Investigation of the correlation between ADMA levels and carotid artery intima-media thickness in rheumatoid arthritis patients [Romatoid artritli hastalarda ADMA düzeyleri ile karotid arter intima-media kali{dotless}nli{dotless}gi{dotless} arasi{dotless}ndaki i·lişkinin saptanmasi{dotless}]

Objective: Plasma asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthesis, is related to increased cardiovascular risks, endothelial dysfunction and atherosclerosis. Carotid artery intima-media thickness (IMT) is closely related to the risk of coronary artery disease. We aimed to investigate plasma ADMA levels and its relation to carotid IMT in patients with rheumatoid arthritis (RA). Materials and Methods: Eighteen Turkish patients with RA (16 females, mean age: 49.44±8.88 years) and 18 age- and gender-matched healthy controls (16 females, mean age: 46.28±4.97 years) were included in the study. Measurement of IMT was done by B-mode ultrasound. Plasma ADMA levels and carotid IMT of both sides were measured in all patients and healthy controls, and the means of the two groups were compared. The correlation between ADMA levels and carotid IMT was assessed in patients with RA. Results: Plasma ADMA levels were significantly higher in patients compared to healthy controls. Although the carotid IMT values were relatively higher in the patient group than in the control group, the difference was not statistically significant. There was no significant correlation between ADMA levels and carotid IMT values. Conclusion: Our findings support the notion that plasma ADMA levels are elevated in patients with RA. Despite lack of correlation between ADMA levels and IMT in our study, ADMA levels can be used to evaluate endothelial dysfunction. © Turkish Journal of Physical Medicine and Rehabilitation, Published by Galenos Publishing

10 H

Breast cancer is one of the leading causes of death in cancer categories, followed by lung, colorectal, and ovarian among the female gender across the world. 10H-3,6-diazaphenothiazine (PTZ) is a thiazine derivative compound that exhibits many pharmacological activities. Herein, we proceed to investigate the pharmacological activities of PTZ toward breast cancer MCF-7 cells as a representative in vitro breast cancer cell model. The PTZ exhibited a proliferation inhibition (IC50 = 0.895 µM) toward MCF-7 cells. Further, cell cycle analysis illustrated that the S-phase checkpoint was activated to achieve proliferation inhibition. In vitro cytotoxicity test on three normal cell lines (HEK293 normal kidney cells, MCF-10A normal breast cells, and H9C2 normal heart cells) demonstrated that PTZ was more potent toward cancer cells. Increase in the levels of reactive oxygen species results in polarization of mitochondrial membrane potential (ΔΨm), together with suppression of mitochondrial thioredoxin reductase enzymatic activity suggested that PTZ induced oxidative damages toward mitochondria and contributed to improved drug efficacy toward treatment. The RT2 PCR Profiler Array (human apoptosis pathways) proved that PTZ induced cell death via mitochondria-dependent and cell death receptor-dependent pathways, through a series of modulation of caspases, and the respective morphology of apoptosis was observed. Mechanistic studies of apoptosis suggested that PTZ inhibited AKT1 pathways resulting in enhanced drug efficacy despite it preventing invasion of cancer cells. These results showed the effectiveness of PTZ in initiation of apoptosis, programmed cell death, toward highly chemoresistant MCF-7 cells, thus suggesting its potential as a chemotherapeutic drug