The effect of proteinuria on urinary zinc and copper excretion was studied in children with nephrotic syndrome (NS). Clearance, fractional excretion, and urinary excretion of zinc and copper were significantly higher in children with relapse of NS than in the same children with remission of NS or in healthy children. A linear correlation was found between proteinuria and urinary zinc and copper excretion in relapse of NS. The results of this study suggest that zinc and copper deficiency in NS may be related also to increased urinary zinc and copper losses.

During the last decades, the application of hybrid quantum mechanical/molecular mechanical (QM/MM) methods has been extended to the field of drug design. In principle, the approximate QM/MM approach offers a more complete description of drug-receptor non-covalent interactions. This is especially true when charge or proton transfer, chelation of metal ions or strong polarization of ligand and protein or surface chemical groups are involved. The aim of this work was to assess the accuracy of calculated non-covalent ligand-protein interaction energies ([Formula: see text]) obtained by the hybrid QM/MM approach employed in QSite/Jaguar of Schrödinger's Small-Molecule Drug Discovery Suite on a set of small-molecule model systems when compared to rigorous QM calculations. The QM/MM approach was used at the density functional theory (DFT) level of theory with 6-31G* basis set, hybrid B3LYP functional and OPLS-2005 force field (DFT-B3LYP/6-31G*//OPLS-2005), a popular combination frequently used in studies on larger and complex biological systems such as drug-receptor complexes. In this work, we did not attempt to compute the most precise interaction energies of the model systems. We rather tried to assess the performance of the approximate QM/MM vs. full QM approach at the same computationally accessible level. For effective use of the QM/MM approach it is essential to select an appropriate QM region of the studied systems. To aid the selection of specific protein residues or functional groups to be included in the QM region, we evaluated the effect of its size, composition and symmetry on the accuracy of the QM/MM calculated [Formula: see text]. This was performed by means of a set of model clusters with well-defined configurations, which mimic the basic types of non-covalent interactions in proteins. Based on these systematic quantitative comparisons, recommendations for the addition of chemical groups or protein residues into the QM region are proposed for the popular DFT-B3LYP/6-31G*//OPLS-2005 QM/MM approach, leading to a more realistic description of ligand-protein interactions. These guidelines can have a significant bearing on computational drug or material research employing hybrid QM/MM methods by providing an estimate of the accuracy that can be expected from QM/MM studies. Graphical abstract An approximate hybrid QM/MM approach at the DFT-B3LYP/6-31G*//OPLS-2005 level was systematically assessed for the accuracy of description of non-covalent interactions on a series of six small-molecule model systems using the QSite and Jaguar modules of Schrödinger. Guidelines for rational selection of receptor residues or function groups to be included in the QM region around the ligand were proposed based on the achieved accuracy of computed ligand-protein interaction energies obtained by QM/MM vs. the full QM approach.

We simulated the use of massive volumes of crystalloid fluids as a treatment of acute plasma loss in a standardized experimental model and studied the factors determining the retention or excretion of the resulting acute hypoproteinemic fluid overload, its distribution within the body, and its treatment with concentrated albumin and diuretics. In accordance with the classic Starling concept, the serum protein level, i.e. the serum colloid osmotic pressure, determined the excretion/retention ratio of a given water and sodium load. Of the total fluid retention, fat and muscle each accommodated 25%, whereas the skin, which contributes only 7% to the total body weight, accounted for 37% and increased its volume by roughly one third. Concentrated albumin promoted fluid excretion in direct proportion to the achieved increment of the serum protein level and abolished the edema of fat, muscle and skin. Furosemide was virtually ineffective. The implications of these results for the 'adult respiratory distress syndrome' and disturbed wound healing are discussed and related to the concept of a critical threshold of the serum protein level.

Although melatonin did not accelerate blood pressure reduction, it attenuated EDCF-contractions and oxidative load and enlarged arterial diameter. These effects may be beneficial for cardiovascular protection.