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91.
92.
Angiotensin-II stimulates nitric oxide release in isolated perfused renal resistance arteries 总被引:3,自引:0,他引:3
C. Thorup Mark Kornfeld Joseph M. Winaver Michael S. Goligorsky Leon C. Moore 《Pflügers Archiv : European journal of physiology》1998,435(3):432-434
Nitric oxide (NO) has been implicated as a modulator of the vascular effects of angiotensin II (ANG II) in the kidney. We
used a NO-sensitive microelectrode to study the effect of ANG II on NO release, and to determine the effect of selective inhibition
of the ANG II subtype I receptor (AT1) with losartan (LOS) and candesartan (CAN). NO release from isolated and perfused renal
resistance arteries was measured with a porphyrin-electroplated, carbon fiber. The vessels were microdissected from isolated
perfused rat kidneys and perfused at constant flow and pressure in vitro. The NO-electrode was placed inside the glass collection
cannula to measure vessel effluent NO concentration. ANG II stimulated NO release in a dose-dependent fashion: 0.1 nM, 10 nM
and 1000 nM ANG II increased NO-oxidation current by 85±18 pA (n = 11), 148±22 pA (n = 11), and 193±29 pA (n = 11), respectively. These currents correspond to changes in effluent NO concentration of 3.4±0.5 nM, 6.1±1.1 nM, and 8.2±1.3 nM,
respectively. Neither LOS (1 μM) nor CAN (1 nM) significantly affected basal NO production, but both AT1-receptor blockers
markedly blunted NO release in response to ANG II (10 nM): 77±6% inhibition with LOS (n = 8) and 63±9% with CAN (n = 8). These results are the first to demonstrate that ANG II stimulates NO release in isolated renal resistance arteries,
and that ANG II-induced NO release is blunted by simultaneous AT1-receptor blockade. Our findings suggest that endothelium-dependent
modulation of ANG II-induced vasoconstriction in renal resistance arteries is mediated, at least in part, by AT1-receptor-dependent
NO release.
Received: 24 September 1997 / Accepted: 20 October 1997 相似文献
93.
The authors describe their experience with maintenance electroconvulsive therapy administered to 10 patients, using an abbreviated or a full maintenance schedule. Recommendation for either form of treatment was made on clinical grounds. Patients with major depressive episodes with delusional features appear to respond best to maintenance ECT. 相似文献
94.
A. Suto H. Leon Bradlow George Y. C. Wong Michael P. Osborne Nitin T. Telang 《Breast cancer research and treatment》1993,27(3):193-202
Summary The polycyclic aromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA) is a metabolism-dependent procarcinogen whose tumorigenicity is modified by dietary and endocrine manipulationsin vivo. DMBA initiates molecular and cellular alterations in the mammary tissue, while dietary components and estrogens affect the post-initiational phase of tumorigenic transformation. The mechanism(s) responsible for modulation of tumorigenic transformation remain unclear. This study examines the effects of selected tumor suppressing agents and estradiol (E2) metabolites onin vitro DMBA carcinogenesis utilizing a newly established mouse mammary epithelial cell line C57/MG. Alteration in DNA repair synthesis, metabolism of E2 via the C2- and C16-hydroxylation pathways, and acquisition of anchorage-independent growth were utilized as molecular, endocrine, and cellular biomarkers to quantitate the cellular transformation by DMBA and its modulation by tumor suppressing agents and E2 metabolites. A single 24 hr exposure of 0.78 µM DMBA to C57/MG cells resulted in a 193.9% increase in DNA repair synthesis and a 73.1% decrease in C2/C16 hydroxylation of E2. The DMBA treated C57/MG cells also exhibited increased anchorage-independencein vitro prior to tumorigenesisin vivo. A simultaneous treatment of cells with DMBA and with the highest non-cytotoxic doses of the tumor suppressing agents 5 µM N-(4-hydroxyphenyl) retinamide (HPR), 50 µM indole-3-carbinol (I3C), or 1 µM tamoxifen (TAM) resulted in a 35.6% to 63.9% decrease in DNA repair synthesis, a 23.8% to 1347.6% increase in C2/C16 hydroxylation of E2, and a 53.8% to 72.4% decrease in anchorage-independent growth. The E2 metabolites at the highest non-cytotoxic doses of 0.76 µM estrone (E1), 0.69 µM 2-hydroxyestrone (2-OHE1), and 0.66 µM 2-methoxyestrone (2-MeOHE1) suppressed DMBA-induced DNA repair synthesis by 56.0% to 68.8%. These tumor suppressing agents and E2 metabolites also effectively suppressed post-initiational, anchorage-independent growth by 24.9% to 72.4%. These results indicate that DMBA induces cellular transformation in part by causing DNA damage, altering C2/C16 hydroxylation in favor of C16-hydroxylation, and inducing anchorage-independent growth prior to tumor development. Effective downregulation of these genotoxic, endocrine and proliferative end points by prototypic tumor suppressing agents and by E2 metabolites generated via the C2-hydroxylation pathway suggest that these agents may influence mammary tumorigenesis by inhibiting early occurring initiational and/or post initiational events.Abbreviations DMBA
7,12-dimethylbenz(a)anthracene
- HPR
N-(4-hydroxyphenyl) retinamide
- I3C
indole-3-carbinol
- TAM
tamoxifen
- E2
17-estradiol
- E1
estrone
- 2-OHE1
2-hydroxyestrone
- 2-MeOHE1
2-methoxyestrone
- 16-OHE1
16-hydroxyestrone
- E3
estriol
- DME/F12
Dulbecco's modified Eagle's medium
- F12
Ham's medium
- HU
hydroxyurea
- PBS
phosphate buffered saline
- NaOH
sodium hydroxide
- SDS
sodium dodecyl sulfate
- TCA
trichloroacetic acid
- [C2-3H] E2
estradiol labeled at C2 position
- [C16-3H] E2
estradiol labeled at C16 position
- ANOVA
analysis of variance 相似文献
95.
We determined the prevalence of recent cocaine and alcohol use among motor vehicle fatalities occurring in New York, NY, from 1984 through 1987. Recent cocaine use was detected at autopsy in 18.2% of the sample and no significant difference between drivers (20.0%) and passengers (13.9%) was found. Both alcohol and cocaine metabolites were found in 10.0% of cases tested. The prevalence of cocaine metabolites or alcohol detected in driver fatalities aged 16 through 45 years did not change significantly when the period prior to the widespread availability of "crack" cocaine (1984 through 1985) was compared with the period immediately following the introduction of crack cocaine (1986 through 1987). Additional studies are needed both to elucidate the association between cocaine use and these fatalities and to determine the value of screening persons seriously injured in traffic accidents in areas where such drug use is endemic. 相似文献
96.
Zbigniew Zylicz D. J. Theo Wagener Marina Garzotto Tom B. Vree Eppo van der Kleijn Leon A. G. M. van den Broek Harry C. J. Ottenheijm 《Investigational new drugs》1990,8(1):25-32
Summary N-pentyl-sparsomycin (PSm) is a lipophilic analogue of sparsomycin (Sm), which is a well known inhibitor of protein synthesis. This compound was selected for preclinical pharmacokinetic studies because of its high in vitro and in vivo antitumor activity. In this study in which the drug was evaluated in beagle dogs under anaesthesia, the drug concentrations in plasma, urine and bile samples were determined using high performance liquid chromatography (HPLC). Plasma protein binding was approximately 54%. The mean t1/2 was 0.2 hours (12 minutes) and t1/2 was 0.75 ± 0.1 hours (45 ± 6 minutes). During continuous infusions up to 5.25 hours, the steady state was reached in 3 out of 6 experiments, suggesting that in some cases the real t1/2 was longer than measured. PSm was actively reabsorbed from the renal tubuli. This process was saturable at the higher doses. Tubular reabsorption played only a minor role in pharmacokinetics as most of the drug (67%) was eliminated by the non-renal clearance. The non-renal clearance was saturable at higher doses of PSm and was the reason for non-linearity of pharmacokinetics. 相似文献
97.
Familial occurrence of gastric cancer in the 2-year experience of a population-based registry 总被引:17,自引:0,他引:17
G Zanghieri C Di Gregorio C Sacchetti R Fante R Sassatelli G Cannizzo A Carriero M Ponz de Leon 《Cancer》1990,66(9):2047-2051
The authors studied the familial occurrence of tumors in 154 individuals with gastric cancer by reviewing the clinical data and the genealogical tree of all patients registered in 1986 through 1987 in the Local Health Care District of Modena, Italy, for cancer of the stomach. Crude and age-adjusted (world population) incidence rates of gastric cancer were 34.0 and 21.4 new cases/100,000/year, respectively, in men, and 24.5 and 10.9 in women, respectively. Among first-degree relatives of the registered patients there were 30 cases of gastric carcinoma versus 15 cases in a control group matched for age and sex (Mantel-Haenszel odds ratio [M-H OR] 3.14, P less than 0.01). This excess of gastric neoplasms was observed in siblings (17 versus 7, M-H OR 4.33, P less than 0.02) but not in parents (13 versus 8, not significant). Besides gastric cancer, there was no significant excess of other type of tumors in case families. The familial occurrence of gastric cancer tended to be more frequent in patients with "diffuse" carcinoma (52%) than in subjects with "intestinal" cancer (33%), although the difference was not statistically significant. In conclusion, the current investigation suggests that a "family history" for gastric neoplasms is usually observed in approximately 10% to 15% of the registered cases. As already described for other common malignancies, therefore, the familial occurrence of gastric carcinoma suggests the existence of a genetic susceptibility to cancer of the stomach, at least in a fraction of these patients. 相似文献
98.
99.
Gomez-Martino J. R.; Miralles J. M.; Leon B. De; Hernandez M. T.; Tabernero J. M. 《Nephrology, dialysis, transplantation》1994,9(3):251-256
The present work studies the urinary excretion of PGE2 and PGI2(6-keto PGF 1) in 11 insulin-dependent diabetic patients withchronic renal failure with a glomerular filtration rate of 33.9±9.03 ml/min who had hyporeninaemic hypoaldosteronismto evaluate the influence of these prostaglandins on the appearanceof this latter process. The results obtained in this group ofpatients were compared with those of a control group of healthyindividuals, another group of nine non-diabetic patients withCRF, and a last group of eight insulin-dependent diabetic patientswith normal renal functión to evaluate to what extentthe possible variations in prostaglandin excretion could berelated to the diabetes, CRF, or a conjunction of both processes. The results of the groups of diabetic patients with CRF wereCcr 33.9 ±9.03 ml/min, decreased (P< 0.0001) withrespect to the control group and with no difference with theCRF group without diabetes; plasma potassium (4.7 ±0.4mEq/l), increased P<0.005) with respect to the values foundin the control group; plasma bicarbonate (17.8 ± 1.8mEq/l), decreased (P< 0.005) with respect to the controlgroup and also, though not significantly, with respect to thegroup of non-diabetic patients with CRF. Plasma aldosterone(pg/ml): resting 44.3±14.9; standing 65.7 ±63.5and post-frusemide 65.5 ±58.6, decreased (P<0.01)with respect to the other three groups. Plasma renin activity(PRA) (ng/ml/h): resting 0.34±0.3; standing 0.6 ±0.4, post-fmsemide 0.9 ±0.5, decreased significantlywith respect to the other three groups. PGE2 (pg/mg Cr): basal1720±397; post-frusemide 2636±462, increased (P<0.05)with respect to the control group and that of the diabetic patientswithout CRF, but with no differences compared with the non-diabeticpatients with CRF. PGI2 (pg/mg cr): basal 369 ±45 andpost-frusemide 699 ± 103, increased (P<0.01) withrespect to the controls and diabetic patients with normal renalfunction and with no differences compared with the non-diabeticpatients with CRF. Our findings indicate that patients with diabetes mellitus andCRF showing hyporeninaemic hypoaldosteronism have high urinaryexcretion of PGE2 and PGI2. The increase in the urinary prostaglandinsis related to CRF. The data rule out the hypothesis that thehyporeninaemic hypoaldosteronism of these patients is due toa deficit of prostaglandins. 相似文献
100.
Mast cells express a peripheral cannabinoid receptor with differential sensitivity to anandamide and palmitoylethanolamide. 总被引:21,自引:1,他引:20
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L Facci R Dal Toso S Romanello A Buriani S D Skaper A Leon 《Proceedings of the National Academy of Sciences of the United States of America》1995,92(8):3376-3380
Mast cells are multifunctional bone marrow-derived cells found in mucosal and connective tissues and in the nervous system, where they play important roles in tissue inflammation and in neuroimmune interactions. Very little is known about endogenous molecules and mechanisms capable of modulating mast cell activation. Palmitoylethanolamide, found in peripheral tissues, has been proposed to behave as a local autacoid capable of downregulating mast cell activation and inflammation. A cognate N-acylamide, anandamide, the ethanolamide of arachidonic acid, occurs in brain and is a candidate endogenous agonist for the central cannabinoid receptor (CB1). As a second cannabinoid receptor (CB2) has been found in peripheral tissues, the possible presence of CB2 receptors on mast cells and their interaction with N-acylamides was investigated. Here we report that mast cells express both the gene and a functional CB2 receptor protein with negative regulatory effects on mast cell activation. Although both palmitoylethanolamide and anandamide bind to the CB2 receptor, only the former downmodulates mast cell activation in vitro. Further, the functional effect of palmitoylethanolamide, as well as that of the active cannabinoids, was efficiently antagonized by anandamide. The results suggest that (i) peripheral cannabinoid CB2 receptors control, upon agonist binding, mast cell activation and therefore inflammation; (ii) palmitoylethanolamide, unlike anandamide, behaves as an endogenous agonist for the CB2 receptor on mast cells; (iii) modulatory activities on mast cells exerted by the naturally occurring molecule strengthen a proposed autacoid local inflammation antagonism (ALIA) mechanism; and (iv) palmitoylethanolamide and its derivatives may provide antiinflammatory therapeutic strategies specifically targeted to mast cells ("ALIAmides"). 相似文献