Study of the Cytotoxic and Bactericidal Effects of Sila‐substituted Thioalkyne and Mercapto‐thione Compounds based on 1,2,3‐Triazole Scaffold

A series of sila‐organosulphur compounds containing 1,2,3‐triazole cores were screened for their cytotoxic activity on human breast cancer cell line MCF‐7. Most of the tested compounds exhibited moderate‐to‐good activity against the cancer cells. Especially, the compound 4‐((2‐(trimethylsilyl)ethynylthio)methyl)‐1‐benzyl‐1H‐1,2,3‐triazole ( 3a) from series of sila‐substituted thioalkyne 1,2,3‐triazoles (STATs) and the compounds 3‐(1‐benzyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐mercapto‐1,1‐bis(trimethylsilyl)propane‐2‐thione ( 4a) and 1‐mercapto‐1,1‐bis(trimethylsilyl)‐3‐(1‐phenethyl‐1H‐1,2,3‐triazol‐4‐yl)propane‐2‐thione ( 4e) from series of sila‐substituted mercapto‐thione 1,2,3‐triazoles (SMTTs) exhibited promising cytotoxicity against MCF‐7 with IC₅₀ values of 35.17, 32.63 and 30.3 μg/mL, respectively. In addition, the possible mechanisms for inhibition of cell growth and induction of apoptotic cell death were explored by DAPI staining, cell cycle analysis and qRT‐PCR. The synthetic compounds were evaluated for their in vitro antibacterial activities, and as a result, the most prominent effects were observed for 3e and 4e . Especially, 3e was found to be quite active against all the tested strains with the MIC values ranging from 15 to 62 μg/mL, except P. aeruginosa. The results of the time‐kill assay suggested that the compound of 3e completely inhibited the growth of both gram‐negative bacteria, A. baumannii, and gram‐positive bacteria, S. aureus. In addition, SEM analysis confirmed morphostructural damage of the bacteria. Our findings could be applicable for developing dual‐targeting anticancer/antibacterial therapeutics.     

The clinical significance of small subarachnoid hemorrhages

With advancing technology, the sensitivity of computed tomography (CT) for the detection of traumatic subarachnoid hemorrhage (tSAH) continues to improve. Increased resolution has allowed for the detection of hemorrhage that is limited to one or two images of the CT exam. At our institution, all patients with a SAH require intensive care unit (ICU) admission, regardless of size. It was our hypothesis that patients with small subarachnoid hemorrhage experience favorable outcomes, and may not require the intensive monitoring offered in the ICU. This retrospective study evaluated 62 patients between 2011 and 2014 who presented to our Level I trauma center emergency room for acute traumatic injuries, and found to have subarachnoid hemorrhages on CT examination. The grade of subarachnoid hemorrhage was determined using previously utilized scoring systems, such as the Fisher, Modified Fisher, and Claassen grading systems. Electronic medical records were used to evaluate for medical decline, neurological decline, neurosurgical intervention, and overall hospital course. Admitting co-morbidities were noted, as were the presence of patient intoxication and use of anticoagulants. Patient outcomes were based on discharge summaries upon which the neurological status of the patient was assessed. Each patient was given a score based on the Glasgow outcome scale. The clinical and imaging profile of 62 patients with traumatic SAH were studied. Of the 62 patients, 0 % underwent neurosurgical intervention, 6.5 % had calvarial fractures, 25.8 % had additional intracranial hemorrhages, 27.4 % of the patients had significant co-morbidities, and 1.6 % of the patients expired. Patients with low-grade tSAH spent less time in the ICU, demonstrated neurological and medical stability during hospitalization. None of the patients with low-grade SAH experienced seizure during their admission. In our study, patients with low-grade tSAH demonstrated favorable clinical outcomes. This suggests that patients may not require as aggressive monitoring as is currently provided for those with tSAH.     

Occupational stress among Swedish audiologists in clinical practice: Reasons for being stressed

Objective: The present study reports on the application of a Swedish translation of the audiologist occupational stress questionnaire (AOSQ) on audiologists working in Sweden. The relations between AOSQ scores and perceived effort, perceived rewards, coping strategies at work, demographic variables such as salary, education length, practise length, and practice type were tested. Design: A cross-sectional e-mail survey using the AOSQ, effort-reward imbalance questionnaire, and demographic questions. Study sample: Four-hundred and four Swedish licensed audiologists working with clients. Results: The Swedish AOSQ translation demonstrated high inter-item correlations and high internal consistency. Several stress factors were identified: time spent at work, accountability, leadership at the workplace, paperwork and practice demands, equipment and clinical protocols, own health concerns, and job control. The outcome on the complete AOSQ questionnaire was related to perceived effort, perceived rewards, coping strategies at work, and age. Conclusions: The Swedish AOSQ translation seems to provide a valid measure of occupational stress among audiologists.     

In-vitro and in-vivo cytotoxicity and efficacy evaluation of novel glycyl-glycine and alanyl-alanine conjugates of chitosan and trimethyl chitosan nano-particles as carriers for oral insulin delivery

Purpose

The aim of this research work was to explore the possibility of providing multifunctional oral insulin delivery system by conjugating several types of dipeptides on chitosan and trimethyl chitosan to be used as drug carriers.

Doxorubicin-conjugated D-glucosamine- and folate- bi-functionalised InP/ZnS quantum dots for cancer cells imaging and therapy

Nanoscaled quantum dots (QDs), with unique optical properties have been used for the development of theranostics. Here, InP/ZnS QDs were synthesised and functionalised with folate (QD-FA), D-glucosamine (QD-GA) or both (QD-FA-GA). The bi-functionalised QDs were further conjugated with doxorubicin (QD-FA-GA-DOX). Optimum Indium to fatty acid (In:MA) ratio was 1:3.5. Transmission electron microscopy (TEM) micrographs revealed spherical morphology for the QDs (11?nm). Energy-dispersive spectroscopy (EDS) spectrum confirmed the chemical composition of the QDs. MTT analysis in the OVCAR-3 cells treated with bare QDs, QD-FA, QD-GA, QD-FA-GA and QD-FA-GA-DOX (0.2?mg/mL of QDs) after 24?h indicated low toxicity for the bare QDs and functionalised QDs (about 80–90% cell viability). QD-FA-GA-DOX nanoparticles elicited toxicity in the cells. Cellular uptake of the engineered QDs were investigated in both folate receptor (FR)-positive OVCAR-3 cells and FR-negative A549 cells using fluorescence microscopy and FACS flow cytometry. The FA-functionalised QDs showed significantly higher uptake in the FR-positive OVCAR-3 cells, nonetheless the GA-functionalised QDs resulted in an indiscriminate uptake in both cell lines. In conclusion, our findings indicated that DOX-conjugated FA-armed QDs can be used as theranostics for simultaneous imaging and therapy of cancer.     

Potential Cardioprotective Effects of Sumac Capsule in Patients With Hyperlipidemia: A Triple-Blind Randomized,Placebo-Controlled Crossover Trial

Objective: Alternative medicine and herbal drugs have been taken into account for managing cardiovascular risk factors. Sumac (Rhus coriaria L.) is rich in biologically active ingredients known to improve cardiovascular health. We investigated the effect of sumac on systolic (SBP) and diastolic (DBP) blood pressure, flow-mediated dilation (FMD), body mass index (BMI), and serum concentrations of lipids and fasting blood sugar (FBS) in participants with hyperlipidemia in a triple-blind randomized placebo- controlled crossover trial.

Methods: Thirty adults with dyslipidemia (mild to moderate elevation of plasma total cholesterol and/or triglycerides [TG; total cholesterol ≥ 6.0 mmol/L or TG ≥ 1.7 mmol/L and TG ≤ 5.0 mmol/L]) were assigned randomly to a sumac or a placebo group. Participants in the sumac group received sumac capsules (500 mg/twice daily) for the first 4 weeks, followed by 2 weeks’ washout period; the patients were then switched to a 4-week interval and received placebo for 4 weeks in the second period. The placebo group received these treatments in reverse order. FMD, BMI, SBP, DBP, lipids, and FBS were measured at baseline and after each period.

Results: Differences between placebo group and sumac group (placebo-sumac) were significantly decreased for BMI (0.21 ± 0.075 kg/m²), SBP (1.87 ± 0.83 mm Hg), DBP (1.32 ± 0.46 mm Hg), and total cholesterol (14.42 ± 4.95 mmol/L) and significantly increased for FMD (?0.23% ± 0.065%). Plasma level of TG did not change significantly across the treatment.

Conclusion: Sumac consumption may decrease cardiovascular risk factors in persons with mild to moderate hyperlipidemia.     

Responsiveness of selected outcome measures of participation restriction and quality of life in patients with multiple sclerosis

Purpose: To evaluate the responsiveness of two outcome measures of participation restriction [as measured by the Community Integration Questionnaire (CIQ)] and quality of life [as measured by the Multiple Sclerosis Quality of Life (MSQOL)] following a physiotherapy intervention in patients with multiple sclerosis (MS). Method: A sample of 265 patients completed both instruments first at the time of initial visit and then after 4–6 weeks physiotherapy. In addition, patients were asked to complete the 7-point global rating scale as an external criterion of change at the post-intervention time. The responsiveness was evaluated using the receiver operating characteristics (ROC) method and the correlation analysis. Two useful statistics were area under the ROC curve (AUC) and the minimally clinically important difference (MCID). The AUC and correlation coefficient greater than 0.70 were considered as acceptable responsiveness. Results: The CIQ achieved the acceptable responsiveness with an AUC of 0.81. However, the AUCs of 0.61 and 0.66 were obtained for the MSQOL physical and mental, respectively. Moreover, good correlation coefficient was obtained for the CIQ (Gamma?=?0.76) while fair correlations of 0.28 and 0.33 were obtained for the MSQOL physical and mental, respectively. The MCIDs were approximately 0.50, 1.5 and 2.5 points for the CIQ, MSQOL physical and mental, respectively. Conclusions: In contrast to the MSQOL, the CIQ was responsive outcome measure in detecting changes in participation restriction of patients with MS. Moreover, the MCID values obtained in this study will help the clinicians and researchers to determine if a patient with MS has experienced a true change following physiotherapy intervention.

• Implications for Rehabilitation

• The results provide valuable information regarding to the ability of two outcome measures (i.e. the CIQ and MSQOL) to detect treatment effects in patients with MS.

• In contrast to the MSQOL, the CIQ is a responsive measure to changes in participation restriction due to physiotherapy.

• A patient with MS had to change at least 0.50 point on the CIQ, 1.5 points on the MSQOL physical and 2.5 points on the MSQOL mental to be judged as having clinically changed.

     

Chronic morphine and tramadol re‐exposure induced an anti‐anxiety effect in prepubertal rats exposed neonatally to the same drugs

Anxiety disorders are among the most common mental disorders. Drugs that are often administered to manage medical problems cause rebound anxiety. The use of morphine and tramadol has increased in recent decades. In the present study, the effects of morphine and tramadol exposure during the neonatal and prepubertal periods on anxiety‐like behaviours in prepubertal rats were investigated. Male neonate rats were injected subcutaneously with saline, morphine or tramadol (3–21 mg/kg) on a daily basis from postnatal Day (P) 8 to P14. On P22, rats were divided into seven groups (saline/saline, saline/tramadol, saline/morphine, tramadol/saline, tramadol/tramadol, morphine/saline and morphine/morphine) and were injected with saline, tramadol or morphine for seven consecutive days. All rats were tested in an elevated plus maze (EPM) on P24 (acute effects), P27 (chronic effects) and P29. Locomotor activity was increased by the second and third exposure to the EPM. Re‐exposure to chronic morphine and tramadol resulted in increased locomotor activity, whereas acute and chronic administration of these drugs induced no notable difference. Anxiety decreased markedly after re‐exposure to tramadol and this anxiolytic‐like behaviour was more dominant in EPM re‐exposure in rats that had received higher doses of tramadol. Re‐exposure to tramadol elicited a stronger anxiolytic‐like behaviour than re‐exposure to morphine. It can be concluded that repeated morphine and tramadol administration during the neonatal period followed by re‐exposure to these drugs at an immature stage produces considerable anxiolytic‐like behaviour. Exposure to chronic morphine and tramadol during the neonatal period may affect the developing brain, which may induce long‐term changes in the opioid response.