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.     

Association between sleep duration and sleep quality with sugar and sugar-sweetened beverages intake among university students

Background and aim

Both short sleep duration and intake of sugar or sugar-sweetened beverages (SSBs) are associated with weight gain; but the linkage between sleep characteristics and sugar or SSBs intake was less studied. We aimed to evaluate the associations of sleep duration and sleep quality with sugar and SSBs intake among Iranian adults.

Method

This cross-sectional study consisted of 395 adults chosen among students of Isfahan University of Medical Sciences, based on a multistage cluster random sampling method. Sleep characteristics and dietary intakes and were assessed using the Pittsburgh Sleep Quality Index (PSQI) and a 147-item validated food frequency questionnaire, respectively.

Results

Mean age and percentage of women in the study population were 22.79 (year) and 51.8%, respectively. No significant difference was observed between sleep duration and sugar intake, but short sleepers (< 6 h/d) had higher consumption of SSBs intake (86.54 vs. 65.73 g/day; P = 0.05) in comparison with those who had more than 8 h/d of sleep. Poor quality sleepers had significantly higher intake of SSBs compared with those with good quality of sleeping (87.09 vs. 56.73 g/day; P = 0.004). No significant correlation was found between sleep duration and SSBs intake. However, sleep quality score was positively correlated with SSBs intake (r_p:0.14, P = 0.007) in whole population, such that higher quality score (defined as poor sleep quality) was correlated with greater consumption of SSBs. Similar results were found in younger individuals (r_p:0.27, P = 0.002) and non-obese participants (r_p:0.14, P = 0.006).

Conclusion

We found that sleep duration was not associated with sugar or SSBs intake in Iranian adults. Poor sleep quality was correlated with high consumption of SSBs, especially in younger and non-obese individuals. More prospective investigations are required to confirm these findings.

     

The Use of Cellulose Nanocrystals for Potential Application in Topical Delivery of Hydroquinone

Nanotechnology‐based drug delivery systems can enhance drug permeation through the skin and improve the drug stability. The biodegradability and biocompatibility of cellulose nanocrystals have made these nanoparticles good candidates to use in biomedical applications. The hyperpigmentation is a common skin disorder that could be caused by number of reasons such as sun exposure and pregnancy. Hydroquinone could inhibit the production of melanin and eliminate the discolorations of skin. This study is aimed at introducing cellulose nanocrystals as suitable carriers for drug delivery to skin. Prepared cellulose nanocrystals were characterized by dynamic light scattering and atomic force microscopy. The size of cellulose nanocrystals determined using dynamic light scattering was 301 ± 10 nm. Hydroquinone–cellulose nanocrystal complex was prepared by incubating of hydroquinone solution in cellulose nanocrystals suspension. The size of hydroquinone–cellulose nanocrystal complex determined using dynamic light scattering was 310 ± 10 nm. The hydroquinone content of the hydroquinone–cellulose complex was determined using UV/vis spectroscopy. Hydroquinone was bound to cellulose nanocrystals representing 79.3 ± 2% maximum binding efficiency when 1.1 mg hydroquinone was added to 1 mL of cellulose nanocrystals suspension (2 mg cellulose nanocrystal). The hydroquinone–cellulose nanocrystal complex showed an approximately sustained release profile of hydroquinone. Approximately, 80% of bound hydroquinone released in 4 h.     

Preparation and Optimization of Chitosan/pDNA Nanoparticles Using Electrospray

Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - Chitosan (CS), as a natural polymer, has received a great deal of attention as a carrier for delivery of...