[Systemic and renal effects of preventing contrast nephrotoxicity with isotonic (0.9%) and hypotonic (0.45%) saline]. / Efectos renales y sistémicos en la prevención de la nefrotoxicidad por contraste con sueros salino (0,9%) e hiposalino (0,45%).

INTRODUCTION AND OBJECTIVES: Physiological and hypotonic saline solutions have been used interchangeably for preventing contrast media nephrotoxicity. No analysis of the possible differential effects of the two solutions on the milieu interieur or intercompartmental fluid volumes has been performed. Our aim was to study the systemic and renal effects of two types of saline solution regularly used to prevent contrast media nephrotoxicity in patients undergoing coronary angiography. METHODS: Changes in electrolyte levels and volume distribution were studied in 71 individuals who were randomized to receive either 0.9% isotonic saline (n=36) or 0.45% hypotonic saline (n=35) during the 12 hours before and after contrast injection (2000 mL in each period). RESULTS: The creatinine level was elevated equally often in the isotonic and hypotonic saline groups. Isotonic saline administration led to reductions in hemoglobin level, hematocrit and plasma albumin level, and to increases in plasma volume, by 12.3% and 10.4% at 24 and 48 hours, respectively. These changes were significant compared with baseline measurements and compared with the group that received hypotonic saline. Neither of the two saline solutions resulted in a change in plasma atrial natriuretic peptide level. Plasma and urine osmolality decreased only with hypotonic saline. The increase in plasma creatinine level was similar with both isotonic and hypotonic saline. CONCLUSIONS: During standard therapy for preventing contrast media nephrotoxicity, (1) isotonic saline, but not hypotonic saline, increased plasma volume; (2) this increase did not raise the atrial natriuretic peptide level; and (3) no difference in the increase in serum creatinine level was observed between the two saline solutions. These findings provide evidence that 0.45% saline, at a dose suitable for preventing contrast media nephrotoxicity, is associated with a lower risk of volume expansion. This result is important for patients with severely impaired ventricular function.

Efectos renales y sistémicos en la prevención de la nefrotoxicidad por contraste con sueros salino (0.9%) e hiposalino (0.45%) / Systemic and renal effects of preventing contrast nephrotoxicity with isotonic (0.9%) and hypotonic (0.45%) saline

Introducción y objetivos. En la prevención de nefrotoxicidad por contraste se han empleado indistintamente suero salino fisiológico o hiposalino, sin analizarse las posibles diferencias de efecto en el medio interno y la distribución compartimental de volumen. Se estudiaron los efectos renales y sistémicos de dos tipos de suero salino, empleados según pauta de prevención de nefrotoxicidad por contraste en coronariografía. Métodos. Se estudiaron aspectos hidroelectrolíticos y de distribución de volumen en 71 individuos, aleatorizados a recibir suero salino isotónico al 0,9% (n = 36) o suero hiposalino al 0,45% (n = 35), durante las 12 h previas y las 12 h tras el contraste (2.000 ml en cada período). Resultados. La incidencia de elevación de creatinina en el grupo salino fue igual que en el hiposalino. El suero salino causó reducción en los valores de hemoglobina, hematocrito y albúmina plasmática, y un incremento del volumen plasmático (el 12,3 y el 10,4%, a las 24 y a las 48 h); estos cambios fueron significativos con respecto al estado basal y al grupo con suero hiposalino. Sin embargo, los sueros administrados no produjeron elevación del péptido natriurético auricular. Las osmolalidades plasmática y urinaria descendieron sólo con el suero hiposalino. Las elevaciones de creatinina plasmática fueron similares con el suero salino y con el hiposalino. Conclusiones. En una pauta preventiva estándar de la nefrotoxicidad por contraste: a) el suero salino, pero no el hiposalino, aumenta el volumen plasmático; b) este aumento no incrementa la concentración de péptido natriurético auricular, y c) no se ha detectado diferencias entre los sueros en la elevación de creatinina sérica. Estos resultados aportan evidencia de que el suero hiposalino, a la dosis preventiva de nefrotoxicidad por contraste, implica menos riesgo de expansión. Este dato es relevante en pacientes con función ventricular críticamente afectada (AU)

Introduction and objectives. Physiological and hypotonic saline solutions have been used interchangeably for preventing contrast media nephrotoxicity. No analysis of the possible differential effects of the two solutions on the milieu interieur or intercompartmental fluid volumes has been performed. Our aim was to study the systemic and renal effects of two types of saline solution regularly used to prevent contrast media nephrotoxicity in patients undergoing coronary angiography. Methods. Changes in electrolyte levels and volume distribution were studied in 71 individuals who were randomized to receive either 0.9% isotonic saline (n=36) or 0.45% hypotonic saline (n=35) during the 12 hours before and after contrast injection (2000 mL in each period). Results. The creatinine level was elevated equally often in the isotonic and hypotonic saline groups. Isotonic saline administration led to reductions in hemoglobin level, hematocrit and plasma albumin level, and to increases in plasma volume, by 12.3% and 10.4% at 24 and 48 hours, respectively. These changes were significant compared with baseline measurements and compared with the group that received hypotonic saline. Neither of the two saline solutions resulted in a change in plasma atrial natriuretic peptide level. Plasma and urine osmolality decreased only with hypotonic saline. The increase in plasma creatinine level was similar with both isotonic and hypotonic saline. Conclusions. During standard therapy for preventing contrast media nephrotoxicity, (1) isotonic saline, but not hypotonic saline, increased plasma volume; (2) this increase did not raise the atrial natriuretic peptide level; and (3) no difference in the increase in serum creatinine level was observed between the two saline solutions. These findings provide evidence that 0.45% saline, at a dose suitable for preventing contrast media nephrotoxicity, is associated with a lower risk of volume expansion. This result is important for patients with severely impaired ventricular function (AU)

Combining experimental data for structure determination of flexible multimeric macromolecules by molecular replacement.

A major effort has been made by the structural biology community to develop user-friendly software for the use of biologists. However, structural projects become more and more challenging and their solution often relies on a combination of information from various sources. Here, it is described how X-ray data, normal-mode analysis (NMA) and electron-microscopy (EM) data can be successfully combined in order to obtain a molecular-replacement (MR) solution for crystal structures containing multimeric molecules. NMA is used to simulate computationally the inherent internal flexibility of the monomer and thus enhance, together with the crystal noncrystallographic symmetry (NCS), the MR capabilities. NCS is also used to obtain a reliable EM reconstruction, which is then employed as a filter to construct oligomers starting from monomers. The feasibility of the direct use of EM reconstructions as a template for MR when the X-ray and EM data resolutions overlap is also discussed.

Crystal structure of an archaeal glycogen synthase: insights into oligomerization and substrate binding of eukaryotic glycogen synthases.

Glycogen and starch synthases are retaining glycosyltransferases that catalyze the transfer of glucosyl residues to the non-reducing end of a growing alpha-1,4-glucan chain, a central process of the carbon/energy metabolism present in almost all living organisms. The crystal structure of the glycogen synthase from Pyrococcus abyssi, the smallest known member of this family of enzymes, revealed that its subunits possess a fold common to other glycosyltransferases, a pair of beta/alpha/beta Rossmann fold-type domains with the catalytic site at their interface. Nevertheless, the archaeal enzyme presents an unprecedented homotrimeric molecular arrangement both in solution, as determined by analytical ultracentrifugation, and in the crystal. The C-domains are not involved in intersubunit interactions of the trimeric molecule, thus allowing for movements, likely required for catalysis, across the narrow hinge that connects the N- and C-domains. The radial disposition of the subunits confers on the molecule a distinct triangular shape, clearly visible with negative staining electron microscopy, in which the upper and lower faces present a sharp asymmetry. Comparison of bacterial and eukaryotic glycogen synthases, which use, respectively, ADP or UDP glucose as donor substrates, with the archaeal enzyme, which can utilize both molecules, allowed us to propose the residues that determine glucosyl donor specificity.

Crystallization and preliminary X-ray analysis of the glycogen synthase from Pyrococcus abyssi.

Glycogen synthase catalyzes the transfer of glucosyl residues from ADP- or UDP-glucose to the non-reducing end of a growing alpha-1,4-glucan chain. To date, no crystallographic structure of an animal/fungal glycogen synthase (family 3 of the glycosyl transferases) or a bacterial/plant glycogen/starch synthase (family 5) has been reported. This paper describes the recombinant expression, crystallization and preliminary X-ray analysis of the glycogen synthase from the hyperthermophilic archaeon Pyrococcus abyssi, the smallest enzyme of the members of families 3 and 5 of the glycosyl transferases. Crystals from this protein and from its selenomethionyl variant were grown in 100 mM sodium citrate pH 5.6 containing 20% PEG and 20% dioxane by the hanging-drop vapour-diffusion method at 293 K. The crystals, which grew as thin needles, diffracted to 3.5 A resolution and belong to space group C2, with unit-cell parameters a = 202, b = 73, c = 149 A, beta = 131 degrees. The crystallographic and biochemical data are consistent with either a dimer or a tetramer in the crystal asymmetric unit and a volume solvent content of 70 or 39%, respectively.

Effects of dehydroepiandrosterone-sulfate on the Apo E genotype influence on plasma lipid levels in prepubertal children.

Gender differences in the apolipoprotein (apo) E genotype effect on plasma lipid levels reported in adults have also been found in pre-pubertal children. In adults, the difference seems to be due to the influence of sexual hormones. The reason why this difference exits between pre-pubertal girls and boys, for whom those sexual hormones are not different, is unclear. However, there is an important difference in Dehydroepiandrosterone-sulfate (DHEA-S) levels between pre-pubertal boys and girls. To evaluate the influence of DHEA-S on apo E genetic determinants of plasma lipids levels in pre-pubertal children we measured plasma DHEA-S in 1045 healthy children (534 males and 511 females) 6 to 8 years old in which a different apoE influence on lipid levels had been reported between girls and boys. Our observations demonstrate that the extent of the lipid increasing or decreasing effects associated with each allele were modulated by DHEA-S. DHEA-S increases the hypolipemic effect of the epsilon2 allele and decreases the hyperlipemic effect of the epsilon4 allele. In conclusion, the interaction of apo E genotype and DHEA-S may represent a critical determinant of TC, LDL-C and apo B levels in children at the prepuberal age.