Liberation of the oxygen radical from peripheral human phagocytes (granulocytes and monocytes) in patients with chronic polyarthritis

Monocytes from patients with definite or classical rheumatoid arthritis show a significantly higher release of O2-radicals in the chemiluminescence assay (2925 X 10(3) cpm) than those of healthy volunteers (267 X 10(3) cpm) (p = 0.01). This difference does not appear in a similar test with granulocytes, which in both groups tested show a mean chemiluminescence of 2739 X 10(3) and 2547 X 10(3) cpm. The chemiluminescence of monocytes is clearly time-course dependent: in the morning we saw the least response, at noon the highest. Following our results, corticosteroids lower chemiluminescence significantly (p = 0.05), while non steroidal antirheumatic drugs and long-term therapy with gold compounds, etc., do not affect chemiluminescence.     

Lung strain and biological response in mechanically ventilated patients

Purpose  

Lung tissue may exhibit a biochemical response to excessive deformation. Since strain has been proposed as a marker of such deformation, we studied the relationships between strain and matrix remodeling and inflammation markers in mechanically ventilated patients with and without acute lung injury (ALI).     

Polymeric systems containing dual biologically active ions

This paper reports the synthesis and characterization of dual functional polymerizable salts containing quaternary ammonium cations ionically linked to non steroidal anti-inflammatory drugs (NSAIDs), and their polymers and copolymeric systems obtained with acrylic monomers of different hydrophilicity, e.g. methyl methacrylate and 2-hydroxyethyl methacrylate. NSAIDs used were meclofenamic acid, ketoprofen and ibuprofen. Sustained release of the NSAID from polymeric and copolymeric samples was observed over a period of 10 days and the hydrophobic/hydrophilic character of both the polymeric system and the drug played a role in the release behaviour. The antimicrobial activity of dual functional monomeric and polymeric derivatives was confirmed against Gram-positive and Gram-negative bacteria and polymeric compounds presented higher bactericidal action than the precursory monomers. The extracts of copolymeric samples had anti-inflammatory activity in a nitric oxide inhibitory assay on RAW 264.7 cells and they produced a NO inhibition around 80% within the first seven days.     

Complete coding sequences and haplotypic associations of HLA-B*0707, -B*1524, -B*4405, -B*4802, -DRB1*0409, -DRB1*0411, -DRB1*1115, -DRB1*1305, and the novel allele -DRB1*0709. Group-specific amplification of cDNA from DRB1 alleles associated to DRB3 and DRB4

We present here the characterization of the complete coding sequences, previously unavailable, of the human leukocyte antigen (HLA) alleles B*0707, B*1524, B*4405, B*4802, DRB1*0409, DRB1*0411, DRB1*1115, DRB1*1305, and that of a new allele, DRB1*0709. For the isolation of cDNA from the DRB1 gene, we designed a novel set of polymerase chain reaction (PCR) primers that makes it possible to amplify separately the groups of DRB1 alleles associated to each of the DRB3 and DRB4 loci. The primary structures, functional features, evolutionary relationships, haplotypic associations, and population distributions of each of the nine HLA-B and -DRB1 alleles reported here are reviewed.     

The silent KIR3DP1 gene (CD158c) is transcribed and might encode a secreted receptor in a minority of humans, in whom the KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1 genes are duplicated

Killer-cell Ig-like receptors (KIR) are structurally and functionally diverse, and enable human NK cells to survey the expression of individual HLA class I molecules, often altered in infections and tumors. Multiple events of non-reciprocal recombination have contributed to the rapid diversification of KIR. We show that approximately 4.5% of the individuals of a Caucasoid population bear a recombinant allele of KIR3DP1, officially designed KIR3DP1*004, that associates tightly with gene duplications of KIR3DP1, KIR2DL4 and KIR3DL1/KIR3DS1. The KIR3DP1 gene is normally silent, but the recombinant allele carries a novel promoter sequence and, as a consequence, is transcribed in all tested individuals. Messenger RNA of KIR3DP1*004 is made up of six exons; of these, exons 1-5 are similar to, and spliced like, those encoding the leader peptide and Ig-domains of KIR3D. By contrast, exon 6 is homologous to no other human KIR sequence, but only to possible homologs in chimpanzees and rhesus macaques, and encodes a short hydrophilic tail. The putative KIR3DP1*004 product, like those of the related genes LAIR-2 and LILRA3/ILT6/LIR4, is predicted to be secreted to the extracellular medium rather than anchored to the cell membrane.     

Antifungal drugs combinations: a patent review 2000-2015

Introduction: Combination therapy has emerged as an approach to improve the efficacy of antifungal drugs. Its main objective is to achieve synergistic interaction with higher antifungal properties and lower toxic effects than each substance alone.

Areas covered: Twenty-four patents disclosed in the period of 2000-2015 were covered in this review. Twenty of them were devoted to pharmacodynamic potentiation, while four were dedicated to pharmacokinetic actions.

Expert opinion: The common characteristic of most patents published in this area is that the main partner is a commercial antifungal drug. In the most innovative combinations the second component was either a modifier of proton homeostasis, an antibody, an inhibitor of the adhesion of epithelial or endothelial cells or a keratinolytic agent that improves the skin penetration. The evaluation of synergism is always made with simple in vitro methods, which constitutes a weakness of the disclosed patents, due to the lack of in vivo studies, since the in vitro tests cannot predict the in vivo behavior. Also, it is surprising that none of the patents analyze the toxicity of the new combinations, taking into account that one of the main objectives of the combinations is to reduce the toxicity of the existing antifungal drugs.