New sulfurated derivatives of cinnamic acids and rosmaricine as inhibitors of STAT3 and NF-kappa B transcription factors

A set of new sulfurated drug hybrids, mainly derived from caffeic and ferulic acids and rosmaricine, has been synthesized and their ability to inhibit both STAT3 and NF-kappa B transcription factors have been evaluated. Results showed that most of the new hybrid compounds were able to strongly and selectively bind to STAT3, whereas the parent drugs were devoid of this ability at the tested concentrations. Some of them were also able to inhibit the NF-kappa B transcriptional activity in HCT-116 cell line and inhibited HCT-116 cell proliferation in vitro with IC50 in micromolar range, thus suggesting a potential anticancer activity. Taken together, our study described the identification of new derivatives with dual STAT3/NF-kappa B inhibitory activity, which may represent hit compounds for developing multi-target anticancer agents

Support team and its effects on house remodeling for aged and handicapped persons

地域で生活する高齢者･障害者にとって,住宅環境の整備は必須の要件である｡津山市では在宅生活を支援する立場にある保健婦やホームヘルパー,作業療法士等保健･福祉関係者と,建築関係者が共同で支援チームをつくり住宅改造に関わってきた｡本研究では,この支援チームが関わった事例と直接関わらないで当事者と業者のみで改造を実施した事例を比較し,支援チームが関わることの効果をみた｡調査方法は,各事例の家庭を訪問して面接聞き取り調査を行った｡調査内容は調査票を用いて改造箇所,生活空間,介護量,外出の状況について尋ねた｡改造前後の変化を比較して,支援チームの効果について以下のことが明らかになった｡ 1.支援チームの関与による浴室の改造は,入浴が可能となり生活空間が広がるなど改善が認められた｡ 2.離床を目的にした玄関･廊下･居室の改造は,外出などの日常生活行動を広げ,本人のQOLを高めることに役立つ｡以上より住宅の改造が,介護者の介護負担を必ずしも直接軽減するとは限らないが,高齢者･障害者の介護の質に変化を与えることが示唆された。The maintenance and improvement of housing environments are essential for aged and handicapped persons living in a local communities. The support team consists of public health nurses, home helpers, occupational therapists and architects took part in giving an advices for house remodeling in Tsuyama City. We compared the effectiveness of the participation of the team before and after remodeling of housing environment. An interview was conducted at each cases for places of remodeling, living spaces, quantity of care and ease of going. The results are as follows ; 1. The remodeling of bathrooms, participating support team improved the living spaces to be able to take bath. 2. The remodeling of entrances and corridors for leaving beds, improved the living space and the QOL of care recipients. The results suggest that the remodeling of houses dose not always lighten care burdens for caring, but changes the quality of care for aged and handicapped persons

Transition of Anesthesia Management and Anesthetics Used for 50 Years Since the Establishment of Anesthesiology Department in Hiroshima University

広島大学麻酔蘇生学教室は1967年1月に盛生倫夫が初代教授に就任し開講した。開講50周年を機に，麻酔科開設以来の麻酔管理に用いた麻酔薬の変遷を辿った。開講当初から１９８５年までは亜酸化窒素とハロタンを中心とした吸入麻酔薬の時代，1990年から2005年はエンフルラン，イソフルラン，セボフルランなどの吸入麻酔薬とフェンタニルの併用の時で，2010年からはプロポフォールとレミフェンタニルの全静脈麻酔あるいはセボフルランあるいはデスフルランとレミフェンタニル併用の時代であった。開講から1980年頃まではスキサメトニウムを主に使ったが，それ以降は非脱分極性筋弛緩薬であるパンクロニウムへ，そしてベクロニウムへ推移し，現在はロクロニウムが主流となっている。使用麻酔薬の変遷は麻酔薬の科学的な評価とそれらを使用する麻酔科医の考え方を反映していた。Department of Anesthesiology and Critical Care, Hiroshima University, started in January 1967 when Dr. Michio Morio became the first professor.　With the 50th anniversary of the establishment of the department, the transition of the anesthetics used in our long history of anesthesia care was investigated since the beginning of the department. Inhalation anesthetics was mainly used in combination with nitrous oxide and halothane from the beginning to 1985. Inhalation anesthetics such as enflurane, isoflurane, sevoflurane and intravenous fentanyl were used from 1990 to 2005, and the total intravenous anesthesia by using propofol and remifentanil was introduced and used currently. Sevoflurane or desflurane combined with remifentanil was also a mainstream since 2010.　From the beginning to 1980, suxamethonium was mainly used for muscle relaxation, followed by pancuronium thereafter and shifted to vecuronium and to rocuronium. The transition of anesthetics applied for clinical anesthesia in our department seemed to be reflecting the selection based on scientific validity

Coffee Polyphenol, Chlorogenic Acid, Suppresses Brain Aging and Its Effects Are Enhanced by Milk Fat Globule Membrane Components

Mice feed with coffee polyphenols (CPP, chlorogenic acid) and milk fat globule membrane (MFGM) has increased survival rates and helps retain long-term memory. In the cerebral cortex of aged mice, CPP intake decreased the expression of the proinflammatory cytokine TNF-α, and lysosomal enzyme cathepsin B. The suppression of inflammation in the brain during aging was thought to result in the suppression of the repressor element 1-silencing transcription factor (REST) and prevention of brain aging. In contrast, CPP increased the expression of REST, cAMP-responsive element binding (CREB) and transforming growth factor β1 (TGF-β1) in the young hippocampus. The increased expression of these factors may contribute to the induction of neuronal differentiation and the suppression of memory decline with aging. Taken together, these results suggest that CPP increases CREB in the young hippocampus and suppresses inflammation in the old brain, resulting in a preventive effect on brain aging. The endotoxin levels were not elevated in the serum of aged mice. Although the mechanism of action of MFGM has not yet been elucidated, the increase in survival rate with both CPP and MFGM intake suggests that adding milk to coffee may improve not only the taste, but also the function

General Anesthesia Management Combined with Thoracic Wall Block for Mastectomy on a Patient with a History of Aortic Valve Replacement

Thoracic wall block is a useful tool for analgesia in a patient receiving mastectomy. To select an analgesic method with sufficient analgesic effect and little influence on cardiovascular dynamics is important for perioperative management of the patients whose cardiovascular dynamics are desirable to be stable. We experienced a patient who had an increased pressure gradient from the left ventricle to the aortic valve, accompanied by the sigmoid shaped ventricular septum developed after aortic valve replacement. By using pectoral nerve block and transversus thoracic muscle plane block combined with general anesthesia, we managed this patient uneventfully and safely.本論文の要旨は，日本麻酔科学会　中国・四国支部　第53回学術集会（2016年，岡山）で発表した

Mouse Models with SGLT2 Mutations: Toward Understanding the Role of SGLT2 beyond Glucose Reabsorption

The sodium–glucose cotransporter 2 (SGLT2) mainly carries out glucose reabsorption in the kidney. Familial renal glycosuria, which is a mutation of SGLT2, is known to excrete glucose in the urine, but blood glucose levels are almost normal. Therefore, SGLT2 inhibitors are attracting attention as a new therapeutic drug for diabetes, which is increasing worldwide. In fact, SGLT2 inhibitors not only suppress hyperglycemia but also reduce renal, heart, and cardiovascular diseases. However, whether long-term SGLT2 inhibition is completely harmless requires further investigation. In this context, mice with mutations in SGLT2 have been generated and detailed studies are being conducted, e.g., the SGLT2−/− mouse, Sweet Pee mouse, Jimbee mouse, and SAMP10-ΔSglt2 mouse. Biological changes associated with SGLT2 mutations have been reported in these model mice, suggesting that SGLT2 is not only responsible for sugar reabsorption but is also related to other functions, such as bone metabolism, longevity, and cognitive functions. In this review, we present the characteristics of these mutant mice. Moreover, because the relationship between diabetes and Alzheimer’s disease has been discussed, we examined the relationship between changes in glucose homeostasis and the amyloid precursor protein in SGLT2 mutant mice

Subacute postoperative myofascial pain diagnosed and treated successfully by ultrasound: a case after laparoscopic hepatectomy

Abstract Background Myofascial pain syndrome is one of the causes of prolonged postoperative pain after abdominal surgery. However, diagnosis and treatment of myofascial pain syndrome, especially its myofascial trigger point (MTrP), have not been well established. Case presentation A 55-year-old man experienced severe subacute abdominal pain after laparoscopic hepatectomy despite aggressive postoperative pain management. He had a positive Carnett’s sign, indicating abdominal wall pain, 2 weeks after the surgery. Ultrasonography showed a hyperechoic spot surrounded by a hypoechoic area in the inner abdominal oblique muscle under the palpable spot that fulfills the criteria of MTrP. The echogenic MTrP disappeared after repetitive ultrasound-guided trigger point injections (USG TPIs) with pain relief. Conclusions Our present case indicates that diagnosing myofascial pain by visualizing the echogenic MTrPs in the abdominal muscles, and subsequent USG TPIs, might provide an accurate maneuver for diagnosis and treatment of subacute myofascial pain after abdominal surgery

Influence of Molecular Structure on O2-Binding Properties and Blood Circulation of Hemoglobin‒Albumin Clusters.

A hemoglobin wrapped covalently by three human serum albumins, a Hb-HSA3 cluster, is an artificial O2-carrier with the potential to function as a red blood cell substitute. This paper describes the synthesis and O2-binding properties of new hemoglobin‒albumin clusters (i) bearing four HSA units at the periphery (Hb-HSA4, large-size variant) and (ii) containing an intramolecularly crosslinked Hb in the center (XLHb-HSA3, high O2-affinity variant). Dynamic light scattering measurements revealed that the Hb-HSA4 diameter is greater than that of either Hb-HSA3 or XLHb-HSA3. The XLHb-HSA3 showed moderately high O2-affinity compared to the others because of the chemical linkage between the Cys-93(β) residues in Hb. Furthermore, the blood circulation behavior of 125I-labeled clusters was investigated by assay of blood retention and tissue distribution after intravenous administration into anesthetized rats. The XLHb-HSA3 was metabolized faster than Hb-HSA3 and Hb-HSA4. Results suggest that the molecular structure of the protein cluster is a factor that can influence in vivo circulation behavior