Effect of antinuclear antibodies on pharmacokinetics of anti-TNF therapy in patients with inflammatory bowel disease.

PURPOSE: The detection of antinuclear antibodies (ANA) in serum of patients with inflammatory bowel disease (IBD) has been associated with a worse response to anti-TNF therapy and the development of cutaneous or arthritic manifestations. The aim of this study was to investigate a possible association of serum ANA with infliximab (IFX) and adalimumab (ADA) trough levels (TLs) and anti-drug antibodies in IBD patients treated with IFX or ADA. METHODS: Consecutive IBD patients under maintenance therapy with IFX or ADA in whom there was at least one available measurement of anti-TNF TLs, antibodies to IFX or ADA, and ANA in serum were included. The correlation of ANA positivity with demographics, clinical characteristics, treatment, TLs and anti-drug antibodies, of all patients was analyzed. RESULTS: One hundred two IBD patients under maintenance therapy with IFX or ADA were enrolled. Of these, 53 (52%) were ANA positive with 28 (27.5%) positive also to anti-ds-DNA in serum. In the univariate analysis ANA positivity was found to be correlated with age (P = 0.008), female gender (P = 0.03), duration of treatment (P = 0.06), arthralgias (P = 0.04) and TLs (P = 0.005). However, in multivariate logistic regression analysis only age and TLs remained significantly associated with the presence of ANA positivity (P = 0.04 and P = = 0.006, respectively). No significant association of ANA positivity with the development of cutaneous or rheumatological manifestations was found. CONCLUSIONS: In IBD patients under maintenance therapy with anti-TNF ANA positivity is associated with lower TLs. The clinical significance of this finding remains to be defined in future larger prospective studies.

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies.

A number of p-pyridinyl oxime carbamate derivatives were prepared upon the reaction of the corresponding oximes with isocyanates. These novel compounds reacted photochemically in the presence of supercoiled plasmid DNA. Structure-activity relationship (SAR) studies revealed that the substituent on the imine group was not affecting the extend of the DNA damage, whereas the substituent of the carbamate group was critical, with the halogenated derivatives to be able to cause extensive single and double stranded DNA cleavages, acting as "synthetic nucleases", independently of oxygen and pH. Calf thymus-DNA affinity studies showed a good-to-excellent affinity of selected both active and non-active derivatives. Preliminary theoretical studies were performed, in an effort to explain the reasons why some derivatives cause photocleavage and some others not, which were experimentally verified using triplet state activators and quenchers. These theoretical studies seem to allow the prediction of the activity of derivatives able to pass intersystem crossing to their triplet energy state and thus create radicals able to damage DNA. With this study, it is shown that oxime carbamate derivatives have the potential to act as novel effective photobase generating DNA-photocleavers, and are proposed as new leads for "on demand" biotechnological applications in drug discovery and medicine.

Association of miRNA-145 Single Nucleotide Polymorphisms in Abdominal Aortic Aneurysms.

BACKGROUND/AIM: MicroRNAs (miRNAs) are non-coding RNA molecules that exert post-transcriptional gene expression regulation in response to cellular or environmental changes. Genetic variation affects their synthesis and cellular actions, and single nucleotide polymorphisms (SNPs) are one example of genetic variants studied in relation to various diseases. Literature indicates that the differentially expressed miRNA-145 in patients' serum is an essential biomarker for abdominal aortic aneurysm (AAA). However, the correlation between specific miR-145 genetic polymorphisms with AAA susceptibility is inadequately studied. MATERIALS AND METHODS: Eighty-seven AAA patients and 122 healthy controls were recruited. Peripheral blood samples were genotyped for miRNA-145 SNPs; rs55945735, rs73798217 and rs353291. RESULTS: The GG genotype of the rs55945735 polymorphism (p=0.047) and the AG genotype of the rs353291 polymorphism (p=0.036) were overrepresented in AAA patients compared to healthy individuals, revealing an association with susceptibility to AAA development. CONCLUSION: SNPs rs55945735 and rs353291 are associated with AAA susceptibility.

B-cell activating factor (BAFF) expression is associated with Crohn's disease and can serve as a potential prognostic indicator of disease response to Infliximab treatment.

BACKGROUND: Several studies correlated elevated B-cell activating factor (BAFF) levels and its polymorphisms (SNPs) in patients with autoimmunity. Limited data existed regarding the role of BAFF in Crohn's Disease (CD) susceptibility and/or treatment response to infliximab. AIM: This study aims to evaluate BAFF expression in CD patients, investigate if its expression can predict response to infliximab treatment, and examine the association of BAFF SNPs with CD susceptibility. METHODS: One hundred twelve CD patients and 164 healthy controls were recruited. Serum BAFF levels were determined using an enzyme-linked immunosorbent assay. Participants were genotyped for rs9514828, rs1041569 and rs2893321 SNPs. RESULTS: Serum BAFF concentration was elevated in CD patients (472.86 ±â€¯223.60 pg/ml) compared with controls (128.16 ±â€¯70.10 pg/ml) before treatment. Responders to IFX treatment had increased serum BAFF levels at baseline (610.03 ±â€¯167.55 pg/ml) compared to non-responders (267.09 ±â€¯107 pg/ml). In responders, BAFF concentration reduced after IFX administration, while increased in non-responders. The rs1041569, TA and AA genotypes frequencies, and the minor allele A were increased significantly in CD patients, indicating an association of the SNP with CD susceptibility. CONCLUSIONS: Our study suggests that BAFF could be a potential biomarker of CD, while SNP rs1041569 was associated with CD susceptibility.