SYNTHESIS, CHARACTERIZATION AND ANTIMICROBIAL STUDIES OF SOME LANTHANIDE (III) COMPLEXES WITH A TRIDENTATE ONO DONOR SCHIFF BASE LIGAND

Some new lanthanide(III) complexes- La(III), Ce(III), Pr(III) and Nd(III) have been synthesised from Schiff base ligand 4-{[(2-hydroxyphenyl)imino]methyl}-1,5-dimethyl-2-phenyl-1,2-dihydro-3H-pyrazol-3-one (L1) whose precursors are 4-antipyrine carboxaldehyde and 2-aminophenol. The metal to ligand ratio (1:2) and the general formula [Ln(L1)2(NO3)2]NO3 were established by elemental analysis, conductivity measurements, spectral techniques such as IR, UV-Visible, 1H NMR as well as magnetic susceptibility measurements. L1 behave as a neutral tridentate (ONO) ligand and Ln(III) ion display coordination number eight in all complexes. The Schiff base and complexes were screened for their in vitro antimicrobial activities against selected human pathogenic bacteria by agar disc diffusion method. Most of the synthesized complexes were found to be more potent bactericides than the corresponding free ligand

Increased Matrix Metalloproteinase (MMPs) Levels Do Not Predict Disease Severity or Progression in Emphysema

Rationale: Though matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema. Methods: Enzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period. Main Results: Compared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline. Conclusions: MMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease. © 2013 D'Armiento et al

Evaluation of copy number variation and gene expression in neurofibromatosis type-1-associated malignant peripheral nerve sheath tumours

Background Neurofibromatosis type-1 (NF1) is a complex neurogenetic disorder characterised by the development of benign and malignant tumours of the peripheral nerve sheath (MPNSTs). Whilst biallelic NF1 gene inactivation contributes to benign tumour formation, additional cellular changes in gene structure and/or expression are required to induce malignant transformation. Although few molecular profiling studies have been performed on the process of progression of pre-existing plexiform neurofibromas to MPNSTs, the integrated analysis of copy number alterations (CNAs) and gene expression is likely to be key to understanding the molecular mechanisms underlying NF1-MPNST tumorigenesis. In a pilot study, we employed this approach to identify genes differentially expressed between benign and malignant NF1 tumours. Results SPP1 (osteopontin) was the most differentially expressed gene (85-fold increase in expression), compared to benign plexiform neurofibromas. Short hairpin RNA (shRNA) knockdown of SPP1 in NF1-MPNST cells reduced tumour spheroid size, wound healing and invasion in four different MPNST cell lines. Seventy-six genes were found to exhibit concordance between CNA and gene expression level. Conclusions Pathway analysis of these genes suggested that glutathione metabolism and Wnt signalling may be specifically involved in NF1-MPNST development. SPP1 is associated with malignant transformation in NF1-associated MPNSTs and could prove to be an important target for therapeutic intervention

Increased matrix metalloproteinase (MMPs) levels do not predict disease severity or progression in emphysema.

RationaleThough matrix metalloproteinases (MMPs) are critical in the pathogenesis of COPD, their utility as a disease biomarker remains uncertain. This study aimed to determine whether bronchoalveolar lavage (BALF) or plasma MMP measurements correlated with disease severity or functional decline in emphysema.MethodsEnzyme-linked immunosorbent assay and luminex assays measured MMP-1, -9, -12 and tissue inhibitor of matrix metalloproteinase-1 in the BALF and plasma of non-smokers, smokers with normal lung function and moderate-to-severe emphysema subjects. In the cohort of 101 emphysema subjects correlative analyses were done to determine if MMP or TIMP-1 levels were associated with key disease parameters or change in lung function over an 18-month time period.Main resultsCompared to non-smoking controls, MMP and TIMP-1 BALF levels were significantly elevated in the emphysema cohort. Though MMP-1 was elevated in both the normal smoker and emphysema groups, collagenase activity was only increased in the emphysema subjects. In contrast to BALF, plasma MMP-9 and TIMP-1 levels were actually decreased in the emphysema cohort compared to the control groups. Both in the BALF and plasma, MMP and TIMP-1 measurements in the emphysema subjects did not correlate with important disease parameters and were not predictive of subsequent functional decline.ConclusionsMMPs are altered in the BALF and plasma of emphysema; however, the changes in MMPs correlate poorly with parameters of disease intensity or progression. Though MMPs are pivotal in the pathogenesis of COPD, these findings suggest that measuring MMPs will have limited utility as a prognostic marker in this disease

Association between quartile of BALF protein expression and clinical parameters.

<p>The mean values of age, pack years, FEV1% predicted, FEV1/FVC % predicted, TLC % predicted, CT score and St. George questionnaire total score were calculated for each quartile of MMP-1, -9, -12 and TIMP-1 BALF protein expression. Bold indicates p<0.05 compared to quartile 1. Parentheses () indicate standard deviation.</p

Quartiles of MMP protein expression.

<p>Minimum to 25% represented quartile 1 (Q1), 26% to Median represented quartile 2 (Q2), Median to 75% represented quartile 3 (Q3) and 75% to Maximum represented quartile 4 (Q4).</p

Correlation between plasma MMP/TIMP levels and % change in FEV1.

<p>Plasma protein levels for MMP-1, -9 and TIMP-1 were correlated with the % change from baseline in FEV1 at 6, 9 and 18 months of follow up. The coefficient of determination (R²) was calculated for each value at each time point.</p

Correlation between BALF MMP/TIMP levels and % change in FEV1.

<p>BALF protein levels for MMP-1, -9 and TIMP-1 were correlated with the % change from baseline in FEV1 at 6, 9 and 18 months of follow up. The coefficient of determination (R²) was calculated for each value at each time point.</p