Modified Bahasa Malaysia version of VF-14 questionnaire: assessing the impact of glaucoma in rural area of Malaysia

Purpose: To evaluate the functional impairment of glaucoma patients, using a modified Bahasa Malaysia version of VF‐14 questionnaire, and to correlate the score with the severity of the disease. Methods: One‐to‐one interview by trained interviewers was conducted on glaucoma patients seen in the eye clinic of Hospital Universiti Sains Malaysia, using a modified validated Bahasa Malaysia version of VF‐14 questionnaire. The severity of glaucoma was determined based on the better‐eye Advanced Glaucoma Intervention Study Scale (AGIS) score of visual field analysis on the latest most reliable visual field. The literacy rate, living situation, better‐eye visual acuity and lens status were also documented. Results: A total of 110 glaucoma patients were recruited (54.5% primary open‐angle glaucoma, 21.8% primary angle‐closure glaucoma, 19.2% normotensive glaucoma and 4.5% pseudoexfoliative glaucoma) and majority with bilateral involvement. Based on the better‐eye AGIS score, 41.5% were in advanced stage, 29.1% moderate and 29.1% mild. There was a significant association between VF‐14 scoring with the better‐eye AGIS score (r =?0. 579, P < 0.001), age (r = ?0.313, P = 0.000) and better‐eye visual acuity (r = ?0.752, P = 0.000). Based on the multivariate analysis, there was a significant association of the questionnaire score and better‐eye AGIS score (P < 0.001). Conclusion: The Bahasa Malaysia version of modified VF‐14 questionnaire is a useful tool in quantifying quality of life among glaucoma patients in rural area with high illiteracy rate and provides moderate correlation with severity of the disease. Customization of quality of life questionnaire according to custom and culture of the community will provide better insight to the functional impairment of glaucoma patients.     

Detection and Specific Elimination of EGFR<Superscript>+</Superscript> Ovarian Cancer Cells Using a Near Infrared Photoimmunotheranostic Approach

Purpose

Targeted theranostics is an alternative strategy in cancer management that aims to improve cancer detection and treatment simultaneously. This approach combines potent therapeutic and diagnostic agents with the specificity of different cell receptor ligands in one product. The success of antibody drug conjugates (ADCs) in clinical practice has encouraged the development of antibody theranostics conjugates (ATCs). However, the generation of homogeneous and pharmaceutically-acceptable ATCs remains a major challenge. The aim of this study is to detect and eliminate ovarian cancer cells on-demand using an ATC directed to EGFR.

Methods

An ATC with a defined drug-to-antibody ratio was generated by the site-directed conjugation of IRDye®700 to a self-labeling protein (SNAP-tag) fused to an EGFR-specific antibody fragment (scFv-425).

Results

In vitro and ex vivo imaging showed that the ATC based on scFv-425 is suitable for the highly specific detection of EGFR⁺ ovarian cancer cell, human tissues and ascites samples. The construct was also able to eliminate EGFR⁺ cells and human ascites cells with IC₅₀ values of 45–66 nM and 40–90 nM, respectively.

Conclusion

Our experiments provide a framework to create a versatile technology platform for the development of ATCs for precise detection and treatment of ovarian cancer cells.

     

Genistein modulation of seizure: involvement of estrogen and serotonin receptors

Genistein, a major source of phytoestrogen exposure for humans and animals, has been shown to mediate neuroprotection in Alzheimer’s disease and status epilepticus. In the present study, we investigated the effect of genistein on pentylenetetrazole-induced seizures in ovariectomized mice and the possible involvement of estrogenic and serotonergic pathways in the probable effects of genistein. Intraperitoneal (i.p.) administration of genistein (10 mg/kg) significantly increased the seizure threshold 30 min prior to induction of seizures 14 days after ovariectomy surgery. Administration of fulvestrant (1 mg/kg, i.p.), an estrogen receptor antagonist, completely reversed the anticonvulsant effect of genistein (10 mg/kg) in ovariectomized mice. Administration of the antagonist of serotonin receptor (5-HT3), tropisetron (10 mg/kg, i.p.), eliminated the anticonvulsant effect of genistein, whereas co-administration of m-chlorophenylbiguanide (5-HT3 receptor agonist; 1 mg/kg) and a non-effective dose of genistein (5 mg/kg) increased the seizure threshold. To conclude, it seems that estrogenic/serotonergic systems might be involved in the anticonvulsant properties of genistein.     

LC determination of glimepiride and its related impurities

Five impurities in glimepiride drug substance were detected and quantified using a simple isocratic reverse phase HPLC method. For the identification and characterization purpose these impurities were isolated from a crude reaction mixture of glimepiride using a normal phase HPLC system. Based on the spectroscopic data like NMR, FTIR, UV and MS these impurities were characterized and used as impurity standards for determining the relative response factor during the validation of the proposed isocratic reverse phase HPLC method. The chromatographic separation was achieved on a Phenomenex Luna C8 (2) 100 Å, 5 μm, 250 mm × 4.6 mm using a mobile phase consisting of phosphate buffer (pH 7.0)–acetonitrile–tetrahydrofuran (73:18:09, v/v/v) with UV detection at 228 nm and a flow rate of 1 ml/min. The column temperature was maintained at 35 °C through out the analysis. The method has been validated as per international guidelines on method validation and can be used for the routine quality control analysis of glimepiride as active pharmaceutical ingredient (API).     

An assessment of the current practice of community pharmacists for the disposal of medication waste in the United Arab Emirates: A deep analysis at a glance

ObjectiveThe study aimed to identify the current practice carried out by community pharmacists to dispose of expired medications in their workplace and assess any practical steps utilized to reduce medication waste.MethodA cross-sectional study was conducted among community pharmacists in the United Arab Emirates (UAE). The participants were asked about their routine practice in disposing of different expired medications and the current actions taken to reduce the number of disposed medicines.ResultsThe study included (n = 418) community pharmacists. More than a third of expired liquid, solid, and semi-solid dosage forms were collected by licensed contractors. In addition, more than a third of the pharmacists disposed of different dosage forms via unauthorized methods (general garbage, sink and toilet). Most expired drugs were skin and hair products, antibiotics and analgesics. The majority of pharmacists (68.4 %, n = 286) agreed that expired pharmaceutical and non-pharmaceutical products, other than those disposed of via contractor, should be done through a specialized centre. This opinion was found to be strongly associated with years of practice as community pharmacists (P < 0.05).ConclusionPart of the existing disposal practices for expired pharmaceutical products in the UAE is carried out by contractors licensed by health authorities. However, concern remains regarding some pharmaceutical and non-pharmaceutical products that have not been disposed of correctly. Additionally, there is a need for a specialized center for medication disposal (p < 0.05). A stock limitation is the best practice for managing medication quantities in stock (p < 0.05).     

Selective synthesis of alpha monoglycerides by a clean method: Techno-economic and environmental assessment

This work proposes an alternative green and selective biocatalytic route for Glycerin Monostearate (α-monostearin) production. The conventional method of production uses an elevated temperature. Apart from the high energy consumption, such high temperatures darken the final product's color, lead to random reactions, and produce high orders of diglycerides and triglycerides instead of monoglycerides. The proposed production process was performed by esterifying stearic acid with glycerin in an organic medium using Candida antarctica lipase (Novozym 435) at a mild temperature. The reaction conditions were optimized using the response surface methodology (RSM): optimum conditions were a temperature of 60 °C, glycerin to stearic acid molar ratio of 8:1, and Novozym 435 amount of 6% w/w. The solvent addition remarkably improved the α-monostearin yield to nearly 80% without the need for the energy-intensive distillation step. The conventional autocatalytic esterification (AUT) process was also performed to investigate the comparative monoglyceride yield, and it was found to be 22.5%. Proton nuclear magnetic resonance and gas-chromatography confirmed that α-monostearin could be produced with the highest purity using the proposed enzymatic method (ENZ). Economic and environmental analyses were also conducted for the proposed ENZ process, and the results were compared with those of the AUT process. The total capital investment of α-monostearin production, considering a projected capacity of 4950 t year^?1 and 11% interest for the proposed ENZ process, was favorably 2.5 times lower than that of the AUT process, suggesting a promising investment opportunity. However, the total production costs showed unfavorable negative net present value (NPV) and return on investment (ROI) for the ENZ process and favorable positive NPV and ROI for the AUT process, indicating that the proposed venture is not profitable for α-monostearin production. However, the process can be profitable at improved operational stability of Novozym 435 up to 1 kg per 3-ton product. The carbon footprint was calculated on the basis of the given capacity and conditions of 50 and 656 t CO₂ eq./year for the ENZ and AUT processes, respectively. The synthesis of α-monostearin using the proposed route can be considered a building block toward a cleaner large-scale production of α-monoglycerides.     

Validation of a New Sensitive Method for the Detection and Quantification of R and S-Epimers of Ergot Alkaloids in Canadian Spring Wheat Utilizing Deuterated Lysergic Acid Diethylamide as an Internal Standard

Ergot sclerotia effect cereal crops intended for consumption. Ergot alkaloids within ergot sclerotia are assessed to ensure contamination is below safety standards established for human and animal health. Ergot alkaloids exist in two configurations, the R and S-epimers. It is important to quantify both configurations. The objective of this study was to validate a new ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for quantification of six R and six S-epimers of ergot alkaloids in hard red spring wheat utilizing deuterated lysergic acid diethylamide (LSD-D₃) as an internal standard. Validation parameters such as linearity, limit of detection (LOD), limit of quantification (LOQ), matrix effects, recovery and precision were investigated. For the 12 epimers analyzed, low LOD and LOQ values were observed, allowing for the sensitive detection of ergot epimers. Matrix effects ranged between 101–113% in a representative wheat matrix. Recovery was 68.3–119.1% with an inter-day precision of <24% relative standard deviation (RSD). The validation parameters conform with previous studies and exhibit differences between the R and S-epimers which has been rarely documented. This new sensitive method allows for the use of a new internal standard and can be incorporated and applied to research or diagnostic laboratories.     

Effect of sinapic acid on aripiprazole pharmacokinetics in rats: Possible food drug interaction

Dietary supplements and foods can interact with various drugs, leading to possible clinical concerns. This study aimed to investigate the effect of orally administered sinapic acid (SA) on the pharmacokinetics of aripiprazole (APZ) in rats and its possible modulatory effects on hepatic cytochrome P450 (CYP3A2 and CYP2D6) expression in the liver tissues. Single dose and multiple dose parallel groups of wistar rats were categorized into six groups (n = 6 each) which abstained from food for 12 h prior to the experiment, while water was allowed ad libitum. The investigation was carried out for single dose: Group I was treated with normal saline orally for 15 days (normal control). Group II was administered normal saline orally for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group III received SA (20 mg/kg p.o.) for 15 days and received APZ (3 mg/kg p.o.) on day 15. Group IV was treated with SA (20 mg/kg p.o.) for 15 days. For the multiple dose study, Group I was treated with normal saline orally for 15 days (normal control); Group II received APZ (3 mg/kg p.o.) daily for 15 days; Group III was administered with SA (20 mg/kg p.o.) and APZ (3 mg/kg p.o.) for 15 days and Group IV received SA (20 mg/kg p.o.) for 15 days. The group I and IV were kept common in single and multiple dose groups. After last APZ dose, plasma samples were collected and APZ concentrations were determined using an UPLC-MS/MS technique. The pharmacokinetic parameters were calculated using a non-compartmental analysis. The concomitant administration of APZ with SA (as single or multiple dose) resulted in an increase in APZ absorption and a decrease on its systemic clearance. This was associated with a reduction in CYP3A2 and CYP2D6 protein expressions by 33–43% and -71–68% after the single and multiple co-administration, which are two enzymes responsible of the metabolism of APZ. Therefore, a reduction in the metabolic clearance appears to be the mechanism underlying the drug interaction of dietary supplement containing SA with APZ. Therefore, the concomitant administration of SA and APZ should be carefully viewed. Further investigations are required to assess the clinical significance of such observations in humans.     

Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects

Cancer remains the topmost disorder of the mankind and number of cases is unceasingly growing at unprecedented rates. Although the synthetic anti-cancer compounds still hold the largest market in the modern treatment of cancer, natural agents have always been tried and tested for potential anti-cancer properties. Thymoquinone (TQ), a monoterpene and main ingredient in the essential oil of Nigella sativa L. has got very eminent rankings in the traditional systems of medicine for its anti-cancer pharmacological properties. In this review we summarized the diverse aspects of TQ including its chemistry, biosynthesis, sources and pharmacological properties with a major concern being attributed to its anti-cancer efficacies. The role of TQ in different aspects involved in the pathogenesis of cancer like inflammation, angiogenesis, apoptosis, cell cycle regulation, proliferation, invasion and migration have been described. The mechanism of action of TQ in different cancer types has been briefly accounted. Other safety and toxicological aspects and some combination therapies involving TQ have also been touched. A detailed literature search was carried out using various online search engines like google scholar and pubmed regarding the available research and review accounts on thymoquinone upto may 2019. All the articles reporting significant addition to the activities of thymoquinone were selected. Additional information was acquired from ethno botanical literature focusing on thymoquinone. The compound has been the centre of attention for a long time period and researched regularly in quite considerable numbers for its various physicochemical, medicinal, biological and pharmacological perspectives. Thymoquinone is studied for various chemical and pharmacological activities and demonstrated promising anti-cancer potential. The reviewed reports confirmed the strong anti-cancer efficacy of thymoquinone. Further in-vitro and in-vivo research is strongly warranted regarding the complete exploration of thymoquinone in ethnopharmacological context.     

Enhanced antitumour activity of doxorubicin and simvastatin combination loaded nanoemulsion treatment against a Swiss albino mouse model of Ehrlich ascites carcinoma

Doxorubicin (DOX) is the most commonly used anticancer drug; however, it has limited use because prolonged administration may result in severe cardiotoxicity. Simvastatin (SIM), generally prescribed for hypercholesterolaemia, has also shown salubrious results in the monotherapy or combinational drug therapy of different cancers in various models. Nanoparticle drug delivery systems are a novel way of improving therapeutics and also improving the absorption and specificity of drugs towards tumour cells. In this study, we exploited this technology to increase drug specificity and minimize imminent adverse effects. In this study, the antitumour activity of the combination formulas of DOX and SIM, either loaded in water (DOX‐SIM‐Solution) or nanoemulsions (NEs) (DOX‐SIM‐NE), was evaluated in a Swiss albino mouse model of Ehrlich ascites carcinoma. The anticancer effect was assessed by quantifying the change in body weight, mean survival time, and percent increase in lifespan (%ILS), determining haematological and serum biochemical parameters (liver function test, kidney function test and lipid profile parameters) as well as studying the histopathological alterations in liver tissues. We observed a clear increase in %ILS of the DOX‐SIM‐Solution group (265.30) that was double the %ILS of the DOX‐SIM‐NE group (134.70). However, DOX‐SIM‐NE had a non‐toxic effect on the haematological parameters, whereas DOX‐SIM‐Solution increased the levels of haemoglobin and lymphocytes. Furthermore, the encapsulation of SIM and DOX into NEs improved the levels of all serum biochemical parameters compared to the DOX‐SIM‐Solution. A reduction in the side effects of DOX‐SIM‐NE on the liver was also established using light microscopy, which revealed that the morphologies of the hepatocytes of the mice were less affected by administration of the DOX‐SIM‐NE treatment than with the DOX‐SIM‐Solution treatment. The study showed that incorporating SIM into the DOX‐loaded‐NE formulation remarkably improved its efficiency and simultaneously reduced its adverse effects.