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
Serial DWIs were performed in a patient with CJD who developed symptoms acutely and progressed rapidly. DWI discloed an increased signal in the frontal and parietal inner cortical areas, and in the caudate nuclei and putamina 20 days after the onset of symptoms. T2-weighted images showed only signal abnormality in the caudate nuclei and putamina, but not in the cerebral cortex. In the CSF obtained 15 days after the onset of symptoms, total tau protein was markedly elevated and 14-3-3 protein was positive. Measurement of these proteins are highly specific and sensitive for the diagnosis of CJD, but not available as a rapid routine examination at present. DWI is not specific, but useful for making the diagnosis of CJD in the early stage of the disease. 相似文献
Abstract Substance P is a neuropeptide which is present in peripheral C nerve endings and released from them. Free nerve endings of C nerve are present in human epidermis. The effects of substance P on the transmembrane signaling system of pig epidermal sheets were previously reported. In these studies, a small amount of cells other than keratinocytes contaminated the epidermal sheets and the species difference from human was also noticed. Therefore we investigated the effects of substance P on cultured normal human epidermal keratinocytes. Alteration of intracellular free calcium (Ca2+) in single living keratinocytes was studied using an inverted fluorescence microscope and Ca2+ -sensitive dye, Fura 2-AM. Treatment of normal human epidermal kertinocytes with substance P resulted in an increase in inositol 1,4,5-trisphosphate and in intracellular Ca2+. Substance P inhibited DNA synthesis of the keratinocytes in a dose-dependent manner. These results are consistent with the view that substance P stimulates phosphatidylinositol-4,5-bisphosphate hydrolysis of human keratinocytes, resulting in inositol 1,4,5-trisphosphate-Ca2+ signal. 相似文献
In view of the high binding ability of cardiac glycosides to the myocardial Na,K-ATPase, radioiodinated digoxin derivatives were surveyed as candidates for myocardial imaging, with particular emphasis on the noninvasive monitoring of cardiac glycoside therapy. Among the radioiodinated digoxin derivatives surveyed, 125I-digoxin-iodohistamine(bis(O-carboxymethyloxime)) showed the highest accumulation in the myocardium and similar binding ability to Na,K-ATPase as digoxin itself against ouabain displacement, as indicated by in vivo and in vitro studies. Based on these results, 123I labeling of digoxin-histamine(bis(O-carboxymethyloxime)) and imaging in a dog demonstrated uptake in the myocardium. 相似文献
For intracavitary high dose-rate radiation therapy, a thermoluminescent [TL] sheet for in vivo measurement of spatial dose distribution around source has been recently developed. The TL sheet was found to have a linear response with a very wide dynamic range from at least 0.002 cGy to 5000 cGy for 60Co gamma-rays. This TL sheet (40 cm x 50 cm x 200 microns), which is composed of Teflon mixed with BaSO4:Eu doped powder, is very flexible and can be cut to the desired size. In addition, this sheet is easy to handle because of its insensitivity to room light. The spatial dose distribution is displayed in a color mode by using a newly developed TL sheet readout system. For a clinical application, the TL sheet was wrapped on an applicator for intracavitary radiation therapy of a rectal cancer and was inserted into the rectum. The location of the TL sheet could be confirmed with diagnostic X ray film. After irradiation with high dose-rate 60Co source, the in vivo relative dose distribution on the surface of the rectum was determined. This TL sheet provided a convenient means of measuring the relative dose distributions around 60Co sources of various patterns in intracavitary radiation therapy. 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
Obesity is a risk factor for cardiovascular disease and thromboembolic events. We investigated the effects of weight reduction by a 12-week calorie-restricted diet with or without aerobic exercise (diet group and diet plus exercise group) on leptin and anticoagulation proteins levels. Forty-two obese nondiabetic individuals were evaluated for blood levels of leptin, protein C activity, free protein S antigen and for body fat area calculated on computerized tomography before and after intervention. Before intervention, serum levels of leptin and free protein S antigen correlated positively with several adiposity-related parameters. After the program, body weight and fat area were significantly decreased in both groups. Body mass index and leptin levels decreased in both groups, with a larger change in the diet plus exercise group than in the diet group. Although protein C activity levels did not change in both groups, free protein S antigen levels decreased significantly in the diet plus exercise group. In conclusion, the 12-week programs had significant effects on the initial weight reduction and body fat mass, decreasing lepin levels in obese nondiabetic individuals. To clarify whether aerobic exercise has additional or direct effects on the anticoagulation system, a study in a large number of individuals is needed. 相似文献
Aim: This study aims to establish a pressure ulcers model that visualizes the microcirculation, and to examine the participation of ischemia‐reperfusion injury in the pathophysiology of pressure ulcers. Methods: An original system composed of a new skinfold chamber and compression device allowed loading quantitative vertical stress to the skin. An intravital microscopic technique enabled direct visualization of the microcirculation in the physiological condition and in response to pressure application. To estimate the effect of ischemia‐reperfusion injury, animals were divided into two groups: the compression‐release group in which the animals received four cycles of compression‐release which consisted of 2 hours of compression followed by 1 hour of pressure release; and the compression alone group in which the animals underwent continuous compression for 8 hours. Functional capillary density was quantified before the compression procedure and on day1 (35 hours) after the first evaluation. Results and Conclusions: The cyclic compression‐release procedure significantly decreased functional capillary density as compared to continuous compression, indicating that in our experimental setting repetition of ischemia‐reperfusion cycle more severely damaged the microcirculation than single prolonged ischemic insult. The finding supports the significant contribution of ischemia‐reperfusion injury to the pathophysiology of pressure ulcers at the level of dynamic in vivo microcirculation. 相似文献