Search

The epithelial sodium channel (ENaC) plays an essential role in transepithelial sodium reabsorption in the renal connecting tubule and collecting duct. Therefore, controlling ENaC activity is an important regulatory event in electrolyte and extracellular volume homeostasis, and thus in the control of blood pressure. Many independent signaling pathways converge on ENaC, although the most important for its physiological role is the enhancement of channel activity by the steroid hormone aldosterone. In this review, we briefly summarize current knowledge about ENaC regulation and the different chemical compounds available to directly or indirectly modify channel function. In addition, current and possible clinical uses of ENaC and aldosterone antagonists are highlighted.

Extensive communication is believed to occur between eukaryotes and prokaryotes via signaling molecules; this field of research is now called interkingdom signaling. Recently, it has been discovered that many different plant-associated bacteria possess a protein closely related to the quorum-sensing (QS) LuxR-family protein that binds and responds to plant compounds. This LuxR protein does not have a cognate N-acyl homoserine lactone (AHL) signal synthase and therefore is regarded as a 'solo' or 'orphan'. The protein is involved in interkingdom signaling in rhizobia, xanthomonads, and pseudomonads, regulating processes important for plant-bacteria interaction. In this review, we focus on this new interkingdom signaling circuit, which is widespread among pathogenic and beneficial plant-associated bacteria., (Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.)

The biosorption of As(III) on iron-coated fungal biomass of Paecilomyces sp. was studied in this work. It was found that the biomass was very efficient removing the metal in solution, using Atomic Absorption, reaching the next percentage of removals: 64.5%. The highest adsorption was obtained at pH 6.0, at 30°C after 24 hours of incubation, with 1 mg/L of modified fungal biomass.

A chromium-resistant fungus isolated from contaminated air with industrial vapors can be used for reducing toxic Cr(VI) to Cr(III). This study analyzes in vitro reduction of hexavalent chromium using cell free extract(s) of the fungus that was characterized based on optimal temperature, pH, use of electron donors, metal ions and initial Cr(VI) concentration in the reaction mixture. This showed the highest activity at 37°C and pH 7.0; there is an increase in Cr(VI) reductase activity with addition of NADH as an electron donor, and it was highly inhibited by Hg(2+), Ca(2+) and Mg(2+), and azide, EDTA, and KCN.

2,5-Piperazinediones (2,5-diketopiperazines, DKPs) can be viewed as privileged building blocks for the synthesis of heterocyclic systems. This tutorial review aims at underscoring the large number and structural variety of nitrogen heterocycles that are available by suitable manipulation of DKP starting materials, including many bioactive compounds and natural products.

Xanthomonas oryzae pv. oryzae (Xoo) is the second most important rice pathogen, causing a disease called bacterial leaf blight. Xoo colonizes and infects the vascular tissue resulting in tissue necrosis and wilting causing significant yield losses worldwide. In this study Xoo infected vascular fluid (xylem sap) was recovered and analyzed for secreted Xoo proteins. Three independent experiments resulted in the identification of 324 different proteins, 64 proteins were found in all three samples which included many of the known virulence-associated factors. In addition, 10 genes encoding for the identified proteins were inactivated and one mutant displayed statistically a significant loss in virulence when compared to the wild type Xoo, suggesting that a new virulence-associated factor has been revealed. The usefulness of this approach in understanding the lifestyle and unraveling the virulence-associated factors of phytopathogenic vascular bacteria is discussed., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Predialysis hemoglobin (Hb) may overestimate the true erithropoiesis-stimulating agents (ESA) requirements. We tested whether predialysis Hb is a reliable predictor of the postdialysis level to better control ESA dosage, and evaluated the relation between ESA, Hb and cardiovascular events (CVE)., Methods: Cohort study including 67 stable hemodialysis patients. Pre- and post-dialysis Hb concentrations were measured, and ESA doses were calculated. A model to predict post-dialysis Hb is proposed. During 18 months follow-up, CVE, hospitalizations and mortality were collected., Results: After dialysis, Hb concentration rise by 6.1 ± 5.6%. Using postdialysis Hb, the weight-adjusted ESA dosage would be lower respect to the prescription using predialysis Hb: 104 ± 120 vs 128 ± 124 U/kg/week (P < 0.001). Using predialysis Hb, 40.2% of subjects had a Hb level above 12 g/dL, whereas this percent increased to 70.1% using postdialysis Hb. During the follow-up, 15 patients had a CVE, without differences in Hb levels respect to subjects without CVE. However, patients with CVE had received higher ESA doses: 186 ± 180 vs 111 ± 98 U/Kg/week (P = 0.001). The prediction model is: Postdialysis Hb (g/dL) = 1.636 + 0.871 x predialysis Hb* (g/dL) + 0.099 x UF rate** (mL/kg/h) - 0.39 for women***. [R2 = 0.74; *P < 0,001; **P = 0.001; ***P = 0.03)., Conclusions: Postdialysis Hb can be a better reflect of the real Hb level in hemodialysis patients. Using postdialysis Hb would avoid the use of inappropriately high ESA doses. The prediction of postdialysis Hb with an adjusted model would help us to identify those patients at risk for ESA overdosification.

In this work we summarizes the steps that allowed the identification of the fibroblast growth factor (FGF) 23/Klotho axis as the principal regulator of phosphate homeostasis, exerting actions on intestine, bone, parathyroid glands, and kidney. We review the not fully understood mechanisms of action of this axis on the regulation of mineral homeostasis and, in addition, we discuss its potential role in the pathophysiology of chronic kidney disease and the associated complications. We also reflect the actual tendency to consider the components of this system as better predictors of the pathological conditions frequently associated to mineral disorders, and review some recent studies linking these components to cardiovascular disease even in population without mineral disorders. Finally, we consider the numerous processes in which Klotho is involved, including anti-ageing and mineral control processes, independently of its functions as obligated-coreceptor for FGF23., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Unlabelled: Dexmedetomidine has demonstrated to be useful in several clinical fields due to its respiratory safety and cardiovascular stability. We undertook this study to determine its usefulness in plastic surgery. Sixty patients were divided into two parallel groups. A group received dexmedetomidine--fentanyl and the comparison group received nalbuphine--propofol, both with same dose of midazolam. Blood pressure, heart rate and oxygen saturation were determined during the preoperative, intraoperative and recuperation periods., Results: In both groups, hemodynamic constants decreased intraoperatively. Dexmedetomidine--fentanyl decreased more than in the nalbuphine--propofol (systolic blood pressure, p = 0.006; diastolic blood pressure, p = 0.01 and heart rate, p = 0.007). Comparatively, oxygen saturation was greater in the dexmedetomidine--fentanyl group vs. nalbuphine--propofol (p = 0.0001). Recovery time for the nalbuphine--propofol group was shorter than in the dexmedetomidine--fentanyl group (p = 0.0001)., Conclusions: Dexmedetomidine shows the same cardiovascular stability but with absence of respiratory depression.

Diabetes mellitus and its complications are becoming one of the most important health problems in the world. Diabetic nephropathy is now the main cause of end-stage renal disease. The mechanisms leading to the development and progression of renal injury are not well known. Therefore, it is very important to find new pathogenic pathways to provide opportunities for early diagnosis and targets for novel treatments. At the present time, we know that activation of innate immunity with development of a chronic low grade inflammatory response is a recognized factor in the pathogenesis of diabetic nephropathy. Numerous experimental and clinical studies have shown the participation of different inflammatory molecules and pathways in the pathophysiology of this complication.

The biosorption of mercury (II) on 14 fungal biomasses, Aspergillus flavus I-V, Aspergillus fumigatus I-II, Helminthosporium sp., Cladosporium sp., Mucor rouxii mutant, M. rouxii IM-80, Mucor sp 1 and 2, and Candida albicans, was studied in this work. It was found that the biomasses of the fungus M. rouxii IM-80, M. rouxii mutant, Mucor sp1, and Mucor sp 2 were very efficient removing the metal in solution, using dithizone, reaching the next percentage of removals: 95.3%, 88.7%, 80.4%, and 78.3%, respectively. The highest adsorption was obtained at pH 5.5, at 30°C after 24 hours of incubation, with 1 g/100 mL of fungal biomass.

Background: To obtain information on cardiovascular morbidity, hypertension control, anemia and mineral metabolism based on the analysis of the baseline characteristics of a large cohort of Spanish patients enrolled in an ongoing prospective, observational, multicenter study of patients with stages 3 and 4 chronic kidney diseases (CKD)., Methods: Multicenter study from Spanish government hospital-based Nephrology outpatient clinics involving 1129 patients with CKD stages 3 (n = 434) and 4 (n = 695) defined by GFR calculated by the MDRD formula. Additional analysis was performed with GFR calculated using the CKD-EPI and Cockcroft-Gault formula., Results: In the cohort as a whole, median age 70.9 years, morbidity from all cardiovascular disease (CVD) was very high (39.1%). In CKD stage 4, CVD prevalence was higher than in stage 3 (42.2 vs 35.6% p < 0.024). Subdividing stage 3 in 3a and 3b and after adjusting for age, CVD increased with declining GFR with the hierarchy (stage 3a < stage 3b < stage 4) when calculated by CKD-EPI (31.8, 35.4, 42.1%, p 0.039) and Cockcroft-Gault formula (30.9, 35.6, 43.4%, p 0.010) and MDRD formula (32.5, 36.2, 42.2%,) but with the latter, it did not reach statistical significance (p 0.882). Hypertension was almost universal among those with stages 3 and 4 CKD (91.2% and 94.1%, respectively) despite the use of more than 3 anti-hypertensive agents including widespread use of RAS blockers. Proteinuria (> 300 mg/day) was present in more than 60% of patients and there was no significant differences between stages 3 and 4 CKD (1.2 ± 1.8 and 1.3 ± 1.8 g/day, respectively). A majority of the patients had hemoglobin levels greater than 11 g/dL (91.1 and 85.5% in stages 3 and 4 CKD respectively p < 0.001) while the use of erythropoiesis-stimulating agents (ESA) was limited to 16 and 34.1% in stages 3 and 4 CKD respectively. Intact parathyroid hormone (i-PTH) was elevated in stage 3 and stage 4 CKD patients (121 ± 99 and 166 ± 125 pg/mL p 0.001) despite good control of calcium-phosphorus levels., Conclusion: This study provides an overview of key clinical parameters in patients with CKD Stages 3 and 4 where delivery or care was largely by nephrologists working in a network of hospital-based clinics of the Spanish National Healthcare System.

Statements of the Problem: Diabetic nephropathy (DN) is the main cause of end-stage renal disease (ESRD). Renin-angiotensin system (RAS) blockade is the standard of care; however, a significant proportion of patients progress to ESRD. Pentoxifylline (PTF) possesses properties suggesting potential renoprotective efficacy. The aim of the Pentoxifylline for Renoprotection in Diabetic Nephropathy (PREDIAN) study is to test the efficacy of PTF addition to RAS blockade on the progression of DN. Here we report the study design and the baseline patient characteristics., Methods: This is an investigator-initiated, single-center, prospective, randomized, controlled, clinical trial without any commercial interest, funded by the Spanish Ministry of Science and Innovation. One hundred and sixty-nine type 2 diabetic patients with Stage 3 and 4 chronic kidney disease (CKD) were randomized to a control group (n=87) or an active group (n=82), which will receive PTF (1200 mg/day) for 24 months. The primary outcome measure is the difference in estimated glomerular filtration rate (eGFR) between the groups at the end of the study., Results: The baseline characteristics of the subjects are as follows: 116 patients (68.6%) with Stage 3 CKD and 53 (31.3%) Stage 4 CKD, age 69±9 years, duration of diabetes 15±3 years, eGFR 37±12 ml/min per 1.73 m(2), albuminuria 1.39±1.16 g/day, blood pressure 142±8/86±8 mmHg. Inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-10) and polymorphisms of the coding genes for these molecules are studied., Conclusions: The PREDIAN study will provide evidence on the renoprotective benefit of PTF in addition to interventions of proven efficacy (RAS blockade) in DN., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background and Objectives: Hyperphosphatemia and subclinical endotoxemia are important sources of inflammation in HD. Proinflammatory cytokines are strong correlates of soluble CD14 (sCD14) concentrations, an independent predictor of mortality in this population. We evaluated the effects of calcium acetate and sevelamer hydrochloride on serum inflammatory profile, endotoxin concentrations, and sCD14 levels in HD patients., Design, Setting, Participants, & Measurements: Prospective, randomized, open-label, parallel design trial. Fifty-nine stable HD patients, 30 receiving sevelamer, and 29 receiving calcium acetate were evaluated. Serum levels of inflammatory parameters (high-sensitivity C-reactive protein [hs-CRP], TNF-α, interleukin (IL)-1, -6, -10, and -18), as well as endotoxin and sCD14 concentrations, were measured at baseline and after 3 months of therapy., Results: Serum IL-6 increased in patients receiving calcium acetate, whereas hs-CRP and IL-6 significantly decreased in subjects treated with sevelamer, with IL-10 experiencing a trend to increase (P = 0.052). Serum endotoxin and sCD14 levels did not change after treatment with calcium acetate. However, these parameters decreased by 22.6% and 15.2%, respectively (P < 0.01), in patients receiving sevelamer. Multiple regression analysis showed that variation in serum endotoxin concentrations was the strongest factor associated with IL-6 change, whereas the only variables independently associated with changes in sCD14 levels were the variations in serum IL-6 and endotoxin concentrations., Conclusions: Administration of the noncalcium phosphate binder sevelamer to maintenance HD patients is associated with a significant decrease in hs-CRP, IL-6, serum endotoxin levels and sCD14 concentrations.

Many lines of evidence, ranging from in vitro experiments and pathological examinations to epidemiological studies, show that inflammation is a cardinal pathogenetic mechanism in diabetic nephropathy. Thus, modulation of inflammatory processes in the setting of diabetes mellitus is a matter of great interest for researchers today. The relationships between inflammation and the development and progression of diabetic nephropathy involve complex molecular networks and processes. This Review, therefore, focuses on key proinflammatory molecules and pathways implicated in the development and progression of diabetic nephropathy: the chemokines CCL2, CX3CL1 and CCL5 (also known as MCP-1, fractalkine and RANTES, respectively); the adhesion molecules intercellular adhesion molecule 1, vascular cell adhesion protein 1, endothelial cell-selective adhesion molecule, E-selectin and α-actinin 4; the transcription factor nuclear factor κB; and the inflammatory cytokines IL-1, IL-6, IL-18 and tumor necrosis factor. Advances in the understanding of the roles that these inflammatory pathways have in the context of diabetic nephropathy will facilitate the discovery of new therapeutic targets. In the next few years, promising new therapeutic strategies based on anti-inflammatory effects could be successfully translated into clinical treatments for diabetic complications, including diabetic nephropathy.

Diabetes mellitus and its complications have become one of the most important health problems in the world. Nowadays, diabetic nephropathy is the main cause of end-stage renal failure and need for renal substitutive therapy. The exact mechanisms leading to the development and progression of renal damage in diabetes are not yet completely known. Growing evidence indicates that activation of innate immunity with the development of a chronic low-grade inflammatory response is a recognized factor in the pathogenesis of this disease. Inflammatory molecules and pathways, including metabolic routes, oxidative stress, growth factors, chemokines, adhesion molecules and inflammatory cytokines, interact in manifold ways leading to renal injury responsible for the development and progression of this complication. The increasing knowledge and understanding of the role of these inflammatory mechanisms, with an integrative comprehension of this network, will facilitate the identification of new therapeutic targets and the development of new strategies that can be translated successfully into clinical applications., (Copyright © 2011 S. Karger AG, Basel.)

Infectious spondylodiscitis is an infection seen with increasing frequency in patients receiving chronic hemodialysis. Often accompanied by bacteremia, it is associated with the use of central venous catheters for hemodialysis access. Initial symptoms can be relatively insidious and nonspecific. Therefore, the clinician must have a low threshold for diagnostic testing that goes beyond blood cultures. This, in addition to early empiric antibiotic therapy, may improve the outcome of this potentially catastrophic infection., (© 2010 Wiley Periodicals, Inc.)

A resistant and capable fungal strain in removing hexavalent chromium was isolated from an environment near of Chemical Science Faculty, located in the city of San Luis Potosí, Mexico. The strain was identified as Paecilomyces sp., by macro- and microscopic characteristics. Strain resistance of the strain to high Cr (VI) concentrations and its ability to reduce chromium were studied. When it was incubated in minimal medium with glucose, another inexpensive commercial carbon source like unrefined and brown sugar or glycerol, in the presence of 50 mg/L of Cr (VI), the strain caused complete disappearance of Cr (VI), with the concomitant production of Cr (III) in the growth medium after 7 days of incubation, at 28 degrees C, pH 4.0, 100 rpm, and an inoculum of 38 mg of dry weight. Decrease of Cr (VI) levels from industrial wastes was also induced by Paecilomyces biomass. These results indicate that reducing capacity of chromate resistant filamentous fungus Cr (VI) could be useful for the removal of Cr (VI) pollution.

Background and Objectives: Mineral metabolism abnormalities and inflammation are concerns in chronic kidney disease (CKD). Interrelationships among these parameters have not been analyzed., Design, Setting, Participants, and Measurements: The study included 133 patients with CKD not on dialysis and not receiving calcium (Ca) supplements, phosphate binders, or vitamin D. Estimated GFR (eGFR) was 34.1 +/- 6.8 ml/min/1.73 m(2); 107 participants had stage 3 CKD, and 26 had stage 4., Results: Patients were classified by tertiles of Ca, phosphorus (P), Ca-P product (Ca x P), and parathyroid hormone (PTH). After adjustment for age, gender, and eGFR, the levels of C-reactive protein (CRP) and IL-6 (IL-6) of the third tertile of P, Ca x P, and PTH were significantly higher than those of the first and second tertiles. Serum P and Ca x P directly correlated with CRP and IL-6, whereas HDL-cholesterol and eGFR inversely correlated with the levels of the inflammatory parameters. After partial correlation analysis, the previous associations between CRP and eGFR, and serum P, as well as the relationship between IL-6 and eGFR, and serum P, remained significant. Multiple regression analysis demonstrated that eGFR and serum P were independently associated with CRP and IL-6. Finally, logistic regression analysis using the presence/absence of an inflammatory state as the dependent variable showed that eGFR was a protective factor, whereas serum P was an independent risk factor for the presence of an inflammatory state., Conclusions: Elevated serum P might play a role in the development of inflammation in CKD.

Activation of innate immunity with the subsequent development of a chronic low-grade inflammatory response is now recognized as a critical factor in the pathogenesis of diabetes mellitus and diabetic complications, including diabetic nephropathy. In the setting of diabetic nephropathy, there is now evidence of the relevant contribution of pro-inflammatory cytokines, with special participation of tumor necrosis factor-alpha (TNF-alpha). This new pathogenic perspective leads to new therapeutic implications derived from modulation of inflammation and inflammatory cytokines. Experimental studies have shown the beneficial renal actions derived from TNF-alpha inhibition with the use of soluble TNF-alpha receptor fusion proteins, chimeric monoclonal antibodies and pentoxifylline (PTF). Clinical application of this strategy is nowadays limited to PTF administration, which has demonstrated significant beneficial effects in patients with diabetic nephropathy. Overall, these studies indicate that inhibition of TNF-alpha might be an efficacious treatment for renal disease secondary to diabetes mellitus.

Diabetes and its complications have become a public health problem. One of the most important complications is diabetic nephropathy, which is nowadays the main cause of chronic renal failure. In spite of our greater understanding of this complication, the intimate mechanisms leading to the development and progression of renal injury are not well understood. New perspectives in activated innate immunity and inflammation appear to be relevant factors in the pathogenesis of diabetes. Moreover, different inflammatory molecules, including adipokines, Toll-like receptors, chemokines, adhesion molecules and pro-inflammatory cytokines, may be critical factors in the development of microvascular diabetic complications, including nephropathy. This new pathogenic perspective leads to important therapeutic considerations, with new pathogenic pathways becoming important therapeutic targets that can be translated into clinical treatments for diabetic nephropathy.

Magnesium (Mg) is the fourth most abundant cation in the body, mainly located within bone and skeletal muscle. The normal total plasma Mg concentration varies in a narrow range, with approximately 60% present as free Mg ions, the biologically active form. The kidney plays a principal role in Mg balance. Approximately 70-80% of plasma Mg is ultrafilterable, and under normal circumstances, 95% of the filtered load of Mg is reabsorbed. As chronic renal failure (CRF) progresses, urinary Mg excretion may be insufficient to balance intestinal Mg absorption and dietary Mg intake becomes a major determinant of serum and total body Mg levels. Until severe reductions in glomerular filtration rate (<30 ml/min), serum Mg levels are usually normal; with lower rates of renal function, serum Mg is increased. Concerning dialysis patients, dialysate Mg plays a critical role in maintaining Mg homeostasis, with serum Mg being largely dependent on the concentration of the ion in the dialysis solution. Magnesium has been implicated in diverse consequences, both beneficial and deleterious, in patients with CRF and dialysis. Potential harmful effects of elevated Mg include altered nerve conduction velocity, increased pruritus, and alterations to osseous metabolism and parathyroid gland function (mineralization defects, contribution to osteomalacic renal osteodystrophy, and adynamic bone disease). Hypermagnesemia also may retard vascular calcification. Low Mg levels have been associated with impairment of myocardial contractility, intradialytic hemodynamic instability, and hypotension. In addition, low Mg has been also linked to carotid intima-media thickness, a marker of atherosclerotic vascular disease and a predictor of vascular events.

Objectives: To investigate the relationship between inflammatory parameters [high-sensitivity C-reactive protein (hs-CRP), serum tumor necrosis factor-alpha (TNF-alpha) and urinary TNF-alpha] with subclinical cardiac and renal markers of early target organ damage (TOD) in essential hypertension., Methods: Preclinical TOD [left ventricular hypertrophy (LVH) and microalbuminuria (MAB)] was evaluated in 40 newly diagnosed never-treated patients with essential hypertension. Serum and urinary TNF-alpha and hs-CRP were measured as inflammatory parameters. Twenty-one BMI-matched and sex-matched normotensive, healthy individuals were included as control group., Results: The serum levels of hs-CRP and the urinary TNF-alpha excretion were higher in hypertensive patients with MAB, whereas patients with LVH presented higher levels of urinary TNF-alpha. The only difference between hypertensive patients without TOD and healthy controls was the higher urinary excretion of TNF-alpha. Partial correlation analysis showed a significant association between urinary albumin excretion (UAE) and systolic blood pressure (r=0.62, P<0.0001), hs-CRP (r=0.64, P<0.001), urinary TNF-alpha (r=0.55, P=0.001) and Cornell product (r=0.33, P<0.05), whereas the Cornell product was related to UAE (r=0.34, P<0.05), urinary TNF-alpha (r=0.45, P<0.01), and hs-CRP (r=0.32, P<0.05). Multiple regression analysis demonstrated that the parameters independently correlated with UAE were mean blood pressure, Cornell product, hs-CRP and urinary TNF-alpha (adjusted R2=0.77, P<0.001), whereas UAE, urinary TNF-alpha and hs-CRP were independently correlated with Cornell product (adjusted R2=0.66, P<0.001). Multiple logistic regression analysis with TOD as the dependent variable showed that hs-CRP [2.24 (1.17-4.28), P<0.05] and urinary TNF-alpha [1.21 (1.02-1.44), P<0.05] were independently related to TOD., Conclusion: Urinary TNF-alpha is independently correlated with UAE and Cornell product in essential hypertension, suggesting that inflammation may participate in the development of TOD. In addition, urinary excretion of TNF-alpha might be an early marker of preclinical TOD in hypertensive patients. Finally, these results may be a basis to study the effect of the blockade of TNF-alpha activity on the development and progression of TOD in essential hypertension.

Cytokines act as pleiotropic polypeptides regulating inflammatory and immune responses through actions on cells. They provide important signals in the pathophysiology of a range of diseases, including diabetes mellitus. Chronic low-grade inflammation and activation of the innate immune system are closely involved in the pathogenesis of diabetes and its microvascular complications. Inflammatory cytokines, mainly IL-1, IL-6, and IL-18, as well as TNF-alpha, are involved in the development and progression of diabetic nephropathy. In this context, cytokine genetics is of special interest to combinatorial polymorphisms among cytokine genes, their functional variations, and general susceptibility to diabetic nephropathy. Finally, the recognition of these molecules as significant pathogenic mediators in diabetic nephropathy leaves open the possibility of new potential therapeutic targets.