Hemolacria or bloody tears in presumed lacrimal endometriosis: a case report / Hemolacria o lágrimas hemáticas en sospecha de endometriosis lacrimal: reporte de un caso

Background: Hemolacria or the presence of blood in tears is a rare condition, and there are only a few cases reported in the literature. Hemolacria is associated with multiple underlying diseases, including vicarious menstruation due to extragenital endometriosis. Case report: We present a 26-year-old woman with hemolacria and abdominal pain related to her menstrual cycle. The patient was diagnosed with bilateral ovarian endometriomas. After ruling out other possible causes of hemolacria, a progestin-only treatment was applied, with improvement of the abdominal pain and complete remission of hemolacria. Conclusions: When faced with hemolacria, a thorough anamnesis and physical examination must be performed, sometimes involving more than one specialist to reach a diagnosis. Considering hemolacria is a sign of a subjacent pathology, its treatment should be specific one for the disease in each case.

Antecedentes: La hemolacria o presencia de sangre en las lágrimas es una afección poco frecuente y sólo hay unos pocos casos descritos en la literatura. La hemolacria se asocia a múltiples enfermedades subyacentes, incluida la menstruación vicaria debida a endometriosis extragenital. Caso clínico: Presentamos a una mujer de 26 años con hemolacria y dolor abdominal relacionado con su ciclo menstrual. La paciente fue diagnosticada de endometriomas ováricos bilaterales. Tras descartar otras posibles causas de hemolacria, se aplicó un tratamiento sólo con progestágenos, con mejoría del dolor abdominal y remisión completa de la hemolacria. Conclusiones: Ante una hemolacria se debe realizar una anamnesis y exploración física minuciosa, en la que a veces interviene más de un especialista para llegar al diagnóstico. Teniendo en cuenta que la hemolacria es signo de una patología subyacente, su tratamiento debe ser el específico para la enfermedad en cada caso.

Analysis of the effects of low/intermediate dose of coagulation factor Ⅷ on 30 adult patients with severe hemophilia A in a single center / 中华血液学杂志

Objective: To evaluate the clinical effects of low- and intermediate-dose factor Ⅷ (F Ⅷ) prophylaxis in Chinese adult patients with severe hemophilia A. Methods: Thirty adult patients with severe hemophilia A who received low- (n=20) /intermediate-dose (n=10) F Ⅷ prophylaxis at Nanjing Drum Tower Hospital affiliated with Nanjing University Medical College were included in the study. The annual bleeding rate (ABR), annual joint bleeding rate (AJBR), number of target joints, functional independence score of hemophilia (FISH), quality of life score, and health status score (SF-36) before and after preventive treatment were retrospectively analyzed and compared. Results: The median follow-up was 48 months. Compared with on-demand treatment, low- and intermediate-dose prophylaxis significantly reduced ABR, AJBR, and the number of target joints (P<0.05) ; the improvement in the intermediate-dose prophylaxis group was better than that in the low-dose prophylaxis group (P<0.05). Compared with on-demand treatment, the FISH score, quality of life score, and SF-36 score significantly improved in both groups (P<0.05), but there was no significant difference between the two groups (P>0.05) . Conclusion: In Chinese adults with severe hemophilia A, low- and intermediate-dose prophylaxis can significantly reduce bleeding frequency, delay the progression of joint lesions, and improve the quality of life of patients as compared with on-demand treatment. The improvement in clinical bleeding was better with intermediate-dose prophylaxis than low-dose prophylaxis.

Antiagregación plaquetaria: stents, isquemia y sangrado ¿Qué sabemos al respecto? / Platelet antiaggregation: stents, ischemia and bleeding What do we know about it?

Antiplatelet therapy and percutaneous coronary intervention are two of the most important interventions in the management of coronary artery disease. In the last 20 years there has been groundbreaking advances in the pharmacotherapy and stent technology. Bleeding is the most feared complication of antiplatelet therapy, mainly due to the increase in major adverse cardiovascular events besides the bleeding itself. Different clinical decision tools have developed with the aim to define which patients have a high ischemic or bleeding risk, thus individualizing treatment.

Congenital factor X deficiency: a retrospective analysis of 11 cases / 中华血液学杂志

Objective: To analyze the clinical characteristics, laboratory examination, diagnosis, treatment, and outcome of hereditary factor Ⅹ (FⅩ) deficiency. Methods: Clinical data of 11 patients with congenital FⅩ deficiency were retrospectively analyzed from July 2009 to February 2021. Results: There were 3 males and 8 females. Median age was 39 (5-55) years. The media duration of follow-up was 81.67 (1.87-142.73) months. Of the 11 patients, 10 had bleeding symptoms, 7 had ecchymosis or hemorrhage after skin bump, 7 had nosebleed, 6 had gingival hemorrhage, and 1 had muscle hematoma. Among the female patients, 6 had menorrhagia and 1 experienced bleeding after vaginal delivery. Family history of FⅩ deficiency was found in one case. Eight patients had a history of surgery, and four had postoperative bleeding. Laboratory findings were characterized by significantly prolonged activated partial thromboplastin time, prothrombin time, and decreased FⅩ activity (FⅩ∶C) . Four cases underwent gene mutation analysis and five new mutations were found. Four cases were treated with prothrombin complex concentrates (PCC) and seven cases with fresh frozen plasma (FFP) . One female patient had significantly reduced menstrual volume after PCC prophylactic therapy. One patient received FFP for prophylactic infusion with no bleeding during and after the operation. Conclusion: Most patients with congenital FⅩ deficiency had bleeding symptoms and there was no significant correlation between severity of bleeding symptoms and FⅩ∶C. Prophylaxis should be applied in patients with severe bleeding tendencies. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of congenital FX deficiency.

Biological compatibility of oxidized cellulose vs. porcine gelatin to control bleeding in liver lesions in rats

ABSTRACT Purpose: To compare biological compatibility, hemostasis, and adhesion formation between oxidized regenerated cellulose and lyophilized hydrolyzed porcine collagen in liver trauma. Methods: Forty male Wistar rats constituted two groups: group A (oxidized cellulose) and group B (lyophilized hydrolyzed collagen). Standardized liver trauma was made, and the hemostatic agent was applied. Animals in subgroups A7 and B7 were submitted to euthanasia and relaparotomy after seven days, and in subgroups A14 and B14 after 14 days. Macroscopic and microscopic results were evaluated. Results: There was no fluid in the cavity in any of the animals, and adhesions were present in all of them. In the analysis after seven days, the adhesions were grades 3 or 4 and consisted of omentum, small intestine, and abdominal wall (p<0.05). In both groups, the mesh was surrounded by a capsule, which was not observed after 14 days. In the evaluation after 14 days, adhesions were grades 2 or 3 (p>0.05). The microscopic examination showed subacute and chronic reactions, in both groups and in both timepoints, with similar frequency. The intensity of fibrosis always presented positive scores. Microabscesses and xanthomatous macrophages were observed in both groups. Conclusions: There was no superiority of one agent over the other.

Protective effect of dexmedetomidine against organ dysfunction in a two-hit model of hemorrhage/resuscitation and endotoxemia in rats

Dexmedetomidine (DEX), a selective agonist of α2-adrenergic receptors, has anti-inflammation properties and potential beneficial effects against trauma, shock, or infection. Therefore, this study aimed to investigate whether DEX might protect against multiple-organ dysfunction in a two-hit model of hemorrhage/resuscitation (HS) and subsequent endotoxemia. Eighty Wistar rats were randomized into four groups: NS (normal saline), HS/L (HS plus lipopolysaccharide), HS/L+D (HS/L plus dexmedetomidine), and HS/L+D+Y (HS/L+D plus yohimbine). Six hours after resuscitation, blood gas (PaO2) and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urine nitrogen (BUN), creatinine (Cr), TNF-α, IL-β, IL-6, IL-8, IL-10, and nitric oxide (NO) were measured. The histopathology was assayed by staining. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels and heme oxygenase-1 (HO-1) were assayed. The PaO2 levels in HS/L rats were lower whereas the ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, IL-10, and NO levels were higher compared to the control group. The HS/L+D increased PaO2 and further increased IL-10 and decreased ALT, AST, BUN, Cr, TNF-α, IL-β, IL-6, IL-8, and NO levels of the HS/L groups. In addition, the MDA in the HS/L groups increased whereas SOD activity decreased compared to the control group. Moreover, the HO-1 expression levels were increased by DEX administration in lung, liver, and kidney tissues. Lungs, livers, and kidneys of the HS/L group displayed significant damage, but such damage was attenuated in the HS/L+D group. All of the above-mentioned effects of DEX were partly reversed by yohimbine. DEX reduced multiple organ injury caused by HS/L in rats, which may be mediated, at least in part, by α2-adrenergic receptors.

Anti-ophidian activity of Bredemeyera floribunda Willd. (Polygalaceae) root extract on the local effects induced by Bothrops jararacussu venom

Bredemeyera floribunda roots are popularly used to treat snakebites in the semiarid region of Northeast Brazil, and previous studies indicate the anti-ophidian actions of triterpenoid saponins found in its roots. To assess B. floribunda root extract (BFRE) activity against the effects of Bothrops jararacussu venom (BjuV), antiphospholipasic, antiproteolytic, antihemorrhagic, antinecrotic, and anti-edematogenic activities were investigated in mice. Phytochemical analysis revealed the presence of saponins, flavonoids, and sugars, with rutin and saccharose being the major constituents of BFRE. Acute toxicity was determined and BFRE was nontoxic to mice. Phospholipase A2 and proteolytic activities induced by BjuV were inhibited in vitro by BFRE at all concentrations tested herein. BFRE (150 mg/kg) inhibited paw edema induced by BjuV (50 µg/animal), reducing total edema calculated by area under the curve, but carrageenan-induced paw edema was unchanged. Hemorrhagic and necrotizing actions of BjuV (50 µg/animal) were considerably decreased by BFRE treatment. Thus, BFRE blocked the toxic actions of B. jararacussu venom despite having no anti-inflammatory activity, which points to a direct inhibition of venom's toxins, as demonstrated in the in vitro assays. The larger amounts of rutin found in BFRE may play a role in this inhibition, since 3′,4′-OH flavonoids are known inhibitors of phospholipases A2.

Disminución de hemorragia post adenoamigdalectomía mediante la utilzación de subgalato de bismuto / Decrease of post adenoamigdalectomy hemorrhage through the use of bismutal subgalate / Diminuição da hemorragem pós adenotonsilectomia através do uso do subgalato de bismuto

Introducción: la cirugía de amígdalas y adenoides es la más frecuentemente realizada en otorrinolaringología. La incidencia de complicaciones es baja, siendo la hemorragia la más frecuente y seria. Se estima que la incidencia de hemorragia post adenoamigdalectomia es entre 0,1 y 8,1%. Dentro de las técnicas hemostáticas se utilizan suturas, electrocauterio, radiofrecuencia, presión con packs, vasoconstrictores u otras sustancias hemostáticas. Entre estas últimas el subgalato de bismuto (activa el factor XII de la coagulación) ha sido empleado durante décadas para hemostasia de diferentes sitios quirúrgicos. El objetivo de este trabajo es determinar la eficacia de la pasta de subgalato de bismuto en la disminución de hemorragias post adenoamigdalectomías. Material y método: Trabajo retrospectivo con pacientes adultos y pediátricos intervenidos quirúrgicamente de amigdalectomía/ adenoidectomía mediante técnica de Daniels y cureta de Beckmann, a los que se dividió en dos grupos: Uno, sin la utilización de subgalato de bismuto y otro utilizando la pasta hemostática intraoperatoria. Posteriormente se comparó la incidencia de hemorragia postquirúrgica entre ambos grupos. Resultados: El primer grupo incluyó a 2.125 pacientes operados y el porcentaje de hemorragias post quirúrgicas sin la utilización del subgalato de bismuto fue de 4,56% (N=97). El otro grupo se conformó con 1.647 pacientes a los que se les aplicó la pasta de subgalato de bismuto en el lecho sangrante y el porcentaje de hemorragias post quirúrgicas descendió a 1,33% (N=22). La diferencia entre ambos grupos fue estadísticamente significativa p=0,001. Conclusiones: La pasta de subgalato de bismuto disminuye la incidencia de hemorragia post amigdalectomía.

Backgruond: tonsils and adenoid surgery are the most frequently performed in otorhinolaryngology. The incidence of complications is low, being the hemorrhage the most frequent and serious one (estimated between 0.1% and 8.1%). The hemostatic techniques used during surgery are sutures, electrocautery, radio frequency, pressure with packs, vasoconstrictors and other haemostatic substances. Between these last substances, Bismuth Subgalate (activates factor XII of coagulation) has been used during decades for hemostasis in different surgical sites. The objective is to determine the efficacy of Bismuth Subgalate paste in the reduction of postadenotonsillectomy hemorrhage. Material and method: Retrospective study including adult and pediatric patients who underwent tonsilectomy / adenoidectomy using the Daniels technique and Beckmann’s curette, which were divided into two groups: one without the use of bismuth subgalate and another using the intraoperative hemostatic paste. Subsequently, the incidence of postoperative hemorrhage between the two groups was compared. Results: The first group included 2,125 patients operated. The percentage of postoperative hemorrhages without the use of the bismuth subgalate was 4.56% (N = 97). The other group consisted of 1,647 patients in whom the Bismuth Subgalate paste was used as a hemostatic agent during surgery. The percentage of postoperative hemorrhage fell to 1.33% (N = 22). The difference between both groups was statistically significant p = 0.001. Conclutions: Bismuth subgalate paste decreases the incidence of post adenotonsillectomy hemorrhage.

Introdução: amígdalas e adenóides cirurgia é a mais realizada na otorrinolaringologia. A incidência de complicações é baixa, sendo o sangramento mais frequentes e graves. Estima-se que a incidência de hemorragia pós-adenotonsilectomia é entre 0,1 e 8,1%. Entre as técnicas hemostáticos, electrocauterização, suturas, radiofrecuecia, pacotes de pressão vasoconstritores ou outras substâncias hemostáticos são utilizados. O subgalato de bismuto ( ativa o fator de coagulação XII) tem sido usada há décadas para hemostasia de diferentes locais cirúrgicos. O objectivo é determinar a eficiência de pasta de subgalato de bismuto na redução de hemorragias pós-adenoamigdalectomia. Material e método: Estudo retrospectivo com pacientes adultos e pediátricos submetidos á cirurgia de adenoidectomia/ amigdalectomia pela técnica Daniels e cureta Beckmann, que foi dividido em dois grupos: um sem o uso de subgalato de bismuto e a outra usando pasta hemostática intraoperatória subsequentemente na incidência de hemorragia pós-cirúrgica entre os dois grupos foi comparado. Resultados: O primeiro grupo incluiu 2125 pacientes operados e a porcentagem de hemorragias pós-cirúrgico, sem o uso de subgalato de bismuto foi 4,56% (97n) o outro grupo foi formada com 1647 pacientes o qual foi aplicada uma pasta de subgalato de bismuto e a percentagem de hemorragia pós-cirurgia caiu para 1,33% (22n), a diferença entre ambos grupos foi estatisticamente significativa (p:0,001). Conclusões: a pasta de subgalato de bismuto diminui a incidencia de hemorragia pós-adenoamigdalectomia.

Safety and efficacy of intravesical alum for intractable hemorrhagic cystitis: a contemporary evaluation

ABSTRACT Introduction: Hemorrhagic cystitis (HC) represents a challenging clinical entity. While various intravesical agents have been utilized in this setting, limited data exist regarding safety or efficacy. Herein, then, we evaluated the effectiveness and complications associated with intravesical alum instillation for HC in a contemporary cohort. Materials and Methods: We identified 40 patients treated with intravesical alum for HC between 1997-2014. All patients had failed previous continuous bladder irrigation with normal saline and clot evacuation. Treatment success was defined as requiring no additional therapy beyond normal saline irrigation after alum instillation. Results: Median patient age was 76.5 years (IQR 69, 83). Pelvic radiation was the most common etiology for HC (n=38, 95%). Alum use decreased patient's transfusion requirement, with 82% (32/39) receiving a transfusion within 30 days before alum instillation (median 4 units) versus 59% (23/39) within 30 days after completing alum (median 3 units) (p=0.05). In total, 24 patients (60%) required no additional therapy prior to hospital discharge. Moreover, at a median follow-up of 17 months (IQR 5, 38.5), 13 patients (32.5%) remained without additional treatment for HC. Adverse effects were reported in 15 patients (38%), with bladder spasms representing the most common event (14/40; 35%). No clinical evidence of clinically significant systemic absorption was detected. Conclusion: Intravesical alum therapy is well-tolerated, with resolution of HC in approximately 60% of patients, and a durable response in approximately one-third. Given its favorable safety/efficacy profile, intravesical alum may be considered as a first-line treatment option for patients with HC.

Seguridad y eficacia de facto VII recombinante activado para el tratamiento de pacientes con hemofilia a severa con presencia de inhibidores y alto riesgo de eventos agudos de sangrado o hemorragia que no responden al concentrado de complejo protrombínico activado / Safety and efficacy de facto Recombinant VII activated for the treatment of patients with hemophilia to severe with inhibitors and high risk of acute bleeding or bleeding events that do not respond to activated prothrombin complex concentrate

INTRODUCCIÓN: Antecedentes: El presente informe expone la evaluación del Facto VII recombinante en el manejo de pacientes con diagnóstico de Hemofilia A severa, con presencia de inhibidores y que presentan o estén en riesgo de presentar evento agudo de sangrado o hemorragia, con el objetivo de prevenir muerte por sangrado no controlado. Aspectos Generales: La hemofilia es un desorden hematológico congénito ligado al cromossoma X. Se han identificado dos tipos principalmente, la Hemofilia A que es causado por deficiencia de factor de coagulación VIII (FVIII) y la Hemofilia B que es causado por deficiencia de factor de coagulación IX (FIX). La deficiencia de estos factoes es el resultado de mutaciones en los genes de los factores de coagulación respectivos. Tecnología Sanitaria de Interés: Factor VII Recombinante Activado-RFVIIA (Novoseven - Marca Registrada): El RFVIIA es un glicoproteina dependiente de la vitamina K que consiste em 406 residuos de aminoácidos (MW 50K Dalton). Es estructuramente similar al factor VIIa derivado de plasma hmano y actúa de manera semejante al factor VII en la cascada de coagulación. Debido a que el factor VII actúa directamente sobre el factor X independientemente del facto VIII y IX, este medicamento puede ser usado en pacientes con hemofilia que han desarrollado inhibidores a los factores VII oIX. METODOLOGIA: Estratégia de Búsqueda: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de Factor VII recombinante activado con diagnóstico de Hemofilia A severa, con presencia de inhibidores altos respondedores definido por presentar una alta respuesta (>= 5 unidades Bethesda UB), que presentan o estén en alto riesgo de presentar evento agudo de sangrado o hemorragia y que haya usado aPCC previamente. RESULTADOS: Se realizó la búsqueda bibliografica y de evidencia cientifica para el sustento del uso del Factor VII recombinante activado en pacientes con Hemofilia A severa con titulos elevados de inhibidores, que sean altos respondedores (>= 5 unidades Bethesda UB), que tengan o estén en alto riesgo de presentar evento agudo de sangrado y que hayan usado aPCC previamente. CONCLUSIONES: En la presente evaluación de tecnología sanitaria se ha encontrado escasa evidencia que muestre que facto VII recombinante activado (rFVIIa) ofrezca beneficios para los pacientes con diagnóstico de hemofilia A severa con presencia de inhibidores y con alto riesgo de hemorragia de evento agudo de sangrado o hemorragia que hayan usado el concentrado de complejo protrombínico activado (aPCC). La evidencia que respalda esto uso de rFVIIa es aún muy limitada, se establece que el efecto de rFVIIa se evaluará con los datos de los pacientes que los hayan recibido por el periodo de vigencia de este Dictamen, para determinar el impacto de su usi en los desenlaces de interés de este Dictamen. Esta información será tomada en cuenta en la reevaluación de este medicamento para efectos de un nuevo dictamen al terminar la vigencia del presente Dictamen Preliminar.

Control perioperatorio de la anticoagulación con antagonistas de la vitamina K en cirugía electiva

Los pacientes anticoagulados crónicamente que son sometidos a cirugías electivas requieren la suspensión temporaria de los antagonistas de vitamina K. El objetivo del presente trabajo fue evaluar la incidencia de eventos tromboembólicos y hemorrágicos en pacientes anticoagulados sometidos a un procedimiento invasivo, aplicando un protocolo de manejo de anticoagulación en el perioperatorio. Se realizó un estudio descriptivo, con datos obtenidos de manera prospectiva, donde se incluyeron mayores de 18 años que ingresaron para la realización de una cirugía electiva. Recibieron sustitución con enoxaparina aquellos con fibrilación auricular(FA) de moderado y alto riesgo de evento tromboembólico, pacientes con reemplazo con válvula cardíaca mecánica(VCM) de moderado y alto riesgo de evento tromboembólico y con tromboembolismo venoso(TEV) de alto riesgo de evento tromboembólico. Se evaluaron los eventos embólicos y hemorrágicos en el perioperatorio. Setenta y ocho recibieron sustitución con enoxaparina en el perioperatorio, edad promedio de 69.4 ± 11.9 años. Veintiocho tenían FA (36.4%), 12 TEV (15.6%) y 37 VCM (48.1%). En el postoperatorio hubo un evento embólico (1.6%) y 12 eventos hemorrágicos (15.4%) de los cuales 10 fueron menores (12.8%) y 2mayores (2.6%). La seguridad de la sustitución con enoxaparina aún es cuestionable, y se deberán esperar estudios aleatorizados, comparando diferentes estrategias de sustitución con heparinas versus la suspensión del tratamiento anticoagulante en el período perioperatorio para una conclusión definitiva.

Anti-coagulated patients who undergo elective surgery require temporary interruption of vitamin K antagonists. The aim of this study was to evaluate the incidence of thromboembolic events and bleeding complications in anti-coagulated patients undergoing elective invasive procedures by using an institutional management protocol. This was a descriptive study with prospective follow-up that included patients over 18 year old anti-coagulated with vitamin K antagonists, undergoing elective surgery. Those with atrial fibrillation (AF) at moderate and high risk of thromboembolic events, with mechanical heart valve (MCV) at moderate and high risk of thromboembolic events, and patients' venous thromboembolism (VTE) at high risk of thromboembolic events received bridging therapy with enoxaparin. Embolic and bleeding events in the pre-operative period were recorded. Seventy- eight received bridging, mean age 69.4 ± 11.9 years. Twenty-eight had AF (36.4 %), 12 had VTE (15.6 %) and 37 had MCV (48.1 %). Postoperatively, 1 embolic event (1.6 %) and 12 bleeding events (15.4 %) were documented, of which 10 were minor (12.8 %) and 2 major (2.6 %). The safety of bridging therapy is still under debate, and we should await the result of randomized studies comparing different strategies of bridging vs. interruption of anticoagulant therapy in the pre-operative period prior to reaching a definitive conclusion.

Rebleeding after Initial Endoscopic Hemostasis in Peptic Ulcer Disease

Endoscopic hemostasis is the first-line treatment for upper gastrointestinal bleeding (UGIB). Although several factors are known to be risk factors for rebleeding, little is known about the use of antithrombotics. We tried to verify whether the use of antithrombotics affects rebleeding rate after a successful endoscopic hemostasis for peptic ulcer disease (PUD). UGIB patients who underwent successful endoscopic hemostasis were included. Rebleeding was diagnosed when the previously treated lesion bled again within 30 days of the initial episode. Of 522 UGIB patients with PUD, rebleeding occurred in 93 patients (17.8%). The rate of rebleeding was higher with aspirin medication (P=0.006) and after a long endoscopic hemostasis (P<0.001). Of all significant variables, procedure time longer than 13.5 min was related to the rate of rebleeding (OR, 2.899; 95% CI, 1.768-4.754; P<0.001) on the logistic regression analysis. The rate of rebleeding after endoscopic hemostasis for PUD is higher in the patients after a long endoscopic hemostasis. Endoscopic hemostasis longer than 13.5 min is related to rebleeding after a successful endoscopic hemostasis for PUD.

Reversal of the anticoagulant and anti-hemostatic effect of low molecular weight heparin by direct prothrombin activation

Lopap, found in the bristles of Lonomia obliqua caterpillar, is the first exogenous prothrombin activator that shows serine protease-like activity, independent of prothrombinase components and unique lipocalin reported to interfere with hemostasis mechanisms. To assess the action of an exogenous prothrombin activator reversing the anticoagulant and antihemostatic effect induced by low molecular weight heparin (LMWH), male New Zealand rabbits (N = 20, weighing 3.8-4.0 kg) allocated to 4 groups were anticoagulated with 1800 IU/kg LMWH (iv) over 2 min, followed by iv administration of saline (SG) or recombinant Lopap (rLopap) at 1 µg/kg (LG1) or 10 µg/kg (LG10), 10 min after the injection of LMWH, in a blind manner. Control animals (CG) were treated only with saline. The action of rLopap was assessed in terms of activated partial thromboplastin time (aPTT), prothrombin fragment F1+2, fibrinogen, and ear puncture bleeding time (BT) at 5, 10, 15, 17, 20, 30, 40, 60, and 90 min after initiation of LMWH infusion. LG10 animals showed a decrease of aPTT in more than 50% and BT near to normal baseline. The level of prothrombin fragment F1+2 measured by ELISA had a 6-fold increase with rLopap treatment (10 µg/kg) and was inversely proportional to BT in LMWH-treated animals. Thus, Lopap, obtained in recombinant form using E. coli expression system, was useful in antagonizing the effect of LMWH through direct prothrombin activation, which can be a possible strategy for the reversal of bleeding and anticoagulant events.

Anti-venom potential of aqueous extract of stem bark of Mangifera indica L. against Daboia russellii (Russell’s viper) venom.

Several plant extracts rich in pharmacologically active compounds have shown to antagonize venom of several species. Mangifera indica has been used against snakebite by the traditional healers, However, there is paucity of scientific data in support. In this study, we evaluated the antivenom potential of aqueous extract of stem bark of M. indica against D. russellii venom-induced pharmacological effects such as life myotoxicity, edema, LD50 etc. The extract inhibited the phospholipase, protease, hyaluronidase, 5`nucleotidase, ATPase and alkaline phosphomonoesterase activities with varying IC50 values. It significantly inhibited both metalloproteases and serine proteases activities. Further, the extract significantly reduced the myotoxicity of the venom, as evident by the reduction of serum creatin kinase and lactate dehydrogenase activities. Though the extract completely inhibited in vitro PLA2 activity, it was unable to completely inhibit in situ hemolytic and in vivo edema-inducing activities, usually brought about by PLA2s. In lethality studies, co-injection of the venom preincubated with the extract showed higher protection than the independent injection of venom, followed by the extract in the mice. However, in both the cases the extract -a cocktail of inhibitors significantly increased the survival time, when compared to that of mice injected (i.p) with the venom alone. These results encourage further studies on the potential use of cocktail of inhibitors in improving the treatment of snake envenomation. Further, this study substantiates the use of M. indica as an antidote against snakebite by the traditional healers.