RESUMEN
Pregabalin is a prescription medicine that has recently been approved for individuals who suffer from fibromyalgia, neuropathic pain, anxiety disorder, or epilepsy. Pregabalin has the side effects of dizziness, sleepiness, and angioedema. Pregabalin-induced rhabdomyolysis has been rarely reported, with only four reports to date. We report two cases of rhabdomyolysis after pregabalin treatment. A man aged older than 90 years presented with exhaustion, muscle aches, and a high serum creatine kinase concentration after taking 75 mg of pregabalin on the first day of treatment. A woman in her 90s with long-term use of pregabalin presented with considerably elevated serum creatine kinase concentrations. Both patients had a long history of taking statins. Pregabalin therapy was stopped, high-volume intravenous fluids were administered, and serum electrolytes were frequently checked. Alkalinisation was performed with excellent outcomes. The Naranjo Adverse Drug Reaction scale and previous research suggest an association between pregabalin and rhabdomyolysis. Clinicians should be alert to the possibility of rhabdomyolysis occurring with the use of pregabalin, especially when taking statins.
Asunto(s)
Pregabalina , Rabdomiólisis , Humanos , Pregabalina/efectos adversos , Rabdomiólisis/inducido químicamente , Femenino , Masculino , Anciano de 80 o más Años , Analgésicos/efectos adversos , Analgésicos/uso terapéutico , Creatina Quinasa/sangreRESUMEN
BACKGROUND: Given its narrow treatment window, high toxicity, adverse effects, and individual differences in its use, we collected and sorted data on tacrolimus use by real patients with kidney diseases. We then used machine learning technology to predict tacrolimus blood concentration in order to provide a basis for tacrolimus dose adjustment and ensure patient safety. METHODS: This study involved 913 hospitalized patients with nephrotic syndrome and membranous nephropathy treated with tacrolimus. We evaluated data related to patient demographics, laboratory tests, and combined medication. After data cleaning and feature engineering, six machine learning models were constructed, and the predictive performance of each model was evaluated via external verification. RESULTS: The XGBoost model outperformed other investigated models, with a prediction accuracy of 73.33%, F-beta of 91.24%, and AUC of 0.5531. CONCLUSIONS: Through this exploratory study, we could determine the ability of machine learning to predict TAC blood concentration. Although the results prove the predictive potential of machine learning to some extent, in-depth research is still needed to resolve the XGBoost model's bias towards positive class and thereby facilitate its use in real-world settings.
Asunto(s)
Glomerulonefritis Membranosa , Síndrome Nefrótico , Humanos , Tacrolimus/uso terapéutico , Síndrome Nefrótico/tratamiento farmacológico , Inmunosupresores/efectos adversos , Glomerulonefritis Membranosa/diagnóstico , Glomerulonefritis Membranosa/tratamiento farmacológico , Resultado del Tratamiento , Quimioterapia Combinada , TecnologíaRESUMEN
BACKGROUND: Vacuum sealing drainage (VSD) and epidermal growth factor (EGF) both play an important role in the treatment of wounds. This study aims to explore the effects of the combination of VSD and EGF on wound healing and the optimal concentration and time of EGF. METHODS: We tested the proliferation and migration capacity of HaCaT and L929 cells at different EGF concentrations (0, 1, 5, 10, and 100 ng/ml) and different EGF action times (2, 10, and 30 min). A full-thickness skin defect model was established using male, 30-week-old Bama pigs. The experiment included groups as follows: routine dressing change after covering with sterile auxiliary material (Control), continuous negative pressure drainage of the wound (VSD), continuous negative pressure drainage of the wound and injection of EGF 10 min followed by removal by continuous lavage (V + E 10 min), and continuous negative pressure drainage of the wound and injection of EGF 30 min followed by removal by continuous lavage (V + E 30 min). The wound healing rate, histological repair effect and collagen deposition were compared among the four groups. RESULTS: An EGF concentration of 10 ng/ml and an action time of 10 min had optimal effects on the proliferation and migration capacities of HaCaT and L929 cells. The drug dispersion effect was better than drug infusion after bolus injection effect, and the contact surface was wider. Compared with other groups, the V + E 10 min group promoted wound healing to the greatest extent and obtained the best histological score. CONCLUSIONS: A recombinant human epidermal growth factor (rhEGF) concentration of 10 ng/ml can promote the proliferation and migration of epithelial cells and fibroblasts to the greatest extent in vitro. VSD combined with rhEGF kept in place for 10 min and then washed, can promote wound healing better than the other treatments in vivo.
Asunto(s)
Factor de Crecimiento Epidérmico/uso terapéutico , Hormona de Crecimiento Humana/uso terapéutico , Terapia de Presión Negativa para Heridas/normas , Cicatrización de Heridas/efectos de los fármacos , Animales , Factor de Crecimiento Epidérmico/farmacología , Hormona de Crecimiento Humana/farmacología , Terapia de Presión Negativa para Heridas/métodos , PorcinosRESUMEN
Twelve new steroidal saponins, including eleven furostanol saponins, terrestrinin J-T (1-11), and one spirostanol saponin, terrestrinin U (12), together with seven known steroidal saponins 13-19 were isolated from T. terrestris. The structures of the new compounds were established on the basis of spectroscopic data, including 1D and 2D NMR and HRESIMS, and comparisons with published data.
Asunto(s)
Extractos Vegetales/química , Saponinas/química , Espirostanos/química , Esteroles/química , Tribulus/química , Medicamentos Herbarios Chinos/química , Estructura Molecular , Saponinas/aislamiento & purificación , Espirostanos/aislamiento & purificación , Esteroles/aislamiento & purificaciónRESUMEN
INTRODUCTION: The present study was designed to test the hypothesis that local angiotensin converting enzyme (ACE) was involved in the cardiac hypertrophy induced by sinoaortic denervation (SAD) in rats. METHODS: Experiment 1: Six weeks after SAD of rats, components of renin-angiotensin system (RAS) in left ventricles were assayed by quantitative real-time PCR and Western blotting analysis. Experiment 2: Rats were divided into five groups treated as follows: (1) sham-operated group; (2) SAD group; (3) SAD group treated with angiotensin II type 1 receptor (AT1R) antagonist losartan (10 mg·kg(-1)·day(-1), orally); (4) SAD group treated by ACE inhibitor ramipril (1 mg·kg(-1)·day(-1), orally); (5) SAD group treated by ramipril and the B2-kinin receptor selective antagonist HOE-140 (0.25 mg·kg(-1)·day(-1), subcutaneously). RESULTS: SAD led to augmentation of the mRNA levels and protein expression of left ventricular ACE and AT1R. Both losartan and ramipril ameliorated SAD-induced left ventricular hypertrophy. Both losartan and ramipril abated oxidative stress, suppressed inflammation, and reduced expression TGFß-R in left ventricles. In addition, the protective effect of ramipril could be abolished by HOE-140. CONCLUSION: Local ACE is involved in the left ventricular hypertrophy induced by sinoaortic denervation in rats, via both angiotensin II/AT1R and bradykinin/B2R pathways.
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Cardiomegalia/metabolismo , Peptidil-Dipeptidasa A/metabolismo , Sistema Renina-Angiotensina/fisiología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Animales , Aorta/inervación , Aorta/cirugía , Western Blotting , Desnervación , Masculino , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Meropenem is a carbapenem antibiotic with a wide spectrum of activity against both Gram-positive and Gram-negative bacteria. Because of its clinical efficacy, meropenem is an excellent choice for the treatment of serious infections in both adults and children. The knowledge of tissue concentrations of antibiotic in an infection site is valuable for the prediction of treatment outcome. The aim of the present study is to investigate the effect of borneol on the concentration of meropenem in rat brain and blood and to find the potential relationships of the combined use of medicine and traditional Chinese medicine. Analysis of meropenem in the dialysates was achieved using the microdialysis technique and HPLC. At 40 min after the administration of an intraperitoneal injection of meropenem, the concentration of meropenem in brain in borneol+meropenem group was 2.25 (0.35) µg ml(-1), which was significantly higher than that in meropenem group [1.20 (0.12) µg ml(-1); P < 0.01]. Within 80 min of drug administration, the AUCbrain/AUCblood (area under the curve, AUC) in the borneol+meropenem group was 1.2 times that of the meropenem group. Borneol can increase the concentration of meropenem in the cerebrospinal fluid, but has no influence on its blood concentration. This study represents a successful application of the microdialysis technique, which is an effective method for the study of pharmacokinetics of meropenem.
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Antibacterianos/farmacocinética , Canfanos/farmacocinética , Tienamicinas/análisis , Tienamicinas/farmacocinética , Adulto , Animales , Antibacterianos/análisis , Antibacterianos/sangre , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/efectos de los fármacos , Canfanos/análisis , Canfanos/sangre , Canfanos/química , Niño , Cromatografía , Cromatografía Líquida de Alta Presión , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Masculino , Medicina Tradicional China , Meropenem , Microdiálisis , Estructura Molecular , Ratas , Ratas Wistar , Tienamicinas/administración & dosificación , Tienamicinas/sangre , Tienamicinas/químicaRESUMEN
Tamoxifen resistance remains to be a huge obstacle in the treatment of hormone-dependent breast cancer, and this therefore highlights the dire need to explore the underlying mechanisms. The epithelial-mesenchymal transition (EMT) is a molecular process through which an epithelial cell transfers into a mesenchymal phenotype. Roles of EMT in embryo development, cancer invasion and metastasis have been extensively reported. Herein, we established tamoxifen-resistant MCF-7/TR breast cancer cells and showed that MCF-7/TR cells underwent EMT driven by enhanced endogenous TGF-ß/Smad signaling. Ectopic supplement of TGF-ß promoted in MCF-7 cells a mesenchymal and resistant phenotype. In parallel, we demonstrated that resveratrol was capable of synergizing with tamoxifen and triggering apoptosis in MCF-7/TR cells. Further Western blot analysis indicated that the chemosensitizing effects of resveratrol were conferred with its modulation on endogenous TGF-ß production and Smad phosphorylation. In particular, 50 µM resveratrol had minor effects on MCF-7/TR cell proliferation, but could significantly attenuate endogenous TGF-ß production and the Smad pathway, ultimately leading to reversion of EMT. Collectively, our study highlighted distinct roles of EMT in tamoxifen resistance and resveratrol as a potential agent to overcome acquired tamoxifen resistance. The molecular mechanism of resveratrol chemosensitizing effects is, at least in part, TGF-ß/Smad-dependent.