Rosiglitazone, Myocardial Ischemic Risk, and Recent Regulatory Actions

Bourg, Catherine A.; Phillips, Beth Bryles

doi:10.1345/aph.1q400

Cited by 26 publications

(21 citation statements)

References 25 publications

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“…The mechanism through which rosiglitazone causes cardiovascular events is unclear, but is thought to be related to unfavorable effects on triglycerides, low-density lipoprotein cholesterol (LDL-C) particle size and density, and greater affinity for PPAR-gamma than other TZD drugs [109– 112]. To evaluate the extent to which these hypotheses were consistent with information utilized by the PSI-double + triple model, we reconstructed the pathways of predicates and concepts that were consistent with the inferred discovery patterns used to make this prediction.…”

Section: Resultsmentioning

confidence: 99%

Identifying plausible adverse drug reactions using knowledge extracted from the literature

Shang

Rindflesch

et al. 2014

Journal of Biomedical Informatics

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Pharmacovigilance involves continually monitoring drug safety after drugs are put to market. To aid this process; algorithms for the identification of strongly correlated drug/adverse drug reaction (ADR) pairs from data sources such as adverse event reporting systems or Electronic Health Records have been developed. These methods are generally statistical in nature, and do not draw upon the large volumes of knowledge embedded in the biomedical literature. In this paper, we investigate the ability of scalable Literature Based Discovery (LBD) methods to identify side effects of pharmaceutical agents. The advantage of LBD methods is that they can provide evidence from the literature to support the plausibility of a drug/ ADR association, thereby assisting human review to validate the signal, which is an essential component of pharmacovigilance. To do so, we draw upon vast repositories of knowledge that has been extracted from the biomedical literature by two Natural Language Processing tools, MetaMap and SemRep. We evaluate two LBD methods that scale comfortably to the volume of knowledge available in these repositories. Specifically, we evaluate Reflective Random Indexing (RRI), a model based on concept-level co-occurrence, and Predication-based Semantic Indexing (PSI), a model that encodes the nature of the relationship between concepts to support reasoning analogically about drug-effect relationships. An evaluation set was constructed from the Side Effect Resource 2 (SIDER2), which contains known drug/ADR relations, and models were evaluated for their ability to “rediscover” these relations. In this paper, we demonstrate that both RRI and PSI can recover known drug-adverse event associations. However, PSI performed better overall, and has the additional advantage of being able to recover the literature underlying the reasoning pathways it used to make its predictions.

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Section: Resultsmentioning

confidence: 99%

Identifying plausible adverse drug reactions using knowledge extracted from the literature

Shang

Rindflesch

et al. 2014

Journal of Biomedical Informatics

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“…Yet the use of this drug in a perinatal context is not without problems. Rosiglitazone as an oral antidiabetic in humans has been withdrawn by the European medicines agency in 2010 due to evidence of an increased risk of cardiovascular disorders after chronic use [21,22]. Another concern is that the drug has never been approved for use in pregnant women, although animal studies [23] and several case reports in humans [24,25] have not been able to demonstrate any teratogenic effect.…”

Section: Discussionmentioning

confidence: 99%

Transplacental Administration of Rosiglitazone Attenuates Hyperoxic Lung Injury in a Preterm Rabbit Model

Richter

Toelen²,

Nagatomo³

et al. 2015

Fetal Diagn Ther

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Introduction: Continuous improvements in perinatal care have allowed the survival of increasingly more prematurely born infants. The establishment of respiration in an extremely immature yet still developing lung results in chronic lung injury with significant mortality and morbidity. We experimentally evaluated a novel medical strategy to prevent hyperoxia-induced lung injury by prenatal rosiglitazone. Materials and Methods: Pregnant rabbits were injected with saline or rosiglitazone (3 mg/kg) 48 and 24 h prior to preterm delivery at 28 days of gestation (term = 31 days). The pups were held in normoxia (21% O₂) or hyperoxia (>95% O₂), and assessment was done at three different time points (1 h, 24 h and 7 days). Results: The administration of rosiglitazone resulted in a significant decrease in tissue damping (resistance) on day 7. Furthermore, significantly increased expression of vascular endothelial growth factor, fetal liver kinase 1 and surfactant protein B immediately after delivery was noted by immunohistochemistery. On day 7, there was a more mature lung parenchymal architecture in rosiglitazone-exposed pups. Discussion: In a preterm rabbit model, prenatal maternal administration of rosiglitazone attenuates neonatal hyperoxic lung injury and results in a more mature pulmonary parenchyma.

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“…Pretreatmentprotective interventions have already been successful in other clinical situations, such as coronary artery bypass grafting and acute myocardial infarction (AMI) (9,35,44,60). Clinically, rosiglitazone treatment has been associated with exacerbation of heart failure and an enhanced incidence of myocardial infarction in non-CKD populations (10,32,42). However, as discussed above, pioglitazone also has experimental data to support a role in activation of the RISK pathway.…”

Section: Rosiglitazone Therapy Resensitized the Uremic Heart To Cardimentioning

confidence: 99%

Uremic cardiomyopathy is characterized by loss of the cardioprotective effects of insulin

Semple

Bhandari

Seymour

2012

American Journal of Physiology-Renal Physiology

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Chronic kidney disease is associated with a unique cardiomyopathy, characterized by a combination of structural and cellular remodeling, and an enhanced susceptibility to ischemia-reperfusion injury. This may represent dysfunction of the reperfusion injury salvage kinase pathway due to insulin resistance. The susceptibility of the uremic heart to ischemia-reperfusion injury and the cardioprotective effects of insulin and rosiglitazone were investigated. Uremia was induced in Sprague-Dawley rats by subtotal nephrectomy. Functional recovery from ischemia was investigated in vitro in control and uremic hearts ± insulin ± rosiglitazone. The response of myocardial oxidative metabolism to insulin was determined by (13)C-NMR spectroscopy. Activation of reperfusion injury salvage kinase pathway intermediates (Akt and GSK3β) were assessed by SDS-PAGE and immunoprecipitation. Insulin improved postischemic rate pressure product in control but not uremic hearts, [recovered rate pressure product (%), control 59.6 ± 10.7 vs. 88.9 ± 8.5, P < 0.05; uremic 19.3 ± 4.6 vs. 28.5 ± 10.4, P = ns]. Rosiglitazone resensitized uremic hearts to insulin-mediated cardioprotection [recovered rate pressure product (%) 12.7 ± 7.0 vs. 61.8 ± 15.9, P < 0.05]. Myocardial carbohydrate metabolism remained responsive to insulin in uremic hearts. Uremia was associated with increased phosphorylation of Akt (1.00 ± 0.08 vs. 1.31 ± 0.11, P < 0.05) in normoxia, but no change in postischemic phosphorylation of Akt or GSK3β. Akt2 isoform expression was decreased postischemia in uremic hearts (P < 0.05). Uremia is associated with enhanced susceptibility to ischemia-reperfusion injury and a loss of insulin-mediated cardioprotection, which can be restored by administration of rosiglitazone. Altered Akt2 expression in uremic hearts post-ischemia-reperfusion and impaired activation of the reperfusion injury salvage kinase pathway may underlie these findings.

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Rosiglitazone, Myocardial Ischemic Risk, and Recent Regulatory Actions

Cited by 26 publications

References 25 publications

Identifying plausible adverse drug reactions using knowledge extracted from the literature

Identifying plausible adverse drug reactions using knowledge extracted from the literature

Transplacental Administration of Rosiglitazone Attenuates Hyperoxic Lung Injury in a Preterm Rabbit Model

Uremic cardiomyopathy is characterized by loss of the cardioprotective effects of insulin

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