Hydration and nutritional status in patients on home-dialysis-A single centre study.

BACKGROUND: Over-hydration (OH) and malnutrition are prevalent among patients on dialysis therapy. The prevalence of OH and malnutrition as well as the risk factors associated with OH and malnutrition in our patients on home peritoneal dialysis (PD) and home haemodialysis (HD) are examined. DESIGN AND METHODS: This was a cross-sectional study. The hydration and nutritional status of the study groups were assessed by a Body Composition Monitor. Patients who were stable on home dialysis therapy for over one year were invited to participate. Univariate and multivariate analyses were performed to identify associated factors and determine the predictors of OH and malnutrition, respectively. RESULTS: Eighty-eight patients (41 PD and 47 home HD) were recruited. A 32.95% of our patients on home dialysis therapy were in OH status. There was a significance difference in the prevalence of hydration status between patients on PD and home HD (p = 0.014), as overhydration was more common in patients on PD than home HD (46.34 vs. 21.28%). Dehydration was more common in patients on home HD than PD (29.79 vs. 9.76%). Male gender, decreasing haemoglobin level and presence of diabetes mellitus (DM) were risk factors of OH on multivariable analysis. There was no significance difference in the prevalence of malnutrition between patients on PD and home HD (p = 0.27). Increasing Fat Tissue Index (FTI), height and patients on PD therapy were at higher risk of malnutrition. CONCLUSION: OH and malnutrition were prevalent patients on home dialysis therapy.

Degradation mechanism of a Golgi-retained distal renal tubular acidosis mutant of the kidney anion exchanger 1 in renal cells.

Distal renal tubular acidosis (dRTA) can be caused by mutations in the SLC4A1 gene encoding the anion exchanger 1 (AE1). Both recessive and dominant mutations result in mistrafficking of proteins, preventing them from reaching the basolateral membrane of renal epithelial cells, where their function is needed. In this study, we show that two dRTA mutants are prematurely degraded. Therefore, we investigated the degradation pathway of the kidney AE1 G701D mutant that is retained in the Golgi. Little is known about degradation of nonnative membrane proteins from the Golgi compartments in mammalian cells. We show that the kidney AE1 G701D mutant is polyubiquitylated and degraded by the lysosome and the proteosome. This mutant reaches the plasma membrane, where it is endocytosed and degraded by the lysosome via a mechanism dependent on the peripheral quality control machinery. Furthermore, we show that the function of the mutant is rescued at the cell surface upon inhibition of the lysosome and incubation with a chemical chaperone. We conclude that modulating the peripheral quality control machinery may provide a novel therapeutic option for treatment of patients with dRTA due to a Golgi-retained mutant.

Functional rescue of a kidney anion exchanger 1 trafficking mutant in renal epithelial cells.

Mutations in the SLC4A1 gene encoding the anion exchanger 1 (AE1) can cause distal renal tubular acidosis (dRTA), a disease often due to mis-trafficking of the mutant protein. In this study, we investigated whether trafficking of a Golgi-retained dRTA mutant, G701D kAE1, or two dRTA mutants retained in the endoplasmic reticulum, C479W and R589H kAE1, could be functionally rescued to the plasma membrane of Madin-Darby Canine Kidney (MDCK) cells. Treatments with DMSO, glycerol, the corrector VX-809, or low temperature incubations restored the basolateral trafficking of G701D kAE1 mutant. These treatments had no significant rescuing effect on trafficking of the mis-folded C479W or R589H kAE1 mutants. DMSO was the only treatment that partially restored G701D kAE1 function in the plasma membrane of MDCK cells. Our experiments show that trafficking of intracellularly retained dRTA kAE1 mutants can be partially restored, and that one chemical treatment rescued both trafficking and function of a dRTA mutant. These studies provide an opportunity to develop alternative therapeutic solutions for dRTA patients.

Síndrome de atrapamiento del nervio interóseo anterior / Trapping syndrome of the anterior interosseous verve

Introducción: el síndrome de atrapamiento del nervio interóseo anterior es una enfermedad que se presenta con poca frecuencia, no obstante, acuden a consulta un mayor número de personas que las reportadas. Esto se debe, entre otros factores, al desconocimiento de la enfermedad, lo cual provoca un diagnóstico erróneo y un tratamiento insuficiente. Objetivo: evaluar los resultados obtenidos con el tratamiento quirúrgico de esta enfermedad. Métodos: se realizó un estudio quasiexperimental en 18 pacientes portadores de un síndrome de atrapamiento del nervio interóseo anterior tratados quirúrgicamente en el servicio de miembros superiores del Complejo Científico Ortopédico Internacional Frank País, entre el Primero de diciembre de 2003 y el 31 de marzo de 2009. Los resultados se evaluaron mediante la aplicación de un score modificado para el grupo de estudio a partir de los score de Cooney y de Shah y Jones. Resultados: la edad promedio del grupo fue de 31,8 años con un rango entre 17 y 58 años, de ellos 14 del sexo femenino y 4 masculino; el tiempo de latencia de 5,7 meses con un rango entre 3 y 9 meses. El dolor, signo de Tinel positivo para el nervio interóseo, se presenta en 100 por ciento de los casos. Los resultados se evaluaron entre buenos y excelentes en 14 pacientes (77, 8 por ciento). En ningún caso fueron evaluados de malos. Conclusiones: el tratamiento quirúrgico es un método de elección eficaz ante un síndrome de atrapamiento del nervio interóseo anterior, que puede verse afectado por un período de latencia prolongado

Introduction: trapping syndrome of anterior interosseous nerve is an uncommon disease, however, a great number than reported came to consultation. This is due to among other factors, to the lack of knowledge of this entity leading to a misdiagnosis and a insufficient treatment. Objective: to assess the results obtained with surgical treatment of this disease. Methods: a quasi-experimental study was conducted in 18 patients diagnosed with trapping syndrome of anterior interosseous nerve operated on the upper extremities services of the Frank País International Orthopedic Scientific Complex from December 1, 2003 to March 31, 2009. Results were assessed by application of a modified score for the study group from the Cooney and Shah and Jones score. Results: the mean age of group was of 31.8 years with a rank between 17 and 58 years which included 14 female patients and 4 male patients; the latency time was of 5.7 months with a rank between 3 and 9 months. The pains, a positive Tinel sign for interosseous nerve; is present in the 100 percent of cases. Results were assessed between good and excellent in 14 patients (77.8 percent). In any case the results were assessed as poor. Conclusions: the surgical treatment is an effective choice method in face a trapping syndrome of anterior interosseous nerve t hat may be involved for a longstanding latency period

Síndrome de atrapamiento del nervio interóseo anterior / Trapping syndrome of the anterior interosseous verve

Introducción: el síndrome de atrapamiento del nervio interóseo anterior es una enfermedad que se presenta con poca frecuencia, no obstante, acuden a consulta un mayor número de personas que las reportadas. Esto se debe, entre otros factores, al desconocimiento de la enfermedad, lo cual provoca un diagnóstico erróneo y un tratamiento insuficiente. Objetivo: evaluar los resultados obtenidos con el tratamiento quirúrgico de esta enfermedad. Métodos: se realizó un estudio quasiexperimental en 18 pacientes portadores de un síndrome de atrapamiento del nervio interóseo anterior tratados quirúrgicamente en el servicio de miembros superiores del Complejo Científico Ortopédico Internacional Frank País, entre el Primero de diciembre de 2003 y el 31 de marzo de 2009. Los resultados se evaluaron mediante la aplicación de un score modificado para el grupo de estudio a partir de los score de Cooney y de Shah y Jones. Resultados: la edad promedio del grupo fue de 31,8 años con un rango entre 17 y 58 años, de ellos 14 del sexo femenino y 4 masculino; el tiempo de latencia de 5,7 meses con un rango entre 3 y 9 meses. El dolor, signo de Tinel positivo para el nervio interóseo, se presenta en 100 por ciento de los casos. Los resultados se evaluaron entre buenos y excelentes en 14 pacientes (77, 8 por ciento). En ningún caso fueron evaluados de malos. Conclusiones: el tratamiento quirúrgico es un método de elección eficaz ante un síndrome de atrapamiento del nervio interóseo anterior, que puede verse afectado por un período de latencia prolongado(AU)

Introduction: trapping syndrome of anterior interosseous nerve is an uncommon disease, however, a great number than reported came to consultation. This is due to among other factors, to the lack of knowledge of this entity leading to a misdiagnosis and a insufficient treatment. Objective: to assess the results obtained with surgical treatment of this disease. Methods: a quasi-experimental study was conducted in 18 patients diagnosed with trapping syndrome of anterior interosseous nerve operated on the upper extremities services of the Frank País International Orthopedic Scientific Complex from December 1, 2003 to March 31, 2009. Results were assessed by application of a modified score for the study group from the Cooney and Shah and Jones score. Results: the mean age of group was of 31.8 years with a rank between 17 and 58 years which included 14 female patients and 4 male patients; the latency time was of 5.7 months with a rank between 3 and 9 months. The pains, a positive Tinel sign for interosseous nerve; is present in the 100 percent of cases. Results were assessed between good and excellent in 14 patients (77.8 percent). In any case the results were assessed as poor. Conclusions: the surgical treatment is an effective choice method in face a trapping syndrome of anterior interosseous nerve t hat may be involved for a longstanding latency period(AU)

Mis-trafficking of bicarbonate transporters: implications to human diseases.

Bicarbonate is a waste product of mitochondrial respiration and one of the main buffers in the human body. Thus, bicarbonate transporters play an essential role in maintaining acid-base balance but also during fetal development as they ensure tight regulation of cytosolic and extracellular environments. Bicarbonate transporters belong to two gene families, SLC4A and SLC26A. Proteins from these two families are widely expressed, and thus mutations in their genes result in various diseases that affect bones, pancreas, reproduction, brain, kidneys, eyes, heart, thyroid, red blood cells, and lungs. In this minireview, we discuss the current state of knowledge regarding the effect of SLC4A and SLC26A mutants, with a special emphasis on mutants that have been studied in mammalian cell lines and how they correlate with phenotypes observed in mice models.

Band 3 Edmonton I, a novel mutant of the anion exchanger 1 causing spherocytosis and distal renal tubular acidosis.

dRTA (distal renal tubular acidosis) and HS (hereditary spherocytosis) are two diseases that can be caused by mutations in the gene encoding the AE1 (anion exchanger 1; Band 3). dRTA is characterized by defective urinary acidification, leading to metabolic acidosis, renal stones and failure to thrive. HS results in anaemia, which may require regular blood transfusions and splenectomy. Mutations in the gene encoding AE1 rarely cause both HS and dRTA. In the present paper, we describe a novel AE1 mutation, Band 3 Edmonton I, which causes dominant HS and recessive dRTA. The patient is a compound heterozygote with the new mutation C479W and the previously described mutation G701D. Red blood cells from the patient presented a reduced amount of AE1. Expression in a kidney cell line showed that kAE1 (kidney AE1) C479W is retained intracellularly. As kAE1 is a dimer, we performed co-expression studies and found that, in kidney cells, kAE1 C479W and G701D proteins traffic independently from each other despite their ability to form heterodimers. Therefore the patient carries one kAE1 mutant that is retained in the Golgi (G701D) and another kAE1 mutant (C479W) located in the endoplasmic reticulum of kidney cells, and is thus probably unable to reabsorb bicarbonate into the blood. We conclude that the C479W mutant is a novel trafficking mutant of AE1, which causes HS due to a decreased cell-surface AE1 protein and results in dRTA due to its intracellular retention in kidney.

Comparison of sequence and structure-based datasets for nonredundant structural data mining.

Structural data mining studies attempt to deduce general principles of protein structure from solved structures deposited in the protein data bank (PDB). The entire database is unsuitable for such studies because it is not representative of the ensemble of protein folds. Given that novel folds continue to be unearthed, some folds are currently unrepresented in the PDB while other folds are overrepresented. Overrepresentation can easily be avoided by filtering the dataset. PDB_SELECT is a well-used representative subset of the PDB that has been deduced by sequence comparison. Specifically, structures with sequences that exhibit a pairwise sequence identity above a threshold value are weeded from the dataset. Although length criteria for pairwise alignments have a structural basis, this automated method of pruning is essentially sequence-based and runs into problems in the twilight zone, possibly resulting in some folds being overrepresented. The value-added structure databases SCOP and CATH are also a potential source of a nonredundant dataset. Here we compare the sequence-derived dataset PDB_SELECT with the structural databases SCOP (Structural Classification Of Proteins) and CATH (Class-Architecture-Topology-Homology). We show that some folds remain overrepresented in the PDB_SELECT dataset while other folds are not represented at all. However, SCOP and CATH also have their own problems such as the labor-intensiveness of the update process and the problem of determining whether all folds are equally or sufficiently distant. We discuss areas where further work is required.

Evolution of distinct EGF domains with specific functions.

EGF domains are extracellular protein modules cross-linked by three intradomain disulfides. Past studies suggest the existence of two types of EGF domain with three-disulfides, human EGF-like (hEGF) domains and complement C1r-like (cEGF) domains, but to date no functional information has been related to the two different types, and they are not differentiated in sequence or structure databases. We have developed new sequence patterns based on the different C-termini to search specifically for the two types of EGF domains in sequence databases. The exhibited sensitivity and specificity of the new pattern-based method represents a significant advancement over the currently available sequence detection techniques. We re-annotated EGF sequences in the latest release of Swiss-Prot looking for functional relationships that might correlate with EGF type. We show that important post-translational modifications of three-disulfide EGFs, including unusual forms of glycosylation and post-translational proteolytic processing, are dependent on EGF subtype. For example, EGF domains that are shed from the cell surface and mediate intercellular signaling are all hEGFs, as are all human EGF receptor family ligands. Additional experimental data suggest that functional specialization has accompanied subtype divergence. Based on our structural analysis of EGF domains with three-disulfide bonds and comparison to laminin and integrin-like EGF domains with an additional inter-domain disulfide, we propose that these hEGF and cEGF domains may have arisen from a four-disulfide ancestor by selective loss of different cysteine residues.