DARU Journal of Pharmaceutical Sciences最新文献

Introduction: Typical antipsychotics are known to produce extrapyramidal side effects such as drug induced parkinsonism, acute dystonia, akathisia, tardive dyskinesias and rabbit syndrome. Rabbit syndrome is characterized by vertical rhythmic motion of the mouth and lips, resembling chewing movements of a rabbit.

Reason for the report: Rabbit syndrome seen in patients on antidopaminergic therapies is characterized by vertical rhythmic movements of perioral region, has a late onset, and characteristically spares the tongue. The main aim of the report is to highlight atypical manifestation of antipsychotic associated Rabbit syndrome in the presence of a serotonergic antidepressant. An elderly patient presented with atypical rabbit syndrome with relatively acute onset, horizontal movements of jaw and marked tongue involvement after haloperidol-escitalopram initiation.

Outcome: The patient improved with discontinuation of antipsychotic. The tongue involvement was believed to be secondary to escitalopram use.

Purpose: Despite the advances in treatment, lung cancer is a global concern and necessitates the development of new treatments. Biguanides like metformin (MET) and artemisinin (ART) have recently been discovered to have anti-cancer properties. As a consequence, in the current study, the anti-cancer effect of MET and ART co-encapsulated in niosomal nanoparticles on lung cancer cells was examined to establish an innovative therapy technique.

Methods: Niosomal nanoparticles (Nio-NPs) were synthesized by thin-film hydration method, and their physicochemical properties were assessed by FTIR. The morphology of Nio-NPs was evaluated with FE-SEM and AFM. The MTT assay was applied to evaluate the cytotoxic effects of free MET, free ART, their encapsulated form with Nio-NPs, as well as their combination, on A549 cells. Apoptosis assay was utilized to detect the biological processes involved with programmed cell death. The arrest of cell cycle in response to drugs was assessed using a cell cycle assay. Following a 48-h drug treatment, the expression level of hTERT, Cyclin D1, BAX, BCL-2, Caspase 3, and 7 genes were assessed using the qRT-PCR method.

Results: Both MET and ART reduced the survival rate of lung cancer cells in the dose-dependent manner. The IC₅₀ values of pure ART and MET were 195.2 μM and 14.6 mM, respectively while in nano formulated form their IC₅₀ values decreased to 56.7 μM and 78.3 μM, respectively. The combination of MET and ART synergistically decreased the proliferation of lung cancer cells, compared to the single treatments. Importantly, the combination of MET and ART had a higher anti-proliferative impact against A549 lung cancer cells, with lower IC₅₀ values. According to the result of Real-time PCR, hTERT, Cyclin D1, BAX, BCL-2, Caspase 3, and Caspase 7 genes expression were considerably altered in treated with combination of nano formulated MET and ART compared to single therapies.

Conclusion: The results of this study showed that the combination of MET and ART encapsulated in Nio-NPs could be useful for the treatment of lung cancer and can increase the efficiency of lung cancer treatment.

Purpose: Colloid and/or co-load may be more effective than crystalloid for preventing postspinal anesthesia hypotension. We tested five different prophylactic norepinephrine dosages combined with colloid co-load infusion in patients receiving cesarean section and spinal anesthesia.

Methods: Patients were randomly allocated to receive different prophylactic norepinephrine dosages (0 [NE 0 group], 0.025 [NE 25 group], 0.05 [NE 50 group], 0.075 [NE 75 group], or 0.1 [NE 100 group] µg/kg/min) combined with 500 mL 6% hydroxyethyl starch (130/0.4) immediately following spinal anesthesia (n = 35 per group). The primary endpoint was the incidence of postspinal anesthesia hypotension (systolic blood pressure [SBP] < 80% of baseline). Secondary endpoints included severe hypotension, bradycardia, nausea or vomiting, hypertension, SBP stability control versus baseline, the 50% (effective dose, ED50) and 90% (ED90) dose effective for preventing postspinal anesthesia hypotension, Apgar scores, and umbilical cord blood gases.

Results: The incidence of postspinal anesthesia hypotension was 48.6%, 31.3%, 17.1%, 14.3%, and 5.7% in the respective groups. As the prophylactic norepinephrine dosage increased, the incidence of postspinal anesthesia hypotension declined (p < 0.001), and SBP remained stable relative to baseline (median performance error [MDPE], p < 0.001; median absolute performance error [MDAPE], p = 0.001). The ED50 and ED90 values were -0.006 (95% CI -0.046-0.013) and 0.081 (95% CI 0.063-0.119) µg/kg/min. Other endpoints were comparable across the groups.

Conclusion: An initial prophylactic norepinephrine dosage of 0.05 µg/kg/min combined with 500 mL 6% hydroxyethyl starch (130/0.4) co-load infusion was optimal for preventing postspinal anesthesia hypotension during cesarean section.

Trial registration: NCT05133817, registration date: 12 Nov, 2021.

Background: Acute myeloid leukemia (AML) is a hematopoietic malignancy. Chidamide has shown anti-cancer effect in different malignancies. The function of Chidamide in glycolysis in AML cells remains unclear.

Methods: AML cells were treated with 1000 nM Chidamide for 48 h. The levels of long non-coding RNA-GNAS-AS1, miR-34a-5p, glycolysis-related proteins, and Ras homolog gene family (RhoA)/Rho-associated protein kinase (ROCK) signaling-related proteins were detected by qRT-PCR or western blot. Cell viability and apoptosis were measured by CCK-8 and flow cytometry. Glycolysis levels were measured by assay kits. GNAS-AS1 N6-methyladenosine (m6A) modification level was detected by methylated RNA immunoprecipitation sequencing. The combined targets of miR-34a-5p were validated using a dual-luciferase reporter assay. BALB/C nude mice were selected for subcutaneous tumor validation. Chidamide at a dosage of 25 mg/kg was used in the animal study.

Results: GNAS-AS1 promoted glycolysis in AML cells by upregulating the expression of glycolysis-related proteins and increasing glucose consumption, lactate production, ATP generation, and the extracellular acidification rate. Chidamide treatment suppressed WT1-associated protein (WTAP)-mediated RNA m6A modification of GNAS-AS1. Chidamide downregulated GNAS-AS1 to inhibit glycolysis in AML cells. GNAS-AS1 targeted miR-34a-5p to promote insulin-like growth factor 2 mRNA-binding protein (IGF2BP2) expression. IGF2BP2 inhibition reversed the promoting effect of miR-34a-5p knockdown on glycolysis and RhoA/ROCK pathway in Chidamide-treated cells. GNAS-AS1 overexpression abolished the inhibitory effect of Chidamide on AML tumorigenesis in vivo by modulating the RhoA/ROCK pathway.

Conclusion: Chidamide inhibited glycolysis in AML by repressing WTAP-mediated GNAS-AS1 m6A modification and then regulating the miR-34a-5p/IGF2BP2 axis.

Introduction: Idiopathic granulomatous mastitis (IGM) is a rare chronic inflammatory lesion of the breast that mimics breast cancer or infection. Immunological pathogenesis is strongly suggested for the disease.

Reason for the report: The treatment remains controversial, comprising a spectrum from observation or NSAIDs to immunosuppressive agents and surgery. Intractable cases are not uncommon and represent a major treatment challenge. Therefore in this study, we examine the effect of a topical immunomodulator agent, imiquimod, on refractory IGM. Patient 1 had IGM for 9 months and had not responded to the existing treatments. She responded to a 7-week course of imiquimod. In patient 2, the disease had begun 4 months sooner and had been resistant to all treatments; it responded to imiquimod after 4 weeks. Ulcers appeared on the skin of both patients but resolved safely.

Outcome: Both patients were very satisfied with the results. Imiquimod can be an appropriate local treatment with limited adverse effects in refractory IGM. We propose similar studies to assess the efficacy of imiquimod in IGM further, paying attention to the possibility of developing skin wounds.

Background: Recent research indicates a prevalence of typical lung infections, such as pneumonia, in lung cancer patients. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii stand out as antibiotic-resistant pathogens. Given this, there is a growing interest in alternative therapeutic avenues. Boron and zinc derivatives exhibit antimicrobial, antiviral, and antifungal properties.

Objectives: This research aimed to establish the effectiveness of ZnO and ZB NPs in combating bacterial infections in lung cancer cell lines.

Methods: Initially, this study determined the minimal inhibitory concentration (MIC) and fractional inhibitory concentration (FIC) of zinc oxide nanoparticles (ZnO NPs) and zinc borate (ZB) on chosen benchmark strains. Subsequent steps involved gauging treatment success through a lung cancer-bacteria combined culture and immunohistochemical analysis.

Results: The inhibitory impact of ZnO NPs on bacteria was charted as follows: 0.97 µg/mL for K. pneumoniae 700603, 1.95 µg/mL for P. aeruginosa 27853, and 7.81 µg/mL for Acinetobacter baumannii 19,606. In comparison, the antibacterial influence of zinc borate was measured as 7.81 µg/mL for Klebsiella pneumoniae 700603 and 500 µg/mL for both P. aeruginosa 27853 and A.baumannii 19606. After 24 h, the cytotoxicity of ZnO NPs and ZB was analyzed using the MTT technique. The lowest cell viability was marked in the 500 µg/mL ZB NPs group, with a viability rate of 48.83% (P < 0.001). However, marked deviations appeared at ZB concentrations of 61.5 µg/mL (P < 0.05) and ZnO NPs at 125 µg/mL.

Conclusion: A synergistic microbial inhibitory effect was observed when ZnO NP and ZB were combined against the bacteria under investigation.

Purpose: Current clinical practice recommends switching innovator intravenous trastuzumab (IV-TZM_i) to subcutaneous trastuzumab (SC-TZM) to save healthcare resources. However, with the availability of biosimilar intravenous trastuzumab (IV-TZM_b), there is a need to re-evaluate the recommendation. Hence, this study aims to compare the cost and resource use of SC-TZM and IV-TZM_b in a Malaysian public healthcare facility.

Methods: This activity-based costing study consists of (1) a retrospective medical record abstraction to determine patient details to estimate drug costs and (2) a time-motion study to quantify personnel time, patient time, and consumables used. The total cost of both SC-TZM and IV-TZM_b were then compared using a cost-minimization approach, while differences were explored using an independent t-test. A sensitivity analysis was also conducted to determine the impact of uncertainties in the analysis.

Results: The mean total cost of SC-TZM and IV-TZM_b was USD 13,693 and USD 5,624 per patient respectively. The cost difference was primarily contributed by savings in drug cost of IV-TZM_b, a reduction of USD 8,546 (SD = 134), p < 0.001 compared to SC-TZM. Interestingly, SC-TZM had a significantly lower cost than IV-TZM_b for both the consumable and personnel cost, a reduction by USD 300 (SD = 17.6); p < 0.001 and USD 176 (SD = 7.3); p < 0.001 respectively. The sensitivity analysis demonstrated that the total cost difference between the formulation was mainly driven by drug costs.

Conclusion: The study evidenced that IV-TZM_b was a more economically viable option in Malaysian public healthcare currently compared to SC-TZM.

Objectives: Veterinarians and pharmacists are familiar with the efficacy and safety aspects attributed to active pharmaceutical ingredients included in medicines, but they are rarely concerned with the safety of excipients present in medicines. Although generally recognized as safe, excipients are not chemically inert and may produce adverse events in certain animal populations. This review aims to present excipients of concern to these populations and highlight their relevance for rational veterinary pharmacotherapy.

Evidence acquisition: A comprehensive review of the literature about the existence of adverse reactions in animals caused by pharmaceutical excipients was carried out based on an exploratory study. An overview of the correct conditions of use and safety of these excipients has also been provided, with information about their function, the proportion in which they are included in the different pharmaceutical dosage forms and the usual routes of administration.

Results: We identified 18 excipients considered of concern due to their potential to cause harm to the health of specific animal populations: bentonite, benzalkonium chloride, benzoic acid, benzyl alcohol, ethanol, lactose, mannitol, mineral oil, monosodium glutamate, polyethylene glycol, polysorbate, propylene glycol, sodium benzoate, sodium carboxymethylcellulose, sodium lauryl sulfate, sulfites, polyoxyethylene castor oil derivatives, and xylitol. Among the 135 manuscripts listed, only 24 referred to studies in which the substances were correctly evaluated as excipients.

Conclusions: Based on the information presented in this review, the authors hope to draw the attention of professionals involved in veterinary pharmacotherapy to the existence of excipients of concern in medicines. This information contributes to rational veterinary pharmacotherapy and supports veterinary pharmacovigilance actions. We hope to shed light on the subject and encourage studies and new manuscripts that address the safety of pharmaceutical excipients to the animal population.

Background: Renal cell carcinoma (RCC) is a common malignancy. Local anesthetics were displayed powerful effects against various cancers. This study aims to probe the functions and molecular mechanism of ropivacaine in RCC.

Methods: Different concentrations of ropivacaine were performed to administrate RCC cells including 786-O and Caki-1 cells. Cell viability and cell apoptosis were examined using CCK-8 and flow cytometry, respectively. Cell migration and invasion were determined by transwell assay. RMRP and CCDC65 expression was firstly predicted using TCGA dataset and further validated in RCC cells using qRT-PCR and western blot. The interactions among RMRP, EZH2 and CCDC65 were verified by RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays.

Results: Ropivacaine effectively suppressed RCC cell viability, migration and invasion and enhanced cell apoptosis rate. Aberrantly elevated RMRP expression in RCC tissues was predicted by TCGA database. Interestingly, overexpressed RMRP observed in RCC cells could be also blocked upon the administration of ropivacaine. Likewise, RMRP knockdown further strengthened ropivacaine-mediated tumor suppressive effects on RCC cells. In terms of mechanism, RMRP directly interacted with EZH2, thereby modulating the histone methylation of CCDC65 to silence its expression. Moreover, ropivacaine inhibited tumor growth in mice bearing RCC tumor through regulating RMRP/EZH2/CCDC65 axis.

Conclusion: In sum up, our work revealed that ropivacaine suppressed capacities of RCC cell viability, migration and invasion through modulating the RMRP/EZH2/CCDC65 axis, which laid the experimental foundation of ropivacaine for clinical application in the future.

Purpose: As classical health technology assessment models fail to predict the complexities of related impacts, the application of modeling techniques such as systems dynamics simulation (SD) is essential. This study aimed to develop an SD model to predict the outcomes of access to a new medicine in Iran.

Methods: This study extracted the important and influential variables in providing access to new pharmaceutical technologies by comprehensively reviewing previous research and combining the technical knowledge of experts in this field. The variables were incorporated into the systems thinking framework and modeled using dynamic systems tools, followed by simulation and testing in VENSIM. The model was piloted for deferoxamine and deferasirox in thalassemia. Various tests were used to evaluate the validity and reliability of the model. The model was designed for a ten-year horizon (2018-2028) for medicines selected as the pilot.

Results: The variables extracted from the panel of experts encompassed the primary and short-term impacts of access to newly emerged medicine and long-term impacts regarding the economy, health, and society. After modeling, the leverage points presented for the problem with the greatest impact or effectiveness in access to new medicine included the policy determining the amount of medicine supply, the import and production of medicine, the prevalence and incidence of disease, insurance coverage, and treatment adherence.

Conclusion: The SD models allow the researchers to evaluate the efficiency and health outcomes of a new pharmaceutical more precisely in the health system in Iran.