分娩時大量出血後21年経過した部分的Sheehan症候群に対し、ホルモン補充療法を行った1例

京都府立医科大学北部医療センター　総合診療科Department of General internal medicine , North Medical Center , Kyoto Prefectural University of Medicine分娩時大量出血のエピソードより21年経過したSheehan症候群を経験した。症例は59歳女性。意識障害と原因不明の発熱、低血圧、低Na血症で入院した。低血圧が遷延し、下垂体性副腎不全を疑われた。ホルモン負荷試験により下垂体性副腎皮質機能不全と重症成長ホルモン分泌不全症との確定診断に至り、副腎皮質ホルモン、成長ホルモン補充療法の導入にてQOLを改善した

Eicosapentaenoic Acid Suppresses the Proliferation of Synoviocytes from Rheumatoid Arthritis

Eicosapentaenoic acid (EPA) is essential for normal cell growth, and may play an important role in inflammatory and autoimmune disorders including rheumatoid arthritis. We investigate that EPA could suppress the proliferation of fibroblast like synoviocytes in vitro. We treated synoviocytes with 1 to 50 µM EPA and measured cell viabilities by the modified MTT assay. We sorted the number of them in sub G1 stage by fluorescence-activated cell sorting caliber. And we stained them by light green or Hoechst 33258, and investigate microscopic appearance. The cell viabilities were decreased at 30 µM, 40 µM, and 50 µM of EPA comparing to 0 µM of EPA. The half maximal concentration of synoviocytes inhibition was approximately 25 µM. At day 1 and day 3, cell number was also decreased at 50 µM EPA comparing to control. FACS caliber indicated the number of synoviocytes in sub G1 stage did not increase in each concentration of EPA. Hoechst staining indicated normal chromatin pattern and no change in a nuclear morphology both in EPA treated synoviocytes and in untreated synoviocytes. These findings suggest that EPA could suppress the proliferation of synoviocytes in vivo dose dependently and time dependently, however, the mechanism is not due to apoptosis

Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Δ12,14-Prostaglandin J2

15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-γ ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ2 can suppress interleukin (IL)-1β-induced prostaglandin E2 (PGE2) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE2 synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ2 led to a significant increase in IL-1α-induced COX-2 expression and PGE2 production in a dose dependent manner. The effect of 15d-PGJ2 was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ2 exerts a positive feedback regulation of the arachidonate cascade of PGE2 in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis

Loxoprofen Sodium, a Non-Selective NSAID, Reduces Atherosclerosis in Mice by Reducing Inflammation

Recently, it is suggested that the use of nonsteroidal anti-inflammatory drugs (NSAID) may contribute to the occurrence of cardiovascular events, while the formation of atherosclerotic lesions is related to inflammation. Loxoprofen sodium, a non-selective NSAID, becomes active after metabolism in the body and inhibits the activation of cyclooxygenase. We fed apoE−/− mice a western diet from 8 to 16 weeks of age and administered loxoprofen sodium. We measured atherosclerotic lesions at the aortic root. We examined serum levels of cholesterol and triglycerides with HPLC, platelet aggregation, and urinary prostaglandin metabolites with enzyme immune assay. Atherosclerotic lesion formation was reduced to 63.5% and 41.5% as compared to the control in male and female apoE−/− mice treated with loxoprofen sodium respectively. Urinary metabolites of prostaglandin E2, F1α, and thromboxane B2, and platelet aggregation were decreased in mice treated with loxoprofen sodium. Serum levels of cholesterol and triglycerides were not changed. We conclude that loxoprofen sodium reduced the formation of early to intermediate atherosclerotic lesions at the proximal aorta in mice mediated by an anti-inflammatory effect

レムデシビル、デキサメタゾンを投与し改善したCOVID-19の3例

京都府立医科大学附属北部医療センター　総合診療科Department of General medicine, North Medical Center, Kyoto Prefectural University of Medicine今回我々は中等症I、II及び重症COVID-19肺炎の3例を経験した。いずれの症例も生活習慣病や喫煙などの重症化リスク因子を複数持っており肺炎症状が増悪したが、レムデシビルとデキサメタゾンを投与し軽快退院に至った。COVID-19はウイルス性呼吸器感染症と宿主免疫の過剰反応が関与して重症肺炎に至る2つの側面を持っている。COVID-19の臨床的改善を得るには、病期を理解しそれぞれの病態に対して適した薬剤投与を行うことが重要である。(著者抄録

末梢神経障害の残存する好酸球性多発血管炎性肉芽腫症に対して免疫グロブリン大量療法が奏功した一例

京都府立医科大学附属北部医療センター　総合診療科Department of General internal medicine , North Medical Center , Kyoto Prefectural University of Medicine好酸球性多発血管炎性肉芽腫症(EGPA)は1951年にChurgとStraussによって報告された疾患で、以前はChurg-Strauss症候群やアレルギー性肉芽腫性血管炎と呼ばれていた。EGPAは、好酸球の組織浸潤、小型から中型血管の壊死性血管炎によって特徴付けられる稀な全身性疾患である。EGPAの臨床症状としては、気管支喘息、アレルギー性鼻炎、好酸球の組織浸潤(心臓、消化管、皮膚、腎臓)、末梢神経障害などの血管炎症状である。EGPAの予後を改善させる上で、早期診断と早期治療は極めて重要であり、末梢神経障害による運動麻痺が出現すればQOLは著しく低下する可能性がある。しかし、その一方でEGPAの診断には難渋することが多く、その理由としては慢性好酸球性肺炎、好酸球増多症候群、他の一次性全身性血管炎などと臨床的特徴が類似または重複するためと考えられる。今回、我々は顔面浮腫と関節痛を初発症状とし、末梢血好酸球増多の鑑別をしている際に末梢神経障害を発症し、EGPAの診断に至った症例を経験した。Prednisolone(PSL)による寛解導入後も末梢神経障害は残存していたため、早期に免疫グロブリン大量療法(IVIg)を施行したところ、末梢神経障害の著明な改善を得た。EGPAの早期診断と末梢神経障害に対するIVIgの有効性に関して、文献を踏まえた考察を行い、報告する。(著者抄録

15-Deoxy-Δ12,14 Prostaglandin J2 Reduces the Formation of Atherosclerotic Lesions in Apolipoprotein E Knockout Mice

AIM: 15-deoxy-Δ¹²,¹⁴ prostaglandin J₂ (15d-PGJ₂) is a ligand of peroxisome proliferator-activated receptor γ (PPARγ) having diverse effects such as the differentiation of adipocytes and atherosclerotic lesion formation. 15d-PGJ₂ can also regulate the expression of inflammatory mediators on immune cells independent of PPARγ. We investigated the antiatherogenic effect of 15d-PGJ₂. METHODS: We fed apolipoprotein (apo) E-deficient female mice a Western-type diet from 8 to 16 wk of age and administered 1 mg/kg/day 15d-PGJ₂ intraperitoneally. We measured atherosclerotic lesions at the aortic root, and examined the expression of macrophage and inflammatory atherosclerotic molecules by immunohistochemical and real-time PCR in the lesion. RESULTS: Atherosclerotic lesion formation was reduced in apo E-null mice treated with 15d-PGJ₂, as compared to in the controls. Immunohistochemical and real-time PCR analyses showed that the expression of MCP-1, TNF-α, and MMP-9 in atherosclerotic lesions was significantly decreased in 15d-PGJ₂ treated mice. The 15d-PGJ₂ also reduced the expression of macrophages and RelA mRNA in atherosclerotic lesions. CONCLUSION: This is the first report 15d-PGJ₂, a natural PPARγ agonist, can improve atherosclerotic lesions in vivo. 15d-PGJ₂ may be a beneficial therapeutic agent for atherosclerosis

京都府立医科大学附属北部医療センターでの院内採用抗菌薬変更による抗菌薬院内処方日数の減少と緑膿菌抗菌薬感受性の改善について

京都府立医科大学附属北部医療センター総合診療科North medical center, kyoto prefectural university of medicine. Department of general internal medicineThe trend of antimicrobial resistant bacteria is a globally significant problem. At the Annual Meeting of the World Health Organization (WHO) in 2011, antimicrobial resistance (AMR) was featured as a major topic. In this study, we compared trends in oral antibiotic use in the hospital before and after the addition of CEX and CTM to the formulary. Antimicrobial days of therapy (DOT) of oral antimicrobial agents for every year between January 1, 2010 and December 31, 2018 and the trends of resistance to antimicrobial agents of Pseudomonas aeruginosa were analyzed to evaluate the proper use of antimicrobial agents. We observed a significant decrease in the average yearly consumption of third-generation cephalosporins (5.5, 2.9 P<0.01). Concerning the antimicrobial drug sensitivity (%) of Pseudomonas aeruginosa, the Meropenem sensitivity before and after the start of activities was 74 and 100%, respectively