The association of sensitive systemic inflammation markers with bronchial asthma.

BACKGROUND: Airway inflammation is a characteristic feature of bronchial asthma. Previous studies have shown an increased local inflammatory activity in the airway mucosa of asthma patients. OBJECTIVES: To analyze the association of asthma with three sensitive markers of systemic inflammation, C-reactive protein, serum amyloid-A (SAA), and plasma fibrinogen. METHODS: A cross-sectional, population-based study including 1,513 Finnish men aged 45 to 74 years, who participated in a chronic disease risk factor survey in 1997. Of the participating men, 97 were classified as asthma patients. The odds ratios of asthma were analyzed by quartile of each inflammation marker. RESULTS: In logistic regression models the age-adjusted odds ratios (second, third, and fourth quartile as compared with the first quartile) of asthma increased gradually with increasing quartile of C-reactive protein (1.28, 1.19, 1.96, P for trend = 0.039), SAA (1.20, 3.00, 3.49, P for trend < 0.001), and fibrinogen (1.22, 1.79, 3.16, P for trend < 0.001). The associations were independent of smoking. Further adjustment for waist-to-hip ratio, a marker of central obesity, and symptoms of chronic bronchitis weakened the observed association, but the increasing trend in the association of SAA and fibrinogen with asthma remained highly significant. CONCLUSIONS: Sensitive markers of systemic inflammation, particularly SAA and fibrinogen, were positively and significantly associated with asthma prevalence. These findings support the hypothesis that not only local, but also systemic, inflammation exist in bronchial asthma.     

Raman and UV–vis spectroscopic study of polyaniline membranes containing a bulky cationic additive

Electrically conducting soluble polyaniline (PANI), containing different amounts of a bulky lipophilic cationic additive, tridodecylmethylammonium chloride (TDMACl), was studied by Raman (λ_exc=780 nm) and UV–vis spectroscopy. PANI was made simultaneously electrically conducting and soluble with bis[4-(1,1,3,3-tetramethylbutyl)phenyl]phosphoric acid in dichloromethane. The PANI membranes were prepared by drop casting on glassy carbon or ITO substrates. Raman and UV–vis measurements were carried out in a 0.1 M CaCl₂ solution at potentials between 400 and ?600 mV (vs. SCE) at pH 6, or alternatively at the open circuit potential at pH 10. The results of Raman, UV–vis and cyclic voltammetric measurements confirm that the incorporation of TDMACl into the PANI membrane facilitates the oxidation and reduction of PANI.     

CDK4 is a probable target gene in a novel amplicon at 12q13.3-q14.1 in lung cancer

Several chromosomal regions are recurrently amplified or deleted in lung tumors, but little is known about the underlying genes, which could be important mediators in tumor formation or progression. In lung cancer, the RB1-CCND1-CDKN2A pathway, involved in the G1-S transition, is damaged in nearly all tumors. In the present study, we localized a novel amplicon in lung tumors to a fragment of less than 0.5 Mb at 12q13.3-q14.1 by using comparative genomic hybridization (CGH) on cDNA microarrays. This approach enabled us to identify 10-15 genes with the most consistent amplifications. Semiquantitative RT-PCR analyses of 13 genes in this region showed that four of them (CDK4, CYP27B1, METTL1, and TSFM) were also highly up-regulated. Immunohistochemical (IHC) analysis of 141 tumor samples on a tissue microarray showed that CDK4 was expressed at a high level in 23% of lung tumors. Six (21.4%) of the tumors with high CDK4 expression (n = 28) were shown by fluorescence in situ hybridization (FISH) to contain the 12q13.3-q14.1 amplification. For CDK4, a positive correlation was found between gene copy number (FISH and CGH array), mRNA expression (RT-PCR), and level of protein expression (IHC). CDK4 expression did not correlate with CDKN2A methylation status. Amplification of CDK4 has been described in other tumor types, but its role in lung cancer remains to be elucidated. Although CDK4 amplification seems to be a relatively rare event (4.3%) in lung tumors, it indicates the significance of the RB1-CCND1 pathway in lung tumorigenesis.     

Bioactive glass as bone-graft substitute for posterior spinal fusion in rabbit

Bioactive glass S53P4 and autogenous bone were studied as bone graft materials for spinal fusion in a rabbit model. Sixteen rabbits underwent surgery by a dorsal approach. A bioactive glass, a combination of bioactive glass and autogenous bone (70/30 vol%), and autogenous bone were implanted at two thoracolumbar vertebraes for 4 and 12 weeks. The volume, consolidation to vertebrae, and fusion of the graft material were evaluated with plain-film radiology, computed tomography (CT) and bone-mineral density measurements, and compared with histomorphometrical measurements. Radiological consolidation by CT of bone graft to underlying vertebrae at 12 weeks was observable in all groups. This was histologically confirmed as bone was growing from the vertebrae into the graft material. Radiologic fusion of vertebraes was, at 12 weeks, observable in all groups in 50--75% of the cases. The radiologic fusion seen at the CT scans could, however, not be confirmed by histology in any of the three groups. Significant differences for graft material and observation period with the use of bone-mineral density measurements (Hounsfield units) were also observable, with the highest measured values for the bioactive glass group and the lowest for the autogenous bone group. The results indicate that bioactive glass have potential as bone-graft material in spinal fusion. The reliability of radiologic evaluation methods in spinal surgery using bone substitutes is also questioned and discussed.     

Delivery and stability of LHRH and Nafarelin in human skin: the effect of constant/pulsed iontophoresis.

Poor absorption and stability of peptides are the major obstacles concerning the development of therapeutically relevant iontophoretic devices for the transdermal delivery of peptides. The present study examined the impact of constant and pulsed (direct/alternating) current profiles on the transport and stability of two decapeptides LHRH and Nafarelin. The stability of these peptides was studied in a physiological buffer solution, with electrical current, and when the peptide solution was exposed to the stratum corneum or to the epidermal/dermal side of human skin. Pulsed direct current profile was shown to be the most efficient in transporting both LHRH and Nafarelin across the human epidermis. Furthermore, the percentage of intact LHRH in the receiver phase was slightly higher when a pulsed current profile was used. Both the peptides were stable in a physiological buffer and under the influence of current, but LHRH was degraded especially in contact with the dermal side of the skin. Altogether five hydrolytic degradation products of LHRH were observed, and they were identified by LC-ESI/MS and LC-ESI/MS/MS. No degradation products of Nafarelin were observed. It is concluded that the pulsed direct current profile may provide at least a partial solution for the transdermal delivery of peptides in terms of improved transport efficacy and peptide stability.     

Short DNA sequences and bacterial DNA induce esophageal,gastric, and colorectal cancer cell invasion

Toll‐like receptor 9 (TLR9) recognizes both bacterial and self‐DNA and it is abundantly expressed in the gastrointestinal tract. In this study, we investigated the influences of both bacterial DNA and specific short DNA sequences on TLR9‐mediated gastrointestinal cancer cell invasion. We assessed the effect of various DNA ligands on cellular invasion and on TLR9 and matrix metalloproteinase expression of three gastrointestinal cancer cell lines. DNA‐ligands described in this study include CpG‐ODN M362, 9‐mer (hairpin), human telomeric sequence h‐Tel22 G‐quadruplex, and bacterial DNAs from Escherichia coli and Helicobacter pylori. All of the DNAs studied were demonstrated to induce invasion in the studied cells. The DNA‐induced invasion was inhibited with a broad‐spectrum MMP inhibitor and partly also with chloroquine suggesting that it could be mediated via MMP activation, endosomal signaling, and TLR9. Interestingly, H. pylori DNA was shown to induce a more pronounced invasion in a gastric cancer cell line than in the other cell lines. Our results suggest that bacterial DNA as well as deoxynucleotides having stable secondary structures (i.e. hairpins or G‐quadruplex structures) may serve as endogenous, invasion‐inducing TLR9‐ligands and promote local progression and metastasis of cancers in the alimentary tract.