Comparison of preventive effects of combined furosemide and mannitol versus single diuretics, furosemide or mannitol, on cisplatin-induced nephrotoxicity.

Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m2, and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m2) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients.

Efficacy of 3-day versus 5-day aprepitant regimens for long-delayed chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is an ongoing problem. While effectiveness of triplet antiemetic regimens in the delayed CINV phase (24-120 hours after administration of chemotherapy) has been studied, their effectiveness in the long-delayed phase (120-168 hours post-administration) is unknown. We compared the efficacy of 3- and 5-day courses of a triplet antiemetic prophylaxis containing aprepitant (APR) in controlling long-delayed CINV after cisplatin (CDDP)-based chemotherapy. RESEARCH DESIGN AND METHODS: We obtained patient-level data from a nationwide, multicenter, prospective observational study in Japan. The incidence and timing of CINV after 3- and 5-day APR-containing regimens were compared using inverse probability treatment weighting. RESULTS: The analysis included 380 patients. The incidence rates of long-delayed nausea and vomiting were significantly reduced for the 5-day compared with the 3-day regimen (29.1% vs. 22.2%, p = 0.0042; 6.7% vs. 0%, p < 0.0001, respectively). Among those without CINV, vomiting was not reported after day 2 in the 5-day APR group but increased after day 4 in the 3-day APR group. CONCLUSION: A 5-day regimen triplet antiemetic prophylaxis with APR decreased long-delayed vomiting compared with a 3-day regimen in patients receiving CDDP-based chemotherapy. However, the 5-day regimen showed no advantage over the 3-day regimen against long-delayed nausea.

Adrenaline-resistant anaphylactic shock caused by contrast medium in a patient after risperidone overdose: a case report.

BACKGROUND: In Japan, the use of risperidone in combination with adrenaline is contraindicated, except in cases of anaphylaxis. Therefore, there is limited clinical evidence regarding the interaction of these two drugs. Here, we report the clinical course of a case of adrenaline-resistant anaphylactic shock induced by a contrast medium injection after a risperidone overdose. CASE PRESENTATION: A man in his 30s was transported to our hospital after attempting suicide by taking 10 mg of risperidone and jumping from a height of 10 m. To determine the location and severity of his injuries, he was injected with an iodinated contrast medium, after which he developed generalized erythema and hypotension and was diagnosed with anaphylactic shock. A 0.5 mg dose of adrenaline was administered with no improvement, followed by another 0.5 mg dose that did not change his blood pressure. After infusion of a sodium bicarbonate solution (8.4%), administration of fresh frozen plasma, and additional administration of adrenaline (0.6-1.2 µg/min), his blood pressure improved, and he recovered from the anaphylactic shock. CONCLUSIONS: This was a rare case of a risperidone overdose followed by adrenaline-resistant anaphylactic shock. The resistance is likely associated with the high blood concentration of risperidone. Our findings indicate that the potential for decreased adrenergic responsiveness should be considered in patients undergoing risperidone treatment in the event of anaphylactic shock.

Effectiveness of Palonosetron, 1-Day Dexamethasone, and Aprepitant in Patients Undergoing Carboplatin-Based Chemotherapy.

INTRODUCTION: Dexamethasone (DEX)-sparing strategy with 5-hydroxytryptamine-3 receptor antagonist (5HT3RA) and aprepitant (APR), as triplet antiemetic prophylaxis, is associated with poor control of delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving carboplatin (CBDCA)-based chemotherapy. This study aimed to evaluate whether using palonosetron (PALO) as a 5HT3RA provides superior control with CINV than first-generation (1st) 5HT3RA in triplet antiemetic prophylaxis with a DEX-sparing strategy. METHODS: Pooled patient-level data from a nationwide, multicenter, and prospective observational study were analyzed to compare the incidence of CINV between patients administered PALO and 1st 5HT3RA in combination with 1-day DEX and APR. RESULTS: No significant differences were observed in the incidence of CINV, pattern of CINV, or severity of nausea by type of 5HT3RA in triplet antiemetic prophylaxis with DEX-sparing strategy. In both groups, the incidence of nausea gradually increased from day 3, peaked on day 4 or 5, and then declined slowly. The visual analog scale scores in the delayed phase remained high throughout the 7-day observation period. CONCLUSION: Careful patient selection and symptom monitoring are needed when implementing the DEX-sparing strategy in triplet antiemetic prophylaxis for patients undergoing CBDCA-based chemotherapy. Furthermore, additional strategies may be needed to achieve better control of delayed CINV.

Therapeutic effect of anti-HMGB1 antibody in a mouse model of 4-h middle cerebral artery occlusion: comparison with tissue plasminogen activator.

OBJECTIVE: Delayed tissue plasminogen activator (tPA) treatment increases the risk of intracerebral hemorrhage in patients with ischemic stroke. We previously demonstrated that tPA treatment caused hemorrhagic complications in a 4-h middle cerebral artery occlusion (MCAO) mouse model when administered after reperfusion. In the present study, we administered an anti-high mobility group box 1 (αHMGB1) antibody to 4-h MCAO mice to evaluate the usability of αHMGB1 antibody treatment in the delayed phase of ischemia, beyond the therapeutic time window of tPA. METHODS: αHMGB1 antibody, tPA and control IgG were dissolved in normal saline and administered intravenously into the tail vein of the mice after reperfusion. Infarct volume, hemorrhagic volume, brain swelling, functional outcomes and levels of pro-inflammatory cytokines, such as HMGB1, interleukin (IL)-6 and tumor necrosis factor (TNF)-α, were evaluated 24 h after MCAO. RESULTS: tPA treatment was not only ineffective but also caused a massive intracerebral hemorrhage. Treatment with αHMGB1 antibody reduced the infarct volume and swelling and ameliorated neurologic impairment and motor coordination without hemorrhagic complications by inhibiting HMGB1 activity. Moreover, the αHMGB1 antibody suppressed pathways of secondary inflammatory responses, such as IL-6 and TNF-α, after cerebral ischemia. CONCLUSION: These results indicate that αHMGB1 antibody may be therapeutically efficient in the delayed phase of ischemia, where tPA treatment is no longer an eligible option. Treatment with an αHMGB1 antibody may be an effective therapeutic option in patients who exceed the tPA therapeutic time window.

Preventive effect of 20 mEq and 8 mEq magnesium supplementation on cisplatin-induced nephrotoxicity: a propensity score-matched analysis.

PURPOSE: The protective effect of magnesium (Mg) supplementation against cisplatin (CDDP)-induced nephrotoxicity has been widely described; however, the optimal dose of Mg supplementation is unclear. The aim of this study was to investigate whether 20 mEq of Mg supplementation is more effective than 8 mEq Mg in preventing CDDP-induced nephrotoxicity, as well as the associated risk factors, in cancer patients treated with CDDP-based chemotherapy. METHODS: Pooled data of 272 patients receiving 20 mEq or 8 mEq Mg supplementation to CDDP-based chemotherapy from a multicenter, retrospective, observational study were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify the risk factors for renal failure induced by each treatment dose. RESULTS: There was no significant difference in the incidence of nephrotoxicity between the 8 mEq and 20 mEq groups (P = 0.926). There was also no significant difference in the severity of nephrotoxicity, elevated serum creatinine levels, and decreased estimated creatinine clearance levels between the two groups. Cardiac disease and albumin levels were identified as independent risk factors for CDDP-induced nephrotoxicity. CONCLUSION: We did not find an advantage of 20 mEq over 8 mEq Mg supplementation in terms of a preventive effect against CDDP-induced nephrotoxicity. The optimal dose of Mg supplementation for the prevention of CDDP-induced nephrotoxicity remains unknown, and further studies are warranted.

IEEE P7001: A Proposed Standard on Transparency.

This paper describes IEEE P7001, a new draft standard on transparency of autonomous systems. In the paper, we outline the development and structure of the draft standard. We present the rationale for transparency as a measurable, testable property. We outline five stakeholder groups: users, the general public and bystanders, safety certification agencies, incident/accident investigators and lawyers/expert witnesses, and explain the thinking behind the normative definitions of "levels" of transparency for each stakeholder group in P7001. The paper illustrates the application of P7001 through worked examples of both specification and assessment of fictional autonomous systems.

Understanding the degradation mechanisms of InGaN/GaN multiple quantum well UV photodetectors submitted to different current stresses.

The degradation characteristics of InGaN/GaN multiple quantum well (MQW) photodetectors (PDs) stressed at 100 and 200 mA over 480 h are investigated. We have observed that the luminescence intensity, short circuit current density, and open circuit voltage decrease strongly, whereas the leakage current increases intensely due to the constant current stress. The strong activity of the Mg dopant and trap-assisted tunneling under the direct current stress are critical factors in the degradation of InGaN/GaN MQW PDs. Further, the photocurrent spectroscopy results reveal that for 100 mA stress current, the peak value of relative external quantum efficiency (EQE) slightly increases due to the widening of the space-charge region while, for the 200 mA of stress current, the peak value of EQE decreases (∼15.4%) due to some permanent damages in the active region and/or the metal/semiconductor interface, and the associated resistive effects.

Synchronous Primary Lung Adenocarcinoma and Hepatocellular Carcinoma Successfully Treated with a Combination of Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel.

Chemotherapy for multiple primary malignancies is challenging. We herein report a case of synchronous primary lung adenocarcinoma and hepatocellular carcinoma (HCC). A 72-year-old man was admitted for the evaluation of an abnormal shadow on his lung. Computed tomography revealed a lung nodule in the right upper lobe and multiple liver masses. He was diagnosed with synchronous primary lung adenocarcinoma and HCC. Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) chemotherapy was efficacious for both tumors. ABCP chemotherapy may be a potential treatment option for synchronous primary lung adenocarcinoma and HCC.

[Effects of Recommended Consultation Practice Using Fracture Risk Assessment Tool and Fracture Evaluation Questionnaire for Early Detection of Osteoporosis at Community Pharmacies].

As one of the strategies for the early detection and treatment of osteoporosis, we have recommended visiting a hospital, based on the Fracture Risk Assessment Tool (FRAX®) and evaluation questionnaire for osteoporotic fracture risk. In this study, we evaluated the impact of intervention by community pharmacists by integrating our data for the FRAX® and questionnaire. The measurement of FRAX® and the questionnaire survey were conducted through participation in health seminars organized by a community general support center from June 2018 to December 2019. Participants with a FRAX® score more than 15% and at least one item in the questionnaire were considered to have "suspected osteoporosis" were recommended medical consultation. The medical treatment status for the participants considered to have "suspected osteoporosis" aged 40-90 years were analyzed. Of the 84 participants, 54 had a FRAX® score more than 15%, and 44 participants fulfilled at least one item in the questionnaire. Medical consultation was recommended to 26 of these 44 participants, excluding 18 under treatment. Of the 25 participants, six (excluding one who disagreed) received consultation, and medical treatment was started for four of them (66.7%). However, consultation with the attending physician was recommended to five of the 18 participants who were initially on treatment but discontinued it at the time of the survey. Consequently, two participants resumed their osteoporosis treatment. Our data suggest advantages of community pharmacists' intervention using FRAX® and a questionnaire for osteoporotic fracture risk measurement for early detection and medical treatment.

Efficacy of one-day versus multiple-day dexamethasone for chemotherapy-induced nausea and vomiting in lung cancer patients receiving carboplatin-based chemotherapy: a propensity score-matched analysis.

PURPOSE: Dexamethasone (DEX)-sparing strategies (one-day DEX) with palonosetron as doublet antiemetic prophylaxis have previously been studied. However, DEX-sparing regimens with 5-hydroxytryptamine-3 receptor antagonist (5-HT3RA) and aprepitant (APR), as triplet antiemetic prophylaxis, have not been evaluated. This study aimed to evaluate the efficacy of a combination of 5-HT3RA, APR, and DEX on day 1 of carboplatin (CBDCA)-based chemotherapy in patients with lung cancer. METHODS: Data were pooled from a nationwide, multicenter, prospective observational study using propensity score-matched analysis to compare the incidence of chemotherapy-induced nausea and vomiting (CINV) between one- and multiple-day DEX regimens in combination with 5-HT3RA plus APR. RESULTS: Incidence of delayed nausea was significantly higher in the one-day than in the multiple-day DEX group. Incidence of nausea was also significantly higher in the one-day than in the multiple-day DEX group on days 3-5. Kaplan-Meier curves for nausea showed a significant difference between the two groups; however, there was no significant difference in the occurrence of vomiting or the Kaplan-Meier curves of time to vomiting. CONCLUSION: To the best of our knowledge, this study is the first to evaluate the efficacy of a DEX-sparing regimen by comparing one- and multiple-day DEX combined with 5-HT3RA and APR concerning CINV incidence in lung cancer patients receiving CBDCA-based chemotherapy. Antiemetic regimens of one-day DEX result in poor control of delayed nausea; therefore, we recommend the application of the DEX-sparing strategy only after careful patient selection while considering the development of nausea.

Chemotherapy-induced nausea and vomiting (CINV) with carboplatin plus pemetrexed or carboplatin plus paclitaxel in patients with lung cancer: a propensity score-matched analysis.

BACKGROUND: Patients with lung cancer who are treated with carboplatin-based chemotherapy regimens often experience chemotherapy-induced nausea and vomiting (CINV). However, knowledge on the effect of regimen and cofactors on the risk of CINV is limited. This study aimed to analyze and compare the incidence of CINV between lung cancer patients undergoing carboplatin plus pemetrexed (CBDCA+PEM) and those undergoing carboplatin plus paclitaxel (CBDCA+PTX) chemotherapy. METHODS: Pooled data of 240 patients from two prospective observational studies were compared using propensity score matching. Separate multivariate logistic regression analyses were used to identify risk factors for nausea and vomiting following chemotherapy. RESULTS: Delayed nausea was significantly more common in patients treated with CBDCA+PEM than in those treated with CBDCA+PTX (51.1% vs. 36.2%, P = 0.04), but the incidence of vomiting did not significantly differ between the two groups (23.4% vs. 14.9%, P = 0.14). The occurrence of CINV peaked on day 4 in the CBDCA+PTX group and on day 5 in the CBDCA+PEM group. Multivariate analysis showed that female sex, younger age, and CBDCA+PEM regimen were independent risk factors for delayed nausea, while female sex was an independent risk factor for delayed vomiting. CONCLUSIONS: The CBDCA + PEM regimen has a higher risk of causing delayed nausea than the CBDCA + PTX regimen, and aggressive antiemetic prophylaxis should be offered to patients treated with CBDCA + PEM.

5HT3 RA plus dexamethasone plus aprepitant for controlling delayed chemotherapy-induced nausea and vomiting in colorectal cancer.

Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L-OHP)-based chemotherapy. Whether neurokinin-1 receptor antagonist addition to a first-generation 5HT3 antagonist (1st 5-HT3 RA) and dexamethasone (DEX) is beneficial to these patients remains controversial. Furthermore, whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV is unclear. We, therefore, investigated whether PALO+DEX or 1st 5-HT3 RA+DEX+APR was more effective in controlling delayed CINV, and the risk factors for delayed CINV, in CRC patients undergoing L-OHP-based chemotherapy. Data were pooled from two prospective observational Japanese studies and a phase III trial to compare CINV incidence between the PALO + DEX (PALO) and 5-HT3 RA+DEX+APR (APR) groups by propensity score-matched analysis. CINV risk factors were identified using logistic regression models. The CINV incidence was higher in the PALO group than in the APR group. Logistic regression analysis revealed alcohol consumption, motion sickness, and the PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and the PALO+DEX regimen as those for delayed vomiting. Compared with prophylactic PALO + DEX, 1st 5-HT3 RA+DEX+APR was more effective in controlling delayed CINV. Thus, CRC patients receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR.

Antithrombin gamma attenuates macrophage/microglial activation and brain damage after transient focal cerebral ischemia in mice.

AIMS: Thrombin formation is increased in patients with acute cerebral ischemic stroke, and augments coagulation and inflammation in the brain. Administration of antithrombin (AT) was previously reported to be protective against renal and myocardial ischemic injury. Thus, we hypothesized that treatment with AT would be neuroprotective against cerebral ischemic injury. This study evaluated the effects of AT treatment on ischemic inflammation and brain damage in mice subjected to middle cerebral artery occlusion (MCAO). MAIN METHODS: A mouse model of 4-hour MCAO was used to induce ischemic brain injury. Recombinant AT gamma was administered intravenously immediately after reperfusion at 4 h after MCAO. Infarct volume, neurological deficit, and regional cerebral blood flow (rCBF) were measured at 24 h after MCAO. To evaluate the effect of AT gamma on ischemic inflammation, we measured the number of Iba1-positive cells (marker of macrophage/microglial activation) and levels of proinflammatory cytokines. Further, we investigated the direct anti-inflammatory effects of rAT in the J774.1 cell line. KEY FINDINGS: Treatment with AT gamma (480 U/kg) reduced infarct volume and neurological deficit, and improved rCBF, in MCAO mice. Moreover, AT gamma treatment decreased the number of Iba1-positive cells and levels of proinflammatory cytokines. In vitro, treatment with thrombin significantly increased proinflammatory cytokine levels, which was significantly reduced by pretreatment with AT gamma. SIGNIFICANCE: Treatment with AT showed neuroprotective effects via anticoagulation actions, as well as direct anti-inflammatory effects on macrophage/microglial activation. These data suggest that AT may be a useful new therapeutic option for cerebral ischemia.

[Evaluation of the Collaboration between Community Interprofessionals and Pharmacists for Early Detection of Dementia].

The purpose of this study is to evaluate the collaboration system between Muscat Pharmacy and community general support center by verifying the results of tests for early detection of dementia, and the early support response for the participants with suspected dementia by the center. From December 2016 to November 2018, we conducted measurement sessions using a touch panel-type test, MSP-1100 at 23 events that included health promotion classes and local community events directed by community general support center. At a later date, a visit survey was administered by the center to the participants with suspected dementia those who received a score lower than 12, and their individual records of early support responses and follow-ups were evaluated and analyzed. During the period, 597 participants had measurements taken with the touch panel-type test. Among them, 89 (14.9% of total) participants received a score lower than 12. The contents of the support by the center for the low-scoring participants were classified into nine categories. Forty of the 89 low-scoring participants were judged to have no problems. Others were cooperatively followed up with medical consultation recommendation, receiving home care management, and/or having their information provided physicians by the Muscat pharmacy and the center. The results of our study indicate that the cooperation between community pharmacy and community general support centers could allow for the early detection of dementia and follow-ups for suspected dementia.

Long-Term Treatment with Thrombomodulin Improves Functional Outcomes after Cerebral Ischemia Even if Administration is Delayed.

Our previous study indicated that recombinant human soluble thrombomodulin (rhsTM) could attenuate brain damage when administered as a bolus in the cerebral ischaemic early phase. Then, we considered that treatment with rhsTM may show therapeutic effects even when administered in the ischaemic delayed phase, because rhsTM has an action of inhibiting high-mobility group box 1 (HMGB1) as a late mediator of lethal systemic inflammation. This study was performed to investigate the effects of delayed treatment with rhsTM on ischaemic brain damage induced by high HMGB1 level in mice subjected to 4-hour middle cerebral artery occlusion (MCAO). One day after MCAO, rhsTM was administered intraperitoneally at a dose of 1 or 5 mg/kg once a day for 7 days. Neurological score, motor coordination and HMGB1 levels were measured 1, 3 and 7 days after MCAO. The presence of activated microglia was evaluated 7 days after MCAO. Systemic HMGB1 levels increased 1 to 7 days after MCAO and were higher at 7 days compared with day 1. At the same time, survival rate decreased, and activated microglia increased in the infarct area. Treatment with rhsTM improved neurological score, motor coordination, survival and prevented brain damage. Moreover, rhsTM decreased both HMGB1 level and number of activated M1 microglia. The results of this study indicated that rhsTM improved functional outcomes via inhibition of HMGB1 up-regulation and M1 microglial activation in the cerebral ischaemic delayed phase. rhsTM may become a new therapeutic agent with a wide therapeutic time window in patients with cerebral ischaemia.

Influence of Quantum-Well Width on the Electroluminescence Properties of AlGaN Deep Ultraviolet Light-Emitting Diodes at Different Temperatures.

The influence of quantum-well (QW) width on electroluminescence properties of AlGaN deep ultraviolet light-emitting diodes (DUV LEDs) was studied at different temperatures. The maximum external quantum efficiency (EQE) ratios of LED with 3.5 nm QW to that with 2 nm increased from 6.8 at room temperature (RT) to 8.2 at 5 K. However, the ratios for LED with 3.5 nm QW to that with 5 nm QW decreased from 4.8 at RT to 1.6 at 5 K. The different changes of EQE ratios were attributed to the decrease of non-radiative recombination and the increase of volume of the active region. From theoretical analysis, the LED with 2-nm wells had a shallowest barrier for electron overflow due to the quantum-confined effect, whereas the LED with 5-nm wells showed the least overlap of electron and hole due to the large internal field. Therefore, the LED with 3.5 nm QW had the highest maximum EQE at the same temperature. As temperature decreased, the current for maximum EQE decreased for all the LEDs, which was believed to be due to the increase of electron which overflowed out of QWs and the decrease of hole concentration. The results were helpful for understanding the combination of polarization effect and electron overflow in DUV LEDs.

The clinical impact of edoxaban for the patients with postoperative anemia after total hip arthroplasty.

BACKGROUND: Postoperative anemia is a common complication after total hip arthroplasty (THA). However, the effect of edoxaban on postoperative anemia after THA remains unclear. Here, we retrospectively evaluated the clinical assessment of postoperative anemia and the associated changes of coagulation parameters in patients undergoing thromboprophylaxis with edoxaban compared with fondaparinux as a conventional anticoagulant thromboprophylactic agent after THA. METHODS: One hundred and forty-nine patients who underwent THA from July 2010 to June 2012 were divided into two groups, according to whether they were operated on before or after the approval of edoxaban: the fondaparinux group (Group F: 86 patients) and the edoxaban group (Group E: 63 patients). The frequency of postoperative anemia and blood coagulation values were investigated. RESULTS: Postoperative anemia developed more frequently in Group E than in Group F after surgery. However, the degree of postoperative anemia showed no significant difference between the groups. Meanwhile, prothrombin time (PT), prothrombin time-international normalized ratio (PT-INR), and activated partial thromboplastin time were markedly higher in patients with edoxaban-associated postoperative anemia, which showed an increased potential to predict the occurrence of postoperative anemia. Additionally, both PT and PT-INR in Group E were also correlated with the volume of estimated blood loss. CONCLUSION: The frequency of postoperative anemia was increased in patients treated with edoxaban, compared to fondaparinux, after THA. Edoxaban thromboprophylaxis might, therefore, require more careful monitoring to prevent postoperative anemia. Additionally, particular prolongation of PT and PT-INR induced by edoxaban treatment might predict postoperative anemia.

Goreisan Prevents Brain Edema after Cerebral Ischemic Stroke by Inhibiting Aquaporin 4 Upregulation in Mice.

BACKGROUND: Aquaporin 4 (AQP4) is a water-selective transport protein expressed in astrocytes throughout the central nervous system. AQP4 level increases after cerebral ischemia and results in ischemic brain edema. Brain edema markedly influences mortality and motor function by elevating intracranial pressure that leads to secondary brain damage. Therefore, AQP4 is an important target to improve brain edema after cerebral ischemia. The Japanese herbal Kampo medicine, goreisan, is known to inhibit AQP4 activity. Here, we investigated whether goreisan prevents induction of brain edema by cerebral ischemia via AQP4 using 4-hour middle cerebral artery occlusion (4h MCAO) mice. METHODS: Goreisan was orally administered at a dose of 500 mg/kg twice a day for 5 days before MCAO. AQP4 expression and motor coordination were measured by Western blotting and rotarod test, respectively. RESULTS: Brain water content of 4h MCAO mice was significantly increased at 24 hours after MCAO. Treatment with goreisan significantly decreased both brain water content and AQP4 expression in the ischemic brain at 24 hours after MCAO. In addition, treatment with goreisan alleviated motor coordination deficits at 24 hours after MCAO. CONCLUSIONS: The results of this study suggested that goreisan may be a useful new therapeutic option for ischemic brain edema.