Human urotensin-II (U-II) is the most potent vasoactive peptide identified to date, and may be involved in hypertension and atherosclerosis. We investigated the effects of the interactions between U-II or other vasoactive agents and mildly oxidized low-density lipoprotein (mox-LDL) or hydrogen peroxide (H2O2) on the induction of vascular smooth muscle cell (VSMC) proliferation. Growth-arrested rabbit VSMCs were incubated with vasoactive agents (U-II, endothelin-1, angiotensin-II, serotonin, or thromboxane-A2) in the presence or absence of mox-LDL or H2O2. [3H]Thymidine incorporation into DNA was measured as an index of VSMC proliferation. On interaction with mox-LDL or H2O2, U-II induced the greatest increase in [3H]thymidine incorporation among these vasoactive agents. A low concentration of U-II (10 nmol/l) enhanced the potential mitogenic effect of low concentrations of mox-LDL (120 to 337%) and H2O2 (177 to 226%). U-II at 50 nmol/l showed the maximal mitogenic effect (161%), which was abolished by G protein inactivator (GDP-beta-S), c-Src tyrosine kinase inhibitor (radicicol), protein kinase C (PKC) inhibitor (Ro31-8220), extracellular signal-regulated kinase (ERK) kinase inhibitor (PD98059), or Rho kinase inhibitor (Y27632). Mox-LDL at 5 microg/ml showed the maximal mitogenic effect (211%), which was inhibited by free radical scavenger (catalase), intracellular and extracellular antioxidants (N-acetylcysteine and probucol), nicotinamide adenine dinucleotide phosphate oxidase inhibitor (diphenylene iodonium), or c-Jun N-terminal kinase (JNK) inhibitor (SP600125). These results suggested that U-II acts in synergy with mox-LDL in inducing VSMC DNA synthesis at the highest rate among these vasoactive agents. Activation of the G protein/c-Src/PKC/ERK and Rho kinase pathways by U-II together with the redox-sensitive JNK pathway by mox-LDL may explain the synergistic interaction between these agents. 相似文献
Electrogastrograms (EGGs) were recorded in patients both before and after receiving proximal gastrectomy plus jejunal interposition (PGJI) or just after receiving total gastrectomy plus jejunal interposition (TGJI). Intraluminal pressure was also recorded in some postoperative patients. The EGG 3 cpm component (2.5-4.9 cpm) remained after PGJI, but subsequently decreased with a significant reduction in the preoperative to postoperative ratio of the 3 cpm components (P<0.05). The mean frequency of the 3 cpm components increased significantly after PGJI (P<0.05) and its instability factor increased. The EGG 10 cpm components became relatively dominant compared to other frequency components in 2 out of 8 of patients having PGJI but the mean amplitude of 10 cpm decreased. In TGJI patients, only the 10 cpm component was conspicuous in EGG as in the case of total gastrectomy and Roux en Y anastomosis procedures. The spectral frequencies of intraluminal pressure in the interposed jejunum were similar to the EGG of 10 cpm components both in the case of PGJI and TGJI patients. In conclusion, surface EGG could record the electrical activities of the interposed jejunum more easily in patients having had TGJI than in PGJI. 相似文献
Recent studies of the effectiveness of ursodeoxycholic acid (UDCA) therapy in patients with primary biliary cirrhosis (PBC) reported that UDCA therapy did not necessarily stop the progression of liver fibrosis in all patients, even those with early stage PBC. Thus, there is a need for more effective treatments that could prevent asymptomatic PBC from progressing to the icteric stage. Bezafibrate is effective in approximately two-thirds of non-icteric patients who have not shown a complete response to UDCA. Serum bilirubin, aspartate aminotransferase and γ-guanosine 5'-triphosphate levelswere significantly lower in patients who responded to additional bezafibrate on univariate analysis. The putative mechanism by which bezafibrate acts in cholestasis is by increasing phospholipid output into bile, which forms micelles with the hydrophobic bile acid that reduces its toxicity. 相似文献
We report on the rare and surgical treatment of a senile patient of infected intralobar pulmonary sequestration. A 56-year-old male who had complained of headache, vomiting, cough, sputum production, and high fever was admitted to our hospital. Chest computed tomography (CT) showed an infected intralobar pulmonary sequestration as an 8x6 cm cystic mass with multiple air-fluid cavities in the left lower basal segment and severe pneumonia in the left upper and lower lobes around the mass. A 3-D CT showed an aberrant artery entering the consolidation from the descending aorta. A standard lower lobectomy was performed with a ligation of the aberrant artery with a diameter of 1 cm supplying the posterior segment of the left lower lobe. A histological examination of the lung revealed acute and chronic broncho-bronchiolitis with cystic dilatation consistent with intralobar pulmonary sequestration. We discuss the characters of senile patients compared with juvenile patients, with reference to a collective review of patients older than 50 reported in the literature. 相似文献
In the present study, the results of living donor liver transplantation (LDLT) for 125 hepatocellular carcinoma (HCC) patients were analyzed to determine optimal criteria exceeding the Milan criteria (MC) but still with predictably good outcomes. On the basis of pretransplant imaging studies, 70 patients met the MC, and 55 patients did not. Patients who exceeded the MC but presented with 相似文献
Polymyositis/Dermatomyositis (PM/DM) is a chronic inflammatory disorder that culminates in injury to the skin and muscle and, sometimes, is accompanied by interstitial lung disease (ILD). A number of autoantibodies are associated with myositis, including those specific for aminoacyl-tRNA synthetase (anti-ARS), signal recognition particle (anti-SRP), and Mi-2. These autoantibodies have proven to be useful in the diagnosis and classification of the diseases and are predictive of prognosis. It has been known that certain patients may have typical DM skin manifestations without clinical evidence of myositis for at least 2 years (Clinically Amyopathic DM; C-ADM). Although classical myositis-related antibodies are well known, specificities related to C-ADM have not been examined in detail. Therefore, we have examined sera from 15 Japanese patients with C-ADM to identify additional autoantibodies associated with this disease. Eight sera of C-ADM patient recognized a polypeptide of approximately 140 kDa and we named this new antibody specificity anti-CADM-140. Anti-CADM-140 antibodies were detected in 8 of 42 patients with DM, but not in patients with other connective tissue diseases or idiopathic pulmonary fibrosis. It is noteworthy that DM patients with anti-CADM-140 had significantly more rapidly progressive ILD when compared to patients without anti-CADM-140 (50% vs 6%, P=0.008). Further studies of the pathogenicity of these autoantibodies specificity may provide insight into the pathogenic mechanisms of PM/DM accompanied by rapidly progressive ILD. 相似文献
Background: The aim of this study was to investigate the effects of two imidazoline-derived intravenous anesthetics, etomidate and midazolam, on vascular adenosine triphosphate-sensitive potassium (KATP) channel activity.
Methods: In isolated rat aorta, isometric tension was recorded to examine the anesthetic effects on vasodilator response to levcromakalim, a selective KATP channel opener. Using the patch clamp method, the anesthetic effects were also examined on the currents through (1) native vascular KATP channels, (2) recombinant KATP channels with different combinations of various types of inwardly rectifying potassium channel (Kir6.0 family: Kir6.1, 6.2) and sulfonylurea receptor (SUR1, 2A, 2B) subunits, (3) SUR-deficient channels derived from a truncated isoform of Kir6.2 subunit (Kir6.2[DELTA]C36 channels), and (4) mutant Kir6.2[DELTA]C36 channels with reduced sensitivity to adenosine triphosphate (Kir6.2[DELTA]C36-K185Q channels).
Results: Etomidate (>= 10-6 m), but not midazolam (up to 10-6 m), inhibited the levcromakalim-induced vasodilation, which was sensitive to glibenclamide (IC50: 7.21 x 10-8 m; maximum inhibitory concentration: 1.22 x 10-4 m). Etomidate (>= 3 x 10-6 m), but not midazolam (up to 10-4 m), inhibited the native KATP channel activity in both cell-attached and inside-out configurations with IC50 values of 1.68 x 10-5 m and 1.52 x 10-5 m, respectively. Etomidate (10-5 m) also inhibited the activity of various types of recombinant SUR/Kir6.0KATP channels, Kir6.2[DELTA]C36 channels, and Kir6.2[DELTA]C36-K185Q channels with equivalent potency. 相似文献