The Experts below are selected from a list of 3648 Experts worldwide ranked by ideXlab platform
Walter R Hasibeder - One of the best experts on this subject based on the ideXlab platform.
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sympathetic Overstimulation during critical illness adverse effects of adrenergic stress
Journal of Intensive Care Medicine, 2009Co-Authors: Martin W. Dünser, Walter R HasibederAbstract:The term ‘‘adrenergic’’ originates from ‘‘adrenaline’’ and describes hormones or drugs whose effects are similar to those of epinephrine. Adrenergic stress is mediated by stimulation of adrenergic receptors and activation of post-receptor pathways. Critical illness is a potent stimulus of the sympathetic nervous system. It is undisputable that the adrenergic-driven ‘‘fight-flight response’’ is a physiologically meaningful reaction allowing humans to survive during evolution. However, in critical illness an overshooting stimulation of the sympathetic nervous system may well exceed in time and scope its beneficial effects. Comparable to the overwhelming immune response during sepsis, adrenergic stress in critical illness may get out of control and cause adverse effects. Several organ systems may be affected. The heart seems to be most susceptible to sympathetic Overstimulation. Detrimental effects include impaired diastolic function, tachycardia and tachyarrhythmia, myocardial ischemia, stunning, apoptosis ...
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sympathetic Overstimulation during critical illness adverse effects of adrenergic stress
Journal of Intensive Care Medicine, 2009Co-Authors: Martin W. Dünser, Walter R HasibederAbstract:The term ''adrenergic'' originates from ''adrenaline'' and describes hormones or drugs whose effects are similar to those of epinephrine. Adrenergic stress is mediated by stimulation of adrenergic receptors and activation of post-receptor pathways. Critical illness is a potent stimulus of the sympathetic nervous system. It is undisputable that the adrenergic-driven ''fight-flight response'' is a physiologically meaningful reaction allowing humans to survive during evolution. However, in critical illness an overshooting stimulation of the sympathetic nervous system may well exceed in time and scope its beneficial effects. Comparable to the overwhelming immune response during sepsis, adrenergic stress in critical illness may get out of control and cause adverse effects. Several organ systems may be affected. The heart seems to be most susceptible to sympathetic Overstimulation. Detrimental effects include impaired diastolic function, tachycardia and tachyarrhythmia, myocardial ischemia, stunning, apoptosis and necrosis. Adverse catecholamine effects have been observed in other organs such as the lungs (pulmonary edema, elevated pulmonary arterial pressures), the coagulation (hypercoagulability, thrombus formation), gastrointestinal (hypoperfusion, inhibition of peristalsis), endocrinologic (decreased prolactin, thyroid and growth hormone secretion) and immune systems (immunomodulation, stimulation of bacterial growth), and metabolism (increase in cell energy expenditure, hyperglycemia, catabolism, lipolysis, hyperlactatemia, electrolyte changes), bone marrow (anemia), and skeletal muscles (apoptosis). Potential therapeutic options to reduce excessive adrenergic stress comprise temperature and heart rate control, adequate use of sedative/analgesic drugs, and aiming for reasonable cardiovascular targets, adequate fluid therapy, use of levosimendan, hydrocortisone or supplementary arginine vasopressin.
Martin W. Dünser - One of the best experts on this subject based on the ideXlab platform.
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sympathetic Overstimulation during critical illness adverse effects of adrenergic stress
Journal of Intensive Care Medicine, 2009Co-Authors: Martin W. Dünser, Walter R HasibederAbstract:The term ‘‘adrenergic’’ originates from ‘‘adrenaline’’ and describes hormones or drugs whose effects are similar to those of epinephrine. Adrenergic stress is mediated by stimulation of adrenergic receptors and activation of post-receptor pathways. Critical illness is a potent stimulus of the sympathetic nervous system. It is undisputable that the adrenergic-driven ‘‘fight-flight response’’ is a physiologically meaningful reaction allowing humans to survive during evolution. However, in critical illness an overshooting stimulation of the sympathetic nervous system may well exceed in time and scope its beneficial effects. Comparable to the overwhelming immune response during sepsis, adrenergic stress in critical illness may get out of control and cause adverse effects. Several organ systems may be affected. The heart seems to be most susceptible to sympathetic Overstimulation. Detrimental effects include impaired diastolic function, tachycardia and tachyarrhythmia, myocardial ischemia, stunning, apoptosis ...
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sympathetic Overstimulation during critical illness adverse effects of adrenergic stress
Journal of Intensive Care Medicine, 2009Co-Authors: Martin W. Dünser, Walter R HasibederAbstract:The term ''adrenergic'' originates from ''adrenaline'' and describes hormones or drugs whose effects are similar to those of epinephrine. Adrenergic stress is mediated by stimulation of adrenergic receptors and activation of post-receptor pathways. Critical illness is a potent stimulus of the sympathetic nervous system. It is undisputable that the adrenergic-driven ''fight-flight response'' is a physiologically meaningful reaction allowing humans to survive during evolution. However, in critical illness an overshooting stimulation of the sympathetic nervous system may well exceed in time and scope its beneficial effects. Comparable to the overwhelming immune response during sepsis, adrenergic stress in critical illness may get out of control and cause adverse effects. Several organ systems may be affected. The heart seems to be most susceptible to sympathetic Overstimulation. Detrimental effects include impaired diastolic function, tachycardia and tachyarrhythmia, myocardial ischemia, stunning, apoptosis and necrosis. Adverse catecholamine effects have been observed in other organs such as the lungs (pulmonary edema, elevated pulmonary arterial pressures), the coagulation (hypercoagulability, thrombus formation), gastrointestinal (hypoperfusion, inhibition of peristalsis), endocrinologic (decreased prolactin, thyroid and growth hormone secretion) and immune systems (immunomodulation, stimulation of bacterial growth), and metabolism (increase in cell energy expenditure, hyperglycemia, catabolism, lipolysis, hyperlactatemia, electrolyte changes), bone marrow (anemia), and skeletal muscles (apoptosis). Potential therapeutic options to reduce excessive adrenergic stress comprise temperature and heart rate control, adequate use of sedative/analgesic drugs, and aiming for reasonable cardiovascular targets, adequate fluid therapy, use of levosimendan, hydrocortisone or supplementary arginine vasopressin.
Christian Grasshoff - One of the best experts on this subject based on the ideXlab platform.
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midazolam is effective to reduce cortical network activity in organotypic cultures during severe cholinergic Overstimulation with soman
Toxicology Letters, 2018Co-Authors: Berthold Drexler, Thomas Seeger, Franz Worek, Horst Thiermann, Bernd Antkowiak, Christian GrasshoffAbstract:Abstract Intoxication with organophosphorus compounds can result in life-threatening organ dysfunction and refractory seizures. Sedation or hypnosis is essential to facilitate mechanical ventilation and control seizure activity. The range of indications for midazolam includes both hypnosis and seizure control. Since benzodiazepines cause sedation and hypnosis by dampening neuronal activity of the cerebral cortex, we investigated the drug’s effect on action potential firing of cortical neurons in brain slices. Extensive cholinergic Overstimulation was induced by increasing acetylcholine levels and simultaneously treating the slices with soman to block acetylcholinesterase activity. At control conditions midazolam reduced discharge rates (median/95% confidence interval) from 8.8 (7.0–10.5) Hz (in the absence of midazolam) to 2.2 (1.4–2.9) Hz (10 μM midazolam) and 1.6 (0.9–2.2) Hz (20 μM midazolam). Without midazolam, cholinergic Overstimulation significantly enhanced neuronal activity to 13.1 (11.0–15.2) Hz. Midazolam attenuated firing rates during cholinergic Overstimulation to 6.5 (4.8–8.2) Hz (10 μM midazolam) and 4.1 (3.3–6.0) Hz (20 μM midazolam), respectively. Thus, high cholinergic tone attenuated the drug’s efficacy only moderately. These results suggest that midazolam is worth being tested as a promising drug to induce sedation and hypnosis in patients suffering from severe organophosphorous intoxication.
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anaesthetic potency of diazepam is resistant to cholinergic Overstimulation
Toxicology Letters, 2011Co-Authors: Berthold Drexler, Thomas Seeger, Horst Thiermann, Bernd Antkowiak, Stefan Zinser, Christian GrasshoffAbstract:Abstract Patients suffering from organophosphorus intoxication are compromised by generalised seizures and respiratory insufficiency, either being potentially lethal. In these patients induction of general anaesthesia to allow artificial ventilation is an important therapeutic option. Previously, it has been demonstrated that cholinergic Overstimulation impaired network depressing effects of etomidate and sevoflurane. In this study we tested the impact of cholinergic Overstimulation on inhibitory effects of diazepam in organotypic slice cultures of cerebrocortical neurons. Effects of clinically relevant concentrations of diazepam on spontaneous action potential activity were assessed by extracellular action potential recordings under basal cholinergic tone as well as in the presence of acetylcholine (1 μM). Diazepam at anaesthetic concentrations (25–500 μM) impeded spontaneous network activity in a concentration dependent manner (EC50 80.5 ± 8.0 μM). In the presence of 1 μM acetylcholine the potency of diazepam was not significantly altered (EC50 83.6 ± 8.4 μM). The results demonstrate that the potency of diazepam to depress neocortical network-excitability is not significantly impaired by cholinergic Overstimulation. Diazepam thereby differs from other anaesthetics like etomidate or sevoflurane whose potencies and efficacies were severely attenuated. Hence diazepam might be preferable for induction and maintenance of general anaesthesia in patients suffering from nerve agent intoxication.
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atropine increases sevoflurane potency in cortical but not spinal networks during cholinergic Overstimulation
Toxicology, 2010Co-Authors: Berthold Drexler, Horst Thiermann, Bernd Antkowiak, Christian GrasshoffAbstract:In the event of mass destruction with nerve agents a number of victims can be expected to suffer from symptoms of cholinergic Overstimulation due to intoxication as well as from physical trauma. Since previous studies have demonstrated that cholinesterase inhibitors may reverse general anaesthesia in humans this scenario raises the question of how these patients can be anaesthetised in order to enable surgical interventions. A likely reason for this reversal is a reduction of anaesthetic potency by acetylcholine as observed for volatile anaesthetics in vitro. In order to test whether a combination of cholinergic antagonists with general anaesthetics improves their potency, we investigated the effects of clinically relevant concentrations of atropine on sevoflurane potency in cortical and spinal slice cultures during cholinergic Overstimulation. As the spinal cord and neocortex are important substrates for general anaesthetics cultured spinal and cortical tissue slices were obtained from embryonic and newborn mice, respectively. Drug effects were assessed by extracellular voltage recordings of spontaneous action potential activity. Application of acetylcholine elevated spontaneous activity in neocortical and spinal slices. Atropine (10 nM) reduced discharge rates and reversed the increase of spontaneous activity induced by acetylcholine. In the presence of acetylcholine and atropine sevoflurane caused a concentration-dependent decrease of neuronal activity in neocortical (EC(50)=0.35+/-0.33 MAC) and spinal slices (EC(50)=0.43+/-0.03 MAC). Comparing our results with previous studies which investigated the effects of acetylcholine on anaesthetic potency it is concluded that small concentrations of atropine increase sevoflurane potency in cortical networks during cholinergic Overstimulation. Thus, in a clinical setting, we recommend that anaesthetic drugs should be co-applied with atropine for adequate performance of general anaesthesia.
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effects of cholinergic Overstimulation on isoflurane potency and efficacy in cortical and spinal networks
Toxicology, 2007Co-Authors: Christian Grasshoff, Berthold Drexler, Bernd AntkowiakAbstract:Abstract In scenarios of terrorist attacks with organophosphorus compounds it appears likely that medical aid is required by victims not only suffering from the intoxication but also from physical trauma. These subjects may have to undergo surgical interventions, raising the need for anaesthesia. This prompts the question of how anaesthetic agents work in intoxicated patients. Organophosphates block acetylcholinesterase activity, thereby inducing excessive cholinergic Overstimulation in the central nervous system. As the neocortex and spinal cord are important substrates for general anaesthetics, we investigated to what extent cholinergic Overstimulation affects the potency and efficacy of the commonly used volatile anaesthetic isoflurane in depressing action potential activity of cortical and spinal neurons. We first quantified the effects of isoflurane in the absence of acetylcholine by performing extracellular voltage recordings in cultured tissue slices. Isoflurane induced a concentration-dependent decrease of neuronal activity in neocortical (EC 50 = 0.43 ± 0.08 MAC) and spinal slices (EC 50 = 0.41 ± 0.03 MAC). At concentrations above 1.5 MAC, the anaesthetic almost completely depressed action potential firing in both preparations. Next, we studied the effects of acetylcholine (10 μM) in the absence of isoflurane. Acetylcholine approximately doubled spontaneous activity in neocortical and spinal slices. When applying isoflurane together with acetylcholine, different interactions between these agents were observed in neocortical and spinal networks. Acetylcholine significantly reduced both the potency and efficacy of the anaesthetic in neocortical (efficacy 83%; EC 50 = 1.16 ± 0.02 MAC) but not in spinal (efficacy 100%; EC 50 = 0.41 ± 0.04 MAC) slices. Our results indicate that cholinergic Overstimulation increases the requirement for anaesthetic agents in patients suffering from organophosphorus poisoning via enhancing neuronal background activity of neocortical and spinal neurons and in addition via decreasing drug potency and efficacy in the cortex. Raising anaesthetic concentrations into a high-dose range may not be an appropriate alternative to compensate the increased excitability, since high concentrations of anaesthetics may worsen cardiac abnormalities and hemodynamic instability frequently observed in these patients.
A Bjorklund - One of the best experts on this subject based on the ideXlab platform.
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Overstimulation and beta cell function
Diabetes, 2001Co-Authors: V Grill, A BjorklundAbstract:Previous and present evidence ascribes an important role to Overstimulation of beta-cells for the secretory abnormalities associated with type 2 diabetes. The abnormality most clearly linked to Overstimulation is the elevated ratio of circulating proinsulin to insulin. Evidence obtained in human pancreatic islets suggests that aberrations in insulin oscillations that occur in type 2 diabetes could at least in part be linked to abnormalities in cytoplasmic Ca2+ oscillations induced by Overstimulation. Furthermore, in a transplantation model, we have obtained evidence for long-lasting, perhaps irreversible, effects of Overstimulation, implying that this is a causative factor for the well-recognized deterioration of insulin secretion with increasing duration of type 2 diabetes. The mechanisms behind the effects of Overstimulation are only partly clarified, but it is clear that reduced insulin secretion after Overstimulation is only partly explained by decreased insulin stores. In cultured human pancreatic islets, Overstimulation by high glucose leads to a rise in cytoplasmic Ca2+ levels, which persists after normalization of the glucose levels. Persistent elevation of cytoplasmic Ca2+ may trigger apoptosis, thus participating in long-term irreversible deterioration of beta-cell function. These data provide sufficient rationale for clinical studies to test the beneficial effects of relative beta-cell rest in type 2 diabetic patients.
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Overstimulation and β cell function
Diabetes, 2001Co-Authors: V Grill, A BjorklundAbstract:Previous and present evidence ascribes an important role to Overstimulation of β-cells for the secretory abnormalities associated with type 2 diabetes. The abnormality most clearly linked to Overstimulation is the elevated ratio of circulating proinsulin to insulin. Evidence obtained in human pancreatic islets suggests that aberrations in insulin oscillations that occur in type 2 diabetes could at least in part be linked to abnormalities in cytoplasmic Ca 2+ oscillations induced by Overstimulation. Furthermore, in a transplantation model, we have obtained evidence for long-lasting, perhaps irreversible, effects of Overstimulation, implying that this is a causative factor for the well-recognized deterioration of insulin secretion with increasing duration of type 2 diabetes. The mechanisms behind the effects of Overstimulation are only partly clarified, but it is clear that reduced insulin secretion after Overstimulation is only partly explained by decreased insulin stores. In cultured human pancreatic islets, Overstimulation by high glucose leads to a rise in cytoplasmic Ca 2+ levels, which persists after normalization of the glucose levels. Persistent elevation of cytoplasmic Ca + may trigger apoptosis, thus participating in long-term irreversible deterioration of β-cell function. These data provide sufficient rationale for clinical studies to test the beneficial effects of relative β-cell rest in type 2 diabetic patients.
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glucose induced ca2 i abnormalities in human pancreatic islets important role of Overstimulation
Diabetes, 2000Co-Authors: A Bjorklund, Anders Lansner, V GrillAbstract:Chronic hyperglycemia desensitizes beta-cells to glucose. To further define the mechanisms behind desensitization and the role of Overstimulation, we tested human pancreatic islets for the effects of long-term elevated glucose levels on cytoplasmic free Ca2+ concentration ([Ca2+]i) and its relationship to Overstimulation. Islets were cultured for 48 h with 5.5 or 27 mmol/l glucose. Culture with 27 mmol/l glucose obliterated postculture insulin responses to 27 mmol/l glucose. This desensitization was specific for glucose versus arginine. Desensitization was accompanied by three major [Ca2+]i abnormalities: 1) elevated basal [Ca2+]i, 2) loss of a glucose-induced rise in [Ca2+]i, and 3) perturbations of oscillatory activity with a decrease in glucose-induced slow oscillations (0.2-0.5 min(-1)). Coculture with 0.3 mmol/l diazoxide was performed to probe the role of Overstimulation. Neither glucose nor diazoxide affected islet glucose utilization or oxidation. Coculture with diazoxide and 27 mmol/l glucose significantly (P < 0.05) restored postculture insulin responses to glucose and lowered basal [Ca2+]i and normalized glucose-induced oscillatory activity. However, diazoxide completely failed to revive an increase in [Ca2+]i during postculture glucose stimulation. In conclusion, desensitization of glucose-induced insulin secretion in human pancreatic islets is induced in parallel with major glucose-specific [Ca2+]i abnormalities. Overstimulation is an important but not exclusive factor behind [Ca2+]i abnormalities.
Yehoash Raphael - One of the best experts on this subject based on the ideXlab platform.
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scar formation and debris elimination during hair cell degeneration in the adult dtr mouse
Neuroscience, 2021Co-Authors: Sungsu Lee, Takaomi Kurioka, Min Young Lee, Lisa A Beyer, Donald L Swiderski, Elaine K Ritter, Yehoash RaphaelAbstract:Abstract The auditory sensory epithelium of the mammalian inner ear is a highly organized structure that contains sensory hair cells (HCs) and non-sensory supporting cells (SCs). Following the partial loss of HCs after cochlear insults such as Overstimulation or ototoxic drugs, SCs seal the luminal epithelial surface (reticular lamina) and reorganize its cellular pattern. Here we investigated the changes in the sensory epithelium following a rapid and severe cochlear insult in the diphtheria toxin receptor (DTR) mouse, where diphtheria toxin (DT) injection leads to a HC-specific lesion resulting in a complete HC loss. We found that DT-induced selective HC ablation could lead to a pattern of scar formation and apical cell–cell adherens and tight junction reorganization similar to that occurring after other types of cochlear insult. Prestin, an outer HC-specific protein, was present in amorphous clumps at the sites where SCs had expanded to fill the spaces vacated by the dead HCs for up to 2 months after the DT induced lesion. Many of the prestin clumps appeared to occupy spaces within SCs, suggesting that SCs participate in the removal process of HC corpses in the DTR deafness model. Prestin clumps could be seen in different areas all along the length of the SCs, and appeared to be inside the SCs as well as in the inter-cellular spaces between SCs. The findings suggest that HC elimination in the DTR deafness model follows a mechanism similar to that in Overstimulation or ototoxicity models, making the DTR mouse useful for understanding the process underlying HC elimination and the role of SCs in this process.
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re innervation patterns of chick auditory sensory epithelium after acoustic Overstimulation
Hearing Research, 1996Co-Authors: Yu Wang, Yehoash RaphaelAbstract:There is evidence from several studies showing that sensory cells which are destroyed by trauma in the chick auditory epithelium are replaced by new cells. The fate of neurons that innervate the injured and degenerating sensory cells in the lesion, and the temporal sequence of re-innervation of regenerated hair cells are not well understood. This study examined efferent terminals in the chick auditory sensory epithelium following acoustic Overstimulation using synapsin-specific immunocytochemistry. Chicks were exposed to an octave band noise (1.5 kHz center frequency, 116 dB SPL, 16 h) and killed on each day from 0 to 9 days postexposure. In the proximal half of control whole mounts of the basilar papillae, synapsin-specific immunoreactivity stained efferent terminals throughout the abneural portion of the sensory epithelium (the short hair cell region). In this area, the labeling appeared as 2-3 bouton-shaped clusters along the abneural edge of each hair cell. After acoustic Overstimulation, a lesion was observed at the abneural edge of the papilla where many short hair cells were lost. The center of the lesion was located at 40% distance from the proximal end of each traumatized papilla. Synapsin-specific labeling was not found in sites where expanded supporting cells had replaced missing hair cells. Hair cells which survived the trauma exhibited a shrunken apical area, and synapsin-labeled boutons were observed near their basal domains. New hair cells, which first appeared in the papilla 4 days after trauma, were not initially associated with synapsin-labeled boutons. Regenerated hair cells first displayed contacts with synapsin-labeled boutons 7 days after trauma. Nine days after acoustic Overstimulation, most new hair cells appeared to be associated with synapsin-labeled boutons which resembled the normal horseshoe configuration of efferent terminals. The data suggest that direct contact with functional efferent synapses is not necessary for the generation and differentiation of new hair cells.
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pure tone Overstimulation protects surviving avian hair cells from acoustic trauma
Hearing Research, 1991Co-Authors: Yehoash RaphaelAbstract:Abstract It was found that intense pure-tones which damage hair cells in chicks, also result in damage to the tectorial membrane (™). This study was designed to elucidate the effects of a second pure-tone insult on hair cells which survived a priming pure-tone exposure. Chicks were exposed to a pure-tone of 1.5 kHz at 124 dB SPL. Lesion was found in both ™ and hair cells, but the area of damage to the ™ was much larger than that to the hair cells. Following this exposure, chicks were exposed to a second intense pure-tone at 2.2 kHz 124 dB SPL. The frequency of the second exposure corresponded to a region where the ™ did, but hair cells did not appear to be injured by the first exposure. The second exposure caused significantly less hair cell damage in chicks already exposed to the 1.5 kHz pure-tone than in controls which were not primed with the first exposure. This finding suggests that the first exposure provides a degree of protection for the surviving hair cells, perhaps by uncoupling them from the ™.
