Title: Teneligliptin, a dipeptidyl peptidase-4 inhibitor, attenuated pro-inflammatory phenotype of perivascular adipose tissue and inhibited atherogenesis in normoglycemic apolipoprotein-E-deficient mice Salim HM, Fukuda D, Higashikuni Y, Tanaka K, Hirata Y, Yagi S, Soeki T, Shimabukuro M, Sata M Ref: Vascul Pharmacol, 96-98:19, 2017 : PubMed
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have various cellular effects that are associated with vascular protection. Here, we examined whether teneligliptin alters the pro-inflammatory phenotype of perivascular adipose tissue (PVAT) and inhibits atherogenesis. METHODS AND RESULTS: Teneligliptin (60mg/kg/day) was administered orally to apolipoprotein-E-deficient (ApoE(-/-)) mice for 20weeks. Teneligliptin significantly inhibited the development of atherosclerosis in the aortic arch compared with vehicle (P<0.05), without alteration of blood glucose level or blood pressure. Histological analyses demonstrated that teneligliptin decreased lipid deposition and MCP-1 expression (P<0.05, respectively), and tended to decrease macrophage accumulation in atherosclerotic plaques. The results of quantitative RT-PCR analysis demonstrated that teneligliptin reduced the expression of inflammatory molecules such as TNF-alpha and MCP-1 in the abdominal aorta. Furthermore, teneligliptin reduced the expression of a macrophage marker and Nox-4, a major NADPH oxidase subunit in adipocytes, in PVAT around the aortic arch. Administration of teneligliptin for 8weeks ameliorated endothelium-dependent vasodilation and reduced oxidative stress as determined by urinary 8-OHdG excretion (P<0.05) compared with vehicle. In vitro experiments demonstrated that exendin-4 (Ex-4), a GLP-1 analog, decreased the expression of inflammatory molecules in RAW264.7 cells. Also, Ex-4 decreased Nox4 expression in 3T3-L1 adipocytes. CONCLUSION: Teneligliptin inhibited atherogenesis with attenuation of the inflammatory phenotype in PVAT. A GLP-1 analog suppressed pro-inflammatory activation of macrophages and adipocytes. Suppression of the pro-inflammatory phenotype of PVAT might contribute, at least partially, to the cardioprotective effects of teneligliptin.
The serum ferritin (SF) concentration is a widely available and objective laboratory parameter. SF is also widely recognized as an acute-phase reactant. The purpose of the present study was to identify the chronological changes in the recipient's SF concentration during liver transplantation (LT) and to clarify factors having an effect on the recipient's intraoperative SF level. In addition, the study retrospectively evaluated the usefulness of measuring SF during LT. Ninety-eight pediatric recipients were retrospectively analyzed. The data were analyzed and compared according to the SF level in the recipient. Patients were classified into 2 groups based on the intraoperative peak SF levels of </=1000 ng/mL (low-SF group) or >1000 ng/mL (high-SF group). The SF value increased dramatically after reperfusion and fell to normal levels within the early postoperative period. The warm ischemia time (WIT) was significantly longer in the high-SF group (47.0 versus 58.5 minutes; P = 0.003). In addition, a significant positive correlation was observed between the peak SF value and WIT (r = 0.35; P < 0.001). There were significant positive correlations between the peak SF value and the donors' preoperative laboratory data, including transaminases, cholinesterase, hemoglobin, transferrin saturation, and SF, of which SF showed the strongest positive correlation (r = 0.74; P < 0.001). The multivariate analysis revealed that WIT and donor's SF level were a significant risk factor for high SF level in the recipient (P = 0.007 and 0.02, respectively). In conclusion, the SF measurement can suggest the degree of ischemia/reperfusion injury (IRI). A high SF level in the donor is associated with the risk of further acute reactions, such as IRI, in the recipient. Liver Transpl 21:1419-1427, 2015. (c) 2015 AASLD.
Title: Elevated frequency of sister chromatid exchanges of lymphocytes in sarin-exposed victims of the Tokyo sarin disaster 3 years after the event Li Q, Hirata Y, Kawada T, Minami M Ref: Toxicology, 201:209, 2004 : PubMed
We previously reported that the frequency of sister chromatid exchanges (SCEs) among victims of the Tokyo subway sarin disaster was significantly higher than that of controls 2-3 months after the disaster. It has been reported that the victims were also exposed to the by-products generated during sarin synthesis, i.e., diisopropyl methylphosphonate (DIMP), diethyl methylphosphonate (DEMP) and N,N-diethylaniline (DEA) during the disaster and we previously found that DIMP, DEMP and DEA induced a significant SCE increase in human lymphocytes in vitro. To monitor the genetic aftereffects of the sarin exposure, SCEs of peripheral blood lymphocytes were measured in fire fighters and police officers involved in the disaster 3 years after the event. We found that the frequency of SCEs was still significantly higher in the exposed subjects than the controls, suggesting a risk of the genetic aftereffects of the sarin exposure. We further found a significant positive correlation between the frequency of SCEs and the inhibition of serum cholinesterase activity in the exposed subjects, suggesting that the elevated frequency of SCEs is related to the sarin exposure. On the other hand, there was no significant difference in natural killer activity between the exposed and the controls.
The new simple technique of rectal mucosal punch biopsy has been used successfully in 170 cases for diagnosing Hirschsprung's disease. The presented punch biopsy method, using a test tube with a side hole and laryngeal biopsy forceps, has proven to be superior to the rectal suction biopsy method associated with several demerits.
Castrated dogs showed a slightly weak erectile response to cavernous nerve stimulation compared with normal dogs. Intracavernous injection of acetylcholine induced a dose-dependent increase of intracavernous pressure in normal dogs, however, there was almost no penile response in castrated dogs. Histological study showed a significant higher ratio of collagen tissue/smooth muscle in the corpus cavernosum of castrated dogs, but no difference in acetylcholine-esterase staining and the number of endothelial cells lining the sinusoidal spaces between castrated and normal dogs. These results indicate that the corpus cavernosum of castrated dogs nearly lost responsiveness to acetylcholine probably due to a high ratio of collagen/smooth muscle fibers and that there are different mechanisms for erectile response to nerve stimulation and intracavernous injection of acetylcholine.
Title: A new case of familial lecithin: cholesterol acyltransferase (LCAT) deficiency--paradoxical findings regarding LCAT mass and activity in 23 members of a family Takata K, Kajiyama G, Horiuchi I, Watanabe T, Tokumo H, Hirata Y Ref: Jpn J Med, 28:765, 1989 : PubMed
LCAT activity and mass were assayed simultaneously in 23 members of a new family case, revealing two homozygotes with a markedly low HDL--cholesterol level and ester cholesterol ratio. The LCAT mass in these patients was only 0.8 and 0.9 micrograms/ml, respectively (normal range 4.4-8.1) and their LCAT activity was 4 and 6 nM/ml/h 37 degrees C (normal range 60-120). Apolipoprotein (Apo) A-I and II levels were significantly low; however, apolipoprotein E tended to be high. In two-dimensional electrophoresis, apo A-I isoform visualized the increase of immature apo A-I; that is, A-I2. One subject showed the clinical characteristics of classic LCAT deficiency; however, the other, who was a vegetarian, showed corneal opacities and red cell deformity, but not proteinuria. This suggests that a low fat diet which decreases the level of atherogenic large LDL, may lead to a more favourable prognosis with a reduced risk for renal insufficiency. There were two different types of LCAT abnormality in this family series. Among the 10 examined paternal kindred of the proband who was one of two homozygotes, seven had a low LCAT mass but normal LCAT activity with the exception of one kindred who had a low mass and low activity. In contrast, among his seven maternal kindred examined, two had a low LCAT activity but normal mass.
