Green and High Throughput Assay Using 96-Microwell Base to Determine Metformin Hydrochloride in the Tablet Dosage Form.

Metformin (MET) is an oral antidiabetic drug widely used as the primary treatment for type 2 diabetes mellitus (T2DM). While various spectrophotometric assays exist for determining MET in pharmaceutical formulations, they often have limited throughput for quality control purposes. This study describes the validation of a 96-microwell plate spectrophotometer method using charge-transfer complexes (CTCs) with chloranilic acid (CLA) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) for the quality control and detected of MET. This reaction was carried out in 96-microwell plates, and the absorbance of the colored complexes of CLA and DDQ were measured at 530 nm and 460 nm, respectively, using an absorbance microplate reader. This study aims to identify and quantify the use of a 96-microwell plate spectrophotometer analytical technique for assessing complicated formulations. The method was successfully used for the quantification of MET in the tablet dosage form. The results showed good correlation coefficients (0.996 and 0.997) with CLA and DDQ, respectively. The present method showed high precision with RSD % not exceeding 2.17%. The accuracy of the method was obtained by recovery percentage, with percentage values less than ±5%. The Analytical Greenness Metric (AGREE) was used to evaluate greenness of the assays. The result show that the microwell assay method is greenness and suitable for handling large samples on a daily used with high throughput analysis. The use of the 96-microwell-plate method is superior to the existing method in terms of simplicity of the procedure, the low economic cost, and its consumption of low amounts of reagents and organic ethanol solvent, making it an environmentally friendly method. Therefore, these advantages make them suitable and rapid alternatives method to current methods for routine metformin analysis in quality control laboratories.

Determination of the extremolyte ectoine in plasma and a pharmacokinetic study in rats by a validated and BAGI-evaluated UPLC-MS/MS method.

Ectoine (ECT) has recently gained considerable interest in the healthcare sector due to its promising therapeutic benefits in a variety of human disorders. This research aimed to quantify the ECT plasma level in rats by creating and optimizing a sensitive and validated UPLC-MS/MS method. Prior to analysis, ECT extraction from the plasma samples was conducted via a protein precipitation procedure, using hydroxyectoine as an internal standard (IS). A 1.7 µm UPLC C8 column (100 mm × 2.1 mm) was selected for the chromatographic separation, using a gradient mobile phase consisting of acetonitrile and 0.05% formic acid. The electrospray ionization mass spectrometry (ESI-MS) was used to detect ECT in the positive ion mode. To determine the specific precursor and the product ions of ECT, multiple reaction monitoring (MRM) methods were carried out. The selected ion pair of ECT was 143.1 > 97 and 159.1 > 113.13 for the IS. The ECT's linearity range in rat plasma was found to be 1-1000 ng/mL, with a recovery rate of 96.48-97.37%. Consistent with FDA guidelines for bio-analytical method validation, the suggested method was validated. The method was efficiently employed to quantify the studied drug in spiked rat plasma with good accuracy and precision with no significant matrix effects. Furthermore, it was effectively used to investigate the pharmacokinetic behavior of ECT in rats after a single oral dose of 30 mg/kg.

Voltammetric analysis of pholcodine on graphene-modified GNPs/PTs with green assessment.

Pholcodine, an anti-tussive medication widely used as an over-the-counter, OTC drug, has recently faced restrictions in several countries. This paper presents a sensitive electrochemical approach for pholcodine detection. The electrochemical method involved fabricating a graphene nanoplatelets electrode, incorporating polythiophene nanospheres polymer to promote electron transfer and increase the activated surface area. Characterization of the fabricated electrode was performed using transmission electron microscopy, ATR-Fourier-transform infrared spectroscopy, X-ray crystallography, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. The electrochemical behavior of pholcodine with the fabricated electrode was investigated using cyclic voltammetry, chronoamperometry, square wave voltammetry (SWV), and differential pulse voltammetry (DPV). The developed electrode led to a linear response for pholcodine ranging from 10 to 45 mg/L with detection limits of 1.41 and 1.51 mg/mL for SWV and DPV, respectively and quantification limits of 4.27 and 4.57 mg/L for SWV and DPV, respectively. The proposed method has accurately recovered pholcodine in spiked serum samples with a recovery percentage ranging from 1.2 to 2.9%. The optimized method is found to be accurate, precise, and robust by applying validation parameters provided by International Council for Harmonization. Two green metrics were computed to assess the method's greenness, the findings showed that the developed method is environmentally friendly with minimum sample preparation steps.

Ecofriendly single-step HPLC and TLC methods for concurrent analysis of ternary antifungal mixture in their pharmaceutical products.

Two accurate, sensitive, and selective methods for simultaneous determination of miconazole nitrate (MIC), nystatin (NYS), and metronidazole (MET) in pure state or drug product were established and verified. First, RP-HPLC-DAD was designed. Separation was accomplished using a ZOBRAX Eclipse Plus RP-C8 column that was running under an isocratic elution of methanol: 0.05% aqueous solution of sodium dodecyl sulphate (40: 60 v/v), with a flow rate that was regulated at 0.8 mL/min. The column temperature was adjusted at 25 °C and diode array detector was monitored at 220 nm. The linearity range of the proposed method was achieved at the concentration of 5-50, 4-50, and 4-40 µg/mL and the attained retention time for the studied drugs was 2.52, 3.52 and 4.99 min for MIC, NYS, and MET, correspondingly. Second, a TLC-densitometric approach was used to resolve the three compounds. Resolution of the three cited drugs was carried out using TLC aluminum plates pre-coated with 0.25 mm silica gel 60 F254. A developing solvent comprised ethyl acetate: toluene: methanol: triethyl amine: formic acid (3: 1: 7: 0.3: 0.1 by volume) (pH = 5.5) was utilized and scanning of the resolved bands at 215 nm. Linearity of the developed TLC method was evaluated and evident to be 0.4-2, 0.4-2.2, and 0.4-2 µg/band for MIC, NYS, and MET, in that order. The suggested chromatographic methods were verified according to ICH directives. The findings of the developed chromatographic procedures were statistically compared with the results of the reported ones using student's t-test and F-test. Furthermore, two green assessment tools evaluated the indicated methods' level of greenness (GAPI and AGREE).

A computational investigation of thymidylate synthase inhibitors through a combined approach of 3D-QSAR and pharmacophore modelling.

Thymidylate synthase (TS) is a crucial target of cancer drug discovery and is mainly involved in the De novo synthesis of the DNA precursor thymine. In the present study, to generate reliable models and identify a few promising molecules, we combined QSAR modelling with the pharmacophore hypothesis-generating technique. Input molecules were clustered on their similarity, and a cluster of 74 molecules with a pyrimidine moiety was chosen as the set for 3D-QSAR and pharmacophore modelling. Atom-based and field-based 3D-QSAR models were generated and statistically validated with R2 > 0.90 and Q2 > 0.75. The common pharmacophore hypothesis(CPH) generation identified the best six-point model ADHRRR. Using these best models, a library of FDA-approved drugs was screened for activity and filtered via molecular docking, ADME profiling, and molecular dynamics simulations. The top ten promising TS-inhibiting candidates were identified, and their chemical features profitable for TS inhibitors were explored.Communicated by Ramaswamy H. Sarma.

Antioxidant and Anti-Aging Phytoconstituents from Faucaria tuberculosa: In Vitro and In Silico Studies.

Research targeting natural cosmeceuticals is now increasing due to the safety and/or limited side effects of natural products that are highly valued in cosmetology. Within a research program exploring botanical sources for valuable skincare antioxidant components, the current study investigated the phytochemical content and the biological potential of Faucaria tuberculosa. Phytochemical investigation of F. tuberculosa extract resulted in purification and characterization of six phytoconstituents, including a new one. The structure of the new constituent was elucidated as (-) catechin-(2→1',4→2')-phloroglucinol (4). The structural identity of all isolated compounds were confirmed on the basis of extensive physical and spectral (1D, 2D-NMR and HRESIMS) investigations. The ethanolic extract exhibits a rich content of total phenolics (TPC) and total flavonoids (TFC), estimated as 32 ± 0.034 mg GAE/g and 43 ± 0.004 mg RE/g, respectively. In addition, the antioxidant (ABTS and FRAP), antihyaluronidase and antityrosinase activities of all purified phytoconstituents were evaluated. The results noted (-) catechin-(2→1',4→2') phloroglucinol (4) and phloroglucinol (1) for their remarkable antioxidant activity, while isorhamnetin 3-O-rutinoside (3) and 3,5-dihydroxyphenyl ß-D-glucopyranoside (2) achieved the most potent inhibitory activity against tyrosinase (IC50 22.09 ± 0.7 µM and 29.96 ± 0.44 µM, respectively) and hyaluronidase enzymes (IC50 49.30 ± 1.57 µM and 62.58 ± 0.92, respectively) that remarkably exceeds the activity of the standard drugs kojic acid (IC50 = 65.21 ± 0.47 µM) and luteolin, (IC50 = 116.16 ± 1.69 µM), respectively. A molecular docking study of the two active compounds (3 and 2) highlighted their high potential to bind to the active sites of the two enzymes involved in the study.

Comparative Study of Augmented Classical Least Squares Models for UV Assay of Co-Formulated Antiemetics Together with Related Impurities.

The classical least squares (CLS) model and three augmented CLS models are adopted and validated for the analysis of pyridoxine HCl (PYR), cyclizine HCl (CYC), and meclizine HCl (MEC) in a quinary mixture with two related impurities: the CYC main impurity, Benzhydrol (BEH), which has carcinogenic and hepatotoxic effects, and the MEC official impurity, 4-Chlorobenzophenone (BEP). The proposed augmented CLS models are orthogonal signal correction CLS (OSC-CLS), direct orthogonal signal correction CLS (DOSC-CLS), and net analyte processing CLS (NAP-CLS). These models were applied to quantify the three active constituents in their raw materials and their corresponding dosage forms using their UV spectra. To evaluate the CLS-based models sensibly, we design a comparative study involving two sets: the training set to construct models and the validation set to assess the prediction abilities of these models. A five-level, five-factor calibration design was established to produce 25 mixtures for the calibration set. In addition, 16 experiments were performed for a test set distributed equally between the in-space and out-space samples. The primary criterion for comparing the models' performance was the validation set's root mean square error of prediction (RMSEP) value. Finally, augmented CLS models showed acceptable results for assaying the three analytes. The results were compared statistically with the reported HPLC methods; however, the DOSC-CLS model proved the best for assaying the dosage forms.

Novel nasal niosomes loaded with lacosamide and coated with chitosan: A possible pathway to target the brain to control partial-onset seizures.

This work aimed to develop and produce lacosamide-loaded niosomes coated with chitosan (LCA-CTS-NSM) using a thin-film hydration method and the Box-Behnken design. The effect of three independent factors (Span 60 amount, chitosan concentration, and cholesterol amount) on vesicle size, entrapment efficiency, zeta potential, and cumulative release (8 h) was studied. The optimal formulation of LCA-CTS-NSM was chosen from the design space and assessed for morphology, in vitro release, nasal diffusion, stability, tolerability, and in vivo biodistribution for brain targeting after intranasal delivery. The vesicle size, entrapment, surface charge, and in vitro release of the optimal formula were found to be 194.3 nm, 58.3%, +35.6 mV, and 81.3%, respectively. Besides, it exhibits sustained release behavior, enhanced nasal diffusion, and improved physical stability. Histopathological testing revealed no evidence of toxicity or structural damage to the nasal mucosa. It demonstrated significantly more brain distribution than the drug solution. Overall, the data is encouraging since it points to the potential for non-invasive intranasal administration of LCA as an alternative to oral or parenteral routes.

Quetiapine Albumin Nanoparticles as an Efficacious Platform for Brain Deposition and Potentially Improved Antipsychotic Activity.

Quetiapine (QP) is a second-generation short-acting antipsychotic drug extensively metabolized in the liver, producing pharmacologically inactive metabolites and leading to diminished bioavailability. Therefore, this study aimed to develop an intravenous QP albumin nanoparticles (NPs) system for improving QP antipsychotic activity and brain targeting. QP-loaded albumin NPs were prepared by the desolvation method. The fabricated NPs were characterized in terms of particle size, zeta potential, entrapment efficiency (EE%), and in vitro drug release. In vivo pharmacokinetics and biodistribution in rats were studied. In addition, the antipsychotic activity of the optimized platform was also investigated. Human serum albumin (HSA) concentration, pH, and stirring time were modulated to optimize QP albumin NPs with a particle size of 103.54 ± 2.36 nm and a QP EE% of 96.32 ± 3.98%. In addition, the intravenous administration of QP albumin NPs facilitated QP brain targeting with a 4.9-fold increase in targeting efficiency compared to the oral QP solution. The QP albumin NPs improved the QP antipsychotic activity, indicated by suppressing rats' hypermobility and reducing the QP's extrapyramidal side effects. The obtained results proposed that intravenous QP- NPs could improve QP brain targeting and its antipsychotic efficiency.

Intranasal Nanotransferosomal Gel for Quercetin Brain Targeting: I. Optimization, Characterization, Brain Localization, and Cytotoxic Studies.

Numerous neurological disorders have a pathophysiology that involves an increase in free radical production in the brain. Quercetin (QER) is a nutraceutical compound that shields the brain against oxidative stress-induced neurodegeneration. Nonetheless, its low oral bioavailability diminishes brain delivery. Therefore, the current study aimed to formulate QER-loaded transferosomal nanovesicles (QER-TFS) in situ gel for QER brain delivery via the intranasal route. This study explored the impacts of lipid amount, edge activator (EA) amount, and EA type on vesicle diameter, entrapment, and cumulative amount permeated through nasal mucosa (24 h). The optimum formulation was then integrated into a thermosensitive gel after its physical and morphological characteristics were assessed. Assessments of the optimized QER-TFS showed nanometric vesicles (171.4 ± 3.4 nm) with spherical shapes and adequate entrapment efficiency (78.2 ± 2.8%). The results of short-term stability and high zeta potential value (-32.6 ± 1.4 mV) of QER-TFS confirmed their high stability. Compared with the QER solution, the optimized QER-TFS in situ gel formulation exhibited sustained release behavior and augmented nasal mucosa permeability. CT scanning of rat brains demonstrated the buildup of gold nanoparticles (GNPs) in the brains of all treatment groups, with a greater level of GNPs noted in the rats given the transferosomal gel. Additionally, in vitro studies on PCS-200-014 cells revealed minimal cytotoxicity of QER-TFS in situ gel. Based on these results, the developed transferosomal nanovesicles may be a suitable nanocarrier for QER brain targeting through the intranasal route.

Evaluation of Brain Targeting and Antipsychotic Activity of Nasally Administrated Ziprasidone Lipid-Polymer Hybrid Nanocarriers.

The feasibility of using lipid-polymer hybrid (LPH) nanocarriers as a potential platform for the intranasal delivery of ziprasidone (ZP), a second-generation antipsychotic, was explored. Different ZP-loaded LPH composed of a PLGA core and cholesterol-lecithin lipid coat were prepared using a single step nano-precipitation self-assembly technique. Modulation of polymer, lipid and drug amounts, as well as stirring-speed-optimized LPH with a particle size of 97.56 ± 4.55 nm and a ZP entrapment efficiency (EE%) of 97.98 ± 1.22%. The brain deposition and pharmacokinetics studies proved the efficiency of LPH to traverse the blood-brain barrier (BBB) following intranasal delivery with a 3.9-fold increase in targeting efficiency compared to the intravenous (IV) ZP solution with a direct nose-to-brain transport percentage (DTP) of 74.68%. The ZP-LPH showed enhanced antipsychotic activity in terms of animals' hypermobility over an IV drug solution in schizophrenic rats. The obtained results showed that the fabricated LPH was able to improve ZP brain uptake and proved its antipsychotic efficiency.

9-Methoxyellipticine: Antibacterial Bioactive Compound Isolated from Ochrosia elliptica Labill. Roots.

Antibacterial resistance bears a major threat to human health worldwide, causing about 1.2 million deaths per year. It is noteworthy that carbazole derivatives have shown a potential antibacterial activity, for example, 9-methoxyellipticine, which was isolated from Ochrosia elliptica Labill. roots (Apocynaceae) in the present study. An in vitro screening of the antibacterial activity of 9-methoxyellipticine was investigated against four multidrug-resistant (MDR) Klebsiella pneumoniae and Shiga toxin-producing Escherichia coli (STEC O157) as Gram-negative bacteria, in addition to Methicillin-resistant Staphylococcus aureus (MRSA) with Bacillus cereus as Gram-positive bacteria. The compound had significant antibacterial activity against the two Gram-negative isolates and lower activity against the Gram-positive ones. The synergistic use of 9-methoxyellipticine and antibiotics was successfully effective in reducing the MDR microorganisms. Lung pneumonia and kidney infection mice models were used to investigate the compound's efficacy in vivo for the first time. Noteworthy reductions in K. pneumoniae and STEC shedding and the colonization were observed, with a reduction in pro-inflammatory factors and immunoglobulin levels. Other related lesions such as inflammatory cell infiltration, alveolar interstitial congestion, and edema were noticed to occur, lessened to different limits. The anti-STEC and anti-K. pneumoniae activities of 9-methoxyellipticine were revealed, providing a new alternative against MDR nosocomial infections.

Luteolin 4'-Neohesperidoside Inhibits Clinically Isolated Resistant Bacteria In Vitro and In Vivo.

Multidrug resistance (MDR) pathogens are usually associated with higher morbidity and mortality rates. Flavonoids are good candidates for the development of new potential antimicrobials. This research investigated whether luteolin 4'-neohesperidoside (L4N) has antibacterial and synergistic activities against four antibiotic-resistant pathogens: methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, fosA-positive shiga toxin producing the Escherichia coli serogroup O111 (STEC O111), and Bacillus cereus. In vitro antimicrobial susceptibility testing revealed highly potent anti-MRSA (MIC of 106.66 ± 6.95 µg/mL), anti-K. pneumoniae (MIC of 53.33 ± 8.47 µg/mL) and anti-STEC O111 (MIC of 26.66 ± 5.23 µg/mL) activities. Significant synergistic combination was clearly noted in the case of gentamycin (GEN) against Gram-negative bacteria. In the case of B. cereus, the combination of vancomycin (VAN) with L4N could efficiently inhibit bacterial growth, despite the pathogen being VAN-resistant (MIC of 213.33 ± 7.9 µg/mL). In vivo evaluation of L4N showed significant decreases in K. pneumoniae and STEC shedding and colonization. Treatment could significantly diminish the levels of pro-inflammatory markers, tumor necrosis factor-alpha (TNF-α), and immunoglobulin (IgM). Additionally, the renal and pulmonary lesions were remarkably enhanced, with a significant decrease in the bacterial loads in the tissues. Finally, this study presents L4N as a potent substitute for traditional antibiotics with anti-STEC O111 and anti-K. pneumoniae potential, a finding which is reported here for the first time.

Public Perceptions Regarding the Preparedness of Government to Combat the Third Wave of COVID-19 (SARS-CoV-2) Infection Across Various States of India.

India has already passed through 2 waves of the coronavirus disease (COVID-19) pandemic losing many lives. The reason for losing lives may be due to the unpreparedness of the health care system of India for this unprecedented pandemic. To assess the government's preparedness, an institutional-based cross-sectional prospective survey was conducted among the adult population of selected states in India. A self-administered 30-item questionnaire divided into 5 sections (demography of the participants, steps to create awareness, prevent spread of infection, handle the emergency, and prognosis) was distributed online through Google Forms. The responses were collected in an Excel file. SPSS software was used to perform the descriptive statistics and analysis of variance (ANOVA). Nearly a quarter of the participants "strongly disagree"/"disagree" about the government's preparedness for the third wave. Considering their perception, it cannot be assured that the government is well prepared to handle the emergency. So, the government must maintain emergency funding and develop a health infrastructure. The government should take steps to reduce social stigma, prevent spreading of unscientific propagation, and make people aware of the World Health Organization (WHO) as the reliable source of information for health emergencies to avoid a human crisis in the future.

Ameliorative Effect of Curcumin Nanoparticles against Monosodium Iodoacetate-Induced Knee Osteoarthritis in Rats.

Aim: This study is aimed at evaluating the use of curcumin-loaded polylactic-co-glycolic acid nanoparticles (CUR-loaded PLGA NPs) as a treatment against monosodium iodoacetate- (MIA-) induced knee OA. Materials and Methods: Eighteen rats were assigned to three groups (n = 6), namely, normal control group that received intra-articular injections (IAIs) of saline, an OA control group that received an IAIs of MIA (2 mg/50 µL), and a treatment group (MIA+CUR-loaded PLGA NPs) that received IAIs of CUR-loaded PLGA NPs (200 mg/kg b.wt). Results: The CUR NP treatment against knee OA alleviated radiographic alternations and histopathological changes and inhibited the upregulation in the serum levels of interleukin-1ß, tumor necrosis factor-α, interleukin-6, and transforming growth factor-beta and the downregulation in interleukin-10. CUR NP-treated joints also decreased the mRNA expression of nuclear factor-kappa B and inducible nitric oxide synthase and the protein expression of matrix metalloproteinase-13 and caspase-3. Finally, CUR-loaded PLGA NP treatment mitigated the loss of type II collagen, which resulted in a significant reduction in malondialdehyde level and increased the glutathione content and superoxide dismutase activity compared with that of the OA group. Conclusion: This study demonstrated that the administration of CUR NPs could provide effective protection against MIA-induced OA and knee joint histological deteriorated changes due to its anti-inflammatory, antioxidant, and antiapoptotic properties.

Antibiotic consumption in hospitals during COVID-19 pandemic: a comparative study.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) results in similar clinical characteristics as bacterial respiratory tract infections and can potentially lead to antibiotic overuse. This study aimed to determine the changes in hospital antimicrobial usage before and during the COVID-19 pandemic. METHODOLOGY: We compared antimicrobial consumption data for 2019 and 2020. Inpatient antibiotic consumption was determined and expressed as a defined daily dose (DDD) per 100 occupied bed days, following the World Health Organization (WHO) methods. The WHO Access, Watch, and Reserve (AWaRe) classification was used. RESULTS: The total antimicrobial consumption in 2020 increased by 16.3% compared to consumption in 2019. In 2020, there was a reduction in fourth-generation cephalosporins (-30%), third-generation cephalosporins (-29%), and combinations of penicillins (-23%). In contrast, antibiotics that were consumed more during 2020 compared with 2019 included linezolid (374%), vancomycin (66.6%), and carbapenem (7%). Linezolid is the only antibiotic from the Reserve group on the hospital's formulary. Antibiotic usage from the Access group was reduced by 17%, while antibiotic usage from the Watch group and the Reserve group was increased by 3% and 374%, respectively. CONCLUSIONS: The findings show a significant shift in antibiotic usage from the Access group to the Watch and Reserve groups. The Watch and Reserve groups are known to be associated with increased resistance to antibiotics. Therefore, antimicrobial stewardship should be increased and maintained during the pandemic to ensure appropriate antibiotic use.

Unveiling Antimicrobial and Antioxidant Compositional Differences between Dukkah and Za'atar via SPME-GCMS and HPLC-DAD.

Interest in plant-based diets has been on the rise in recent years owing to the potential health benefits of their individual components and the notion that plant-based diets might reduce the incidence of several diseases. Egyptian dukkah and Syrian za'atar are two of the most historic and famous Middle Eastern herbal blends used for their anti-inflammatory, hypolipidemic, and antidiabetic effects. Headspace SPME-GCMS and HPLC-DAD were adopted for characterizing the aroma profile and phenolic compounds of both herbal blends, respectively. Further, vapor-phase minimum inhibitory concentration was employed for assessing each blend's antibacterial potential, while their antioxidant potential was estimated via in vitro antioxidant assays. SPME headspace analysis indicated the abundance of ethers and monoterpene hydrocarbons, while HPLC revealed the presence of several phenolics including rosmarinic acid, ferulic acid, and rutin. Biological investigations affirmed that vapor-phase of the tested blends exhibited antibacterial activities against Gram-positive and Gram-negative pathogens, while the antioxidant potential of the blends was investigated and expressed as Trolox (125.15 ± 5.92 to 337.26 ± 13.84 µM T eq/mg) and EDTA (18.08 ± 1.62 to 51.69 41 ± 5.33 µM EDTA eq/mg) equivalent. The presented study offers the first insight into the chemical profile and biological activities of both dukkah and za'atar.

Comparison of the Treatment Efficacy of Rosuvastatin versus Atorvastatin Loading Prior to Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction.

The aim of this study was to compare the effect of a single high-dose rosuvastatin versus atorvastatin preloading in ST-elevation myocardial infarction (STEMI) patients receiving primary percutaneous coronary intervention (PCI.) Methods: A total of 99 patients presented with STEMI and were randomly divided into three groups­a control group (n = 33) with no statin treatment, an atorvastatin group (n = 33) with a single 80 mg atorvastatin dose and the rosuvastatin group (n = 33) with a single 40 mg rosuvastatin dose in the emergency room (ER) prior to PCI. Post-interventional thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) were recorded, and ST-segment resolution was measured. Results: CTFC was significantly lower for the atorvastatin group (p-value < 0.01) than in the control group. A final TIMI flow grade 3 was achieved in 32 (97.0%) patients in the rosuvastatin group and 28 (84.8%) patients in the atorvastatin group compared with only 25 (75.8%) patients in the control group (p = 0.014). Peak CK-MB in the rosuvastatin group (263.2 [207.2−315.6]) and the atorvastatin group (208 [151.0−314.1]) was lower compared to that in the control group (398.4 [303.9−459.3]); p < 0.001. Conclusions: A single extensive dose of lipophilic atorvastatin prior to primary PCI in STEMI patients showed better improvement in microvascular myocardial perfusion compared to hydrophilic rosuvastatin.

Facile Conversion of the Quinone-Semicarbazone Chromophore of Naftazone into a Fluorescent Quinol-Semicarbazide: Kinetic Study and Analysis of Naftazone in Pharmaceuticals and Human Serum.

Naftazone is a quinone-semi carbazone drug that possesses a strong orange color, and hence it was usually analyzed colorimetrically or by HPLC-UV. However, these methods are not sensitive enough to determine naftazone in biological samples. Naftazone lacks intrinsic fluorescence and does not possess easily derivatizable functional groups. In this contribution, we introduced the first spectrofluorimetric method for naftazone assay through reduction-elicited fluorogenic derivatization through the reduction of its quinone-semicarbazone moiety to the corresponding quinol-semicarbazide derivative by potassium borohydride as a reduction probe. The solvent-dependent fluorescence of the reaction product was studied in various protic and aprotic solvents. Eventually, the fluorescence of the reduced naftazone was measured in 2-propanol at λemission of 350 nm after excitation at λecxitation of 295 nm. The relative fluorescence intensity was linearly correlated to the drug concentration (r = 0.9995) from 10.0 to 500 ng/mL with high sensitivity, where the lower detection limit was 2.9 ng/mL. Hence, the method was effectively applied for naftazone tablets quality control with a mean %recovery of 100.3 ± 1.5, and the results agreed with those of the comparison HPLC-UV method. Furthermore, a new salting-out assisted liquid-liquid extraction (SALLE) method was established for naftazone extraction from human serum, followed by its determination using the developed reduction-based fluorogenic method. The developed SALLE method showed excellent recovery for naftazone from human serum (92.3-106.5%) with good precision (RSD ≤ 6.8%). Additionally, the reaction of naftazone with potassium borohydride was kinetically monitored, and it was found to follow pseudo-first-order kinetics with an activation energy of 43.8 kcal/mol. The developed method's greenness was approved using three green analytical chemistry metrics.

Rutin and Quercetin Counter Doxorubicin-Induced Liver Toxicity in Wistar Rats via Their Modulatory Effects on Inflammation, Oxidative Stress, Apoptosis, and Nrf2.

The presented study was performed to verify whether rutin and/or quercetin can inhibit liver injury induced by doxorubicin (DXR) in male Wistar rats. In this study, male Wistar rats were treated via the oral route with rutin and quercetin (50 mg/kg) either alone or in combination every other day for five weeks concomitant with receiving intraperitoneal DXR (2 mg/kg) two times a week for five successive weeks. Quercetin, rutin, and their combination significantly improved the deteriorated serum AST, ALT, and ALP activities and total bilirubin level, as well as albumin, AFP, and CA 19.9 levels in DXR-injected rats. Treatments of the DXR-injected group with quercetin and rutin prevented the elevation in liver lipid peroxidation and the reduction in superoxide dismutase, glutathione-S-transferase and glutathione peroxidase activities, and glutathione content. Treatments with quercetin and rutin significantly repressed the elevated expression of liver p53 and TNF-α and enhanced Nrf2 expression. Furthermore, the treatments significantly reduced DXR-induced liver histological changes. In conclusion, rutin and quercetin either alone or in combination may have potential preventive effects against DXR-induced hepatotoxicity through inhibiting oxidative stress, inflammation, and apoptosis as well as modulating the Nrf2 expression.