: A. Kłodzińska, E. Chojnacka-wójcikAbstract:TFMPP andm-CPP, non-selective 5-HT agonists, administered in doses of 1–20 mg/kg evoked Hyperthermia in rats at a high ambient temperature (28°C). The hyperthermic effect of TFMPP (10 mg/kg) orm-CPP (10 mg/kg) was dose-dependently antagonized by the 5-HT1c and 5-HT2 receptor antagonists mesulergine (0.5–4 mg/kg), ketanserin (0.6–2.5 mg/kg) and ritanserin (0.5–2 mg/kg) and by the non-selective 5-HT antagonist metergoline (0.5–1 mg/kg), or was attenuated by the 5-HT1A, 5-HT2 and dopamine receptor antagonist spiperone (3 mg/kg, but not 0.3 or 1 mg/kg). On the other hand, the 5-HT1A, 5-HT1B andβ adrenoceptor antagonists pindolol (2 mg/kg) and cyanopindolol (2 mg/kg), the 5-HT1A receptor agonist/antagonist ipsapirone (10 and 35 mg/kg) and haloperidol (0.25 and 0.5 mg/kg) showed a tendency towards enhancing the TFMPP- orm-CPP-induced Hyperthermia. The 5-HT1A and α1-adrenoceptor antagonist NAN-190 (1–4 mg/kg), the 5-HT3 antagonists tropisetron (0.01–1 mg/kg) and zacopride (0.5 and 1 mg/kg), theβ-blockers betaxolol (8 mg/kg) and ICI 118, 551 (8 mg/kg), which have no affinity for 5-HT receptors and prazosin (1 mg/kg), did not affect the hyperthermic effect of TFMPP orm-CPP. The Hyperthermias studied were not modified, in animals with 5-HT lesion produced byp-chloroamphetamine (PCA) either. All the drugs used as putative receptor antagonists, as well as PCA, did not change or decreased (ipsapirone) the body temperature in heat-adapted rats. The obtained results suggest that the Hyperthermia induced by TFMPP orm-CPP is mediated by 5-HT2, and maybe also by 5-HT1c receptors — those which are located postsynaptically.
Xi Ling Jiang - One of the best experts on this subject based on the ideXlab platform.
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development of a mechanism based pharmacokinetic pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice
Acta Pharmaceutica Sinica B, 2016Co-Authors: Xi Ling Jiang, Hong Wu Shen, Donald E. Mager, Stephan SchmidtAbstract:We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)-induced Hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. Harmaline-induced hypothermia and 5-MeO-DMT-elicited Hyperthermia were attributable to the loss of heat through the activation of 5-HT1A receptor and thermogenesis via the stimulation of 5-HT2A receptor, respectively. Thus serotonergic 5-MeO-DMT-induced Hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. This PK/PD model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-MeO-DMT and harmaline PK properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results revealed a 4-fold decrease of apparent SC50 value (1.88-0.496 µmol/L) for 5-MeO-DMT when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent MAOI harmaline on 5-MeO-DMT-induced Hyperthermia. In addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5-MeO-DMT, although the body temperature profiles were mispredicted by the model. The results indicate that current PK/PD model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation.
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Development of a mechanism-based pharmacokinetic/pharmacodynamic model to characterize the thermoregulatory effects of serotonergic drugs in mice
Acta pharmaceutica Sinica. B, 2016Co-Authors: Xi Ling Jiang, Hong Wu Shen, Donald E. Mager, Stephan SchmidtAbstract:We have shown recently that concurrent harmaline, a monoamine oxidase-A inhibitor (MAOI), potentiates serotonin (5-HT) receptor agonist 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)-induced Hyperthermia. The objective of this study was to develop an integrated pharmacokinetic/pharmacodynamic (PK/PD) model to characterize and predict the thermoregulatory effects of such serotonergic drugs in mice. Physiological thermoregulation was described by a mechanism-based indirect-response model with adaptive feedback control. Harmaline-induced hypothermia and 5-MeO-DMT-elicited Hyperthermia were attributable to the loss of heat through the activation of 5-HT1A receptor and thermogenesis via the stimulation of 5-HT2A receptor, respectively. Thus serotonergic 5-MeO-DMT-induced Hyperthermia was readily distinguished from handling/injection stress-provoked hyperthermic effects. This PK/PD model was able to simultaneously describe all experimental data including the impact of drug-metabolizing enzyme status on 5-MeO-DMT and harmaline PK properties, and drug- and stress-induced simple hypo/hyperthermic and complex biphasic effects. Furthermore, the modeling results revealed a 4-fold decrease of apparent SC50 value (1.88-0.496 µmol/L) for 5-MeO-DMT when harmaline was co-administered, providing a quantitative assessment for the impact of concurrent MAOI harmaline on 5-MeO-DMT-induced Hyperthermia. In addition, the hyperpyrexia caused by toxic dose combinations of harmaline and 5-MeO-DMT were linked to the increased systemic exposure to harmaline rather than 5-MeO-DMT, although the body temperature profiles were mispredicted by the model. The results indicate that current PK/PD model may be used as a new conceptual framework to define the impact of serotonergic agents and stress factors on thermoregulation.
A. Kłodzińska - One of the best experts on this subject based on the ideXlab platform.
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Hyperthermia induced bym-trifluoromethylphenylpiperazine (TFMPP) orm-chlorophenylpiperazine (m-CPP) in heat-adapted rats
Psychopharmacology, 1992Co-Authors: A. Kłodzińska, E. Chojnacka-wójcikAbstract:TFMPP and m -CPP, non-selective 5-HT agonists, administered in doses of 1–20 mg/kg evoked Hyperthermia in rats at a high ambient temperature (28°C). The hyperthermic effect of TFMPP (10 mg/kg) or m -CPP (10 mg/kg) was dose-dependently antagonized by the 5-HT_1c and 5-HT_2 receptor antagonists mesulergine (0.5–4 mg/kg), ketanserin (0.6–2.5 mg/kg) and ritanserin (0.5–2 mg/kg) and by the non-selective 5-HT antagonist metergoline (0.5–1 mg/kg), or was attenuated by the 5-HT_1A, 5-HT_2 and dopamine receptor antagonist spiperone (3 mg/kg, but not 0.3 or 1 mg/kg). On the other hand, the 5-HT_1A, 5-HT_1B and β adrenoceptor antagonists pindolol (2 mg/kg) and cyanopindolol (2 mg/kg), the 5-HT_1A receptor agonist/antagonist ipsapirone (10 and 35 mg/kg) and haloperidol (0.25 and 0.5 mg/kg) showed a tendency towards enhancing the TFMPP- or m -CPP-induced Hyperthermia. The 5-HT_1A and α_1-adrenoceptor antagonist NAN-190 (1–4 mg/kg), the 5-HT_3 antagonists tropisetron (0.01–1 mg/kg) and zacopride (0.5 and 1 mg/kg), the β -blockers betaxolol (8 mg/kg) and ICI 118, 551 (8 mg/kg), which have no affinity for 5-HT receptors and prazosin (1 mg/kg), did not affect the hyperthermic effect of TFMPP or m -CPP. The Hyperthermias studied were not modified, in animals with 5-HT lesion produced by p -chloroamphetamine (PCA) either. All the drugs used as putative receptor antagonists, as well as PCA, did not change or decreased (ipsapirone) the body temperature in heat-adapted rats. The obtained results suggest that the Hyperthermia induced by TFMPP or m -CPP is mediated by 5-HT_2, and maybe also by 5-HT_1c receptors — those which are located postsynaptically.
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Hyperthermia induced by m-trifluoromethylphenylpiperazine (TFMPP) or m-chlorophenylpiperazine (m-CPP) in heat-adapted rats.
Psychopharmacology, 1992Co-Authors: A. Kłodzińska, E. Chojnacka-wójcikAbstract:TFMPP andm-CPP, non-selective 5-HT agonists, administered in doses of 1–20 mg/kg evoked Hyperthermia in rats at a high ambient temperature (28°C). The hyperthermic effect of TFMPP (10 mg/kg) orm-CPP (10 mg/kg) was dose-dependently antagonized by the 5-HT1c and 5-HT2 receptor antagonists mesulergine (0.5–4 mg/kg), ketanserin (0.6–2.5 mg/kg) and ritanserin (0.5–2 mg/kg) and by the non-selective 5-HT antagonist metergoline (0.5–1 mg/kg), or was attenuated by the 5-HT1A, 5-HT2 and dopamine receptor antagonist spiperone (3 mg/kg, but not 0.3 or 1 mg/kg). On the other hand, the 5-HT1A, 5-HT1B andβ adrenoceptor antagonists pindolol (2 mg/kg) and cyanopindolol (2 mg/kg), the 5-HT1A receptor agonist/antagonist ipsapirone (10 and 35 mg/kg) and haloperidol (0.25 and 0.5 mg/kg) showed a tendency towards enhancing the TFMPP- orm-CPP-induced Hyperthermia. The 5-HT1A and α1-adrenoceptor antagonist NAN-190 (1–4 mg/kg), the 5-HT3 antagonists tropisetron (0.01–1 mg/kg) and zacopride (0.5 and 1 mg/kg), theβ-blockers betaxolol (8 mg/kg) and ICI 118, 551 (8 mg/kg), which have no affinity for 5-HT receptors and prazosin (1 mg/kg), did not affect the hyperthermic effect of TFMPP orm-CPP. The Hyperthermias studied were not modified, in animals with 5-HT lesion produced byp-chloroamphetamine (PCA) either. All the drugs used as putative receptor antagonists, as well as PCA, did not change or decreased (ipsapirone) the body temperature in heat-adapted rats. The obtained results suggest that the Hyperthermia induced by TFMPP orm-CPP is mediated by 5-HT2, and maybe also by 5-HT1c receptors — those which are located postsynaptically.
