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We tested the hypothesis that in isolated cardiac myocytes, the negative functional effects of cyclic GMP would be blunted
when the level of cyclic AMP was increased and that this interaction would be altered in renal hypertensive (One-Kidney-One-Clip,
1K1C) cardiac hypertrophic rabbits. Using isolated control and 1K1C ventricular myocytes, cyclic AMP and cell shortening (%)
data were collected: 1) at baseline, 2) after the addition of 8-Br-cGMP 10−7, −6, −5 M, and 3) after forskolin (10−6 M), and adenylate cyclase activator, followed by 8-Br-cGMP 10−7, −6,−5 M. Basal levels of cyclic AMP were similar in control vs. 1K1C myocytes (10.2 ± 1.6 vs. 11.3 ± 2.6 pmol/105 myocytes). We found that 8-Br-cGMP decreased the percent shortening in a dose related manner in both control myocytes (5.1
± 0.6 to 3.2 ± 0.4%) and hypertrophic myocytes (5.2 ± 0.4 to 3.6 ± 0.5). The level of cyclic AMP significantly increased after
the addition of 8-Br-cGMP in control myocytes (14.1 ± 2.1), but not in 1K1C myocytes. Forskolin increased the percent shortening
in the control myocytes (3.8 ± 0.1 to 4.8 ± 0.4), but no significant increase was noted in the hypertrophic myocytes (3.6
± 0.3 to 3.7 ± 0.3). The level of cyclic AMP significantly increased after the addition of forskolin in both control (13.9
± 2.0), and 1K1C cells (14.6 ± 3.8). Forskolin attenuated the negative functional effects of 8-Br-cGMP in the control (4.8
± 0.4 to 3.2 ± 0.1) and 1K1C myocytes (3.7 ± 0.3 to 2.7 ± 0.3). The adition of 8-Br-cGMP did not affect the level of cyclic
AMP after forskolin in either control (13.9 ± 2.0 to 14.8 ± 2.5) or 1K1C myocytes (14.6 ± 3.8 to 13.8 ± 1.9). These data indicated
that in hypertrophic cardiac myocytes the negative functional effects of 8-Br-cGMP were similar to control, but the positive
functional effects of cyclic AMP were blunted. There was an increase in cyclic AMP levels after addition of 8-Br-cGMP in control
but not 1K1C cells. We conclude that in control and hypertrophic myocytes, the effects of cyclic GMP were blunted after forskolin,
but this did not seem to be related to cyclic AMP phosphodiesterase activity.
Received: 12 October 1999, Returned for 1. revision: 24 November 1999, 1. Revision received: 23 March 2000, Returned for 2.
revision: 26 May 2000, 2. received: 16 June 2000, Accepted: 12 July 2000 相似文献
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Kalaimaran Francina Cecilia Ramalingam Ravindhran Munusamy Rajiv Gandhi Appadurai Daniel Reegan Kedike Balakrishna Savarimuthu Ignacimuthu 《Parasitology research》2014,113(9):3477-3484
The mosquitocidal activity of different fractions and isolated compounds from the ethyl acetate extract of Ecbolium viride root was assessed on larvae and pupae of Culex quinquefasciatus Say (Diptera: Culicidae). The larvae and pupae were exposed to concentrations of 6.125, 12.5, 25 and 50 ppm for fractions and 1, 2.5, 5 and 10 ppm for compound. Among the 12 fractions screened, fraction 6 from the ethyl acetate extract of E. viride was recorded to have the highest larvicidal and pupicidal activities against C. quinquefasciatus. The lethal concentration (LC50 and LC90) values of fraction 6 were 4.26 and 9.0 ppm against C. quinquefasciatus larvae and 6.55 and 12.19 ppm against C. quinquefasciatus pupae, respectively, in 24 h. Fraction 7 was recorded to have moderate activity with LC50 and LC90 values of 11.25 and 25.02 ppm against C. quinquefasciatus larvae and 13.33 and 31.15 ppm against C. quinquefasciatus pupae, respectively, in 24 h. Ecbolin A and ecbolin B were identified from fractions 7 and 6, respectively. The structure of the isolated compounds was identified on the basis of spectral data (1H NMR and 13C NMR) and compared with literature spectral data. Further, the isolated compound, ecbolin B, from fraction 6 was recorded to have strong larvicidal and pupicidal activities than ecbolin A. The LC50 and LC90 values of ecbolin B on C. quinquefasciatus larvae were 1.36 and 2.76 ppm, and on pupae, these were 1.54 and 3.51 ppm, respectively. The present results suggest that ecbolin B could be used as a mosquitocidal agent against C. quinquefasciatus. 相似文献
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Huyen Tran Tim Brighton Andrew Grigg Simon McRae Joanna Dixon Daniel Thurley Maher K. Gandhi Matt Truman Paula Marlton John Catalano 《British journal of haematology》2014,167(2):243-251
The efficacy of a fixed‐dose rituximab schedule was prospectively explored in primary/acute refractory, relapsed or chronic (platelet count >10 × 109/l and ≤50 × 109/l) idiopathic thrombocytopenic purpura (ITP). Patients received two doses of rituximab (1000 mg) on days 1 and 15 and were followed‐up on weeks 1–8, 12, 26, 39 and 52. A total of 122 patients were included in the safety population; efficacy was analysed in 108 patients. Overall response rate (ORR) at week 8, defined as the proportion of patients achieving complete response (CR; platelet count >150 × 109/l) or partial response (PR; platelet count >50 × 109/l) was 44%. Therapeutic response, defined as achieving a response at week 8, with at least a minor response (MR; platelet count >30 × 109/l), sustained up to weeks 26 and 52 and accompanied by a reduction in ITP medications, was achieved in 44% (week 26) and 35% (week 52) of patients, respectively. Treatment was well tolerated with no safety concerns. While this study failed to meet its primary endpoint of an ORR of 50%, the efficacy of two fixed doses of rituximab appear to provide similar efficacy to the standard 375 mg/m2 four‐dose schedule in relapsed/chronic ITP. 相似文献
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