Depression is a serious medical condition, typically treated by antidepressants. Conventional monotherapy can be effective only in 60–80% of patients, thus modern psychiatry deals with the challenge of new methods development. At the same moment, interactions between antidepressants and the occurrence of potential side effects raise serious concerns, which are even more exacerbated by the lack of relevant data on exact molecular mechanisms. Therefore, the aims of the study were to provide up-to-date information on the relative mechanisms of action of single antidepressants and their combinations. In this study, we evaluated the effect of single and combined antidepressants administration on mouse hippocampal neurons after 48 and 96 h in terms of cellular and biochemical features in vitro. We show for the first time that co-treatment with amitriptyline/imipramine + fluoxetine initiates in cells adaptation mechanisms which allow cells to adjust to stress and finally exerts less toxic events than in cells treated with single antidepressants. Antidepressants treatment induces in neuronal cells oxidative and nitrosative stress, which leads to micronuclei and double-strand DNA brakes formation. At this point, two different mechanistic events are initiated in cells treated with single and combined antidepressants. Single antidepressants (amitriptyline, imipramine or fluoxetine) activate cell cycle arrest resulting in proliferation inhibition. On the other hand, treatment with combined antidepressants (amitriptyline/imipramine + fluoxetine) initiates p16-dependent cell cycle arrest, overexpression of telomere maintenance proteins and finally restoration of proliferation. In conclusion, our findings may pave the way to better understanding of the stress-related effects on neurons associated with mono- and combined therapy with antidepressants.
The purpose of this study was to analyse the influence of simultaneous pancreas-kidney or kidney transplantation on endothelial function and systemic inflammation in type 1 diabetic patients with end-stage renal disease. In 39 simultaneous pancreas-kidney, 39 type 1 diabetic kidney and 52 non-diabetic kidney recipients, flow-mediated dilatation was measured. Additionally, blood glycated haemoglobin, serum creatinine and lipids, plasma nitrites [Formula: see text] and nitrates, asymmetric dimethylarginine, soluble vascular cell adhesion molecule-1, intercellular adhesion molecule-1, and E-selectin, high-sensitivity C-reactive protein, tumour necrosis factor-α, interleukin 1β and interleukin 6 concentrations were assessed. During 58 ± 31 months follow-up period, flow-mediated dilatation and [Formula: see text] were greater in simultaneous pancreas-kidney than in type 1 diabetic kidney recipients [10.4% ± 4.7% vs 7.7% ± 4.2%, p < 0.05 and 0.94 (0.74-1.34) vs 0.24 (0.20-0.43) μmol/L, p < 0.01, respectively]. In type 1 diabetic patients after simultaneous pancreas-kidney or kidney transplantation, [Formula: see text] correlated with flow-mediated dilatation (r = 0.306, p < 0.05) and with blood glycated haemoglobin (r = -0.570, p < 0.001). The difference in [Formula: see text] was linked to blood glycated haemoglobin and estimated glomerular filtration rate, whereas the difference in flow-mediated dilatation was linked to [Formula: see text]. The levels of inflammatory markers (except soluble vascular cell adhesion molecule-1) were similar in simultaneous pancreas-kidney and type 1 diabetic kidney recipients. Improved endothelial function in type 1 diabetic patients with end-stage renal disease after simultaneous pancreas-kidney compared to kidney transplantation is associated with normalisation of glucose metabolism but not with improvement in plasma pro-inflammatory cytokines.
The study introduces a case of a 51-year old patient with Caroli's disease of left liver lobe. In 2011 the patient was admitted to Clinic of General, Vascular and Transplantation Surgery. She was after first in her life incident of an acute pancreatitis and subsequent ERCP procedure with left hepatic biliary tract drainage. The lady was qualified to left-hemihepatoctomy, which was successfully conducted in our clinic. The only complication of the procedure was surgical site infection which was properly treated with typical antibiotics. One-year observation occurred no other complications and liver function was fine.
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