Plasma protein binding in uremia: Extraction and characterization of an inhibitor

Plasma protein binding in uremia: Extraction and characterization of an inhibitor. The impairment of binding of drugs and other substances to serum albumin in patients with uremia can be restored to normal or near normal levels by adsorption with charcoal or synthetic polymers at pH 3. We used a nonionic poly-styrene-divinylbenzene copolymer to treat uremic plasma at pH 3. We observed a marked improvement of binding. Subsequent elution of this resin with ethanol produced a substance that, when dried and recombined with normal plasma, caused dose-dependent impairment of phenytoin and tryptophan binding. Restoration of normal binding affinity occurred after retreatment of this abnormalized plasma with resin at pH 3. Plasma and pleural fluid exudate from patients with uremia yielded, after extraction by the above technique, an inhibitor(s) of phenytoin binding in amounts averaging five times that extracted from equal volumes of normal plasma. This inhibitor (Ix) is water soluble, heat stable, and dialyzable across cellophane membranes. Unlike fatty acids, which can also interfere with binding, Ix partitions primarily in the water phase in solvent partition studies but undergoes a sharp transition in the pH 4 to 5 range, suggesting the presence of a carboxyl group. These findings lend further support to the hypothesis that a retained ligand(s) is responsible for impaired plasma binding associated with uremia and suggests a role for organic acids known to accumulate in renal failure.Liaison aux protéines plasmatiques dans l'urémie: Extraction et caractérisation d'un inhibiteur. L'altération de la liaison de drogues et d'autres substances à l'albumine sérique au cours de l'urémie peut être complètement ou presque complètement supprimée par l'adsorption sur du charbon ou des polymères synthétiques à pH 3. Nous avons utilisé un co-polymère non ionique polystyrènedivinylbenzène pour traiter le plasma urémique à pH 3 et observé une amélioration importante de la liaison. L'élution ultérieure de cette résine par l'éthanol produit une substance qui, lorsqu'elle est séchée et recombinée avec du plasma normal, détermine une altération dose dépendante de la liaison de la diphényl-hydantoïne et du tryptophane. La récupération d'une affinité de liaison normale a été obtenue après un nouveau traitement du plasma par la résine à pH 3. Le plasma et le liquide pleural de malades urémiques a donné, après extraction par la technique ci-dessus, un inhibiteur(s) de la liaison de la phénylhydantoïne en quantité cinq fois plus grande que celle extraite devolumes identiques de plasma normal. Cet inhibiteur (Ix) est soluble dans l'eau, thermostable et dialysable à travers des membranes de cellophane. A la différence des acides gras, qui peuvent aussi interférer avec la liaison, Ix passe dans la phase aqueuse au cours des études de partition dans des solvants, mais subit une transition brusque dans la gamme de pH 4 à 5, ce qui suggère la présence d'un groupe carboxyle. Ces constatations apportent des arguments supplémentaires à l'hypothèse selon laquelle un ligand (ou des ligands) retenus au cours de l'urémie est responsable de l'altération de la liaison plasmatique et suggère un rôle des acides organiques dont l'accumulation est connue dans l'insuffisance rénale

Mean curvature flow with triple junctions in higher space dimensions

We consider mean curvature flow of n-dimensional surface clusters. At (n-1)-dimensional triple junctions an angle condition is required which in the symmetric case reduces to the well-known 120 degree angle condition. Using a novel parametrization of evolving surface clusters and a new existence and regularity approach for parabolic equations on surface clusters we show local well-posedness by a contraction argument in parabolic Hoelder spaces.Comment: 31 pages, 2 figure

The effect of frequent hemodialysis on nutrition and body composition: frequent Hemodialysis Network Trial.

We investigated the effects of frequency of hemodialysis on nutritional status by analyzing the data in the Frequent Hemodialysis Network Trial. We compared changes in albumin, body weight, and composition among 245 patients randomized to six or three times per week in-center hemodialysis (Daily Trial) and 87 patients randomized to six times per week nocturnal or three times per week conventional hemodialysis, performed largely at home (Nocturnal Trial). In the Daily Trial, there were no significant differences between groups in changes in serum albumin or the equilibrated protein catabolic rate by 12 months. There was a significant relative decrease in predialysis body weight of 1.5 ± 0.2 kg in the six times per week group at 1 month, but this significantly rebounded by 1.3 ± 0.5 kg over the remaining 11 months. Extracellular water (ECW) decreased in the six times per week compared with the three per week hemodialysis group. There were no significant between-group differences in phase angle, intracellular water, or body cell mass (BCM). In the Nocturnal Trial, there were no significant between-group differences in any study parameter. Any gain in 'dry' body weight corresponded to increased adiposity rather than muscle mass but was not statistically significant. Thus, frequent in-center hemodialysis reduced ECW but did not increase serum albumin or BCM while frequent nocturnal hemodialysis yielded no net effect on parameters of nutritional status or body composition

Effect of frequent hemodialysis on residual kidney function.

Frequent hemodialysis can alter volume status, blood pressure, and the concentration of osmotically active solutes, each of which might affect residual kidney function (RKF). In the Frequent Hemodialysis Network Daily and Nocturnal Trials, we examined the effects of assignment to six compared with three-times-per-week hemodialysis on follow-up RKF. In both trials, baseline RKF was inversely correlated with number of years since onset of ESRD. In the Nocturnal Trial, 63 participants had non-zero RKF at baseline (mean urine volume 0.76 liter/day, urea clearance 2.3 ml/min, and creatinine clearance 4.7 ml/min). In those assigned to frequent nocturnal dialysis, these indices were all significantly lower at month 4 and were mostly so at month 12 compared with controls. In the frequent dialysis group, urine volume had declined to zero in 52% and 67% of patients at months 4 and 12, respectively, compared with 18% and 36% in controls. In the Daily Trial, 83 patients had non-zero RKF at baseline (mean urine volume 0.43 liter/day, urea clearance 1.2 ml/min, and creatinine clearance 2.7 ml/min). Here, treatment assignment did not significantly influence follow-up levels of the measured indices, although the range in baseline RKF was narrower, potentially limiting power to detect differences. Thus, frequent nocturnal hemodialysis appears to promote a more rapid loss of RKF, the mechanism of which remains to be determined. Whether RKF also declines with frequent daily treatment could not be determined

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study. The ongoing HEMO Study, a National Institutes of Health (NIH) sponsored multicenter trial to test the effects of dialysis dosage and membrane flux on morbidity and mortality, was preceded by a Pilot Study (called the MMHD Pilot Study) designed to test the reliability of methods for quantifying hemodialysis. Dialysis dose was defined by the fractional urea clearance per dialysis determined by the predialysis BUN and the equilibrated postdialysis BUN after urea rebound is completed (eKt/V). In the Pilot Study the blood side standard for eKt/V was calculated from the predialysis, postdialysis, and 30-minute postdialysis BUN. Four techniques of approximating eKt/V that eliminated the requirement for the 30-minute postdialysis sample were also evaluated. The first adjusted the single compartment Kt/V using a linear equation with slope based on the relative rate of solute removal (K/V) to predict eKt/V (rate method). The second and third techniques used equations or mathematical curve fitting algorithms to fit data that included one or more samples drawn during dialysis (intradialysis methods). The fourth technique (dialysate-side) predicted eKt/V from an analysis of the time-dependent profile of dialysate urea nitrogen concentrations (BioStat method; Baxter Healthcare, Inc., Round Lake, IL, USA). The Pilot Study demonstrated the feasibility of conventional and high dose targets of about 1.0 and 1.4 for eKt/V. Based on the blood side standard method, the mean ± SD eKt/V for patients randomized to these targets was 1.14 ± 0.11 and 1.52 ± 0.15 (N = 19 and 16 patients, respectively). Single-pool Kt/Vs were about 0.2 Kt/V units higher. Results were similar when eKt/V was based on dialysate side measurements: 1.10 ± 0.11 and 1.50 ± 0.11. The approximations of eKt/V by the three blood side methods that eliminated the delayed 30-minute post-dialysis sample correlated well with eKt/V from the standard blood side method: r = 0.78 and 0.76 for the single-sample (Smye) and multiple-sample intradialysis methods (N = 295 and 229 sessions, respectively) and 0.85 for the rate method (N = 295). The median absolute difference between eKt/V computed using the standard blood side method and eKt/V from the four other methods ranged from 0.064 to 0.097, with the smallest difference (and hence best accuracy) for the rate method. The results suggest that, in a dialysis patient population selected for ability to achieve an equilibrated Kt/V of about 1.45 in less than a 4.5 hour period, use of the pre and postdialysis samples and a kinetically derived rate equation gives reasonably good prediction of equilibrated Kt/V. Addition of one or more intradialytic samples does not appear to increase accuracy of predicting the equilibrated Kt/V in the majority of patients. A method based on dialysate urea analysis and curve-fitting yields results for equilibrated Kt/V that are similar to those obtained using exclusively blood-based techniques of kinetic modeling

CX3CR1 Polymorphisms are associated with atopy but not asthma in German children

Chemokines and their receptors are involved in many aspects of immunity. Chemokine CX3CL1, acting via its receptor CX3CR1, regulates monocyte migration and macrophage differentiation as well as T cell-dependent inflammation. Two common, nonsynonymous polymorphisms in CX3CR1 have previously been shown to alter the function of the CX3CL1/CX3CR1 pathway and were suggested to modify the risk for asthma. Using matrix-assisted laser desorption/ionization time-of-flight technology, we genotyped polymorphisms Val249Ile and Thr280Met in a cross-sectional population of German children from Munich (n = 1,159) and Dresden ( n = 1,940). For 249Ile an odds ratio of 0.77 (95% confidence interval 0.63-0.96; p = 0.017) and for 280Met an odds ratio of 0.71 ( 95% confidence interval 0.56-0.89; p = 0.004) were found with atopy in Dresden but not in Munich. Neither polymorphism was associated with asthma. Thus, amino acid changes in CX3CR1 may influence the development of atopy but not asthma in German children. Potentially, other factors such as environmental effects may modify the role of CX3CR1 polymorphisms. Copyright (c) 2007 S. Karger AG, Basel

I-care-an interaction system for the individual activation of people with dementia

I-CARE is a hand-held activation system that allows professional and informal caregivers to cognitively and socially activate people with dementia in joint activation sessions without special training or expertise. I-CARE consists of an easy-to-use tablet application that presents activation content and a server-based backend system that securely manages the contents and events of activation sessions. It tracks various sources of explicit and implicit feedback from user interactions and different sensors to estimate which content is successful in activating individual users. Over the course of use, I-CARE’s recommendation system learns about the individual needs and resources of its users and automatically personalizes the activation content. In addition, information about past sessions can be retrieved such that activations seamlessly build on previous sessions while eligible stakeholders are informed about the current state of care and daily form of their protegees. In addition, caregivers can connect with supervisors and professionals through the I-CARE remote calling feature, to get activation sessions tracked in real time via audio and video support. In this way, I-CARE provides technical support for a decentralized and spontaneous formation of ad hoc activation groups and fosters tight engagement of the social network and caring community. By these means, I-CARE promotes new care infrastructures in the community and the neighborhood as well as relieves professional and informal caregivers

DESEMPENHO DE CORDEIROS NATURALMENTE INFECTADOS COM PARASITAS GASTRINTESTINAIS UTILIZANDO O TRATAMENTO SELETIVO COM O MÉTODO FAMACHA E O TRATAMENTO PREVENTIVO

The objective of the present workwas to evaluate the weight gain in lambs using twosystems of parasite control in between 14/11/04 and14/03/05. Thirty four animals of the Ile de Francebreed where used in two groups of 17 animals(G1 and G2). The G1 group was evaluated at14-days interval using Famacha, diarrhea and bodycondition score and fecal exam (EPG) at the samefrequency being treated with moxidectin in casethey manifested any clinical sign. The G2 group wastreated with the same compound at 30-days interval.The correlation of Famacha 2, 3 and 4 and thevariables EPG and weight was of 0,903 and 0,662,respectively. The groups demonstrated no differenceon their final weight gain (P=0,110). There was thepredominance of the Haemonchus contortus speciesfor G1 (62,94%) and G2 (64,14%). The option totreat animals using the selective system reduced by87,5% the treatment cost when compared with thepreventive regime. The target selective treatmentusing the Famacha method allows a very efficientparasite control when there is a high prevalence ofthe parasite H. contortus. The data permit inferringabout the possibility to select less tolerant animalsduring a period of heavier parasite challenge.O objetivo do presente trabalho foiavaliar o ganho de peso em cordeiros utilizandoduas práticas de controle parasitário entre 14/11/04a 14/03/05. Trinta e quatro animais da raça Ile deFrance compuseram dois grupos de 17 animais (G1e G2). O grupo G1 foi avaliado em intervalos de 14dias utilizado o método Famacha, o escore de diarréia,exame de fezes (OPG) e o escore de condiçãocorporal na mesma freqüência, sendo tratados commoxidectina caso apresentassem comprometimentoclínico. O grupo G2 foi tratado com o mesmo princípioativo em intervalos de 30 dias. A correlação devalores Famacha entre 2, 3 e 4 e as variáveis OPGe peso foi de 0,903 e 0,662, respectivamente. Osgrupos não apresentaram diferença no ganho depeso total (P=0,110). Houve predominância da espécieHaemonchus contortus para G1 (62,94%) eG2 (64,14%). A opção de tratar os animais com osistema seletivo reduziu em 87,5% o custo do tratamento,quando comparado com o regime preventivo.O tratamento seletivo com o método Famachapermite um controle parasitário eficiente quandoexiste alta prevalência do parasita H. contortus. Estesdados permitem inferir sobre a possibilidade deseleção de animais menos tolerantes durante umperíodo de maior desafio parasitário