DARU Journal of Pharmaceutical Sciences最新文献

Objective: Urine alkalinization prevents nephrotoxicity in patients receiving high-dose methotrexate (HDMTX). While the standard approach involves IV sodium bicarbonate, alternative oral bicarbonate regimens are crucial in drug shortages and outpatient settings. This study aims to review the efficacy and safety of such regimens.

Methods: PubMed, WOS, and Scopus were systematically searched using the PRISMA protocol for relevant studies involving human subjects, including randomized clinical trials, retrospective, prospective, cohort, case reports, and case series studies. There were no restrictions on language, time, or age group. Qualified and eligible papers were used to extract data on efficacy and safety indicators, and the final relevant records were assessed for quality using the Risk of Bias in Non-Randomized Studies-of Interventions (ROBINS-I) assessment tool.

Results: 12 studies with 1212 participants were included in the systematic review, with pooled data from 8 studies used for meta-analysis. No significant differences in mean differences (MDs) or odds ratio (OR) were found after the oral bicarbonate regimen, except for when urine pH fell to < 7 (MD: 0.91, 95% CI: 0.32, 1.5, P < 0.05) and the incidence of diarrhea (OR: 2.92, 95% CI: 1.69, 5.05, P < 0.05).

Conclusion: An oral bicarbonate regimen is a safe and effective way to alkalize HDMTX urine, providing a viable and cost-effective alternative to IV protocols. Further prospective multicenter studies are necessary. Systematic review registration identifier: CRD42023379666.

Background: Myocardial ischemia/reperfusion injury (MIRI) seriously threatens the health of people. The mitochondrial dysfunction in cardiomyocytes can promote the progression of MIRI. Dexmedetomidine (Dex) could alleviate the myocardial injury, which was known to reverse mitochondrial dysfunction in lung injury. However, the function of Dex in mitochondrial dysfunction during MIRI remains unclear.

Objective: To assess the function of Dex in mitochondrial dysfunction during MIRI.

Methods: To investigate the function of Dex in MIRI, H9C2 cells were placed in condition of hypoxia/reoxygenation (H/R). CCK8 assay was performed to test the cell viability, and the mitochondrial membrane potential was evaluated by JC-1 staining. In addition, the binding relationship between Sirt3 and Prdx3 was explored by Co-IP assay. Furthermore, the protein expressions were examined using western blot.

Results: Dex could abolish H/R-induced mitochondrial dysfunction in H9C2 cells. In addition, H/R treatment significantly inhibited the expression of Sirt3, while Dex partially restored this phenomenon. Knockdown of Sirt3 or Prdx3 obviously reduced the protective effect of Dex on H/R-induced mitochondrial injury. Meanwhile, Sirt3 could enhance the function of Prdx3 via deacetylation of Prdx3.

Conclusion: Dex was found to attenuate H/R-induced mitochondrial dysfunction in cardiomyocytes via activation of Sirt3/Prdx3 pathway. Thus, this study might shed new lights on exploring new strategies for the treatment of MIRI.

Purpose: Various risk factors are mentioned for osteoporosis, sarcopenia, and osteosarcopenia. Our aim is to assess the impacts of anti-diabetic drugs on these disorders.

Methods: To perform this study, the participants' data was extracted from the Bushehr Elderly Health (BEH) program in Iran. Afterward, the data were categorized into three subgroups: osteoporosis, sarcopenia, and osteosarcopenia, based on WHO and European Working Group on Sarcopenia in Older People (EWGSOP-2) working group definitions. Demographic characteristics, anthropometric measures, past medical history, and current medications were recorded. Pearson chi-squared and simple/multiple logistic regression using Python (3.11.4) and R (4.3.1) programming software assessed the association between anti-diabetic agents and these bone disorders.

Results: Out of 1995 participants, 820, 848, and 404 had osteoporosis, sarcopenia, or osteosarcopenia, respectively. Among all types of anti-diabetic drugs, a significant protective association between osteoporosis and consumption of second-generation sulfonylureas was found; Adjusted Odd Ratio (AOR) = 0.65 ([95% CI: 0.45-0.94], p-value = 0.023). No associations were found between sarcopenia and consumption of anti-diabetic agents. A significant association was observed between using Meglitinides and the risk of osteosarcopenia; AOR = 4.98 ([95% CI: 1.5-16.55], p-value = 0.009).

Conclusion: In conclusion, a protective association between consumption of second-generation sulfonylureas and osteoporosis was found. Moreover, a positive association was found between the consumption of meglitinides and osteosarcopenia. However, to support these findings, further studies are recommended.

Purpose: Chronic diseases often hinder the natural healing process, making wound infections a prevalent clinical concern. In severe cases, complications can arise, potentially leading to fatal outcomes. While allopathic treatments offer numerous options for wound repair and management, the enduring popularity of herbal medications may be attributed to their perceived minimal side effects. Hence, this review aims to investigate the potential of herbal remedies in efficiently treating wounds, presenting a promising alternative for consideration.

Methods: A literature search was done including research, reviews, systematic literature review, meta-analysis, and clinical trials considered. Search engines such as Pubmed, Google Scholar, and Scopus were used while retrieving data. Keywords like Wound healing 'Wound healing and herbal combinations', 'Herbal wound dressing', Nanotechnology and Wound dressing were used.

Result: This review provides valuable insights into the role of natural products and technology-based formulations in the treatment of wound infections. It evaluates the use of herbal remedies as an effective approach. Various active principles from herbs, categorized as flavonoids, glycosides, saponins, and phenolic compounds, have shown effectiveness in promoting wound closure. A multitude of herbal remedies have demonstrated significant efficacy in wound management, offering an additional avenue for care. The review encompasses a total of 72 studies, involving 127 distinct herbs (excluding any common herbs shared between studies), primarily belonging to the families Asteraceae, Fabaceae, and Apiaceae. In research, rat models were predominantly utilized to assess wound healing activities. Furthermore, advancements in herbal-based formulations using nanotechnology-based wound dressing materials, such as nanofibers, nanoemulsions, nanofiber mats, polymeric fibers, and hydrogel-based microneedles, are underway. These innovations aim to enhance targeted drug delivery and expedite recovery. Several clinical-based experimental studies have already been documented, evaluating the efficacy of various natural products for wound care and management. This signifies a promising direction in the field of wound treatment.

Conclusion: In recent years, scientists have increasingly utilized evidence-based medicine and advanced scientific techniques to validate the efficacy of herbal medicines and delve into the underlying mechanisms of their actions. However, there remains a critical need for further research to thoroughly understand how isolated chemicals extracted from herbs contribute to the healing process of intricate wounds, which may have life-threatening consequences. This ongoing research endeavor holds great promise in not only advancing our understanding but also in the development of innovative formulations that expedite the recovery process.

Background: Dexamethasone-induced neurotoxicity has been previously reported. However, the molecular mechanisms are still not completely understood.

Objectives: The current work aimed to investigate the modulatory effects of α- and β-adrenergic receptors on dexamethasone-induced neurotoxicity in rats focused on changes in β-arrestin2 and molecular markers of neural injury in cerebral cortex.

Methods: Male Wistar rats were subcutaneously injected with dexamethasone (10 mg/kg/day) for 7 days to induce neural injury in the cerebral cortex. The experiment involved 5 groups: control, dexamethasone, carvedilol, propranolol, and doxazosin. In the last 3 groups, drugs were given 2 hours before dexamethasone injection. At the end of experiment, brain samples were collected for measurement of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), kinase activity of protein kinase B (Akt), diacylglycerol (DAG), α-smooth muscle actin (α-SMA), Smad3, β-amyloid and phospho-tau protein levels in addition to histopathological examination of brain tissue using hematoxylin-eosin, Nissl, and Sirius red stains. Moreover, β-arrestin2 levels in the cerebral cortex were measured using immunohistochemical examination.

Results: Dexamethasone slightly reduced brain weight and significantly decreased BDNF, Akt kinase activity and β-arrestin2 but markedly induced degeneration of cortical neurons and significantly increased GFAP, DAG, α-SMA, Smad3, β-amyloid and phospho-tau protein levels compared to controls. Carvedilol, propranolol, and doxazosin reversed all dexamethasone-induced molecular changes and slightly ameliorated the histopathological changes. Carvedilol significantly increased brain weight and β-arrestin2 levels compared to dexamethasone, propranolol, and doxazosin groups.

Conclusion: blocking α- and/or β-adrenergic receptors alleviate dexamethasone-induced neurotoxicity despite their distinct effects on β-arrestin2 levels in the cerebral cortex.

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.

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.

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: 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.

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.