AIm: The aim of this study was to analyze the correlation between serum levels of inflammatory cytokines Il-1β, Il-6, TnF-α and vegF and the presence and severity of diabetic retinopathy (dR) in patients with type 2 diabetes mellitus (dM). PAtIents And methods: In this prospective study we included 38 healthy volunteers (group 1) and 39 patients with type 2 dM (group 2). all participants underwent routine ophthalmological examination and laboratory analysis of the serum cytokines Il-1β, Il-6, TnF-α and vegF. group 2 patients were additionally examined by colour fundus photography and fluorescein angiography to determine the dR stage. We studied the correlation of Il-1β, Il-6, TnF-α and vegF with the presence of dM, the presence and severity of dR, the duration of dM and dR, the serum levels of glycosylated haemoglobin, as well as with hyperlipidemia and the general indicators of inflammation -erythrocyte sedimentation rate (eSR) and fibrinogen. results: The group 2 patients had statistically significantly higher levels of Il-1β (р = 0.01) and Il-6 (р = 0.029) and elevated TnF-α and vegF levels in comparison with group 1 patients. group 2 patients were divided into 5 subgroups depending on the severity of dR: patients without dR (n = 11), patients with mild non-proliferative dR (n = 10), patients with moderate non-proliferative dR (n = 5), and patients with severe non-proliferative dR (n = 2) (total number of non-proliferative dR (n = 17)) and patients with proliferative dR (n = 11). The comparative analysis showed statistically significant differences in the serum levels of Il-1β (р = 0.003), TnF-α (р = 0.002) and vegF (р = 0.005) between the different subgroups. Patients with proliferative dR showed significantly higher values of serum Il-1β (р < 0.0001), Il-6 (р = 0.007), TnF-α (р = 0.002) and vegF (р < 0.0001) compared with the patients with non-proliferative dR. The cytokine serum levels did not correlate with the duration of dM, the duration of dR (except for Il-1β, р = 0.045), and hyperlipidemia (except for TnF-α, р = 0.05). TnF-α (р = 0.05) and vegF (р = 0.047) serum levels correlated with the levels of glycosylated hemoglobin, and Il-1β, TnF-α and vegF correlated with the general indicators of inflammation (eSR and fibrinogen). conclusIon: Serum concentrations of Il-1β, TnF-α and vegF have an effect on the development and progression of dR. They correlate with the presence and severity of the disease. Whether serum cytokines can play the role of a prognostic factor or serve as a means to choose a proper therapeutic agent for the treatment of diabetic retinopathy should be analyzed by further more extensive prospective longitudinal studies in future. key words: diabetic retinopathy, cytokines, interleukins, tumor necrosis factor-α, vascular endothelial growth factor abbreviations useD in the stuDy:

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Quantitative data on melatonin in stroke patients are scarce. A gender‐ and age‐matched cross‐sectional case–control study in 33 patients with ischaemic stroke was performed and associations between nocturnal melatonin and other factors (e.g. cortisol) were evaluated. Clinical and laboratory (e.g. melatonin and cortisol) measurements (03.00 h and 08.00 h) with statistical techniques [e.g. multifactorial regressions, receiver operating characteristic (ROC) curve and curvilinear estimations] were used. We identified mean value and 95% confidence interval (CI) (69.70 pg/ml; 95% CI = 53.86–85.54) for control levels of nocturnal melatonin in healthy subjects. The patients with stroke had lower melatonin (48.1 ± 35.9 pg/ml) and higher cortisol (297.3 ± 157.8 nmol/l) at 03.00 h (P < 0.05) but not at 08.00 h (P > 0.05). Stroke was the strongest factor of disturbed nocturnal cortisol (P < 0.001), whereas decreased melatonin depended on stroke (P = 0.010) and gender (P = 0.018). At the same time, vice versa, only nocturnal measures were associated with an increased probability of the presence of stroke (accuracy > 75%, Pmodel < 0.001). Thus, a hypothesis that a decrease of melatonin with 1.0 pg/ml might be associated with > 2% increase in the probability of the presence of stroke [adjusted odds ratio (OR) = 1.020; 95% CI = 1.002–1.037] was also suggested. The ROC curve (0.67, P = 0.0119) and optimisation techniques indicated that a novel best cut‐off < 51.5 pg/ml for decreased nocturnal melatonin in the view of the presence of stroke (OR = 3.12, P = 0.0463) might exist. The classification performance of such a cut‐off might be confirmed by existing nocturnal melatonin and cortisol differences between the sub‐groups; potential differences in diurnal melatonin were also suggested. In conclusion, a novel melatonin cut‐off of 51.5 pg/ml may be associated with the presence of ischaemic stroke. As a single marker (84% sensitivity, 74% specificity), it is hypothesised that modelling performance was independent of age, gender and cortisol. These new results, including the suggested hypothesis, might be further tested in follow‐up (cohort), longitudinal studies and be applied to explore melatonin disturbances as targets in high‐risk pre‐stroke and post‐stroke patients.

The results we obtained about the changes of melatonin in women with PCOS could help in elucidating the complex pathophysiological pattern of this disease.

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