Diels-Alder反応を用いた数種の多環式天然物の全合成

制度:新 ; 文部省報告番号:甲2602号 ; 学位の種類:博士(工学) ; 授与年月日:2008/3/15 ; 早大学位記番号:新476

Thiazolidinediones and Edema: Recent Advances in the Pathogenesis of Thiazolidinediones-Induced Renal Sodium Retention

Thiazolidinediones (TZDs) are one of the major classes of antidiabetic drugs that are used widely. TZDs improve insulin resistance by activating peroxisome proliferator-activated receptor gamma (PPARγ) and ameliorate diabetic and other nephropathies, at least, in experimental animals. However, TZDs have side effects, such as edema, congestive heart failure, and bone fracture, and may increase bladder cancer risk. Edema and heart failure, which both probably originate from renal sodium retention, are of great importance because these side effects make it difficult to continue the use of TZDs. However, the pathogenesis of edema remains a matter of controversy. Initially, upregulation of the epithelial sodium channel (ENaC) in the collecting ducts by TZDs was thought to be the primary cause of edema. However, the results of other studies do not support this view. Recent data suggest the involvement of transporters in the proximal tubule, such as sodium-bicarbonate cotransporter and sodium-proton exchanger. Other studies have suggested that sodium-potassium-chloride cotransporter 2 in the thick ascending limb of Henle and aquaporins are also possible targets for TZDs. This paper will discuss the recent advances in the pathogenesis of TZD-induced sodium reabsorption in the renal tubules and edema

Hemodynamic Changes in the Brachial Artery Induced by Acupuncture Stimulation on the Lower Limbs: A Single-Blind Randomized Controlled Trial

Acupuncture is commonly performed at acupoints. No comparisons of quantitative physiological alterations in the brachial artery (BA) induced by the stimulation of different acupoints in the lower limbs have been performed in humans. Therefore, we investigated changes in blood flow volume (BFV) in the BA as an indicator of the physiological effects induced by stimulation at 3 points. Seventy-five healthy participants aged 33 ± 9 years (mean ± SD) were enrolled and randomly assigned to 3 groups; they received stimulation at 3 different points located on the lower limbs: ST36, LR3, and a non-acupoint. Stimulation was performed bilaterally with manual rotation of the needles. Using ultrasonography, BFV was measured continuously from rest to 180 seconds after stimulation. LR3 stimulation significantly increased BFV compared to that before needle insertion. Meanwhile, stimulation at ST36 and the non-acupoint significantly decreased BFV compared to that before needle insertion. Stimulation at LR3 elicited a significant increase in BFV compared to that at ST36 and the non-acupoint. The results suggest that the stimulation of different points on the lower limbs causes distinct physiological effects on BFV in the BA

Insulin Resistance, Obesity, Hypertension, and Renal Sodium Transport

Sodium transport through various nephron segments is quite important in regulating sodium reabsorption and blood pressure. Among several regulators of this process, insulin acts on almost all the nephron segments and is a strong enhancer of sodium reabsorption. Sodium-proton exchanger type 3 (NHE3) is a main regulator of sodium reabsorption in the luminal side of proximal tubule. In the basolateral side of the proximal tubule, sodium-bicarbonate cotransporter (NBCe1) mediates sodium and bicarbonate exit from tubular cells. In the distal nephron and the connecting tubule, epithelial sodium channel (ENaC) is of great importance to sodium reabsorption. NHE3, NBCe1, and ENaC are all regulated by insulin. Recently with-no-lysine (WNK) kinases, responsible for familial hypertension, stimulating sodium reabsorption in the distal nephron, have been found to be also regulated by insulin. We will discuss the regulation of renal sodium transport by insulin and its roles in the pathogenesis of hypertension in insulin resistance

Haemodynamic Changes in the Superior Mesenteric Artery Induced by Acupuncture Stimulation on the Lower Limbs

Acupuncture is commonly performed on acupoints. A comparison of quantitative physiological alterations induced by stimulation on different acupoints has never been performed in the superior mesenteric artery (SMA) in humans. Therefore, we investigated changes in blood flow volume (BFV) in the SMA as an indicator of physiological effects induced by stimulation on 3 points. Thirty healthy participants aged 29 ± 10 years (mean ± SD) were enrolled. All participants underwent stimulations on 3 points located in the lower legs: ST36, LR3, and a non-acupoint. Control pertains to a condition with no-stimulation. Stimulation was performed bilaterally with manual rotation of the needles. BFV was measured by ultrasonography before insertion and 10, 20, 30, and 60 minutes after stimulation. Following acupuncture on ST36, BFV increased significantly 20 and 30 minutes after stimulation, compared to BFV before insertion (P < 0.05). Following stimulation on LR3 and the non-acupoint, no significant differences in BFV could be found. Relative to the no-stimulation group, stimulation on LR3, and the non-acupoint, stimulation on ST36 elicited a significant increase in BFV (P < 0.05). The results suggest that stimulation on the different points causes distinct physiological effects in BFV in the SMA