Molecularly imprinted polymeric coatings for sensitive and selective gravimetric detection of artemether

Monitoring antimalarial drugs is necessary for clinical assays, human health, and routine quality control practices in pharmaceutical industries. Herein, we present the development of sensor coatings based on molecularly imprinted polymers (MIPs) combined with quartz crystal microbalance (QCM) for sensitive and selective gravimetric detection of an antimalarial drug: artemether. The MIP coatings are synthesized by using artemether as the template in a poly(methacrylic acid-co-ethylene glycol dimethacrylate) matrix. Artemether-MIP and the non-imprinted polymer (NIP) control or reference layers are deposited on 10 MHz dual-electrode QCM by spin coating (187 ± 9 nm layer thickness after optimization). The coatings are characterized by FTIR spectroscopy and atomic force microscopy that reveal marked differences among the MIP and NIP. The MIP-QCM sensor exhibits high sensitivity (0.51 Hz ppm⁻¹) with sub-10 ppm detection and quantification limits. The MIP-QCM sensor also exhibits a 6-fold higher sensitivity compared to the NIP-QCM, and a dynamic working range of 30–100 ppm. The response time of MIP-QCM devices for a single cycle of analyte adsorption, signal saturation, and MIP regeneration is less than 2.5 min. The sensor also demonstrates selectivity factors of artemether-MIP of 2.2 and 4.1 compared to artemisinin and lumefantrine, respectively. Reversibility tests reveal less than 5% variation in sensor responses over three cycles of measurements at each tested concentration. The MIP-QCM showed lower detection limits than conventional HPLC-UV, and faster response time compared to HPLC-UV and liquid chromatography-mass spectrometry (LC-MS).

Chemical structures of the antimalarial drugs: artemisinin, artemether (a methyl ether derivative of artemisinin), and lumefantrine.     

Investigation of antioxidant and anti-nociceptive potential of isoxazolone,pyrazolone derivatives,and their molecular docking studies

A series of new isoxazolone ( 3a – d ) and pyrazolone ( 4a – d ) derivatives were synthesized and assessed for their antioxidant and analgesic activity. Among synthesized compounds, 3b and 4b having nitro (NO₂) group show high analgesic activity at a dose of 6 mg/kg. Analgesic activity was further proceeded to explore the contribution of opioidergic mechanisms in the mediation of analgesic effects. Animals were administered with naloxone, a nonselective opioid inverse agonist, at the dose of 0.5 mg/kg. The results obtained suggested that the analgesic effects of the synthesized compounds were not reversed by naloxone, specifying that the compounds 3b and 4b do not follow the opioidergic pathway in order to relieve pain in animal models. Further, the binding interactions of compounds 3b and 4b were analyzed by docking them against nonopioid receptors COX-1 (3N8X) and COX-2 (3LN1). The results demonstrate the analgesic potential of isoxazolone and pyrazolone derivatives, especially compounds 3b and 4b can be considered promising lead molecules for further investigation and development into potent analgesic drugs. In addition, the antioxidant potential of compounds was also found to be related to better analgesic activity, thus providing an insight into the role of oxidative stress in the mediation of analgesia.     

Assessment of Circulating Biochemical Markers in Mice Receiving Cinnamon and Glycyrrhizin Under Carbon Tetrachloride Induced Hepatic Injury

The study evaluated the hepatoprotective activity of plant extracts of cinnamon and glycyrrhizin in distinct dosage ways to minimize the oxidative stress induced by carbon tetrachloride (CCl₄) in BALB/cJ inbred albino mice. Fifteen albino mice were divided into five groups, each group containing three mice. Group A was referred as positive control while group B, C, D and E were injected intraperitoneally with 1 mL/kg body weight of CCl₄ twice a week for 1 month. Group C and D were treated orally with isolated extracts of cinnamon @50 mg/kg and glycyrrhizin @50 mg/kg respectively on daily basis for 1 month. However, group E was treated orally with combination dose of cinnamon @50 mg/kg + glycyrrhizin @50 mg/kg body weight. The increase in the levels of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP), triglyceride (TG), malondialdehyde (MDA) and glucose were recorded in CCl₄ induced liver injury in mice while there is decrease in the levels of total protein (TP), reduced glutathione (GSH), Superoxide dismutase (SOD) and catalase (CAT) in CCL₄ intoxicated mice. Isolated therapy of plant extracts of cinnamon and glycyrrhizin decreased the levels of ALT, AST, ALP, MDA, TG and glucose whereas increase in TP, GSH, SOD and CAT was observed in plant extracts treated mice. The best restoration of all the above said parameters near to control was observed in group of mice treated with combination dose of cinnamon and glycyrrhizin @50 mg/kg. Therefore, the present study declared the antioxidative, anti-inflammatory and hepatoprotective activity of standardized extracts of cinnamon and glycyrrhizin and their potent defensive property.

     

Graphene oxide based crosslinker for simultaneous enhancement of mechanical toughness and self-healing capability of conventional hydrogels

Extraordinary self-healing efficiency is rarely observed in mechanically strong hydrogels, which often limits the applications of hydrogels in biomedical engineering. We have presented an approach to utilize a special type of graphene oxide-based crosslinker (GOBC) for the simultaneous improvement of toughness and self-healing properties of conventional hydrogels. The GOBC has been prepared from graphene oxide (GO) by surface oxidation and further introduction of vinyl groups. It has been designed in such a way that the crosslinker is able to form both covalent bonds and noncovalent interactions with the polymer chains of hydrogels. To demonstrate the efficacy of GOBC, it was incorporated in a conventional polyacrylamide (PAM) and polyacrylic acid (PAA) hydrogel matrix, and the mechanical and self-healing properties of the prepared hydrogels were investigated. In PAM-GOBC hydrogels, it has been observed that the mechanical properties such as tensile strength, Young''s modulus, and toughness are significantly improved by the incorporation of GOBC without compromising the self-healing efficiency. The PAM-GOBC hydrogel with a modulus of about 0.446 MPa exhibited about 70% stress healing efficiency after 40 h. Whereas, under the same conditions a PAM hydrogel with commonly used crosslinker N,N′-methylene-bis(acrylamide) of approximately the same modulus demonstrated no self-healing at all. Similar improvement of self-healing properties and toughness in PAA-GOBC hydrogel has also been observed which demonstrated the universality of the crosslinker. This crosslinker-based approach to improve the self-healing properties is expected to offer the possibility of the application of commonly used hydrogels in many different sectors, particularly in developing artificial tissues.

Introduction of a two-dimensional graphene oxide-based crosslinker simultaneously improve the mechanical and self-healing properties of hydrogels by offering an interesting combination of covalent and reversible hydrogen bonds to polymer backbones.     

What to listen for in the consultation. Breast cancer patients’ own focus on talking about acceptance-based psychological coping predicts decreased psychological distress and depression

Objective

To analyze whether qualitative themes in breast cancer patients’ self-presentations predicted symptoms of psychological distress and depression in order to improve the consultation process.

Methods

Ninety-seven breast cancer patients gave unstructured, 10-min self-presentations at their first consultation in a clinical registered trial (CRT identifier: NCT00990977). Self-presentations were categorized thematically and the most prevalent themes investigated as predictors for scores on the symptom check-list 90-revised (SCL-90-R) and the center for epidemiological studies depression scale (CES-D).

Results

Among the qualitative themes, only the percentage of words spent on talking about ‘Acceptance-based psychological coping’ was related to symptoms. In regression models controlling for age, education and time since diagnosis, a stronger focus on acceptance-based coping predicted less psychological distress and depression, respectively. A cross-validation including only the first few minutes of speech per patient confirmed these results and supported their practical utility in health consultations.

Conclusion

Patients’ focus on acceptance-based coping significantly predicted decreased psychological distress and depression, respectively. No other qualitative themes predicted symptoms. Doctor–patient studies may benefit from combined qualitative–quantitative methods.

Practice implications

While quantitative symptom assessment is important for a consultation, health care providers may improve their understanding of patients by attending to patients’ presentations of acceptance-based psychological coping.     

A systematic review and meta-analysis of biological treatments targeting tumour necrosis factor α for sciatica

Purpose

Systematic review comparing biological agents, targeting tumour necrosis factor α, for sciatica with placebo and alternative interventions.

Methods

We searched 21 electronic databases and bibliographies of included studies. We included randomised controlled trials (RCTs), non-RCTs and controlled observational studies of adults who had sciatica treated by biological agents compared with placebo or alternative interventions.

Results

We pooled the results of six studies (five RCTs and one non-RCT) in meta-analyses. Compared with placebo biological agents had: better global effects in the short-term odds ratio (OR) 2.0 (95 % CI 0.7–6.0), medium-term OR 2.7 (95 % CI 1.0–7.1) and long-term OR 2.3 [95 % CI 0.5 to 9.7); improved leg pain intensity in the short-term weighted mean difference (WMD) −13.6 (95 % CI −26.8 to −0.4), medium-term WMD −7.0 (95 % CI −15.4 to 1.5), but not long-term WMD 0.2 (95 % CI −20.3 to 20.8); improved Oswestry Disability Index (ODI) in the short-term WMD −5.2 (95 % CI −14.1 to 3.7), medium-term WMD −8.2 (95 % CI −14.4 to −2.0), and long-term WMD −5.0 (95 % CI −11.8 to 1.8). There was heterogeneity in the leg pain intensity and ODI results and improvements were no longer statistically significant when studies were restricted to RCTs. There was a reduction in the need for discectomy, which was not statistically significant, and no difference in the number of adverse effects.

Conclusions

There was insufficient evidence to recommend these agents when treating sciatica, but sufficient evidence to suggest that larger RCTs are needed.

Electronic supplementary material

The online version of this article (doi:10.1007/s00586-013-2739-z) contains supplementary material, which is available to authorized users.     

Approximate relative fatigue life estimation methods for thin-walled monolithic ceramic crowns

Objectives

The objective is to establish an approximate relative fatigue life estimation method under simulated mastication load for thin-walled monolithic restorations.