المؤلفون: Kim Jiramongkolchai, Paul Sternberg, Stephen J. Kim, Maziar Lalezary, Franco M. Recchia, Anupam Agarwal

المصدر: Retina. 31:679-685

مصطلحات موضوعية: Male, Pars plana, medicine.medical_specialty, Intraocular pressure, genetic structures, medicine.medical_treatment, Visual Acuity, Ocular hypertension, Glaucoma, Vitrectomy, Tonometry, Ocular, Retinal Diseases, Risk Factors, Diabetes mellitus, Ophthalmology, Humans, Medicine, Postoperative Period, Intraocular Pressure, Retrospective Studies, business.industry, Incidence, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, eye diseases, Vitreous Hemorrhage, medicine.anatomical_structure, Female, Ocular Hypertension, sense organs, business, Glaucoma, Open-Angle, Pseudophakia, Follow-Up Studies

الوصف: Purpose To evaluate the effect of vitrectomy on intraocular pressure (IOP). Methods Retrospective cohort study. Medical records of 101 eyes of 101 patients undergoing nonemergent vitrectomy were reviewed for rates of open-angle glaucoma, increased IOP of >4 mmHg from baseline, change in IOP from baseline, and cataract formation. Preoperative and last measured IOPs were recorded. Baseline risk characteristics including lens status and diabetes were analyzed. Main outcome measures were 1) incidence of open-angle glaucoma; 2) increase in IOP of >4 mmHg; and 3) change in IOP. Results Mean follow-up was 49 months (range, 12-105 months). Mean baseline IOP was 15.3 mmHg, and mean final IOP was 15.8 mmHg (P = 0.3). At the most recent examination, 35 study eyes had a decrease in IOP from baseline, while 14 eyes had no change and 52 eyes had an increase in IOP. Four study eyes were newly diagnosed with ocular hypertension. No study eye developed open-angle glaucoma or required medical, laser, or surgical treatment for glaucoma. Incidence of increased IOP of >4 was 7% at 4 years and 34% at 8 years. Subgroup analysis of 66 patients comparing study eyes with nonvitrectomized fellow eyes demonstrated no significant difference in rates of increased IOP of >4 (P = 0.85). Neither diabetes nor pseudophakia was associated with significantly increased IOP. Conclusion In this series, vitrectomy does not appear to increase IOP even after removal of the crystalline lens.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ac509946207a6a529bb13a3f768a66bbTest
https://doi.org/10.1097/iae.0b013e3181ff0d5aTest

المؤلفون: Francisco J. Schopfer, Franca Golin-Bisello, Y. Eugene Chen, Bruce A. Freeman, Nicholas K.H. Khoo, Jifeng Zhang, Subhashini Bolisetty, Philip M. Bauer, Anupam Agarwal, Muhammad Ali, Marsha P. Cole, Tanja K. Rudolph, Volker Rudolph, Uche N Motanya, Steven R. Woodcock, Jeffrey W. Wertz

المصدر: Circulation Research. 105:965-972

مصطلحات موضوعية: Neointima, Smooth muscle cell migration, Physiology, Oleic Acids, Inflammation, Pharmacology, Nitric Oxide, Article, Gene Expression Regulation, Enzymologic, Nitric oxide, Mice, chemistry.chemical_compound, Cell Movement, In vivo, medicine, Animals, Mice, Knockout, Platelet-Derived Growth Factor, Neointimal hyperplasia, Nitro Compounds, medicine.disease, Rats, Up-Regulation, Femoral Artery, Heme oxygenase, medicine.anatomical_structure, chemistry, Biochemistry, Heme Oxygenase (Decyclizing), medicine.symptom, Tunica Intima, Cardiology and Cardiovascular Medicine, Oxidation-Reduction, Blood vessel

الوصف: Rationale : Fatty acid nitroalkenes are endogenously generated electrophilic byproducts of nitric oxide and nitrite-dependent oxidative inflammatory reactions. Existing evidence indicates nitroalkenes support posttranslational protein modifications and transcriptional activation that promote the resolution of inflammation. Objective : The aim of this study was to assess whether in vivo administration of a synthetic nitroalkene could elicit antiinflammatory actions in vivo using a murine model of vascular injury. Methods and Results : The in vivo administration (21 days) of nitro-oleic acid (OA-NO 2 ) inhibited neointimal hyperplasia after wire injury of the femoral artery in a murine model (OA-NO 2 treatment resulted in reduced intimal area and intima to media ratio versus vehicle- or oleic acid (OA)-treated animals, P 2 in both cultured aortic smooth muscle cells and in vivo. Inhibition of HO by Sn(IV)-protoporphyrin or HO-1 small interfering RNA reversed OA-NO 2 –induced inhibition of platelet-derived growth factor-stimulated rat aortic smooth muscle cell migration. The upregulation of HO-1 expression also accounted for the antistenotic actions of OA-NO 2 in vivo, because inhibition of neointimal hyperplasia following femoral artery injury was abolished in HO-1 −/− mice (OA-NO 2 –treated wild-type versus HO-1 −/− mice, P =0.016). Conclusions : In summary, electrophilic nitro-fatty acids induce salutary gene expression and cell functional responses that are manifested by a clinically significant outcome, inhibition of neointimal hyperplasia induced by arterial injury.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::798b702081514a205c103b90d679989bTest
https://doi.org/10.1161/circresaha.109.199075Test

المؤلفون: Wei Mu, Li Zhang, Mark A. Atkinson, Xiaosen Ouyang, Pedro E. Cruz, Richard J. Johnson, David A. Long, Olena Glushakova, William W. Hauswirth, Anupam Agarwal, Carlos Roncal, Terry R. Flotte, Vince A. Chiodo, Bernardo Rodriguez-Iturbe

المصدر: Journal of the American Society of Nephrology. 16:3651-3660

مصطلحات موضوعية: Male, Nephrology, medicine.medical_specialty, medicine.medical_treatment, Renal function, Kidney Function Tests, Sensitivity and Specificity, Nephropathy, Rats, Sprague-Dawley, chemistry.chemical_compound, Reference Values, Internal medicine, medicine, Animals, RNA, Messenger, Creatinine, Kidney, Reverse Transcriptase Polymerase Chain Reaction, business.industry, Biopsy, Needle, Glomerulosclerosis, General Medicine, medicine.disease, Fibrosis, Immunohistochemistry, Interleukin-10, Rats, Disease Models, Animal, Proteinuria, Endocrinology, medicine.anatomical_structure, Cytokine, Gene Expression Regulation, chemistry, Immunology, Cytokines, Kidney Failure, Chronic, Nephritis, Interstitial, Chemokines, business, Kidney disease

الوصف: IL-10 is a pluripotent cytokine that plays a pivotal role in the regulation of immune and inflammatory responses. Whereas short-term administration of IL-10 has shown benefit in acute glomerulonephritis, no studies have addressed the potential benefits of IL-10 in chronic renal disease. Chronically elevated blood levels of IL-10 in rats were achieved by administration of a recombinant adeno-associated virus serotype 1 IL-10 (rAAV1-IL-10) vector. Control rats were given a similar dose of rAAV1-GFP. Four weeks after injection, IL-10 levels in serum were measured by ELISA, and chronic renal disease was induced by a 5/6 nephrectomy (n = 6 in each group). Eight weeks later, rats were killed and renal tissue was obtained for RNA, protein, and immunohistochemical analysis. Serum levels of IL-10 were 12-fold greater in the rAAV1-IL-10 group by 4 wk after rAAV1-IL-10 administration (345 +/- 169 versus 28 +/- 15 pg/ml; P = 0.001), and levels were maintained throughout the experiment. rAAV1-IL-10 treatment resulted in less proteinuria (P < 0.05), lower serum creatinine (P < 0.05), and higher creatinine clearances (P < 0.01) compared with rAAV1-GFP-treated rats. Renal interstitial infiltration was significantly attenuated by rAAV1-IL-10 administration as assessed by numbers of CD4+, CD8+, monocyte-macrophages (ED-1+) and dendritic (OX-62+) cells (P < 0.05), and this correlated with reductions in the renal expression of monocyte (renal monocyte chemoattractant protein-1 mRNA and protein) and T cell (RANTES mRNA) chemokines. rAAV1-IL-10 administration decreased mRNA levels of IFN-gamma and IL-2 in the kidney. The reduction in inflammatory cells was associated with a significant reduction in glomerulosclerosis and interstitial fibrosis. It is concluded that IL-10 blocks inflammation and improves renal function in this model of chronic renal disease. The feasibility of long-term overexpression of a gene using the AAV serotype 1 vector system in a model of renal disease is also demonstrated.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c08c6764829872edf06afe20c262f98eTest
https://doi.org/10.1681/asn.2005030297Test

المؤلفون: Anupam Agarwal, Christopher Latham, Hailan Zhou, Gary A. Visner, Dani S. Zander, Fuhua Lu

المصدر: Transplantation. 76:650-656

مصطلحات موضوعية: Transplantation, Pathology, medicine.medical_specialty, medicine.medical_treatment, Granulation tissue, Interleukin, Biology, Heme oxygenase, Lesion, medicine.anatomical_structure, Cytokine, medicine, Immunohistochemistry, Respiratory epithelium, medicine.symptom, Allotransplantation

الوصف: BACKGROUND Heme oxygenase (HO)-1, long believed to be a cytoprotective protein, has recently been identified as a graft survival gene. This study evaluates the role of HO-1 in a murine heterotopic tracheal allograft model for obliterative bronchiolitis. METHODS Mice with deficient or experimentally enhanced HO-1 expression underwent subcutaneous implantation of murine tracheal isografts and allografts. Grafts were excised after 9, 16, or 21 days and evaluated by histologic examination, immunohistochemistry for HO-1 and interleukin (IL)-10 proteins, and terminal deoxynucleotide transferase-mediated dUTP nick-end labeling. To evaluate the relationships between IL-10 and HO-1, the effects of modulation of HO-1 expression on IL-10 expression were evaluated and HO-1 expression was examined in tracheal transplants from IL-10 null mice. RESULTS Isografts demonstrated normal histology with minimal HO-1 staining, whereas allografts showed features of human airway rejection (loss of respiratory epithelium, luminal granulation tissue, lymphocytic tracheitis) with increased HO-1 staining in macrophages and mesenchymal cells. HO-1-deficient mice demonstrated a more rapid progression of the tracheal allograft injury as compared with control allografts, and this was associated with a decrease in the anti-inflammatory cytokine, IL-10. Tracheal transplants using IL-10-deficient mice also resulted in a more severe injury, and this was accompanied by a decrease in HO-1 staining. CONCLUSIONS HO-1 protein expression is increased in murine heterotopic airway rejection, and deficiency of HO-1 accelerates the development of the obliterative bronchiolitis-like lesion. IL-10 protein expression parallels expression of HO-1, suggesting that IL-10 may participate in the genesis of HO-1's effects on the inflammatory processes triggered by allotransplantation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::1adb6d8019de01eaa2a2cc3d7ddf28cbTest
https://doi.org/10.1097/01.tp.0000080069.61917.18Test

المؤلفون: Jawed Alam, Arthur J. Matas, Anupam Agarwal, Youngki Kim, Karl A. Nath

المصدر: Transplantation. 61:93-98

مصطلحات موضوعية: Transplantation, Kidney, Oxygenase, biology, Molecular biology, Nitric oxide, Nitric oxide synthase, Heme oxygenase, chemistry.chemical_compound, medicine.anatomical_structure, chemistry, Immunology, medicine, biology.protein, Macrophage, Heme

الوصف: Gases are now viewed as biologic messengers, and in this regard, carbon monoxide and nitric oxide are incriminated in signaling processes in neural tissue. Carbon monoxide is generated by heme oxygenase (HO), an enzyme inducible by heme, cytokines, and oxidative stress and considered an antioxidant response; nitric oxide is generated by nitric oxide synthase, an enzyme also inducible by cytokines. Since mononuclear cells infiltrate the acutely rejecting kidney, and foster within the kidney oxidative stress and a cytokine-enriched milieu, we examined the expression of these enzymes in acute renal allograft rejection (AR) (Brown Norway kidney to a Lewis rat ; n=17) and in control isografts (Lewis kidney to a Lewis rat ; n=17). No immunosuppressives were used. We found marked induction of HO mRNA and protein in renal allografts at day 5 after transplantation. Prominent expression of HO protein, as detected by immunofluorescence, was observed in the mononuclear cells infiltrating the renal allograft. More than 80% of these cells were macrophages, as identified by positive staining with ED1 antibody. ED1 + cells were rare in isografts and did not stain for HO. We also found co-expression of mRNA and protein for the inducible isoform of nitric oxide synthase (iNOS) in AR at day 5 after transplantation. Induction of HO and iNOS may reflect the cellular effect of diverse cytokines elaborated in the rejecting kidney. HO may enable the macrophage to degrade heme-containing proteins released from erythrocytes and other damaged cells ; alternatively, induction of HO may defend the macrophage against oxidant injury. Increased nitric oxide, as a result of iNOS activity, may antagonize the vasoconstrictive effects of a number of mediators (i.e., thromboxane and endothelin) present in acute rejection ; conversely, nitric oxide may prove cytotoxic through a number of recognized effects. Our studies provide the first demonstration of the induction of HO in the rejecting renal allograft as well as the first demonstration in vivo for the induction of HO in macrophages at the site of an inflammatory response. Such expression, linked as it is to the expression of iNOS, indicates that the macrophage mimics the behavior of neural cells by generating these gaseous messengers ; thus, neural cells are not alone in deploying these mediators. Through a number of effects, these products of HO and iNOS may influence the nature and severity of tissue injury in AR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::ae5f2303f6532ff429146940934266ecTest
https://doi.org/10.1097/00007890-199601150-00019Test