ABSTRACT
OBJECTIVE: To determine the effect on the need for transfusion when intravenous tranexamic acid (TXA) is administered intraoperatively in patients undergoing total hip arthroplasty (THA). METHOD: A prospective, double blinded, randomised control trial of 88 patients undergoing THA was randomly allocated to receive 1 g of intravenous TXA or normal saline on induction of anaesthesia. All patients received spinal anaesthesia. The primary outcome measure was transfusion rate, and the secondary outcomes were intraoperative blood loss, haemoglobin levels, length of hospital stay, functional scores, and thromboembolic complications. RESULTS: 19.0% of patients given TXA required a blood transfusion, compared with 20.5% given placebo (p=0.87). Secondary outcomes included mean intraoperative blood loss, which was 536.5 ml in the TXA group and 469.8 ml in the placebo group (p=0.87). Secondary outcomes included mean intraoperative blood loss, which was 536.5 ml in the TXA group and 469.8 ml in the placebo group (p=0.87). Secondary outcomes included mean intraoperative blood loss, which was 536.5 ml in the TXA group and 469.8 ml in the placebo group (p=0.87). Secondary outcomes included mean intraoperative blood loss, which was 536.5 ml in the TXA group and 469.8 ml in the placebo group (p=0.87). Secondary outcomes included mean intraoperative blood loss, which was 536.5 ml in the TXA group and 469.8 ml in the placebo group (p=0.87). Secondary outcomes included mean intraoperative blood loss, which was 536.5 ml in the TXA group and 469.8 ml in the placebo group (. CONCLUSIONS: 1 g IV TXA administered on induction did not significantly reduce the need for blood transfusion, postoperative blood loss, functional scores, or the length of stay in patients undergoing THA. This trial is registered with ACTRN12610001065088.
ABSTRACT
The human immunodeficiency virus type-1 (HIV-1) accessory gene vpr encodes a conserved 96-amino-acid protein that is necessary and sufficient for the HIV-1-induced block of cellular proliferation. Expression of vpr in CD4+ lymphocytes results in G2 arrest, followed by apoptosis. In a previous study, we identified the ataxia telangiectasia-mutated (ATM) and Rad3-related protein (ATR) as a cellular factor that mediates Vpr-induced cell cycle arrest. In the present study, we report that the breast cancer-associated protein-1 (BRCA1), a known target of ATR, is activated in the presence of Vpr. In addition, the gene encoding the growth arrest and DNA damage-45 protein alpha (GADD45alpha), a known transcriptional target of BRCA1, is upregulated by Vpr in an ATR-dependent manner. We demonstrate that RNAi-mediated silencing of either ATR or GADD45alpha leads to nearly complete suppression of the proapoptotic effect of Vpr. Our results support a model in which Vpr-induced apoptosis is mediated via ATR phosphorylation of BRCA1, and consequent upregulation of GADD45alpha.
Subject(s)
Apoptosis/physiology , Cell Cycle Proteins/metabolism , Gene Products, vpr/metabolism , HIV-1/metabolism , Nuclear Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Ataxia Telangiectasia Mutated Proteins , BRCA1 Protein/metabolism , CD4-Positive T-Lymphocytes/metabolism , Caspase Inhibitors , G2 Phase/physiology , HeLa Cells , Humans , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation , Serine/metabolism , T-Lymphocyte Subsets/metabolism , vpr Gene Products, Human Immunodeficiency VirusABSTRACT
The human survivin gene belongs to the family of inhibitor of apoptosis proteins (IAP) and is involved in apoptosis inhibition and regulation of cell division. The survivin gene is the only member of the IAP family whose expression is known to be regulated through the cell cycle. Survivin expression reaches the highest levels during the G(2)/M transition and then is rapidly degraded during the G(1) phase. Here we report that the human immunodeficiency virus type 1 (HIV-1) upregulates Survivin expression via survivin promoter transactivation. Vpr, an HIV-1 accessory protein that induces cell cycle arrest in G(2)/M, is necessary and sufficient for this effect. Blocking Vpr-induced G(2)/M arrest leads to elimination of the survivin promoter transactivation by Vpr. Our results suggest that Survivin may be actively involved in regulating cell viability during HIV-1 infection.
