Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and s...Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and several pharmacological strategies are used to augment it. Several reviews including meta-analyses have been published, but the efficacy of augmentation therapy for clozapine-resistant patients is not adequately supported. Though there is a weak connection between the oral dose and plasma concentration of clozapine, there is no report of augmentation therapy considering the plasma concentration of clozapine. Blonanserin is reported to be effective in treatment of both positive and negative symptoms of schizophrenia and well tolerated. Methods: We obtained consent to evaluate clinical presentations and clozapine plasma concentrations at the Okayama Psychiatric Medical Center and had not identified the individual for ethical reasons. This is a case report. Results: This case fulfilled the diagnostic criteria of neuroleptic-induced dopamine supersensitivity psychosis. Monotherapy with blonanserin was not effective, but augmentation of blonanserin with clozapine was effective and well tolerated by a clozapine-resistant schizophrenia patient. Conclusion: Because clozapine may ameliorate dopamine supersensitivity psychosis, the addition of blonanserin to clozapine may be effective even if monotherapy with blonanserin was not.展开更多
AIMTo evaluate the characteristics of pupillo-accommodative functions in patients with idiopathic tonic pupil according to the time of onset, gender, and age.
Action potential,which is the foundation of physiology and electrophysiology,is most vital in physiological research.This work starts by detecting cardiac electrophysiology(tachyarrhythmias),combined with all spontane...Action potential,which is the foundation of physiology and electrophysiology,is most vital in physiological research.This work starts by detecting cardiac electrophysiology(tachyarrhythmias),combined with all spontaneous discharge phenomena in vivo such as wound currents and spontaneous neuropathic pain,elaborates from generation,induction,initiation,to all of the features of spontaneous high-frequency action potential--SSL action potential mechanism,i.e.,connecting-end hyperpolarization initiates spontaneous depolarization and action potential in somatic membrane.This work resolves the conundrums of in vivo spontaneous discharge in tachyarrhythmias,wounds,denervation supersensitivity,neurogenic pain(hyperalgesia and allodynia),epileptic discharge and diabetic pain in pathophysiological and clinical researches that have puzzled people for a hundred years.展开更多
BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopam...BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits. OBJECTIVE： To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed. METHODS： The authors＇ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed. RESULTS： An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine （L-dopa）. These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D 1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements （walking） and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements. CONCLUSIONS： The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.展开更多
High sensitivity and fast response are the figures of merit for benchmarking commercial sensors.Due to the advantages of intrinsic signal amplification,bionic ability,and mechanical flexibility,electrochemical transis...High sensitivity and fast response are the figures of merit for benchmarking commercial sensors.Due to the advantages of intrinsic signal amplification,bionic ability,and mechanical flexibility,electrochemical transistors(ECTs)have recently gained increasing popularity in constructing various sensors.In the current work,we have proposed a pulse-driven synaptic ECT for supersensitive and ultrafast biosensors.By pulsing the presynaptic input(drain bias,VD)and setting the modulation potential(gate bias)near transconductance intersection(VG,i),the synaptic ECT-based pH sensor can achieve a record high sensitivity up to 124 mV pH^(-1)(almost twice the Nernstian limit,59.2 mV pH^(-1))and an ultrafast response time as low as 8.75 ms(7169 times faster than the potentiostatic sensors,62.73 s).The proposed synaptic sensing strategy can effectively eliminate the transconductance fluctuation issue during the calibration process of the pH sensor and significantly reduce power consumption.Besides,the most sensitive working point at VG,i has been elaborately figured out through a series of detailed mathematical derivations,which is of great significance to provide higher sensitivity with quasi-nonfluctuating amplification capability.The proposed electrochemical synaptic transistor paired with an optimized operating gate offers a new paradigm for standardizing and commercializing high-performance biosensors.展开更多
文摘Background: Clozapine is the most efficacious among antipsychotics for patients with schizophrenia. Nevertheless, clozapine is not effective in more than about 50% of treatment refractory schizophrenia patients, and several pharmacological strategies are used to augment it. Several reviews including meta-analyses have been published, but the efficacy of augmentation therapy for clozapine-resistant patients is not adequately supported. Though there is a weak connection between the oral dose and plasma concentration of clozapine, there is no report of augmentation therapy considering the plasma concentration of clozapine. Blonanserin is reported to be effective in treatment of both positive and negative symptoms of schizophrenia and well tolerated. Methods: We obtained consent to evaluate clinical presentations and clozapine plasma concentrations at the Okayama Psychiatric Medical Center and had not identified the individual for ethical reasons. This is a case report. Results: This case fulfilled the diagnostic criteria of neuroleptic-induced dopamine supersensitivity psychosis. Monotherapy with blonanserin was not effective, but augmentation of blonanserin with clozapine was effective and well tolerated by a clozapine-resistant schizophrenia patient. Conclusion: Because clozapine may ameliorate dopamine supersensitivity psychosis, the addition of blonanserin to clozapine may be effective even if monotherapy with blonanserin was not.
文摘AIMTo evaluate the characteristics of pupillo-accommodative functions in patients with idiopathic tonic pupil according to the time of onset, gender, and age.
基金supported by a grant of the Korean Health Technology R&D Project,Ministry for Health,Welfare & Family Affairs,Republic of Korea(Grant No.A 092125)
文摘Action potential,which is the foundation of physiology and electrophysiology,is most vital in physiological research.This work starts by detecting cardiac electrophysiology(tachyarrhythmias),combined with all spontaneous discharge phenomena in vivo such as wound currents and spontaneous neuropathic pain,elaborates from generation,induction,initiation,to all of the features of spontaneous high-frequency action potential--SSL action potential mechanism,i.e.,connecting-end hyperpolarization initiates spontaneous depolarization and action potential in somatic membrane.This work resolves the conundrums of in vivo spontaneous discharge in tachyarrhythmias,wounds,denervation supersensitivity,neurogenic pain(hyperalgesia and allodynia),epileptic discharge and diabetic pain in pathophysiological and clinical researches that have puzzled people for a hundred years.
文摘BACKGROUND： Parkinson＇s disease （PD） is a common, age-dependent degenerative neurological disorder impairing motor control function and cognition. A key pathology of PD is a degeneration of the nigrostriatal dopamine system, leading to a severe dopamine denervation in the striatum and dynsfunction of the striatal neural circuits. OBJECTIVE： To better understand the pathophysiology of the nigrostriatal dopamine denervation and to discover better treatments, animal PD models are needed. METHODS： The authors＇ original research on the transcription factor Pitx3 null mutant mice and the relevant literature were reviewed. RESULTS： An important feature of an animal PD model is the severe, PD-like nigrostriatal dopamine denervation. This feature is provided in the transcription factor Pitx3 null mutant mice. These mice have a severe and bilateral nigral dopamine neuron loss and dopamine denervation in the dorsal striatum, while the dopamine neuron loss in the ventral tegmental area and dopamine denervation in the ventral striatum are moderate, creating a dorsal-ventral dopamine loss gradient and mimicking the dopamine denervation pattern in PD. Pitx3 null mice show motor function deficits in the balance beam and pole tests and these deficits are reversed by L-3,4-dihydroxyphenylalanine （L-dopa）. These mice also show impaired cognitive functions as indicated by reduced motor learning and avoidance memory. L-dopa, D 1 agonists and, to a lesser extent, D2 agonists, induce normal horizontal movements （walking） and also dyskinesia-like movements consisting of vertical body trunk movements and waving paw movements. CONCLUSIONS： The easy-to-maintain Pitx3 null mice with an autogenic, consistent and gradient dopamine denervation are a convenient and suitable mouse model to study the consequences of dopamine loss in PD and to test dopaminergic replacement therapies for PD.
基金National Natural Science Foundation of China,Grant/Award Numbers:61703298,51975400,52073031,52175542Natural Science Foundation of Shanxi Province,Grant/Award Number:20210302123136+3 种基金China Postdoctoral Science Foundation,Grant/Award Number:2020M673646National Key Research and Development Program of China,Grant/Award Numbers:2021YFB3200304,2016YFA0202703Beijing Nova Program,Grant/Award Number:Z211100002121148Patent Transformation Special Program of Shanxi Province,Grant/Award Number:202304012。
文摘High sensitivity and fast response are the figures of merit for benchmarking commercial sensors.Due to the advantages of intrinsic signal amplification,bionic ability,and mechanical flexibility,electrochemical transistors(ECTs)have recently gained increasing popularity in constructing various sensors.In the current work,we have proposed a pulse-driven synaptic ECT for supersensitive and ultrafast biosensors.By pulsing the presynaptic input(drain bias,VD)and setting the modulation potential(gate bias)near transconductance intersection(VG,i),the synaptic ECT-based pH sensor can achieve a record high sensitivity up to 124 mV pH^(-1)(almost twice the Nernstian limit,59.2 mV pH^(-1))and an ultrafast response time as low as 8.75 ms(7169 times faster than the potentiostatic sensors,62.73 s).The proposed synaptic sensing strategy can effectively eliminate the transconductance fluctuation issue during the calibration process of the pH sensor and significantly reduce power consumption.Besides,the most sensitive working point at VG,i has been elaborately figured out through a series of detailed mathematical derivations,which is of great significance to provide higher sensitivity with quasi-nonfluctuating amplification capability.The proposed electrochemical synaptic transistor paired with an optimized operating gate offers a new paradigm for standardizing and commercializing high-performance biosensors.
