ABSTRACT
PTSD is associated with disturbed hepatic morphology and metabolism. Neuronal mitochondrial dysfunction is considered a subcellular determinant of PTSD, but a link between hepatic mitochondrial dysfunction and hepatic damage in PTSD has not been demonstrated. Thus, the effects of experimental PTSD on the livers of high anxiety (HA) and low anxiety (LA) rats were compared, and mitochondrial determinants underlying the difference in their hepatic damage were investigated. Rats were exposed to predator stress for 10 days. Then, 14 days post-stress, the rats were evaluated with an elevated plus maze and assigned to HA and LA groups according to their anxiety index. Experimental PTSD caused dystrophic changes in hepatocytes of HA rats and hepatocellular damage evident by increased plasma ALT and AST activities. Mitochondrial dysfunction was evident as a predominance of small-size mitochondria in HA rats, which was positively correlated with anxiety index, activities of plasma transaminases, hepatic lipids, and negatively correlated with hepatic glycogen. In contrast, LA rats had a predominance of medium-sized mitochondria. Thus, we show links between mitochondrial dysfunction, hepatic damage, and heightened anxiety in PTSD rats. These results will provide a foundation for future research on the role of hepatic dysfunction in PTSD pathogenesis.
Subject(s)
Stress Disorders, Post-Traumatic , Animals , Rats , Anxiety Disorders , Anxiety/etiology , Liver , MitochondriaABSTRACT
The differential diagnosis of prostate cancer is problematic due to the lack of markers with high diagnostic accuracy. We previously demonstrated the increased binding of IgG to human plasminogen (PLG) in plasma of patients with prostate cancer (PC) compared to healthy controls. Heavy and light chains of PLG (PLG-H and PLG-L) were immobilized on 96-well plates and the binding of IgG to PLG-H and PLG-L was analyzed in serum from 30 prostate cancer (PC) patients, 30 patients with benign prostatic hyperplasia (BPH) and 30 healthy controls using enzyme-linked immunosorbent assay (ELISA). Our results demonstrate that IgG from PC sera bind to PLG-H but not to PLG-L. This interaction occurred through the free IgG C-terminal lysine (Lys) that becomes exposed as a result of IgG conformational changes associated with proteolysis. Circulating levels of modified IgG with exposed C-terminal Lys (IgG-Lys) were significantly higher in PC patients than in healthy controls and in BPH. We used Receiver Operating Characteristic (ROC) analysis to calculate the sensitivity (SN) and specificity (SP) of circulating IgG-Lys for differentiating PC from BPH as 77% and 90%, respectively. The area under the curve (AUC) was 0.87. We demonstrated that the diagnostic accuracy of circulating levels of IgG-Lys is much higher than diagnostic accuracy of total PSA (tPSA).
ABSTRACT
OBJECTIVE: To review the mechanisms of endometriosis development, including those related to epigenetic mutations, cellular dysregulation, inflammatory processes, and oxidative stress. METHODS: A systematic literature review regarding current aspects of endometriosis etiology, genesis and development was performed using the PubMed, Google Scholar, and eLibrary databases. Keywords included endometriosis, etiology, development, genesis, associations and mechanisms. A multilingual search was performed. RESULTS: Several mechanisms underline the pathophysiological pathways for endometriosis development. Epigenetic mutations, external and internal influences, and chronic conditions have a significant impact on endometriosis development, survival and regulation. Several historically valid theories on endometriosis development were discussed, as well as updated findings. CONCLUSION: Despite recent advances, fundamental problems in understanding endometriosis remain unresolved. The identification of unknown circulating epithelial progenitors or stem cells that are responsible for epithelial growth in both the endometrium and endometriotic foci seems to be the next step in solving these questions.