In almost 30 years since the introduction of HMG-CoA reductase inhibitors (statins), no other class of lipid modulators has entered the market. Elevation of high-density lipoprotein-cholesterol ...(HDL-C) via inhibiting cholesteryl ester transfer protein (CETP) is an attractive strategy for reducing the risk of cardiovascular events in high-risk patients. Transfer of triglyceride and cholesteryl ester (CE) between lipoproteins is mediated by CETP; thus inhibition of this pathway can increase the concentration of HDL-C. Torcetrapib was the first CETP inhibitor evaluated in phase III clinical trials. Because of off-target effects, torcetrapib raised blood pressure and increased the concentration of serum aldosterone, leading to higher cardiovascular events and mortality. Torcetrapib showed positive effects on cardiovascular risk especially in patients with a greater increase in HDL-C and apolipoprotein A-1 (apoA-1) levels. The phase III clinical trial of dalcetrapib, the second CETP inhibitor that has entered clinical development, was terminated because of ineffectiveness. Dalcetrapib is a CETP modulator that elevated HDL-C levels but did not reduce the concentration of low-density lipoprotein cholesterol (LDL-C). Both heterotypic and homotypic CE transfer between lipoproteins are mediated by some CETP inhibitors, including torcetrapib, anacetrapib, and evacetrapib, while dalcetrapib only affects the heterotypic CE transfer. Dalcetrapib has a chemical structure that is distinct from other CETP inhibitors, with a smaller molecular weight and a lack of trifluoride moieties. Moreover, dalcetrapib is a pro-drug that must be hydrolyzed to a pharmacologically active thiol form. Two other CETP inhibitors, anacetrapib and evacetrapib, are currently undergoing evaluation in phase III clinical trials. Both molecules have shown beneficial effects by increasing HDL-C and decreasing LDL-C concentration. The success of anacetrapib and evacetrapib remains to be confirmed upon the completion of phase III clinical trials in 2017 and 2015, respectively. Generally, the concentration of HDL-C has been considered a biomarker for the activity of CETP inhibitors. However, it is not clear whether a fundamental relationship exists between HDL-C levels and the risk of coronary artery diseases. The most crucial role for HDL is cholesterol efflux capacity in which HDL can reverse transport cholesterol from foam cells in atherosclerotic plaques. In view of the heterogeneity in HDL particle size, charge, and composition, the mere concentration of HDL-C may not be a good surrogate marker for HDL functionality. Recent clinical studies have reported that increased HDL functionality inversely correlates with the development of atherosclerotic plaque. Future development of CETP inhibitors may therefore benefit from the use of biomarkers of HDL functionality.
Acrylamide is converted to glycidamide as a reactive metabolite by the monooxygenase isozyme CYP2E1. Since the latter is known to be induced in diabetic patients, increased acrylamide toxicity in ...such patients is suspected.
Differences in acrylamide toxicokinetics in non-diabetic and diabetic rats receiving acrylamide (50 mg/kg) orally or via i.p. injection were investigated in this report. Blood was collected at various time points, acrylamide and glycidamide in plasma were determined by reversed-phase high-performance liquid chromatography, and the data were analyzed for toxicokinetic parameters using the proper software.
Mean maximum plasma concentration, the apparent clearance, and area under the curve in non-diabetic rats were significantly higher than in diabetics, an important fact to be considered in xenobiotic exposure of diabetic individuals.
Radiodermatitis in breast cancer patients varies from mild irritation to life‐threatening lesions. Several studies suggest a role for topical corticosteroid ointments in the treatment of ...radiodermatitis. Yet, to avoid the adverse effects of corticosteroids, many authors recommend the use of topical herbal products instead. The therapeutic role of herbal treatments has yet to be fully understood. This systematic review evaluates the role of topical or oral herbal medicines in radiodermatitis prevention and treatment. A systematic search of four databases (Embase, PubMed, Web of Science, and Scopus) was performed without language and time restrictions from their inception until April 2023. The bibliographies of potential articles were also searched manually. Studies evaluated and compared the effects of herbal preparations with the control group, on dermatitis induced by radiotherapy for breast cancer. The Cochrane risk of bias tool was used to assess the included studies. Thirty‐five studies were included in the systematic review. Studies which used herbal drugs including topical and oral formulations were evaluated. Herbal monotherapy and combination therapy were reported, and their effects on radiodermatitis were explained in the systematic review. In conclusion, henna ointments, silymarin gel, and Juango cream were reported to reduce the severity of radiodermatitis. These agents should be considered for radiodermatitis prophylaxis and treatment. The data on aloe gel and calendula ointment were conflicting. Further randomized controlled trials of herbal medications and new herbal formulations are required to determine their effects on breast cancer radiodermatitis.
Cardiac complications including arrhythmia and especially atrial fibrillation (AF) are common causes of death in β‐thalassemia patients. The main factor in the etiopathogenesis of these complications ...is iron overload, which results in increased oxidative stress. Although there is a known association between cardiac complications and iron overload in β‐thalassemia patients, there is no comprehensive review on AF and excessive iron with a focus on oxidative stress in these patients. The aim of this article was to review the different aspects of AF in β‐thalassemia patients with a focus on the prevention and treatment of AF by using iron chelators and/or anti‐oxidants. AF in β‐thalassemia patients is more common than in the general population. One of the most important causes of AF is cardiac iron overload and the harmful effects of increased oxidative stress. Iron‐induced AF can be reversed by using an intensive iron chelation regimen. Based on a few experimental studies, the combination of iron chelators with some anti‐oxidants, including NAC, vitamin C, and acetaminophen, can lead to improved cardiac protection. However, the effect of such combinations on cardiac arrhythmias should be further evaluated with animal and human studies.
In this article, the authors review studies evaluating the incidence rate of AF in β‐TM patients. Next, we focus on AF etiology and oxidative stress in patients with β‐TM, and finally, we discuss studies that have evaluated the effect of iron chelators on oxidative stress and arrhythmias, especially AF.
Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including ...breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negatively impact multiple diverse entities including nerves and vascular structures, insulin‐like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP450, Mdr
1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy‐dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed.
Several studies have indicated an association between inflammation and the recurrence of Atrial Fibrillation (AF), especially after ablation, which is a therapeutic option leading to local ...inflammation. On the other hand, each AF can lead to another AF, as a general rule. Thus, preventing recurrences of AF is extremely important for patient outcomes. In this paper, we attempted to review the effect of medicinal agents with anti-inflammatory properties on the prevention of AF recurrence. There are several randomized controlled trials (RCTs) and meta-analyses on the prevention of AF recurrence using agents with anti-inflammatory properties, which include steroids, colchicine, statins, and n-3 fatty acids (n-3 FA). Clinical trials evaluating the efficacy of anti-inflammatory drugs in preventing the recurrence of AF led to inconsistent results for corticosteroids, statins and n-3 FAs. These results may be related to the fact that inflammation is not the only factor responsible for triggering recurrences of AF. For example, the presence of structural, mechanical and electrical remodeling could potentially be the most important factors that trigger recurrences of AF but these factors have not been addressed in most of the reported studies. Therefore, future clinical trials are needed to compare the efficacy of anti-inflammatory drugs in AF patients with, or without other factors. For colchicine, a potent anti-inflammatory drug, there are limited studies. However, all the studies investigating colchicine in the context of AF were consistent and promising, especially when colchicine was used on a short-term basis following ablation in patients with paroxysmal AF. Therefore, colchicine could be a promising candidate for further clinical studies involving recurrent AF.
Oral mucositis (OM) is a complication of head and neck cancer (HNC) therapy with negative impact on the quality of life. Although definitive treatment has not yet been established, there is interest ...towards the use of natural compounds owing to their few side effects. Curcumin has a variety of biological and pharmacological properties including anticancer and anti‐inflammatory effects.
Aim
The aim of this study is to evaluate the effect of curcumin in the form of nanomicelle on OM in HNC patients receiving radiotherapy.
Methods
In this clinical trial, 32 HNC patients were allocated to case and control groups, and respectively received nanocurcumin or placebo during radiotherapy.
Results
We found a statistically significant difference in the severity of mucositis between the 2 groups at all visits. In contrast to the control‐group patients, who all developed OM in the 2nd week of radiotherapy, only 32% of the case group developed OM with no obvious oral or systemic side effects.
Conclusion
Our data show that nanomicelle curcumin is an effective agent in the prevention of OM or reducing its severity. Thus, the administration of nanocurcumin can be considered as a reasonable approach to hinder the development of OM in HNC patients requiring radiotherapy.
The SARS‐CoV‐2 COVID‐19 pandemic has emerged as an unprecedented emergency state in healthcare system and global challenge. In recent decade, the function of exogenous H2S in the treatment of ...respiratory diseases has been investigated using H2S‐donor agents. Ferula foetida is a medicinal plant that is traditionally used in respiratory diseases including asthma and viral respiratory diseases. The oleo‐gum of this plant is a rich source of several organic sulfides including thiophenes, disulfides and polysulfide derivatives, which can act as H2S‐donor agents. The purpose of this study was to investigate the efficacy of Covexir® (F. foetida oleo‐gum) treatment as a rich source of H2S‐donor compounds in clinical presentations of patients with COVID‐19. The efficacy of Covexir® was evaluated in a randomized, double‐blind, placebo‐controlled trial in outpatients with COVID‐19. Covexir® could significantly inhibit cough when compared to the placebo group (p < .01 and p < 001, respectively). Moreover, there was a significant difference (p < 001) between the two groups in dyspnea symptom at follow‐up interval of 7 day after receiving Covexir®. Furthermore, on days 3 and 7, statistically significant differences were observed in myalgia, anorexia, anosmia, and sense of taste severity between two groups. Our findings revealed that Covexir® was very safe in the treatment of COVID‐19 patients with mild to moderate symptoms and it can be recommended to improve clinical presentations of patients with COVID‐19 such as cough, shortness of breath, myalgia, anorexia, anosmia, and sense of taste.
High‐density lipoprotein (HDL) function rather than level may better predict cardiovascular disease (CVD). However, the contribution of the impaired antioxidant function of HDL that is associated ...with increased HDL lipid peroxidation (HDLox) to the development of clinical CVD remains unclear. We have investigated the association between serum HDLox with incident CVD outcomes in Mashhad cohort. Three‐hundred and thirty individuals who had a median follow‐up period of 7 years were recruited as part of the cohort. The primary end point was cardiovascular event, including myocardial infarction, stable angina, unstable angina, or coronary revascularization. In both univariate/multivariate analyses adjusted for traditional CVD risk factors, HDLox was an independent risk factor for CVD (odds ratio, 1.62; 95% confidence interval, 1.41–1.86;
p < 0.001). For every increase in HDLox by 0.1 unit, there was an increase in CVD risk by 1.62‐fold. In an adjusted analysis, there was a >2.5‐fold increase in cardiovascular risk in individuals with HDLox higher than cutoff point of 1.06 compared to those with lower scores, suggesting HDLox > 1.06 is related to the impaired HDL oxidant function and in turn exposed to elevated risk of CVD outcomes (hazard ratio, 2.72; 95% CI, 1.88–3.94). Higher HDLox is a surrogate measure of reduced HDL antioxidant function that positively associated with cardiovascular events in a population‐based cohort.
Higher HDL lipid peroxidation (HDLox) is a surrogate measure of reduced HDL antioxidant function that positively associated with cardiovascular events in a population‐based cohort. In an adjusted analysis, there was a >2.5‐fold increase in cardiovascular risk in individuals with HDLox higher than cutoff point compared to those with lower scores, suggesting higher HDLox is related to the impaired HDL oxidant function and subsequently exposed to the elevated risk of CVD outcomes (hazard ratio, 2.72; 95% confidence interval, 1.88–3.94). No association was found between baseline serum HDL cholesterol and incident cardiovascular events in multivariate model
While coronary artery calcification (CAC) is recognized as a reliable marker for coronary atherosclerosis, the relationship between the concentration of C-reactive protein (CRP) and the incidence and ...progression of CAC remains controversial.
PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies until October 2023. The methodological quality of the included studies was evaluated using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was employed to calculate pooled odd ratios (OR) and corresponding 95% confidence intervals, considering heterogeneity among the studies.
Out of the 2545 records, 42 cross-sectional and 9 cohort studies were included in the systematic review. The meta-analysis on 12 eligible cross-sectional studies revealed no significant association between CAC and CRP pooled OR: 1.03 (1.00, 1.06). Additionally, an insignificant association was found between CAC and CRP through meta-analysis on three eligible cohort studies pooled OR: 1.05 (0.95, 1.15) with no considerable heterogeneity across studies. Sensitivity analyses indicated that the meta-analysis models were robust. There was no evidence of publication bias.
Based on the meta-analysis findings, elevated levels of CRP did not emerge as a valuable prognostic maker for CAC incidence and progression prediction.
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