Clinical Pharmacology : Advances and Applications最新文献

Background: Knee pain causes functional limitations, eventually compromising the quality of life. We evaluated the efficacy of our water-dispersible turmeric formulation (60% natural curcuminoids, TurmXTRA 60N^®-WDTE60N), which exhibited better PK profile at low dose (250 mg) than standard turmeric extract, in alleviating symptoms of chronic knee pain.

Methods: In this randomized, double-blind, placebo-controlled trial, subjects received either 250 mg WDTE60N capsule (150 mg curcuminoids; n = 53) or appearance-matched placebo capsule (n = 53) once daily for 90 days. Primary endpoint was change in pain score on the visual analogue scale (VAS) after 80-m fast-paced walk test.

Results: A total of 96 subjects completed the study. WDTE60N reduced VAS score from baseline (5.4 ± 0.9) to day 90 (3.8 ± 0.8) with greater mean reduction than placebo (-1.5 ± 0.7 vs -0.6 ± 0.8, p < 0.0001; 2.5 times). It also significantly improved the time taken for 80-m fast-paced walk test and 9-step stair-climb test; and improved all biomarkers compared to placebo (p > 0.05). Three adverse events occurred but were unrelated to study products.

Conclusion: WDTE60N 250 mg administered once daily for 3 months, alleviated knee pain, improved joint function in healthy subjects with chronic knee pain, was well tolerated and safe.

Background: Acokanthera schimperi is traditionally used for the treatment of wounds and various bacterial infections. Due to the ongoing escalation of antimicrobial resistance, there is an increasing demand for the appropriate wound care and hence, the present study was initiated to investigate the wound healing effects of the leaf extract ointments of A. schimperi in mice and its in-vitro antioxidant activity.

Methods: The crude extract was prepared as 5% and 10% w/w ointments for topical use in mice. Wound contraction and epithelialization period were determined in excision and infected models, whereas tensile strength was determined in an incision model. Besides, its antioxidant activity was evaluated using the DPPH method.

Results: In this study, the 10% w/w extract ointment did not cause toxicity at the 2000 mg/kg limit dose. In the excision model, the 10% w/w ointment exhibited a significant wound contraction effect starting from day 6 to 14 with a complete epithelization shown on day 13. Besides, the 5%w/w ointment showed a significant wound contraction effect starting from day 6 onwards, and a significant decrease in the epithelization period observed on day 16. Conversely, both the 10% w/w and 5% w/w ointments showed significant wound contraction effects starting from day 4 and onwards in the infected model. However, a complete epithelization period was observed on days 14 and 18 in the 10%w/w and 5% w/w/extract ointment treated groups, respectively. In the incision model, the 10% (w/w) and 5% (w/w) extract ointments showed a significant increase in tensile strength by 36.80 and 32.23%, respectively. Moreover, the antioxidant activity of the extract was concentration-dependent with an IC50 value of 5.49± 0.38 µg/µL.

Conclusion: The potential wound healing effects of this plant may provide a candidate source in the discovery of new drugs for the treatment of wounds.

Acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a great potential to overwhelm the world healthcare systems that may lead to high morbidity and mortality. It also affects world economic development in the future. Currently, no proven effective drugs or vaccines are available for the management of COVID-19 disease. The pace of normal drug development progression is unacceptable in the context of the current pandemic. Therefore, repurposing the existing drugs that were used for the treatment of malaria, Ebola, and influenza helps rapid drug development for COVID-19. Currently, several repurposing candidate drugs are in a clinical trial including, chloroquine monoclonal antibodies, convalescent plasma, interferon, and antiviral therapies. Antiviral drugs like arbidol, remdesiv and favirnavir are the most promising due to the similarities of the viruses regarding viral entry, fusion, uncoating, and replication. This review article provides an overview of the potential therapeutic agent, which displayed better clinical treatment outcomes. Moreover, with further understanding of the SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise, and investigations on these novels anti-SARSCoV- 2 agents are also reviewed.

The current era of preventive cardiology continues to emphasize on low-density lipoprotein cholesterol (LDL-C) reduction to alleviate the burden of atherosclerotic cardiovascular disease (ASCVD). In this regard, the pharmacological inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) enzyme via monoclonal antibodies has emerged as a novel lipid-lowering therapy, leading to a marked reduction in circulating LDL-C levels and subsequent improvement of cardiovascular outcomes. As these agents are increasingly used in current clinical practice, mounting scientific and clinical evidence supports that PCSK9 inhibitors offer an excellent safety and tolerability profile with a low incidence of adverse events. Notably, the most frequently reported side effects are injection-site reactions. In contrast to statins, PCSK9 inhibitors do not appear to exert a detrimental effect on glycemic control or to increase the incidence of new-onset diabetes mellitus. Accumulating evidence also indicates that PCSK9 inhibitors are a safe, well-tolerated and effective therapeutic strategy for patients with statin intolerance. On the other hand, as PCSK9 inhibitors reduce LDL-C to unprecedented low levels, a large body of current research has examined the effects of their long-term administration on neurocognition and on levels of vitamin E and other fat-soluble vitamins, providing encouraging results. This review aims to present and discuss the current clinical and scientific evidence pertaining to the safety and tolerability of PCSK9 inhibitors.

Background: Tardive dyskinesia (TD) remains a significant burden especially among patients taking psychotropic medications, and it is associated with adverse effects that can lead to subjective suffering, stigma, poor compliance to medication, and poor quality of life. However, it is unrecognized and overlooked in clinical settings. So, this study aimed to assess the magnitude of tardive dyskinesia and associated factors among mentally ill patients attending follow-up treatment at Jimma University Medical Center Psychiatry clinic, Jimma, Southwest Ethiopia, 2019.

Methods: Institutional-based cross-sectional study design was conducted in 417 samples. Participants were selected by systematic random sampling techniques. Data were collected by a semi-structured interviewer-administered questionnaire, and the document was reviewed to obtain the patient's profile. Tardive dyskinesia was assessed by using the Extrapyramidal Symptom Rating Scale after informed consent was obtained from respondents. Data entry was done by EpiData version 3.1, and analysis was done by using SPSS 22.0 statistical software. Binary logistic regression and multivariate logistic regression were used to see the association and to identify independent factors at a p-value of <0.05.

Results: Prevalence of drug-induced tardive dyskinesia was 15.4% (CI 95%: 12.0, 19.3). Female, age range between 30 and 44 years, having a diagnosis of major depressive disorder with the psychotic feature, taking chlorpromazine equivalent dose ˃600mg, and taking anticholinergic medications were variables positively associated with tardive dyskinesia, whereas cigarette smoking was negatively associated with tardive dyskinesia.

Conclusion: The prevalence of drug-induced tardive dyskinesia in this study was high. Prescribing medications less than 600mg equivalent dose of chlorpromazine, giving attention for female patients, patients having a diagnosis of major depressive disorder, and reducing giving anticholinergic medications will be important measures for clinicians to reduce the occurrence of tardive dyskinesia.

Background: Ciprofloxacin is an antimicrobial that is commonly used to treat several types of infections. It exerts its antimicrobial activity through interfering with bacterial DNA replication and transcription, leading to increase oxidative stress and eventually bacterial death. Vitamin D, on the other hand, has been found to have DNA protective and antioxidant effects. In the current study, the possible interactive effect of vitamin D on ciprofloxacin-induced cytotoxicity was investigated in various standard bacterial strains.

Methods: The bacterial strains that were used include Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Acinetobacter baumannii, Proteus mirabilis, and Klebsiella pneumoniae. The antibacterial effect of ciprofloxacin with and without vitamin D treatment of the bacteria was assessed using disc diffusion method and by measuring the minimum inhibitory concentration (MIC) and zones of inhibition of bacterial growth. Moreover, reactive oxygen species (ROS) generation after pretreatment of E. Coli cells with ciprofloxacin and/or vitamin D was measured as a function of as a function of hydrogen peroxide generation.

Results: Ciprofloxacin demonstrated a potent antibacterial effect against the tested strains of bacteria. Moreover, pretreatment with vitamin D resulted in protecting the bacteria from the cytotoxicity of ciprofloxacin, this was indicated by the significantly smaller zones of inhibition and higher MIC values compared to ciprofloxacin alone as well as reduced ciprofloxacin-induced ROS generation after treatment with vitamin D.

Conclusion: Results revealed the possible reduction in the activity of ciprofloxacin when used in combination with vitamin D. This could be explained by the ability of vitamin D to reduce oxidative stress in the bacterial cells.

Background: The morbidity and mortality rate from diabetic mellitus are increasing in the world especially in low- and middle-income countries; hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes mellitus. Therefore, the aim of this study was to evaluate the hypoglycemic effect of 80% methanol root extract of Acanthus polystachyus in normoglycemic, hyperglycemic, and streptozotocin-nicotinamide induced diabetic rats.

Methods: Male albino Wistar rats were divided into five groups (n=6) in all three models. In all models, group one rats served as a negative control and were received vehicle (10mL/kg distilled water), whereas group two (APRE100), three (APRE200), and four (APRE400) were treated with 100, 200, and 400mg/kg of extract, respectively, and group five were treated with glibenclamide (5mg/kg) and served as a positive control. Blood glucose levels were measured at different time points by taking blood from their tails. Data were analyzed using one-way ANOVA followed by Tukey's post hoc test to carry out comparisons between and within-group and P < 0.05 was considered as statistically significant.

Results: The root of Acanthus polystachyus reduces peak blood sugar levels significantly after the loading of oral glucose at all tested doses. In streptozotocin-nicotinamide-induced type 2 diabetic rats, the daily oral administration of the crude extracts showed a significant reduction of blood glucose level at all tested doses compared to the negative control group. However, the extract did not reduce blood glucose levels in normoglycemic rats at all tested doses compared to both negative and positive control.

Conclusion: From this study, it can be concluded that the root extract of Acanthus polystachyus showed an antihyperglycemic effect in hyperglycemic and diabetic rats but lack hypoglycemic effect in normoglycemic rats. Hence, the plant root may be a good candidate for the development of new antidiabetic drugs.

Purpose: Given the beneficial effect of MgSO₄ on the cardiovascular system, this study was designed to investigate the effect of MgSO₄ administration on suppressing some atherosclerotic risk factors in moderate coronary artery disease patients with one or two atherosclerotic vessels.

Patients and methods: In a randomized double-blind placebo-controlled clinical trial study, 64 patients with moderate coronary artery disease (55-69% stenosis) were selected according to angiography findings. Patients were divided into four groups including patients with one or two atherosclerotic vessels treated with MgSO₄ (Mg-treated-VR1, Mg-treated-VR2, respectively), placebo treated patients with one or two atherosclerotic vessels (Control-VR1, Control-VR2, respectively). The patients received either placebo or MgSO₄ supplement capsule containing 300 mg MgSO₄ for six months on a daily basis. ESR, Ca/Mg ratio, urine Mg level, serum Mg, fibrinogen, homocysteine, uric acid, Na, K, Ca, CRP, T3, T4, TSH, BUN, and Cr concentrations were measured at baseline and every three months.

Results: Serum T3, Ca, K, homocysteine, CRP, and Mg concentrations were significantly improved in Mg-treated groups compared to placebo groups.

Conclusion: The results of this study showed that despite the slight change in serum magnesium level, oral administration of MgSO₄for six months could slightly reduce the serum levels of some inflammatory and vascular factors in moderate coronary artery disease patients.