Plant and Soil 40, 445-451 (1974) Ms. 2294 SHORT COMMUNICATIONEvaluation of a rapid test for the hidden hunger of zinc in plants SummaryFresh leaf discs/pieces of wheat, gram, maize and mustard were incubated in a substrate consisting of 4 ml 0.2M phosphate buffer (pH 6.8), 4 ml 0.2M NaFICO3 and 0.2 ml 0.002% bromthymol blue at 0 to 4°C for 120-240 seconds. The conversion of light blue colour due to the activity of zinc dependent carbonic anhydrase into yellowish green and greenish yellow was used as an index for zinc deficiency and sufficiency, respectively, in the plant tissues. A correlation coefficient value of r = > + 0.9 between the different parameters of rapid tissue test and standard enzyme extraction method, indicated the feasibility of using the present method.

Epigenetics refers to a heritable change in the pattern of gene expression that is mediated by a mechanism specifically not due to alterations in the primary nucleotide sequence. Well known epigenetic mechanisms encompass DNA methylation, chromatin remodeling (histone modifications) and RNA interference. Functionally, epigenetics provides an extra layer of transcriptional control and plays a crucial role in normal physiological development, as well as in pathological conditions. Aberrant DNA methylation is implicated in immune dysfunction, inflammation and insulin resistance. Epigenetic changes may be responsible for “metabolic memory” and development of micro- and macrovascular complications of diabetes. MicroRNAs are critical in the maintenance of glomerular homeostasis and hence RNA interference may be important in the progression of renal disease. Recent studies have shown that epigenetic modifications orchestrate the epithelial-mesenchymal transition and eventually fibrosis of the renal tissue. Oxidative stress, inflammation, hyperhomocysteinemia and uremic toxins could induce epimutations in chronic kidney disease. Epigenetic alterations are associated with inflammation and cardiovascular disease in patients with chronic kidney disease. Reversible nature of the epigenetic changes gives an unique opportunity to halt or even reverse the disease process through targeted therapeutic strategies.

Objective Lipopolysaccharide or endotoxin constitutes most part of the outer portion of the cell wall in the gram negative bacteria. Sub-clinical endotoxemia could contribute to increased inflammation and mortality in hemodialysis patients. Endotoxin level and clinical effect are determined by its soluble receptor sCD14 and high density lipoprotein. We examine the hypothesis that endotoxin level correlates with mortality. Methods In this cohort study, endotoxin levels were measured in 306 long-term hemodialysis patients who were then followed for up to 42 months. Soluble CD14 and cytokines levels were also measured. Results The mean (±SD) endotoxin level was 2.31±3.10 EU/ml (min: 0.26 EU/ml, max: 22.94 EU/ml, inter-quartile range: 1.33EU/ml, median: 1.27EU/ml). Endotoxin correlated with C-reactive protein (r = 0.11, p<0.04). On multivariate logistic regression analysis, high body mass index (BMI) and low HDL cholesterol levels were associated with higher endotoxinemia (endotoxin below or above of median). In multivariable Cox regression analysis adjusted for case-mix and nutritional/inflammatory confounders, endotoxin levels in the 3rd quartile vs. 1st quartile was associated with a trend towards increased hazard ratio (HR) for death (HR 1.83, 95% confidence interval: 0.93–3.6, p=0.08). Conclusions In this hemodialysis cohort, we found associations between endotoxinemia and CRP, body composition and HDL. A moderately high endotoxin levels tended to correlate with increased mortality than the highest circulating endotoxin level. Additional studies are required to asses the effect of endotoxemia on mortality in dialysis population.

Nuclear receptor coactivator PRIP (peroxisome proliferator-activated receptor (PPAR␥)-interacting protein) and PRIP-interacting protein with methyltransferase activity, designated PIMT, appear to serve as linkers between cAMP response element-binding protein-binding protein (CBP)/p300-anchored and PBP (PPAR␥-binding protein)-anchored coactivator complexes involved in the transcriptional activity of nuclear receptors. To assess the biological significance of PRIP, we disrupted the PRIP gene in mice by homologous recombination. Mice nullizygous for PRIP died between embryonic day 11.5 and 12.5 (postcoitum) due in most part to defects in the development of placenta, heart, liver, nervous system, and retardation of embryonic growth. Transient transfection assays using fibroblasts isolated from PRIP ؊/؊ embryos revealed a significant decrease in the capacity for ligand-dependent transcriptional activation of retinoid X receptor ␣ and to a lesser effect on PPAR␥ transcriptional activity. These observations indicate that PRIP like PBP, CBP, and p300 is an essential and nonredundant coactivator.Our understanding of the mechanisms underlying transcriptional activation by nuclear receptors has been advanced by the identification of nuclear receptor coactivators or coregulators that appear to influence embryonic development, cell proliferation, and differentiation (1). These include p160/SRC-1 1 (steroid receptor coactivator-1) family with three members (SRC-1, TIF/GRIP1/SRC-2, and pCIP/AIB1/ACTR/RAC3/TRAM1/SRC3) (2-6), CREB-binding protein (CBP) (7), adenovirus E1A-binding protein p300 (8), peroxisome proliferator-activated receptor-␥ (PPAR␥)-binding protein (PBP) (9), PPAR-interacting protein (PRIP/ASC-2/RAP250/TRBP/NRC) (10 -14) and PPAR␥ coactivator-1 (PGC-1) (15), among others. Nuclear receptor coactivators contain one or more conserved LXXLL (where L is leucine and X any amino acid) signature motif, which has been found to be necessary and sufficient for ligand-dependent interactions with the activation function-2 domain present in the C-terminal hormone-binding region of the nuclear receptors (1, 6). It is generally held that coactivators play a central role in mediating nuclear receptor transcriptional activity by functioning as at least two large multiprotein complexes formed either sequentially or combinatorially (1). The first complex anchored by CBP/p300 and containing p/160 cofactors/SRC-1 cofactors exhibits histone acetyltransferase activity necessary for remodeling chromatin (1,4,7,16), while the second multiprotein complex, variously referred to as TRAP/DRIP/ARC mediator complex, which is anchored by PBP (17-19), facilitates interaction with RNA polymerase II complexes of the basal transcription machinery (1). Deletion of CBP/p300 and PBP genes in the mouse results in embryonic lethality around E11.5 days, indicating that disruption of these pivotal anchoring coactivators affects the integrity of the cofactor complexes, thus altering the function of many nuclear receptors and most likely of other transcript...

Cardiovascular disease (CVD) remains a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Numerous CVD risk factors in CKD patients have been described, but these do not fully explain the high pervasiveness of CVD or increased mortality rates in CKD patients. In CKD the loss of urinary excretory function results in the retention of various substances referred to as “uremic retention solutes”. Many of these molecules have been found to exert toxicity on virtually all organ systems of the human body, leading to the clinical syndrome of uremia. In recent years, an increasing body of evidence has been accumulated that suggests that uremic toxins may contribute to an increased cardiovascular disease (CVD) burden associated with CKD. This review examined the evidence from several clinical and experimental studies showing an association between uremic toxins and CVD. Special emphasis is addressed on emerging data linking gut microbiota with the production of uremic toxins and the development of CKD and CVD. The biological toxicity of some uremic toxins on the myocardium and the vasculature and their possible contribution to cardiovascular injury in uremia are also discussed. Finally, various therapeutic interventions that have been applied to effectively reduce uremic toxins in patients with CKD, including dietary modifications, use of prebiotics and/or probiotics, an oral intestinal sorbent that adsorbs uremic toxins and precursors, and innovative dialysis therapies targeting the protein-bound uremic toxins are also highlighted. Future studies are needed to determine whether these novel therapies to reduce or remove uremic toxins will reduce CVD and related cardiovascular events in the long-term in patients with chronic renal failure.