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181.
S F Bolling M A Groh A M Mattson R A Grinage K P Gallagher 《The Annals of thoracic surgery》1992,54(1):93-98
To test if acadesine (5-aminoimidazole-4-carboxamide riboside), a purine precursor, has cardioprotective effects, 16 dogs were placed on total cardiopulmonary bypass and subjected to global myocardial ischemia. Hemodynamic recovery was compared between a control (n = 8) group receiving standard cardioplegia and an acadesine (n = 8) group pretreated with intravenous acadesine (2.5 mg.kg-1.min-1 for 5 minutes, then 0.5 mg.kg-1.min-1) before ischemia, during ischemia, and until 10 minutes after removal of the aortic cross-clamp. Additionally, in the acadesine group the cardioplegia also contained 20 mumol/L acadesine. While the dogs were on cardiopulmonary bypass, global warm myocardial ischemia was induced by aortic cross-clamping for 5 minutes under normothermic conditions to simulate an angioplasty accident. Five minutes after aortic cross-clamping, hypothermic cardioplegia (30 mL/kg) was administered. The left anterior descending coronary artery was occluded before the first infusion of cardioplegia to simulate poor cardioplegia delivery that can occur during an emergency coronary artery bypass procedure after an angioplasty accident. The left anterior descending artery occlusion was released, and additional cardioplegia (15 mL/kg) infusions were made every 30 minutes thereafter during 120 minutes of cardioplegic ischemia. Thirty minutes after reperfusion, all animals in both groups were weaned from bypass and recovery data were obtained to compare with baseline preischemic values. There were no significant differences in heart rate, left atrial pressure, or systemic vascular resistance between groups after weaning from bypass. Peak developed pressure recovered to 79% +/- 19% (mean +/- standard deviation) of baseline in the acadesine group compared with 56% +/- 22% in the control group (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
182.
Phosphoinositide 3-kinase is involved in the induction of the human sperm acrosome reaction downstream of tyrosine phosphorylation 总被引:7,自引:4,他引:3
Fisher HM; Brewis IA; Barratt CL; Cooke ID; Moore HD 《Molecular human reproduction》1998,4(9):849-855
In somatic cells phosphoinositide 3-kinase (PI 3-kinase) is activated upon
interaction with both receptor tyrosine kinases (RTK) and G- proteins
resulting in the production of moieties involved in the inositol
phospholipid signalling pathway. As G proteins, RTK and the inositol
phospholipids have all been implicated in the human sperm acrosome
reaction, experiments were carried out to determine whether PI 3-kinase was
also involved in this phenomenon. Wortmannin is a selective inhibitor of PI
3-kinase and was shown to significantly inhibit the acrosome reaction
induced by both mannose-bovine serum albumin (mannose-BSA) (10, 50 and 100
nM) and a polyclonal antibody raised against an extracellular region of the
sperm zona receptor kinase (ZRK, at 100 nM only). Wortmannin did not
inhibit the A23187- or progesterone-induced acrosome reaction. These
results suggest that PI 3- kinase is involved in the human sperm acrosome
reaction. The levels of tyrosine phosphorylation of sperm proteins as
detected by Western blotting using antiphosphotyrosine antibodies was not
affected by wortmannin in agonist (A23187 and mannose-BSA)-stimulated
spermatozoa. This indicated that PI 3-kinase operates downstream of
tyrosine phosphorylation in the signal transduction cascade which leads to
the human sperm acrosome reaction.
相似文献
183.
H Awaya E L May M D Aceto L S Harris J V Silverton K C Rice M V Mattson A E Jacobson 《Journal of medicinal chemistry》1987,30(5):947-950
9-Methylene- and 9-ethylidene-5-(m-methoxyphenyl)-2-methylmorphans (1, 2) and refluxing 48% HBr have given rearrangement products 3 and 4, respectively. The structure of 4 [4a-ethyl-2,4a,5,6,7,7a-hexahydro-4-(3-hydroxyphenyl)-1-methyl-1H-1- pyrindine] was determined by X-ray crystallography and that of 3 [1,4a-dimethyl-2,4a,5,6,7,7a-hexahydro-4-(3-hydroxyphenyl)-1-methyl-1H- pyrindine] follows from analogy and NMR data. Compounds 3 and 4 are opioid antagonists of about the potency of nalorphine in the tail-flick vs. morphine assay and precipitate a complete abstinence syndrome in morphine-dependent monkeys. Both are nearly devoid of antinociceptive activity and they have about 0.025 times the affinity of nalorphine for the mu opioid receptor. 相似文献
184.
Magnetic resonance angiography 总被引:6,自引:0,他引:6
Pulse sequences that permit selective detection of moving spins in a magnetic resonance image have been developed. Experiments were performed by the authors to produce projected angiographic data without the use of contrast agents, with the intensity of each image pixel determined by the macroscopic velocity of the detected spins. With this method, suppression of nonmoving spins is essentially complete, yielding a high dynamic range in signal intensity for detected vessels. Selective detection of moving spins is not dependent on pulsatile flow. Consequently, not only arterial structures, but also venous structures can easily be visualized. High-resolution angiographic images can be obtained by combining the flow experiment with surface coil techniques. 相似文献
185.
A Niiranen M Kajanti L Tammilehto K Mattson 《American journal of clinical oncology》1990,13(2):113-116
Eighty-nine patients over 70 years old with untreated lung cancer, of various cell type and in various stages, were randomly assigned to chemotherapy (CT) alone or CT combined with medroxyprogesterone acetate (MPA). CT consisted of cisplatin, 60 mg/m2 i.v., along with etoposide (VP-16), 150 mg/m2 i.v., on day 1. The VP-16 was increased to 200 mg/m2, orally, on day 3. The entire regimen was given every 4 weeks for a maximum of six cycles. MPA was administered in daily 500-mg doses, i.m., 5 days a week for 1 month, followed by 1000 mg i.m., once a week, for 5 months. Changes in body weight and appetite were documented. After two cycles of CT, 64 patients were found to be evaluable for response. Forty-five had non-small-cell lung cancer (NSCLC) and 19 had small-cell lung cancer (SCLC). Thirty-seven patients had received CT alone and 27 CT plus MPA. In NSCLC, the objective response to CT alone was 36% versus 37% with CT plus MPA. In SCLC, the corresponding figures were 63% and 22%. The overall objective response rate was 60% in NSCLC and 48% in SCLC. Median survival using CT alone was 10 months for NSCLC patients and 11 months for SCLC patients. Using CT plus MPA, it was 10 months for NSCLC patients and 7 months for SCLC patients. In the control arm, 1-year survival was 42% for NSCLC patients and 48% for SCLC patients; in those who were given MPA, it was 48% for NSCLC patients and 9% for SCLC patients. Improved appetite and weight gain were reported more frequently by MPA patients, and they did not complain of CT's usual side effects. The fact that MPA had no significant effect on CT response or survival in patients also treated with a combination of cisplatin and VP-16, along with the small survival advantage for the control group in SCLC patients, suggests that combining MPA and CT may result in improved quality of life. 相似文献
186.
Pharmacokinetics of apomorphine in parkinsonian patients 总被引:1,自引:0,他引:1
E. Nicolle P. Pollak F. Serre-Debeauvais P. Richard CL Gervason E. Broussolle and M. Gavend 《Fundamental & clinical pharmacology》1993,7(5):245-252
Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa-induced on-off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high-performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the Tmax was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half-life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter-subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half-life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions. 相似文献
187.
188.
Bone marrow transplantation (BMT) is often followed by significant morbidity and mortality due to protracted immunodeficiency. We have hypothesized that the bone marrow-ablative regimen may delay the recovery of normal immune function following transplantation by impairing the interaction of host endothelial cells with circulating graft-derived lymphocytes. This report compares the relative effects of busulfan (an alkylating drug) and gamma-irradiation on the tissue- specific localization potential of lymphocytes and the eventual recovery of immune function within syngeneic murine transplant recipients. Localization of normal lymphocytes into peripheral lymph nodes of irradiated BMT recipients was markedly less (less than 50%) than in busulfan-treated or normal mice over the first 2 months post- BMT. This finding correlated with irradiation-induced endothelial cell edema and microvascular occlusions within lymphocyte-receptive areas of the nodal microvasculature. The effect of both preparative regimens on the recovery of contact hypersensitivity (CHS) was also analyzed. This response recovered more quickly (between 1 and 2 months) in busulfan- pretreated animals. Further experiments demonstrated that the decrease in CHS responsiveness appeared, in part, related to a depression in the capacity of lymphocytes to localize into skin sites of antigen deposition within irradiated mice. The impairment of tissue-specific lymphocyte localization may represent a novel mechanism by which whole body irradiation can contribute to delayed immunologic reconstitution following bone marrow transplantation. 相似文献
189.
D Rudman H S Nagraj D E Mattson P R Erve I W Rudman 《Journal of the American Geriatrics Society》1986,34(6):427-430
Plasma somatomedin C (SmC) concentration was compared in three groups of men: 58 healthy independent men aged 26 to 45 years; 28 independent men aged 52 to 87 years; and 50 male nursing home residents aged 51 to 95 years. Somatomedin C (mean +/- SE) was 0.73 +/- .04 U/mL, 0.41 +/- .03 U/mL, and 0.33 +/- .03 U/mL in these three groups, respectively (P less than .05 for the differences between all three groups). Somatomedin C less than 0.25 U/mL, a range consistent with severe growth hormone deficiency in children, occurred in 0% of the independent younger men, in 15% of the independent elderly, and in 37% of the nursing home men. Somatomedin C was inversely correlated with age in the independent elderly, but the excess of hyposomatomedinemia in the nursing home men was not explained by age. 相似文献
190.
B Ryberg Y Tielemans J Axelson E Carlsson R H?kanson H Mattson F Sundler G Willems 《Gastroenterology》1990,99(4):935-942
The enterochromaffinlike cells in the rat stomach are rich in histamine and are thought to be under the influence of gastrin. The effect of sustained endogenous and exogenous hypergastrinemia on the activity and proliferation rate of the enterochromaffinlike cells was studied by determining the histidine decarboxylase activity and histamine concentration and by combining histamine immunocytochemistry and autoradiography after in vivo labeling with [3H]thymidine. The proliferation rate of the stem cells in the oxyntic mucosal progenitor zone was also studied. Exogenous hypergastrinemia was induced by infusion of rat gastrin-17 (60 nmol.kg-1.day-1). Endogenous hypergastrinemia was induced by inhibition of gastric acid secretion with omeprazole (80 mumol.kg-1.day-1) or ranitidine (1200 mumol.kg-1.day-1). The effect of omeprazole was also studied in antrectomized rats. In intact rats, all treatments resulted in elevated plasma gastrin levels and were accompanied by an increase in the histidine decarboxylase activity and the histamine content of the oxyntic mucosa. This resulted in an increase in the enterochromaffinlike cell proliferation rate, leading to enterochromaffinlike cell hyperplasia. The number of labeled stem cells was increased, but this effect was not as pronounced as in the enterochromaffinlike cells. In antrectomized rats, the inhibition of acid secretion by omeprazole did not result in elevated plasma gastrin or in an increase in the activity or number of enterochromaffinlike cells, indicating that omeprazole per se had no effect on these cells. These data support the view that gastrin stimulates the proliferation rate of both enterochromaffinlike cells and stem cells. Gastrin also stimulates the activity of the enterochromaffinlike cells. 相似文献