The latest medical research on Clinical Pharmacology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about clinical pharmacology gathered by our medical AI research bot.

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Biosafety Considerations for Viral Vector Gene Therapy: An Explanation and Guide for the Average Everyday-Hero Pharmacist.

Journal of Pharmacy and Pharmacology

An overview of the multi-faceted biosafety points that must be taken into consideration by pharmacists and pharmacies in order to provide viral vector gene therapy to their practice site.

As science and medicine evolves, pharmacists and other healthcare workers are continually faced with unique challenges in the workplace. They are expected to be informed and proficient on new therapies and standards of practice, and be able to apply this knowledge appropriately for their patients. One such advancement that seems to be picking up speed in recent years is gene therapy, which is often achieved with the assistance of a viral vector. As these viral vector doses move closer to mainstream medicine, a host of issues and concerns for the pharmacists, nurses, and caregivers that are involved in the process begin to rise to the surface, often rooted in the critical concern: "How do we dispense, utilize, and administer these doses safely?" Unfortunately, there is no singular, concise source of information for addressing biosafety with viral vector products, and guidance must be gathered from a variety of resources in order to mesh together a reasonable working process. Conclusion: While this may seem to be a daunting task, facilities that already meet USP 797 and USP 800 guidelines are well on their way to being ready to provide viral vector doses. By incorporating additional steps and reviewing biosafety specific resources, these sites can easily adapt to provide these new and novel therapies for their patient population.

Oxytocin as an adolescent treatment for methamphetamine addiction after early life stress in male and female rats.

Neuropsychopharmacology

Early life stress (ELS) is associated with perturbed neural development and augmented vulnerability to mental health disorders, including addiction...

The preventive effects of different doses of atorvastatin on contrast-induced acute kidney injury after CT perfusion.

Clinical Laboratory

Contrast-induced acute kidney injury (CI-AKI) is a severe complication among patients receiving intravascular contrast media. The purpose of this study was to investigate the preventive effects of pretreatment of atorvastatin at intensive doses on CI-AKI after computed tomography (CT) perfusion.

The levels of serum creatinine (SCR), blood urea nitrogen (BUN), Cystatin C (CysC), estimated glomerular filtration rate (eGFR), high-sensitivity C-reactive protein (hs-CRP), and interleukin-6 (IL-6) in patients were compared between the observation group receiving 40 mg/kg atorvastatin and the control group receiving 20 mg/kg atorvastatin before and 72 h after CT examination. In addition, the incidence of CI-AKI was recorded.

Compared with the control group, the incidence of renal injury in the observation group was significantly reduced, from 8% to 2% (χ2  = 6.62, p = 0.010). In addition, there was no notable difference in the levels of Scr, BUN, CysC, hs-CRP, and IL-6 before CT examination between two groups (p > 0.05). The levels of SCR, BUN, CysC, hs-CRP, and IL-6 were increased, while the levels of eGFR were decreased in the control group at 72 h after CT examination (p < 0.05). At 72 h after CT enhancement, the levels of BUN, CysC, and hs-CRP were prominently increased in the observation group (p < 0.05), while SCR, eGFR, and IL-6 did not change (p > 0.05). Compared with the control group, the levels of SCR, BUN, CysC, eGFR, hs-CRP, and IL-6 in the observation group were significantly decreased at 72 h after CT examination (p < 0.05).

Intensive dose of atorvastatin pretreatment can prevent CI-AKI undergoing CT perfusion through lowering inflammation as well as renal function indexes SCR, CysC, BUN, and eGFR.

Safety evaluation of mutagenicity, genotoxicity, and cytotoxicity of Lactobacillus spp. isolates as probiotic candidates.

Clinical Laboratory

Probiotics promote a healthy balance of gut bacteria and have many beneficial effects on human digestive physiology. Although, few side effects of probiotics have been reported. This study aimed to assess the safety of five probiotic candidate Lactobacillus strains isolated from healthy individuals by examining mutagenicity, genotoxicity, and oral toxic effects.

Five selected candidate probiotic (SCPs) strains were evaluated for genotoxicity (Ames test with Salmonella typhimurium), in vitro mammalian chromosome aberration test and an in vivo mouse micronucleus assay on peripheral blood of mice. To evaluate the oral dose toxicity, BALB/c mice models were treated repeatedly (2000, 1000, and 500 mg/kg body weight /day) for 28-days.

The Ames test performed for two S. typhimurium strains TA 98 and TA100 (both in the absence and in the presence of S-9 metabolic activation system) did not show an increase in reverse mutation because of exposure to the SCPs in any of the doses (5.0, 2.5, 1.25, 0.625, and 0.3125 mg/plate). There was no genotoxicity in the SCPs treatment in the vitro chromosome aberration assay with Chinese hamster ovary cells (CHO-K1). In addition, none of the tested strains increased the frequency of micronucleated reticulocytes in reticulocytes, the SCPs with the studied doses caused no substantial variation in the experimental groups compared to the negative control group (p > 0.05). SCPs were not acutely toxic when administered to male and female BALB/c mice by single gavage at (2000, 1000, and 500 mg/kg b.w/day) with no mortality or clinical signs, change in body weight or macroscopic abnormalities were observed in this dose range.

As a result, SCPs did not induce mutagenic potential in vitro with bacterial reverse mutation, clastogenicity, and in vivo tests in the ranges of concentrations evaluated in our study.

Impact of Pharmacist-Led Interventions to Improve Clinical Outcomes for Adults With Type 2 Diabetes at Risk of Developing Cardiovascular Disease: A Systematic Review and Meta-analysis.

Journal of Pharmacy and Pharmacology

The aim of this systematic review and meta-analysis of randomised controlled trials is to evaluate the impact of pharmacist-led interventions on cardiovascular disease (CVD) risk factors among patients with type 2 diabetes.

A literature review was conducted according to PRISMA guidelines using 4 electronic databases: Embase, MEDLINE, CINHAL and the Cochrane Central Register of Controlled Trials. We searched for pharmacist interventions among adults with type 2 diabetes and cardiovascular disease in randomised controlled trials from inception to May 2021 in primary care, diabetes clinics and hospitals. The clinical outcomes measured glycosylated haemoglobin (HbA1c), blood pressure (BP) and lipid profile. The non-clinical outcomes included medication adherence, smoking, health-related quality of life and the cost of the intervention. For the meta-analysis, clinical outcomes were pooled with the random effect model in RevMan 5.3. The Cochrane risk-of-bias tool was used to assess the quality of the included studies.

We retrieved 223 studies,141 of which were included in the review. Ten published articles met the inclusion criteria and were included in the meta-analysis. The pharmacists delivered the interventions alone or collaboratively with other healthcare professionals in hospitals or similar settings. The overall result showed a significant reduction in HbA1c (n = 10; standard deviation in mean value [SDM]: -.53%, 95% CI: -.84, -.23) and systolic BP (n = 10; [SDM]: -.35 mmHg, 95% CI: -.51, -.20) in pharmacist intervention groups. For the non-clinical outcomes, the review revealed variable results from pharmacist intervention compared with those standard care.

Pharmacy interventions provide evidence for pharmacists' decisive role in diabetes care management and reducing cardiovascular risk factors among adults with type 2 diabetes.

Astrocyte regulation of synaptic signaling in psychiatric disorders.

Neuropsychopharmacology

Over the last 15 years, the field of neuroscience has evolved toward recognizing the critical role of astroglia in shaping neuronal synaptic activi...

Polypharmacy and potentially inappropriate medications in stroke rehabilitation: prevalence and association with outcomes.

International Journal of Epidemiology

Background Evidence is scarce regarding polypharmacy and potentially inappropriate medications (PIMs) in rehabilitation medicine. Aim To investigat...

Hsa_circ_0001982 promotes the proliferation, invasion, and multidrug resistance of osteosarcoma cells.

Clinical Laboratory

Osteosarcoma (OS) is the most common bone cancer mostly seen in people aged 10-25 years. This research aims to clarify the function of hsa_circ_0001982 in osteosarcoma (OS) and its effect on drug resistance, preliminarily exploring its mechanism.

The expression of hsa_circ_0001982 and miR-143 in OS clinical tissues and cells was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR), MTT, colony formation assay, and transwell assay assessed cell proliferation, colony formation, migration, and invasion, respectively. The targeted relationship of hsa_circ_0001982 and miR-143 was verified by a dual-luciferase reporter assay.

The expression of hsa_circ_0001982 was significantly increased in OS tissues and cells (MG63), as in well as chemoresistant OS tissues and cells (MG63/Dox). Overexpression of hsa_circ_0001982 promoted proliferation, colony formation, migration, invasion, and multidrug resistance in MG63 cells. By contrast, knockdown of hsa_circ_0001982 markedly reduced the resistance of MG63/Dox cells to doxorubicin (IC50 evidently reduced). Bioinformatic prediction showed that miR-143 was a target miRNA of hsa_circ_0001982, and a dual-luciferase reporter assay proved this. Further experiments revealed that miR-143 expression was notably downregulated in OS tissues, chemoresistant OS tissues, and MG63/Dox cells. Moreover, miR-143 was negatively correlated with hsa_circ_0001982 in OS cells and tissues.

The regulation of malignant behaviors such as proliferation, invasion, migration, and multidrug resistance of OS cells by hsa_circ_0001982 may be achieved by targeting miR-143. Moreover, hsa_circ_0001982 is a potential target for early diagnosis and targeted therapy of OS.

Serum transfer RNA-derived fragment tRF-31-79MP9P9NH57SD acts as a novel diagnostic biomarker for non-small cell lung cancer.

Clinical Laboratory

tRNA-derived fragments (tRFs) have been found to have a crucial function in the pathophysiology of cancers. However, the function of tRFs in non-small cell lung cancer (NSCLC) is yet unknown. The goal of this study was to assess the tRF-31-79MP9P9NH57SD serum expression from NSCLC patients and to determine its diagnostic usefulness.

By using stem-loop quantitative real-time PCR, we were able to detect various tRF-31-79MP9P9NH57SD expressions in 96 NSCLC serum samples, 96 healthy controls, and 20 pairs of NSCLC serum samples pre- and post-surgery (qRT-PCR). After that, we analyzed its diagnostic effectiveness using the receiver operating characteristic (ROC) curve.

Serum tRF-31-79MP9P9NH57SD expression was higher in NSCLC patients, and levels of tRF-31-79MP9P9NH57SD were linked to the clinical stage (p = 0.002) and the malignancy of lymph node (p = 0.012). In addition, after the procedure, the serum tRF-31-79MP9P9NH57SD expression in NSCLC patients dropped. With 48.96 percent sensitivity and 90.62 percent specificity, the area under ROC curve (AUC) was 0.733.

serum tRF-31-79MP9P9NH57SD possibly is a new and groundbreaking biomarker for the NSCLC.

circ_0004872 inhibits proliferation, invasion, and glycolysis of oral squamous cell carcinoma by sponged miR-424-5p.

Clinical Laboratory

Oral squamous cell carcinoma (OSCC) is one of the most common oral malignant tumors. circ_0004872 can inhibit the progression of gastric cancer, but its effect on the growth and metastasis of OSCC is still unclear.

qRT-PCR was used to detect the expression levels of circ_0004872 and miR-424-5p in cancer tissues of OSCC patients and adjacent normal tissues, OSCC cell lines, and human normal oral keratinocytes (HOK). CCK-8, cell colony formation, flow cytometry, and transwell assay were used to detect cell proliferation rate, viability, apoptosis rate, and invasion ability. Use glucose/lactic acid kit to assay cell glycolysis ability. The dual-luciferase reporter gene experiment and RIP experiment verified the relationship between circ_0004872 and miR-424-5p. The protein levels were examined by Western blot.

The expression of circ_0004872 was significantly downregulated in OSCC tissues and cells, and the overexpression of circ_0004872 inhibited the proliferation, vitality, invasion, and glycolysis of OSCC cells, and promoted apoptosis. The expression of miR-424-5p was greatly upregulated in OSCC tissues and OSCC cells. circ_0004872 can adsorb miR-424-5p in OSCC cells, and circ_0004872 can reverse the promoting effect of miR-424-5p overexpression on the process of OSCC cells.

circ_0004872 suppresses the proliferation, invasion, and glycolysis of OSCC cells by sponged miR-424-5p, and promotes apoptosis, which can be used as a potential target for early diagnosis and targeted therapy of OSCC.

Association between nontraditional lipid profiles and the severity of obstructive sleep apnea: A retrospective study.

Clinical Laboratory

Due to the significant role of dyslipidemia, cardiovascular diseases (CVDs) are very common in obstructive sleep apnea (OSA). Nontraditional lipid indices are considered to be a better predictive index for cardiovascular risk. Nevertheless, the association between nontraditional lipid profiles and the severity of OSA is not clear.

A retrospective study was proceeded on 635 patients. Subjects were diagnosed with OSA through polysomnography (PSG). The association between severe OSA and nontraditional lipid profiles [triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio, total cholesterol (TC)/HDL-C ratio, low-density lipoprotein cholesterol (LDL-C)/HDL-C ratio, non-high-density lipoprotein cholesterol (non-HDL-C), atherogenic index (AI), and lipoprotein combine index (LCI)] was examined by utilizing the restricted cubic spline and multivariate logistic regression analysis.

All nontraditional lipid indices had positive relationships with the severity of OSA. By multivariable adjustment, the per SD increment of the TG/HDL-C, TC/ HDL-C, LDL-C/HDL-C, non-HDL-C, AI, and LCI were significantly associated with 88%, 50%, 42%, 40%, 50%, and 125% higher risk for severe OSA respectively. Compared with the lowest tertiles, the adjusted ORs (95% CI) were 2.42 (1.57-3.75), 2.39 (1.53-3.73), 2.35 (1.52-3.64), 1.86 (1.21-2.86), 2.39 (1.53-3.73), and 2.23 (1.43-3.48) for the top tertiles of TG/HDL-C, TC/ HDL-C, LDL-C/HDL-C, non-HDL-C, AI, and LCI respectively.

All nontraditional lipid indices had positive relationship with the severity of OSA. In addition, TG/HDL-C, TC/HDL-C, and AI had better performance than the other nontraditional lipid indices for predicting severe OSA. These findings could help to determine the risk of cardiovascular diseases and improve the dyslipidemia management of OSA patients.

Development and validation of apoptosis-related signature and molecular subtype to improve prognosis prediction in osteosarcoma patients.

Clinical Laboratory

Previous evidence has shown that apoptosis performs integral functions in the tumorigenesis and development of various tumors. Therefore, this study aimed to establish a molecular subtype and prognostic signature based on apoptosis-related genes (ARGs) to understand the molecular mechanisms and predict prognosis in patients with osteosarcoma.

The GEO and TARGET databases were utilized to obtain the expression levels of ARGs and clinical information of osteosarcoma patients. Consensus clustering analysis was used to explore the different molecular subtypes based on ARGs. GO, KEGG, GSEA, ESTIMATE, and ssGSEA analyses were performed to examine the differences in biological functions and immune characteristics between the distinct molecular subtypes. Then, we constructed an ARG signature by LASSO analysis. The prognostic significance of the ARG signature in osteosarcoma was determined by Kaplan-Meier plotter, Cox regression, and nomogram analyses.

Two apoptosis-related subtypes were identified. Cluster 1 had a better prognosis, higher immunogenicity, and immune cell infiltration, as well as a better response to immunotherapy than Cluster 2. We discovered that patients in the high-risk cohort had a lower survival rate than those in the low-risk cohort according to the ARG signature. Furthermore, Cox regression analysis confirmed that a high risk score independently acted as an unfavorable prognostic marker. Additionally, the nomogram combining risk scores with clinical characteristics can improve prediction efficiency.

We demonstrated that patients suffering from osteosarcoma may be classified into two apoptosis-related subtypes. Moreover, we developed an ARG prognostic signature to predict the prognosis status of osteosarcoma patients.