RESUMEN
PURPOSE: In this study, we aimed to investigate the effects of hyperbaric oxygen therapy and enoxaparin sodium, which are known to accelerate bone tissue healing as well as tendon and soft tissue healing, on the healing of Achilles tendon rupture. METHODS: Thirty-six rats were used in the present study. All rats were divided into groups of nine. The groups were the enoxaparin sodium group, enoxaparin sodium and hyperbaric oxygen group, hyperbaric oxygen group and control group. After 21 days, the process was completed, and the rats were sacrificed. Achilles tendon samples were evaluated histopathologically. RESULTS: The groups were compared according to the results of statistical analysis based on the histopathological data. There was no significant difference between the groups in terms of acute inflammation (p = 0.785) or chronic inflammation (p = 0.827) scores, but there were significant differences in neovascularization (p = 0.009), proliferation (p < 0.001) and fibrosis (p = 0.006) scores. CONCLUSION: Our study showed that the use of enoxaparin sodium and hyperbaric oxygen had a positive effect on the healing of the Achilles tendon. Based on these results, we believe that the use of enoxaparin sodium and hyperbaric oxygen therapy after Achilles tendon rupture will be beneficial for healing and preventing complications.
Asunto(s)
Tendón Calcáneo , Enoxaparina , Oxigenoterapia Hiperbárica , Traumatismos de los Tendones , Cicatrización de Heridas , Animales , Oxigenoterapia Hiperbárica/métodos , Tendón Calcáneo/lesiones , Tendón Calcáneo/patología , Tendón Calcáneo/efectos de los fármacos , Ratas , Traumatismos de los Tendones/terapia , Cicatrización de Heridas/efectos de los fármacos , Rotura , Enoxaparina/uso terapéutico , Enoxaparina/farmacología , Masculino , Modelos Animales de Enfermedad , Recuperación de la Función/efectos de los fármacos , Ratas Wistar , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Recent studies suggest that enoxaparin may have therapeutic effects on oral squamous cell carcinoma. We aimed to assess this effect utilizing xenograft mouse model through evaluations of proliferation and angiogenesis markers at the RNA and protein levels. METHODS: Mice were divided into enoxaparin treatment (n = 4), positive control (n = 4) and negative control (n = 3) groups. Immunohistochemical analyses were performed utilizing Bcl-2, Bax and Ki-67 antibodies. Expression levels of proliferation and apoptosis related genes were calculated utilizing qRT-PCR. Time-dependent proliferation assays were performed in OSC-19 and HEK293 cell-lines. RESULTS: Bax antibody showed positive staining in the cytoplasm and nuclei of tumor cells, while Bcl-2 antibody displayed staining only in the cytoplasm. A proliferation index of 15%-20% was found in all groups with the Ki-67 marker indicating no metastasis. Enoxaparin treatment caused decrease in BCL2, BAX and CCNB1 genes' expressions. Compared to HEK293, proliferation assays demonstrated higher division rates in OSC-19 with a significant decrease in viability after 96 h. CONCLUSION: Reduced BCL-2 expression indicates a regression of tumor growth, but reduced BAX expression is not correlated with increased apoptosis. Despite the aggressive nature of OSC-19, our results showed a low cell viability with a high division rate when compared with the control HEK293. This paralleled our in vivo findings that showed absence of lymph node metastasis across all mice groups. This discrepancy with the literature suggests that further investigations of the underlying mechanisms and protein-level analyses are needed to draw definitive conclusions about the effect of enoxaparin on OSC-19 behavior.
Asunto(s)
Carcinoma de Células Escamosas , Proliferación Celular , Enoxaparina , Neoplasias de la Boca , Animales , Enoxaparina/uso terapéutico , Enoxaparina/farmacología , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/patología , Proyectos Piloto , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Proliferación Celular/efectos de los fármacos , Ratones , Proteínas Proto-Oncogénicas c-bcl-2 , Apoptosis/efectos de los fármacos , Proteína X Asociada a bcl-2 , Modelos Animales de Enfermedad , Antígeno Ki-67 , Línea Celular Tumoral , Células HEK293 , Ensayos Antitumor por Modelo de Xenoinjerto , Ciclina B1 , Ratones Desnudos , XenoinjertosRESUMEN
Low-molecular-weight heparins are a class of drugs derived from the enzymatic depolymerization of unfractionated heparin that includes enoxaparin. Several studies have been performed on enoxaparin in recent years, in particular for the prevention and treatment of venous thromboembolism and for the treatment of acute coronary syndrome. Furthermore, the use of enoxaparin has been extended to other clinical situations that require antithrombotic pharmacological prevention, such as hemodialysis and recurrent abortion. In this review, we report the main clinical experiences of using enoxaparin in the prevention of VTE in nonsurgical patients.
Asunto(s)
Síndrome Coronario Agudo , Enoxaparina , Femenino , Embarazo , Humanos , Enoxaparina/farmacología , Enoxaparina/uso terapéutico , Heparina , Heparina de Bajo-Peso-Molecular , PacientesRESUMEN
BACKGROUND: COVID-19 causes consequences such as imbalance of the immune system and thrombotic events. During the infection process, NETs in excess induce a pro-inflammatory response and disseminated intravascular coagulation. We evaluated the role of enoxaparin as a potential inhibitor of NETs. METHODS: K18-hACE2 animals infected with the SARS-CoV-2 virus and a group of 23 individuals admitted to the hospital with COVID-19 treated with enoxaparin or without treatment and controls without the disease were included. RESULTS: Enoxaparin decreased the levels of NETs, reduced the signs of the disease and mitigated lung damage in the animals infected with SARS-CoV-2. These effects were partially associated with prevention of SARS-CoV-2 entry and NETs synthesis. Clinical data revealed that treatment with enoxaparin decreased the levels of inflammatory markers, the levels of NETs in isolated neutrophils and the organ dysfunction. CONCLUSION: This study provides evidence for the beneficial effects of enoxaparin in COVID-19 in addition to its anticoagulant role.
Asunto(s)
COVID-19 , Trampas Extracelulares , Humanos , Animales , Neutrófilos , Enoxaparina/farmacología , SARS-CoV-2RESUMEN
The aim of this study was to investigate the anti-melanoma and anti-angiogenic effects of enoxaparin surface-coated dacarbazine-loaded chitosan nanoparticles (Enox-Dac-Chi NPs). The prepared Enox-Dac-Chi NPs had a particle size of 367.95 ± 1.84 nm, zeta potential of -7.12 ± 0.25 mV, efficiency of drug loading (DL%) of 73.90 ± 3.84 %, and attached enoxaparin percentage of 98.53 ± 0.96 %. Both drugs had extended-release profiles and approximately 96 % of enoxaparin and 67 % dacarbazine were released within 8 h. The Enox-Dac-Chi NPs with IC50 of 59.60 ± 1.25 µg/ml were the most cytotoxic against melanoma cancer cells compared with chitosan nanoparticles containing only dacarbazine (Dac-Chi NPs) and free dacarbazine. There was no significant difference between the cellular uptake of Chi NPs and enoxaparin coated Chi NPs (Enox-Chi NPs) in B16F10 cells. Enox-Chi NPs with an average anti-angiogenic score of 1.75 ± 0.125 had more anti-angiogenic effect than enoxaparin. The results showed that simultaneous delivery of dacarbazine and enoxaparin by chitosan nanoparticles can enhance the anti-melanoma effect of dacarbazine. Additionally, enoxaparin can prevent the melanoma metastasis by its anti-angiogenic activity. Thus, the designed nanoparticles can be introduced as effective drug delivery vehicles for the treatment and prevention of metastatic melanoma.
Asunto(s)
Quitosano , Melanoma , Nanopartículas , Humanos , Enoxaparina/farmacología , Dacarbazina/farmacología , Dacarbazina/uso terapéutico , Quitosano/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Melanoma/tratamiento farmacológicoRESUMEN
Cerebral sinus venous thrombosis (CSVT) is an uncommon disease that is usually treated with anticoagulation (heparin, low-molecular heparin, or vitamin K-antagonists). We compared treatment with edoxaban, an oral factor Xa-antagonist, that has not been approved in patients with CSVT, with enoxaparin, a well-established therapy, in a rat model of CSVT. Fifty male Wistar rats were randomized into 5 groups (10 animals each) and subjected to aluminum chloride (AlCl3)-induced thrombosis of the superior sagittal sinus (SSS) or sham procedure. Animals with thrombosis of the SSS were treated with edoxaban, enoxaparin, or placebo. Diagnostic workup included neurological examination, MRI imaging, MR-flow measurements of the SSS, and immunohistochemical staining. Neurological examination revealed no differences between treatment groups. Seven days after initial thrombosis, flow in the SSS was lower in the active treatment group as compared to sham-operated animals (p < 0.05). Flow in the SSS in the active treatment groups (edoxaban 1 h prior to thrombosis: 0.16 cm/s ± 0.06 cm/s; edoxaban 6 h after thrombosis: 0.13 cm/s ± 0.05 cm/s; enoxaparin: 0.13 cm/s ± 0.04 cm/s; placebo: 0.07 cm/s ± 0.02 cm/s) was higher as compared to placebo (p < 0.05), but there were no differences between the active treatment groups (p > 0.05). Immunohistochemical staining showed no differences in the actively treated animals. Edoxaban proved to be similar to enoxaparin in a model of experimental AlCl3-induced CSVT.
Asunto(s)
Enoxaparina , Trombosis , Humanos , Masculino , Ratas , Animales , Enoxaparina/farmacología , Enoxaparina/uso terapéutico , Seno Sagital Superior , Ratas Wistar , Inhibidores del Factor Xa/farmacología , Inhibidores del Factor Xa/uso terapéutico , Heparina/farmacología , Trombosis/inducido químicamente , Trombosis/tratamiento farmacológicoRESUMEN
We investigated in vitro the management of intraprocedural anticoagulation in patients requiring immediate percutaneous coronary intervention (PCI) while using regular direct oral anticoagulants (DOACs). Twenty-five patients taking 20 mg of rivaroxaban once daily comprised the study group, while five healthy volunteers included the control group. In the study group, a beginning (24 h after the last rivaroxaban dose) examination was performed. Then, the effects of basal and four different anticoagulant doses (50 IU/kg unfractionated heparin (UFH), 100 IU/kg UFH, 0.5 mg/kg enoxaparin, and 1 mg/kg enoxaparin) on coagulation parameters were investigated at the 4th and 12th h following rivaroxaban intake. The effects of four different anticoagulant doses were evaluated in the control group. The anticoagulant activity was assessed mainly by anti-factor Xa (anti-Xa) levels. Beginning anti-Xa levels were significantly higher in the study group than in the control group (0.69 ± 0.77 IU/mL vs. 0.20 ± 0.14 IU/mL; p < 0.05). The study group's 4th and 12th-h anti-Xa levels were significantly higher than the beginning level (1.96 ± 1.35 IU/mL vs. 0.69 ± 0.77 IU/mL; p < 0.001 and 0.94 ± 1.21 IU/mL vs. 0.69 ± 0.77 IU/mL; p < 0.05, respectively). Anti-Xa levels increased significantly in the study group with the addition of UFH and enoxaparin doses at the 4th and 12th h than the beginning (p < 0.001 at all doses). The safest anti-Xa level (from 0.94 ± 1.21 to 2.00 ± 1.02 IU/mL) was achieved 12 h after rivaroxaban with 0.5 mg/kg enoxaparin. Anticoagulant activity was sufficient for urgent PCI at the 4th h after rivaroxaban treatment, and additional anticoagulant administration may not be required at this time. Twelve hours after taking rivaroxaban, administering 0.5 mg/kg of enoxaparin may provide adequate and safe anticoagulant activity for immediate PCI. This experimental study result should confirm with clinical trials (NCT05541757).
Asunto(s)
Enoxaparina , Intervención Coronaria Percutánea , Humanos , Enoxaparina/farmacología , Enoxaparina/uso terapéutico , Heparina/uso terapéutico , Heparina/farmacología , Rivaroxabán/uso terapéutico , AnticoagulantesRESUMEN
BACKGROUND: The military has used topical hemostatic agents to successfully treat life-threatening external bleeding for years. In contrast to the military environment, the general population are increasingly prescribed anticoagulants. There are only few comparative evaluations of topical hemostatic agents with anticoagulated human blood. It is important to understand the impact of these agents on those who take anticoagulants. STUDY DESIGN AND METHODS: Citrated blood of patients treated with enoxaparin, heparin, and acetylsalicylic acid, apixaban or phenprocoumon was incubated with different hemostatic agents (QuikClot Gauze, Celox Granules, Celox Gauze, Chito SAM 100, WoundClot Trauma Gauze, QuikClot Gauze Moulage Trainer and Kerlix) and rotational thromboelastometry was performed with non-activated thromboelastometry (NATEM reagent). RESULTS: All tested agents improved the onset of coagulation in all anticoagulants, mostly to a significant degree. Most significant improvements were produced by QuikClot Gauze and QuikClot Gauze Moulage Trainer, followed by the tested chitosans (Celox Granules, Celox Gauze, Chito SAM 100). Of the anticoagulant groups, the most significant improvements were seen in enoxaparin. This was followed in order by apixaban, heparin, and acetylsalicylic acid, and phenprocoumon. DISCUSSION: All the hemostatic agents tested were able to activate the clotting cascade earlier and initiate faster clot formation in anticoagulated blood. A definitive head-to-head comparison is not feasible, because of the limitations of an in-vitro analysis. However, the sometimes-presented hypothesis that kaolin-based hemostatic agents are ineffective in anticoagulated blood is inaccurate according to our data. Hemostasis with hemostatic agents appears most challenging with phenprocoumon.
Asunto(s)
Hemostáticos , Humanos , Hemostáticos/farmacología , Fenprocumón , Enoxaparina/farmacología , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Heparina/farmacología , Aspirina/farmacología , Aspirina/uso terapéuticoRESUMEN
OBJECTIVE: The study aimed to investigate the protection of enoxaparin (E) against experimental ischemic (I) and ischemic-reperfusion (I/R) injury in rat ovaries on in vitro fertilization outcomes. METHODS: In total, 56 adult female Sprague-Dawley albino rats were randomly assigned to 6 groups of 8 animals each: Sham, Ischemia, I/R, Sham+E, I+E, and I/R+E. Ischemia groups were subjected to bilateral adnexal torsion for 3 h. In contrast, I/R and I/R+E groups received subsequent detorsion for 3 h. Enoxaparin (0.5 mg/kg s.c.) was administered 30 min prior to ischemia (I+platelet-rich plasma) or reperfusion (I/R+I+platelet-rich plasma). Ovaries were stimulated through intraperitoneal injection of 150-300 internal units IU/kg pregnant mare serum gonadotropin. Anti-Müllerian hormone levels were measured before and after surgery in all groups. RESULTS: When the number of metaphase II oocytes was evaluated, statistically significant differences were observed between the I and I+E (p=0.001) and I/R and I/R+E (p=0.000) groups. When both I and I+E groups and I/R and I/R+E groups were compared, it was found that E application increased the number of fertilized oocytes. The number of embryos on the second day was higher in the I/R+E group than that in the I/R group. Statistically significant differences were found in the number of grade 1 embryos between the I/R and I/R+E groups (p=0.003). In comparing anti-Müllerian hormone values within the group, the highest decrease was observed in the I and I/R groups. CONCLUSION: Enoxaparin effectively minimizes ovarian damage and preserves ovarian reserve following ovarian torsion.
Asunto(s)
Enfermedades del Ovario , Daño por Reperfusión , Animales , Humanos , Ratas , Femenino , Antioxidantes , Enfermedades del Ovario/tratamiento farmacológico , Enfermedades del Ovario/prevención & control , Enoxaparina/farmacología , Enoxaparina/uso terapéutico , Hormona Antimülleriana , Ratas Sprague-Dawley , Daño por Reperfusión/prevención & control , Isquemia , Fertilización In VitroRESUMEN
Unfractionated heparin (UFH) and enoxaparin (Enox) were substituted with a photoswitch (PS) showing quantitative trans-cis and cis-trans photoisomerizations. Long half-life of the cis photoisomer enabled comparison of the properties of heparins substituted with both PS photoisomers. Hydrodynamic diameter, Dh, of UFH-PS decreased upon trans-cis photoisomerization, the change being more pronounced for UFH-PS with a higher degree of substitution (DS), while Dh of Enox-PS did not significantly change. The anticoagulative properties of substituted heparins were significantly attenuated compared to non-substituted compounds. The interaction of UFH-PS with HSA, lysozyme, and protamine was studied with ITC. Under serum-free conditions, UFH-PS-trans with a high DS stimulated proliferation of murine fibroblasts, while UFH-PS-cis decreased the viability of these cells. Under serum conditions, both UFH-PS-cis and UFH-PS-trans decreased cell viability, the reduction for UFH-PS-cis being higher than that for UFH-PS-trans. Neither Enox-PS-trans nor Enox-PS-cis influenced the viability at concentrations prolonging aPTT, while at higher concentrations their cytotoxicity did not differ.
Asunto(s)
Enoxaparina , Heparina , Animales , Ratones , Heparina/farmacología , Resultado del Tratamiento , Enoxaparina/farmacología , AnticoagulantesRESUMEN
BACKGROUND: Central venous catheters are prone to clotting, particularly in patients with cancer. Although low-molecular-weight heparin and direct oral anticoagulants, such as apixaban and rivaroxaban, have been evaluated for the prevention of catheter thrombosis, their efficacy remains uncertain. OBJECTIVES: Compare apixaban and rivaroxaban with enoxaparin for the prevention of catheter-induced clotting in vitro. METHODS: To address this uncertainty, we used a well-established microplate-based assay to compare the effects of enoxaparin, apixaban, and rivaroxaban on catheter-induced thrombosis and thrombin generation in human plasma. RESULTS: Consistent with our previous findings, catheter segments shortened the clotting time and promoted thrombin generation. When compared at concentrations with similar anti-factor Xa activity as enoxaparin, apixaban and rivaroxaban were >20-fold less potent than enoxaparin for the prevention of catheter-induced clotting and thrombin generation. CONCLUSION: The prevention of catheter thrombosis in patients with cancer is challenging. Clinical trials are needed to compare the efficacy of low-molecular-weight heparin with that of direct oral anticoagulants both for the prevention and treatment of catheter thrombosis.
Asunto(s)
Neoplasias , Trombosis , Humanos , Enoxaparina/farmacología , Enoxaparina/uso terapéutico , Rivaroxabán/uso terapéutico , Anticoagulantes/uso terapéutico , Trombina , Piridonas/farmacología , Piridonas/uso terapéutico , Heparina de Bajo-Peso-Molecular/uso terapéutico , Trombosis/etiología , Trombosis/prevención & control , Catéteres , Neoplasias/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéuticoRESUMEN
BACKGROUND: Management of anticoagulant therapy in COVID-19 patients is critical. Low-molecular-weight heparin (LMWH) thromboprophylaxis is already recommended, and anti-Factor Xa (anti-FXa) monitoring has been used to titrate LMWH doses. METHODS: Through a cross-sectional study, we evaluated anti-FXa activity in patients admitted to the ICU, receiving intermediate dose (30, 40, 50 mg, subcutaneously [SC], twice daily) or therapeutic dose (1 mg/kg, SC, Q12h) of enoxaparin to find whether the patients in these two groups achieved anti-FXa levels in the accepted thromboprophylaxis range. RESULTS: The occurrence of deep vein thrombosis was 26% in the therapeutic-dose group and 17% in the intermediate-dose group. D-dimer values were nearly 3.5-fold higher in those who received a therapeutic dose of anticoagulants than in those who received intermediate-dose thromboprophylaxis. Patients in the therapeutic-dose group had significantly higher IL-6 levels (p ≤ 0.001). More than one-third of the patients in the therapeutic-dose group (n = 8; 42.18%) and approximately half of the patients in the intermediate-dose group (n = 12; 52.2%) achieved the target range level of anti-FXa. Patients who received therapeutic doses were more likely to have anti-FXa levels above the expected range (47.4 vs 13% in the intermediate-dose group; p < 0.05). CONCLUSION: Therapeutic dose of enoxaparin in critically ill COVID-19-infected patients did not reduce the incidence of thromboembolic events and, on the other hand, may predispose these patients to increased risk of bleeding by increasing anti-FXa activity above the desired level. Administration of intermediate-dose thromboprophylaxis is suggested to achieve anti-FXa levels in the accepted thromboprophylaxis range.
Asunto(s)
COVID-19 , Tromboembolia Venosa , Humanos , Enoxaparina/uso terapéutico , Enoxaparina/farmacología , Anticoagulantes , Heparina de Bajo-Peso-Molecular/uso terapéutico , Factor Xa , Estudios Transversales , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control , Tromboembolia Venosa/tratamiento farmacológico , Inhibidores del Factor Xa/uso terapéuticoRESUMEN
BACKGROUND: Cats placed on anticoagulant medication require frequent monitoring. The veterinary viscoelastic coagulation monitor (VCM-Vet) could provide a convenient and cost-effective monitoring, enabling therapeutic decision making. HYPOTHESIS/OBJECTIVES: Enoxaparin will lead to changes in VCM-Vet variables and these will correlate with antiXa activity. ANIMALS: Twenty-one healthy cats. METHODS: Cats were randomized to receive either enoxaparin (1 mg/kg) subcutaneously or 0.9% NaCl (equal volume) and crossed over with a 7-day washout period. The investigators were blinded to group allocation until data analysis. Jugular blood samples were drawn at time 0, and 2, 4, and 8 hours after injection for VCM-Vet analysis within 2 min of collection. Citrated plasma was frozen at -80°C for antiXa activity analysis. A Generalized Linear Model was completed to assess changes between baseline measurements and all time points. RESULTS: Significant differences between the enoxaparin-treated cats and controls at for T0h and T2h were found and presented as mean ± SD for clotting time (enoxaparin, 593.4 ± 78.0 s; control, 448.5 ± 50.3 s, P < .001), clot formation time (enoxaparin, 183.1 ± 41.7 s; control, 155.4 ± 28.0 s, P = .001), and alpha angle (enoxaparin, 52.4 ± 6.1°; control, 56.9 ± 3.7 s, P = .003). AntiXa activity was significantly different between T0 and all other timepoints for the enoxaparin group (P < .001). There was no correlation between changes in clotting time and antiXa activity. CONCLUSIONS AND CLINICAL IMPORTANCE: The VCM-Vet detects a difference at 2 hours after single-dose enoxaparin administration and it can be useful for anticoagulant therapy monitoring in cats.
Asunto(s)
Anticoagulantes , Enoxaparina , Gatos , Animales , Enoxaparina/farmacología , Enoxaparina/uso terapéutico , Estudios Cruzados , Anticoagulantes/uso terapéutico , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea/veterinariaRESUMEN
Background and objectives: Cementless total hip arthroplasty is a common surgical procedure and perioperative thromboprophylaxis is used to prevent deep vein thrombosis or pulmonary embolism. Osseointegration is important for long-term implant survival, and there is no research on the effect of different thromboprophylaxis agents on the process of osseointegration. Materials and Methods: Seventy rats were allocated as follows: Group I (control group), Group II (enoxaparin), Group III (nadroparin), and Group IV (fondaparinux). Ovariectomy was performed on all subjects, followed by the introduction of an intramedullary titanium implant into the femur. Thromboprophylaxis was administered accordingly to each treatment group for 35 days postoperatively. Results: Group I had statistically significantly lower anti-Xa levels compared to treatment groups. Micro-CT analysis showed that nadroparin had lower values compared to control in bone volume (0.12 vs. 0.21, p = 0.01) and percent bone volume (1.46 vs. 1.93, p = 0.047). The pull-out test showed statistically significant differences between the control group (8.81 N) compared to enoxaparin, nadroparin, and fondaparinux groups (4.53 N, 4 N and 4.07 N, respectively). Nadroparin had a lower histological cortical bone tissue and a higher width of fibrous tissue (27.49 µm and 86.9 µm) at the peri-implant area, compared to control (43.2 µm and 39.2 µm), enoxaparin (39.6 µm and 24 µm), and fondaparinux (36.2 µm and 32.7 µm). Conclusions: Short-term administration of enoxaparin, nadroparin, and fondaparinux can reduce the osseointegration of titanium implants, with nadroparin having the most negative effect. These results show that enoxaparin and fondaparinux are preferred to be administered due to a lesser negative impact on the initial implant fixation.
Asunto(s)
Nadroparina , Tromboembolia Venosa , Femenino , Ratas , Animales , Nadroparina/farmacología , Nadroparina/uso terapéutico , Fondaparinux , Enoxaparina/farmacología , Enoxaparina/uso terapéutico , Titanio/uso terapéutico , Oseointegración , Factor X , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Tromboembolia Venosa/tratamiento farmacológicoRESUMEN
OBJECTIVE: With this study we aimed at investigating the impact of enoxaparin (E) and α-lipoic acid (α-LA) on ischemia/reperfusion (I/R) damage in an experimental ovarian torsion (T) detorsion (D) model. MATERIALS AND METHODS: The study comprised 80 female albino rats aged 12 weeks. They were divided into 8 groups as follows, with 10 rats in each group: Group 1 (Sham), Group 2 (Ischemia, 3 hours), Group 3 (I/R, 6 hours reperfusion), Group 4 (I/R, 3 days reperfusion), Group 5 (I/R, E, 6 hours), Group 6 (I/R, E, 3 days), Group 7 (I/R, E+α-LA, 6 hours), and Group 8 (I/R, E+α-LA, 3 days). Immediately after detorsion, enoxaparin (0.5 mg/kg/day, sc) or α-LA (100 mg/kg/day, ip) were administered. Ovarian levels of malondialdehyde (MDA), glutathione peroxidase (GPx), and catalase were measured. In addition to total Antioxidant Status (TAS) and Total Oxidative Stress (TOS), the Oxidative Stress Index (OSI) was calculated. Serum levels of AMH, FSH, LH, E2, and progesterone were measured. Ovarian samples were histopathologically examined and they underwent Tag staining for apoptosis. RESULTS: Compared with the sham group, there was a significant increase in TOS, OSI, and MDA levels in I/R group (p<0.001). Compared to Group 2, a significant increase was determined in TOS and OSI in Group 3 (p<0.05). In Group 4, a significant increase was found compared to Group 2 (p<0.01). The lowest level of I/R damage and the highest level of antioxidants were found in Group 2, 7, and 8. The highest values of TOS, OSI, and MDA were found in Group 3, Group 4, Group 5, and Group 6 (p<0.001). When the sham group and Group 4 were compared, it was found that AMH and E2 levels decreased (p<0.001), while FSH levels increased (p<0.001). In Group 6, AMH and E2 values were significantly decreased compared to the sham group (p<0.001). In the histopathological examination, the findings were observed to be parallel to those of the biochemical markers. CONCLUSIONS: Combined use of α-Lipoic acid and enoxaparin prevents oxidative stress and ovarian damage due to ischemia-reperfusion injury better than the use of drugs alone.
Asunto(s)
Daño por Reperfusión , Ácido Tióctico , Femenino , Ratas , Antioxidantes/metabolismo , Antioxidantes/farmacología , Biomarcadores , Catalasa , Enoxaparina/farmacología , Hormona Folículo Estimulante , Glutatión Peroxidasa , Isquemia , Malondialdehído , Estrés Oxidativo , Progesterona , Reperfusión , Daño por Reperfusión/patología , Ácido Tióctico/farmacología , AnimalesRESUMEN
Novel and efficient strategies need to be developed to interfere with the SARS-CoV-2 virus. One of the most promising pharmaceutical targets is the nucleocapsid protein (N), responsible for genomic RNA packaging. N is composed of two folded domains and three intrinsically disordered regions (IDRs). The globular RNA binding domain (NTD) and the tethered IDRs are rich in positively charged residues. The study of the interaction of N with polyanions can thus help to elucidate one of the key driving forces responsible for its function, i.e., electrostatics. Heparin, one of the most negatively charged natural polyanions, has been used to contrast serious cases of COVID-19 infection, and we decided to study its interaction with N at the molecular level. We focused on the NTR construct, which comprises the NTD and two flanking IDRs, and on the NTD construct in isolation. We characterized this interaction using different nuclear magnetic resonance approaches and isothermal titration calorimetry. With these tools, we were able to identify an extended surface of NTD involved in the interaction. Moreover, we assessed the importance of the IDRs in increasing the affinity for heparin, highlighting how different tracts of these flexible regions modulate the interaction.
Asunto(s)
Enoxaparina , Proteínas de la Nucleocápside , SARS-CoV-2 , COVID-19 , Enoxaparina/farmacología , Humanos , Proteínas de la Nucleocápside/química , Proteínas de la Nucleocápside/genética , Polielectrolitos , ARN , SARS-CoV-2/efectos de los fármacosRESUMEN
Background. Due to the interactions between neuroinflammation and coagulation, the neural effects of lipopolysaccharide (LPS)-induced inflammation (1 mg/kg, intraperitoneal (IP), n = 20) and treatment with the anti-thrombotic enoxaparin (1 mg/kg, IP, 15 min, and 12 h following LPS, n = 20) were studied in C57BL/6J mice. Methods. One week after LPS injection, sensory, motor, and cognitive functions were assessed by a hot plate, rotarod, open field test (OFT), and Y-maze. Thrombin activity was measured with a fluorometric assay; hippocampal mRNA expression of coagulation and inflammation factors were measured by real-time-PCR; and serum neurofilament-light-chain (NfL), and tumor necrosis factor-α (TNF-α) were measured by a single-molecule array (Simoa) assay. Results. Reduced crossing center frequency was observed in both LPS groups in the OFT (p = 0.02), along with a minor motor deficit between controls and LPS indicated by the rotarod (p = 0.057). Increased hippocampal thrombin activity (p = 0.038) and protease-activated receptor 1 (PAR1) mRNA (p = 0.01) were measured in LPS compared to controls, but not in enoxaparin LPS-treated mice (p = 0.4, p = 0.9, respectively). Serum NfL and TNF-α levels were elevated in LPS mice (p < 0.05) and normalized by enoxaparin treatment. Conclusions. These results indicate that inflammation, coagulation, neuronal damage, and behavior are linked and may regulate each other, suggesting another pharmacological mechanism for intervention in neuroinflammation.
Asunto(s)
Enoxaparina , Lipopolisacáridos , Animales , Modelos Animales de Enfermedad , Enoxaparina/farmacología , Inflamación/metabolismo , Lipopolisacáridos/farmacología , Ratones , Ratones Endogámicos C57BL , ARN Mensajero/genética , Receptor PAR-1 , Trombina , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Since the COVID-19 pandemic started, mesenchymal stromal cells (MSC) appeared as a therapeutic option to reduce the over-activated inflammatory response and promote recovery of lung damage. Most clinical studies use intravenous injection for MSC delivery, raising several concerns of thrombogenic risk due to MSC procoagulant activity (PCA) linked to the expression of tissue factor (TF/CD142). This is the first study that demonstrated procoagulant activity of TF+ human immature dental pulp stromal cells (hIDPSC, NestaCell® product) with the percentage of TF+ cells varied from 0.2% to 63.9% in plasma of healthy donors and COVID-19 heparin-treated patients. Thrombogenic risk of TF+ hIDPSCs was evaluated by rotational thromboelastometry (in vitro) and in critically ill COVID-19 patients (clinical trial). We showed that the thromboelastography is not enough to predict the risk of TF+ MSC therapies. Using TF-negative HUVEC cells, we demonstrated that TF is not a unique factor responsible for the cell's procoagulant activity. However, heparin treatment minimizes MSC procoagulant (in vitro). We also showed that the intravenous infusion of hIDPSCs with prophylactic enoxaparin administration in moderate to critically ill COVID-19 patients did not change the values of D-dimer, neither in the PT and PTT times. Our COVID-19 clinical study measured and selected the therapeutic cells with low TF (less than 25% of TF+ hIDPSCs). Our data indicate that the concomitant administration of enoxaparin and low TF-loaded is safe even for critically ill COVID-19 patients.
Asunto(s)
COVID-19 , Tromboplastina , Tratamiento Basado en Trasplante de Células y Tejidos , Ensayos Clínicos como Asunto , Enfermedad Crítica , Enoxaparina/farmacología , Enoxaparina/uso terapéutico , Heparina , Humanos , Pandemias , Tromboplastina/metabolismoRESUMEN
BACKGROUND: Low-molecular-weight heparin enoxaparin is widely used in pharmacological thromboprophylaxis after coronary artery bypass grafting (CABG). The aim of this study was to compare anti-factor X activity (anti-Xa) levels when the thromboprophylactic dose of enoxaparin was provided after CABG, with two different administration routes: continuous intravenous infusion (CIV) and subcutaneous bolus (SCB) injection. We hypothesized that the current standard method of SCB administration might lead to lower anti-Xa levels than recommended in other patient groups, due to reduced bioavailability. METHODS: In this prospective, randomized, controlled clinical trial, 40 patients scheduled for elective CABG were randomized to receive 40 mg of enoxaparin per day either as CIV or SCB for 72 h. Enoxaparin was initiated 6-10 h after CABG. Anti-Xa levels were measured 12-14 times during the study period. The primary outcome, that is, the maximum anti-Xa concentration over 0-24 h (Cmax0-24h ), was calculated from these measured values. Secondary outcomes were Cmax25-72h and the trough concentration of anti-Xa after 72 h of enoxaparin initiation (C72h ). RESULTS: Twenty patients were randomized to the CIV-group and 19 to the SCB-group. The median anti-Xa Cmax0-24h was significantly lower in the CIV-group than in the SCB-group: 0.15 [interquartile range (IQR) 0.13-0.19] IU/ml versus 0.25 (IQR 0.18-0.32) IU/ml, p < .005. The median anti-Xa Cmax25-72h was 0.12 (IQR, 0.1-0.17) IU/ml versus 0.23 (IQR 0.19-0.31) IU/ml, respectively, p < .005. At 72 h, there was no difference between the groups in their anti-Xa levels. CONCLUSIONS: In this low-risk CABG patient population, SCB administration of a thromboprophylactic dose of enoxaparin provided anti-Xa levels that are considered sufficient for thromboprophylaxis in other patient groups. CIV administration resulted in lower anti-Xa levels compared to the SCB route.