The relation of C - reactive protein to chronic kidney disease in African Americans: the Jackson Heart Study

<p>Abstract</p> <p>Background</p> <p>African Americans have an increased incidence and worse prognosis with chronic kidney disease (CKD - estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m²) than their counterparts of European-descent. Inflammation has been related to renal disease in non-Hispanic whites, but there are limited data on the role of inflammation in renal dysfunction in African Americans in the community.</p> <p>Methods</p> <p>We examined the cross-sectional relation of log transformed C-reactive protein (CRP) to renal function (eGFR by Modification of Diet and Renal Disease equation) in African American participants of the community-based Jackson Heart Study's first examination (2000 to 2004). We conducted multivariable linear regression relating CRP to eGFR adjusting for age, sex, body mass index, systolic and diastolic blood pressure, diabetes, total/HDL cholesterol, triglycerides, smoking, antihypertensive therapy, lipid lowering therapy, hormone replacement therapy, and prevalent cardiovascular disease events. In a secondary analysis we assessed the association of CRP with albuminuria (defined as albumin-to-creatinine ratio > 30 mg/g).</p> <p>Results</p> <p>Participants (n = 4320, 63.2% women) had a mean age ± SD of 54.0 ± 12.8 years. The prevalence of CKD was 5.2% (n = 228 cases). In multivariable regression, CRP concentrations were higher in those with CKD compared to those without CKD (mean CRP 3.2 ± 1.1 mg/L vs. 2.4 ± 1.0 mg/L, respectively p < 0.0001). CRP was significantly associated with albuminuria in sex and age adjusted model however not in the multivariable adjusted model (p > 0.05).</p> <p>Conclusion</p> <p>CRP was associated with CKD however not albuminuria in multivariable-adjusted analyses. The study of inflammation in the progression of renal disease in African Americans merits further investigation.</p

Smoking patterns and chronic kidney disease in US Hispanics: Hispanic Community Health Study/Study of Latinos

Intermittent smoking is prevalent among Hispanics, but little is known about whether this smoking pattern associates with increased chronic kidney disease (CKD) risk in this population. The objective of the present study is to identify patterns of exposure associated with CKD in US Hispanics

Specific Thiazolidinediones Inhibit Ovarian Cancer Cell Line Proliferation and Cause Cell Cycle Arrest in a PPARγ Independent Manner

Peroxisome Proliferator Activated Receptor gamma (PPARγ) agonists, such as the thiazolinediones (TZDs), have been studied for their potential use as cancer therapeutic agents. We investigated the effect of four TZDs--Rosiglitazone (Rosi), Ciglitazone (CGZ), Troglitazone (TGZ), and Pioglitazone (Pio)--on ovarian cancer cell proliferation, PPARγ expression and PPAR luciferase reporter activity. We explored whether TZDs act in a PPARγ dependent or independent manner by utilizing molecular approaches to inhibit or overexpress PPARγ activity.Treatment with CGZ or TGZ for 24 hours decreased proliferation in three ovarian cancer cell lines, Ovcar3, CaOv3, and Skov3, whereas Rosi and Pio had no effect. This decrease in Ovcar3 cell proliferation was due to a higher fraction of cells in the G(0)/G(1) stage of the cell cycle. CGZ and TGZ treatment increased apoptosis after 4 hours of treatment but not after 8 or 12 hours. Treatment with TGZ or CGZ increased PPARγ mRNA expression in Ovcar3 cells; however, protein levels were unchanged. Surprisingly, luciferase promoter assays revealed that none of the TZDs increased PPARγ activity. Overexpression of wild type PPARγ increased reporter activity. This was further augmented by TGZ, Rosi, and Pio indicating that these cells have the endogenous capacity to mediate PPARγ transactivation. To determine whether PPARγ mediates the TZD-induced decrease in proliferation, cells were treated with CGZ or TGZ in the absence or presence of a dominant negative (DN) or wild type overexpression PPARγ construct. Neither vector changed the TZD-mediated cell proliferation suggesting this effect of TZDs on ovarian cancer cells may be PPARγ independent.CGZ and TGZ cause a decrease in ovarian cancer cell proliferation that is PPARγ independent. This concept is supported by the finding that a DN or overexpression of the wild type PPARγ did not affect the changes in cell proliferation and cell cycle

Genetic Association for Renal Traits among Participants of African Ancestry Reveals New Loci for Renal Function

Chronic kidney disease (CKD) is an increasing global public health concern, particularly among populations of African ancestry. We performed an interrogation of known renal loci, genome-wide association (GWA), and IBC candidate-gene SNP association analyses in African Americans from the CARe Renal Consortium. In up to 8,110 participants, we performed meta-analyses of GWA and IBC array data for estimated glomerular filtration rate (eGFR), CKD (eGFR <60 mL/min/1.73 m2), urinary albumin-to-creatinine ratio (UACR), and microalbuminuria (UACR >30 mg/g) and interrogated the 250 kb flanking region around 24 SNPs previously identified in European Ancestry renal GWAS analyses. Findings were replicated in up to 4,358 African Americans. To assess function, individually identified genes were knocked down in zebrafish embryos by morpholino antisense oligonucleotides. Expression of kidney-specific genes was assessed by in situ hybridization, and glomerular filtration was evaluated by dextran clearance. Overall, 23 of 24 previously identified SNPs had direction-consistent associations with eGFR in African Americans, 2 of which achieved nominal significance (UMOD, PIP5K1B). Interrogation of the flanking regions uncovered 24 new index SNPs in African Americans, 12 of which were replicated (UMOD, ANXA9, GCKR, TFDP2, DAB2, VEGFA, ATXN2, GATM, SLC22A2, TMEM60, SLC6A13, and BCAS3). In addition, we identified 3 suggestive loci at DOK6 (p-value = 5.3×10−7) and FNDC1 (p-value = 3.0×10−7) for UACR, and KCNQ1 with eGFR (p = 3.6×10−6). Morpholino knockdown of kcnq1 in the zebrafish resulted in abnormal kidney development and filtration capacity. We identified several SNPs in association with eGFR in African Ancestry individuals, as well as 3 suggestive loci for UACR and eGFR. Functional genetic studies support a role for kcnq1 in glomerular development in zebrafish

Quantitative modeling of the physiology of ascites in portal hypertension

Although the factors involved in cirrhotic ascites have been studied for a century, a number of observations are not understood, including the action of diuretics in the treatment of ascites and the ability of the plasma-ascitic albumin gradient to diagnose portal hypertension. This communication presents an explanation of ascites based solely on pathophysiological alterations within the peritoneal cavity. A quantitative model is described based on experimental vascular and intraperitoneal pressures, lymph flow, and peritoneal space compliance. The model's predictions accurately mimic clinical observations in ascites, including the magnitude and time course of changes observed following paracentesis or diuretic therapy

Intraperitoneal therapy for peritoneal tumors: biophysics and clinical evidence

In patients with tumors confined to the peritoneal cavity, there is established pharmacokinetic and tumor biology-related evidence that intraperitoneal drug administration is advantageous. Three large randomized trials in patients with stage III ovarian cancer who underwent optimal cytoreduction have demonstrated a significant survival benefit when intraperitoneal chemotherapy was added to systemic therapy. Although intraperitoneal therapy is associated with locoregional toxic effects, recent trials suggest that with some modification of the local delivery methods this approach is safe in 80% of patients in an ambulatory setting. Surgical cytoreduction immediately followed by intraoperative hyperthermic intraperitoneal chemoperfusion (HIPEC) ensures intraperitoneal delivery of the drug to all peritoneal surfaces and the advantages of combined hyperthermia to be exploited. An increasing number of centers are initiating this multimodality therapy in ovarian cancer and colorectal cancer. Clearly, intraperitoneal drug delivery is an important adjunct to surgery and systemic chemotherapy in selected patients. The optimal drug, dose and schedule for intraperitoneal delivery, the exact role of added HIPEC compared with cytoreduction alone, and the potential role of HIPEC in ovarian cancer and peritoneal mesothelioma are still undefined. Several randomized controlled trials addressing these uncertainties have been initiated

Cultural and Chemical Practices for Quality Improvement of Overseeded Bermudagrass [Cynodon dactlyon (L.) Pers. × C. transvaalensis Burtt-Davy] and Annual Bluegrass (Poa annua L.) Suppression

Dormant bermudagrass (Cynodon dactlyon (L.) Pers. × C. transvaalensis Burtt-Davy) is overseeded with perennial ryegrass (Lolium perenne L.) to maintain green color through the fall and winter. Annual bluegrass (Poa annua L.) control is critical for overseeding success, as this weed can greatly decrease aesthetic quality and playability of turfgrass due to excessive seedhead production. Research was conducted to evaluate the infl uence of pre-seeding cultural practices (scalping, solid-tine aerifi cation, vertical mowing, and vertical mowing plus scalping) on overseeding establishment. The effect of increasing overseeding rates of perennial ryegrass (111, 222, 444, and 888 kg pure live seed·ha–1; 100, 200, 400, and 800 lb·A–1) and roughstalk bluegrass (Poa trivialis L.) (55, 111, and 222 kg pure live seed·ha–1; 50, 100, and 200 lb·A–1) on annual bluegrass populations was also investigated. Additionally, plant growth regulators (PGRs) were evaluated for annual bluegrass seedhead suppression and turf injury. Mefl uidide at 0.056 kg ae·ha–1 (0.05 lb ae·A–1), and paclobutrazol, fl urprimidol, trinexapac-ethyl, and trinexapac-ethyl plus ethephon at 0.28, 0.42, 0.382, and 0.095 plus 3.82 kg ai·ha–1 (0.25, 0.37, 0.34, 0.085 plus 3.4 lb ai·A–1), respectively, were applied twice, sequentially with a four-week interval. Contrary to previous research, pre-seeding cultural practices did not improve overseeding success. Annual bluegrass density decreased with increasing perennial ryegrass overseeding rates from 50% in the non-overseeded to 14 to 17% when overseeded with rates up to 222 kg pure live seed·ha–1, and 4 to 8% when overseeded with rates between 444 and 888 kg pure live seed·ha–1. Roughstalk bluegrass overseeded reduced annual bluegrass density from 50% in the non-overseeded, to 7 to 13% when overseeded with 55, 111, or 222 kg pure live seed·ha–1, regardless of the overseeding rate. Overseeding bermudagrass with roughstalk bluegrass or perennial ryegrass increased turfgrass green cover during winter, especially 100 days after seeding. Paclobutrazol, flurprimidol, and trinexapac-ethyl were successful at suppressing annual bluegrass seedheads and were not injurious to perennial ryegrass. Mefluidide resulted in efficient annual bluegrass seedhead suppression; however, unacceptable turfgrass injury occurred in 2012