Novel multimeric IL-1 receptor antagonist for the treatment of rheumatoid arthritis

Protein therapeutics targeting inflammatory mediators have shown great promise for the treatment of autoimmunities such as rheumatoid arthritis (RA). However, a significant challenge in this area has been their low in vivo stability and consequently their severely compromised therapeutic efficacy. One such therapeutic molecule IL-1 receptor antagonist (IL-1ra), used in the treatment of rheumatoid arthritis, has displayed only modest efficacy in human clinical trials owing to its short biological half-life. Herein, we report a novel approach to conglomerate individual protein entities into a drug depot by incorporation of an amyloidogenic motif Lys-Phe-Phe-Glu (KFFE) thereby dramatically improving their systemic persistence and in turn their therapeutic efficacy in a mice model of autoimmune arthritis. (C) 2014 Elsevier Ltd. All rights reserved.

Absence of systemic toxicity in mouse model towards BaTiO3 nanoparticulate based eluate treatment

One of the existing issues in implant failure of orthopedic biomaterials is the toxicity induced by the fine particles released during long term use in vivo, leading to acute inflammatory response. In developing a new class of piezobiocomposite to mimic the integrated electrical and mechanical properties of bone, bone-mimicking physical properties as well as in vitro cytocompatibility properties have been achieved with spark plasma sintered hydroxyapatite (HA)-barium titanate (BaTiO3) composites. However, the presence of BaTiO3 remains a concern towards the potential toxicity effect. To address this issue, present work reports the first result to conclusively confirm the non-toxic effect of HA-BaTiO3 piezobiocomposite nanoparticulates, in vivo. Twenty BALB/c mice were intraarticularly injected at their right knee joints with different concentrations of HA-BaTiO3 composite of up to 25 mg/ml. The histopathological examination confirmed the absence of any trace of injected particles or any sign of inflammatory reaction in the vital organs, such as heart, spleen, kidney and liver at 7 days post-exposure period. Rather, the injected nanoparticulates were found to be agglomerated in the vicinity of the knee joint, surrounded by macrophages. Importantly, the absence of any systemic toxicity response in any of the vital organs in the treated mouse model, other than a mild local response at the site of delivery, was recorded. The serum biochemical analyses using proinflammatory cytokines (TNF-alpha and IL-1 beta) also complimented to the non-immunogenic response to injected particulates. Altogether, the absence of any inflammatory/ adverse reaction will open up myriad of opportunities for BaTiO3 based piezoelectric implantable devices in biomedical applications.

Compressive flow behavior of Al-Si based alloy: Role of heat treatment

The flow characteristics of a near eutectic Al-Si based cast alloy have been examined in compression at strain rates varying from 3 x 10(-4) to 10(2) s(-1) and at three different temperatures, i.e., room temperature (RT), 100 degrees C and 200 degrees C. The dependence of the flow behavior on heat treatment is studied by testing the alloy in non-heat treated (NHT) and heat treated (HT) conditions. The heat treatment has strong influence on strain rate sensitivity (SRS), strength and work hardening behavior of the alloy. It is observed that the strength of the alloy increases with increase in strain rate and it increases more rapidly above the strain rate of 10(-1) s(-1) in HT condition at all the temperatures, and at 100 degrees C and 200 degrees C in NHT condition. The thermally dependent process taking place in the HT matrix is responsible for the observed greater SRS in HT condition. The alloy in HT condition exhibits a larger work hardening rate than in NHT condition during initial stages of straining. However, the hardening rate decreases more sharply at higher strains in HT condition due to precipitate shearing and higher rate of Si particle fracture. Thermal hardening is observed at 200 degrees C in NHT condition due to precipitate formation, which results in increased SRS at higher temperatures. Thermal softening is observed in HT condition at 200 C due to precipitate coarsening, which leads to a decrease in SRS at higher temperatures. Stress simulations by a finite element method support the experimentally observed particle and matrix fracture behavior. A negative SRS and serrated flow are observed in the lower strain rate regime (3 x 10(-4)-10(-2) s(-1)) at RT and 100 degrees C, in both NHT and HT conditions. The observations show that both dynamic strain aging (DSA) and precipitate shearing play a role in serrated flow. (C) 2015 Elsevier B.V. All rights reserved.

Effects of Interface Treatment on the Fatigue Behavior of Shape Memory Alloy Reinforced Polymer Composites

Interfacial properties of Shape Memory Alloy (SMA) reinforced polymer matrix composites can be enhanced by improving the interfacial bonding. This paper focuses on studying the interfacial stresses developed in the SMA-epoxy interface due to various laser shot penning conditions. Fiber-pull test-setup is designed to understand the role of mechanical bias stress cycling and thermal actuation cycling. Phase transformation is tracked over mechanical and thermal fatigue cycles. A micromechanics based model developed earlier based on shear lag in SMA and energy based consistent homogenization is extended here to incorporate the stress-temperature phase diagram parameters for modeling fatigue.

Additive effect of zoledronic acid and alfacalcidol in the treatment of disuse osteoporosis in rats

Objectives: Disuse by bed rest, limb immobilization or space flight causes rapid bone loss. We conducted the present study to investigate the therapeutic effects of zoledronic acid (ZOL), alone and in combination with alfacalcidol (ALP) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were divided into four groups: 1 - RHLI positive control; 2 - RHLI plus ZOL (50 mu g/kg, i.v. single dose); 3 - RHLI plus ALP (0.5 mu g/kg, oral gauge daily); 4- RHLI plus ALP (0.5 mu g/kg, oral gauge daily) plus ZOL (50 mu g/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of the treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: Combination therapy with ZOL plus ALP was more effective in decreasing bone porosity than each drug administered as monotherapy in RHLI rats. With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment of ZOL plus ALP was more effective than each drug administered as a monotherapy. Moreover, combination therapy using ZOL plus ALF was more effective in improving dry bone and ash weight, than single-drug therapy using ZOL or ALP in RHLI rats. Conclusions: These data suggest that combination therapy with ZOL plus ALP represents a potentially useful therapeutic option for the treatment of disuse osteoporosis. (C) 2014 Elsevier Editora Ltda. All rights reserved.

Biodiesel Exhaust Treatment with Dielectric Barrier Discharges Coupled with Industrial Waste Byproducts

Biodiesel run engines are gaining popularity since the last few years as a viable alternative to conventional petro-diesel based engines. In biodiesel exhaust the content of volatile organic compounds, oil mist, and mass of particulate matter is considerably lower. However, the concentration of oxides of nitrogen (NOx) is relatively higher. In this paper the biodiesel exhaust from a stationary engine is treated under controlled laboratory conditions for removal of NOx using dielectric barrier discharge plasma in cascade with adsorbents prepared from abundantly available industrial waste byproducts like red mud and copper slag. Results were compared with gamma-alumina, a commercial adsorbent. Two different dielectric barrier discharge (DBD) reactors were tested for their effectiveness under Repetitive pulses /AC energization. NOx removal as high as 80% was achieved with pulse energized reactors when cascaded with red mud as adsorbent.

Computation of power released during corona treatment on polymeric insulators under ac and dc excitation

With increasing energy demand, it necessitates to generate and transmit the electrical power with minimal losses. High voltage power transmission is the most economical way of transmitting bulk power over long distances. Transmission insulator is one of the main components used as a mechanical support and to electrically isolate the conductor from the tower. Corona from the hardware and conductors can significantly affect the performance of the polymeric insulators. In the present investigation a methodology is presented to evaluate the corona performance of the polymeric shed material under different environment conditions for both ac and dc excitation. The results of the comprehensive analysis on various polymeric samples and the power released from the corona electrode for both the ac and dc excitation are presented. Some interesting results obtained from the chemical analysis confirmed the presence of nitric acid species on the treated sample which in long term will affect the strength of the insulator, also the morphological changes were found to be varying for different experimental conditions. (C) 2015 The Authors. Published by Elsevier Ltd.

Biodiesel Exhaust Treatment with HFAC Plasma supported by Red Mud: Study on DeNOx and power consumption

The concentration of Nitrogen Oxides (NOx) in engines which use biodiesel as fuel is higher compared to conventional diesel engine exhaust. In this paper, an attempt has been made to treat this exhaust using a combination of High frequency AC (HFAC) plasma and an industrial waste, Red Mud which shows proclivity towards Nitrogen dioxide (NO2) adsorption. The high frequency AC source in combination with the proposed compact double dielectric plasma reactors is relatively more efficient in converting Nitric Oxide (NO) to NO2. It has been shown that the plasma treated gas enhances the activity of red mud as an adsorbent/catalyst and about 60-72% NOx removal efficiency was observed at a specific energy of 250 J/L. The advantage in this method is the cost effectiveness and abundant availability of the waste red mud in the industry. Further, power estimation studies were carried out using Manley's equation for the two reactors employed in the experiment and a close agreement between experimental and predicted powers was observed. (C) 2015 The Authors. Published by Elsevier Ltd.

Effect of combined treatment with zoledronic acid and propranolol on mechanical strength in an rat model of disuse osteoporosis

Objectives: A model that uses right hind-limb unloading of rats is used to study the consequences of skeletal unloading during various conditions like space flights and prolonged bed rest in elderly. This study was aimed to investigate the additive effects of antiresorptive agent zoledronic acid (ZOL), alone and in combination with propranolol (PRO) in a rat model of disuse osteoporosis. Methods: In the present study, 3-month-old male Wistar rats had their right hind-limb immobilized (RHLI) for 10 weeks to induce osteopenia, then were randomized into four groups: 1-RHLI positive control, 2-RHLI plus ZOL (50 mu g/kg, i.v. single dose), 3-RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week), 4-RHLI plus PRO (0.1 mg/kg, s.c. 5 days per week) plus ZOL (50 mu g/kg, i.v. single dose) for another 10 weeks. One group of non-immobilized rats was used as negative control. At the end of treatment, the femurs were removed and tested for bone porosity, bone mechanical properties, and bone dry and ash weight. Results: With respect to improvement in the mechanical strength of the femoral mid-shaft, the combination treatment with ZOL plus PRO was more effective than ZOL or PRO monotherapy. Moreover, combination therapy using ZOL plus PRO was more effective in improving dry bone weight and preserved the cortical bone porosity better than monotherapy using ZOL or PRO in right hind-limb immobilized rats. Conclusions: These data suggest that this combined treatment with ZOL plus PRO should be recommended for the treatment of disuse osteoporosis. (C) 2014 Elsevier Editora Ltda. All rights reserved.

Surface modification of titania aerogel films by oxygen plasma treatment for enhanced dye adsorption

Titania aerogels were synthesized by sol-gel route followed by ambient pressure subcritical drying technique. The aerogels synthesized in the present work possess a maximum surface area of 252 m(2)/g. The pore size distribution is between 2 and 30 nm which confirms their mesoporosity. The oxygen plasma treatment on titania aerogel thin films improved the surface area up to 273 m(2)/g and produced additional hydrophilic groups on the surface. It is confirmed by BET surface area, XPS and thermal analysis in conjunction with dye adsorption studies. After plasma treatment the dye adsorption capacity was increased 2.5 times higher than that of untreated aerogel film. The increased surface area and the hydrophilic groups generated on the titania aerogel surface during plasma treatment are responsible for enhanced dye adsorption. The overall nanoporous morphology of titania aerogel is preserved after plasma treatment. (C) 2015 Elsevier B.V. All rights reserved.

Successful treatment of biofilm infections using shock waves combined with antibiotic therapy

Many bacteria secrete a highly hydrated framework of extracellular polymer matrix on suitable substrates and embed within the matrix to form a biofilm. Bacterial biofilms are observed on many medical devices, endocarditis, periodontitis and lung infections in cystic fibrosis patients. Bacteria in biofilm are protected from antibiotics and >1,000 times of the minimum inhibitory concentration may be required to treat biofilm infections. Here, we demonstrated that shock waves could be used to remove Salmonella, Pseudomonas and Staphylococcus biofilms in urinary catheters. The studies were extended to a Pseudomonas chronic pneumonia lung infection and Staphylococcus skin suture infection model in mice. The biofilm infections in mice, treated with shock waves became susceptible to antibiotics, unlike untreated biofilms. Mice exposed to shock waves responded to ciprofloxacin treatment, while ciprofloxacin alone was ineffective in treating the infection. These results demonstrate for the first time that, shock waves, combined with antibiotic treatment can be used to treat biofilm infection on medical devices as well as in situ infections.

Effect of semi-solid heat treatment on elevated temperature plasticity of 304L stainless steel

The present work explores the potential of semi-solid heat treatment technique by elucidating its effect on the plastic behavior of 304L SS in hot working domain. To accomplish this objective, hot isothermal compression tests on 304L SS specimens with semi-solid heat treatment and conventional annealing heat treatment have been carried out within a temperature range of 1273-1473 K and strain rates ranging from 0.01 to 1 s(-1). The dynamic flow behavior of this steel in its conventional heat-treated condition and semi-solid heat-treated condition has been characterized in terms of strain hardening, temperature softening, strain rate hardening, and dynamic flow softening. Extensive microstructural investigation has been carried out to corroborate the results obtained from the analysis of flow behavior. Detailed analysis of the results demonstrates that semi-solid heat treatment moderates work hardening, strain rate hardening, and temperature sensitivity of 304L SS, which is favorable for hot deformation. The post-deformation hardness values of semi-solid heat-treated steel and conventionally heat-treated steel were found to remain similar despite the pre-deformation heat treatment conditions. The results obtained demonstrate the potential of semi-solid heat treatment as a pre-deformation heat treatment step to effectively reduce the strength of the material to facilitate easier deformation without affecting the post-deformation properties of the steel.

Dual Drug Conjugate Loaded Nanoparticles for the Treatment of Cancer

Two antineoplastic agents, Imatinib (IM) and 5-Fluorouracil (FU) were conjugated by hydrolysable linkers through an amide bond and entrapped in polymeric Human Serum Albumin (HSA) nanoparticles. The presence of dual drugs in a common carrier has the advantage of reaching the site of action simultaneously and acting at different phases of the cell cycle to arrest the growth of cancer cells before they develop chemoresistance. The study has demonstrated an enhanced anticancer activity of the conjugate, and conjugate loaded stealth HSA nanoparticles (NPs) in comparison to the free drug in A-549 human lung carcinoma cell line and Zebra fish embryos (Danio rerio). Hydrolysability of the conjugate has also been demonstrated with complete hydrolysis being observed after 12 h. In vivo pharmacodynamics study in terms of tumor volume and pharmacokinetics in mice for conjugate (IM-SC-FU) and conjugate loaded nanoparticles showed significant anti-cancer activity. The other parameters evaluated were particle size (86nm), Poly Dispersive Index (PDI) (0.209), zeta potential (-49mV), drug entrapment efficiency (96.73%) and drug loading efficiency (89%). Being in stealth mode gives the potential for the NPs to evade Reticulo-Endothelial system (RES), achieve passive targeting by Enhanced Permeation Retention (EPR) effect with controlled release of the therapeutic agent. As the conjugate cleaves into individual drugs in the tumor environment, this promises better suppression of cancer chemoresistance by delivering dual drugs with different modes of action at the same site, thereby synergistically inhibiting the growth of cancerous tissue.