RESUMEN
BACKGROUND: To study the various factors affecting the anticoagulant effect of warfarin, and to promote the rational use of warfarin. METHODS: We collected the medical records of 125 hospitalized patients who used warfarin from January 2018 to December 2019. Statistical analysis was performed on characteristics such as gender, age, treatment, diabetes, hyperlipidemia, hyperthyroidism, hypothyroidism, hepatitis, renal insufficiency, and nephritis; along with other pathological factors, such as aspirin, clopidogrel, spironolactone, amiodarone, amlodipine, trimetazidine, bisoprolol, isosorbide, atorvastatin, furosemide, digoxin, metoprolol, acarbose, levamlodipine, enoxaparin, moxifloxacin, levofloxacin, other drug interactions, and comorbidities. RESULTS: Gender and age did not have a significant effect on the efficacy of warfarin. Infection and bleeding extended the number of days of warfarin administration. Acarbose, enoxaparin, and moxifloxacin had a likely effect on warfarin treatment-related indicators. CONCLUSIONS: Warfarin anticoagulation is affected by many factors. Therefore, medical personnel should pay close attention to the impact of these factors on the anticoagulant effect of warfarin. This study found that warfarin-related bleeding adverse drug reactions and anticoagulant effects have a significant association. Bleeding not only affected the total number of days hospitalized, but also extended the number of days of warfarin administration. However, in terms of patients' pathological states, international normalized ratio values combined with drugs used were not associated with disease and may only be a reference for bleeding risk.
Asunto(s)
Anticoagulantes , Warfarina , Anticoagulantes/efectos adversos , Interacciones Farmacológicas , Hemorragia , Humanos , Relación Normalizada Internacional , Warfarina/efectos adversosRESUMEN
Uremic toxin accumulation is one possible reason for alterations in hepatic drug metabolism in patients with chronic kidney disease (CKD). However, the types of uremic toxins and underlying mechanisms are poorly understood. In this study, we report the role of advanced oxidation protein products (AOPPs), a modified protein uremic toxin, in the downregulation of cytochromes P450 1A2 (CYP1A2) and P450 3A4 (CYP3A4) expression levels and activities. We found that AOPP accumulation in plasma in a rat CKD model was associated with decreased protein levels of CYP1A2 and CYP3A4. CYP1A2 and CYP3A4 metabolites (acetaminophen and 6ß-hydroxytestosterone, respectively,) in liver microsomes were also significantly decreased. In human hepatocytes, AOPPs significantly decreased CYP1A2 and CYP3A4 protein levels in a dose- and time-dependent manner and downregulated their activities; however, bovine serum albumin (BSA), a synthetic precursor of AOPPs, had no effect on these parameters. The effect of AOPPs was associated with upregulation of p-IKKα/ß, p-IκBα, p-NF-κB, and inflammatory cytokines protein levels and increases in p-IKKα/ß/IKKα, p-IκBα/IκBα, and p-NF-κB/NF-κB phosphorylation ratios. Further, NF-kB pathway inhibitors BAY-117082 and PDTC abolished the downregulatory effects of AOPPs. These findings suggest that AOPPs downregulate CYP1A2 and CYP3A4 expression and activities by increasing inflammatory cytokine production and stimulating NF-κB-mediated signaling. Protein uremic toxins, such as AOPPs, may modify the nonrenal clearance of drugs in patients with CKD by influencing metabolic enzymes.
Asunto(s)
Productos Avanzados de Oxidación de Proteínas/farmacología , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP3A/metabolismo , Regulación hacia Abajo/efectos de los fármacos , FN-kappa B/metabolismo , Animales , Línea Celular , Modelos Animales de Enfermedad , Células Hep G2 , Humanos , Masculino , Microsomas Hepáticos/metabolismo , Ratas , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Honokiol (HNK), the main active component of Magnolia officinalis, has shown a variety of pharmacological activities. In the present study, we measured the antidepressant-like effects of HNK in a rat model of chronic unpredictable mild stress (CUMS) and explored its possible mechanisms. The antidepressant-like effects of HNK were assessed in rats by an open field test (OFT), sucrose preference test (SPT) and forced swimming test (FST). Then, serum levels of corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) and hippocampal brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor α (GRα) levels were assessed to explore the possible mechanisms. We identified that HNK treatment (2, 4, and 8 mg/kg) alleviated the CUMS-induced behavioural deficits. Treatment with HNK also normalized the CUMS-induced hyperactivity of the limbic hypothalamic-pituitary-adrenal (HPA) axis, as indicated by reduced CRH, ACTH and CORT serum levels. In addition, HNK increased the expression of GRα (mRNA and protein) and BDNF (mRNA and protein) in the hippocampus. These data confirmed the antidepressant-like effects of HNK, which may be related to its normalizing the function of the HPA axis and increasing the BDNF level in the hippocampus.
Asunto(s)
Antidepresivos/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Lignanos/uso terapéutico , Sistema Hipófiso-Suprarrenal/metabolismo , Estrés Psicológico/metabolismo , Animales , Compuestos de Bifenilo/farmacología , Enfermedad Crónica , Relación Dosis-Respuesta a Droga , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Lignanos/farmacología , Masculino , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Ratas , Ratas Wistar , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/psicología , Resultado del TratamientoRESUMEN
Phosphodiesterase-4 (PDE4) inhibitors prevent the breakdown of the second messenger cAMP and have been demonstrated to improve learning in several animal models of cognition. In this study, we explored the antioxidative effects of rolipram in Alzheimer's disease (AD) by using bilateral Aß25-35 injection into the hippocampus of rats, which were used as an AD model. Rats received 3 intraperitoneal (i.p.) doses of rolipram (0.1, 0.5 and 1.25 mg/kg) daily after the injection of Aß25-35 for 25 days. Chronic administration of rolipram prevented the memory impairments induced by Aß25-35, as assessed using the passive avoidance test and the Morris water maze test. Furthermore, rolipram significantly reduced the oxidative stress induced by Aß25-35, as evidenced by the decrease in the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and restored the reduced GSH levels and superoxide dismutase (SOD) activity. Moreover, western blotting and real-time reverse transcription polymerase chain reaction (RT-PCR) analysis showed that rolipram remarkably upregulated thioredoxin (Trx) and inhibited the inducible nitric oxide synthase/nitric oxide (iNOS/NO) pathway in the hippocampus. These results demonstrated that rolipram improved the learning and memory abilities in an Aß25-35-induced AD rat model. The mechanism underlying these effects may be due to the noticeable antioxidative effects of rolipram.