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      Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia–reperfusion injury in rats

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          Abstract

          Objectives

          To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model.

          Materials and methods

          Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined.

          Results

          Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group ( P<0.0001, P=0.015, and P<0.01, respectively). Polymorphonuclear leukocyte infiltration, pulmonary partial destruction, consolidation, alveolar edema, and hemorrhage scores were significantly lower in alprostadil- and iloprost-treated groups ( P=0.017 and P=0.001; P<0.01 and P<0.0001). Polymorphonuclear leukocyte infiltration scores in skeletal muscle tissue were significantly lower in the iloprost-treated group than the scores found in the nontreated I/R group ( P<0.0001).

          Conclusion

          Alprostadil and iloprost significantly reduce lung tissue I/R injury. Alprostadil has more prominent protective effects against renal I/R injury, while iloprost is superior in terms of protecting the skeletal muscle tissue against I/R injury.

          Most cited references30

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          Prognostic stratification in critically ill patients with acute renal failure requiring dialysis.

          Despite the widespread availability of dialytic and intensive care unit technology, the probability of early mortality in critically ill persons with acute renal failure is distressingly high. Previous efforts to predict outcome in this population have been limited by small sample size and the absence of uniform exclusion criteria. Additionally, data obtained decades ago may not apply today owing to changes in case mix. The medical records of 132 consecutive patients in the intensive care unit with acute renal failure who required dialysis from 1991 through 1993 were evaluated by a blinded reviewer. The overall in-hospital mortality rate was 70%. Twelve readily available historical, clinical, and laboratory variables were significantly associated with in-hospital mortality. Multivariate logistic regression analysis showed that mechanical ventilation, malignancy, and nonrespiratory organ system failure were independently associated with in-hospital mortality. Using a 95% positivity criterion, this model identified 24% of high-risk patients who died, without misclassification of any survivors. Of those who survived to hospital discharge, 33% were dialysis dependent and 28% were institutionalized long-term. Among critically ill patients, acute renal failure requiring dialysis is an ominous condition with a high risk of in-hospital mortality. This risk appears to depend largely on comorbid conditions, such as the need for mechanical ventilation and underlying malignancy. While this prognostic model requires prospective validation, it appears to identify a substantial fraction of patients for whom dialysis may be of limited or no benefit.
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            Organ crosstalk: the role of the kidney.

            Acute kidney injury (AKI) continues to contribute significantly to morbidity and mortality in the ICU setting, especially when associated with distant organ dysfunction. There is increasing evidence that AKI directly contributes to organ dysfunction in lung, brain, liver, heart and other organs. This review will examine our current understanding of the deleterious organ crosstalk in the critically ill, which can provide a framework for developing novel therapeutics. The majority of studies correlating AKI with distant organ dysfunction have demonstrated the pathophysiological importance of proinflammatory and proapoptotic pathways as well as oxidative stress and reactive oxygen species (ROS) production. Leukocyte activation and infiltration, changes in levels of soluble factors such as cytokines and chemokines, and regulation of cell death in extra-renal organs are potentially important mechanisms by which AKI modulates multiorgan dysfunction. There is increasing knowledge of AKI and deleterious interorgan crosstalk that arises, at least in part, due to the imbalance of immune, inflammatory, and soluble mediator metabolism that attends severe insults to the kidney. Further studies can build on these new mechanistic observations to develop strategies to improve outcomes in the critically ill patient.
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              Importance of dietary gamma-linolenic acid in human health and nutrition.

              Considerable debate remains regarding the distinct biological activities of individual polyunsaturated fatty acids (PUFA). One of the most interesting yet controversial dietary approaches has been the possible prophylactic role of dietary gamma-linolenic acid (GLA) in treating various chronic disease states. This strategy is based on the ability of diet to modify cellular lipid composition and eicosanoid (cyclooxygenase and lipoxygenase) biosynthesis. Recent studies demonstrate that dietary GLA increases the content of its elongase product, dihomo-gamma-linolenic acid (DGLA), within cell membranes without concomitant changes in arachidonic acid (AA). Subsequently, upon stimulation, DGLA can be converted by inflammatory cells to 15-(S)-hydroxy-8,11,13-eicosatrienoic acid and prostaglandin E1. This is noteworthy because these compounds possess both anti-inflammatory and antiproliferative properties. Although an optimal feeding regimen to maximize the potential benefits of dietary GLA has not yet been determined, it is the purpose of this review to summarize the most recent research that has focused on objectively and reproducibly determining the mechanism(s) by which GLA may ameliorate health problems.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2016
                19 August 2016
                : 10
                : 2651-2658
                Affiliations
                [1 ]Department of Cardiovascular Surgery
                [2 ]Department of Pathology, Gazi University Medical Faculty
                [3 ]Department of Pharmacology, Yıldırım Beyazıt University Medical Faculty
                [4 ]Department of Oral and Maxillofacial Surgery, Ankara University Faculty of Dentistry, Besevler, Ankara
                [5 ]Department of Physiology, Kırıkkale University Medical Faculty, Kırıkkale
                [6 ]Department of Anesthesiology and Reanimation, Gazi University Medical Faculty, Ankara
                [7 ]Department of Physiology, Dumlupınar University Medical Faculty, Kütahya, Turkey
                Author notes
                Correspondence: Mustafa Arslan, Department of Anesthesiology and Reanimation, Gazi University Medical Faculty, Besevler, 06510, Ankara, Turkey, Tel +90 312 202 67 39, Email mustarslan@ 123456gmail.com
                [*]

                These authors contributed equally to this work

                Article
                dddt-10-2651
                10.2147/DDDT.S110529
                5003013
                27601882
                4ba048c0-19da-4e77-aa59-aa912123df22
                © 2016 Erer et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                alprostadil,iloprost,ischemia reperfusion injury,rat,renal,lung,skeletal muscle

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