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Xuyu Zu Ruilan Yan Sarah Robbins Paulette A Krishack Duan-Fang Liao Deliang Cao 《Toxicological sciences》2007,97(2):562-568
Acrolein is a highly reactive alpha,beta-unsaturated aldehyde produced endogenously during lipid peroxidation and naturally distributed pervasively in living environments, posing serious threats to human health if not properly metabolized. In this study, we report aldose reductase-like-1 (ARL-1) as a novel enzyme that catalyzes the reduction of acrolein and protects cells from their toxicity. Using purified ARL-1 protein, we determined its enzymatic activity in response to acrolein and defined its steady-state kinetics with K(m) and V(max) at 0.110 +/- 0.012 mM and 3122.0 +/- 64.7 nmol/mg protein/min, respectively. By introducing a functional Enhanced Green Fluorescent Protein (EGFP)/ARL-1 fusion protein into 293T cells, we demonstrated that plating efficiency in liquid culture and focus formation in soft agar increased by more than 60% (p < 0.05), compared to the vector control cells. More significantly, at a low dose of 5 microM acrolein, EGFP/ARL-1 expression enhanced both plating efficiency and focus formation by more than threefold, and the foci (in soft agar) of 293T cells expressing EGFP/ARL-1 were significantly larger than those of the vector control cells. At high concentrations of acrolein (25 and 50 microM), EGFP/ARL-1 protein prevented oncotic death of 293T cells induced by acrolein. In summary, our data demonstrated for the first time that the ARL-1 protein protects 293T cells from acrolein toxicity. Due to the high toxicity and wide distribution of acrolein, this finding is important to the understanding of its detoxification mechanisms. 相似文献
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The lipid-lowering agents, statins, are the most commonly prescribed class of drugs in the western world. Because of their
widespread use, many patients undergo surgical procedures while on statins. Statins, in addition to cholesterol-lowering effects,
also have anticoagulant, immunosuppressive, and antiproliferative properties that may affect the risk of local wound complications.
This study investigated the relationship between statins and postoperative wound complications in a large cohort of patients
undergoing inguinal or ventral hernia repair. Data mining was performed in the Veterans Integrated Service Network (VISN)16
Data Warehouse. This database contains clinical and demographic information about all veterans cared for at the ten VA Medical
Centers that comprise the South Central VA Healthcare Network in the mid-south region of the US. Aggregate data (age, body
mass index, smoking history, gender, race, history of diabetes, statin use, and postoperative wound complications) were obtained
for all patients who underwent inguinal or ventral hernia repair during the period October 1, 1996–November 30, 2004. During
the period of the query, 10,782 patients (10,676 male, 106 female), 1,242 (11.5%) of whom received statins, underwent herniorrhaphy.
Statin use did not affect the risk of wound infection or delayed wound healing. Statin use was, however, associated with an
increased rate of local postoperative bleeding complications (P=0.01). When the type of hernia, age, smoking, diabetes, and body mass index were included in a multivariate analysis, statins
remained borderline significant as an independent predictor of wound hematoma/postoperative bleeding (P=0.04), odds ratio 1.6 (95% CI 1.03–2.44). Patients who undergo inguinal herniorrhaphy while on statins have an increased
risk of postoperative wound hematoma/hemorrhage. Focus on additional factors that may affect the propensity to postoperative
bleeding and on meticulous intraoperative hemostasis are particularly important in such patients. 相似文献
37.
Sequential comparison of low dose rate and hyperfractionated high dose rate endobronchial radiation for malignant airway occlusion. 总被引:2,自引:0,他引:2
M Mehta D Petereit L Chosy M Harmon J Fowler S Shahabi B Thomadsen T Kinsella 《International journal of radiation oncology, biology, physics》1992,23(1):133-139
A pilot trial (S2) was conducted at the University of Wisconsin to determine the feasibility, efficacy, and toxicity of hyperfractionated high dose rate endobronchial radiation. To avoid multiple bronchoscopies, an optimized hyperfractionated schema was derived from the linear-quadratic model. Utilizing a single bronchoscopy, 31 patients with malignant airway occlusion received 4 Gy x 4 fractions over 2 days at 2 cm from source center using a high dose rate remote afterloader. Response and morbidity were compared to a previous trial (S1) in which 66 patients were treated with conventional low dose rate endobronchial radiation. Response was assessed by change in performance status, symptom resolution, percent of lifetime rendered symptom-free or improved, and radiographic reaeration. These parameters were highly comparable between the two groups. The mean ECOG performance status improved from 2.2 to 1.8 for S1 and 2.1 to 1.6 for S2; symptom improvement or resolution was noted in 78% for S1 and 79% for S2; lifetime rendered symptom-free or improved was 54% for S1 and 57% for S2; and the overall radiographic response rate was 78% for S1 and 85% for S2. The overall incidence of fistulae was 7/101. We conclude that endobronchial radiation is an effective and safe modality for palliation, and hyperfractionated high dose rate endobronchial radiation achieves responses similar to low dose rate endobronchial radiation with a similar complication rate. 相似文献
38.
R. Parker Ward MD Mouaz H. Al-Mallah MD Gabriel B. Grossman MD PhD Christopher L. Hansen MD Robert C. Hendel MD Todd C. Kerwin MD Benjamin D. McCallister Jr MD Rupa Mehta MD Donna M. Polk MD MPH Peter L. Tilkemeier MD Aseem Vashist MD Kim Allan Williams MD David G. Wolinsky MD Edward P. Ficaro PhD 《Journal of nuclear cardiology》2007,14(6):911-e38
39.
R. Parker Ward Mouaz H. Al-Mallah Gabriel B. Grossman Christopher L. Hansen Robert C. Hendel Todd C. Kerwin Benjamin D. McCallister Rupa Mehta Donna M. Polk Peter L. Tilkemeier Aseem Vashist Kim Allan Williams David G. Wolinsky Edward P. Ficaro 《Journal of nuclear cardiology》2007,14(6):e26-e38
Conclusion The ACCF/ASNC AC for SPECT MPI provides recommendations for the appropriate use of SPECT MPI. After the publication of the
AC document in 2005, the AC has been used by nuclear cardiology practices with many clinical studies evaluating the list of
indications in routine clinical practice. From these data. ASNC recommends minor but important changes to the indication list,
suggesting the addition of 6 new indications and the modification of the definitions for “chest pain syndrome” and “CHD high
risk.”. An objective review of existing indications focused on only those indications that had significant variability among
the reviewers (n=20). These indications were reviewed in the presence of existing and new evidence-based data, and ASNC recommends
that the grades for 6 indications be re-evaluated.
The AC for SPECT MPI will require periodic review as new evidence becomes available or as clinical practice evolves. ASNC
recognizes the importance of these criteria to improve the quality of patient care, and it will continue to play a key role
in assembling the information for this ongoing review. From the current summary of evidence, ASNC consensus opinions, and
ASNC recommendations in this document, ASNC strongly recommends that the AC guidelines be reviewed
Prepared by the American Society of Nuclear Cardiology Quality Assurance Subcommittee for Quality in Imaging Standards.
Reviewed by members of the American Society of Nuclear Cardiology Quality Assurance Committee.
Approved by the American Society of Nuclear Cardiology Board of Directors, September 6, 20. 相似文献
40.
Thalidomide protects endothelial cells from doxorubicin-induced apoptosis but alters cell morphology 总被引:3,自引:0,他引:3
V. Kaushal G. P. Kaushal † S. N. Melkaveri P. Mehta ‡ 《Journal of thrombosis and haemostasis》2004,2(2):327-334
Summary. Antiangiogenesis agents are now being used in clinical trials to reduce the risk of recurrence of cancer. Several of these agents, however, are associated with thrombosis, especially when used in combination with chemotherapy. Antiangiogenesis and thrombosis are both endothelial-related activities, and we therefore evaluated one presumed antiangiogenesis agent (thalidomide) on intact cultured endothelial cells, and on cultured endothelial cells injured by preincubation with doxorubicin. We evaluated cell viability, caspase-3 activation, morphology of cells using light microscopy, and protease activated receptor-1 (PAR-l) expression. In our experiments, doxorubicin induced a dose- and incubation time-dependent and caspase-3-mediated apoptosis of endothelial cells. Thalidomide alone caused no changes in intact endothelial cells in terms of morphology, cell viability or activation of caspase-3. In contrast, when thalidomide was added to doxorubicin-injured endothelial cells, there was protection from cell death, increase in viability of endothelial cells, induction of differentiation and formation of neotubules. Doxorubicin reduced the expression of thrombin receptor, PAR-1, as evaluated by immunostaining and flow cytometry. Thalidomide did not alter PAR-1 expression in untreated cells but restored its expression reduced by doxorubicin. These findings suggest that thalidomide may be procoagulant, not by enhancing doxorubicin-mediated endothelial cell injury, but by altering the expression of PAR-1 on injured endothelium and resulting in endothelial dysfunction, which may explain hypercoagulability in patients treated with chemotherapy followed by thalidomide. 相似文献