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41.
Thalidomide attenuates nitric oxide-driven angiogenesis by interacting with soluble guanylyl cyclase
Syamantak Majumder Megha Rajaram Ajit Muley Himabindu S Reddy KP Tamilarasan Gopi Krishna Kolluru Swaraj Sinha Jamila H Siamwala Ravi Gupta R Ilavarasan S Venkataraman KC Sivakumar Sharmila Anishetty Pradeep G Kumar Suvro Chatterjee 《British journal of pharmacology》2009,158(7):1720-1734
Background and purpose:
Nitric oxide (NO) promotes angiogenesis by activating endothelial cells. Thalidomide arrests angiogenesis by interacting with the NO pathway, but its putative targets are not known. Here, we have attempted to identify these targets.Experimental approach:
Cell-based angiogenesis assays (wound healing of monolayers and tube formation in ECV304, EAhy926 and bovine arterial endothelial cells), along with ex vivo and in vivo angiogenesis assays, were used to explore interactions between thalidomide and NO. We also carried out in silico homology modelling and docking studies to elucidate possible molecular interactions of thalidomide and soluble guanylyl cyclase (sGC).Key results:
Thalidomide inhibited pro-angiogenic functions in endothelial cell cultures, whereas 8-bromo-cGMP, sildenafil (a phosphodiesterase inhibitor) or a NO donor [sodium nitroprusside (SNP)] increased these functions. The inhibitory effects of thalidomide were reversed by adding 8-bromo-cGMP or sildenafil, but not by SNP. Immunoassays showed a concentration-dependent decrease of cGMP in endothelial cells with thalidomide, without affecting the expression level of sGC protein. These results suggested that thalidomide inhibited the activity of sGC. Molecular modelling and docking experiments revealed that thalidomide could interact with the catalytic domain of sGC, which would explain the inhibitory effects of thalidomide on NO-dependent angiogenesis.Conclusion and implications:
Our results showed that thalidomide interacted with sGC, suppressing cGMP levels in endothelial cells, thus exerting its anti-angiogenic effects. These results could lead to the formulation of thalidomide-based drugs to curb angiogenesis by targeting sGC. 相似文献42.
Background:
Compartment syndrome is a potentially devastating condition. Increased intracompartmental pressure has been incriminated as the primary pathogenic factor in compartment syndrome. The purpose of this prospective study was to monitor the anterior compartmental pressure and differential pressure to minimize the incidence of acute compartment syndrome.Materials and Methods:
Seventy-five consecutive cases of closed fractures of leg presenting within six hours of injury were taken for measurement of anterior compartment pressure at the level of fracture and at 5 cm and 10 cm away from the fracture site, using the Whitesides'' infusion technique. A differential pressure of less than 30 mm Hg was taken as the criterion for diagnosis of compartment syndrome.Results:
Two patients (2.67%) developed acute compartment syndrome. The mean anterior compartment pressures were highest at the level of the fracture and went on decreasing as we went away from the fracture site, which was found to be statistically significant (P < 0.001).Conclusion:
Compartment pressure measurement is the most reliable and objective method for early diagnosis of compartment syndrome. Whitesides'' infusion technique is a relatively easy and inexpensive method to come to a diagnosis of compartment syndrome in a developing country like India. Differential pressure is more reliable than absolute pressure in predicting the development of an impending compartment syndrome. 相似文献43.
44.
45.
IJ Webb ; CE Eickhoff ; AD Elias ; LJ Ayash ; CA Wheeler ; GN Schwartz ; GD Demetri ; KC Anderson 《Transfusion》1996,36(2):160-167
BACKGROUND: Peripheral blood progenitor cells (PBPCs) are commonly collected and used to reconstitute hematopoiesis after high-dose chemotherapy. However, strategies for optimal collection and assessment of leukapheresis components are not standardized. STUDY DESIGN and METHODS: Hematopoietic progenitor cell assays were performed on 369 leukapheresis components collected from 95 patients who had received doxorubicin-based chemotherapy and/or granulocyte-colony-stimulating factor (G-CSF). Precollection patient hematologic values, leukapheresis collection values, component hematopoietic progenitor cell assays, and patient outcome measures were summarized. The kinetics of mononuclear cell (MNC) and PBPC mobilization were assessed among four patient groups. RESULTS: Patient group was a significant predictor of the peripheral blood MNC count on the day of collection (p<0.0001), and that value was a significant predictor of granulocyte-macrophage– colony-forming unit (CFU-GM) yield (p<0.0001). This relationship between the peripheral blood MNC count on the day of collection and CFU- GM yield differed according to patient group (p<0.0001). CFU-GM made up a larger fraction of peripheral blood MNCs collected from patients who received chemotherapy plus G-CSF than collected from those who received G-CSF alone. Moreover, the peripheral blood MNC count and the corresponding CFU-GM yield increased significantly on consecutive days of collection in patient groups receiving chemotherapy and G-CSF but were unchanged or decreased in patients receiving G-CSF alone. CONCLUSION: The relationship between peripheral blood MNC count and leukapheresis component CFU-GM yield differed significantly between patients who received chemotherapy and G-CSF and those who received G- CSF alone for the mobilization of PBPCs. Patient peripheral blood MNC count and component CFU-GM yield are useful for both assessing and suggesting revisions to PBPC mobilization and collection strategies. 相似文献
46.
Clinical and patient‐reported outcomes of Chinese patients undergoing haemodialysis in hospital or in the community: A 1‐year longitudinal study 下载免费PDF全文
47.
48.
Surgical bacterial infections and antimicrobial susceptibility patterns at Lilongwe Central Hospital
RM Banda AS Muula GR Gwaza DC Namarika KC Ng'oma FE Chintolo H Yamakazi AP Muyco 《Malawi medical journal : the journal of Medical Association of Malawi》2001,13(3):27-29
A cross sectional study was done between October 1999 and February 2000 to determine antimicrobial susceptibility patterns of consecutive bacterial isolates of 102 clinical samples among surgical in-patients at Lilongwe Central Hospital (LCH), Malawi. Antimicrobial susceptibility was determined using comparative disc diffusion techniques. 83 (81.4%) samples were culture positive for bacterial growth while 19 (18.6%) grew nothing. Of the 93 culture positive specimens, Staphylococcus aureus was the predominant organism 43(51.8%) followed by Proteus species 8(9.6%) and E. coli 7(8.4%). Overall, 98.6% of all isolates tested against ciprofloxacin were susceptible, and against gentamicin and flucloxacin were 84.8% and 66.7% respectively. 59.3% of isolates tested against chloramphenicol were resistant. We recommend a review on the use of chloramphenicol as first-line antimicrobial therapy among surgical in-patients at Lilongwe Central Hospital. We also recommend restricted use of antimicrobials so as to minimise development of drug resistance. Periodic susceptibility studies are necessary to guide judicious use of antibiotics. 相似文献
49.
WCG Peh KC Cheng WY Ho IKL Chan 《Journal of Medical Imaging and Radiation Oncology》1998,42(2):102-105
A 71-year-old woman presenting with severe low back pain was found to have a large oval area of increased sacral uptake on Tc-99m MDP scan, with corresponding T1-hypointense and T2-hyperintense areas on magnetic resonance (MR) images, highly suggestive of malignancy. Open biopsies showed only callus formation. The patient responded clinically to conservative measures, with twice-repeated follow-up Tc-99m MDP and MR scans documenting resolution of transient bone marrow oedema. We suggest that this form of marrow oedema represents a variant pattern of sacral insufficiency fractures. 相似文献
50.
TANYA NAZEMI ANTON GALICH LYNETTE SMITH KC BALAJI 《International journal of urology》2006,13(3):248-251
BACKGROUND: The da Vinci Surgical Robotic System is being increasingly used to perform complex urological operations by minimally invasive techniques. Prior abdominal surgery associated with intra-abdominal adhesions may complicate robotic surgery. METHODS: We used a cohort of consecutive 49 patients undergoing a variety of robotic urological procedures at our institution to study the impact of prior abdominal operations on early perioperative complications. RESULTS: A total of 21/49 (43%) patients (Group A) had no history of prior abdominal surgery and the rest 28/49 (57%; Group B) had undergone prior abdominal surgery. The incidence of peritoneal adhesions was significantly higher in patients with prior abdominal surgery compared to the rest of the cohort, 54% versus 10% (P=0.002). The median operative time, estimated blood loss, postoperative drop in hemoglobin, time to hospital discharge, postoperative narcotic analgesic use and postoperative complication rate between group A and group B were not statistically different. The overall perioperative complication rate for the entire cohort was 14.3%, with 6-8% of complications occurring in each of the two groups (P=1.0). Comparative subset analysis of 28 patients in Group B, 15 (54%) and 13 (46%) with or without intra-abdominal adhesions did not reveal a significant difference in perioperative complication rates either. However, operative time was longer in patients with intra-abdominal adhesions compared to patients without, median of 590 (281-922) and 434 (153-723) min respectively, although not statistically significant (P=0.059). CONCLUSION: Our study demonstrates that robotic urological surgery can be performed in patients with prior abdominal surgery without increased perioperative complications. 相似文献