Developing a highly validated and sensitive HPLC method for simultaneous estimation of cefotaxime and paracetamol in pure and pharmaceutical preparations

An isocratic HPLC technique was exploited and validated for the quick simultaneous separation and measurement of cefotaxime and paracetamol in vials dosage forms, with a total analysis time of 3 minutes. The process of separation was carried out on a Thermo Scientific® Venusil XBPC18 (L) (5µm, 4.6x250 mm) using a mobile phase of ACN: distilled water (70:30, v/v) at the ambient temperature. The flow rate used in the experiment was 1 mL/min, and the highest level of absorption was determined by high-performance liquid chromatography with photodiode array detection (HPLC-PDA) employing a PDA detector set at a wavelength of 255 nm. The established retention times for cefotaxime and paracetamol were 1.79 and 2.97 minutes, respectively, suggesting reduced analysis duration. The observed limits of detection for ceftaxime and paracetamol were 4.2×10-5 and 1.2×10-5 µg/mL, respectively, indicating a significant level of sensitivity in the approach. The approach was subsequently verified in accordance with the requirements set out by the Food and Drug Administration (FDA) for the quantification of medicines in vial dosage form

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Can brain natriuretic peptide predict the outcome in patients with acute pulmonary embolism?

Risk of death is high in patients with pulmonary embolism (PE) because of right ventricular (RV) failure. Plasma levels of brain natriuretic peptide (BNP) are increased in cases of isolated chronic right ventricular dysfunction (RVD) and chronic pulmonary hypertension. However, little is known about BNP secretion during acute RVD caused by acute PE. The aim of this study is to determine BNP levels in patients with acute PE with and without RVD and to assess its role in prediction of severity and outcome of these patients. Patients and methods: This study was conducted on 47 patients with confirmed acute PE who were admitted to the intensive care unit (ICU) of Chest Department, Zagazig University Hospitals. Patients enrolled in this study were subjected to: (a) Transthoracic echocardiography, (b) Measurement of BNP plasma levels, (c) Measurement of D-dimer serum levels and d) Computed tomography pulmonary angiography (CTPA). Results: There was statistically highly significant increase in plasma level of BNP (pg/mL) in patients with RVD than those without it. There were highly significant positive correlations between plasma level of BNP (pg/mL) and both RV diameter (mm) and RVSP (mmHg). A plasma BNP level >72.5 pg/mL can predict occurrence of RVD, while a plasma level of BNP >150 pg/mL can predict death in patients with acute PE. Conclusion: An elevated plasma level of BNP is a prognostic factor for short-term mortality and overall short-term complicated clinical outcome, and it is a powerful indicator of RVD in patients with acute PE in the absence of left ventricular dysfunction (LVD)

Thonningia sanguinea Extract: Antioxidant and Cytotoxic Activities Supported by Chemical Composition and Molecular Docking Simulations

The current study was designed to investigate the antioxidant and cytotoxic activities of Thonningia sanguinea whole-plant extract. The total phenolic content was determined using Folin–Ciocalteu reagent and found to be 980.1 mg/g, calculated as gallic acid equivalents. The antioxidant capacity was estimated for the crude extract and the phenolic portion of T. sanguinea, whereupon both revealed a dose-dependent scavenging rate of DPPH• with EC50 values of 36.33 and 11.14 µg/mL, respectively. Chemical profiling of the plant extract was achieved by LC-ESI-TOF-MS/MS analysis, where 17 compounds were assigned, including ten compounds detected in the negative mode and seven detected in the positive mode. The phenolic portion exhibited promising cytotoxic activity against MCF-7 and HepG2 cells, with IC50 values of 16.67 and 13.51 μg/mL, respectively. Phenolic extract treatment caused apoptosis in MCF-7 cells, with total apoptotic cell death 18.45-fold higher compared to untreated controls, arresting the cell cycle at G2/M by increasing the G2 population by 39.7%, compared to 19.35% for the control. The apoptotic investigation was further validated by the upregulation of proapoptotic genes of P53, Bax, and caspases-3,8 9, and the downregulation of Bcl-2 as the anti-apoptotic gene. Bcl-2 inhibition was also virtualized by good binding interactions through a molecular docking study. Taken together, phenolic extract exhibited promising cytotoxic activity in MCF-7 cells through apoptosis induction and antioxidant activation, so further fractionation studies are recommended for the phenolic extract for specifying the most active compound to be developed as a novel anti-cancer agent

GC-MS/MS Quantification of EGFR Inhibitors, <i>β</i>-Sitosterol, Betulinic Acid, (+) Eriodictyol, (+) Epipinoresinol, and Secoisolariciresinol, in Crude Extract and Ethyl Acetate Fraction of <i>Thonningia sanguinea</i>

Medicinal plants are widely used in folk medicine to treat various diseases. Thonningia sanguinea Vahl is widespread in African traditional medicine, and exhibits antioxidant, antibacterial, antiviral, and anticancer activities. T. sanguinea is a source of phytomedicinal agents that have previously been isolated and structurally elucidated. Herein, gas chromatography combined with tandem mass spectrometry (GC-MS/MS) was used to quantify epipinoresinol, β-sitosterol, eriodictyol, betulinic acid, and secoisolariciresinol contents in the methanolic crude extract and its ethyl acetate fraction for the first time. The ethyl acetate fraction was rich in epipinoresinol, eriodictyol, and secoisolariciresinol at concentrations of 2.3, 3.9, and 2.4 mg/g of dry extract, respectively. The binding interactions of these compounds with the epidermal growth factor receptor (EGFR) were computed using a molecular docking study. The results revealed that the highest binding affinities for the EGFR signaling pathway were attributed to eriodictyol and secoisolariciresinol, with good binding energies of −19.93 and −16.63 Kcal/mol, respectively. These compounds formed good interactions with the key amino acid Met 769 as the co-crystallized ligand. So, the ethyl acetate fraction of T. sanguinea is a promising adjuvant therapy in cancer treatments