Isometric exercise induces analgesia and reduces inhibition in patellar tendinopathy

BACKGROUND: Few interventions reduce patellar tendinopathy (PT) pain in the short term. Eccentric exercises are painful and have limited effectiveness during the competitive season. Isometric and isotonic muscle contractions may have an immediate effect on PT pain. METHODS: This single-blinded, randomised cross-over study compared immediate and 45 min effects following a bout of isometric and isotonic muscle contractions. Outcome measures were PT pain during the single-leg decline squat (SLDS, 0-10), quadriceps strength on maximal voluntary isometric contraction (MVIC), and measures of corticospinal excitability and inhibition. Data were analysed using a split-plot in time-repeated measures analysis of variance (ANOVA). RESULTS: 6 volleyball players with PT participated. Condition effects were detected with greater pain relief immediately from isometric contractions: isometric contractions reduced SLDS (mean±SD) from 7.0±2.04 to 0.17±0.41, and isotonic contractions reduced SLDS (mean±SD) from 6.33±2.80 to 3.75±3.28 (p<0.001). Isometric contractions released cortical inhibition (ratio mean±SD) from 27.53%±8.30 to 54.95%±5.47, but isotonic contractions had no significant effect on inhibition (pre 30.26±3.89, post 31.92±4.67; p=0.004). Condition by time analysis showed pain reduction was sustained at 45 min postisometric but not isotonic condition (p<0.001). The mean reduction in pain scores postisometric was 6.8/10 compared with 2.6/10 postisotonic. MVIC increased significantly following the isometric condition by 18.7±7.8%, and was significantly higher than baseline (p<0.001) and isotonic condition (p<0.001), and at 45 min (p<0.001). CONCLUSIONS: A single resistance training bout of isometric contractions reduced tendon pain immediately for at least 45 min postintervention and increased MVIC. The reduction in pain was paralleled by a reduction in cortical inhibition, providing insight into potential mechanisms. Isometric contractions can be completed without pain for people with PT. The clinical implications are that isometric muscle contractions may be used to reduce pain in people with PT without a reduction in muscle strength.

Targeting VEGF with LNA-stabilized G-rich oligonucleotide for efficient breast cancer inhibition

In this study, we investigated the efficacy of an LNA (locked nucleic acid)-modified DNA aptamer named RNV66 targeting VEGF against various breast cancer cell lines. Our results demonstrate that RNV66 efficiently inhibits breast cancer cell proliferation both in vitro and in vivo. Introduction of LNA nucleotides were crucial for higher efficacy. Furthermore, the binding interaction of RNV66 with VEGF was investigated using molecular dynamic simulations leading to the first computational model of the LNA aptamer-VEGF complex blocking its interaction with VEGF-receptor.

Competitive inhibition of survivin using a cell-permeable recombinant protein induces cancer-specific apoptosis in colon cancer model

Endogenous survivin expression has been related with cancer survival, drug resistance, and metastasis. Therapies targeting survivin have been shown to significantly inhibit tumor growth and recurrence. We found out that a cell-permeable dominant negative survivin (SurR9-C84A, referred to as SR9) competitively inhibited endogenous survivin and blocked the cell cycle at the G1/S phase. Nanoencapsulation in mucoadhesive chitosan nanoparticles (CHNP) substantially increased the bioavailability and serum stability of SR9. The mechanism of nanoparticle uptake was studied extensively in vitro and in ex vivo models. Our results confirmed that CHNP-SR9 protected primary cells from autophagy and successfully induced tumor-specific apoptosis via both extrinsic and intrinsic apoptotic pathways. CHNP-SR9 significantly reduced the tumor spheroid size (three-dimensional model) by nearly 7-fold. Effects of SR9 and CHNP-SR9 were studied on 35 key molecules involved in the apoptotic pathway. Highly significant (4.26-fold, P≤0.005) reduction in tumor volume was observed using an in vivo mouse xenograft colon cancer model. It was also observed that net apoptotic (6.25-fold, P≤0.005) and necrotic indexes (3.5-fold, P≤0.05) were comparatively higher in CHNP-SR9 when compared to void CHNP and CHNP-SR9 internalized more in cancer stem cells (4.5-fold, P≤0.005). We concluded that nanoformulation of SR9 did not reduce its therapeutic potential; however, nanoformulation provided SR9 with enhanced stability and better bioavailability. Our study presents a highly tumor-specific protein-based cancer therapy that has several advantages over the normally used chemotherapeutics.

Synergistic effects of sodium lauroyl sarcosinate and glutamic acid in inhibition assembly against copper corrosion in acidic solution

© 2015 Elsevier B.V. All rights reserved. A self-assembled multilayer (SAM) from sodium lauroyl sarcosinate (SLS) and glutamic acid (GLU) is formed on copper surface. Its inhibition ability against copper corrosion is examined by electrochemical analysis and weight loss test. In comparison to SAM formed by just SLS or GLU, a synergistic effect is observed when the coexistence of SLS and GLU in SAM. The SLS/GLU SAM has an acicular multilayer structure, and SAM prepared under the condition of 5 mM SLS and 1 mM GLU shows the best protection efficiency. PM6 calculation reveals that the synergistic effect stems from interactions between SLS, GLU and cupric ions.

An acetylcholinesterase inhibition biosensor based on a reduced graphene oxide/silver nanocluster/chitosan nanocomposite for detection of organophosphorus pesticides

A sensitive electrochemical acetylcholinesterase (AChE) biosensor based on a reduced graphene oxide (rGO) and silver nanocluster (AgNC) modified glassy carbon electrode (GCE) was developed. rGO and AgNC nanomaterials with excellent conductivity, catalytic activity and biocompatibility offered an extremely hydrophilic surface, which facilitated the immobilization of AChE to fabricate the organophosphorus pesticide biosensor. Carboxylic chitosan (CChit) was used as a cross-linker to immobilize AChE on a rGO and AgNC modified GCE. The AChE biosensor showed favorable affinity to acetylthiocholine chloride (ATCl) and could catalyze the hydrolysis of ATCl. Based on the inhibition effect of organophosphorus pesticides on the AChE activity, using phoxim as a model compound, the inhibition effect of phoxim was proportional to its concentration ranging from 0.2 to 250 nM with a detection limit of 81 pM estimated at a signal-to-noise ratio of 3. The developed biosensor exhibited good sensitivity, stability and reproducibility, thus providing a promising tool for analysis of enzyme inhibitors and direct analysis of practical samples.

Inhibition of the secretion of LH in ovariectomised pigs by sustained but not repeated acute elevation of cortisol in the absence but not the presence of oestradiol

Prolonged stress is known to impair reproduction. It has been proposed that reproduction will also be impaired when a severe acute stress occurs during a period of elevated plasma concentrations of oestradiol, such as during the follicular phase of the oestrous cycle. In this experiment, we hypothesised that repeated acute and sustained elevation of cortisol would suppress the secretion of LH in ovariectomised pigs and that these effects would be enhanced in the presence of oestradiol negative feedback. Cortisol (or vehicle) was administered 12 hourly to ovariectomised pigs (n=6/treatment) for 8 days in the absence of oestradiol treatment and for a further 8 days during treatment with oestradiol. Vehicle was administered to 'control' pigs, 10 or 20 mg cortisol was administered i.v. to pigs to produce 'repeated acute' elevation of cortisol and 250 mg cortisol was administered i.m. to pigs to give a 'sustained' elevation of cortisol. Both before and during treatment with oestradiol, plasma concentrations of LH were monitored on the day before treatment, on the 4th and 8th days of treatment and following an i.v. injection of GnRH at the end of the 8th day of treatment. The repeated acute elevation of cortisol did not impair any parameters of LH secretion (i.e. mean plasma concentrations of LH, pulse amplitude or frequency, pre-LH pulse nadir or the LH response to GnRH) in the absence or in the presence of oestradiol. In contrast, when the elevation of cortisol was sustained, the mean plasma concentrations of LH and the pre-LH pulse nadir were significantly (P<0.05) lower on the 8th day of treatment than on the day before treatment and on the 4th day of treatment. Nevertheless, no other parameters of LH secretion were affected and these effects only occurred in the absence (not in the presence) of oestradiol. In conclusion, cortisol needed to be elevated for more than 4 days to impair the secretion of LH, and oestradiol did not enhance the impact of cortisol on LH secretion in ovariectomised pigs.

Comparative microarray analysis identifies commonalities in neuronal injury: evidence for oxidative stress, dysfunction of calcium signalling, and inhibition of autophagy-lysosomal pathway

Mitochondrial dysfunction, ubiquitin-proteasomal system impairment and excitotoxicity occur during the injury and death of neurons in neurodegenerative conditions. The aim of this work was to elucidate the cellular mechanisms that are universally altered by these conditions. Through overlapping expression profiles of rotenone-, lactacystin- and N-methyl-D-aspartate-treated cortical neurons, we have identified three affected biological processes that are commonly affected; oxidative stress, dysfunction of calcium signalling and inhibition of the autophagic-lysosomal pathway. These data provides many opportunities for therapeutic intervention in neurodegenerative conditions, where mitochondrial dysfunction, proteasomal inhibition and excitotoxicity are evident.

Electrochemical and DFT studies of quinoline derivatives on corrosion inhibition of AA5052 aluminium alloy in NaCl solution

Two quinoline derivatives, 8-aminoquinoline (8-AQ) and 8-nitroquinoline (8-NQ), have been used as inhibitors to examine their corrosion protection effect on AA5052 aluminium alloy in 3% NaCl solution. The weight-loss and electrochemical measurement have indicated that 8-AQ and 8-NQ play as anodic inhibitor to retard the anodic electrochemical process. SEM/EDS analysis clearly shows that 8-AQ and 8-NQ form a protective film on the AA5052 alloy surface. Density functional theory (DFT) calculation confirmed the formation of strong hybridization between the p-orbital of reactive sites in the inhibitor molecules and the sp-orbital of the Al atom. 8-aminoquinoline and 8-nitroquinoline may be useful as effective corrosion inhibitors for aluminium alloys.

Combination of calcium and magnesium ions prevents substrate inhibition and promotes biomass and lipid production in thraustochytrids under higher glycerol concentration

Effect of calcium and magnesium ions was studied in detail in batch mode in shake flask cultures of two fast growing strains of thraustochytrids (Aurantiochytrium sp. DBTIOC-18 and Schizochytrium sp. DBTIOC-1) for biomass and lipid production. These strains were previously isolated from Indian marine biodiversity. Screening of these two strains on different carbon and nitrogen sources revealed the suitability of glycerol over glucose and sodium nitrate over yeast extract for the cultivation of these strains. The presence of higher concentration of glycerol in the medium inhibited the glycerol utilization by the cell thus resulting in lower biomass and lipid production in both the strains. Supplementing media with calcium and magnesium ions promoted glycerol utilization thus resulted in a substantial rise in volumetric production of biomass (55.12 g L-1, 48.12 g L-1), fatty acid for biodiesel (27.14 g L-1, 22.15 g L-1) and docosahexaenoic acid (14.57 g L-1, 10.12 g L-1) with both strains Aurantiochytrium sp. DBTIOC-18 and Schizochytrium sp. DBTIOC-1, respectively. Growth profile study of these two strains showed further improvement in production of biomass, fatty acid for biodiesel and docosahexaenoic acid when cultures were extended up to 7 days. Finding of this work underlines the importance of calcium and magnesium salts in designing new fermentation strategies to prevent substrate inhibition and achieve high cell density culture under high nutrient concentration especially carbon sources.