摘要：
Lipoprotein lipase (LPL) is a rate-limiting enzyme that hydrolyzes circulating triglyceride-rich lipoproteins such as very low-density lipoproteins and chylomicrons. A decrease in LPL activity is associated with an increase in plasma triglycerides (TG) and a decrease in plasma high-density lipoprotein cholesterol (HDL-C). The increase in plasma TG and decrease in plasma HDL-C are risk factors for cardiovascular disease. Tsutsumi et al. hypothesized that elevating LPL activity would cause a reduction of plasma TG and an increase in plasma HDL-C, resulting in protection against the development of atherosclerosis. To test this hypothesis, Otsuka Pharmaceutical Factory, Inc. synthesized the LPL activator NO-1886. NO-1886 increased LPL mRNA and LPL activity in adipose tissue, myocardium and skeletal muscle, resulting in an elevation of postheparin plasma LPL activity and LPL mass in rats. NO-1886 also decreased plasma TG concentration and caused a concomitant rise in plasma HDL-C. Long-term administration of NO-1886 to rats and rabbits with experimental atherosclerosis inhibited the development of atherosclerotic lesions in coronary arteries and aortas. Multiple regression analysis suggested that the increase in plasma HDL-C and the decrease in plasma TG protect from atherosclerosis. The atherogenic lipid profile is changed to an antiatherogenic profile by increasing LPL activity, resulting in protection from of atherosclerosis. Therefore, the LPL activator NO-1886 or other possible LPL activating agents are potentially beneficial for the treatment of hypertriglyceridemia, hypo-HDL cholesterolemia, and protection from atherosclerosis.
期刊：
CANCER SCIENCE,2003年94(9):796-801 ISSN：1347-9032
通讯作者：
Gan, RL
作者机构：
[Gan, RL] Nanhua Univ, Sch Med, Canc Res Inst, Hengyang 421001, Peoples R China.;Cent S Univ, Chinese Hlth Minist, Key Lab Carcinogenesis, Changsha 410078, Peoples R China.
通讯机构：
[Gan, RL] N;Nanhua Univ, Sch Med, Canc Res Inst, Hengyang 421001, Peoples R China.
摘要：
We previously constructed human peripheral blood lymphocyte (hu-PBL)/severe combined immunodeficiency mouse (SCID) chimeras and induced human B-cell lymphomas associated with Epstein-Barr virus (EBV) in SCID mice. However, a number of SCID mice died of graft-versus-host disease (GVHD) during the early experimental course. The aim of this study was to test the efficacy of cyclosporine A (CSA) for prevention of GVHD and to define how CSA inhibits the occurrence of GVHD and the production of soluble interleukin (IL) 2 receptor (sIL-2R) in hu-PBL/SCID mice. No mouse died in the active EBV infection group with CSA administration, while 17 mice in three groups without CSA administration died of GVHD. Mortalities in these three groups were 55.56% (5/9),30.43% (7/23), and 27.78% (5/18), and the medium life span was 17 days. Over the first 33 days after hu-PBL transplantation, serum level of human sIL-2R in hu-PBL/SCID chimeras was stable in the active EBV infection plus CSA group, while sIL-2R concentration gradually increased in the sera of mice with active EBV infection without CSA administration and peaked at 22 days. Thirty-two mice developed tumors among the 43 surviving SCID mice. There was no significant difference of tumor incidence between the active EBV infection groups with CSA and without CSA administration (P>0.05). From their morphological and immunohistochemical features, as well as detection of human Alu-sequence and EBV in tumor cells, these EBV-induced tumors were identified as human B-cell lymphomas. Thus, CSA can strikingly inhibit GVHD in hu-PBL/SCID chimeras, and should therefore be effective to establish a stable SCID mouse model of human lymphoma associated with EBV. Treatment with CSA had no effect on the tumor incidence in hu-PBL/SCID chimeras after active EBV infection. Accordingly, serum level of sIL-2R is a valuable indicator of GVHD occurrence in hu-PBL/SCID chimeras.
摘要：
The synthetic compound NO-1886 ([4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester, CAS 133208-93-2) is a lipoprotein lipase activator which decreases plasma triglycerides and elevates high-density lipoprotein cholesterol (HDL-C) levels. However, the effects of NO-1886 on plasma glucose level and atherosclerosis in diabetes are not clear. The aim of this study was to ascertain whether the compound lowers plasma glucose and suppresses atherosclerosis in New Zealand White rabbits with high fat/high sucrose-induced mild diabetes. High fat/high sucrose feeding increased plasma total cholesterol, triglyceride and glucose levels and decreased HDL-C levels resulting in atherosclerosis in the aorta. Administration of NO-1886 to the rabbits resulted in decreased plasma total cholesterol, triglyceride and glucose levels and increased HDL-C levels after 20 weeks of treatment. Furthermore, NO-1886 provided protection against the development of atherosclerosis in the aorta. These data indicate that NO-1886 not only ameliorates the lipid disorder, but also lowers plasma glucose levels and suppresses atherosclerosis in the aorta of diabetic rabbits.
摘要：
Objective. To investigate the different effects of an angiotensin II type 1 (AT1) receptor antagonist, losartan, and an angiotensin converting enzyme (ACE) inhibitor, fosinopril, on cardiomyocyte apoptosis, myocardial fibrosis, and angiotensin II (Ang II) in the left ventricle of spontaneously hypertensive rats (SHR). Methods. SHRs of 16-week-old were randomly divided into 3 groups: SHR-L (treated with losartan, 30 mg · kg-1 · d-1), SHR-F (treated with fosinopril, 10 mg · kg-1 · d-1), and SHR-C (treated with placebo). Each group consisted of 10 rats. Five rats, randomly selected from each group, were killed at the 8th and 16th week after treatment. Cardiomyocyte apoptosis, collagen volume fraction (CVF), perivascular collagen area (PVCA) and Ang II concentrations of plasma and myocardium were examined. Results. Compared with the controls at the 8th and 16th week, systolic blood pressures were similarly decreased in both treatment groups. Left ventricular weight and left ventricular mass indexes were significantly lower in both treatment groups. However, the latter parameter at the 16th week was reduced to a less extent in the fosinopril group than that in the losartan group. Compared with the controls, cardiomycyte apoptotic index was significantly reduced at the 8th week only in the fosinopril group, and at the 16th week in both treatment groups. The index of the fosinopril group was lower than that of the losartan group at the latter endpoint examined. Compared with the controls, the left ventricular collagen volume fraction and perivascular collagen area at the 8th and 16th weeks were significantly reduced in the SHRs treated with either fosinopril or losartan. However, the collagen volume fraction at the latter endpoint in the fosinopril group was lower than that in the losartan group. Compared with the controls at endpoints, plasma and myocardium Ang II levels were significantly increased in the losartan group. However, plasma Ang II concentrations were not altered, and myocardium Ang II concentrations at the 8th and 16th weeks were significantly reduced in the fosinopril group. Conclusions. Both losartan and fosinopril could effectively inhibit cardiomyocyte apoptosis and myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these cardioprotective effects, suggesting that the effects of both drugs are related to the inhibition of myocardium renin-angiotension-aldsterone system.
作者机构：
Cent S Univ, Xiangya Med Coll, Dept Pathophysiol, Changsha 410078, Peoples R China.;Nanhua Univ, Inst Cardiovasc Res, Hengyang 421001, Hunan, Peoples R China.;[Yuan, ZH] Department of Pathphysiology, Xiangya Medical College, Central South University;[Yang, YZ; Yang, XY] Institute of Cardiovascular Research of Nanhua University
通讯机构：
Department of Pathphysiology, Xiangya Medical College, Central South University, China
摘要：
Objective To study the resistance mechanism of clinical isolates of Ureaplasma urealyticum resistant to fluoroquinolones. Methods Thirteen isolates of Ureaplasma urealyticum resistant to six fluoroquinolones were selected out of 184 clinical isolates and their QRDRs (quinolone resistance-determining region) gyrA, gyrB, parC and parE were amplified by PCR. Sequencing results were compared to those susceptible reference strains and a comparison of deduced amino acid sequences were performed. Results Sequence comparison revealed a C to A change at 87nt of gyrA QRDR leading to the substitution of Asp95 with glutamic acid and a C to T change at 50nt of parC QRDR leading to the substitution of Ser8O with leucine. Conclusion These results suggest that a C to A change at 87nt of gyrA QRDR and a C to T change at 50nt of parC QRDR are associated with fluoroquinolone resistance of Ureaplasma urealyticum.
摘要：
Objective. To investigate the expression of hypoxia-inducible factor 1 alpha (HIF-1α) and inducible nitric oxide synthase (iNOS) genes in rats' pulmonary arteries in different phases of hypoxia-incluced pulmonary hypertension development. Methods. Models of chronic hypoxic pulmonary hypertension rat were duplicated by intermittent hypoxia. Mean pulmonary arterial pressure (mPAP) was measured by right-heart catheterization. HIF-1α and iNOS messenger ribonucleic acid (mRNA) were detected by in situ hybridization. HIF-1α and iNOS protein were measured by immunohistochemical analysis. Results. Expression of HIF-1α protein was upregulated in pulmonary arterial tunica intimae of all hypoxic rats. In pulmonary arterial tunica media, the level of HIF-1α protein was markedly upregulated at days 3 and 7 of hypoxia (P < 0.01), then tended to restore at 14 days and 21 days. HIF-1α mRNA levels in pulmonary arteries of rats began to increase significantly at day 14 of hypoxia (P < 0.01). Expression of iNOS mRNA and protein in pulmonary arteries of rats were upregulated by hypoxia for 3 days (P < 0.01), then reached its peak and maitained the same level while the extension of hypoxia. Linear correlation analysis showed that iNOS protein was associated with both mean pulmonary arterial pressure (r = 0.74, P < 0.01) and hypoxic pulmonary vascular remodeling (r = 0.78, P < 0.01), whereas the inverse was associated with HIF-1α protein (r = - 0.52, P < 0.01). Conclusions. HIF-1α and iNOS are both involved in the pathogenesis of hypoxia-induced pulmonary hypertension in rat. HIF-1α protein may upregulate the expression of iNOS gene by transcriptional activation; in addition, iNOS protein may inhibit the expression of HIF-1α protein.
摘要：
To establish the applied anatomy of the V-shaped fibular osteomyocutaneous flap pedicled on the peroneal vessels, cadaver dissections were made in 60 lower limbs and 40 calcanei were examined to sum up the features of calcaneal biomechanics on the stability of the foot and the blood supply of the fibular osteomyocutaneous flap. There were four anastomoses and large communicating branches between the lower segment of the peroneal artery and the anterior and posterior tibial arteries. The flap was well supplied by a retrograde circulation through these anastomoses. A suitable length of pedicle was 20 cm. In the sagittal section of the calcaneus passing through the center of the articular surface for the cuboid bone, the arrangement of the trabeculae formed a triangular zone. The V-shaped flap corresponds nicely with the calculated lines of stress evoked by the weight of the body. The procedure may provide a new method for hindfoot reconstruction. This flap meets the criteria outlined for composite tissue reconstruction of defects of the extremities and biomechanics of the hindfoot, especially for calcaneal and cuboid defects.
摘要：
INTRODUCTIONIt has been well known that MNNG is one of thestrong and multipotential carcinogens that havebeen frequently reported inducing malignant peptictumors.We have successfully induced rat and doggastric adenocarcinomas,squamous cell carcinomasof rat forestomach and gastric leiomyosarcoma of
