Evaluation of tranexamic acid in reducing blood loss and transfusions in total knee replacement

Background: Total knee replacement (TKR) is associated with substantial blood loss and thus the need for blood transfusions. Risks and costs of allogenic blood transfusions requires strategies to reduce blood loss in surgery. The objective of this study was to assess the efficacy of tranexamic acid treatment in reducing blood loss and blood transfusion requirements during TKR.Methods: A randomized controlled trial was conducted on 60 patients who were operated for unilateral TKR from January 2016 to January 2019 in Shadan Institute of Medical Sciences. 30 patients were in each control and study groups. In study group 12 mg/kg bolus of tranexamic acid was given as a slow IV dose, 40 minutes before deflation of tourniquet followed by 1.2 mg/kg/hr infusion for 12 hours with standard treatment of hospital and compared to the control group. Later blood loss was compared both intra and post operatively. Fall in haemoglobin after surgery was also compared.Results: Total blood loss in tranexamic acid group was 543.3±184.85 ml (control group 685.83±176.74 ml) which is statistically significant (p<0.05). Blood loss was markedly decreased in tranexamic acid group (379.16±174 ml in tranexamic acid vs. 513.33±143.89 ml in control group) statistically significant (p<0.05).Conclusions: Tranexamic acid is an effective strategy to reduce blood loss in patients undergoing total knee replacement and thus minimizing the need for blood transfusions

Analytic study of functional outcome of retrograde intramedullary nailing for distal femoral fractures in adults

Background: The purpose of this Study was to evaluate the clinical and functional outcome of retrograde intramedullary nailing for distal femur fractures.Methods: This 2 years observational study was done between December 2018 to January 2021, 60 patients with distal femoral fractures were surgically treated at our hospital using retrograde intramedullary nail. The patient was placed supine on fracture table with affected limb flexed to 60 degrees. Through a Transpatellar approach, the nail was introduced in retrograde method after serial reaming. Postoperatively knee range of motion was started immediately and weight bearing was progressed after signs of fracture union were noted on x-rays. The outcome was evaluated for time taken for fracture union, complications and functional outcome with various types of fractures.Results: All the fractures in the present study healed at an average of 13 weeks. However 25 to 40% of these patients underwent bone grafting primarily with reports of delayed union and non-union. Shortening occurred in two patients (3.33%) did affect the final functional outcome. average range of motion is 120 deg. for all fractures, 119 deg. for extra-articular fractures and 118 deg. for intra-articular fractures. Infection rates are low (0% to 8%).Conclusions: The study shows distal femoral fractures were common due to high velocity injuries, retrograde nailing is an excellent technique for management of distal femoral fractures as it promotes high rate of fracture union with less complications

Lupane Triterpenoids—Betulin and Betulinic acid derivatives induce apoptosis in tumor cells

In the present investigation the antiproliferative activity of thirteen derivatives of betulinic acid and betulin was tested against five different tumor cell lines. The toxicity against normal human fibroblasts (WWO70327) and the mode of cell death on HT-29 (colon cancer) as well as caspase activity induced by the most active compounds, 9 (3-O-chloroacetylbetulinic acid) and 15 (28-O-chloroacetylbetulin) were determined. Investigated derivatives exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. Treatment of HT-29 cells for 24 h with 9 and 15 induced apoptosis, as observed by dye exclusion test (trypan blue) and confirmed by the appearance of a typical ladder pattern in the DNA fragmentation assay

Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions

<p>Abstract</p> <p>Background</p> <p>Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied.</p> <p>Methods</p> <p>In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses.</p> <p>Results</p> <p>Under normoxic conditions, a half maximal inhibitory concentration (IC₅₀) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions.</p> <p>Conclusion</p> <p>Our results suggest that BA is capable of improving the effects of tumor therapy in human malignant glioma cells, particularly under hypoxic conditions. Further investigations are necessary to characterize its potential as a radiosensitizer.</p

Small structural changes of pentacyclic lupane type triterpenoid derivatives lead to significant differences in their anticancer properties

In the present investigations five new derivatives of betulinic and betulonic acid were synthesized and the effect of this structural variations on anticancer activity was studied and discussed. The antiproliferative activity of betulinic and betulonic acid derivatives was studied against eight tumor cell lines of different histogenic origin. The derivatives exerted a dose dependent antiproliferative action at micromolar concentrations toward target tumor cell lines. The apoptotic mode of cell death on colon cancer cell line HT-29 was induced by the most active compounds 5, 2-amino-3-hydroxy-2-(hydroxymethyl)propyl (3-O-acetyl)betulinate, and 9, 2-amino-3-hydroxy-2-(hydroxymethyl)propyl betulonate. Treatment of HT-29 cells with 5 and 9 induced apoptosis, as observed by dye exclusion test (trypan blue) and by the appearance of a typical ladder pattern in the DNA fragmentation assay and FITC annexin V assay. Cell cycle perturbations caused by compound 5 are also presented

Processes For The Preparation of ({(12aR)-12-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin-­11-yl]-6,8-dioxo-3,4,6,8,12,12a-hexahydro-1H-[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazin-7-yl}oxy)methyl methyl carbonate

The present invention relates to processes for the preparation of ({(12aR)-12-[(11S)-7,8-difluoro-6,11-dihydrodibenzo[b,e]thiepin­11-yl]-6,8-dioxo-3,4,6,8,12,12a-hexahydro-1H -[1,4]oxazino[3,4-c]pyrido[2,1-f][1,2,4]triazin-7-yl}oxy)methyl methyl carbonate