Some clinical trials are ongoing in patients with FLT3-mutated AML at various treatment stages, such as induction therapy, maintenance therapy, and treatment after hematopoietic stem cell transplantation. In conclusion, in vitro, in vivo, and clinical data indicate that gilteritinib fumarate is an effective treatment option in adult patients with relapsed or refractory FLT3-mutated AML in Japan.In recent years, the success rate of drug development has declined, and along with it, R&D costs have continued to rise. The rate of discontinuation of drug development due to safety reasons remains unchanged from 20 years ago. Therefore, it is important to check the safety of candidate compounds early in drug discovery in order to improve drug discovery efficiency. Under such circumstances, each company is focusing on establishing a low-cost, high-precision, and high-throughput safety screening system. The zebrafish is expected as a new experimental animal that serves as a bridge between in vitro and in vivo, and the progress of research in the last 15 years has been remarkable. At present, zebrafish are becoming a major experimental animal in Japan. At the same time, the gap between ideal and reality began to be seen, and it was time to once again understand the characteristics of zebrafish and think about its usage. This paper summarizes the points to be noted in the screening using zebrafish and introduces the use for actual safety evaluation.Glutathione (GSH) is a tripeptide consisting of glutamate, cysteine, and glycine that acts as an important neuroprotective molecule in the central nervous system. In neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease, GSH levels in the brain would be decreased before the onset, and GSH dysregulation is considered to be involved in the development of these neurodegenerative diseases. Cysteine uptake into neurons is the rate-limiting step for GSH synthesis. Excitatory amino acid carrier 1 (EAAC1), which is a glutamate/cysteine cotransporter, is responsible for the neuronal cysteine uptake, and EAAC1 dysfunction reduces GSH levels in the brain and has a significant influence on the process of neurodegeneration. Since miR-96-5p, which is one of microRNAs, suppresses EAAC1 expression, it is conceivable that miR-96-5p inhibitor suppresses the onset or slows the progression of neurodegenerative diseases by increasing EAAC1 levels leading to promoting neuronal GSH production.Ischemic stroke is one of the most prevalent brain disorders and the major cause of long-term disability. In particularly, hippocampal injury after ischemia-reperfusion is a serious problem as it contributes to vascular dementia. Many researches have revealed that ischemia-reperfusion causes increase in reactive oxygen species production and disruption of neuronal Zn2+ homeostasis in the hippocampus, which induces hippocampal neuron death. Glutathione (GSH) is present in all mammalian cells and plays a crucial role in neuronal cell defense against oxidative stress. On the other hand, thiol group of GSH chemically chelates Zn2+ and functions as a regulator of neuronal Zn2+ homeostasis. These evidences suggest that neuronal GSH levels could be an important factor affecting neuronal surviving. The synthesis of GSH is largely influenced by intracellular cysteine availability. In neurons, excitatory amino acid carrier type 1 (EAAC1) acts as a cysteine transporter and provides cysteine substrate for GSH synthesis. Recently, several animal studies have revealed that promotion of neuronal GSH synthesis through EAAC1 reduces ischemia-induced hippocampal neuron death. This review aims to describe neuroprotective role of GSH against hippocampal injury following ischemia-reperfusion, focusing on EAAC1.Recently, it has been reported that dysfunction of astrocytes is involved vulnerability of neuronal cells in several neurological disorders. Glutathione (GSH) is the most abundant intrinsic antioxidant in the central nervous system, and its substrate cysteine is readily becomes the oxidized dimeric cystine. Since neurons lack a cystine transport system, neuronal GSH synthesis depends on cystine uptake via the cystine/glutamate exchange transporter (xCT), GSH synthesis and release in/from surrounding astrocytes. The expression and release of the zinc-binding protein metallothionein (MT) in astrocytes, which is a strong antioxidant, is induced and exerts neuroprotective in the case of dopaminergic neuronal damage. In addition, the transcription factor Nrf2 induces expression of MT-1 and GSH related molecules. We previously revealed that several antiepileptic drugs, serotonin 5-HT1A receptor agonists, plant-derived chemicals (phytochemicals) increased xCT expression, Nrf2 activation, GSH or MT expression and release in/from astrocytes, and exerted a neuroprotective effect against dopaminergic neurodegeneration in Parkinson's disease model. Our serial studies on neuroprotection via antioxidant defense mechanism of astrocytes have found three target molecular systems of astrocytes for neuroprotection (1) xCT-GSH synthetic system, (2) Nrf2 system and (3) 5-HT1A receptor-Nrf2-MT system, 5-HT1A-S100β system. In this article, possible neuroprotective strategy for Parkinson's disease has been reviewed targeting antioxidative molecules in astrocytes.A 54-year-old woman had been resuscitated after ventricular fibrillation and her electrocardiogram showed a QT prolongation (QTc=510 ms), and genetic screening revealed a missense variant, R1644C, in the SCN5A gene. She was therefore diagnosed with congenital long-QT syndrome (LQTS) type 3. However, the patient had left ventricular dysfunction, and based on the findings of cardiac magnetic resonance imaging, positron emission tomography and pathological examinations, she was diagnosed with cardiac sarcoidosis. Although both are rare diseases, their overlapping presence in this case may have led to an increased cardiovascular risk compared with either alone. Thus, not only genetic but comprehensive clinical examinations are important for making a correct diagnosis.The case was a 76-year-old man with chronic limb-threatening ischemia. Plain old balloon angioplasty (POBA) was performed on the popliteal artery. Subsequently, he suffered from cellulitis around the POBA site, followed by reocclusion. Staphylococcus aureus was detected in a blood culture. After re-revascularization with POBA, both purulent gonitis and an infected popliteal aneurysm were observed to occur. We performed aneurysmectomy and bypass grafting with the saphenous vein and then continued antibiotic therapy. this website Although treatment consisted of endovascular therapy (EVT) with nothing left behind, management was difficult because of secondary infectious complications. We conclude that prophylactic antibiotics before EVT should be considered in such cases.