Increased expression of the proprotein convertase enzyme FURIN in rheumatoid arthritis.

OBJECTIVE: FURIN is a proprotein convertase enzyme that inhibits the proinflammatory function of T cells and myeloid cells. Elevated FURIN expression levels have been reported in immune-mediated diseases, such as primary Sjögren's syndrome. Here, we investigated the levels of FURIN in peripheral blood (PB) and synovial fluid (SF) leucocytes from patients with rheumatoid arthritis (RA). METHOD: FURIN mRNA expression in PB and SF cells was determined by quantitative reverse transcription-polymerase chain reaction and FURIN plasma levels were measured using enzyme-linked immunosorbent assay. Associations between FURIN levels and demographic and clinical characteristics of the patients were determined. RESULTS: FURIN levels were significantly elevated in PB and SF mononuclear cells, T cells, and monocytes from RA patients compared to healthy controls. High FURIN levels were significantly associated with the prevailing prednisolone treatment, higher prednisolone doses, and increased C-reactive protein levels and Health Assessment Questionnaire values. CONCLUSION: FURIN is significantly upregulated in RA PB and SF leucocytes, suggesting that it may have a role in the pathogenesis of RA. In addition, our results suggest that elevated FURIN expression is associated with the indicators of more severe RA.

Finnish Dentists Find Smoking Cessation Important but Seldom Offer Practical Support for Their Patients.

OBJECTIVES: To investigate Finnish dentists' smoking cessation related attitudes, consultation practices and familiarity with the local treatment guideline on smoking cessation. BASIC RESEARCH DESIGN: An online questionnaire was sent to 1740 dentists, which corresponds to 39% of dentists in Finland. A total of 456 dentists responded (response rate 26%), of whom 435 (95%) were clinicians. The dentists' smoking cessation practices were also compared to ones reported in a previous study in Finnish physicians. RESULTS: Dentists found smoking cessation important and often discussed and recommended quitting to the patients, but concrete withdrawal actions were seldom provided. The local treatment guideline on smoking cessation was actively utilized by 36% of the dentists. Adherence to the guideline was associated with higher rates of smoking cessation activities and success in them. Smoking cessation activity among dentists was significantly lower than in Finnish physicians. In accordance with the literature, among dentists, the most common barriers for smoking cessation were lack of time (44%) and education (42%). CONCLUSION: Although smoking cessation is discussed with patients, dentists are less active in taking concrete actions to support the patient on withdrawal. Adherence to the local treatment guideline was associated with better capabilities in dealing with tobacco withdrawal and a more active role in smoking cessation. The results suggest that more education on the local smoking cessation treatment guideline and cessation intervention is needed in order to overcome the remaining barriers to promoting effective smoking cessation in dental practice.

Assessment of PARP protein expression in epithelial ovarian cancer by ELISA pharmacodynamic assay and immunohistochemistry.

Targeting Poly (ADP-ribose) polymerase 1 (PARP-1) involved in base excision repair (BER) has been shown to be a clinically effective treatment strategy in epithelial ovarian cancer (EOC) defective in homologous recombination (HR). The aim of this study was to evaluate fresh EOC tumor tissue in regard to PAR (Poly (ADP-ribose)) concentration as a surrogate marker for PARP activity and PARP protein expression in archival samples by immunohistochemistry (IHC). The prospective study cohort consisted of 57 fresh tumor samples derived from patients undergoing primary (n = 38) or interval debulking surgery (n = 19) for EOC and parallel archival paraffin-embedded tumor samples. PARP activity in fresh frozen tumor tissue was assessed by an enzymatic chemiluminescence assay and PARP protein expression in paraffin-embedded tumor tissue by IHC. No correlation was detected between PARP enzyme activity and PARP staining by IHC (p = 0.82). High PARP activity was associated with platinum sensitivity both in the entire study cohort (p = 0.022) and in the high-grade subgroup (p = 0.017). High PARP activity was also associated with improved progression-free survival (PFS) (32 vs 14 months, log-rank p = 0.009). However, PARP immunostaining pattern was not predictive of patient survival. In conclusion, we present a novel finding of high PARP activity associated with platinum sensitivity and improved PFS in EOC. There was no association between PARP IHC and pharmacodynamic assay, and the correlation of PARP IHC with clinico-pathological characteristics and patient survival was poor. Pharmacodynamic assay rather than IHC seems to reflect better biologically significant PARP.