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Gupta PK Subramani J Leo MD Sikarwar AS Parida S Prakash VR Mishra SK 《European journal of pharmacology》2008,591(1-3):171-176
The present study examined the role of voltage-gated potassium (K(v)) channels and myo-endothelial gap junctions in 4-aminopyridine-induced inhibition of acetylcholine-evoked endothelium-dependent relaxation and NO release in the rat carotid artery. The acetylcholine-induced relaxation was drastically inhibited by 94% and 82%, respectively in the presence of either 100 microM N(G)-nitro-l-arginine methyl ester (L-NAME) or 10 microM 1H-[1,2,4]oxadiazolo[4,3,a]quinoxalin-1-one (ODQ), while it was abolished following endothelium removal. 4-aminopyridine (1 mM), a preferential blocker of the K(v) channels significantly decreased the vasodilator potency, as well as efficacy of acetylcholine (pD(2) 5.7+/-0.09, R(max) 86.1+/-3.5% versus control 6.7+/-0.10 R(max) 106+/-3.5%, n=6), but had no effect on the relaxations elicited by either sodium nitroprusside (SNP) or 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP). 4-AP (1 mM) also inhibited acetylcholine (3 microM)-stimulated nitrite release in the carotid artery segments (99.4+/-4.93 pmol/mg tissue weight wt; n=6 versus control 123.8+/-7.43 pmol/mg tissue weight wt, n=6). 18alpha-glycyrrhetinic acid (18alpha-GA, 5 microM), a gap junction blocker, completely prevented the inhibition of acetylcholine-induced relaxation, as well as nitrite release by 4-AP. In the pulmonary artery, however antagonism of acetylcholine-evoked relaxation by 4-AP was not reversed by 18alpha-GA. These results suggest that 4-AP-induced inhibition of endothelium-dependent relaxation and NO release involves electrical coupling between vascular smooth muscle and endothelial cells via myo-endothelial gap junctions in the rat carotid artery, but not in the pulmonary artery. Further, direct activation of 4-AP-sensitive vascular K(v) channels by endothelium-derived NO is not evident in the carotid blood vessel, while this appears to be an important mechanism of acetylcholine-induced relaxation in the pulmonary artery. 相似文献
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Sadananda Rao Manjunath Ganapathi Ramanan Vidyasagar Devaprasad Dedeepiya Hiroshi Terunuma Xuewen Deng Subramani Baskar Rajappa Senthilkumar Paramasivam Thamaraikannan Thangavelu Srinivasan Senthilkumar Preethy Samuel J.K. Abraham 《Case reports in oncology》2012,5(1):114-118
Current therapeutic modalities for ovarian cancer such as chemotherapy, radiotherapy and surgery have been reported to yield only marginal success in improving survival rates of patients and have associated adverse effects. We report here a case of recurrent stage IV ovarian cancer, treated with cell-based autologous immune enhancement therapy (AIET) along with chemotherapy and followed up for 18 months. A 54-year-old female was diagnosed with a recurrence of ovarian carcinoma 1 year after initial surgical removal followed by chemotherapy for stage IIIC ovarian carcinoma. When diagnosed in 2010 with recurrence, she had liver and spleen metastases with a CA-125 level of 243 U/ml and a stage IV clinical status. Six infusions of AIET using autologous in vitro expanded and activated natural killer (NK) cells (CD3–CD56+) and activated T lymphocytes (CD3+CD56+) were administered in combination with 6 cycles of chemotherapy with carboplatin and doxorubicin. Following this treatment, CA-125 decreased to 4.7 U/ml along with regression of the metastatic lesions and an improved quality of life. No adverse reactions were reported after the AIET transfusions. Eighteen months of follow-up revealed a static nonprogressive disease. Combining AIET with chemotherapy and other conventional treatments has been found to be effective in our experience, as reported earlier, even in patients with advanced ovarian cancer, and we recommend this strategy be considered in treating similar cases.Key words: Autologous immune enhancement therapy, Recurrent ovarian carcinoma, Natural killer cells (CD3–CD56+), • Activated T lymphocytes (CD3+CD56+) 相似文献
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Yadvinder Singh M.D. Bhupinder Singh M.D. Shivakumar Bhairappa D.M. Khamitkar Shankar Rao Subramani D.M. Naviluru M. Prasad D.M. Manjunath C. Nanjappa D.M. 《Echocardiography (Mount Kisco, N.Y.)》2013,30(6):E171-E174
A previously healthy 16‐year‐old girl presented with history of fever of 3 months duration without any significant clinical finding on examination. Transthoracic echocardiography (TTE) revealed moderate pericardial effusion and later diagnosed as tubercular in etiology. Besides, TTE also showed an incidental finding of large left ventricular (LV) diverticulum in submitral region along the postero‐basal segment and left ventricular noncompaction (LVNC). Nonapical LV diverticulum is a rare variant of this uncommon congenital condition and its association with LVNC has not been reported in literature. Patient was discharged on antitubercular therapy for pericardial effusion and advised for 6 monthly follow‐up for diverticulum. 相似文献
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Subramani Mani 《J Am Med Inform Assoc》2010,17(5):614-Oct;17(5):614