Tramadol Pretreatment Enhances Ketamine-Induced Antidepressant Effects and Increases Mammalian Target of Rapamycin in Rat Hippocampus and Prefrontal Cortex

Several lines of evidence have demonstrated that acute administration of ketamine elicits fast-acting antidepressant effects. Moreover, tramadol also has potential antidepressant effects. The aim of this study was to investigate the effects of pretreatment with tramadol on ketamine-induced antidepressant activity and was to determine the expression of mammalian target of rapamycin (mTOR) in rat hippocampus and prefrontal cortex. Rats were intraperitoneally administrated with ketamine at the dose of 10 mg/kg or saline 1 h before the second episode of the forced swimming test (FST). Tramadol or saline was intraperitoneally pretreated 30 min before the former administration of ketamine or saline. The locomotor activity and the immobility time of FST were both measured. After that, rats were sacrificed to determine the expression of mTOR in hippocampus and prefrontal cortex. Tramadol at the dose of 5 mg/kg administrated alone did not elicit the antidepressant effects. More importantly, pretreatment with tramadol enhanced the ketamine-induced antidepressant effects and upregulated the expression of mTOR in rat hippocampus and prefrontal cortex. Pretreatment with tramadol enhances the ketamine-induced antidepressant effects, which is associated with the increased expression of mTOR in rat hippocampus and prefrontal cortex

Hypoxia-inducible factor-2a is associated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma

<p>Abstract</p> <p>Background</p> <p>Breast cancer is the most common cancer and the leading cause of cancer mortality in women worldwide. Hypoxia is an important factor involved in the progression of solid tumors and has been associated with various indicators of tumor metabolism, angiogenesis and metastasis. But little is known about the contribution of Hypoxia-Inducible Factor-2a (HIF-2a) to the drug resistance and the clinicopathological characteristics in breast cancer.</p> <p>Methods</p> <p>Immunohistochemistry was employed on the tissue microarray paraffin sections of surgically removed samples from 196 invasive breast cancer patients with clinicopathological data. The correlations between the expression of HIF-2a and ABCG2 as well as other patients' clinicopathological data were investigated.</p> <p>Results</p> <p>The results showed that HIF-2a was expressed in different intensities and distributions in the tumor cells of the breast invasive ductal carcinoma. A positive staining for HIF-2a was defined as a brown staining observed mainly in the nucleus. A statistically significant correlation was demonstrated between HIF-2a expression and ABCG2 expression (p = 0.001), histology-grade (p = 0.029), and Ki67 (p = 0. 043) respectively.</p> <p>Conclusion</p> <p>HIF-2a was correlated with ABCG2 expression, histology-grade and Ki67 expression in breast invasive ductal carcinoma. HIF-2a could regulate ABCG2 in breast cancer cells, and could be a novel potential bio-marker to predict chemotherapy effectiveness. The hypoxia/HIF-2a/ABCG2 pathway could be a new mechanism of breast cancer multidrug-resistance.</p> <p>Virtual slides</p> <p>http://www.diagnosticpathology.diagnomx.eu/vs/2965948166714795</p

Most of the pelvic floor muscle functions in women differ in different body positions, yet others remain similar: systematic review with meta-analysis

ObjectivesThis systematic literature review and meta-analysis aimed to determine the effect of body position on the measurement of pelvic floor muscle (PFM) contractility and to analyze the influential factors.Data sourcesFive databases (PubMed, Web of Science, EMBASE, Cochrane Library and Scopus) were searched for relevant studies published up to 12nd October 2023.Study selection or eligibility criteriaIncluded cross-sectional studies had to involve the assessment of pelvic floor muscle function in at least two positions.Study appraisal and synthesis methodsWe calculated standardized mean difference (SMD) with 95% confidence intervals (CI) to ascertain the potential effect of body position on outcomes.ResultsIn total, we included 11 cross-sectional studies to ascertain the potential effect of body position on outcomes. There was no statistical difference in the results of maximum voluntary contraction (MVC) of the pelvic floor muscles when assessed in between supine and standing positions (SMD −0.22; 95% CI −0.72 to 0.28; p = 0.38). The results of the meta-analysis showed significantly larger values of resting voluntary contractions (RVC) measured in the standing position compared to the supine position (SMD −1.76; 95% CI −2.55 to −0.97; p &lt; 0.001). Moreover, pelvic floor muscle movement during pelvic floor muscle contraction in the standing position was significantly better than that measured in the supine position (SMD −0.47; 95% CI −0.73 to 0.20; P &lt; 0.001).ConclusionThe results of this study showed that the RVC and PFM movement varied with the position of the assessment. In contrast, MVC values are independent of the assessment position and can be selected according to clinical needs.Systematic review registrationPROSPERO, identifier CRD42022363734, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022363734