Intraoperative Use of Epsilon Amino Caproic Acid and Tranexamic Acid in Surgeries Performed Under Cardiopulmonary Bypass: a Comparative Study To Assess Their Impact On Reopening Due To Postoperative Bleeding

BACKGROUND: Open heart surgeries under cardiopulmonary bypass are associated with excessive perioperative bleeding that often requires reoperation. Antifibrinolytics like epsilon aminocaproic acid and tranexamic acid are widely used to control bleeding. There are limited studies primarily showing the impact of these drugs on the incidence of reopening following open heart surgical procedures. The goal of this study was to compare incidence of reopening following open heart surgeries in patients who were administered either epsilon amino caproic acid or tranexamic acid for control of perioperative bleeding.METHODS: A prospective, randomized, controlled trial was performed among seventy-eight patients of either sex in the age group of 18 to 65 years scheduled for open heart surgeries under cardiopulmonary bypass. They were randomly allocated into three groups where group A (n=26) received epsilon aminocaproic acid, group B (n=26) received tranexamic acid and group C (control group, n=26) received intravenous 0.9% normal saline. Patients had similar anaesthetic protocols, and were monitored for twenty-four hours postoperatively to assess reopening rates because of excessive bleeding.RESULTS: Two patients in each group receiving either tranexamic acid or epsilon aminocaproic acid had excessive bleeding requiring reopening after surgery whereas three patients in the control group had undergone reopening for excessive bleeding (p>0.05).CONCLUSIONS: Epsilon aminocaproic acid and tranexamic acid exhibit similar and comparable effect to placebo on incidence of reopening for excessive bleeding following open heart surgeries under cardiopulmonary bypassKEYWORDS: Bleeding, CPB, CABG, antifibrinilytic

Novel curcumin- and emodin-related compounds identified by in silico 2D/3D conformer screening induce apoptosis in tumor cells

BACKGROUND: Inhibition of the COP9 signalosome (CSN) associated kinases CK2 and PKD by curcumin causes stabilization of the tumor suppressor p53. It has been shown that curcumin induces tumor cell death and apoptosis. Curcumin and emodin block the CSN-directed c-Jun signaling pathway, which results in diminished c-Jun steady state levels in HeLa cells. The aim of this work was to search for new CSN kinase inhibitors analogue to curcumin and emodin by means of an in silico screening method. METHODS: Here we present a novel method to identify efficient inhibitors of CSN-associated kinases. Using curcumin and emodin as lead structures an in silico screening with our in-house database containing more than 10(6 )structures was carried out. Thirty-five compounds were identified and further evaluated by the Lipinski's rule-of-five. Two groups of compounds can be clearly discriminated according to their structures: the curcumin-group and the emodin-group. The compounds were evaluated in in vitro kinase assays and in cell culture experiments. RESULTS: The data revealed 3 compounds of the curcumin-group (e.g. piceatannol) and 4 of the emodin-group (e.g. anthrachinone) as potent inhibitors of CSN-associated kinases. Identified agents increased p53 levels and induced apoptosis in tumor cells as determined by annexin V-FITC binding, DNA fragmentation and caspase activity assays. CONCLUSION: Our data demonstrate that the new in silico screening method is highly efficient for identifying potential anti-tumor drugs

Identification of pyrogallol as an antiproliferative compound present in extracts from the medicinal plant Emblica officinalis: Effects on in vitro cell growth of human tumor cell lines.

In this study we compared the in vitro antiproliferative activity of extracts from medicinal plants toward human tumor cell lines, including human erythromyeloid K562, B-lymphoid Raji, T-lymphoid Jurkat, erythroleukemic HEL cell lines. Extracts from Emblica officinalis were the most active in inhibiting in vitro cell proliferation, after comparison to those from Terminalia arjuna, Aphanamixis polystachya, Oroxylum indicum, Cuscuta reflexa, Aegle marmelos, Saraca asoka, Rumex maritimus, Lagerstroemia speciosa, Red Sandalwood. Emblica officinalis extracts have been studied previously, due to their hepatoprotective, antioxidant, antifungal, antimicrobial and anti-inflammatory medicinal activities. Gas chromatography/mass spectrometry analyses allowed to identify pyrogallol as the common compound present both in unfractionated and n-butanol fraction of Emblica officinalis extracts. Antiproliferative effects of pyrogallol were therefore determined on human tumor cell lines thus identifying pyrogallol as an active component of Emblica officinalis extracts