Topical Tranexamic Acid Compared With Anterior Nasal Packing for Treatment of Epistaxis in Patients Taking Antiplatelet Drugs: Randomized Controlled Trial

Objective

We evaluated the efficacy of topical application of the injectable form of tranexamic acid (TXA) compared with anterior nasal packing (ANP) for the treatment of epistaxis in patients taking antiplatelet drugs (aspirin, clopidogrel, or both) who presented to the emergency department (ED).

Methods

A randomized, parallel‐group clinical trial was conducted at two EDs. A total of 124 participants were randomized to receive topical TXA (500 mg in 5 mL) or ANP, 62 patients per group. The primary outcome was the proportion of patients in each group whose bleeding had stopped at 10 minutes. Secondary outcomes were the rebleeding rate at 24 hours and 1 week, ED length of stay (LOS), and patient satisfaction.

Results

Within 10 minutes of treatment, bleeding was stopped in 73% of the patients in the TXA group, compared with 29% in the ANP group (difference = 44%, 95% confidence interval, 26% to 57%; p < 0.001). Additionally, rebleeding was reported in 5 and 10% of patients during the first 24 hours in the TXA and the ANP groups, respectively. At 1 week, 5% of patients in the TXA group and 21% of patients in the ANP group had experienced recurrent bleeding (p = 0.007). Patients in the TXA group reported higher satisfaction scores (median [interquartile range {IQR}], 9 [8–9.25]) compared with the ANP group (median [IQR] = 4 [3–5]; p < 0.001). Discharge from the ED in <2 hours was achieved in 97% of patients in the TXA group versus 13% in the ANP group (p < 0.001). There were no adverse events reported in either group.

Conclusions

In our study population, epistaxis treatment with topical application of TXA resulted in faster bleeding cessation, less rebleeding at 1 week, shorter ED LOS, and higher patient satisfaction compared with ANP.     

An in vitro study on the effect of vinca alkaloid,vinorelbine, on chromatin histone,HMGB proteins and induction of apoptosis in mice non-adherent bone marrow cells

Context: Vinoreline is a vinca alkaloid anticancer drug widely used in cancer therapy. Drugs are not target specific, therefore might affect normal tissues/cells, in which bone marrow is the important one. Objective: To elucidate the cytotoxic and genotoxic effect of vinca alkaloid anti cancer drug, vinorelbine, on mice non-adherent bone marrow cells in vitro. Materials and methods: Non-adherent bone marrow cells were isolated and exposed to various concentrations (0–160?µg/ml) for 4?h at 23?°C. The chromatin proteins were analyzed by SDS PAGE and western blot. Fluorescent dye staining of the cells, anion superoxide and DNA fragmentations assays were also employed. Result: The results from MTT and trypan blue exclusion assays represented reduction of the cells viability. Extractability of histones and HMG proteins contrasted with difficulty as their content was decreased on SDS-gel upon increasing drug concentration as western blots confirmed it. The amount of degradation form of PARP (89?KD) increased significantly in a dose dependent manner. Increase in anion superoxide production and DNA fragmentation together with cytological detection of chromatin condensation and cellular damage upon exposure of the cells to vinorelbine were indicative of apoptosis induction in these normal cells. Conclusion: Vinorelbine is genotoxic in non-adherent bone marrow cells as affects chromatin components, DNA, histone and HMGB1 proteins and induces apoptosis.     

DCLK1, a promising colorectal cancer stem cell marker,regulates tumor progression and invasion through miR-137 and miR-15a dependent manner

Cancer stem cells (CSCs) are thought to be a major player in tumor initiation, progression, and metastasis. Targeting CSCs for elimination presents a promising therapeutic strategy; however, this approach will require a stronger understanding of CSC biology and identification of CSC-specific markers. The present study was conducted to examine the correlation between DCLK1 and miR-137 and miR-15a levels in colorectal cancer. A total of 222 samples, including 181 colorectal cancer specimens, 24 adenomatosis, and 17 non-adenomatosis colonic polyps, were stained for DCLK1 expression using immunohistochemistry. Also, expression of miR-137 and miR-15a was assessed in colorectal cancer with high and low DCLK1 expression levels. Most colorectal cancer specimens (76%) showed strong expression of DCLK1, whereas only 21% of adenomatous and none of non-adenomatous colonic polyps showed strong DCLK1 expression. A significant difference in DCLK1 expression was found between colorectal cancer, adenomatous, and non-adenomatous colonic polyps (P < 0.001). Higher expression of DCLK1 was more frequently detected in colorectal cases with larger tumor size (P = 0.03), poor differentiation (P = 0.03), and lymph node involvement (P = 0.04). Comparison of miR-137 and miR-15a in colorectal cancer cases revealed a significant inverse correlation with DCLK1 expression (P = 0.03 and P = 0.04, respectively). DCLK1 may act as a candidate marker for colorectal cancer stem cells. The critical role of DCLK1 in colorectal cancer suggests that it may represent an early diagnostic marker and therapeutic target; however, further investigation is warranted.

     

Protective effects of glycyrrhizin on sub-chronic diazinon-induced biochemical,hematological alterations and oxidative stress indices in male Wistar rats

The aim of this study was to elucidate the protective effect of glycyrrhizin on diazinon-induced changes in body and organ weights, blood hematology, lipid profile, biochemistry parameters and tissue markers of oxidative stress in male Wistar rats over a 7-week period. Rats were orally given sublethal dose of diazinon (10?mg/kg daily; 0.008 LD50), while glycyrrhizin (25?mg kg^?1 daily) was given alone or in combination with diazinon. At the end of 7th week, statistically significant decrease of pseudocholinesterase activity was detected when diazinon- and glycyrrhizin?+?diazinon-treated groups were compared to the control group. Diazinon treated rats showed weight loss and organ weight changes which were comparable to other groups. There was a statistically significance in hematological indices except mean corpuscular hemoglobin (MCH) when diazinon treated group was compared to glycyrrhizin?+?diazinon treated rats. Glycyrrhizin protected the liver and kidney from diazinon toxic effects with significantly decrease in serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and lactate dehydrogenase activities as well as ameliorated hepatic and renal function indices (such as bilirubin, total protein, albumin, BUN, creatinine glucose). In addition, glycyrrhizin minimized the hazardous effect of diazinon on plasma lipids and lipoproteins. The protective effects of glycyrrhizin were confirmed by tissue markers of oxidative stress analysis as glycyrrhizin in combination diminished malondialdehyde and glycyrrhizin alone or in combination enhanced thiol group and the ferric reducing power. In accordance to these results, our observations demonstrated the beneficial effects of glycyrrhizin in reducing the toxicity of diazinon.