Pakistan journal of pharmaceutical sciences最新文献

Background: Entry of air into the extracorporeal circuit and inappropriate anticoagulation are significant factors associated with clotting. Even with systemic heparination, microbubbles can be implicated as sites for thrombosis and accelerate heparin metabolism. Fluid Stop devices, which prevent fluid from flowing during line drainage, have been shown potentially to decrease air embolism and improve hemostasis within circuits, but there is no concrete evidence available regarding simultaneous heparin use.

Objectives: The objective of this trial was to determine whether the use of systemic heparin and a portable fluid stop device can decrease air embolism and clotting within hemodialysis circuits compared with traditional infusion sets. Anticoagulation stability, risk of bleeding, and patient satisfaction were also measured.

Methods: In this prospectively conducted single-center randomized controlled trial, 80 hemodialysis patients receiving maintenance hemodialysis were randomly assigned either to a control group with standard infusion sets or an observation group with fluid-stopping sets and all receiving standard heparin doses. A total of 800 hemodialysis sessions were conducted prospectively with observation for air bubble entrance, line draining, and clotting. Secondary endpoints included ACT variability, satisfaction rates, and instances of bleeding complications.

Results: A significantly lower number of line emptying procedures (3 vs. 24; 5.0% vs. 27.5%), air bubble entries (4 vs. 28; 7.5% vs. 32.5%), and clotting incidents (2 vs. 12; 2.5% vs. 22.5%) were seen in the observation group compared with controls (P < 0.01). The stability of ACT values with smaller ranges of fluctuation was better in the observation group. Scores on satisfaction were higher, and there were no complications seen with bleeding.

Conclusion: Findings from these preliminary studies indicate that fluid-stopping devices may potentially improve heparin efficacy by preventing air embolism and clotting with no loss of safety. Based on these preliminary findings, larger multicenter trials are needed.

Background: In recent years, the incidence of type B aortic dissection (TBAD) has shown an upward trend.

Objective: This study investigated the impact of dual antiplatelet therapy (DAPT) with aspirin and clopidogrel on TBAD, providing valuable insights for clinical management.

Methods: A total of 120 TBAD patients admitted to our hospital between January 2022 and December 2023 were enrolled and randomized into two groups: A control group receiving standard treatment without DAPT and a research group receiving DAPT. Recovery time was measured in both groups. Cardiac function, coagulation parameters, inflammatory markers (interleukin [IL]-1β, IL-6, IL-10, tumor necrosis factor [TNF]-α, and systemic immune-inflammation index [SII]), and oxidative stress indicators (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], and malondialdehyde [MDA]) were assessed before and after treatment. Additionally, pain levels and adverse events, including bleeding and thrombotic risks, were monitored throughout the treatment period.

Results: DAPT significantly shortens postoperative recovery time compared to aspirin monotherapy, highlighting its potential benefits in TBAD treatment. After treatment, analysis revealed more significantly improved cardiac and coagulation functions in the research group. Furthermore, compared with the control group, the research group had significantly lower levels of inflammatory factors and stress response and significantly higher levels of anti-inflammatory factors and antioxidant factors (P<0.05). During the short-term follow-up, the research group showed more pronounced pain relief and a reduced risk of thrombosis, albeit with an increased risk of bleeding.

Conclusion: DAPT with aspirin and clopidogrel is more conducive to enhancing postoperative cardiac and coagulation functions and reducing inflammation in TBAD patients.

Background: Ginkgolide B (GB), a potent platelet-activating factor antagonist with multi-faceted pharmacological effects, suffers from extremely low oral bioavailability due to poor aqueous solubility and permeability. While nanocarriers have been explored, nanocrystal technology offers a carrier-free strategy with ultrahigh drug loading.

Objectives: This study aimed to develop an orally administrable GB nanocrystal (GB-NC) formulation using a Quality by Design (QbD) approach to enhance dissolution rate and absorption potential, while ensuring stability and scalability.

Methods: GB-NC were fabricated via a miniaturized wet bead milling technique. Critical process parameters were optimized using a Box-Behnken design, with particle size, polydispersity index (PDI), and stability index as key quality attributes. Stabilizers were screened, and lyoprotectants were selected for freeze-drying. The optimized nanocrystals were characterized for morphology, crystallinity, in vitro dissolution, stability, and cellular permeability using MDCK cell monolayers.

Results: The optimal formulation, stabilized with PVP K30 (0.51%) and soy lecithin (0.34%) and milled for 10 hours, yielded nanocrystals with a particle size of 82.4 ± 1.97 nm, a low PDI, and good stability. Freeze-drying with glycine/glucose preserved redispersion properties. The GB-NC demonstrated significantly enhanced dissolution (>90% within 20 min) in both simulated gastric and intestinal fluids compared to raw GB. Cellular permeability (P_app) increased significantly, and the freeze-dried product remained stable for 6 months at 4°C and 25°C.

Conclusion: A QbD-guided miniaturized wet bead milling process successfully produced stable GB-NC with markedly improved dissolution and cellular permeability. This presents a promising and scalable strategy to overcome the delivery challenges of GB, laying a foundation for developing effective oral formulations to enhance its bioavailability.

Background: Tumor metastasis is a key factor in cancer progression, yet its molecular mechanisms are not fully understood. ERBB2-positive lung cancer exhibits aggressive behavior, and the role of miR-139 in its metastasis requires investigation.

Objectives: This study aimed to explore the function of miR-139 in ERBB2-positive lung cancer and its underlying molecular mechanism involving the ERBB2/Rac1/NF-κB signaling axis.

Methods: The study utilized A549 lung cancer cells and tissue samples from 106 lung cancer patients. Methods included RT-PCR, bioinformatics analysis, dual-luciferase reporter assay, Western blot, cell migration/invasion assays, wound healing tests, Rac1 activity assays, and rescue experiments using Rac1-Q61L.

Results: MiR-139 expression was significantly downregulated in lung cancer tissues, especially in lymph node metastases (P<0.01). MiR-139 directly targeted the 3'UTR of ERBB2 and inhibited its expression (P<0.01). Overexpression of miR-139 reduced Rac1 activity (P<0.01) without affecting RhoA or Cdc42, and decreased NF-κB signaling activity in ERBB2-positive tissues. MiR-139 overexpression significantly suppressed cell migration and invasion (P<0.01), an effect partially reversed by Rac1-Q61L.

Conclusion: MiR-139 inhibits lung cancer cell migration and invasion by targeting ERBB2, suppressing Rac1 activity, and downregulating NF-κB signaling. Its downregulation promotes metastasis through the ERBB2/Rac1/NF-κB axis.

Background: Quercetin can be enhanced by creating microspheres using polymers, with the quality of these microspheres influenced by manufacturing processes and polymer type.

Objectives: This study compares high-speed stirring with ultra-turrax (method 1) and peristaltic dosing pumps (method 2) for producing quercetin-pectin microspheres.

Methods: The method employed involves the production of quercetin-pectin microspheres by the ionic gelation process. Six formulas were created for each method, utilizing pectin extracted from red dragon skin with oxalic acid, as well as commercial apple pectin and orange peel pectin at concentrations of 1% and 1.5%. Parameters were evaluated, including FTIR, yield, moisture content (MC), polydispersity index, particle size, drug loading (DL), encapsulation efficiency (EE), Scanning Electron Microscope, Carr's Index, Hausner ratio, swelling index and in vitro drug release.

Results: Results showed that the yield obtained ranged for method 1: 83.27-96.37%; yield for method 2: 84.13-93.87%; swelling index of method 1: 92.8±3.25-96.2±3.26%; swelling index of method 2: 94.5±3.41-97.7±2.43%; MC of method 1: 2.58±0.31-3.64±0.57%; MC of method 2: 2.93±0.15-3.64±0.27%; PDI of both method is 0.003%; DL of method 1 was 2.03±0.11-2.37±0.77%; DL of method 2 was 2.75±0.03-2.94±0.51%; EE of method 1 was 70.34±0.72-83.78±1.47%; EE of method 2 was 73.49±0.89-90.61±1.49% in vitro release up to 600 minutes for method 1 was 67.83±5.88-91.94±5.84%; for method 2 was 69.64±3.14-92.29±4.82. The FTIR profile exhibits resemblances between the two approaches, indicating the existence of O-H, C-O, and C-H groups, suggesting commonalities in the composition of quercetin and pectin molecules. The results of the study showed that microspheres produced using a custom-made peristaltic dosing pump yielded better DL, EE, release test, Carr's index, and Hausner ratio values compared to those produced using method 1 (p > 0.05).

Conclusion: Peristaltic dosing pumps produce higher yields, exhibiting enhanced spherical morphology and demonstrate improved microsphere performance relative to ultra-turrax.

Background: Type 2 diabetes mellitus (T2DM) has become a global public health crisis with a steady upward prevalence, and China alone has over 100 million adult T2DM patients. Long-term persistent hyperglycemia damages microvasculature and peripheral nerves, leading to disabling complications such as diabetic foot (DF) and diabetic peripheral neuropathy (DPN). These complications severely reduce patients' quality of life and increase medical burdens, thus creating an urgent need for effective adjunctive therapeutic interventions.

Objectives: To evaluate the efficacy and safety of alprostadil injection in treating type 2 diabetes-related DF or DPN.

Methods: A prospective randomized controlled trial was conducted involving 120 eligible patients (62 with DF, 58 with DPN) recruited from our hospital between 2018 and 2021. Inclusion criteria included confirmed T2DM diagnosis and meeting diagnostic criteria for DF/DPN; exclusion criteria included severe organ dysfunction. Patients were randomly divided into control group (n=60, receiving standard care including blood glucose control and symptom management) and observation group (n=60, standard care plus 40μg alprostadil intravenous infusion daily for 14-21 days). Outcomes included total efficacy rate, lipid profiles (TC, TG, LDL-C, HDL-C), and adverse events.

Results: Clinical outcomes showed significant advantages in the observation group: total efficacy rate was 93.33% (56/60) versus 76.67% (46/60) in the control group (P=0.011). Lipid profiles improved more remarkably in the observation group: TC decreased by (1.24±0.32) mmol/L, TG by (0.86±0.21) mmol/L, LDL-C by (0.92±0.25) mmol/L, and HDL-C increased by (0.35±0.10) mmol/L (all P<0.05). Adverse event rate was 3.33% (2/60) in the observation group, much lower than 18.83% (11/60) in the control group (P=0.008).

Conclusion: Alprostadil injection as an adjunctive therapy for T2DM-related DF or DPN exhibits significant efficacy and good safety. It not only enhances the overall therapeutic response but also effectively improves lipid metabolism disorders, with a low incidence of adverse events.

Background: Pediatric acute laryngitis and laryngeal obstruction can be severe enough to require tubes inserted into the airway and assist with breathing. Dexamethasone is commonly used to treat pediatric acute laryngitis and laryngeal obstruction, but the factors determining the need for intubation despite corticosteroid therapy remain unclear.

Objectives: We aimed to determine the rate of intubation and mechanical ventilation required, identify risk factors for these needs and examine the outcomes in pediatric patients who still require intubation despite dexamethasone treatment.

Methods: A cross-sectional study at Jiangxi Children's Hospital included 160 screened patients with 150 pediatric patients with acute laryngitis and laryngeal obstruction, conducted from January 2020 to December 2024. All patients were given conventional dexamethasone treatment either orally or via IV. Patients were stratified into two groups: Those who required intubation and those who did not. Demographic variables, comorbidity factors, lab values and satisfaction with dexamethasone treatment, with additional support from nebulized epinephrine, were extracted. The variables were then determined via multiple logistic regression analysis.

Results: Among the 160 screened patients, 30 (18.75%) required intubation. Independent risk factors for intubation despite dexamethasone treatment included female gender (OR = 4.07), comorbid pulmonary and systemic disorders (OR = 7.30), increased neutrophil-to-lymphocyte (N/L) ratio (OR = 1.167 per unit increase), and elevated IgM levels (OR = 1.221), all with P < 0.05. These factors were identified as significant predictors for the need for intubation despite steroid therapy.

Conclusion: Despite the widespread use of dexamethasone, the intubation rate remains high in pediatric patients with acute laryngitis and laryngeal obstruction. Identifying females, comorbidities, neutrophil-to-lymphocyte ratio and high levels of IgM as risk factors can assist healthcare professionals in arriving at an early diagnosis.

Background: Psoriasis represents a chronic autoimmune dermatosis that necessitates the implementation of both anti-inflammatory measures and UVA-UVB photoprotection.

Objectives: This study aimed to evaluate the phytochemical profile, antioxidant capacity , photoprotective efficacy, and anti-inflammatory potential of Tagetes erecta flower extracts (TEFE) prepared in different solvents.

Methods: In this study phytochemical analysis and antioxidant properties were performed in various solvent extracts of Tagetes erecta flowers. Photoprotective efficacy was assessed using critical wavelength (λ_c) and SPF measurements under different exposure conditions. Anti-inflammatory activity was evaluated via heat-induced protein denaturation, heat-induced hemolysis, and hypotonicity- induced hemolysis assays.

Results: The result indicated that TEFE contain all the secondary metabolites known for their skin-protective properties. The highest TPC was observed in the methanolic and ethyl acetate extracts, measuring (0.7733 ± 0.0024 and 0.7729 ± 0.0007 mg GAE/mg), respectively. The acetone and ethanolic extracts exhibited the highest flavonoid contents (17.553 ± 0.1064 and 14.904 ± 0.506 mg Rutin/mg) and flavanol contents (4.279 ± 0.268 and 3.829 ± 0.1002 mg Rutin/mg), respectively. At all concentrations, TEFE exhibited λ_c greater than 370 nm, indicating broad-spectrum photoprotective properties. At 800 ppm, TEFE demonstrated SPF values of 29 without exposure, while SPF of 40.2 under sunlight and 32.80 under UV exposure were measured. The Statistical analysis revealed significant differences in photoprotective activity across all tested concentrations (P<0.05).TEFE showed considerable inhibition of protein denaturation, with IC₅₀ = 527.845 µg/mL and exhibited concentration-dependent membrane stabilization, with a maximum inhibition of 69% in heat-induced RBC lysis and 22% in hypotonicity-induced RBC lysis.

Conclusion: These results advocate for a novel phototherapeutic strategy for addressing photoprotection in psoriatic skin and require further clinical research in dermatological preparations.

Background: Septic shock remains a critical condition with high mortality, necessitating reliable prognostic biomarkers and effective adjunct therapies.

Objectives: This study explored prognostic biomarkers and the effect of vitamin C in septic shock.

Methods: This study analyzed 110 patients (January 2023-March 2024), stratified by 28-day outcome into survival (n=90) and death (n=20) groups. Compared to survivors, the death group exhibited significantly lower lymphocyte-to-high-density lipoprotein ratio (LHR), CD3+, CD3+CD4+, CD4+/CD8+ and higher interleukin 6 (IL-6), C-reactive protein (CRP), procalcitonin (PCT), CD3+CD8+.

Results: The receiver operating characteristic analysis showed the combination of LHR, IL-6, CRP, PCT and CD4+/CD8+ predicted death best [area under the receiver operating characteristic curve (AUC) =0.960], outperforming single markers. Patients were randomized to control (hydrocortisone) or observation (hydrocortisone with vitamin C) group. Post-treatment, both groups showed improved mean arterial pressure (MAP), central venous pressure (CVP) (increased), heart rate (HR) (decreased) and reduced PCT, tumor necrosis factor-α (TNF-α), IL-6 and Sequential Organ Failure Assessment (SOFA) score; however, improvements were significantly greater in the vitamin C group.

Conclusion: The combination of LHR, IL-6, CRP, PCT and CD4+/CD8+ has prognostic value. Vitamin C adjunct therapy significantly enhances hemodynamic improvement, reduces inflammation, lowers SOFA scores and improves prognosis in septic shock patients.

Background: The study also emphasizes the deployment of economical synthetic methods for obtaining more potent derivatives of commercially available drugs.

Objective: The present study aimed to synthesize schiff-base (SB) derivatives of atenolol (ATN) and their metal complexes with copper and zinc; further characterized by various spectroscopic techniques as well as biological assay.

Method: The synthesized compounds are subjected to in-silico docking and ADME (using Swiss ADME program) studies to confirm their suitability as lead molecule. Antioxidant, antimicrobial and anticancer activities were carried out using DDPH, disk diffusion method and MTT using HepG2 cell lines respectively. Additionally; Anti-hypertensive activity was tested L-NAME induced hypertensive rat model through invasive method.

Results: Molecular docking studies indicate higher score for 4_c and 5_e than parent drug atenolol (ATN); SB and their metal derivatives also indicate promising therapeutic profile with good GIT absorption parameters. Here 4_a represents potent antioxidant activity with IC50 = 8.95 ± 11μg/ml; when compared to std. drug Ascorbic acid with an IC50= 8.3± 11μg/ml. Furthermore; all the metal complexes are reactive against B.Subtilis a gram +ve bacteria than gram -ve E.Coli, 4a (39.31mm) and 4b (42.02mm) possessed higher antimicrobial activity when compared to std. drug Vancomycin (31.48mm). The results from MTT assay reveals higher anticancer potential (%age inhibition) of 4a (73%), 4d (75%) and 5d (74%) when compared to std. drug Doxorubicin (101.2%) at HepG2 cell lines. In-vitro analysis shows significant results with SB metal derivatives, where, Zn complexes of SB derivatives (5_a-e) represents excellent anti-hypertensive activity in rats in contrast to standard drug alone.

Conclusion: The imine Schiff based derivatives of atenolol and their metal complexes exhibit good biological efficacy as well as multi modal effects when compared to the frequently prescribed drug, atenolol.