Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disorder.

BACKGROUND: In people with intellectual disabilities and/or autism spectrum disorder, oral midazolam (OM) is very effective as premedication for facilitating medical treatment. In this retrospective study, we investigated the optimal dosage of OM for premedication. METHODS: Patients with intellectual disability and/or autism spectrum disorder who were given OM as a premedication were selected from anaesthesia records. The primary outcome variable was the dose of OM (mg/kg) required to produce an adequate sedation. RESULTS: The mean OM dose required was 0.32 ± 0.10 mg/kg. The required OM dose decreased significantly as age and weight increased, and age and weight were also shown to be significantly associated with the dose of OM in the multivariate linear regression analysis. CONCLUSION: The dosage of OM to achieve adequate sedation should decrease as the patient ages. Furthermore, adequate sedation can be achieved with even lower doses of OM in obese people.

Capsaicin May Improve Swallowing Impairment in Patients with Amyotrophic Lateral Sclerosis: A Randomized Controlled Trial.

Patients with neurodegenerative diseases are at an increased risk of dysphagia and aspiration pneumonia. In this study, we examined whether ingestion of capsaicin prior to swallowing changes the temporal dynamics of swallowing in such patients. In a crossover, randomized controlled trial, 29 patients with neurodegenerative diseases were given a soluble wafer containing 1.5 µg capsaicin or an identical placebo 20 min prior to testing. For evaluation with video fluoroscopy (VF), patients consumed a barium-containing liquid plus thickening material. The durations of the latency, elevating and recovery periods of the hyoid were assessed from VF. Overall, no significant differences were observed in the duration of each period between capsaicin and placebo treatments. However, reductions in the latency and elevating periods were positively correlated with baseline durations. In subgroup analyses, that correlation was observed in patents with amyotrophic lateral sclerosis (ALS) but not in patients with Parkinson's disease. The consumption of wafer paper containing capsaicin before the intake of food may be effective in patients with dysphagia related with certain neurodegenerative diseases, particularly ALS patients. Further studies will be needed to validate this finding.

Comparison of Oxygen Saturation Between Nasal High-Flow Oxygen and Conventional Nasal Cannula in Obese Patients Undergoing Dental Procedures With Deep Sedation: A Randomized Crossover Trial.

PURPOSE: In anesthetic management, it is widely accepted that obese patients are more likely to suffer airway obstructions and reductions in arterial oxygen saturation (SpO2). Therefore, it is important to take special measures to prevent oxygen desaturation during the deep sedation of obese patients. This clinical study examined whether the use of nasal high-flow systems (NHFS) keep higher SpO2 and reduced hypoxemia than conventional nasal cannula during the deep sedation of obese patients with intellectual disabilities for dental treatment. MATERIALS AND METHODS: Eighteen obese patients (body mass index: >25) with intellectual disabilities who underwent dental sedation were enrolled. In each case, sedation was induced using propofol and maintained at a bispectral index of 50 to 70. The subjects were randomly assigned to the control oxygen administration (5 L/min via a nasal cannula) or NHFS (40% O2, 40 L/min, 37 °C) arm in alternate shifts as a crossover trial. The primary endpoint was the minimum SpO2 value, and the incidence of hypoxemia during dental treatment was also evaluated. RESULTS: The mean minimum SpO2 value was significantly higher in the NHFS arm than in the control arm (95.8 ± 2.1 % vs 93.6 ± 4.1 %, P = 0.0052, 95% confidence interval: 0.608-3.947). Hypoxemic episodes (SpO2: ≤94%) occurred 3 cases (16.7%) in the NHFS arm and 11 cases (61.1%) in the control arm (P = 0.0076, odds ratio: 0.127, 95% confidence interval 0.0324 - 0.630). CONCLUSION: NHFS resulted in higher minimum SpO2 and reduced hypoxemia than nasal cannula in obese patients during deep sedation for dental treatment.

Remifentanil suppresses increase in interleukin-6 mRNA in the brain by inhibiting cyclic AMP synthesis.

PURPOSE: Neuronal inflammation is caused by systemic inflammation and induces cognitive dysfunction. IL-6 plays a crucial role in therapies for neuronal inflammation and cognitive dysfunction. Remifentanil, an ultra-short-acting opioid, controls inflammatory reactions in the periphery, but not in the brain. Therefore, the anti-inflammatory effects of remifentanil in neuronal tissue and the involvement of cAMP in these effects were investigated in the present study. METHODS: Mice were divided into 4 groups: control, remifentanil, LPS, and LPS + remifentanil. Brain levels of pro-inflammatory cytokine mRNA, and serum levels of corticosterone, catecholamine and IL-6 were measured in the 4 groups. The co-localization of IL-6 and astrocytes in the mouse brain after the LPS injection was validated by immunostaining. LPS and/or remifentanil-induced changes in intracellular cAMP levels in cultured glial cells were measured, and the effects of cAMP on LPS-induced IL-6 mRNA expression levels were evaluated. RESULTS: Remifentanil suppressed increase in IL-6 mRNA levels in the mouse brain, and also inhibited the responses of plasma IL-6, corticosterone, and noradrenaline in an inflammatory state. In the hypothalamus, IL-6 was localized in the median eminence, at which GFAP immunoreactivity was specifically detected. In cultured cells, remifentanil suppressed increase in IL-6 mRNA levels and intracellular cAMP levels after the administration of LPS, and this enhanced IL-6 mRNA expression in response to LPS. CONCLUSION: Remifentanil suppressed increase in IL-6 mRNA levels in the brain in an inflammatory state, and this effect may be attributed to its direct action on neuronal cells through the inhibition of intracellular cAMP rather than corticosterone.

In vitro changes in the proportion of protein-unbound-free propofol induced by valproate.

PURPOSE: It has been reported that oral valproate (VPA) reduces the dose of propofol required for sedation. As  a potential reason for this, it is considered that VPA displaces serum protein-bound propofol and increases the proportion of protein-unbound-free propofol. To examine this hypothesis, the present in vitro study investigated the influence of VPA on the proportion of protein-unbound-free propofol in human serum samples. METHODS: Serum samples were collected from 10 healthy volunteers, who were not taking any medication. VPA (final concentration: 0.05, 0.1 or 1 mg/mL) and propofol (final concentration: 1 or 5 µg/mL) were mixed with serum samples with normal (4.0 g/dL) or low (2.5 g/dL) albumin concentrations. Then, protein-unbound-free propofol was extracted from the samples, and its concentration was measured using high-performance liquid chromatography. We compared the proportion of protein-unbound-free propofol in each of the VPA-containing samples with that in serum samples without VPA (control). RESULTS: In the serum samples with normal albumin concentrations, 1 mg/mL VPA significantly increased the proportion of protein-unbound-free propofol at 1 and 5 µg/mL propofol. Furthermore, in the serum samples with low albumin concentrations, the proportion of protein-unbound-free propofol was significantly increased by both 0.1 and 1 mg/mL VPA at propofol concentrations of 1 and 5 µg/mL. CONCLUSION: VPA might increase the proportion of protein-unbound-free propofol in human serum via displacement reactions.

Effect of carbamazepine or phenytoin therapy on blood level of intravenously administered midazolam: a prospective cohort study.

Dental treatment of intellectually disabled patients is frequently performed under general anesthesia or sedation. Many of these patients have epilepsy and are medicated with antiepileptic drugs (AEDs). Carbamazepine (CBZ) and phenytoin (PHT) are known to promote the metabolism of midazolam, and the blood levels of midazolam in patients medicated with CBZ or PHT may be different from those in healthy individuals. In this study, we clarified the influences of CBZ and PHT on the blood level of intravenously administered midazolam in patients medicated with CBZ or PHT. The subjects were divided into the following groups: not medicated with AEDs (control group), medicated with only CBZ or PHT (mono CBZ/PHT group), and medicated with CBZ or PHT or both and other AEDs (poly CBZ/PHT group). General anesthesia was achieved using midazolam, propofol, and remifentanil, and then the blood midazolam level was measured at 10, 30, and 60 min after intravenous midazolam administration. According to the results, the blood midazolam level was significantly lower in the mono and poly CBZ/PHT groups than in the control group. This finding suggests that intravenously administered midazolam may have a weaker effect in patients medicated with CBZ or PHT.

Female Patients Require a Higher Propofol Infusion Rate for Sedation.

Sedation may minimize physiologic and behavioral stress responses. In our facility, the infusion rate of propofol is adjusted according to the bispectral index (BIS) in all cases of implant-related surgery; multivariate analysis of retrospective data enabled us to extract independent factors that affect the dose of propofol in sedation that are considered useful indicators for achieving adequate sedation. The study population comprised all patients undergoing implant-related surgery under intravenous sedation in Okayama University Hospital from April 2009 to March 2013. The infusion rate of propofol was adjusted to maintain the BIS value at 70-80. The outcome was the average infusion rate of propofol, and potential predictor variables were age, sex, body weight, treatment time, and amount of midazolam. Independent variables that affected the average infusion rate of propofol were extracted with multiple regression analysis. One hundred twenty-five subjects were enrolled. In the multiple regression analysis, female sex was shown to be significantly associated with a higher average infusion rate of propofol. Females may require a higher infusion rate of propofol than males to achieve adequate sedation while undergoing implant-related surgery.

Genetic basis of age-dependent synaptic abnormalities in the retina.

Understanding the normal aging process will help us determine the mechanisms of how age-related diseases are caused and progress. A/J inbred mice have been shown to exhibit accelerated aging phenotypes in the retina including increased inflammation and photoreceptor cell degeneration, which resemble human aging symptoms. C57BL/6J (B6) inbred mice are less susceptible for these abnormalities, indicating the existence of genetic factor(s) that affect their severity. In this study, we determined that another age-dependent phenotype, ectopic synapse formation, is also accelerated in the A/J retina compared to the B6 retina. Through genetic mapping utilizing recombinant inbred strains, we identified quantitative trait loci (QTLs) on chromosome 7 and 19, which contribute to abnormal retinal synapses as well as other age-dependent phenotypes. Using consomic single chromosome substitution lines where a single chromosome is from A/J and the rest of the genome is B6, we investigated the individual effect of each QTL on retinal aging phenotypes. We observed that both QTLs independently contribute to abnormal retinal synapses, reduction in the number of cone cells, and an up-regulation of retinal stress marker, glial fibrillary acidic protein (GFAP). Mice with a single chromosome substitution on chromosome 19 also exhibited an increase in inflammatory cells, which is characteristic of aging and age-related macular degeneration. Thus, we identified QTLs that are independently capable of affecting the severity and progression of age-dependent retinal abnormalities in mice.

Effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans: a crossover double-blind study.

PURPOSE: Recently, attention has been paid to dexmedetomidine, a selective α-2 adrenoceptor agonist, as a possible additive for local anesthesia. However, the effect of locally injected dexmedetomidine on the anesthetic action in humans has not fully been clarified. Thus, the purpose of the present study was to evaluate the effect of dexmedetomidine injected into the oral mucosa in combination with lidocaine on local anesthetic potency in humans. MATERIALS AND METHODS: Twenty healthy volunteers were included in the present crossover double-blinded study. Lidocaine solution or lidocaine plus dexmedetomidine solution was submucosally injected into the alveolar mucosa in a crossover and double-blinded manner. The local anesthetic effect of the solutions was evaluated by measuring the current perception threshold (CPT) in the oral mucosa for 120 minutes after injection. Furthermore, the sedation level, blood pressure, and heart rate of the volunteers were evaluated. For statistical analysis, the Wilcoxon signed rank test and 2-way repeated measures analysis of variation were used. RESULTS: The CPT was increased with the 2 solutions and peaked 10 minutes after injection. CPT values 10 and 20 minutes after injection of lidocaine plus dexmedetomidine solution were considerably higher than those with lidocaine solution. The duration of an important increase in the CPT after injection with lidocaine plus dexmedetomidine solution was longer than that with lidocaine. Furthermore, the area under the time curve of CPT was considerably higher with lidocaine plus dexmedetomidine solution than with lidocaine solution. No volunteer showed a change in sedation level, blood pressure, or heart rate after injection with either test solution throughout the experiment. CONCLUSION: The present study showed that a combination of dexmedetomidine plus lidocaine considerably enhances the local anesthetic potency of lidocaine without any major influences on the cardiovascular system when locally injected into the oral mucosa.

Independent predictors of delay in emergence from general anesthesia.

Some patients with intellectual disabilities spend longer than others in emergence from ambulatory general anesthesia for dental treatment. Although antiepileptic drugs and anesthetics might be involved, an independent predictor for delay of the emergence remains unclear. Thus, a purpose of this study is to identify independent factors affecting the delay of emergence from general anesthesia. This was a retrospective cohort study in dental patients with intellectual disabilities. Patients in need of sedative premedication were removed from participants. The outcome was time until emergence from general anesthesia. Stepwise multivariate regression analysis was used to extract independent factors affecting the outcome. Antiepileptic drugs and anesthetic parameters were included as predictor variables. The study included 102 cases. Clobazam, clonazepam, and phenobarbital were shown to be independent determinants of emergence time. Parameters relating to anesthetics, patients' backgrounds, and dental treatment were not independent factors. Delay in emergence time in ambulatory general anesthesia is likely to be related to the antiepileptic drugs of benzodiazepine or barbiturates in patients with intellectual disability.

Locally injected dexmedetomidine inhibits carrageenin-induced inflammatory responses in the injected region.

BACKGROUND: Dexmedetomidine, a highly selective agonist of α2-adrenoceptors, is a commonly used sedative; however, a potent anti-inflammatory effect has also been found. In the present study we evaluated the inhibitory effect of locally injected dexmedetomidine on inflammatory responses in the injected region. METHODS: Local inflammation was induced in the hindpaws of male mice (aged 6-8 weeks) by intraplantar injection of lambda-carrageenin. To offset the central effect of tested agents, different agents were blindly injected into the left and right paws in the pairs of comparison. The effect of dexmedetomidine on edema (increase in paw volume), the accumulation of leukocytes, and production of tumor necrosis factor-α (TNF-α) and cyclooxygenase-2 (COX-2) were evaluated after carrageenin injection, using water displacement plethysmometry, histological imaging, immunohistochemistry, and Western blotting analysis. Furthermore, we also evaluated the effect of yohimbine, a full antagonist of α2-adrenoceptors, and phenylephrine, an agonist of the α1-adrenoceptor, on dexmedetomidine's action on inflammatory responses. RESULTS: Paw volume and amount of leukocytes in the injected region significantly increased after the injection of carrageenin. Similarly, TNF-α and COX-2 production was found in the subcutaneous region injected with carrageenin, 4 hours after injection. Dexmedetomidine significantly inhibited all increases in paw volume, leukocytes, and production of TNF-α and COX-2. Furthermore, yohimbine significantly antagonized the anti-inflammatory effects of dexmedetomidine, whereas phenylephrine did not significantly alter them. CONCLUSIONS: The findings suggest that locally injected dexmedetomidine exhibits an anti-inflammatory effect against local acute inflammatory responses, mediated by α2-adrenoceptors.

Chronic orofacial pain in dental patients: retrospective investigation over 12 years.

Orofacial pain is often difficult to diagnose and treat. However, there have been few reports on the clinical observation of dental patients with orofacial pain. We retrospectively investigated the characteristics of 221 dental patients who had suffered from persistent orofacial pain. Data were collected from the outpatient medical records in our clinic over the past 12 years. More than half of the patients (53.8%) had suffered with pain for more than 6 months from pain onset until the first visit to our clinic. The main diagnoses were neuropathic pain (30.3%), myofascial pain (23.5%), psychogenic pain (20.4%), odontogenic toothache (17.2%), and others (7.7%) such as temporomandibular disorders and glossitis. The treatments included pharmacotherapy, splint therapy, and others such as nerve block, dental treatment, physiotherapy, and/or psychotherapy. Excluding the patients (52 of 221 initially enrolled patients) with unknown responses to treatment, 65.7% showed remission or a significant improvement in pain in response to treatment. Although only a small group of patients had odontogenic toothache, the rate of improvement was highest for this disorder. In conclusion, early consultation with a dentist is useful to prevent chronicity of odontogenic pain and to make a differential diagnosis in patients with orofacial pain.

Hemodynamic changes by drug interaction of adrenaline with chlorpromazine.

Adrenaline (epinephrine) is included in dental local anesthesia for the purpose of vasoconstriction. In Japan, adrenaline is contraindicated for use in patients receiving antipsychotic therapy, because the combination of adrenaline and an antipsychotic is considered to cause severe hypotension; however, there is insufficient evidence supporting this claim. The purpose of the present study was to clarify the changes in hemodynamics caused by drug interaction between adrenaline and an antipsychotic and to evaluate the safety of the combined use of adrenaline and an antipsychotic in an animal study. Male Sprague-Dawley rats were anesthetized with sodium pentobarbital. A catheter was inserted into the femoral artery to measure blood pressure and pulse rate. Rats were pretreated by intraperitoneal injection of chlorpromazine or chlorpromazine and propranolol, and after 20 minutes, saline or 1 of 3 different doses of adrenaline was administered by intraperitoneal injection. Changes in the ratio of mean arterial blood pressure and pulse rate were measured after the injection of adrenaline. Significant hypotension and tachycardia were observed after the injection of adrenaline in the chlorpromazine-pretreated rats. These effects were in a dose-dependent manner, and 100 µg/kg adrenaline induced significant hemodynamic changes. Furthermore, in the chlorpromazine and propranolol-pretreated rats, modest hypertension was induced by adrenaline, but hypotension and tachycardia were not significantly shown. Hypotension was caused by a drug interaction between adrenaline and chlorpromazine through the activation of the ß-adrenergic receptor and showed a dose-dependent effect. Low-dose adrenaline similar to what might be used in human dental treatment did not result in a significant homodynamic change.

Mutation in archain 1, a subunit of COPI coatomer complex, causes diluted coat color and Purkinje cell degeneration.

Intracellular trafficking is critical for delivering molecules and organelles to their proper destinations to carry out normal cellular functions. Disruption of intracellular trafficking has been implicated in the pathogenesis of various neurodegenerative disorders. In addition, a number of genes involved in vesicle/organelle trafficking are also essential for pigmentation, and loss of those genes is often associated with mouse coat-color dilution and human hypopigmentary disorders. Hence, we postulated that screening for mouse mutants with both neurological defects and coat-color dilution will help identify additional factors associated with intracellular trafficking in neuronal cells. In this study, we characterized a mouse mutant with a unique N-ethyl-N-nitrosourea (ENU)-induced mutation, named nur17. nur17 mutant mice exhibit both coat-color dilution and ataxia due to Purkinje cell degeneration in the cerebellum. By positional cloning, we identified that the nur17 mouse carries a T-to-C missense mutation in archain 1 (Arcn1) gene which encodes the delta subunit of the coat protein I (COPI) complex required for intracellular trafficking. Consistent with this function, we found that intracellular trafficking is disrupted in nur17 melanocytes. Moreover, the nur17 mutation leads to common characteristics of neurodegenerative disorders such as abnormal protein accumulation, ER stress, and neurofibrillary tangles. Our study documents for the first time the physiological consequences of the impairment of the ARCN1 function in the whole animal and demonstrates a direct association between ARCN1 and neurodegeneration.

Anesthetic Management Using Remimazolam in a Hemodialysis Patient.

Remimazolam, an ultra-short-acting benzodiazepine, is a new intravenous anesthetic used for sedation and general anesthesia. Because remimazolam is primarily metabolized by carboxylesterases in the liver and other tissues including the lung and has metabolites with little or no bioactivity, its anesthetic effect is not significantly influenced by renal dysfunction. Therefore, remimazolam may be considered an appropriate agent for hemodialysis patients and may have added benefits beyond midazolam and propofol. Remimazolam has also been suggested to cause less cardiac depression than propofol. This case report presents an 82-year-old female hemodialysis patient with chronic heart failure who underwent partial glossectomy for squamous cell carcinoma of the tongue under general anesthesia with remimazolam and remifentanil. Hemodynamic control was stable during the anesthetic, which was safely completed without any adverse events and resulted in a rapid, clear emergence without flumazenil. Remimazolam and remifentanil may be appropriate as first-line general anesthetic agents for hemodialysis patients with heart failure.

Evaluation of Sedation Levels Using SedLine During Intravenous Sedation for Dental Procedures: A Case-Series Study.

The Patient State Index (PSI) is the numerical value of anesthesia depth as measured using a SedLine Sedation Monitor (Masimo Corporation). In this pilot study, we evaluated PSI values captured during intravenous (IV) moderate sedation for dental treatment. During the dental treatment, a dental anesthesiologist maintained the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score at 3 to 4 by adjusting the administration of midazolam and propofol while PSI values were recorded. The mean (SD) and median (25th percentile, 75th percentile) PSI values during dental treatment under IV moderate sedation were 72.7 (13.6) and 75 (65, 85), respectively.

The influence of oral VPA on the required dose of propofol for sedation during dental treatment in patients with mental retardation: a prospective observer-blinded cohort study.

In sedation of dental patients with moderate or severe mental retardation, it is difficult to identify the optimum sedation level and to maintain it appropriately. Moreover, many patients have concomitant epilepsy and are medicated with oral antiepileptic drugs (AEDs), which influence the drug-metabolizing enzymes. In particular, valproate (VPA) has been demonstrated to inhibit propofol metabolism in vitro. Therefore, the objective of the present study was to investigate the clinical influence of oral VPA on the required dose of propofol for sedation, with use of a prospective cohort study design. We studied 45 patients with moderate or severe mental retardation who underwent dental treatment under sedation. Propofol was infused, and sedation was maintained at the same level in all patients using a bispectral index (BIS) monitor. After the completion of treatment for the scheduled patients, patients were divided into those with oral VPA treatment (VPA group: 20 patients) and without any oral antiepileptic treatment (control group: 25 patients). The propofol dose required for sedation and times to the recovery of the eyelash reflex and spontaneous eye opening were evaluated. The median required propofol doses in the VPA and control groups were 4.15 (range 1.97-5.88) and 5.67 (2.92-7.17) mg/kg/h, respectively. We observed a statistically significant difference between the two patient groups with respect to median VPA dose (p < 0.01). However, no statistically significant differences were noted in the time until eyelash reflex recovery or spontaneous eye opening between the two groups. The results suggest that oral VPA reduces the dose of propofol required for sedation during dental treatment in patients with moderate or severe mental retardation.

Midazolam is associated with delay in recovery and agitation after ambulatory general anesthesia for dental treatment in patients with disabilities: a retrospective cohort study.

PURPOSE: Some patients with intellectual disabilities (IDs) who undergo total intravenous anesthesia (TIVA) have complications associated with the anesthesia such as prolonged recovery. The purposes of this study were to estimate the frequency of TIVA complications among patients with IDs and to identify factors associated with TIVA complications. MATERIALS AND METHODS: This study was designed as a retrospective cohort study. Study samples were selected from the clinical records of patients with IDs who underwent ambulatory general anesthesia in a special dental clinic at the Okayama University Hospital, Okayama, Japan. Predictor variables were patient background, anesthesia-related variables, and dental treatment. Outcome variables were delayed recovery and the complication of agitation. Factors affecting delayed recovery and complications were examined with multivariable analysis. RESULTS: We enrolled 106 cases (81 male and 25 female patients) in this study. The mean age was 23.9 years. Serious complications were not observed in any cases. The amount of intravenous midazolam was an independent determinant of delayed recovery. Oral midazolam contributed to delayed recovery, although it is very useful for induction in patients with a high level of fear. Oral midazolam and a younger age were independent predictors of agitation. CONCLUSIONS: Intravenous midazolam may not have an advantage in ambulatory general anesthesia. Oral midazolam contributes to delayed recovery and is an independent predictor of agitation.

Effects of midazolam and phenobarbital on brain oxidative reactions induced by pentylenetetrazole in a convulsion model.

CONTEXT: Brain oxidative reactions are involved in epilepsy as well as neurodegenerative diseases. In animal convulsion models, some anticonvulsants have been found to suppress oxidative reactions associated with convulsions. However, the effect of anticonvulsants on brain oxidative reactions has not fully been clarified. OBJECTIVE: Midazolam and phenobarbital are often used as an intravenous anesthetic, and are known to have anticonvulsive effect, but antioxidative effect of these drugs has rarely been studied. Thus, the purpose of this study was to evaluate the effects of these drugs on the degree of convulsions and brain oxidative reactions in an animal convulsion model. MATERIALS AND METHODS: In order to evaluate brain oxidative reactions, we measured malondialdehyde (MDA) level and heme oxygenase (HO)-1 mRNA expression level in the brain of mice in a convulsion model generated by a single injection of pentylenetetrazole (PTZ). We evaluated the effects of midazolam and phenobarbital on the degree of PTZ-induced convulsions and on the changes in brain MDA level and HO-1 mRNA expression level. RESULTS: After PTZ injection, severe convulsions were observed in all mice. MDA level was increased in the whole brain, while HO-1 mRNA expression level was increased only in the hippocampus. Both midazolam and phenobarbital prevented the convulsions and suppressed the increase in both MDA level and HO-1 mRNA expression level in the brain. CONCLUSION: In this study, both midazolam and phenobarbital suppressed PTZ-induced MDA and HO-1 reactions in the brain, suggesting that these drugs inhibit brain oxidative reactions in a convulsion model.