Glucose-Dependent Insulinotropic Polypeptide Prevents the Progression of Macrophage-Driven Atherosclerosis in Diabetic Apolipoprotein E-Null Mice

Aim: We recently reported that glucose-dependent insulinotropic polypeptide (GIP) prevents the development of atherosclerosis in apolipoprotein E-null (Apoe 2/2) mice. GIP receptors (GIPRs) are found to be severely down-regulated in diabetic animals. We examined whether GIP can exert anti-atherogenic effects in diabetes. Methods: Nondiabetic Apoe 2/2 mice, streptozotocin-induced diabetic Apoe 2/2 mice, and db/db mice were administered GIP (25 nmol/kg/day) or saline (vehicle) through osmotic mini-pumps for 4 weeks. The animals were assessed for aortic atherosclerosis and for oxidized low-density lipoprotein-induced foam cell formation in exudate peritoneal macrophages. Results: Diabetic Apoe 2/2 mice of 21 weeks of age exhibited more advanced atherosclerosis than nondiabetic Apoe 2/2 mice of the same age. GIP infusion in diabetic Apoe 2/2 mice increased plasma total GIP levels by 4-fold without improving plasma insulin, glucose, or lipid profiles. GIP infusion significantly suppressed macrophage-driven atherosclerotic lesions, but this effect was abolished by co-infusions with [Pro 3]GIP, a GIPR antagonist. Foam cell formation was stimulated by 3-fold in diabetic Apoe 2/2 mice compared with their nondiabetic counterparts, but this effect was halved by GIP infusion. GIP infusion also attenuated the foam cell formation in db/db mice. In vitro treatment with GIP (1 nM) reduced foam cell formation by 15 % in macrophages from diabetic Apoe 2/2 mice, and this attenuating effect was weaker than that attained by the same treatment of macrophages from nondiabetic counterparts (35%). While GIPR expression was reduced by onl

Successful voriconazole treatment of invasive pulmonary aspergillosis in a patient with acute biphenotypic leukemia

A 23-year old woman with acute biphenotypic leukemia (ABL) complained of chest pain with cough, high fever and hemoptysis during induction chemotherapy, although she had been treated with anti-biotics and micafungin. We made a clinical diagnosis of invasive pulmonary aspergillosis (IPA) based on a consolidation in the right upper lung field on a chest radiograph as well as a high level of serum beta-D-glucan (with no evidence of tuberculosis and candidiasis). We changed her treatment from micafungin to voriconazole. Later, we discovered an air-crescent sign by CT scan that supported the diagnosis of IPA. Following voriconazole treatment, clinical symptoms ceased and abnormal chest shadows improved gradually and concurrently with a recovery of neutrophils. IPA must be considered in immunocompromised patients with pulmonary infiltrates who do not respond to broad-spectrum antibiotics. Serological tests and CT findings can aid in early diagnosis of IPA, which, along with treatment for IPA, will improve clinical outcomes.</p

Glucagon-like Peptide-1 Suppresses the Proliferation and Migration of Vascular Smooth Muscle Cells: Implications for Preventive Effects on Atherosclerosis

Our group previously demonstrated the suppressive effect of glucagon-like peptide-1 (GLP-1) on macrophage-driven atherosclerosis in apolipoprotein E-deficient (apoE-/-) mice. In the present study we investigated the suppressive effect of GLP-1 on the atherogenic phenotype of vascular smooth muscle cells (VSMCs) in vivo using apoE-/- mice, and the proliferation and migration of human VSMCs in vitro. A 4-week infusion of GLP-1 in 17-week-old apoE-/- mice significantly reduced the proliferative VSMC phenotype stained with SMemb. Platelet-derived growth factor (PDGF) -BB significantly stimulated the proliferation of human aortic VSMCs by three fold. Both 0.1 and 1nmol/l GLP-1 significantly suppressed the PDGF-induced VSMC proliferation, and this suppressive effect was significantly abolished by the GLP-1 receptor antagonist exendin (9-39) (50nmol/l). The GLP-1 receptor agonists liraglutide (100nmol/l) and exendin-4 (100nmol/l) mimicked GLP-1, significantly suppressing PDGF-induced VSMC proliferation. PDGF-BB significantly stimulated the migration of human aortic VSMCs by 1.7 -fold, and this effect was significantly suppressed by 1nmol/l GLP-1. These findings suggest that GLP-1-related treatments may prevent the progression of atherosclerotic lesions by suppressing the proliferation and migration of VSMCs, which are characteristic features of atherosclerosis

カンタン ニ テキセツ ナ ツヨサ デ ソウチャク デキル ジョウミャク センシ ヨウ クケツタイ ノ カイハツ

看護師が前腕に静脈穿刺をする際にゴム管駆血帯を用いた場合の駆血圧は70-95mmHgが適切と報告されているが、看護師が駆血帯を装着する強さは幅広く分散しており、高すぎる傾向にある。この原因の一つとして、駆血帯には適切な目安が無く、意図した強さで装着することが難しいことが考えられた。そこで、適切なく血圧の指標となるメモリを付けた駆血帯を開発し、その性能について検討した。60名の対象者(平均年齢40.5歳、範囲21-78歳)に駆血帯を上腕周囲径より1-4メモリ短く装着した時の駆血圧の平均はそれぞれ45,76,110,144 mmHgであり、静脈の断面積は3メモリまでは増加したが、4メモリまで短くするとやや減少した。静脈穿刺可能な怒張が得られた対象者はそれぞれ30%,80%,90%,85%で、3メモリまでは増加したが、4メモリ短くするとやや減少した。この駆血帯では上腕周囲径より2-3メモリ短く装着するのが適切と考えられた。When nurses attempt venipuncture at the forearm, they apply a tourniquet at the upper arm to distend the forearm vein. Appropriate gum-tube tourniquet pressure is reported to be between 70-95mmHg. But tourniquet pressure applied by japanese nurses in clinical situations is often too high and widely distributed. One of the reason they do not apply tourniquets with appropriate pressure is that the tourniquets they use have no marks for applying the appropriate pressure. So, we developed a new tourniquet with marks for applying appropriate pressure, and we studied the effectiveness of this tourniquet. Sixty subjects (mean age40.5 years old, range:21-78 years old) were enrolled. When we applied tourniquets with tourniquet lengths 1, 2, 3, and 4 marks shorter than the circumference of the upper arm, mean tourniquet pressures were 45.1±6.7mmHg, 76.0±12.2mmHg,109.6±13.0mmHg, and 143.7±24.7mmHg respectively, and vein cross section area increased according to the stretch strength until 3 marks, then decreased slightly at 4 marks. The percentages of subjects with sufficient vein distention for venipuncture were about 30%, 80%, 90%, and 85% respectively. The results indicated that applying tourniquet with 2 marks or 3 marks shorter is appropriate for venipuncture, while 4 marks is too strong