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A novel research objective is to identify new molecules in more readily accessible biological fluids that could be used in the diagnosis of multiple sclerosis (MS) and other demyelinating disorders. To compare the level of selected cytokines in tears between patients with MS or other demyelinating disorder and healthy controls. 84 patients with diagnosed MS during remission or with other demyelinating disease of the CNS and 70 healthy controls were enrolled in the study. Tears were collected without any stimulation and stored till the day of assessment. The concentration of selected cytokines was measured by the Bio-Plex Pro Human cytokine screening panel 27 cytokines assay according to the manufacturer's instructions. Statistical analysis was performed with Statistica 13. IL-1b level was significantly lower in the study group compared to the control group [3,6 vs 8.71, p < 0.001]. The same pattern was observed for IL-6 [3,1 vs 5.26, p = 0.027] and IL-10 [1,7 vs 10.92, p < 0.001] (Table 1). In the study group, IL-1RA (p = 0.015), IL-5 (p = 0.04), IL-9 (p = 0.014), and IL-15 (p = 0.037) showed significant correlations with age. In the total sample, IL-1Ra (p = 0.016) and IFN-g (p = 0.041) were significantly correlated with age, while in the control group, IL-8 (p = 0.09), MIP-1a (p = 0.009), and RANTES (p = 0.031) showed significant correlations. Our results show that MS and other demyelination diseases lead to decrease in the overall level of cytokines in tears. Further research is needed to determine the role of tear fluid in the assessment of demyelinating disorders like MS. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Patients with relapsing–remitting MS (RRMS) and secondary progressive MS (SPMS) differ in their responses to treatment; therefore, the correct diagnosis of the particular type of MS is crucial, and biomarkers that can differentiate between the forms of MS need to be identified. The aim of this study was to compare the levels of inflammatory parameters in serum samples from patients with RRMS and SPMS. The study group consisted of 60 patients with diagnosed MS. The patients were divided into RRMS and SPMS groups. In the RRMS patients, the usage of disease-modifying treatment was included in our analysis. The serum levels of inflammatory parameters were evaluated. The serum levels of BAFF, gp130 and osteopontin were significantly higher in SPMS patients than in RRMS patients. The serum levels of BAFF correlated with age in both RRMS and SPMS patients. The serum levels of MMP-2 were significantly higher in RRMS patients than in SPMS patients and correlated with the number of past relapses. The serum levels of IL-32 were significantly higher in RRMS treatment-naïve patients than in RRMS patients treated with disease-modifying therapy. Significant differences were found in BAFF, gp130, MMP-2 and osteopontin levels between RRMS and SPMS patients. Serum IL-32 levels were statistically lower in RRMS patients treated with disease-modifying therapy than in treatment-naïve patients. [ABSTRACT FROM AUTHOR]

Der p 23 is a major allergen of Dermatophagoides pteronyssinus, which could contribute to allergic asthma. The study compared the cytokine profile (Il-1beta, Il-4, Il-5, Il-6, Il-13, Il-17, TNF-alpha) in patients with allergic asthma, with confirmed allergy to D. pteronyssinus and with the presence or absence of allergy to Der p 23. Among 173 included patients, the following combinations were analyzed: profile A – Der p 1 (+), Der p 2 (+), and Der p 23 (−) observed in 38 (22%) patients; profile B – Der p 1 (+), Der p 2 (+), and Der p 23 (+) in 87 (50.3%) patients; and profile C – Der p 1 (−), Der p 2 (−), and Der p 23 (+) in 15 (8.7%) patients. The mean concentration of Il-1beta was significantly lower in profile A than in profiles B and C: 10.51 ± 5.22 (pg/ml) vs. 21.92 ± 11.34 vs. 23.1 ± 8.56 (A vs. B for p = 0.03 and A vs. C for p = 0.019). Similar trends were observed for Il-5: 38.5 ± 10.45 (pg/ml) vs. 94.8 ± 54.11 vs. 103.61 ± 34.9 (A vs. B for p = 0.008 and A vs. C for p = 0.001). The higher Il-1 and Il-5 activities observed in profiles B and C with Der p 23 (+) could be responsible for the more effective acceleration of allergic inflammation than in profile A with Der p 23. [ABSTRACT FROM AUTHOR]

10H-1,9-diazaphenothiazine was obtained in the sulphurisation reaction of diphenylamine with elemental sulphur and transformed into new 10-substituted derivatives, containing alkyl and dialkylaminoalkyl groups at the thiazine nitrogen atom. The 1,9-diazaphenothiazine ring system was identified with advanced 1H and 13C NMR techniques (COSY, NOESY, HSQC and HMBC) and confirmed by X-ray diffraction analysis of the methyl derivative. The compounds exhibited significant anticancer activities against the human glioblastoma SNB-19, melanoma C-32 and breast cancer MDA-MB-231 cell lines. The most active 1,9-diazaphenothiazines were the derivatives with the propynyl and N, N-diethylaminoethyl groups being more potent than cisplatin. For those two compounds, the expression of H3, TP53, CDKN1A, BCL-2 and BAX genes was detected by the RT-QPCR method. The proteome profiling study showed the most probable compound action on SNB-19 cells through the intrinsic mitochondrial pathway of apoptosis. The 1,9-diazaphenotiazine system seems to be more potent than known isomeric ones (1,6-diaza-, 1,8-diaza-, 2,7-diaza- and 3,6-diazaphenothiazine). [ABSTRACT FROM AUTHOR]

Many investigators have posited on the significant influence of lead on the immune system function. However, available data on this topic are not conclusive. Therefore, a study was undertaken to examine associations between lead exposure and levels of cytokines related to the T-helper (TH)-1, TH2, and TH17 types of immune response in humans. For these analyses, three population groups were examined: the first consisted of male workers exposed to lead for a short period of time (36–44 days); the second included male workers chronically exposed to lead (13 ± 10 years); and a control group that was composed of male administrative workers with blood lead levels (BLL) < 10 μg/dl. BLL were determined for all study subjects. Thereafter, serum samples were analyzed for the levels of interleukin (IL)-2 (IL-2), IL-4, IL-5, IL-12, IL-13, IL-17A, and interferon (IFN)-γ using a multi-analyte system. The results indicated that the levels of IFNγ IL-2, IL-12 (related to TH1 cells), IL-4, IL-5, IL-13 (related to TH2 cells), and IL-17A (related to TH17 cells) did not change after a short-term exposure to lead (compared to baseline). However, the levels of all of these cytokines were significantly higher in workers chronically exposed to lead than in the controls by 82%, 32%, 81%, 22%, 70%, 42%, and 17% (IFNγ, IL-2, IL-12, IL-4, IL-5, IL-13, IL-17A, respectively). From these studies, we conclude that in humans, a short-term exposure to lead does not affect levels of cytokines related to the TH1-, TH2-, and TH17-mediated immune responses, while chronic exposure modifies their levels. Taken together, these modifications do not evidence an ability of lead to promotespecificallyone type of immune response in an exposed host. [ABSTRACT FROM AUTHOR]

The title compounds were obtained from appropriate 5-substituted uracil derivatives and 1,2-oxy-3-methoxypropane in the presence of sodium hydride. Under similar conditions 5-iodouracil gave 2-methoxymethyl-2,3-dihydro-oxazolo[3,2-c]pyrimidine-5,7-dione as a result of intramolecular cine type nucleophilic substitution. Cytotoxicity of 1-(2-hydroxy-3-methoxypropyl)-5-substituted uracil derivatives against L1210 and macrophage RAW 264.7 cells in vitro was examined. [ABSTRACT FROM AUTHOR]