Promoting the sensitive detection of ethamsylate via a colorimetric sensing platform based on the enhanced oxidase-mimicking activity of ultrathin MnO2 nanosheets.

In this work, we present a novel colorimetric sensing platform for the sensitive detection of ethamsylate (ETM) usingultrathin MnO2 nanosheets with enhancedoxidase-mimicking activity. A facile template-free hydrothermal process was applied to synthesize the MnO2 nanosheets under mild conditions. The nanosheets exhibited oxidase-mimicking activity, facilitating the conversion of TMB into the blue-colored oxTMB in the absence of H2O2. However, the presence of ETM inhibited this activity, resulting in the conversion of oxTMB back to colorless TMB and a substantial decrease in the blue color intensity. The colorimetric response exhibited a linear relationship with ETM concentration over the range of 0.5 to 10.0 µg/mL and a detection limit of 0.156 µg/mL. To further elucidate the underlying mechanism, we performed extensive characterization and kinetic experiments. The findings demonstrated that this unique property is attributed to the remarkable capacity of the MnO2 nanosheets to absorb oxygen, producing superoxide radicals (O2-). The oxidase-mimicking activity of the nanosheets was further confirmed by the reaction kinetics, following Michaelis-Menten's behavior. Moreover, the applicability of the sensing platform was assessed by determining ETM concentrations in various real samples (different pharmaceuticals, human plasma, and environmental water). The well-established platform demonstrates the prospective role that nanomaterials-based sensing platforms may play in clinical diagnostics, pharmaceutical analysis, and other relevant fields.

Oxytocin versus a combination of tranexamic acid and ethamsylate in reducing intraoperative bleeding during abdominal myomectomy: a randomized clinical trial.

OBJECTIVE: Myomectomy is the preferred surgical approach to manage uterine fibroids. However, uterine fibroids are highly vascular tumors and, consequently, extremely susceptible to problems from myomectomy-related hemorrhage. Hence, we aim to compare oxytocin efficacy and safety profile versus tranexamic acid (TA) with ethamsylate for reducing bleeding during myomectomy. METHODS: This randomized, double-blinded multicenter study was performed between 20th August 2020 and 20th October 2020 at El-Galaa Teaching Hospital, El Hussein University Hospital, Al-Azhar University Hospitals of Assiut, and Al-Azhar University Hospitals of Damietta. One hundred and eighty patients were enrolled and divided into three groups: group (1) received an injection of 30 IU of oxytocin in 500 ml of normal saline; group (2) received injections of 1 g of TA, 250 mg of Ethamsylate, and 110 ml of normal saline IV; and group (3) received an injection of 110 ml of normal saline IV just before surgical incision. RESULTS: In 180 premenopausal women, oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy (666.25 ± 183.03, 630.72 ± 145.83, and 646.67 ± 168.92, respectively (P = 0.506)). Non-significant trends were observed for a reduction in operation time (P = 0.760), intra/postoperative blood transfusion (P = 0.624), hospital stay (P = 0.986), postoperative fever (P = 0.659), and wound infection (P = 1). CONCLUSION: Oxytocin and TA with ethamsylate had no significant value in lowering intraoperative blood loss compared with the placebo for abdominal myomectomy which opens a new question about the role of the use of the hemostatic drug during myomectomy especially in centers with limited resources and had higher rates. TRIAL REGISTRATION: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202008739887429 and was approved on 24/08/2020.

Comparative study between oxytocin and combination of tranexamic acid and ethamsylate in reducing intra-operative bleeding during emergency and elective cesarean section after 38 weeks of normal pregnancy.

OBJECTIVE: Cesarean Section (CS) is associated with an increased risk of hemorrhage. Many drugs are used to decrease this risk. We aim to compare the combination of ethamsylate and tranexamic acid, oxytocin, and placebo in women undergoing CS. METHODS: We conducted a double-blinded, randomized, placebo-controlled trial between October and December 2020 in four university hospitals in Egypt. The study included all pregnant women in labor without any complications who accepted to participate in the study between October and December 2020. The participants were divided into three groups. The subjects were randomly allocated to receive either oxytocin (30 IU in 500 ml normal saline during cesarean section), combined one gram of tranexamic acid with 250 mg of ethamsylate once before skin incision, or distilled water. Our main outcome was the amount of blood loss during the operation. The secondary outcomes were the need for blood transfusion, hemoglobin and hematocrit changes, hospital stay, operative complications, and the need for a hysterectomy. The one-way ANCOVA test was used to compare the quantitative variables between the three groups while the Chi-square test was used to compare the qualitative variables. Post hoc analysis then was performed to compare the difference between every two groups regarding the quantitative variables. RESULTS: Our study included 300 patients who were divided equally into three groups. Tranexamic acid with ethamsylate showed the least intra-operative blood loss (605.34 ± 158.8 ml) compared to oxytocin (625.26 ± 144.06) and placebo (669.73 ± 170.69), P = 0.015. In post hoc analysis, only tranexamic acid with ethamsylate was effective in decreasing the blood loss compared to placebo (P = 0.013); however, oxytocin did not reduce blood loss compared to saline (P = 0.211) nor to tranexamic acid with ethamsylate (P = 1). Other outcomes and CS complications showed no significant difference between the three groups except for post-operative thrombosis which was significantly higher in the tranexamic and ethamsylate group, P < 0.00001 and the need for a hysterectomy which was significantly increased in the placebo group, P = 0.017. CONCLUSION: The combination of tranexamic acid and ethamsylate was significantly associated with the least amount of blood loss. However, in pairwise comparisons, only tranexamic acid with ethamsylate was significantly better than saline but not with oxytocin. Both oxytocin and tranexamic acid with ethamsylate were equally effective in reducing intra-operative blood loss and the risk of hysterectomy; however, tranexamic acid with ethamsylate increased the risk of thrombotic events. Further research with a larger number of participants is needed. TRIAL REGISTRATION: The study was registered on Pan African Clinical Trials Registry with the following number: PACTR202009736186159 and was approved on 04/09/2020.

Ethamsylate Attenuates Mutilated Secondary Pathogenesis and Exhibits a Neuroprotective Role in Experimental Model of Spinal Cord Injury.

Deficits in the neuronal connection that succumbs to the impairment of sensory and motor neurons are the hallmarks of spinal cord injury (SCI). Secondary pathogenesis, which initiates after the primary mechanical insult to the spinal cord, depicts a pivotal role in producing inflammation, lesion formation and ultimately causes fibrotic scar formation in the chronic period. This fibrotic scar formed acts as a major hindrance in facilitating axonal regeneration and is one of the root causes of motor impairment. Cascade of secondary events in SCI begins with injury-induced blood spinal cord barrier rupture that promotes increased migration of neutrophils, macrophages, and other inflammatory cells at the injury site to initiate the secondary damages. This phenomenon leads to the release of matrix metalloproteinase, cytokines and chemokines, reactive oxygen species, and other proteolytic enzymes at the lesion site. These factors assist in the activation of the TGF-ß1 signaling pathway, which further leads to excessive proliferation of perivascular fibroblast, followed by deposition of collagen and fibronectin matrix, which are the main components of the fibrotic scar. Subsequently, this scar formed inhibits the propagation of action potential from one neuron to adjacent neurons. Ethamsylate, an anti-hemorrhagic drug, has the potential to maintain early hemostasis as well as restore capillary resistance. Therefore, we hypothesized that ethamsylate, by virtue of its anti-hemorrhagic activity, reduces hemorrhagic ischemia-induced neuronal apoptosis, maintains the blood spinal cord barrier integrity, and decreases secondary damage severity, thereby reduce the extent of fibrotic scar formation, and demonstrates a neuroprotective role in SCI.

The synergistic effect of tranexamic acid and ethamsylate combination on blood loss in pediatric cardiac surgery.

Background: Pediatric patients are at risk for bleeding after cardiac surgery. Administration of antifibrinolytic agents reduces postoperative blood loss. Objective: Evaluation of the efficacy of combined administration of tranexamic acid (TXA) and ethamsylate in the reduction of postoperative blood loss in pediatric cardiac surgery. Methods: This prospective randomized study included 126 children submitted for cardiac surgery, and they were allocated into three groups: control group (n = 42); TXA group (n = 42):- received only TXA; and combined ethamsylate TXA group (n = 42):- received a combination of TXA and ethamsylate. The main collected data included sternal closure time, the needs for intraoperative transfusion of blood and its products, the total amount of blood loss, and the amount of the whole blood and its products transfused to the patients in the first 24 postoperative hours. Results: Blood loss volume in the first 24 postoperative hours was significantly smaller in combined group than the TXA and control groups and was significantly smaller in the TXA group than the control group. The sternal closure time was significantly shorter in the combined group than the other 2 groups and significantly shorter in TXA than the control group. The amount of whole blood transfused to patients in the combined group during surgery and in the first postoperative 24 h was significantly smaller than the other 2 groups and smaller in TXA group than the control group during surgery. Conclusion: Combined administration of ethamsylate and TXA in pediatric cardiac surgery was more effective in reducing postoperative blood loss and whole blood transfusion requirements than the administration of TXA alone.

Effects of haemostatic agents on bond strength - An In Vitro study.

AIM: To evaluate and compare the effect of contamination with haemostatic agents like Tranexamic Acid (TA) and Ethamsylate, on the shear bond strength. MATERIALS AND METHODS: There are about 100 extracted human premolars randomly segregated into four groups each consisting of 25 samples. Group I was bonded with Transbond, Group II was bonded with Transbond after blood contamination, while groups III and IV were bonded with Transbond after contamination with Tranexamic acid and the shear bond strength was measured. The data were compared by One- way ANOVA and Tukey (HSD) tests. RESULTS: Group I had the highest shear bond strength (SBS) while Group II, where the teeth were contaminated with blood showed the least SBS values ANOVA indicated significant differences between the four groups (P < .05). Tukey HSD revealed that contamination with TA (Group III) had a statistically higher SBS that contamination with Ethamsylate (Group IV) (P < .05). CONCLUSION: Since tranexamic acid and ethamsylate reduces the bleeding when used during surgery, these haemostatic agents may be considered in bonding situations where blood contamination is anticipated.

Tranexamic acid adverse reactions: a brief summary for internists and emergency doctors.

Tranexamic acid (TXA) is a synthetic lysine analogue that is well known as antifibrinolytic agent. It can reduce blood loss in clinical use, especially in conditions where fibrinolysis or hyperfibrinolysis are involved, such as trauma or surgery. Moreover, TXA has been approved as second-line prophylactic therapy for hereditary angioedema and further data have been published about a possible use of TXA as maintenance treatment for nonhistaminergic angioedema and treatment for episodes of bradykinin-mediated angioedema induced by ACE inhibitors. TXA can be administered through several routes: orally, topically, or intravenously. Although, it is a drug with a very high safety profile, in few cases hypersensitivity reactions have been described occurring with different clinical manifestations. Ethamsylate can be an alternative in TXA sensitized patients. In this brief article we describe TXA adverse reactions and current protocols which have been proposed to help clinicians to diagnose TXA hypersensitivity.

[Uso de etamsilato para reducir el sangrado posoperatorio y el índice de transfusión en la artroplastia total de cadera. Ensayo clínico controlado]. / Use of ethamsylate to reduce postoperative bleeding and transfusion index in total hip arthroplasty. A randomized clinical trial.

ANTECEDENTES: El sangrado secundario es una de las principales causas de morbilidad después de la cirugía. El etamsilato se ha utilizado con buenos resultados para disminuir el sangrado en diversas patologías, como metrorragias, sangrado intraventricular, prostatectomías, cirugías de catarata y amigdalectomías. El objetivo de este estudio fue evaluar la efectividad del etamsilato para disminuir el sangrado en la cirugía de reemplazo total de cadera. MÉTODO: La población se dividió en dos grupos. En el grupo control se realizó la hemostasia de manera convencional; en el grupo experimental se administró etamsilato. RESULTADOS: Se incluyeron 34 pacientes, de los cuales 17 fueron aleatorizados al grupo de etamsilato y 17 al grupo control. No hubo diferencias en las características de la población entre los dos grupos. Al comparar los valores de hemoglobina preoperatoria y a las 24, 48 y 72 horas posquirúrgicas entre ambos grupos, no se encontraron diferencias estadísticamente significativas. Tampoco hubo diferencia en el hematocrito ni en la cuantificación del gasto por drenaje a las 24 y 48 horas. Hubo tres pacientes transfundidos en el grupo de etamsilato y siete en el grupo de control, lo cual no difirió significativamente (p = 0.62). CONCLUSIÓN: En este estudio no se demostró un efecto sobre la reducción de la hemorragia en pacientes sometidos a reemplazo total de cadera con el uso de etamsilato. BACKGROUND: Secondary bleeding is one of the leading causes of morbidity after the surgery. Ethamsylate has been used with good results to decrease bleeding in various pathologies such as metrorrhagia, intraventricular bleeding, prostatectomies, cataract surgeries and tonsillectomies. The objective of this study was to evaluate the effectiveness of the hemostatic agent ethamsylate to decrease bleeding in total hip replacement surgery. METHOD: The population were divided into two groups, in the control group was performed the hemostasis conventionally; in the experimental group ethamsylate was administered. RESULTS: A total of 34 patients were included, of whom 17 were randomized to the group of ethamsylate and 17 randomized to the control group. There were no differences in the characteristics of the population between the two groups. Comparing preoperative hemoglobin levels and at 24, 48 and 72 postsurgical hours between the control group and ethamsylate group there was no statistically significant difference. There was also no difference in the levels of hematocrit. In the quantification of expenditure by the drainage there was no difference between the groups at 24 and 48 hours. There were three patients transfused in the ethamsylate group and seven in the control group, which did not differ significantly (p = 0.62). CONCLUSION: An effect on the reduction of bleeding in patients undergoing total hip replacement with the use of hemostatic agent ethamsylate was not demonstrated in this study.

Simultaneous determination of some dihydroxybenzenesulphonic acid derivatives and their degradation product and main impurity (hydroquinone) by ion-pair liquid chromatography.

A simple and sensitive high-performance liquid chromatography method was developed and validated for the determination of calcium dobesilate (DOB) or ethamsylate (ETM) in the presence of their degradation product, hydroquinone (HQ). The analyses were carried out on Promosil C18 column (4.6 mM × 250 mM, 5 µm particle size) using an ion-pair mobile phase consisting of methanol-1.5 mM tetra-butyl ammonium bromide in 0.06 M phosphate buffer (25 : 75, v/v) at pH 6.0 with fluorescence detection at 286/333 nm. Pindolol was used as an internal standard. The proposed method was found to be rectilinear over the concentration ranges of 0.05-0.5 µg/mL for DOB, 0.1-0.8 µg/mL for ETM and 0.005-0.1 µg/mL for HQ. The method was applied for the determination of the studied drugs in different dosage forms and biological fluids. The results of the proposed method were statistically compared with those obtained by the comparison methods revealing no significance differences in the performance of the methods regarding accuracy and precision. Moreover, applying a time-programmed fluorescence technique was valuable for the detection of trace amounts of HQ as an impurity and allowed purity testing of ETM or DOB within the BP pharmacopeial limit (0.1%).

Spectrophotometric estimation of ethamsylate and mefenamic Acid from a binary mixture by dual wavelength and simultaneous equation methods.

Two simple, accurate, economical and reproducible spectrophotometric methods for simultaneous estimation of two-component drug mixture of ethamsylate and mefenamic acid in combined tablet dosage form have been developed. The first developed method involves formation and solving of simultaneous equation using 287.6 nm and 313.2 nm as two wavelengths. Second developed method is based on two wavelength calculation. Two wavelengths selected for estimation of ethamsylate were 274.4 nm and 301.2 nm while that for mefenamic acid were 304.8 nm and 320.4 nm. Both the developed methods obey Beer's law in the concentration ranges employed for the respective methods. The results of analysis were validated statistically and by recovery studies.