The Decline in Residual Renal Function in Hemodialysis Is Slow and Age Dependent

Background: Persons on peritoneal dialysis and hemodialysis with preserved residual renal function experience lower mortality rates than those without. Previous studies have shown slower rates of decline of residual renal function for peritoneal dialysis (PD)(2 to 3% decrease/month), compared with hemodialysis (HD)(6 to 7% decrease/month). However, our clinical observations suggested a lower rate of decline in hemodialysis patients. Methods: We evaluated data in 174 hemodialysis patients cared for from January 2000 through October 2001. Eighty‐seven (50%) patients had at least two timed quarterly urine collections to estimate the rate of change of residual renal function over time (urea clearance, or KrU). All patients underwent thrice‐weekly hemodialysis using polysulfone dialyzers with formaldehyde reprocessing. The rate of decline of residual renal function and the effect of KrU on laboratory variables were estimated using a random effects (MIXED) model, adjusting for the effects of age, sex, race, diabetes, and dialysis vintage. Results: The mean KrU at baseline was 3.5 mL/min. Men (P < 0.001) and persons of shorter vintage (P < 0.0001) had more residual renal function at baseline. The estimated rate of decline of residual renal function was ? 0.07 mL/min/month (? 1.9% decrease/month). The rate of decline in residual renal function was unaffected by sex, race, diabetes, or vintage, although the rate of decline was significantly attenuated among older individuals (age x time interaction, P = 0.01). Serum phosphorus (P = 0.03) and the calcium x phosphorus product (P = 0.009) increased over time and were influenced by the level of residual renal function (P = 0.06 and P = 0.006, respectively). Residual renal function did not influence the rate of change of other laboratory variables. Conclusions: In an ethnically diverse cohort of hemodialysis patients, the rate of decline of residual renal function was relatively slow and age dependent, as well as consistent with values others have reported for patients on peritoneal dialysis. Universal use of biocompatible dialyzers and bicarbonate dialysate may have contributed to differences discussed in prior reports. Residual renal function attenuated the increase in calcium–phosphorus product over time. A better understanding of the determinants of the rate of decline in residual renal function, and the specific benefits afforded to patients via maintenance of residual renal function, would help to inform the debates on timing of initiation and various dosing strategies in hemodialysis.     

The inhibition of the viability of myeloma cells and the production of cytokine by two strains of Lactobacillus sakei from meat

Ten strains of lactic acid bacteria were isolated from a dry fermented sausage and tested for stimulation or inhibition of the viability of Vero and myeloma cells. They did not significantly affect the viability of Vero cells but two isolates (CBL/H and CBL/K) showed a strong and moderate inhibition of the myeloma cell viability (at 10⁸ CFU mL^?1, 17.6 and 33.2%, respectively, survival of myeloma cells). The isolates were identified as Lactobacillus sakei by DNA sequencing of the 16S rRNA products of a polymerase chain reaction. No protective effect was found, at the concentrations used, against cytotoxicity of N‐nitrosamines. To test the effect of L. sakei CBL/H and CBL/K on cytokine production [tumour necrosis factor alpha (TNF‐α), interleukin‐1β (IL‐1β) and interleukin‐8 (IL‐8)], the human macrophage cell line (THP‐1) was cultured in the presence and absence of lipopolysaccharide (LPS). Lactobacillus sakei CBL/H and CBL/K induced IL‐1β and IL‐8 release when cells were stimulated with and without LPS. However there was TNF‐α release only in the presence of the LPS.     

Adsorption of Zn(II) by crosslinked acrylic copolymers with amine functional groups

Adsorption of Zn(II) ions from diluted aqueous solutions by the acrylic copolymer based on ethylacrylate : acrylonitrile : divinylbenzene matrix with different crosslinking degrees and ethylenediamine and triethylenetetramine functional groups was investigated. Adsorption experiments were carried out by batch method. The effects of the pH, initial concentration of zinc, time of contact, and the crosslinking degree of the copolymers were studied. On the basis of Langmuir and Freundlich isotherms, the parameters that characterize the adsorption were determined. The maximum Zn(II) retention capacity value (500 mg g^?1) was obtained for the acrylic copolymer with 2% crosslinking degree and ethylenediamine, as functional groups. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 803–808, 2004     

Comprehensive analysis of major and minor chlorogenic acids and lactones in economically relevant Brazilian coffee cultivars

Coffee is the most consumed beverage in the world and a significant source of phenolic compounds, particularly chlorogenic acids (CGA). During coffee roasting, some CGA are partially transformed into chlorogenic acid lactones (CGL). Both CGA and CGL are important compounds for flavor and potentially beneficial to human health. In the present study, using LC–MS and synthetic standards, we investigated major and minor CGA and CGL isomers in green and roasted samples of economically relevant Brazilian Coffea arabica and Coffea canephora coffee cultivars. For the first time, in addition to nineteen previously identified CGA and CGL, 1-feruloylquinic acid, 1-feruloylquinic lactone and 3,4-diferuloylquinic acid were quantified in C. arabica and C. canephora, the contents of 3- and 4-p-coumaroylquinic lactones were reported in C. canephora and 3,4-di-p-coumaroylquinic acid was identified in C. arabica. Despite their low concentrations, the implications of these findings for flavor, cup quality and the biological properties of coffee merit further investigation.     

Photosensitized degradation in water of the phenolic pesticides bromoxynil and dichlorophen in the presence of riboflavin, as a model of their natural photodecomposition in the environment

Within the context of environmentally friendly methods for the elimination of surface-water pollutants, the photodegradation of the phenolic pesticides bromoxynil (BXN) and dichlorophen (DCP) under simulated natural conditions has been studied. The work was done in the presence of the visible-light absorber photosensitizer riboflavin (Rf), usually present in trace quantities in natural waters. Under aerobic conditions, an efficient photooxidation of both pesticides was observed. The relatively intricate photochemical mechanism involves pesticide and oxygen consumption and, to a lesser extent, Rf degradation. The kinetic and mechanistic study supports that both H(2)O(2) and singlet molecular oxygen, O(2)((1)Δ(g)), are involved in the process. Kinetic data for the O(2)((1)Δ(g))-mediated oxidation indicate that BXN and DCP are photodegraded with this species faster than the parent compound phenol, very frequently employed as a model for aquatic contaminants, likely due to their lower pK(a) values. This observation allows the design of phenolic pesticides with different photodegradation rates under environmental conditions.     

Determination of priority polybrominated diphenyl ethers by isotope dilution gas chromatography(electron ionization)MS using 81Br-labeled standards

A mixture of (81)Br-labeled polybrominated diphenyl ethers (PBDEs), previously synthesized in our laboratory, was separated by liquid chromatography for the individual isolation of different (81)Br-labeled PBDEs containing from 3 to 6 bromine atoms. The different fractions were collected, and a mixed labeled standard was then prepared adequate for the determination of priority PBDEs (congeners 28, 47, 99, 100, 153, and 154) in environmental samples. The spike mixture was then characterized using gas chromatography(electron ionization)MS (GC(EI)MS) both in isotope composition and concentration in combination with multiple least-squares. Contamination from natural abundance BDEs 153 and 154 was detected in the spike mixture, and a new isotope dilution equation was developed to take into account the natural abundance contribution from the spike. The spike mixture was shown to be stable during at least 4 months, and no isotope exchange between natural abundance and labeled PBDEs was detected during this period of time. Finally, the (81)Br-labeled PBDEs standard was used for the determination of congeners 28 (+33), 47, 49, 99, 100, 153, and 154 in a standard reference material (Lake Michigan fish tissue SRM 1947) using three different sample to spike ratios. No methodological calibration needed to be prepared, as no isotopic effects were detected using this labeling mode. Concentrations found were in agreement with the certified concentrations (recoveries between 89% and 116%), and reproducibility was always below 7% RSD. Kragten procedure was used to calculate expanded uncertainties. Very low limits of detection were obtained for all compounds (between 0.02 and 0.9 ng·g(-1)) using the procedure developed here.     

Lucifer Yellow as a live cell fluorescent probe for imaging water transport in subcellular organelles

While the water permeability of the plasma membranes of mammalian cells has been studied extensively, water transport across membranes of subcellular compartments (e.g., lysosomes, macropinosomes) has been difficult to study. Here we demonstrate a new method for measuring water flux in late endosomes and lysosomes of intact living cells using time-lapse fluorescence microscopy. Cells were loaded by fluid-phase uptake with a mixture of the Lucifer Yellow dextran (LY-dex), a D(2)O sensitive dye, and a D(2)O insensitive control dye, Alexa fluor 546 dextran (AF546-dex). LY-dex responded linearly to changes in D(2)O concentration and the LY-dex D(2)O sensitivity was not affected by changes in pH, physiological salt, and protein concentrations. The co-loaded control dye, AF546-dex, showed no signal changes as a function of D(2)O concentration. To measure membrane water flux, the LY-dex fluorescence in labeled organelles was recorded during rapid superfusion of cells with isotonic buffers prepared in D(2)O. The time constant of water exchange across the lysosomal membrane of intact cells was determined by fitting the data to a single exponential function. From these data, together with the measured area of the organelles, observed water permeability for intracellular CHO-K1 lysosomes was calculated to be 5.3 × 10(-3) ± 0.3 × 10(-3) cm/s. This work demonstrates the feasibility of measuring water flux into subcellular organelles in live cells using LY-dex.     

Differential Expression of Proteins in an Atypical Presentation of Autoimmune Lymphoproliferative Syndrome

Autoimmune lymphoproliferative syndrome (ALPS) is a rare disease defined as a defect in the lymphocyte apoptotic pathway. Currently, the diagnosis of ALPS is based on clinical aspects, defective lymphocyte apoptosis and mutations in Fas, FasL and Casp 10 genes. Despite this, ALPS has been misdiagnosed. The aim of this work was to go one step further in the knowledge of the disease, through a molecular and proteomic analysis of peripheral blood mononuclear cells (PBMCs) from two children, a 13-year-old girl and a 6-year-old boy, called patient 1 and patient 2, respectively, with clinical data supporting the diagnosis of ALPS. Fas, FasL and Casp10 genes from both patients were sequenced, and a sample of the total proteins from patient 1 was analyzed by label-free proteomics. Pathway analysis of deregulated proteins from PBMCs was performed on the STRING and PANTHER bioinformatics databases. A mutation resulting in an in-frame premature stop codon and protein truncation was detected in the Fas gene from patient 2. From patient 1, the proteomic analysis showed differences in the level of expression of proteins involved in, among other processes, cell cycle, regulation of cell cycle arrest and immune response. Noticeably, the most down-regulated protein is an important regulator of the cell cycle process. This could be an explanation of the disease in patient 1.     

Supplementation with SCFAs Re-Establishes Microbiota Composition and Attenuates Hyperalgesia and Pain in a Mouse Model of NTG-Induced Migraine

Migraine is a common brain-disorder that affects 15% of the population. Converging evidence shows that migraine is associated with gastrointestinal disorders. However, the mechanisms underlying the interaction between the gut and brain in patients with migraine are not clear. In this study, we evaluated the role of the short-chain fatty acids (SCFAs) as sodium propionate (SP) and sodium butyrate (SB) on microbiota profile and intestinal permeability in a mouse model of migraine induced by nitroglycerine (NTG). The mice were orally administered SB and SP at the dose of 10, 30 and 100 mg/kg, 5 min after NTG intraperitoneal injections. Behavioral tests were used to evaluate migraine-like pain. Histological and molecular analyses were performed on the intestine. The composition of the intestinal microbiota was extracted from frozen fecal samples and sequenced with an Illumina MiSeq System. Our results demonstrated that the SP and SB treatments attenuated hyperalgesia and pain following NTG injection. Moreover, SP and SB reduced histological damage in the intestine and restored intestinal permeability and the intestinal microbiota profile. These results provide corroborating evidence that SB and SP exert a protective effect on central sensitization induced by NTG through a modulation of intestinal microbiota, suggesting the potential application of SCFAs as novel supportive therapies for intestinal disfunction associated with migraine.