Chronic Inflammation in Chronic Kidney Disease Progression: Role of Nrf2

Despite recent advances in the management of chronic kidney disease (CKD), morbidity and mortality rates in these patients remain high. Although pressure-mediated injury is a well-recognized mechanism of disease progression in CKD, emerging data indicate that an intermediate phenotype involving chronic inflammation, oxidative stress, hypoxia, senescence, and mitochondrial dysfunction plays a key role in the etiology, progression, and pathophysiology of CKD. A variety of factors promote chronic inflammation in CKD, including oxidative stress and the adoption of a proinflammatory phenotype by resident kidney cells. Regulation of proinflammatory and anti-inflammatory factors through NF-κB– and nuclear factor, erythroid 2 like 2 (Nrf2)–mediated gene transcription, respectively, plays a critical role in the glomerular and tubular cell response to kidney injury. Chronic inflammation contributes to the decline in glomerular filtration rate (GFR) in CKD. Whereas the role of chronic inflammation in diabetic kidney disease (DKD) has been well-elucidated, there is now substantial evidence indicating unresolved inflammatory processes lead to fibrosis and eventual end-stage kidney disease (ESKD) in several other diseases, such as Alport syndrome, autosomal-dominant polycystic kidney disease (ADPKD), IgA nephropathy (IgAN), and focal segmental glomerulosclerosis (FSGS). In this review, we aim to clarify the mechanisms of chronic inflammation in the pathophysiology and disease progression across the spectrum of kidney diseases, with a focus on Nrf2

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Not AvailableWide variability in oil content was observed in 75 germplasm accessions of Pongamia pinnata (L.) Pierre collected from Telengana region of Andhra Pradesh, India. Out of these, fatty acid profiles of 21 accessions with varying seed oil content were examined. Large variation was observed in stearic, oleic and linoleic fatty acid composition i.e. 1.83-11.50%, 46.66-65.35% and 12.02-32.58% respectively while less variation i.e. 9.25-12.87% was found with palmitic acid content. Saponification number (SN), iodine value (IV) and cetane number (CN) of fatty acid methyl esters of oils varied from 183.3 to 200.91, 74.78 to 100.98 and 50.85 to 59.11 respectively. Fatty acid composition, IV and CN were used to predict the quality of fatty acid methyl esters of oil for use as biodiesel. Fatty acid methyl esters of oils of P. pinnata accessions DORPP 49, 72 and 83 were found most suitable (CN more than 56.6) for use as biodiesel and they meet the major specification of biodiesel standards of USA, Germany and European Standard Organization. The range of variability found for various biodiesel standards in accessions of P. pinnata can be utilized for the establishment of plantations of promising genotypes through clonal means for increased productivity.Not Availabl

Giant Cell Myocarditis: Not Always a Presentation of Cardiogenic Shock

Giant cell myocarditis is a rare and often fatal disease. The most obvious presentation often described in the literature is one of rapid hemodynamic deterioration due to cardiogenic shock necessitating urgent consideration of mechanical circulatory support and heart transplantation. We present the case of a 60-year-old man whose initial presentation was consistent with myopericarditis but who went on to develop a rapid decline in left ventricular systolic function without overt hemodynamic compromise or dramatic symptomatology. Giant cell myocarditis was confirmed via endomyocardial biopsy. Combined immunosuppression with corticosteroids and calcineurin inhibitor resulted in resolution of symptoms and sustained recovery of left ventricular function one year later. Our case highlights that giant cell myocarditis does not always present with cardiogenic shock and should be considered in the evaluation of new onset cardiomyopathy of uncertain etiology as a timely diagnosis has distinct clinical implications on management and prognosis

Relation of Variability of Low-Density Lipoprotein Cholesterol and Blood Pressure to Events in Patients With Previous Myocardial Infarction from the IDEAL Trial

In patients with previous myocardial infarction (MI), aggressive hypertension control and low-density lipoprotein cholesterol (LDL-C) reduction are important secondary prevention measures. However, residual risk remains despite aggressive treatment. Whether variability in blood pressure (BP) and LDL-C can explain this residual risk is not known. Patients enrolled in the Incremental Decrease in End Points Through Aggressive Lipid-Lowering trial with at least 1 post-baseline measurement of LDL-C and blood pressure (BP) were included. Visit-to-visit LDL-C and BP variabilities were evaluated using various measures of variability. Primary outcome was any coronary event with the secondary outcomes of any cardiovascular event (CV), MI, stroke, death, and CV death. Among the 8,658 patients included, each 1-SD (10.8 mg/dl) increase in LDL-C variability increased the risk of any coronary event (adjusted HR [HRadj] 1.07; 95% CI 1.04 to 1.11; p <0.0001), any CV event, MI, and death (HRadj 1.19; 95% CI 1.14 to 1.25; p <0.0001). Similarly, each 1-SD (7.2 mm Hg) increase in systolic BP variability increased the risk of any coronary event (HRadj 1.15; 95% CI 1.10 to 1.20; p <0.0001), any CV event, MI, stroke, death (HRadj 1.28; 95% CI 1.18 to 1.38; p <0.0001), and CV death. Compared with the group with low variability for both LDL-C and systolic BP, the group with high variability for both had a significant increase in any coronary event (HRadj 1.48; 95% CI 1.30 to 1.70), any CV event (HRadj 1.43; 95% CI 1.27 to 1.61), and MI (HRadj 1.87; 95% CI 1.46 to 2.41). In conclusions, in patients with a history of MI, variabilities in LDL-C and BP are powerful and independent predictors of CV events including deat

Histology of the ankle joint of the animals.

<p>10× and 40× magnification of paraffin-embedded ankle sections stained with H&E, for the acute phase (day 5) and the chronic phase (day 21). The 40× magnification on day 5 shows leukocyte infiltration in the PG-PS-induced arthritis animals. Slides from the chronic phase in the PG-PS-induced arthritis animals showed fibrosis, pannus formation and severe leukocyte infiltration with more pronounced effects observed in the clopidogrel-treated animals.</p

Platelet aggregation studies using 2MeSADP in PG-PS-induced arthritis model.

<p>Effect of 100 nM of 2MeSADP on platelet aggregation in isolated platelets from untreated animals, clopidogrel-treated animals, PG-PS-induced arthritis animals and PG-PS-induced arthritis+clopidogrel-treated animals. Traces are representative of three independent experiments.</p

Complete chemistry profile of experimental animals.

<p>Serum chemistry of rats following clopidogrel treatment in PG-PS-induced arthritis model (day 21). Values are mean ± SD, (n = 6). There are no statistical differences among groups.</p