ABSTRACT
OBJECTIVE: Over the last two decades, optical control of neuronal activity in the central nervous system has seen rapid development, demonstrating the utility of optogenetics as both an experimental and therapeutic tool. Conversely, applications of optogenetics in the peripheral nervous system have been relatively constrained by the challenges of temporally variable opsin expression, light penetration and immune attack of non-native opsins. Whilst opsin expression can be increased significantly through high-concentration viral induction, subsequent attack by the immune system causes temporal decay and high variability in electrophysiological response. APPROACH: In this study, we present a method to circumvent the aforementioned challenges by locally supplementing all-trans-retinal (ATR) (via a slow release pellet) to increase tissue photosensitivity in transgenic mice expressing channelrhodopsin 2 (ChR2) in nerves. MAIN RESULTS: In mice supplemented with ATR, we demonstrate enhanced electrophysiological activation and fatigue tolerance in response to optical stimulation for six weeks. SIGNIFICANCE: Local supplementation of ATR enables improved optogenetic stimulation efficacy in peripheral nerves. This method enables greater exploration of neurophysiology and development of clinically-viable optogenetic treatments in the peripheral nervous system.
Subject(s)
Optogenetics/methods , Photic Stimulation/methods , Retina/chemistry , Retina/drug effects , Vitamin A/administration & dosage , Animals , Drug Implants/administration & dosage , Electromyography/drug effects , Electromyography/methods , Female , Male , Mice , Mice, Transgenic , Retina/metabolismABSTRACT
Although docosahexaenoic acid (DHA) administration suppresses sodium channels in primary afferent sensory neurons, the acute local effect of DHA on the trigeminal nociceptive reflex remains to be elucidated, in vivo. Therefore, the aim of the present study was to investigate whether local administration of DHA attenuates the nociceptive jaw-opening reflex (JOR) in vivo in the rat. The JOR evoked by electrical stimulation of the tongue was recorded by a digastric muscle electromyogram (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG response was significantly increased in proportion to the electrical stimulation intensity (1-5â¯x threshold). At 3â¯x threshold, local administration of DHA (0.1, 10 and 25â¯mM) dose-dependently inhibited the dEMG response, and lasted 40â¯min. Maximum inhibition of the dEMG signal amplitude was seen within approximately 10â¯min. The mean magnitude of inhibition of the dEMG signal amplitude by DHA (25â¯mM) was almost equal to the local anesthetic, 1% lidocaine (37â¯mM), a sodium channel blocker. These findings suggest that DHA attenuates the nociceptive JOR via possibly blocking sodium channels, and strongly support the idea that DHA is a potential therapeutic agent and complementary alternative medicine for the prevention of acute trigeminal nociception.
Subject(s)
Anesthetics, Local/pharmacology , Docosahexaenoic Acids/pharmacology , Neck Muscles/drug effects , Nociception/drug effects , Reflex/drug effects , Animals , Electric Stimulation , Electromyography/drug effects , Jaw/drug effects , Jaw/physiology , Lidocaine/pharmacology , Male , Neck Muscles/physiology , Nociceptors/physiology , Rats , Rats, Wistar , Reflex/physiology , Trigeminal Nerve/drug effects , Trigeminal Nerve/physiologyABSTRACT
The aim of the present study was to investigate whether, under in vivo conditions, systemic administration of resveratrol could attenuate the rat nociceptive jaw-opening reflex (JOR) via the endogenous opioid system. The JOR evoked by electrical stimulation of the tongue was recorded as digastric muscle electromyograms (dEMG) in pentobarbital-anesthetized rats. The amplitude of the dEMG increased significantly in proportion to the intensity of electrical stimulation (from 1× to 5 × threshold for the JOR). dEMG amplitude in response to 3× threshold electrical stimulation of the tongue was dose-dependently inhibited by intravenous administration of resveratrol (0.5-2mg/kg). Maximum inhibition of dEMG amplitude was seen within approximately 10min. These inhibitory effects were reversible, with dEMG responses returning to control levels after approximately 20min. Pretreatment of rats with naloxone resulted in significant, dose-dependent attenuation of the inhibitory effects of resveratrol on dEMG amplitude compared with control. These findings suggest that resveratrol inhibits the nociceptive JOR via the endogenous opioid system. Further, the findings of the present study strongly support the idea that resveratrol, which is not known to have any toxic side effects, combined with an opioid could be a potential therapeutic agent for the prevention of acute trigeminal nociception.
Subject(s)
Jaw/drug effects , Jaw/physiology , Nociception/drug effects , Opioid Peptides/physiology , Reflex/drug effects , Stilbenes/administration & dosage , Stilbenes/pharmacology , Administration, Intravenous , Animals , Dose-Response Relationship, Drug , Electric Stimulation , Electromyography/drug effects , Male , Naloxone/pharmacology , Rats , Resveratrol , Stilbenes/antagonists & inhibitorsABSTRACT
BACKGROUND: Growth factors such as nerve growth factor (NGF) and insulin-like growth factor-1 (IGF-1) have been shown to play a role in the healing process of nerve injury. Recent researches have also shown that oxytocin administration activates these growth factors of importance for the healing of nerve tissue. The objective of the present study was to evaluate the effects of oxytocin on peripheral nerve regeneration in rats. METHODS: Twenty-four male Sprague-Dawley rats were underwent transection damage model on the right sciatic nerve and defective damage model on the left sciatic nerve. The animals were assigned to one of two groups: control group or treatment group (received 80 mg/kg oxytocin intraperitoneally for 12 weeks). The sciatic nerve was examined, both functionally (on the basis of climbing platform test) and histologically (on the basis of axon count), 3, 6, 9, and 12 weeks after the injury. Also, stereomicroscopic and electrophysiological evaluations were carried out. RESULTS: Significantly greater improvements in electrophysiological recordings and improved functional outcome measures were presented in the treatment group at 12-week follow-up. Stereomicroscopic examinations disclosed prominent increases in vascularization on proximal cut edges in the oxytocin group in comparison with the control group. Higher axon counts were also found in this group. CONCLUSION: Intraperitoneal oxytocin administration resulted in accelerated functional, histological, and electrophysiological recovery after different sciatic injury models in rats.
Subject(s)
Nerve Regeneration/drug effects , Oxytocin/therapeutic use , Peripheral Nerve Injuries/drug therapy , Sciatic Nerve/injuries , Animals , Axons/pathology , Disease Models, Animal , Drug Evaluation, Preclinical/methods , Electromyography/drug effects , Male , Oxytocin/pharmacology , Peripheral Nerve Injuries/physiopathology , Rats, Sprague-Dawley , Recovery of Function , Sciatic Nerve/drug effects , Sciatic Nerve/pathology , Sciatic Nerve/physiologyABSTRACT
BACKGROUND: Chinese medicine xiangshaliujunzi decoction (XSLJZD) plays a key role in treating functional dyspepsia (FD), a common clinical gastrointestinal disorder. However, the mechanism of this disease is unclear. Brain-gut axis regulates food intake behaviour, and this regulatory mechanism is mediated by neuropeptides. Brain-gut axis impairment and neuropeptide alteration may be the pathological mechanisms of FD, and brain-gut axis regulation may influence the action of medicine. METHODS: In our experiment, the effect of XSLJZD on FD was evaluated in terms of food intake, sucrose preference test and electromyogram. Changes in neuropeptides [ghrelin, cholecystokinin (CCK) and vasoactive intestinal polypeptide (VIP)] were detected through immunohistochemistry, real-time PCR and ELISA. RESULTS: XSLJZD increased food intake and the percentage of sucrose preference (>75 %). However, the response to gastric detention decreased. Furthermore, XSLJZD increased ghrelin, CCK, VIP proteins and genes in the stomach. XSLJZD also increased ghrelin, CCK and VIP proteins in serum. By contrast, XSLJZD decreased the mRNA expression of these neuropeptides in the hypothalamus. CONCLUSIONS: XSLJZD alleviated the symptoms of FD by upregulating the production of ghrelin, CCK and VIP and by increasing the levels of these neuropeptides in circulation. This finding can help elucidate the mechanism of FD and can provide further insight into the pharmacokinetics of XSLJZD.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Dyspepsia/drug therapy , Neuropeptides/metabolism , Analysis of Variance , Animals , Disease Models, Animal , Eating/drug effects , Electromyography/drug effects , Enzyme-Linked Immunosorbent Assay , Feeding Behavior/drug effects , Male , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Sucrose/administration & dosage , Vasoactive Intestinal Peptide/metabolismABSTRACT
OBJECTIVES/HYPOTHESIS: To retrospectively determine optimal timing for initiation of nimodipine within a cohort of patients with acute vocal fold paralysis (VFP). STUDY DESIGN: Retrospective patient review. METHODS: Subjects were divided into three groups: initiation within 15 days postinjury (n = 19), between 15 and 30 days postinjury (n = 23), or greater than 30 days postinjury (n = 11). RESULTS: Fifty-one patients (53 paralyzed vocal folds [VFs]) met entrance criteria and were offered and started off-label nimodipine treatment. Thirty-six of 53 VFs recovered purposeful motion (67.9%). There was no significant difference in the rate of VF recovery among patients who began nimodipine within 15 days (68.4%), patients who started nimodipine between 15 and 30 days (73.9%) of nerve injury (P = .1405), and patients who initiated nimodipine after 30 days postinjury (54.5%). CONCLUSIONS: Nimodipine treatment for acute VFP yielded equal VF motion recovery rates regardless of when the medication was initiated. Time to recovery of motion was not different between groups studied.
Subject(s)
Calcium Channel Blockers/administration & dosage , Nimodipine/administration & dosage , Recurrent Laryngeal Nerve Injuries/drug therapy , Vocal Cord Paralysis/drug therapy , Adult , Aged , Calcium Channel Blockers/adverse effects , Drug Administration Schedule , Electromyography/drug effects , Female , Humans , Male , Middle Aged , Nimodipine/adverse effects , Off-Label Use , Prognosis , Prospective Studies , Retrospective Studies , Time FactorsABSTRACT
INTRODUCTION: To study stimulation-related facial electromyographic (FEMG) activity in intensive care unit (ICU) patients, develop an algorithm for quantifying the FEMG activity, and to optimize the algorithm for monitoring the sedation state of ICU patients. METHODS: First, the characteristics of FEMG response patterns related to vocal stimulation of 17 ICU patients were studied. Second, we collected continuous FEMG data from 30 ICU patients. Based on these data, we developed the Responsiveness Index (RI) algorithm that quantifies FEMG responses. Third, we compared the RI values with clinical sedation level assessments and adjusted algorithm parameters for best performance. RESULTS: In patients who produced a clinically observed response to the vocal stimulus, the poststimulus FEMG power was 0.33 µV higher than the prestimulus power. In nonresponding patients, there was no difference. The sensitivity and specificity of the developed RI for detecting deep sedation in the subgroup with low probability of encephalopathy were 0.90 and 0.79, respectively. CONCLUSION: Consistent FEMG patterns were found related to standard stimulation of ICU patients. A simple and robust algorithm was developed and good correlation with clinical sedation scores achieved in the development data.
Subject(s)
Acoustic Stimulation/methods , Algorithms , Electromyography/methods , Facial Muscles/physiology , Intensive Care Units , Neurophysiological Monitoring , Adult , Electromyography/drug effects , Female , Humans , Hypnotics and Sedatives/administration & dosage , Male , Middle Aged , Neurophysiological Monitoring/methodsABSTRACT
The aim of this study was to evaluate different approaches to deactivating myofascial trigger points (MTPs). Twenty-one women with bilateral MTPs in the masseter muscle were randomly divided into three groups: laser therapy, needle treatment and control. Treatment effectiveness was evaluated after four sessions with intervals ranging between 48 and 72 h. Quantitative and qualitative methods were used to measure pain perception/sensation. The Wilcoxon test based on results expressed on a visual analog scale (VAS) demonstrated a significant (P < 0.05) decrease in pain only in the laser and needle treatments groups, although a significant increase in the pressure pain threshold was evident only for needling with anesthetic injection (P = 0.0469), and laser therapy at a dose of 4 J/cm² (P = 0.0156). Based on these results, it was concluded that four sessions of needling with 2% lidocaine injection with intervals between 48 and 72 h without a vasoconstrictor, or laser therapy at a dose of 4 J/cm², are effective for deactivation of MTPs.
Subject(s)
Anesthetics, Local/administration & dosage , Injections, Intramuscular , Low-Level Light Therapy/methods , Masseter Muscle/radiation effects , Temporomandibular Joint Dysfunction Syndrome/radiotherapy , Trigger Points/radiation effects , Adult , Electromyography/drug effects , Electromyography/radiation effects , Female , Follow-Up Studies , Humans , Isometric Contraction/drug effects , Isometric Contraction/radiation effects , Lidocaine/administration & dosage , Masseter Muscle/drug effects , Middle Aged , Pain Measurement , Pain Perception/drug effects , Pain Perception/radiation effects , Pain Threshold/drug effects , Pain Threshold/radiation effects , Radiotherapy Dosage , Range of Motion, Articular/drug effects , Range of Motion, Articular/radiation effects , Temporomandibular Joint Dysfunction Syndrome/drug therapy , Young AdultABSTRACT
It has been reported that the sedative component of pentobarbital is mediated by GABA receptors in an endogenous sleep pathway and the ventrolateral preoptic area (VLPO)-tuberomammillary nucleus (TMN) or VLPO-dorsal raphe nucleus (DRN) neural circuit is important in the sedative response to pentobarbital. Our previous findings indicated that the VLPO-TMN neuronal circuit may play crucial part in the augmentative effect of diltiazem on pentobarbital sleep and the serotonergic system may be involved. This study was designed to investigate the role of DRN and the serotonergic receptors 5-HT(1A) and 5-HT(2A/2C) in the augmentative effect of diltiazem on pentobarbital-induced hypnosis in rats. The results showed that diltiazem (5mg/kg, i.g.) significantly reversed pentobarbital-induced (35 mg/kg, i.p.) reduction of c-Fos expression in 5-HT neurons of DRNV (at -7.5mm Bregma), DRND, DRNVL and MRN (at -8.0mm Bregma). However it did not influence this reducing effect of pentobarbital on non-5-HT neurons either in DRN or in MRN. Moreover, the effect of diltiazem (1 or 2mg/kg, i.g.) on pentobarbital-induced (35 mg/kg, i.p.) hypnosis was significantly inhibited by 5-HT(1A) agonist 8-OH-DPAT (0.5mg/kg, i.p.) and 5-HT(2A/2C) agonist DOI (0.5mg/kg, i.p.), and potentiated by 5-HT(1A) antagonist p-MPPI (2mg/kg, i.p.) and 5-HT(2A/2C) antagonist ritanserin (2mg/kg, i.p.), respectively. From these results, it should be presumed that the augmentative effect of diltiazem on pentobarbital-induced sleep may be related to 5-HT(1A) and 5-HT(2A/2C) receptors, and DRN may be involved. In addition, it also suggested that the DRN may play a multi-modulating role in sleep-wake regulation rather than being recognized simply as arousal nuclei.
Subject(s)
Calcium Channel Blockers/pharmacology , Diltiazem/pharmacology , Hypnotics and Sedatives/pharmacology , Pentobarbital/pharmacology , Raphe Nuclei/physiology , Receptor, Serotonin, 5-HT1A/drug effects , Receptor, Serotonin, 5-HT2A/drug effects , Receptor, Serotonin, 5-HT2C/drug effects , Animals , Brain/cytology , Brain/drug effects , Cell Count , Drug Synergism , Electroencephalography/drug effects , Electromyography/drug effects , Gene Expression/drug effects , Genes, fos/drug effects , Immunohistochemistry , Male , Polysomnography , Raphe Nuclei/drug effects , Rats , Rats, Sprague-Dawley , Serotonergic Neurons/drug effects , Serotonin Antagonists/pharmacology , Serotonin Receptor Agonists/pharmacologyABSTRACT
Many important physiological, behavioral, and psychoemotional effects of intravenous (IV) cocaine (COC) are too fast and transient compared with pharmacokinetic predictions, suggesting a possible involvement of peripheral neural mechanisms in their triggering. In the present study, we examined changes in cortical electroencephalogram (EEG) and neck electromyogram (EMG) induced in freely moving rats by IV COC administration at low, reinforcing doses (0.25-1.0 mg/kg) and compared them with those induced by an auditory stimulus and IV COC methiodide, which cannot cross the blood-brain barrier. We found that COC induces rapid, strong, and prolonged EEG desynchronization, associated with decrease in alpha and increase in beta and gamma activities, and EMG activation and that both begin within 2-6 s following the start of a 10-s injection; immediate components of this effect were dose independent. The rapid COC-induced changes in EEG and EMG resembled those induced by an auditory stimulus; the latter effects had shorter onset latencies and durations and were fully blocked during urethane anesthesia. Although urethane anesthesia completely blocked COC-induced EMG activation and rapid components of EEG response, COC still induced EEG desynchronization that was much weaker, greatly delayed (approximately 60 s), and associated with tonic decreases in delta and increases in alpha, beta, and gamma activities. Surprisingly, IV saline delivered during slow-wave sleep (but not quite wakefulness) also induced a transient EEG desynchronization but without changes in EMG activity; these effects were also fully blocked during anesthesia. Peripherally acting COC methiodide fully mimicked rapid EEG and EMG effects of regular COC, but the effects at an equimolar dose were less prolonged than those with regular COC. These data suggest that in awake animals IV COC, like somato-sensory stimuli, induces cortical activation and a subsequent motor response via its action on peripheral neural elements and involving rapid neural transmission. By providing a rapid neural signal and triggering transient neural activation, such an action might play a crucial role in the sensory effects of COC, thus contributing to the learning and development of drug-taking behavior.
Subject(s)
Cocaine/pharmacology , Dopamine Uptake Inhibitors/pharmacology , Electroencephalography/drug effects , Electromyography/drug effects , Acoustic Stimulation , Anesthesia, General , Anesthetics, Intravenous , Animals , Cocaine/administration & dosage , Cocaine/analogs & derivatives , Cocaine-Related Disorders/physiopathology , Cortical Synchronization/drug effects , Dopamine D2 Receptor Antagonists , Dopamine Uptake Inhibitors/administration & dosage , Dose-Response Relationship, Drug , Injections, Intravenous , Male , Motor Activity/drug effects , Rats , Rats, Long-Evans , Receptors, Dopamine D1/antagonists & inhibitors , UrethaneABSTRACT
L-stepholidine, an active ingredient of the Chinese herb Stephonia, is the first compound known to have mixed dopamine D(1) receptor agonist/D(2) antagonist properties and to be a potential treatment medication for schizophrenia. In schizophrenic patients insomnia is a common symptom and could be partly related to the presumed over-activity of the dopaminergic system. To elucidate whether stepholidine modulates sleep behaviors, we observed its effects on sleep-wake profiles in mice. The results showed that stepholidine administered i.p. at doses of 20, 40 or 80 mg/kg significantly shortened the sleep latency to non-rapid eye movement (non-REM, NREM) sleep, increased the amount of NREM sleep, and prolonged the duration of NREM sleep episodes, with a concomitant reduction in the amount of wakefulness. Stepholidine at doses of 40 and 80 mg/kg increased the number of state transitions from wakefulness to NREM sleep and subsequently from NREM sleep to wakefulness. However, stepholidine had no effect on either the amount of REM sleep or electroencephalogram power density of either NREM or REM sleep. Immunohistochemistry study showed that stepholidine dose-dependently increased c-Fos expression in neurons of the ventrolateral preoptic area, a sleep center in the anterior hypothalamus, as compared with the vehicle control. These results indicate that stepholidine initiates and maintains NREM sleep with activation of the sleep center in mice, suggesting its potential application for the treatment of insomnia.
Subject(s)
Berberine/analogs & derivatives , Dopamine Agonists/pharmacology , Dopamine Antagonists/pharmacology , Drugs, Chinese Herbal/pharmacology , Sleep Stages/drug effects , Animals , Berberine/administration & dosage , Berberine/pharmacology , Dopamine Agonists/administration & dosage , Dopamine Antagonists/administration & dosage , Dopamine D2 Receptor Antagonists , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Electroencephalography/drug effects , Electromyography/drug effects , Injections, Intraperitoneal , Mice , Mice, Inbred C57BL , Polysomnography/drug effects , Preoptic Area/cytology , Preoptic Area/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Reaction Time , Receptors, Dopamine D1/agonists , Signal Processing, Computer-Assisted , Sleep Initiation and Maintenance Disorders/drug therapyABSTRACT
AIM: To explore the antagonism mechanism of inulae and ochrae decoction on toxicity damage of gastrointestinal tissue induced by DDP (cisplatin). METHODS: Twenty-four healthy hybrid rabbits were divided into three groups in random: the control group, DDP group, inulae and ochrae decoction + DDP group. The change of rabbits EGG, the concentration of 5-HT,5-HIAA of serum and the content of sinus ventriculi mucosa and the upper part of duodenum tissue were examined. Ultrastructure changes were observed by transmission electron microscope (TEM). RESULTS: The EGG amplitude of DDP group was increased and the frequency was fast (P < 0.05) after i.v. DDP, meanwhile the concentration of 5-HT, 5-HIAA was increased (P < 0.05), and the content of sinus ventriculi mucosa and the upper part of duodenum tissue were higher than that of Inulae and Ochrae Decoction + DDP group (P < 0.05), and the change was seriously under the TEM observing; while inulae and ochrae decoction could prevent the change of EGG caused by DDP, showing the amplitude decreased, and the frequency was slow, and the concentration of 5-HT, 5-HIAA of serum and the content of tissue became lower than that of DDP group. CONCLUSION: Inulae and ochrae decoction could antagonize the change of EGG caused by DDP, which maybe have relations with the over-releasing of gastrointestinal 5-HT.
Subject(s)
Cisplatin/adverse effects , Drugs, Chinese Herbal/pharmacology , Phytotherapy , Serotonin/metabolism , Stomach/physiopathology , Vomiting/drug therapy , Animals , Antineoplastic Agents/adverse effects , Drugs, Chinese Herbal/therapeutic use , Electromyography/drug effects , Electromyography/methods , Gastric Mucosa/metabolism , Inula/chemistry , Nausea/chemically induced , Nausea/drug therapy , Rabbits , Vomiting/chemically inducedABSTRACT
RATIONALE AND OBJECTIVE: Research on nicotine and attention has mainly utilized samples of deprived smokers and tasks requiring volitional responses, raising the question of whether nicotine improves attention or simply alleviates withdrawal or improves motor speed. This study used the startle eyeblink reflex to assess nicotine effects on auditory attention in nonsmokers. MATERIALS AND METHODS: Sixty-seven healthy young adult nonsmokers completed a tone discrimination task. Acoustic startle probes were presented 60, 120, 240, or 4,500 ms after the onset of two-thirds of the tones and during intertrial intervals. Attention was assessed via (1) short-lead prepulse inhibition (PPI) of startle, a measure of early filtering; (2) long-lead prepulse facilitation (PPF) of startle, a measure of sustained processing; and (3) the modification of PPI and PPF by focused attention. Participants completed two laboratory sessions, once while wearing a 7-mg transdermal nicotine patch and once while wearing a placebo patch. Patches were administered in a double-blind procedure. RESULTS: Nicotine increased overall PPI, eta2(p)=0.09. Attention increased long-lead PPF, eta2(p)=0.25, but not short-lead PPI. Nicotine did not reliably enhance early or late controlled attentional processing in the sample overall. However, correlational analyses demonstrated that nicotine most improved attentional modification of short-lead PPI among participants with the weakest early attentional processing under placebo conditions. CONCLUSIONS: Nicotine enhanced early attentional filtering in general, and the effects of nicotine on early focused attention were dependent upon individual differences in placebo levels of attentional processing. The present data suggest that the effects of nicotine on attention extend beyond the alleviation of withdrawal and simple motor speeding.
Subject(s)
Attention/drug effects , Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Reflex, Startle/drug effects , Smoking/psychology , Acoustic Stimulation , Administration, Cutaneous , Adult , Data Interpretation, Statistical , Electrocardiography/drug effects , Electromyography/drug effects , Female , Heart Rate/drug effects , Humans , Male , Nausea/chemically induced , Nausea/prevention & control , Nicotine/administration & dosage , Nicotine/adverse effects , Nicotinic Agonists/administration & dosage , Nicotinic Agonists/adverse effects , Psychomotor Performance/drug effectsABSTRACT
Schizophrenia patients exhibit deficits in sensory gating as indexed by reduced prepulse inhibition (PPI) and P50 suppression, which have been linked to psychotic symptom formation and cognitive deficits. Although recent evidence suggests that atypical antipsychotics might be superior over typical antipsychotics in reversing PPI and P50 suppression deficits not only in schizophrenia patients, but also in healthy volunteers exhibiting low levels of PPI, the impact of typical antipsychotics on these gating measures is less clear. To explore the impact of the dopamine D2-like receptor system on gating and cognition, the acute effects of haloperidol on PPI, P50 suppression, and cognition were assessed in 26 healthy male volunteers split into subgroups having low vs high PPI or P50 suppression levels using a placebo-controlled within-subject design. Haloperidol failed to increase PPI in subjects exhibiting low levels of PPI, but attenuated PPI in those subjects with high sensorimotor gating levels. Furthermore, haloperidol increased P50 suppression in subjects exhibiting low P50 gating and disrupted P50 suppression in individuals expressing high P50 gating levels. Independently of drug condition, high PPI levels were associated with superior strategy formation and execution times in a subset of cognitive tests. Moreover, haloperidol impaired spatial working memory performance and planning ability. These findings suggest that dopamine D2-like receptors are critically involved in the modulation of P50 suppression in healthy volunteers, and to a lesser extent also in PPI among subjects expressing high sensorimotor gating levels. Furthermore, the results suggest a relation between sensorimotor gating and working memory performance.
Subject(s)
Antipsychotic Agents/pharmacology , Dopamine Antagonists/pharmacology , Electroencephalography/drug effects , Evoked Potentials, Auditory/drug effects , Haloperidol/pharmacology , Reflex, Startle/drug effects , Acoustic Stimulation , Adult , Dopamine D2 Receptor Antagonists , Double-Blind Method , Electromyography/drug effects , Humans , Individuality , Male , Neuropsychological Tests , Psychomotor Performance/drug effectsABSTRACT
OBJECTIVE: To evaluate the effects of Qingre Liqi Granule (QLG) on clinical therapeutic efficacy, electrogastrogram (EGG) and gastric emptying in patients with functional dyspepsia (FD). METHODS: Thirty-two FD patients of dyskinesis type enrolled were treated with QLG by oral taking for 6 days. Scoring on 8 kinds of symptoms, including abdominal distension, abdominal pain, morning gastric fullness, belching, regurgitation, nausea, vomiting, and anorexia, fasting EGG and the gastric emptying determination were performed using single photon emission computed tomography (SPECT) before and after treatment. RESULTS: The total and individual scores of clinical symptoms, expect that of vomiting, significantly decreased after treatment (P < 0.05), and the percentage of patients with tachygastria and bradygastria significantly decreased (P<0.01) at the same time. EGG after treatment showed significantly elevated rates of normal slow wave dominant power, and nearly normalized dominant frequency. An increased gastric emptying rate at different phases after 75 min (P < 0.05), and significantly shortened gastric emptying half-time (P < 0.01) were shown meanwhile in gastric emptying detection. The improvement of symptom score and gastric emptying half-time showed significant positive linear correlation (r =0.8929, P < 0.01). CONCLUSION: QLG can improve symptoms of FD patients by regulating the rhythm and power of gastric electro-wave, increasing gastric motility and enhancing gastric emptying function.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Dyspepsia/drug therapy , Gastric Emptying/drug effects , Myoelectric Complex, Migrating/drug effects , Phytotherapy , Adult , Aged , Double-Blind Method , Electromyography/drug effects , Female , Humans , Male , Middle Aged , Treatment Outcome , Young AdultABSTRACT
The changes of electromyographic activity (EMG seizure) induced by maximal electroshock were studied in comparison with those of behavioral seizures in mice. In addition, the effects of certain antiepileptics on behavioral seizures and EMG seizure induced by maximal electroshock were also studied. High amplitude with high frequency EMG seizure was observed in parallel with the appearance of tonic extensor (TE) seizure and an intimate relationship was observed between the two parameters. On the other hand, to investigate the intensity of TE seizure, the product of the amplitude and the duration in EMG seizure was calculated, and the effects of antiepileptics on the magnitude of EMG seizure were investigated. As a result, a significant difference was observed at the doses of antiepileptics that showed no significant effects on the durations of TE and EMG seizures; that is, phenytoin, phenobarbital, topiramate, and carbamazepine showed significant effects on the magnitude of EMG seizure at doses of 5, 2, 10, and 5 mg/kg, respectively. From these findings, it may be concluded that this index, that is, the magnitude of EMG seizure induced by maximal electroshock, is a more reliable and highly sensitive method for the assessment of the potential activity of antiepileptics.
Subject(s)
Anticonvulsants/pharmacology , Behavior, Animal/drug effects , Seizures/prevention & control , Administration, Oral , Animals , Anticonvulsants/administration & dosage , Carbamazepine/administration & dosage , Carbamazepine/pharmacology , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical/methods , Drug Evaluation, Preclinical/standards , Electromyography/drug effects , Electroshock/adverse effects , Ethosuximide/administration & dosage , Ethosuximide/pharmacology , Fructose/administration & dosage , Fructose/analogs & derivatives , Fructose/pharmacology , Male , Mice , Phenobarbital/administration & dosage , Phenobarbital/pharmacology , Phenytoin/administration & dosage , Phenytoin/pharmacology , Seizures/physiopathology , Time Factors , TopiramateABSTRACT
BACKGROUND: Facial electromyography (FEMG) may have utility in the assessment of nociception during surgery. The difference between state entropy (SE) and response entropy (RE) is an indirect measure of FEMG. This study assesses an automated algorithm for remifentanil administration that is based on maintaining an entropy difference (ED) that is less than an upper boundary condition and greater than a lower boundary condition. METHODS: The algorithm was constructed with a development set (n = 40), and then automated and studied with a validation set (n = 20) of patients undergoing anterior cruciate ligament repair. The percentage of time that the ED was maintained between the two boundary conditions was determined. Remifentanil and propofol predicted effect-site concentrations (Ce) were determined at surgical milestones and, after drug discontinuation, the time to response to verbal stimulation and orientation was measured. RESULTS: The median (25th-75th percentile) per cent of time that the ED was recorded between the boundary conditions was 99.3% (98.1-99.8%). Predicted propofol (microg ml(-1)) and remifentanil (ng ml(-1)) Ce (sd), respectively, were 3.5 and 4.0 at induction, 1.9 (0.8) and 7.2 (3.7) at the end of surgery, and 1.1 (0.5) and 3.2 (2.2) at eye opening. The median time to eye opening and orientation was 3.8 and 6.8 min, respectively. CONCLUSION: This feasibility study supports the concept that remifentanil may be delivered using an algorithm that maintains the difference between SE and RE between the upper and lower boundary condition.
Subject(s)
Analgesics, Opioid/administration & dosage , Drug Monitoring/methods , Piperidines/administration & dosage , Acoustic Stimulation , Adolescent , Adult , Algorithms , Analgesics, Opioid/pharmacology , Anesthesia Recovery Period , Anesthetics, Intravenous , Anterior Cruciate Ligament/surgery , Awareness/drug effects , Drug Administration Schedule , Electromyography/drug effects , Electromyography/methods , Entropy , Feasibility Studies , Female , Humans , Male , Middle Aged , Monitoring, Intraoperative/methods , Movement/drug effects , Piperidines/pharmacology , Propofol , Remifentanil , Signal Processing, Computer-AssistedABSTRACT
The neuropsychological and clinical histories of three male siblings affected by pyridoxine-dependent seizures with known homozygous antiquitin mutations are presented. Neuropsychological evaluation is reported from when the siblings were 11, 9, and 7 years of age. Two of the siblings had received early pyridoxine treatment (antenatal, 2-4 wks into pregnancy) and one had received late treatment (2mo postnatal). However, there was no differential effect on cognitive outcome, with all three siblings having moderate to severe learning disability. Unlike previously reported cases that received early postnatal treatment, none of the siblings had relatively preserved non-verbal cognitive skills. Equally, their intellectual performance over time did not increase above the 1st centile despite high maintenance doses of vitamin B6 (range 16-26 mg/kg/d), and mild sensory neuropathy was reported on nerve conduction studies. The findings in these siblings challenge assumptions that early and high dose pyridoxine treatment can benefit cognition in this population and suggest routine electromyography monitoring may be beneficial.
Subject(s)
Anticonvulsants/administration & dosage , Epilepsy, Generalized/genetics , Homozygote , Intellectual Disability/genetics , Phenotype , Pyridoxine/administration & dosage , Administration, Oral , Adolescent , Aldehyde Dehydrogenase/genetics , Brain/pathology , Child , Child, Preschool , Corpus Callosum/pathology , Dose-Response Relationship, Drug , Drug Administration Schedule , Drug Resistance/genetics , Drug Therapy, Combination , Electroencephalography/drug effects , Electromyography/drug effects , Epilepsy, Generalized/drug therapy , Female , Follow-Up Studies , Genetic Carrier Screening , Humans , Infant , Infant, Newborn , Infusions, Intravenous , Intellectual Disability/drug therapy , Intelligence/drug effects , Intelligence/genetics , Magnetic Resonance Imaging , Male , Mutation , Neurologic Examination/drug effects , Neuropsychological Tests , PregnancyABSTRACT
Sudden intense sensory stimuli elicit a cascade of involuntary responses, including a short-latency skeletal muscular response ('eyeblink startle response') and longer-latency autonomic responses. These responses are enhanced when subjects anticipate an aversive event compared to periods when subjects are resting ('fear potentiation'). It has been reported previously that the anxiolytic diazepam can suppress fear-potentiation of the eyeblink startle response in human volunteers. The present experiment aimed to confirm and extend these observations by examining the effect of another benzodiazepine, lorazepam, on the eyeblink and skin conductance components of the acoustic startle, and on fear-potentiation of these responses. Eighteen male volunteers participated in three weekly sessions in which they received oral treatment with placebo, lorazepam (1 mg) and lorazepam (2 mg), according to a balanced three-period, crossover, double-blind design. Two hours after ingestion of the treatments, electromyographic responses of the orbicularis oculi muscle and skin conductance responses were evoked by sound pulses during alternating periods in which the threat of an electric shock (electrodes attached to the subject's wrist) was present (THREAT) and absent (SAFE). The THREAT condition was associated with significant increase in the amplitude of the electromyographic (EMG) and skin conductance responses; there were also increases in baseline skin conductance, the number and amplitude of 'spontaneous' skin conductance fluctuations and self-rated anxiety. Lorazepam attenuated the effect of THREAT on self-rated anxiety and on the amplitude of the EMG response, but had no significant effect on fear-potentiation of the skin conductance responses. These results extend previous findings of the effect of diazepam on the fear-potentiated eyeblink startle response to lorazepam, and suggest that fear-potentiation of the later autonomic component of the startle response may be less sensitive to benzodiazepines than the fear-potentiated eyeblink response and self-rated anxiety.
Subject(s)
Fear/psychology , Hypnotics and Sedatives/pharmacology , Lorazepam/pharmacology , Reflex, Startle/drug effects , Acoustic Stimulation , Adolescent , Adult , Anxiety/psychology , Blinking/drug effects , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Electromyography/drug effects , Electroshock , Flicker Fusion/drug effects , Galvanic Skin Response/drug effects , Humans , MaleABSTRACT
OBJECTIVE: To observe the effect of Weichangshu (WCS) in treating diabetic gastroparesis (DGP). METHODS: Ninety-six patients with DGP were randomly divided into two groups. Besides the same conventional blood glucose controlling regimen was given to both groups, WSC was given to the treated group and Mosapride Citrate tablet to the control group additionally. The treatment course for them was 4 weeks. Therapeutic effect on clinical syndromes was assessed, the fasting and 2-hr postprandial blood glucose, antro-duodenal interdigestive migrating motor complex (MMC) and electrogastrogram (EGG) were measured before and after treatment. RESULTS: The therapeutic effect in the two groups were similar with no statistical significant difference. The time of MMC phase II was shortened, time of MMC phase III prolonged, and the constriction amplitude of which increased after treatment in both groups, showing significant difference as compared to those before treatment (P < 0.05). EGG were significantly changed after treatment mainly manifested as increase of proportional dominant frequency (PDF) and strengthening of proportional dominant amplitude (PDP ) (P <0.05 or P < 0.01). Besides, WSC also promoted the decrease of post-prandial blood glucose. CONCLUSION: WSC has dual effect in promoting gastric motility and decreasing blood glucose, with less adoerst reaction.