Pharmacology最新文献

Introduction: Mast cells are the principal cells involved in acute and chronic colitis due to radiation, known as radiation-induced colitis (RIC). In this study, we investigated whether pretreatment with tranilast, a mast cell inhibitor, could alleviate chronic RIC.

Methods: A total of 23 Sprague-Dawley rats were randomly divided into three groups: control group (n = 5), radiation group (RG, n = 9), and tranilast-pretreated radiation group (TG, n = 9). The rats in the RG and the TG were irradiated in the pelvic area (1.5 cm from the anus) with a single dose of 20 Gy under general anesthesia. Tranilast (100 mg/kg) was administered intraperitoneally to the rats of the TG for 10 days, starting from the day of pelvic radiation. Ten weeks after radiation, the rats were euthanized. Rectal tissue samples were histologically evaluated for the total inflammation score (TIS) and mast cell count. The expression of MUC2, MUC5AC, and matrix metalloproteinase-9 (MMP-9) was also assessed immunohistochemically.

Results: Both the TIS and specific components of TIS such as epithelial atypia, vascular sclerosis, and colitis cystica profunda (CCP) were significantly higher in the RG than in the TG (p = 0.02, 0.038, 0.025, and 0.01, respectively). Thein number of infiltrating mast cells was significantly higher in the RG than in the TG (median [range]: 20 [3-54] versus 6 [3-25], respectively; p = 0.034). Quantitatively, the number of MMP-9-positive cells was significantly higher in the RG (23.67 ± 19.00) than in the TG (10.25 ± 8.45) (mean ± standard deviation; p < 0.05). TIS and MMP-9 exhibited a strong association (correlation coefficient r = 0.56, p < 0.05). Immunohistochemically, the mucin-lake of CCP showed no staining for MUC5AC but was stained positive for MUC2.

Conclusion: Tranilast pretreatment of chronic RIC showed an anti-inflammatory effect associated with the reduction of mast cell infiltration and MMP-9 expression.

Introduction: Administration of vancomycin dose by continuous infusion (CI) according to population pharmacokinetic (Pop Pk) models is highly recommended in critically ill patients who exhibit pathophysiological changes.

Objective: The objective of this study was to develop and validate a Pop Pk model of vancomycin administered by CI in critically ill patients with normal and impaired renal functions.

Methods: The Pop Pk study was performed using a nonparametric approach (Pmetrics*). The influence of covariates (gender, age, weight, height, and creatinine clearance [Cr-Cl]) was tested on the model's Pk parameters. The performance of the final model was assessed using an external dataset.

Results: A one-compartment model (volume of distribution [Vd], elimination from compartment [Ke]) was found to show a good prediction performance. The influence of covariates has shown that age and Cr-Cl affected significantly Vd and Ke, respectively. The distribution of simulated vancomycin clearance (CLv) according to different renal function levels showed a negative correlation between CLv and the severity of the renal impairment. The internal validation of the final model showed that the plot of individual-predicted concentration versus observed concentration resulted in r2 = 0.86 in the final model. The external validation of the final model showed an acceptable predictive performance.

Conclusion: We developed a Pop Pk model for vancomycin administered by CI in critically ill patients. A significant impact of Cr-Cl and different stages of renal failure on CLv has been demonstrated. The establishment of an individualized proposal dose based on this model may be helpful to achieve the target range which is critical in optimizing the efficacy and safety of this antibiotic.

Background: Cancer is a major cause of death worldwide. Although modern medicine has made strides in treatment, a complete cure for cancer remains elusive.

Summary: Utilization of medicinal plants in traditional medicine for the treatment of multiple diseases, including cancer, is a well-established practice. Sinomenine is an alkaloid extracted from a medicinal plant and has a diverse range of biological properties, including anti-oxidative, anti-inflammatory, and antibacterial effects. Sinomenine exhibits inhibitory effects on various types of tumor cells, including breast, lung, and liver cancers. The anticancer properties of sinomenine are believed to involve stimulation of apoptosis and autophagy as well as suppression of cell proliferation, invasion, and metastasis.

Key message: This review summarizes the current research on sinomenine's potential as an anticancer agent, which may contribute to the discovery of more effective cancer treatments.

Introduction: The prevalence of potential drug-drug interactions (pDDIs) is becoming a major safety concern, as it has been previously linked to a significant number of adverse drug events and could have serious consequences for patients, including death. This is especially relevant for patients with chronic renal failure, as they are particularly vulnerable to drug-drug interactions. The aim of this study was to evaluate the prevalence and associated factors of pDDIs in patients receiving chronic peritoneal dialysis.

Methods: An observational, cross-sectional study was conducted on consecutive peritoneal dialysis patients attending four tertiary care hospitals for regular monthly examination. The primary outcome was the number of pDDIs identified using Lexicomp. Potential predictors were determined using multiple linear regression.

Results: Total number of patients included in the study was 140. The results showed that pDDIs were highly prevalent, especially in patients who use antiarrhythmics (p = 0.001), have diabetes mellitus (p = 0.001), recently started peritoneal dialysis (p = 0.003), or have higher number of prescribed drugs (p < 0.001). Number of prescribed drugs (p < 0.001) remained a significant predictor of high-risk pDDIs in addition to the female gender (p = 0.043).

Conclusion: Clinicians should be particularly cautious when prescribing multiple medications to high-risk patients, such as peritoneal dialysis patients, to mitigate the risk of drug-drug interactions and associated adverse health outcomes.

Introduction: Hyperuricemia may be involved in the phenotypic transformation of vascular smooth muscle cells, thus promoting the occurrence of atherosclerosis, and autophagy may be one of the important links, but little is known about the specific molecular mechanism.

Methods: We established a mouse model of hyperuricemia and studied the relationship between changes in autophagy levels and the phenotypic transformation of muscle cells.

Results: Our study found that high uric acid levels promote the phenotypic transformation of muscle cells by inhibiting autophagy, thus enhancing their proliferation and migration abilities. If autophagy is restored, phenotypic transformation can be reversed by reducing the levels of the transcription factor Kruppel-like factor 4.

Conclusion: Uric acid may induce the phenotypic transformation of muscle cells and promote the occurrence of atherosclerosis by disrupting normal autophagy.

Introduction: The traditional Japanese herbal medicine hochuekkito (TJ-41) has been reported to ameliorate systemic inflammation and malnutrition in patients with chronic obstructive pulmonary disease (COPD). TJ-41 has also been known to have preventive effects against influenza virus infection. However, its role in the acute exacerbation of COPD (AECOPD) remains to be elucidated. Our previous study established a murine model of viral infection-associated AECOPD that was induced by intratracheal administration of porcine pancreatic elastase (PPE) and polyinosinic-polycytidylic acid [poly(I:C)]. Here, we used this model and investigated the effects of TJ-41 in AECOPD.

Methods: Specific pathogen-free C57BL/6J mice were used. A COPD model was induced by treating mice intratracheally with PPE on day 0. To generate the murine model of AECOPD, poly(I:C) was administered intratracheally following PPE treatment on days 22-24. Mice were sacrificed and analyzed on day 25. Mice were fed a diet containing 2% TJ-41 or a control diet.

Results: Daily oral intake of TJ-41 significantly decreased the numbers of neutrophils and lymphocytes in the bronchoalveolar lavage fluid (BALF), which was accompanied by decreased transcripts of CXC chemokines involved in neutrophil migration, viz., Cxcl1 and Cxcl2, in whole lung homogenates and reduced Cxcl2 concentration in BALF.

Conclusion: This study demonstrates the anti-inflammatory effects of TJ-41 in a mouse model of AECOPD, suggesting the effectiveness of TJ-41 for the management of COPD. Clinical investigations evaluating the therapeutic efficacy of TJ-41 in AECOPD would be meaningful.

Introduction: Proton pump inhibitors (PPIs) are known to decrease the risk of gastrointestinal (GI) bleeding. However, concerns have been raised regarding the potential pharmacodynamic interactions of PPIs and antiplatelet drugs with respect to cardiovascular risk. Patients with BCR::ABL1-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia (ET), and polycythemia vera (PV) often suffer from peptic ulcer disease (PUD) and frequently receive low-dose aspirin due to an intrinsically high thrombotic risk.

Method: This retrospective multicenter study from a community setting investigated whether continuous PPI use may affect thrombohemorrhagic risk in ET and PV patients treated with long-term aspirin.

Results: Ninety-four aspirin-treated MPN patients (ET = 36, PV = 58) were included; median age was 69.5 years (range 21-92) and 40 (42.6%) were males. Nineteen (20.2%) patients continuously received PPIs and pantoprazole (n = 15, 78.9%) was the most frequently received PPI. PV phenotype (p = 0.085), male sex (p = 0.011), and prior thrombosis (p = 0.005) were associated with PPI use, whereas no correlations were found with respect to age, disease risk, splenomegaly, mutational status, constitutional symptoms, cardiovascular risk factors, cytoreductive treatment, or any of the blood cell counts (p > 0.050 for all analyses). The median follow-up time was 55.5 months; 19 (20.2%) thrombotic and 13 (13.8%) bleeding events occurred during this time. The use of PPIs was not associated with an increased risk of thrombosis (p = 0.158) or overall bleeding (p = 0.229) and none of the patients treated with PPIs experienced GI bleeding.

Conclusions: Considering that Helicobacter pylori infection and PUD are quite frequent in ET and PV patients, these preliminary results may provide some reassurance to physicians regarding the absence of thrombohemorrhagic risk associated with prolonged PPI use in MPN patients treated with long-term aspirin. Our observations may be even more important in the light of recent evidence suggesting suboptimal platelet inhibition in ET with once-daily when compared to twice- or triple-daily aspirin which may also cause more abdominal discomfort. Limitations of this study are its retrospective design, limited number of patients included, and the lack of pharmacodynamic and pharmacokinetic assessments.