104 research outputs found
Tandem Achmatowicz-Knoevenagel protocol: diastereoselective synthesis and anticancer evaluation of cyclopenta[b]pyrane derivatives
No full textSimultaneous Determination of Pharmaceuticals by Solid-phase Extraction and Liquid Chromatography-Tandem Mass Spectrometry: A Case Study from Sharjah Sewage Treatment Plant
No full textThe present work describes the optimization and validation of a highly selective and sensitive analytical method using solid phase extraction and liquid chromatography tandem mass spectrometry (SPE LC-MS/MS) for the determination of some frequently prescribed pharmaceuticals in urban wastewater received and treated by Sharjah sewage treatment plant (STP). The extraction efficiency of different SPE cartridges was tested and the simultaneous extraction of pharmaceuticals was successfully accomplished using hydrophilic-lipophilic-balanced reversed phase Waters® Oasis HLB cartridge (200 mg/ 6 mL) at pH 3. The analytes were separated on an Aquity BEH C18 column (1.7 µm, 2.1 mm × 150 mm) using gradient elution and mass spectrometric analysis were performed in multiple reactions monitoring (MRM) selecting two precursor ions to produce ion transition for each pharmaceutical using positive electrospray ionization (+ESI) mode. The correlation coefficient values in the linear calibration plot for each target compound exceeded 0.99 and the recovery percentages of the investigated pharmaceuticals were more than 84%. Limit of detection (LOD) varied between 0.1⁻1.5 ng/L and limit of quantification (LOQ) was 0.3⁻5 ng/L for all analytes. The precision of the method was calculated as the relative standard deviation (RSD%) of replicate measurements and was found to be in the ranges of 2.2% to 7.7% and 2.2% to 8.6% for inter and intra-day analysis, respectively. All of the obtained validation parameters satisfied the requirements and guidelines of analytical method validation
Design, synthesis, and biological evaluation of new arylamide derivatives possessing sulfonate or sulfamate moieties as steroid sulfatase enzyme inhibitors
No full textA series of new arylamide derivatives possessing terminal sulfonate or sulfamate moieties was designed and synthesized. The target compounds were tested for in vitro inhibitory effects against the steroid sulfatase (STS) enzyme in a cell-free assay system. The free sulfamate derivative 1j was the most active. It inhibited the enzymatic activity by 72.0% and 55.7% at 20 μM and 10 μM, respectively. Compound 1j was further tested for STS inhibition in JEG-3 placental carcinoma cells with high STS enzyme activity. It inhibited 93.9% of the enzyme activity in JEG-3 placental carcinoma cells at 20 μM with an efficacy near to that of the well-established drug STX64 as reference. At 10 μM, 1j inhibited 86.1% of the STS activity of JEG-3. Its IC50 value against the STS enzyme in JEG-3 cells was 0.421 μM. Thus, 1j represents an attractive new non-steroidal lead for further optimization
Cross-sectional study on urinary metal concentrations in young adult residents of Emirate of Sharjah, United Arab Emirates
No full textAbstract
Background:
Human biomonitoring is crucial for regulatory toxicology, yet data on biomarker concentrations in the UAE are lacking. This study addresses this gap by analyzing urinary concentrations of 16 metals in UAE young adults, assessing correlations with personal characteristics, dietary patterns, and lifestyle habits.
Methods:
A cross-sectional pilot study was conducted among 144 randomly selected young adults (71 males and 73 females) from Sharjah, UAE, between January and March 2023. Participants provided urine samples, which were analyzed for 16 heavy metals using ICP-OES, and completed detailed questionnaires covering sociodemographic factors, lifestyle, and dietary habits. Descriptive statistics were used to summarize participant characteristics, and linear regression analysis was applied to explore associations between metal concentrations and factors such as gender, dietary habits, and exposure to environmental risks. Non-parametric tests, including the Mann-Whitney test, were used to assess differences by gender. Statistical significance was set at p < 0.05. Ethical approval was obtained, and informed consent was secured before participation
Results:
Significant findings include dietary influences on metal exposure, with rice consumption linked to higher metal concentrations. Sex differences were significant, with females showing elevated levels of arsenic, lead, and cadmium. Lifestyle factors, such as smoking and incense use, were correlated with increased barium and boron levels.
Conclusion:
This study highlights the significant role of dietary habits, especially the consumption of rice, in metal exposure among young adults in Sharjah. The findings highlight the urgent need for comprehensive human biomonitoring to understand environmental exposures and reform public health policies. The gender-specific differences in metal distribution suggest the necessity for targeted public health strategies. The study, however, is limited by its cross-sectional nature and the focus on a specific geographic area, warranting further research for broader generalizability. Future investigations, particularly on the impact of incense exposure on metal levels, are essential for developing comprehensive health interventions and preventive strategies in the UAE.Abstract
Background:
Human biomonitoring is crucial for regulatory toxicology, yet data on biomarker concentrations in the UAE are lacking. This study addresses this gap by analyzing urinary concentrations of 16 metals in UAE young adults, assessing correlations with personal characteristics, dietary patterns, and lifestyle habits.
Methods:
A cross-sectional pilot study was conducted among 144 randomly selected young adults (71 males and 73 females) from Sharjah, UAE, between January and March 2023. Participants provided urine samples, which were analyzed for 16 heavy metals using ICP-OES, and completed detailed questionnaires covering sociodemographic factors, lifestyle, and dietary habits. Descriptive statistics were used to summarize participant characteristics, and linear regression analysis was applied to explore associations between metal concentrations and factors such as gender, dietary habits, and exposure to environmental risks. Non-parametric tests, including the Mann-Whitney test, were used to assess differences by gender. Statistical significance was set at p < 0.05. Ethical approval was obtained, and informed consent was secured before participation
Results:
Significant findings include dietary influences on metal exposure, with rice consumption linked to higher metal concentrations. Sex differences were significant, with females showing elevated levels of arsenic, lead, and cadmium. Lifestyle factors, such as smoking and incense use, were correlated with increased barium and boron levels.
Conclusion:
This study highlights the significant role of dietary habits, especially the consumption of rice, in metal exposure among young adults in Sharjah. The findings highlight the urgent need for comprehensive human biomonitoring to understand environmental exposures and reform public health policies. The gender-specific differences in metal distribution suggest the necessity for targeted public health strategies. The study, however, is limited by its cross-sectional nature and the focus on a specific geographic area, warranting further research for broader generalizability. Future investigations, particularly on the impact of incense exposure on metal levels, are essential for developing comprehensive health interventions and preventive strategies in the UAE
Quick and Sensitive UPLC-ESI-MS/MS Method for Simultaneous Estimation of Sofosbuvir and Its Metabolite in Human Plasma
No full textA simple, fast and highly sensitive RP-UPLC-MS/MS method was developed and validated for the simultaneous determination of sofosbuvir (SR) and its metabolite GS331007 in human plasma using ketotifen as an internal standard (IS). The separation was achieved on Acquity UPLC BEH C18 (50 × 2.1 mm, i.d. 1.7 µm, Waters, USA) column using acetonitrile:5 mM ammonium formate:0.1% formic acid (85:15:0.1% v/v/v) as a mobile phase at a flow rate of 0.35 mL/min in an isocratic elution. The Xevo TQD UPLC-MS/MS was operated under the multiple-reaction monitoring mode using positive electrospray ionization. Extraction with dichloromethane was used in the sample preparation. Method validation was performed as per the Food and Drug Administration (FDA) guidelines and the calibration curves of the proposed method were found to be linear in the range of 1–1000 ng/mL for SR and in the range of 10–1500 ng/mL for its metabolite (GS331007) with an elution time of 1.83 min. All validation parameters were within the acceptable range according to the bioanalytical methods validation guidelines. Furthermore, the obtained results of matrix effects indicate that ion suppression or enhancement from human plasma components was negligible under the optimized conditions. The proposed method can be applied in high-throughput analysis required for pharmacokinetic and bioequivalence studies in human samples
Phytochemical composition and antiviral properties of A. fragrantissima methanolic extract on H1N1 virus
No full textBackground: The H1N1 influenza virus continues to pose a substantial risk to public health because of its fast spread and the development of resistance to existing neuraminidase inhibitors. The demand for alternative antiviral drugs, especially those obtained from natural sources, is consistently increasing. Objective: The objective of this work was to examine the antiviral properties of the methanolic extract of A. fragrantissima against the H1N1 influenza virus. The main focus was to assess its neuraminidase enzyme inhibition and its capability to decrease virus-induced cytotoxicity in MDCK cells. Methods: The aerial parts of A. fragrantissima were gathered, dried, and extracted using methanol solvent. Phytochemical profiling of the extract was performed using GC-MS derivatization. The inhibition of neuraminidase was measured by a fluorometric method, and the antiviral activity was investigated in MDCK cells that were infected with H1N1. Results: Bioactive substances, including flavonoids, sesquiterpene lactones, fatty acids, and phenolic acids, were detected by phytochemical analysis. The extract exhibited inhibitory action against neuraminidase, identified by an IC50 value of 203.1 µg/mL. In antiviral tests, the extract treatment at a concentration of 150 µg/mL led to a significant decrease of 38.7% in virus-induced cytotoxicity at the highest viral titer. The MTT assay demonstrated minor cytotoxicity when used in antiviral investigations, with an IC50 value of 328 µg/mL. Conclusion: A. fragrantissima methanolic extract shows significant antiviral action against H1N1 influenza virus, probably via neuraminidase suppression. Bioactive substances with established antiviral, anti-inflammatory, and antioxidant effects highlight the potential of A. fragrantissima as a natural antiviral agent. The presence of bioactive compounds with known antiviral, anti-inflammatory, and antioxidant properties underscores the potential of A. fragrantissima as a natural antiviral agent. Additional research is required to isolate and identify the precise active components accountable for its antiviral properties
Untargeted Metabolomic Plasma Profiling of Emirati Dialysis Patients with Diabetes versus Non-Diabetic: A Pilot Study
No full textDiabetic kidney disease (DKD) is a severe irreversible complication of diabetes mellitus that further disturbs glucose metabolism. Identifying metabolic changes in the blood may provide early insight into DKD pathogenesis. This study aims to determine blood biomarkers differentiating DKD from non-diabetic kidney disease in the Emirati population utilizing the LC-MS/MS platform. Blood samples were collected from hemodialysis subjects with and without diabetes to detect indicators of pathological changes using an untargeted metabolomics approach. Metabolic profiles were analyzed based on clinically confirmed diabetic status and current HbA1c values. Five differentially significant metabolites were identified based on the clinically confirmed diabetic status, including hydroxyprogesterone and 3,4-Dihydroxymandelic acid. Similarly, we identified seven metabolites with apparent differences between Dialysis Diabetic (DD) and Dialysis non-Diabetic (DND) groups, including isovalerylglycine based on HbA1c values. Likewise, the top three metabolic pathways, including Tyrosine metabolism, were identified following the clinically confirmed diabetic status. As a result, nine different metabolites were enriched in the identified metabolic pathways, such as 3,4-Dihydroxymandelic acid. As a result, eleven different metabolites were enriched, including Glycerol. This study provides an insight into blood metabolic changes related to DKD that may lead to more effective management strategies
Nanotechnological Advances for Cutaneous Release of Tretinoin: An Approach to Minimize Side Effects and Improve Therapeutic Efficacy
No full text
Background:
The clinical efficacy of the topical tretinoin is widely studied and has
been well established for many therapeutic interventions, among some, photoaging, acne, and
melasma. However, the side effects, mainly cutaneous irritation, erythema, xerosis and peeling,
remain major obstacle to the patient compliance. Besides, the insight regarding the drug delivery
profile is essential to understand the therapeutic action of the drug.
Methods:
Through bibliographic research in databases we highlight further advances and an update
on tretinoin delivery systems such as liposomes, niosomes, solid lipid nanoparticles, nanostructured
lipid carriers, cyclodextrins, nanostructured polymers and other technological systems
that reduce its side effects and improve the permeation profile to potentiate efficacy and drug
safety on the skin.
Results:
Pharmaceutical preparations were developed and evaluated for permeability in in vitro
models using pig ear, snake, mouse and human skin, and potential for irritation was also verified
using release systems for tretinoin and compared to available commercial formulations. Overall
results indicated the composition, charge and size of the system influences the tretinoin delivery,
modulating the type of release and its retention. Small unilamellar vesicles promoted greater cutaneous
delivery of tretinoin. Negative charge, for both liposomes and niosomes, can improve pig
skin hydration as well as the tretinoin retention. The quantity of solid lipids and the type of oil used
in the composition of solid lipid nanoparticles and nanostructured lipid carriers affected percutaneous
drug delivery.
Conclusion:
As evident from the literature, the tretinoin technological delivery systems consist an
innovative and potential management for increasing the patient compliance presenting safety and
efficacy.
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Metabolic Profiling of Candida auris, a Newly-Emerging Multi-Drug Resistant Candida Species, by GC-MS
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