Pakistan journal of pharmaceutical sciences最新文献

Hospitalized post-operative cardiovascular disease (CVD) patients are often subject to polypharmacy, increasing the risk of potential drug-drug interactions (pDDIs). This observational study assessed 384 post-operative CVD patients for pDDIs using Micromedex Drug-Int® and Lexicomp Interact®. Prevalence, severity, onset and documentation of pDDIs were analyzed using SPSS 23.0, with logistic regression identifying factors associated with at least two major pDDIs or two pDDIs categorized as X, D, or C. Micromedex Drug-Int® revealed a median of 6.23 pDDIs per patient, with 98.7% of patients having ≥1 pDDIs. Of 2,389 pDDIs, 64.1% were major. Lexicomp Interact® data showed a median of 7.15 pDDIs per patient, with 99.2% of patients having ≥1 pDDIs. Class C interactions were the most frequent (62.1%), followed by Classes B, D and X. Additionally, the study identified unique pDDIs from Lexicomp, including Ipratropium-Orphenadrine and Furosemide-Levosulpiride, not listed in Micromedex. The findings highlight the high prevalence of pDDIs in this population, emphasizing the need for regular monitoring. Using pDDI screening tools, clinical pharmacists can be crucial in mitigating these risks, particularly in high-risk patients.

We investigated the effect of Sanhuang ointment on the indwelling time and vein injury repair in patients receiving intravenous infusion via peripheral venous indwelling needles. Patients (n=120) who received infusion via peripheral venous indwelling needles were randomized into Sanhuang ointment, Hirudoid and blank control groups. The indwelling time, venous injury and repair rate, venous intimal roughness rate, vascular wall thickening rate, thrombosis rate and blood flow velocity were compared within 24h and on day 4 post-needle removal. The indwelling time in the Sanhuang ointment group was 7 (6,8) days, significantly longer than that in the Hirudoid (5(4,6) days) and blank control groups (4(3,5) days) (P<0.01). Within 24h of needle removal, differences in venous injury and repair grades, intimal roughness, wall thickening, thrombosis and blood flow were not significant (P>0.05). On day 4, the rates of venous intimal roughness, vascular wall thickening and thrombosis were significantly lower, while the blood flow velocity and venous repair rates were significantly higher in the Sanhuang ointment group than those in the Hirudoid and blank control groups (P<0.05). Sanhuang ointment application extends peripheral venous indwelling time and promotes vein repair without increased injury risk.

In this work, to attempt discovery of novel xanthine oxidase (XO) inhibitors, we developed a method for optimizing the Nigella sativa oil extraction by considering the seed size particles, the liquid seed ratio, the duration of the extraction procedure and the temperature of extraction. On the other hand, new pyrimidine and triazolopyrimidine derivatives were prepared in an attempt to mimic the pyrazolpyrimidine structure of allopurinol (a well-known xanthine oxidase inhibitor drug). Most of the developed compounds were shown to have strong xanthine oxidase inhibitory activities, while Nigella sative extract and compound 6b ranked as the most effective inhibitors (IC₅₀=1.87 and 0.63μg/ml, respectively, versus Allupurinol's IC₅₀=0.62μg/ml). Nigella sative extract and compound 6b showed potent activity (IC₅₀=0.60μg/ml). In addition, compound 6b was formulated as effervescent granules and exhibited good flow-ability properties. To further understand the approach of binding between synthesized compounds 6a-c and xanthine oxidase, a molecular docking investigation was conducted. These findings highlight the discovery of a novel group of xanthine oxidase inhibitors with the potential to improve the state-of-the-art treatment for gout.

Bulbine inflata is one of the species in the genus Bulbine that are yet to be documented for potential medicinal uses. Hence, we carried out its preliminary phytochemical profiling and investigated its antioxidant potential. The leaves were dried using air- and freeze-drying techniques and were extracted by water, methanol, ethyl acetate and hexane. Various common colour tests were used for the presence of phytochemicals. Some of the phytochemicals were further quantified. Phosphomolybdate, 2, 2 diphenyl-1-picryhydrazyl, hydrogen peroxide and metal chelating assays were used to assess the antioxidant potential of B. inflata. Tannin, flavonoids, phenols, glycosides, steroids, coumarins, quinones, saponins and terpenoids were detected phytochemicals in B. inflata leaves. The highest total phenolic, flavonoid and tannin contents, as well as total antioxidant capacity, were recorded for water extract. B. inflata showed moderate to high antioxidant activities against DPPH, H₂O₂ and metal chelating. Freeze-dried samples presented with higher results than air-dried samples in most assays. The results showed the potential of B. inflata for medicinal uses and could expand the ethnomedicinal resources in the communities where it is prevalent and beyond.

Bupropion (Bup), an antidepressant, is used to treat depression and aid in quitting smoking. We aim to investigate the influence of Bup on nicotine withdrawal (NW)-associated disturbances in serotonergic neurotransmission and behavior in mice. Adult albino mice were categorized into control and NW groups. Each group was further divided into saline and Bup-administered (n=6/group). NW groups received nicotine at a concentration of 3.08 mg (equivalent to 1 milligram of free base) in 100 ml of tap water for four weeks, while the control group received nicotine-free water. To induce nicotine withdrawal, the nicotine-containing water was substituted with tap water for 72 hours. Bup (20 mg/kg) and saline were administered (i.p.) three hours before the completion of the 72-hour withdrawal period to the test and control groups, respectively. NW signs were monitored in both groups. Bup-treated NW mice demonstrated a decline in corticosterone levels while concurrently exhibiting an increase in 5-HT synthesis with decreased 5-HT turnover compared to NW saline controls. A positive correlation between plasma corticosterone and 5-HT turnover was also found in Bup-administered NW mice. Taken together, Bup has potential therapeutic effects on nicotine withdrawal-associated somatic signs due to its ability to attenuate 5-HT turnover and plasma corticosterone in dependent mice.

Peperomia dindygulensis is used as an anticancer medicinal plant in China and is rich in a series of novel secolignans, including peperomin E (PE). In our prior study, we demonstrated the significant reduction in tumor weight and volume in vivo in a PCa DU145 cell xenograft tumor mouse model following PE treatment. However, the impact of PE on PCa metabolism remains unclear. Therefore, the objective of this investigation is to examine the influence of PE on metabolism regulation within a PCa mouse model. An untargeted UPLC-Q-TOF-MS plasma metabolomics approach was carried out to explore the mechanism of action of PE in a human prostate cancer DU145 cell xenograft tumour mouse model based on principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), identification of potential biomarkers and pathway analysis. A total of 71 potential plasma metabolite biomarkers were identified in the nude mouse model and 36 of which were reversed to different degrees after the treatment with PE. These identified biomarkers primarily relate to amino acid metabolism, fatty acid metabolism and cholic acid metabolism. These findings showed that PE could improve endogenous metabolism in the DU145 cell xenograft tumor mouse model and offered a reliable foundation for the design of new therapeutic drugs for treating PCa.

Vincristine sulfate (VIN) is commonly employed as a cytotoxic agent in the treatment of hematological malignancies, particularly acute lymphoblastic leukaemia (ALL). However, its maximum therapeutic benefits have been hindered due to the dose-dependent neurotoxic effects it can induce, which traditionally manifest as autonomic and peripheral sensory-motor neuropathy. The innovative approach aimed to address VIN's neurotoxic limitations while preserving its therapeutic efficacy in combating hematological malignancies, including ALL. The liposomes were prepared using the reverse-phase evaporation method. This method involved the encapsulation of VIN within liposomes through a controlled evaporation process. Secondly, PEGylated liposomes were synthesized through PEGylation. The liposomes were examined using scanning electron spectroscopy, revealing a smooth and spherical surface morphology. The particle size of the liposomes ranged from 90±0.5 to 120±0.4 nm. The encapsulation efficiency of the liposomes was found to be 77.24% and the highest drug release reached 95% over 50 hours. Cytotoxicity studies demonstrated that the liposomal formulation exhibited a non-toxic nature. Furthermore, in an in-vivo cellular uptake study, the PEGylated liposomes showed efficient accumulation within tumor cells. The liposomal formulation demonstrated superior effectiveness in treating ALL compared to the pure form of the drug.

Cytarabine (Ara-C) is a commonly used chemotherapeutic drug for the treatment of leukemia, known for its significant tolerability. The down regulation of miR-203 in leukemia cells suggests its potential involvement in the pathogenesis of leukemia. In this study, we investigated the effects and possible mechanisms of miR-203 and Ara-C on proliferation and apoptosis of human leukemia K562 cells which were cultured with Ara-C and/or with transfection of miR-203 expression vectors. Our results showed that the combination of Ara-C and miR-203 synergistically inhibited the proliferation of K562 cells and the sensitivity of leukemia cells to Ara-C was increased by 2.5-fold with trasfection of miR-203. The proportion of apoptotic cells in the Ara-C and miR-203 combination group was higher than Ara-C or control plasmid group. Caspase-3 and caspase-9 activities were increased in Ara-C and miR-203 combination group. miR-203 down regulated the protein level of Bcr/abl in K562 cells compared with plasmid control. In conclusion, Ara-C in combination with miR-203 has a synergistic effect of proliferation inhibition and apoptosis induction in chronic myelogenous leukemia K562 cells, which may be associated with miR-203 down regulating Bcr/abl, thereby inhibiting cell proliferation and promoting cell apoptosis.

This study investigates the effects of rt-PA thrombolytic therapy at varying times on neurological function and complications in acute cerebral infarction (ACI) patients. A total of 120 ACI patients admitted between August 2019 and July 2021 were divided into three groups based on the timing of rt-PA treatment: <3h (40 patients), 3-4.5h (55 patients), and >4.5h (25 patients). All received standard treatment and rt-PA IV thrombolysis. Key comparisons included cerebral oxygen metabolism, oxidative stress, neural markers, hemodynamics, coagulation function, NIHSS scores, ADL, clinical efficacy and complications. Results showed that 48 hours post-treatment, SjvO2 levels were significantly higher in the <3h and 3-4.5h groups compared to the >4.5h group. SOD levels were also higher in the earlier groups, while MDA levels were lower. Three months after treatment, NIHSS scores were significantly lower and ADL scores higher in the <3h and 3-4.5h groups, with lower complication rates. Efficacy was similar within 3 hours and 3-4.5 hours, but complications increased significantly after 4.5 hours.

The progressive form of Alzheimer's disease (AD) is a neurological condition marked by decline in older people's memory and cognition. Scopolamine is a behavioral technique that is frequently used to study cognitive disorders, such as Alzheimer's disease. This investigation aimed to determine the protective effects of ethanolic extracts derived from Sterculia guttata (ESG) on neurological & pathological changes induced by Scopolamine in rats with Alzheimer's. The ESG procured through a 48-hour hot maceration, followed by column chromatography, isolation and characterization using techniques such as FTIR, 1HNMR, 13CNMR and mass spectra. A flavonoid called Diosmin was identified in the extract. Rats were segregated into five groups: normal, scopolamine, scopolamine + Donepezil, scopolamine + ESG (200mg per kg orally), & scopolamine + ESG (400mg per kg orally) for a study of 14 day duration. Memory & learning abilities were assessed using the rectangular maze and Cook's pole climbing model. Additionally, biochemical parameters and brain histology were analyzed. ESG treatment mitigated scopolamine-induced changes in acetylcholinesterase, dopamine, serotonin, glutamate, and GABA levels, suggesting neuroprotection. These findings propose that ethanolic extracts of Sterculia guttata (ESG) show promise as effective preventive or therapeutic agents due to their potential for neuroprotection & cognitive enhancement in AD.