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Patients with diabetes face a 2-4-fold greater cardiovascular risk compared to those without diabetes. Both metformin and acetylsalicylic acid (aspirin) treatment have demonstrated a significant reduction in this risk. This single-center, open-label, sequence randomized, 2 × 2 crossover, single-dose clinical trial evaluated the pharmacokinetics profile and comparative bioavailability of a novel oral fixed-dose combination (FDC) of metformin/acetylsalicylic acid (500/100 mg tablet) versus the reference mono-drugs administered concomitantly, metformin 500 mg tablet and acetylsalicylic acid 100 mg tablet, in 22 healthy Mexican adult volunteers under fasting conditions. Blood samples were collected predose and at specified intervals across a 24-hour period following administration and were analyzed for metformin and salicylic acid using high-performance liquid chromatography coupled with tandem mass spectrometry. Test products were considered to have comparative bioavailability if confidence intervals of natural log-transformed (maximum plasma drug concentration (Cmax), (area under the plasma drug concentration-time curve form 0 up to last sampling time (AUC0 -t), and (area under the plasma drug concentration-time cruve from 0 up to infinity (AUC0 ∞) data were within the range of 80%-125%. The results obtained from the present clinical study demonstrate the comparative bioavailability of the FDC when compared with the coadministration of reference mono-drugs. There were no adverse events or adverse reactions reported throughout the study.

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Pulmonary tuberculosis (TB) inflammation is an underestimated disease complication which anti-inflammatory drugs may alleviate. This study explored the potential use of the COX-2 inhibitors acetylsalicylic acid (ASA) and celecoxib in 12 TB patients and 12 healthy controls using a whole-blood ex vivo model where TNFα, PGE2, and LTB4 plasma levels were quantitated by ELISA; we also measured COX-2, 5-LOX, 12-LOX, and 15-LOX gene expression. We observed a significant TNFα production in response to stimulation with LPS or M. tuberculosis (Mtb). Celecoxib, but not ASA, reduced TNFα and PGE2 production, while increasing LTB4 in patients after infection with Mtb. Gene expression of COX-2 and 5-LOX was higher in controls, while 12-LOX was significantly higher in patients. 15-LOX expression was similar in both groups. We concluded that COX-2 inhibitors downregulate inflammation after Mtb infection, and our methodology offers a straightforward time-efficient approach for evaluating different drugs in this context. Further research is warranted to elucidate the underlying mechanisms and assess the potential clinical benefit.

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Abstract Telomerase enzyme is necessary for the elongation of telomeres while telomerase being critical for aging and cancer. Metformin, ibuprofen, and acetylsalicylic acid used in this research are drugs that millions of people already use and that many are likely to use in future. In this study, the effects of these drugs on telomerase activity of Mus musculus swiss albino mice in liver tissue were investigated and the telomerase activity was measured with a PCR-ELISA based kit. In the study a possible connection between telomerase enzyme activity and activities of antioxidant enzymes was also investigated by determining the activity of superoxide dismutase (SOD) and catalase enzymes. The data obtained show that metformin slightly decreased telomerase enzyme activity in low dose application; however, this change was not statistically significant. In ibuprofen application, there was a significant inhibitory effect when high doses were used; whereas, there was a slight inhibitory effect at low doses. In acetylsalicylic acid application, a slight activator effect was detected; it was not statistically significant, though. Metformin was observed to increase catalase and SOD activities in general while low and high doses of acetyl salicylic acid showed different effects. In addition, ibuprofen caused a statistically significant increase in liver SOD values. It is important to note that this study demonstrated a significant inhibitory effect of ibuprofen on telomerase enzyme activity in animal models..

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La enfermedad valvular cardíaca es una condición muy frecuente en la población general y un porcentaje considerable de estos pacientes requieren un tratamiento intervencionista sobre su valvulopatía para lograr atenuar su evolución natural. En este contexto, en la actualidad ha aumentado el uso de las prótesis valvulares biológicas para su tratamiento y, con ello, surge el dilema del manejo antitrombótico en estos pacientes en términos de prevención de tromboembolias y eventos hemorrágicos. ¿Cuál es el fármaco más efectivo y seguro en el período posoperatorio temprano? ¿Qué antitrombóticos podemos utilizar en el período posoperatorio tardío? ¿Qué estrategia seguimos cuando el paciente presenta otras indicaciones de anticoagulación? El objetivo de esta revisión es valorar la evidencia actual respecto al tratamiento antitrombótico en pacientes portadores de prótesis valvulares biológicas con y sin indicaciones adicionales de anticoagulación.

Heart valve disease is a very common condition in the general population and a considerable percentage of these patients require interventional treatment for their valve disease to mitigate its natural evolution. In this context, the use of biological prosthetic valves for their treatment has now increased, and with this, the dilemma of antithrombotic management in these patients arises, in terms of prevention of thromboembolism and hemorrhagic events. What is the most effective and safe drug in the early postoperative period? What antithrombotics can we use in the late postoperative period? What strategy do we follow when the patient presents other indications for anticoagulation? The objective of this review is to assess the current evidence regarding antithrombotic treatment in patients with biological prosthetic valves with and without additional indications for anticoagulation.

A valvopatia é uma condição muito comum na população geral e uma porcentagem considerável desses pacientes necessita de tratamento intervencionista para sua valvopatia para amenizar sua evolução natural. Nesse contexto, o uso de próteses valvares biológicas para seu tratamento tem aumentado, e com isso surge o dilema do manejo antitrombótico nesses pacientes em termos de prevenção de tromboembolismo e eventos hemorrágicos. Qual é o fármaco mais eficaz e seguro no pós-operatório imediato? Que antitrombóticos podemos usar no pós-operatório tardio? Que estratégia seguimos quando o paciente apresenta outras indicações de anticoagulação? O objetivo desta revisão é avaliar as evidências atuais sobre o tratamento antitrombótico em pacientes com próteses valvares biológicas com e sem indicações adicionais de anticoagulação.

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BACKGROUND: The emergence of resistant isolates has brought challenges to the treatment of sporotrichosis, prompting the search for new therapeutic strategies. Previous studies reported that nonsteroidal anti-inflammatory drugs (NSAIDs) show in vitro activity against several pathogenic fungi, including species of Candida, Cryptococcus, and Trichosporon. AIMS: This study aimed to investigate the in vitro efficacy of three NSAIDs (acetylsalicylic acid, diclofenac sodium, and ibuprofen), alone and in combination with itraconazole, against eleven clinical isolates of Sporothrix brasiliensis and Sporothrix schenckii. METHODS: Minimal inhibitory concentrations were determined by the broth microdilution method. Drug interactions and the fractional inhibitory concentration index of NSAIDs and itraconazole were assessed by the checkerboard method. RESULTS: When used alone, ibuprofen was the most active NSAID, followed by acetylsalicylic acid. Combinations of NSAIDs with itraconazole showed synergistic antifungal activity against nine isolates. It was also found that itraconazole combined with acetylsalicylic acid, diclofenac sodium, or ibuprofen, led to resistance reversal in two, three, and five of the six drug-resistant isolates, respectively. CONCLUSIONS: The results indicate that the combination of itraconazole and the evaluated NSAIDs are a promising strategy for the treatment of sporotrichosis.

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Bacterial nanocellulose (BNC) is a novel nanomaterial known for its large surface area, biocompatibility, and non-toxicity. BNC contributes to regenerative processes in the skin but lacks antimicrobial and anti-inflammatory properties. Herein, the development of bioactive wound dressings by loading antibacterial povidone-iodine (PVI) or anti-inflammatory acetylsalicylic acid (ASA) into bacterial cellulose is presented. BNC is produced using Hestrin-Schramm culture media and loaded via immersion in PVI and ASA. Through scanning electron microscopy, BNC reveals open porosity where the bioactive compounds are loaded; the mechanical tests show that the dressing prevents mechanical wear. The loading kinetic and release assays (using the Franz cell method) under simulated fluids present a maximum loading of 589.36 mg PVI/g BNC and 38.61 mg ASA/g BNC, and both systems present a slow release profile at 24 h. Through histology, the complete diffusion of the bioactive compounds is observed across the layers of porcine skin. Finally, in the antimicrobial experiment, BNC/PVI produced an inhibition halo for Gram-positive and Gram-negative bacteria, confirming the antibacterial activity. Meanwhile, the protein denaturation test shows effective anti-inflammatory activity in BNC/ASA dressings. Accordingly, BNC is a suitable platform for the development of bioactive wound dressings, particularly those with antibacterial and anti-inflammatory properties.

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Os anticoagulantes e antiagregantes plaquetários são medicamentos utilizados por uma grande parcela da população mundial. Eles são utilizados para prevenir que pacientes de risco desenvolvam doenças cardiovasculares, como o infarto agudo do miocárdio (IAM) ou o acidente vascular cerebral (AVC). Por serem muito utilizados, constantemente o cirurgião-dentista poderá se deparar em sua rotina clínica, com pacientes usuários de anticoagulantes ou antiagregantes. Neste caso, o profissional precisará estar ciente das normas mais atuais de manejo com cada um dos tipos de medicamentos, para que o tratamento seja realizado com sucesso. No presente trabalho, é proposto um Protocolo Operacional Padrão (POP), que pode ser seguido no momento de realizar cirurgias orais em pacientes em uso de Varfarina, Ácido Acetil Salicílico, Heparina de Baixo Peso Molecular, Heparina Não Fracionada, Rivaroxabana e Clopidogrel.

Anticoagulants and antiplatelet agents are drugs used by a large portion of the world population. They are used to prevent at-risk patients from developing cardiovascular diseases, such as acute myocardial infarction (AMI) or stroke (stroke). Because they are widely used, the dental surgeon may constantly encounter patients using anticoagulants or anti-aggregating agents in their clinical routine. In this case, the professional will need to be aware of the most current management standards with each type of medication, so that the treatment is carried out successfully. In the present work, a Standard Operational Protocol (POP) is proposed, which can be followed when performing oral surgeries on patients using Warfarin, Acetyl Salicylic Acid, Low Molecular Weight Heparin, Unfractionated Heparin, Rivaroxaban and Clopidogrel.

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The poultry industry suffers from various diseases or stresses. In poultry, apart from being antipyretic, acetylsalicylic acid (ASA) is widely used to cope with different issues including heat stress, and respiratory and digestive orders. This study evaluated the beneficial and toxic effects of ASA at different dose levels in broiler birds. To evaluate these toxic and beneficial effects it is necessary to examine the physical and serum biochemical parameters as well as the histopathological changes with tissue sections taken from broiler birds under experimental trial. This study was conducted on 60 one-day-old broiler chicks purchased from a local market in Faisalabad. Chicks were reared for the first 14 days under similar conditions. On the 15th day, birds were randomly divided into 4 groups (1-4) with 15 birds in each group. Group 4 was kept as control, while groups 1, 2, and 3 were treated with ASA at the dose of 300, 600, and 1200 mg/L of drinking water for 21 days. There were 3 samplings performed at 21, 28, and 35 days post-treatment. The live body weight and carcass weight were noted on each sampling. All the visceral organs were recorded for gross pathological changes. The serum samples were collected for biochemical evaluation. Histopathology of all the visceral organs was performed to observe the microscopic changes. A significant (P<0.05) increase in live body weight at a 300mg/L dose was noted after the first 2 samplings. A significant (P<0.05) increase in the relative organ weight was recorded at 1200 mg/L. The groups treated with ASA 600 and 1200 mg/L showed increased (P<0.05) AST, ALT, and creatinine levels from that of the control group. The group treated with 1200 mg/L of ASA showed increased (P<0.05) urea, serum total protein, and albumin level in all the samplings. Histopathological changes revealed swollen hepatocytes, increased sinusoidal spaces in the liver, congestion and abnormal glomerular spaces in the kidney, congestion and alveolar disruption in the lungs, and generation of villi and cellular degeneration in the intestine in a high-dose group. The study concluded that ASA at a low dose can be used for a long time in broilers and has a growth promontory role, while high-level doses cause hepatorenal toxicity.(AU)

A indústria avícola é afetada por diversas doenças ou estresses. Particularmente devido às aves serem antipiréticas. O ácido acetil salicílico (AAS) é largamente utilizado com diferentes objetivos que incluem o controle do estresse calórico, bem como a atividade respiratória e digestiva. O propósito deste estudo foi a avaliação dos efeitos benéficos e tóxicos do emprego de diferentes dosagens do AAS em frangos de corte. As variáveis analisadas foram: exame físico, parâmetros bioquímicos, bem como as alterações histopatológica em seções de tecidos colhidas das aves em um ensaio experimental. O estudo foi conduzido em 60 frangos de corte com um dia de idade adquiridos em um mercado local de Faisalabad que foram recriados nos primeiros 14 dias em idênticas condições. Então no 15º dia as aves foram distribuídas randomicamente em quatro grupos identificados pelos números 1 a 4, com 15 aves em cada grupo. O grupo 4 foi mantido como grupo controle e os grupos 1, 2 e 3 foram tratados com AAS, respectivamente, nas doses de 300, 600 e 1200 mg/L de água de bebida, durante 21 dias. Foram realizadas três amostragens nos dias 21, 28 e 35 pós-tratamento. O peso vivo corpóreo e da carcaça foi registrado em cada amostragem. Em todos os órgãos viscerais foi analisada a presença de alterações patológicas. As amostras de soro sanguíneo foram colhidas para a avaliação bioquímica. O exame histopatológico de todos os órgãos viscerais foi realizado para a observação de alterações microscópicas. A partir da segunda amostragem foi observado um aumento significante (p<0,05) no peso corpóreo na dosagem de 300mg/L. Um significante aumento no peso relativo dos órgãos foi registrado na dosagem de 1200 mg/L. Os grupos tratados com dosagens de 600 e 1200 mg/L de AAS, apresentaram aumento significante dos níveis de AST, ALT e de creatinina quando comparados ao grupo controle. O grupo tratado com 1200 mg/L de AAS apresentou um aumento significante (P,0,05) de uréia, proteína sérica total e de albumina em todas as amostragens. No grupo de alta dosagem foram observados alterações histopatológicas constituídas por aumento dos hepatócitos, aumento dos espaços sinusoidais no fígado, congestão e anormalidades nos espaços glomerulares nos rins, congestão e ruptura alveolar nos pulmões, degeneração das vilosidades e celular nos intestinos A conclusão obtida foi que em frangos de corte uma baixa dosagem do AAS pode ser utilizada por um período de longa duração, apresentando um efeito promotor do crescimento, contudo as doses elevadas determinam toxicidade hepática e renal.(AU)

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OBJECTIVE: To assess if the low-dose acetylsalicylic acid (ASA) would be capable of modifying endothelial function throughout pregnancy in nulliparous patients. METHODS: A double-blind, randomized clinical trial with 277 were included. A total of 139 were orally administered 100 mg/day of ASA, and 138 received placebo. Endothelial function was assessed by flow-mediated dilation (FMD) in the brachial artery before the start of medication (11-14 weeks) and 20-24 and 30-34 weeks of gestation. The intervention was maintained until 34 weeks. The Mann-Whitney U test was used to compare the placebo and ASA groups. The comparison of FMD during pregnancy was performed using the Friedman test. RESULTS: The groups (ASA and placebo) were similar regarding to age, weight, height, and body mass index (BMI) (p > .005). The comparison of values of FMD (%) between placebo vs. ASA at 11 and 14 weeks (8.9 vs. 9.7%, p: .253), 20 and 24 weeks (8.8 vs. 10.7%, p: .152), and 30 and 34 weeks (10.7 vs. 9.8%, p: .314) did not show significant changes throughout pregnancy. We observed a significant prevalence of PE in the placebo regarding to ASA group [14 (10.2%) vs. 8 (5.8%), p: .171]. CONCLUSION: Acetylsalicylic acid did not modify the endothelial function assessed by FMD of the brachial artery during pregnancy in nulliparous women.

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INTRODUCTION: There is still controversy regarding thrombo-prophylaxis for the reduction of thromboembolic disease in major orthopedic surgery. OBJECTIVE: To answer the following question: is there a difference in the effectiveness and safety in the antithrombotic management of patients with a traditional regimen of enoxaparin against acetyl salicylic acid? MATERIAL AND METHODS: The surgeries were performed by 3 surgeons; the sample was randomized and the patients were subjected to the study criteria. We evaluated efficacy and safety as well as the need for readmission and secondary variables such as infection, acute myocardial infarction (AMI), cerebral vascular disease and death with a follow-up of 90 days. RESULTS: The total sample was 402 patients; 214 in the enoxaparin group and 188 in the aspirin group. There were 5 cases (1.24%) with thromboembolic disease, 3 (1.4%) enoxaparin and 2 (1.06%) aspirin without significant difference (p = 0.23). In terms of safety, major bleeding was zero in both groups, with minor bleeding in 7 patients (1.74%), 4 (1.86%) were from the enoxaparin group and 3 (1.59%) from the aspirin group without significant differences (p = 0.82). Secondary outcomes showed 5 (1.24%) superficial surgical wound infections and one AMI in the first 30 days of the procedure in the enoxaparin group. CONCLUSION: Aspirin as monotherapy is safe, effective in antithrombotic prophylaxis in patients operated on total knee arthroplasty.

INTRODUCCIÓN: Aún existe controversia en cuanto a la tromboprofilaxis para la disminución de la enfermedad tromboembólica en la cirugía ortopédica mayor. OBJETIVO: Responder la siguiente pregunta: ¿existe diferencia en la efectividad y seguridad en el manejo antitrombótico de pacientes con un régimen tradicional de enoxaparina contra ácido acetilsalicílico? MATERIAL Y MÉTODOS: Las cirugías se llevaron a cabo por tres cirujanos, se aleatorizó la muestra y los pacientes fueron sometidos a los criterios del estudio. Evaluamos eficacia y seguridad así como la necesidad de reingreso y variables secundarias como infección, infarto agudo de miocardio, enfermedad vascular cerebral y muerte con un seguimiento de 90 días. RESULTADOS: El total de la muestra fue de 402 pacientes, 214 en el grupo de enoxaparina y 188 en el de aspirina. Se presentaron cinco casos (1.24%) con enfermedad tromboembólica, tres (1.4%) enoxaparina y dos (1.06%) aspirina sin diferencia significativa (p = 0.23). En cuanto a seguridad, el sangrado mayor fue cero en ambos grupos, presentándose sangrado menor en siete pacientes (1.74%), cuatro (1.86%) fueron del grupo enoxaparina y tres (1.59%) del grupo aspirina sin diferencias significativas (p = 0.82). Los resultados secundarios mostraron cinco (1.24%) infecciones de herida quirúrgica superficiales y un IAM en los primeros 30 días del procedimiento en el grupo de enoxaparina. CONCLUSIÓN: La aspirina como monoterapia es segura y eficaz en profilaxis antitrombótica en pacientes operados de artroplastía total de rodilla.

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Several modern drugs, which are derived from traditional herbal medicine are used in contemporary pharmacotherapy. Currently, the study of drug-plant interactions in pain has increased in recent years, looking for greater efficacy of the drug and reduce side effects. The antinociception induced by intragastric co-administration of the combination of pomegranate peel extract (PoPEx) and acetylsalicylic acid (ASA) was assessed using the isobolographic analysis in formalin test (nociceptive and inflammatory pain). The effective dose that produced 30% of antinociception (ED30) was calculated for both drugs from the logarithmic dose-response curves, subsequently generating a curve with the combination on fixed proportions (1:1) of PoPEx and ASA. Through isobolographic analysis, this experimental ED30 was compared with the calculated theoretical additive ED30. The result was a synergistic interaction, the experimental ED30 was significantly smaller (p < 0.05) than the theoretical ED30. The antinociceptive mechanism of the PoPEx-ASA combination involves the l-Arginine/NO/cGMP pathway, antioxidant capacity, and high content of total phenols. These findings suggest that an interaction between PoPEx and ASA could be a novel treatment for inflammatory and nociceptive pain, also diminish the secondary reactions of ASA.

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The effects of dipyrone and acetylsalicylic acid (ASA) on male fertility are still not fully understood, mainly considering the epididymis as a putative target for their anti-fertility effects. Therefore, this study aimed to investigate the effects of dipyrone and ASA on the contractions of distal cauda epididymis duct, serum testosterone levels and sperm parameters in rats. Firstly, we checked the in vitro effects of dipyrone and ASA (10-1000 µM) on the contractions of distal cauda epididymis duct by pharmacological experiments. We also evaluated the effects of in vivo treatment with dipyrone and ASA 100 mg/kg (p.o.) for 15 days on epididymal duct contractions, serum testosterone levels and sperm parameters. In vitro dipyrone or ASA decreased the epididymal duct contractions induced by phenylephrine or carbachol. We observed that in vivo treatment with both drugs decreased the daily sperm production, serum testosterone levels and sperm count through epididymis without altering the epididymal duct contractions and sperm transit time through epididymis. In conclusion, in vitro dipyrone and ASA were able to diminish the contractions of epididymal duct, whilst in vivo administration decreased the sperm count throughout epididymis as a consequence of a low sperm production caused by reduced testosterone levels.

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Polymeric implants loaded with drugs can overcome the disadvantages of oral or injection drug administration and deliver the drug locally. Several methods can load drugs into polymers. Herein, soaking and supercritical CO2 (scCO2) impregnation methods were employed to load aspirin into poly(l-lactic acid) (PLLA) and linear low-density polyethylene (LLDPE). Higher drug loadings (DL) were achieved with scCO2 impregnation compared to soaking and in a shorter time (3.4 ± 0.8 vs. 1.3 ± 0.4% for PLLA; and 0.4 ± 0.5 vs. 0.6 ± 0.5% for LLDPE), due to the higher swelling capacity of CO2. The higher affinity of aspirin explained the higher DL in PLLA than in LLDPE. Residual solvent was detected in LLDPE prepared by soaking, but within the FDA concentration limits. The solvents used in both methods acted as plasticizers and increased PLLA crystallinity. PLLA impregnated with aspirin exhibited faster hydrolysis in vitro due to the catalytic effect of aspirin. Finally, PLLA impregnated by soaking showed a burst release because of aspirin crystals on the PLLA surface, and released 100% of aspirin within 60 days, whereas the PLLA prepared with scCO2 released 60% after 74 days by diffusion and PLLA erosion. Hence, the scCO2 impregnation method is adequate for higher aspirin loadings and prolonged drug release.

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Introducción: El empleo de agentes antiagregantes plaquetarios se ve cada día más extendido en la población mundial. La decisión en relación al manejo endoscópico de este tratamiento debe estar basada en el tipo de indicación médica que justifica el uso de estos medicamentos. Se realizó una revisión de los artículos publicados en las bases de datos Pubmed, Scielo, Medline y Cochrane, relacionados con el tema. Objetivo: Profundizar en los conocimientos relacionados con la terapia antiplaquetaria periendoscópica digestiva. Desarrollo: Los antiagregantes plaquetarios son clave en el tratamiento y prevención de eventos trombóticos vasculares, cardíacos o cerebrales. Se han establecido las indicaciones de los antitrombóticos, también se ha evaluado el riesgo tromboembólico al suspender el tratamiento. El riesgo tromboembólico puede ser bajo o alto, por lo que se debe evaluar el riesgo - beneficio de suspender la terapia en este contexto. Todos los procedimientos endoscópicos presentan un riesgo de hemorragia, se considera el bajo riesgo de sangrado por debajo del 1 y alto riesgo por encima del 1 por ciento. La decisión acerca de la antiagregación en el periodo perioperatorio/ periprocedimiento, no solo depende del balance entre el riesgo trombótico y hemorrágico, sino también del tipo y la indicación del tratamiento antiplaquetario. Conclusiones: La antiagregación plaquetaria en pacientes que serán sometidos a procederes gastrointestinales intervencionistas se observa cada vez con mayor frecuencia. Esto hace necesario el conocimiento acerca de la valoración del riesgo de fenómenos trombóticos al interrumpir estos fármacos, junto con la determinación del riesgo potencial de sangrado según el procedimiento endoscópico realizado(AU)

Introduction: The use of platelet antiaggregant agents is increasingly widespread in the world population. The decision regarding the endoscopic management of this treatment should be based on the type of medical indication that justifies the use of these medications. A review of the articles published in the Pubmed, Scielo, Medline and Cochrane databases related to the subject was made. Objective: To deepen the knowledge related to periendoscopic digestive antiplatelet therapy. Development: Platelet antiaggregant are key in the treatment and prevention of vascular, cardiac or cerebral thrombotic events. Just as the indications of antithrombotic agents have been established, the thromboembolic risk has also been evaluated when treatment is suspended. The thromboembolic risk may be low or high, so the risk-benefit of discontinuing therapy in this context should be evaluated. All endoscopic procedures present a risk of bleeding considering the low risk of bleeding below 1 percent and high risk above 1 percent. The decision about anti-aggregation in the perioperative / periprocedural period depends not only on the balance between thrombotic and hemorrhagic risks, but also on the type and indication of antiplatelet therapy. Conclusions: Platelet anti-aggregation in patients who will undergo interventional gastrointestinal procedures is observed more and more frequently. This makes knowledge about the risk assessment of thrombotic phenomena necessary when interrupting these drugs, together with the determination of the potential risk of bleeding according to the endoscopic procedure performed(AU)

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Resumen: Introducción: Aún existe controversia en cuanto a la tromboprofilaxis para la disminución de la enfermedad tromboembólica en la cirugía ortopédica mayor. Objetivo: Responder la siguiente pregunta: ¿existe diferencia en la efectividad y seguridad en el manejo antitrombótico de pacientes con un régimen tradicional de enoxaparina contra ácido acetilsalicílico? Material y métodos: Las cirugías se llevaron a cabo por tres cirujanos, se aleatorizó la muestra y los pacientes fueron sometidos a los criterios del estudio. Evaluamos eficacia y seguridad así como la necesidad de reingreso y variables secundarias como infección, infarto agudo de miocardio, enfermedad vascular cerebral y muerte con un seguimiento de 90 días. Resultados: El total de la muestra fue de 402 pacientes, 214 en el grupo de enoxaparina y 188 en el de aspirina. Se presentaron cinco casos (1.24%) con enfermedad tromboembólica, tres (1.4%) enoxaparina y dos (1.06%) aspirina sin diferencia significativa (p = 0.23). En cuanto a seguridad, el sangrado mayor fue cero en ambos grupos, presentándose sangrado menor en siete pacientes (1.74%), cuatro (1.86%) fueron del grupo enoxaparina y tres (1.59%) del grupo aspirina sin diferencias significativas (p = 0.82). Los resultados secundarios mostraron cinco (1.24%) infecciones de herida quirúrgica superficiales y un IAM en los primeros 30 días del procedimiento en el grupo de enoxaparina. Conclusión: La aspirina como monoterapia es segura y eficaz en profilaxis antitrombótica en pacientes operados de artroplastía total de rodilla.

Abstract: Introduction: There is still controversy regarding thrombo-prophylaxis for the reduction of thromboembolic disease in major orthopedic surgery. Objective: To answer the following question: is there a difference in the effectiveness and safety in the antithrombotic management of patients with a traditional regimen of enoxaparin against acetyl salicylic acid? Material and methods: The surgeries were performed by 3 surgeons; the sample was randomized and the patients were subjected to the study criteria. We evaluated efficacy and safety as well as the need for readmission and secondary variables such as infection, acute myocardial infarction (AMI), cerebral vascular disease and death with a follow-up of 90 days. Results: The total sample was 402 patients; 214 in the enoxaparin group and 188 in the aspirin group. There were 5 cases (1.24%) with thromboembolic disease, 3 (1.4%) enoxaparin and 2 (1.06%) aspirin without significant difference (p = 0.23). In terms of safety, major bleeding was zero in both groups, with minor bleeding in 7 patients (1.74%), 4 (1.86%) were from the enoxaparin group and 3 (1.59%) from the aspirin group without significant differences (p = 0.82). Secondary outcomes showed 5 (1.24%) superficial surgical wound infections and one AMI in the first 30 days of the procedure in the enoxaparin group. Conclusion: Aspirin as monotherapy is safe, effective in antithrombotic prophylaxis in patients operated on total knee arthroplasty.

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OBJECTIVE: There is an urgent need for effective treatments to prevent or attenuate lung and systemic inflammation, endotheliitis, and thrombosis related to COVID-19. This study aimed to assess the effectiveness of a multidrug-therapy consisting of Ivermectin, Azithromycin, Montelukast, and Acetylsalicylic acid ("TNR4" therapy) to prevent hospitalization and death among ambulatory COVID-19 cases in Tlaxcala, Mexico. DESIGN AND METHODS: A comparative effectiveness study was performed among 768 confirmed SARS-CoV-2 cases aged 18-80 years, who received ambulatory care at the Ministry of Health of Tlaxcala. A total of 481 cases received the TNR4 therapy, while 287 received another treatment (comparison group). All participants received home visits and/or phone calls for clinical evaluation during the 14 days after enrollment. RESULTS: Nearly 85% of cases who received the TNR4 recovered within 14 days compared to 59% in the comparison group. The likelihood of recovery within 14 days was 3.4 times greater among the TNR4 group than in the comparison group. Patients treated with TNR4 had a 75% and 81% lower risk of being hospitalized or death, respectively, than the comparison group. CONCLUSIONS: TNR4 therapy improved recovery and prevented the risk of hospitalization and death among ambulatory COVID-19 cases.

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Resumen El ácido acetilsalicílico (Aspirina) es un inhibidor irreversible de la acetil ciclooxigenasa (COX) y su actividad no es restaurada hasta la formación de nuevas plaquetas. Sus efectos benéficos terapéuticos cardiovasculares lo han convertido en la piedra angular del tratamiento del paciente con enfermedad arterial coronaria. Existe una población de pacientes con indicación absoluta para su uso; sin embargo, la presencia o antecedente de hipersensibilidad a esta molécula conlleva un alto riesgo de complicaciones no relacionadas con enfermedad cardiovascular. En algunos de estos pacientes es crucial conocer e implementar protocolos de desensibilización para el ácido acetilsalicílico y, de esta manera, continuar con el uso de esta estrategia terapéutica necesaria e idónea en esta población.

Abstract Acetylsalicylic acid (Aspirin) is an irreversible inhibitor of acetyl cyclooxygenase (COX) and its activity is not restored until new platelets are formed. Its beneficial therapeutic cardiovascular effects have made it the cornerstone of the treatment of patients with coronary artery disease. There is a population of patients with absolute indication for its use, however, the presence or history of hypersensitivity to this molecule leads to a high risk of complications unrelated to their cardiovascular disease. It is vital to know and implement in some of these patients, desensitization protocols for acetyl salicylic acid and in this way to continue the use of this therapeutic strategy necessary and appropriate in this population.

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Chronic alcohol intake leads to neuroinflammation and cell injury, proposed to result in alterations that perpetuate alcohol intake and cued relapse. Studies show that brain oxidative stress is consistently associated with alcohol-induced neuroinflammation, and literature implies that oxidative stress and neuroinflammation perpetuate each other. In line with a self-perpetuating mechanism, it is hypothesized that inhibition of either oxidative stress or neuroinflammation could reduce chronic alcohol intake and relapse. The present study conducted on alcohol-preferring rats shows that chronic ethanol intake was inhibited by 50% to 55% by the oral administration of low doses of either the antioxidant N-acetylcysteine (40 mg/kg/d) or the anti-inflammatory aspirin (ASA; 15 mg/kg/d), while the co-administration of both dugs led to a 70% to 75% (P < .001) inhibition of chronic alcohol intake. Following chronic alcohol intake, a prolonged alcohol deprivation, and subsequent alcohol re-access, relapse drinking resulted in blood alcohol levels of 95 to 100 mg/dL in 60 minutes, which were reduced by 60% by either N-acetylcysteine or aspirin and by 85% by the co-administration of both drugs (blood alcohol: 10 to 15 mg/dL; P < .001). Alcohol intake either on the chronic phase or following deprivation and re-access led to a 50% reduction of cortical glutamate transporter GLT-1 levels, while aspirin administration fully returned GLT-1 to normal levels. N-acetylcysteine administration did not alter GLT-1 levels, while N-acetylcysteine may activate the cystine/glutamate transport xCT, presynaptically inhibiting relapse. Overall, the study suggests that a neuroinflammation/oxidative stress self-perpetuation cycle maintains chronic alcohol intake and relapse drinking. The co-administration of anti-inflammatory and antioxidant agents may have translational value in alcohol-use disorders.

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Giardia lamblia is a flagellated protozoan responsible for giardiasis, a worldwide diarrheal disease. The adverse effects of the pharmacological treatments and the appearance of drug resistance have increased the rate of therapeutic failures. In the search for alternative therapeutics, drug repositioning has become a popular strategy. Acetylsalicylic acid (ASA) exhibits diverse biological activities through multiple mechanisms. However, the full spectrum of its activities is incompletely understood. In this study we show that ASA displayed direct antigiardial activity and affected the adhesion and growth of trophozoites in a time-dose-dependent manner. Electron microscopy images revealed remarkable morphological alterations in the membrane, ventral disk, and caudal region. Using mass spectrometry and real-time quantitative reverse transcription (qRT-PCR), we identified that ASA induced the overexpression of heat shock protein 70 (HSP70). ASA also showed a significant increase of five ATP-binding cassette (ABC) transporters (giABC, giABCP, giMDRP, giMRPL and giMDRAP1). Additionally, we found low toxicity on Caco-2 cells. Taken together, these results suggest an important role of HSPs and ABC drug transporters in contributing to stress tolerance and protecting cells from ASA-induced stress.

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The Candida parapsilosis complex has been associated with highly refractory infections mainly due to the presence of biofilms. High glucose levels enable the development of this virulence factor which can aggravate the clinical condition of patients with diabetes mellitus, those using parenteral nutrition, with invasive medical device, including others. Combined antifungal therapy, such as azole and cyclooxygenase inhibitors, may be an alternative in such infections since they modulate prostaglandin production favoring the adhesion and development of biofilms. Thus, the present study aimed to evaluate the influence of glucose supplementation in the formation and detection of Candida parapsilosis complex biofilms and to treat them using fluconazole and a cyclooxygenase inhibitor in combination. Protein spectra evaluation allowed the differentiation between species from the complex (score > 2) in our studies. All isolates were able to form active biofilms at different glucose concentrations. In addition, a significant reduction in biofilm formation was observed when fluconazole and acetylsalicylic acid were combined. The ultrastructural analysis presented typical biofilm characteristics by species from the complex. These data support new combined therapies for the treatment of fungal infections, especially with those which are resistant and therapeutic failure is associated with virulence factors.

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