Search

The immune system is a highly advanced and coordinated mechanism that allows a living organism to distinguish between "self" and "non-self". The host uses both innate and adaptive immune response mechanisms to identify and eliminate pathogenic microorganisms. Human immunoglobulin is the prominently used blood product in the clinical practice. Immunoglobulin applications have improved rapidly due to the exploration of its immunomodulatory and anti-inflammatory properties. This made this blood product into a precious and advanced tool in the treatment of numerous disease conditions which are linked with humoral immune deficiency or that cause immune system dysfunction. Human immunoglobulin (Ig) is used for Ig replacement therapy in both primary and secondary immunodeficiency conditions, for prevention and treatment of certain infections. It also acts as an immunomodulatory agent for autoimmune and inflammatory disorders. Therapeutic antibodies have been successfully used for the treatment of diverse pathological conditions. Drug development programs exclusively select highly specific antibodies that recognize a single disease-associated target. Hopefully this review will give an insight towards the immune system, the involvement of the specialized immune cells, their products and involvement in various immune disorders and pathological conditions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The stability and thermodynamic properties of an enzyme are the main factors that governing its applications in industry. With that intention we have immobilized the α-amylase onto synthesized chitosan-magnetite (CSM) composite and its modified forms by gluteraldehyde (CSM-GLA), glyoxal (CSM-GLY) and epichlorohydrin (CSM-ECH). In this study all the immobilized enzymes exhibited improved pH stability about 60-80% of relative activity at pH 9 compared to the free enzyme. The temperature stability at 60 °C is up to 50% of relative activity for covalently immobilized enzymes as enzyme become more rigid by covalent binding and so protected from the conformational changes caused by the environment. The thermal deactivation of the free and immobilized enzymes follows the first order kinetics. The t 1/2 and D-values were prolonged considerably in case of covalently immobilized enzymes, indicating better thermal stability than that of free and adsorbed ones. The Ed values 18.71, 32.00, 27.19 and 20.46 KJmol -1 for CSM-E, CSM-GLY-E, CSM-GLA-E and CSM-ECH-E described the high stability and resistance to heat inactivation. The Km values 0.525 ± 0.04, 0.57 ± 0.06, 0.65 ± 0.04 mg/mL and Vmax values 25 ± 0.06, 19.6 ± 0.02, 16.39 ± 0.01 μmol mg -1 min -1 for CSM-GLY-E, CSM-GLA-E and CSM-ECH-E showing better substrate affinity. The immobilized enzymes have exhibited about 60% of relative activity after 90 days of storage and very good reuse potential., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Despite the versatility of quantum dots (QDs) in optoelectronics and biomedical field, their toxicity risks remain a considerable hindrance for clinical applications. Cytotoxicity of Cadmium containing QDs is well documented and reveals that they are toxic to cells. Reports suggest that the presence of toxic elements at the QD core (e.g., cadmium, selenium) is responsible for its toxicity in in vivo and in vitro levels. Hence, here the toxicity of heavy metal free ZnSe/ZnS QDs on two scenarios were assessed, (i) HEK cells as in vitro system and (ii) Swiss Albino mice as in vivo model. Before toxicity analysis, QDs subjected to various optical and physico-chemical characterization methods such as absorption and emission spectra analysis, observation under U.V light, TEM, DLS, Zeta potential, FTIR, Raman and XPS spectra, ICP-OES, TGA and DTG curve. It is very necessary to characterize the synthesized QDs because their toxicity greatly influenced by the physico-chemical properties. On checking the vulnerability of HEK cells on exposure to ZnSe/ZnS QDs, the obtained results disclose that ZnSe/ZnS QDs showed merest impact on cellular viability at a concentration less than 100 μg/ml. Acute toxicity of 10 mg/kg ZnSe/ZnS QDs was studied in mice and no clinical or behavioural changes were observed. It did not induce any changes in haematological parameters and any loss of body or organ weight. Moderate pathological changes were evident only in the liver, all others organs like kidney, spleen and brain did not show any manifestations of toxicity. Current work lays substantial bedrock for safe biomedical and environmental application of ZnSe/ZnS QDs in near future., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Quantum dots (QDs) comprise an emerging group of materials with innumerable number of possibilities in biological research including cellular labelling. Among the leading members in this category, ZnSe/ZnS quantum dots (QDs) hold greater attractive possibilities in imaging primarily due to their higher biocompatibility and dispersibility. Nevertheless, the inherent toxicity of ZnSe/ZnS QDs is not yet completely explored which largely compromise most of their biomedical application potential. Strong blue emitting water soluble QDs effectively synthesized by aqueous phase route. Synthesized QDs further subjected to various optical and physicochemical characterization. Approximately 5-6 nm sized ZnSe/ZnS QDs illuminated bluish green fluorescence under UV lamp. Present study addresses possible adverse effects of ZnSe/ZnS QDs in hepatic system using HepG2 cells; which is the routinely employed in vitroliver cell model. A bundle of assays wasperformed out to reveal the cytotoxic nature of ZnSe/ZnS QDs and the mechanism behind it. Herein, absorption, distribution, metabolism, excretion and toxicity (ADME and T) of ZnSe/ZnS in mice were profiled in detail followed by intravenous (i.v.) and intraperitoneal (i.p.) administration at a dose of 10 mg/kg body weight. In a short review, it could be state that ZnSe/ZnS QDs did not exhibit any significant in vivo toxicity outcome in mice., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Fullerene comprises the major allotrope of carbon holding several fruitful potentials to be applied in various industrial and biomedical scenarios. Scientists have acquired large number of data on fullerene research using its derivatives like C60, C70 etc. Nevertheless, a precise focus on fullerene soot nanopaticles and its toxic impacts in living tissue is still behind mainstay even if it represents the crude parent form of all other derivatives. Present study addresses an acute toxicity profiling of fullerene soot nanoparticles in alveolar epithelial cells (A549) as a paradigm of pulmonary exposure. Surface functionalization was given for fullerene soot nanoparticles using dextran polymer as a mean to establish a stable homogenous dispersion (denoted as dFSNPs hereafter). Following functionalization, dFSNPs were characterized for various parameters including size, surface charge, morphology and functional groups using DLS, Zeta potential analysis, TEM and FT-IR measurements respectively. Effective dextran functionalization was evident from the characteristic peaks in FTIR spectra. Cell viability assessed using MTT and NRU assays; both of which showed a dose dependent cytotoxic response. Thymidine incorporation also confirmed similar trend in viability rate. In accordance with literatures, DCFHDA assay confirmed free radical scavenging activity of fullerene nanoparticles. An altered cellular morphology was observed under fluorescent microscope. Sub-cellular functionalities including lysosomal integrity and mitochondrial stability were found to be compromised at highest tested concentration of dFSNPs (160 μg/ml) without any genotoxic impacts within nuclear premises. FACS analysis following Annexin-PI staining confirmed apoptotic cell death. Hence the overall study substantiated dose dependent toxicity of dFSNPs which is likely to occur during pulmonary exposure., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Graphene is an sp 2 hybridized allotrope of carbon with a honeycomb lattice structure that has many applications in biomedicine owing to its unique physico-chemical properties. Graphene has attracted much interest from scientists for its biomedical potential, including in drug/gene delivery, fluorescent labeling of target analytes, tissue engineering, regenerative medicine and MRI contrast enhancement. However, there are very limited data available concerning the toxicity of graphene, and efforts have been made to study the bio-nano interactions of Pluronic functionalized reduced graphene oxide (rGO-P) in animal models. The present study aimed to evaluate the systemic toxicity of rGO-P and its ability to cross the blood-brain barrier in Swiss Albino mice subject to acute exposure to 10 mg kg -1 body weight of rGO-P. Prolonged exposure was evaluated in female Wistar rats by analyzing feto-placental transmission and any associated developmental neurotoxicity after intravenous administration of 5 mg kg -1 and 10 mg kg -1 body weight of rGO-P. Biodistribution analysis using confocal Raman mapping indicated that tiny amounts of rGO-P accumulated in major organs of both dams and pups, with no evident toxic response. The accumulation of rGO-P in various tissues of rat pups born to treated dams is ample evidence of feto-placental transmission. The present study clearly suggests that rGO-P is not toxic under any of the experimental conditions. These findings can therefore be carried forward for application of rGO-P in drug/gene delivery, early diagnosis and treatment of various diseases in neonates and adults. The results of the study show that rGO-P is an auspicious and promising material for future healthcare applications.

Elevated application potential of fullerene C 60 paved the way to think on its adverse effect when it reaches to biological system and environment. Though fullerenes are insoluble in water, various strategies are employed to make it soluble. Method of solubilization with organic solvents, yield cytotoxic responses both in vitro and in vivo. In this study, dextran was used to stabilize C 60 particle. Fourier transformed-infrared spectroscopy (FT-IR) and transition electron microscopy (TEM) were used for characterization and it confirms effective surface stabilization and morphological characteristics. This was followed by various cytotoxicity studies to evaluate its bio-nano interactions. The results of the study suggest that the dextran stabilized C 60 nanoparticles (Dex-C 60 ) forms uniform suspension in water and was stable up to 72 h. The C6 glial cell-Dex-C 60 interactions indicated that the Dex-C 60 nanoparticles penetrate deeper into the cells and cause dose dependent toxic response. The result of the study recommended that Dex-C 60 nanoparticles should undergo intensive risk assessment before biomedical applications and should take proper safety measure to avoid its entry to the environment., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chitra Disinfection Gateway is meant for the decontamination of personnel entering a cleaner private space from a public space. This is equipped with an arrangement for generating hydrogen peroxide mist and ultraviolet rays. Hydrogen peroxide mist will decontaminate clothes, hands and the bags a person carries. The ultraviolet system will decontaminate the chamber once the person has moved out. The system is controlled electronically by sensors and actuators. The sensors fixed in the chamber detect the entry of a person and initiates the hydrogen peroxide atomization process. The person is required to walk through the chamber. When the person exits the chamber, the system will put off the hydrogen peroxide atomization system and will turn on the UV lamp inside the chamber to decontaminate it. The ultraviolet system will be ON for a predefined time and after the process, the next person can enter the walkway. The whole process takes a maximum of 40 s. The safety and efficacy of the system have been validated experimentally through both in vivo and in vitro studies., (© Indian National Academy of Engineering 2020.)

Fullerene C70 with symmetric nanostructure and unique properties that open up leeway for both material science and healthcare applications. Poor water dispersity and limited knowledge about its associated toxicity hinders the biomedical scope of C70. These restraining factors need to be addressed. Dextran, natural and water-soluble polymer was used to improve the dispersity of C70 in water. Dextran coating on C70 successfully yielded stable dispersion of C70 in water with remarkable cytocompatibility with L929 fibroblast cells. The dextran-coated C70 was characterized using different characterization techniques such as fourier transformed-infrared spectroscopy (FT-IR), transition electron microscopy (TEM), dynamic light scattering (DLS) and zeta potential. The cell viability assays suggested that the L929 cells retained more than 80% cell viability after 24 h treatment with dextran-coated C70. The mitochontrial membrane potential of the treated cells were found to be uncompromised. Fluorescent imaging techniques done with the aim of evaluating the integrity of lysosomes detected no potential toxicity in L929 cells treated with dextran-coated C70. Actin filaments showed intact organelles when viewed using Rhodamine- phalloidin staining after 24 h post-treatment. DAPI staining also revealed the integrity of nucleus after exposure to dextran-coated C70. The calcein AM/PI flow cytometry analysis further confirmed that dextran-coated C70 kept cell viability of treated cells above 80% for all concentrations. The results points out the scope of dextran-coated C70 for various health care applications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

As obvious from the basic prerequisite of any particle in nanoscale, Zinc oxide nanoparticles (ZnO NPs) possess numerous tunable properties distinct from their bulk formulations. Emerging innovations in various sectors of nanotechnology are exploiting ZnO NPs largely. This inturn picks up the occasions of human exposure irrespective of the application fields. Although the platform of nanotoxicology has been garnished with nano-bio interaction studies using different cell lines, a few are existing so far comprising primary cells which symbolize realistic in vivo environment. The present study addresses the neurotoxic potential of ZnO NPs using primary astrocytes isolated from post-natal 0-2 day old rat pups. Cells were cultured and maintained in DMEM F12 followed by purification. ZnO NPs generated by wet chemical method was then characterized both physico chemically and biologically. All of the techniques confirmed homogenous distribution of NPs and ensured enough colloidal stability. Bio-nano interaction studies commence on cell viability assays (MTT and NRU) and both of which confirmed dose and time dependent cytotoxicity. Alterations within cellular morphology, cytoskeletal arrangement, lysosomal stability, mitochondrial membrane potential (MMP) and caspase activation were evaluated by standardized techniques. All of the assays substantiated significant toxic consequences in astrocytes with characteristic hall marks. Apoptotic cell death was noted without any deformations of nuclear material. A comparative toxicity study using ZnO NPs, ZnCl 2 and ZnO bulk form was performed which confirmed nanospecific toxicity of ZnO NPs. Overall study evidently provide cautious information that ZnO NPs is capable of eliciting serious neuronal tissue damages which can turn out to be fatal during prolonged exposure., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Nano technological research offered uncountable opportunities for engineered nanoparticles (ENPs) in the field of biomedical, pharmaceutical, agricultural, cosmetics, textiles, automobiles and electronic industry. Large scale commercial production and use of nanoparticles with smaller size and characteristic physico-chemical properties enhance the possibility of amenable toxicity to the environment. Primary important species of the ecosystem like bacteria, algae, fishes and plants are at high risk with nanoparticle (NP) toxicity. ENP distributed in air, water and soil can directly affect the livelihood or even the existence of smaller organisms. In day-today life, human beings are getting exposed to thousands of NPs via dermal contact, inhalation or ingestion. Topical application of sunscreens and cosmetics containing ENPs has the potential to induce photo toxicity under ultra violet irradiation. ENP intentionally or non-intentionally enter into the body will affect the entire organ system and execute their toxicity even in reproduction and fetal developmental stages. Unfortunately the existing researches to evaluate the in vivo and in vitro toxic effects of ENPs are inefficient to give the exact nature and depth of toxicity. Hence an effort was made to discuss on the characteristics, classification, synthesis, applications and toxic potentials of various classes of commercially relevant ENPs along with a detailed review on currently available literatures., (Copyright © 2019 Elsevier Inc. All rights reserved.)

2D materials have gained spectacular status across various scientific and technological disciplines owing to their exceptional unique properties. The very recent member of 2D family, Black Phosphorus monolayers, known as Phosphorene have attracted recent scientific attention since its first exfoliation and appreciable rediscovery in 2014. Compared to other 2D materials and graphene analogs, it has outstanding properties like tunable band gap, good carrier mobility, excellent ON-OFF current ratio, potent in vivo biocompatibility and non-toxic biodegradability. Although the outlook of this material seems to be a promising candidate for future biomedical technology, its practical applications are still highly challenging. Unveiling those challenges by proper characterization and functionalization makes this material a mile stone for future theranostic and biomedicine scenario. This review has given precise attention to familiarize with the unique fundamental properties of black phosphorus, which makes it an excellent platform for future biomedical applications. Also underlines various synthesis procedures applicable for BP nanosheets and quantum dot synthesis. Its various biomedical applications including biosensors, cancer therapy, imaging and photothermal/photo acoustic/photodynamic therapy, drug delivery, neuronal regeneration, 3D printing scaffold etc., are subsequently reviewed. Furthermore this review briefly focused on the toxicity of this emerging material., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Recent developments in the field of fullerene C 60 and its derivatives suggest its suitability in a wide range of applications ranging from photovoltaic instruments, development of solar based cells, cosmetics to enzyme inhibition treatment, and so on. These innovative applications raised possibilities of intentional or oblivious human-particle contact leading to possible deleterious effects on human health. The current study deals with the interaction of dextran functionalized fullerene C 60 (Dex-C 60 ) on Chinese Hamster Ovary cells. The results showed that the cell viability was not affected by Dex-C 60 treatment even at higher concentrations. Treatment of Dex-C 60 did not affect mitochondrial membrane potential and the integrity of lysosomal and cytoskeletal membrane. DNA ladder assay and nuclear staining showed that the DNA remains intact, and no fragmentation or nuclear condensation was visible. From flow cytometry analysis, the viable population of treated cells was seemed to be remaining similar to that of untreated cells. Hence, from the current result, it is concluded that Dex-C 60 can be a potential candidate for various biomedical applications.

Graphene, sp 2 hybridized carbon framework of one atom thickness, is reputed as the strongest material to date. It has marked its impact in manifold applications including electronics, sensors, composites, and catalysis. Current state-of-the-art graphene research revolves around its biomedical applications. The two-dimensional (2D) planar structure of graphene provides a large surface area for loading drugs/biomolecules and the possibility of conjugating fluorescent dyes for bioimaging. The high near-infrared absorbance makes graphene ideal for photothermal therapy. Henceforth, graphene turns out to be a reliable multifunctional material for use in diagnosis and treatment. It exhibits antibacterial property by directly interacting with the cell membrane. Potential application of graphene as a scaffold for the attachment and proliferation of stem cells and neuronal cells is captivating in a tissue regeneration scenario. Fabrication of 2D graphene into a 3D structure is made possible with the help of 3D printing, a revolutionary technology having promising applications in tissue and organ engineering. However, apart from its advantageous application scope, use of graphene raises toxicity concerns. Several reports have confirmed the potential toxicity of graphene and its derivatives, and the inconsistency may be due to the lack of standardized consensus protocols. The present review focuses on the hidden facts of graphene and its biomedical application, with special emphasis on drug delivery, biosensing, bioimaging, antibacterial, tissue engineering, and 3D printing applications.

Titanate nanotubes (TiONts) are promising agents for biomedical applications. Microglial activation and associated oxidative burst are major challenges in drug delivery applications across the brain. Here, TiONts were designed for drug delivery systems by functionalizing them with (3-aminopropyl) triethoxysilane (APTES), their interactions and biocompatibility were studied in vitro using murine microglial BV-2 cells. TiONts-APTES exposure resulted in increased ROS production and transient mitochondrial hyperpolarization. However, there was no indication of microglial proliferation in BV-2 cells as suggested by cell cycle analysis and morphology evaluation. The endocytosis as well as passive diffusion mediated TiONts-APTES internalization were proved by transmission electron microscopy (TEM) with and without amiloride, an endocytosis inhibiting agent. In addition, the TiONts-APTES exhibited good biocompatibility on microglial BV-2 cells as revealed by the plasma membrane integrity, lysosmal membrane integrity, morphology and viability analysis., (Copyright © 2018. Published by Elsevier Inc.)

Phenolic heterocyclic imine based Schiff bases from Thiophene-2-carboxaldehyde and Pyrrole-2-carboxaldehyde were synthesized and characterized as novel antioxidants. The solvent effects of these Schiff bases were determined and compared with standard antioxidants, BHA employing DPPH assay and ABTS assay. Fixed reaction time and Steady state measurement were used for study. IC 50 and EC 50 were calculated. Structure-activity relationship revealed that the electron donating group in the phenolic ring increases the activity where as the electron withdrawing moiety decreases the activity. The Schiff base derivatives showed antioxidant property by two different pathways namely SPLET and HAT mechanisms in DPPH assay. While in ABTS method, the reaction between ABTS radical and Schiff bases involves electron transfer followed by proton transfer (ET-PT) mechanism. The cytotoxicity of these compounds has been evaluated by MTT assay. The results showed that all these compounds are non toxic in nature., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background & Objectives: Polyethylene terephthalate (PET) graft, designed and developed at our institute for vascular reconstruction, is porous to promote optimal incorporation and neointima formation, requiring pre-clotting or biomodification by sealing the pores before implantation. The objective of this study was to characterize, test and perform preclinical evaluation of hydrogel (alginate dialdehyde cross-linked gelatin) sealed fluoropassivated PET vascular prosthesis in pig model, so as to avoid pre-clotting, for its safety and efficacy before employing the indigenous and less expensive graft for clinical use., Methods: Hydrogel sealed, fluoropassivated PET vascular prosthesis were tested for haemocompatibility and toxicity followed by small animal toxicology tests and in vivo experiments in pigs receiving implantation at thoracic aorta. All 33 animals received test as well as control grafts with a plan for phased explantation at 2, 12 and 26 weeks. All animals underwent completion angiogram at the end of procedure as well as before graft explantation., Results: Haemocompatibility tests for haemolysis and toxicity tests showed no adverse events in tested mice and rabbits. Completion angiogram showed intact anastamosis and patent graft in each animal in post-operative period and at explantation. Gross and histopathological examination showed well-encapsulated grafts, clean glistening neointima and no evidence of thrombus in both test and control grafts., Interpretation & Conclusions: Hydrogel sealed, fluoropassivated PET vascular prosthesis was found non-toxic, haemocompatible and remained patent in in vivo studies at planned intervals., Competing Interests: None.

Zinc oxide nanoparticles (ZnO NPs) are widely used in a variety of products and are currently being investigated for biomedical applications. However, they have the potential to interact with macromolecules like proteins, lipids and DNA within the cells which makes the safe biomedical application difficult. The toxicity of the ZnO NP is mainly attributed reactive oxygen species (ROS) generation. Different strategies like iron doping, polymer coating and external supply of antioxidants have been evaluated to minimize the toxic potential of ZnO NPs. Melatonin is a hormone secreted by the pineal gland with great antioxidant properties. The melatonin is known to protect cells from ROS inducing external agents like lipopolysaccharides. In the present study, the protective effect of melatonin on ZnO NPs mediated toxicity was evaluated using C6 glial cells. The Cytotoxicity, mitochondrial membrane potential and free radical formation were measured to study the effect of melatonin. Antioxidant assays were done on mice brain slices, incubated with melatonin and ZnO NPs. The results of the study reveal that, instead of imparting a protective effect, the melatonin pre-treatment enhanced the toxicity of ZnO NPs. Melatonin increased antioxidant enzymes in brain slices., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Graphene, a 2D carbon material has found vast application in biomedical field because of its exciting physico-chemical properties. The large planar sheet like structure helps graphene to act as an effective carrier of drug or biomolecules in enormous amount. However, limited data available on the biocompatibility of graphene upon interaction with the biological system prompts us to evaluate their toxicity in animal model. In this study organ distribution, clearance and toxicity of PEGylated reduced nanographene (PrGO) on Swiss Albino mice was investigated after intraperitoneal and intravenous administration. Biodistribution and blood clearance was monitored using confocal Raman mapping and indicated that PrGO was distributed on major organs such as brain, liver, kidney, spleen and bone marrow. Presence of PrGO in brain tissue suggests that it has the potential to cross blood brain barrier. Small amount of injected PrGO was found to excrete via urine. Repeated administration of PrGO induced acute liver injury, congestion in kidney and increased splenocytes proliferation in days following exposure. Hence the result of the study recommended that PrGO should undergo intensive safety assessment before clinical application or validated to be safe for medical use., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Although the toxicity/biocompatibility of hydroxyapatite nanoparticles (nano HA), a prospective nano biomaterial is extensively studied, its interaction on biological systems following chronic exposure is less exploited. In the present study, Wistar rats were given various concentrations of nano HA in the diet to determine the chronic toxicity and potential carcinogenicity. Altogether 140 rats were used for the study under various administration dosages along with control. The animals were sacrificed after 12months of controlled continuous dosing. All in-life parameters, including body weight, food consumption, clinical observations, survival, biochemical and hematology, were unaffected by the chronic exposure of nano HA orally. Similarly, gross and histopathological evaluation was also unchanged following exposure to nano HA. No evidence of nano HA-related lesions or Nano HA-induced neoplasia was suggested in this rodent bioassay study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A new bioactive calcium sulfate-based formulation (named 'BioCaS') has been developed for bone filler applications. This is a self-setting injectable cement where the preset form comprises bassanite obtained from the uniform submicron-sized precursor crystals of gypsum, modified with hydrogen orthophosphate ions. The results of the safety and efficacy evaluation of BioCaS cement, done as per the International Standards and guidelines, are presented in this paper. The study plan consisted of in vitro screening tests of cytotoxicity and haemolysis and in vivo biocompatibility evaluation, including an acute systemic toxicity test (in mice), an intracutaneous reactivity test (in rabbits), a pyrogen test (in rabbits) and a maximization sensitization test (in guinea pigs). The efficacy of the material in healing bone defects was investigated by implanting it in artificially created defects in rabbit femora, with clinically established hydroxyapatite porous ceramic as the control, followed by histological analysis at 12, 26 and 52 weeks. Set BioCaS cement consisted of hydrogen orthophosphate incorporating low-dimensional gypsum crystal lattices, the bioactivity of which has been identified by immersion in simulated body fluid. BioCaS was proved to be non-cytotoxic and non-haemolytic in the screening tests. In the live/dead assay, human osteoblast-like human osteosarcoma cells adhered well and spread on the surface of the material, attaining typical morphology and affirming the bone cell compatibility of the material. In the biocompatibility evaluation there were no acute systemic effects and the material proved non-pyrogenic. There was no intracutaneous erythemic or oedematous reactivity and no hypersensitivity observed in the Magnusson-Kligman method. The material satisfied the biocompatibility requirements. Bone implantation study revealed BioCaS to be osteoconductive and its efficacy of healing the experimental bone defects in rabbit femora is on a par with that of hydroxyapatite ceramic. The material resorbed at a pace matching that of new bone formation. This property of osteotransductivity will help the defect to heal and gain strength faster.

Some new Schiff bases (H 1 -H 7 ) have been synthesized by the condensation of 2-aminophenol, 2-amino-4-nitrophenol, 2-amino-4-methylphenol, 2-amino benzimidazole with thiophene-2-carboxaldehyde and pyrrole-2-carboxaldehyde. The structures of newly synthesized compounds were characterized by elemental analysis, FT-IR, 1 H NMR, UV-VIS, and single crystal X-ray crystallography. The in vitro antibacterial activity of the synthesized compounds has been tested against Salmonella typhi, Bacillus coagulans, Bacillus pumills, Escherichia coli, Bacillus circulans, Pseudomonas, Clostridium and Klebsilla pneumonia by disk diffusion method. The quantitative antimicrobial activity of the test compounds was evaluated using Resazurin based Microtiter Dilution Assay. Ampicillin was used as standard antibiotics. Schiff bases individually exhibited varying degrees of inhibitory effects on the growth of the tested bacterial species. The antioxidant activity of the synthesized compounds was determined by the 1,1-diphenyl-2-picrylhydrazyl(DPPH) method. IC 50 value of synthesized Schiff bases were calculated and compared with standard BHA., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The urge for the development and manufacture of new and effective antimicrobial agents is particularly demanding especially in the present scenario of emerging multiple drug resistant microorganisms. A promising initiative would be to converge nanotechnology to develop novel strategies for antimicrobial treatment. These distinct nano scale properties confer impressive antimicrobial capabilities to nanomaterials that could be exploited. Nanotechnology particularly modulates the physicochemical properties of organic and inorganic nanoparticles, rendering them suitable for various applications related to antimicrobial therapy compared to their bulk counterparts. However, a major issue associated with such usage of nanomaterials is the safety concern on heath care system. Hence, a thorough put knowledge on biocompatible nanostructures intended for antimicrobial therapy is needed., Methods: A systematic review of the existing scientific literature is being attempted here which includes the properties and applications of a few nano structured materials for antimicrobial therapy and also the mechanism of action of nanomaterials as antimicrobial agents. Silver (Ag), Graphene, Quantum dots (QDs), Zinc oxide (ZnO) and chitosan nanoparticles are taken as representatives of metals, semiconductors, metal oxides and organic nanoparticles that have found several applications in antimicrobial therapy are reviewed in detail., Results and Conclusion: An ideal anti microbial should selectively kill or inhibit the growth of microbes but cause little or no adverse effect to the host. Each of the engineered nanomaterials reviewed here has its own advantages and disadvantages. Nanomaterials in general directly disrupt the microbial cell membrane, interact with DNA and proteins or they could indirectly initiate the production of reactive oxygen species (ROS) that damage microbial cell components and viruses. Some like silver nanoparticles have broad spectrum antibacterial activity while others like cadmium containing QDs shows both antibacterial as well as antiprotozoal activity. Nano material formulations can be used directly or as surface coatings or as effective carriers for delivering antibiotics. Polycationic nature of Chitosan NPs helps in conjugation and stabilization of metallic nanoparticles which will enhance their effective usage in antimicrobial therapy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Iron oxide nanoparticles present an attractive choice for carcinogenic cell destruction via hyperthermia treatment due to its small size and magnetic susceptibility. Dextran stabilized iron oxide nanoparticles (DIONPs) synthesized and characterized for this purpose were used to evaluate its effect on cellular uptake, cytotoxicity, and oxidative stress response in human peripheral blood lymphocytes. In the absence of efficient internalization and perceptible apoptosis, DIONPs were still capable of inducing significant levels of reactive oxygen species formation shortly after exposure. Although these particles did not cause any genotoxic effect, they enhanced the expression of a few relevant oxidative stress and antioxidant defense related genes, accompanied by an increase in the glutathione peroxidase activity. These results indicate that under the tested conditions, DIONPs induced only minimal levels of oxidative stress in lymphocytes. Understanding the biological interaction of DIONPs, the consequences as well as the associated mechanisms in vitro, together with information obtained from systemic studies, could be expected to advance the use of these particles for further clinical trials.

Diastase α-amylase extracted from malt, catalyses break down of starch into maltose. It is commonly used in food and fermentation industry. In the present study nano zinc oxide is used as support for this starch hydrolyzing enzyme. IR study revealed that the enzyme got adsorbed via electrostatic interaction with the functional groups on the support. The immobilized enzyme possessed a better heat-resistance than free enzyme. The kinetic parameters were determined using Lineweaver-Burk plot. The immobilized enzyme showed higher Km 2.08mg/ml than the free enzyme whose Km is 0.45±.05mg/ml. The Vmax of immobilized enzyme was about 2.92±.02mg/ml/min and that of free enzyme was 7.14±.02mg/ml/min, showing decrease in activity after immobilization. The immobilized enzyme showed 70% activity after 30days of storage while free enzyme lost its activity within 7days. About 80% of enzyme retained activity after 4 cycles of reuse., (Copyright © 2016. Published by Elsevier Ltd.)

Advancement in the field of nanoscience and technology has alarmingly raised the call for comprehending the potential health effects caused by deliberate or unintentional exposure to nanoparticles. Iron oxide magnetic nanoparticles have an increasing number of biomedical applications and hence a complete toxicological profile of the nanomaterial is therefore a mandatory requirement prior to its intended usage to ensure safety and to minimize potential health hazards upon its exposure. The present study elucidates the toxicity of in house synthesized Dextran stabilized iron oxide nanoparticles (DINP) in a regulatory perspective through various routes of exposure, its associated molecular, immune, genotoxic, carcinogenic effects and bio distribution profile. Synthesized ferrite nanomaterials were successfully coated with dextran (<25nm) and were physicochemically characterized and subjected to in vitro and in vivo toxicity evaluations. The results suggest that surface coating of ferrite nanoparticles with dextran helps in improvising particle stability in biological environments. The nanoparticles do not seem to induce oxidative stress mediated toxicological effects, nor altered physiological process or behavior changes or visible pathological lesions. Furthermore no anticipated health hazards are likely to be associated with the use of DINP and could be concluded that the synthesized DINP is nontoxic/safe to be used for biomedical applications., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Extensive use of superparamagnetic iron oxide nanoparticles (SPIONS) in theranostics prompted us to investigate the acute changes in cell morphology and function following intravenous administration of surface-modified SPIONS in a rat model. Dextran-coated (DEX) and polyethylene glycol-coated (PEG) SPIONS were synthesized and characterized, and cytocompatibility was evaluated in vitro. Haematological, histopathological, ultrastructural and oxidative stress analyses were carried out 24h post intravenous administration in vivo. In test groups, SGPT and SGOT enzymes were significantly altered when compared to saline-only controls. Anti-oxidant imbalance and lipid peroxidation were observed in all major organs. Histology revealed iron-laden Kupffer cells and macrophages in liver and lung respectively. Iron overload was observed in the convoluted tubules of the kidney. Mast cell infiltration and distribution were observed differentially in test groups. Although surface modification of SPIONS improved biocompatibility in vitro, they affected anti-oxidant and tissue nitrite levels, which greatly influenced mast cell infiltration in vivo., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cellular and organ responses to nanoparticles are relevant in the context of use of nanoparticles for biomedical applications. The purpose of the present study was to determine the potential of dextran stabilized iron oxide nanoparticles (DIONPs) to influence hepatic uptake and consequently induce hepatotoxic response in rats following intravenous administration. Inductively coupled plasma atomic emission spectroscopy analysis revealed that DIONPs are rapidly taken up into the liver, progressively broken down to iron constituents and exported into blood, with a part of it being retained in the liver. The potential of DIONPs to induce oxidative stress response was determined by evaluating the time-dependent redox defense status. Maximum alterations in antioxidant activities were observed to occur within a period of 7days. However, this effect was not followed by significant increase in lipid peroxidation or modulation of hepatic enzymes such as alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and bilirubin levels. Overall, these data imply that the liver retains functional integrity with a dose of 10mg/kg DIONPs, although with brief activation of redox defenses., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Graphene, a material with great application potential is expected to revolutionize various fields in the near future particularly biomedical field with its inherent properties. However, significant increase in the research on graphene in the recent years has created anxiety about their safety/biocompatibility towards living organisms. Though there is increase in reports on graphene synthesis and application, in parallel reports on unwanted toxic effects of these materials is under scrutiny. Before exploiting their use, any engineered nanomaterials should undergo through investigation regarding the risk and health hazards imposed by them. Toxicity of nanomaterial depends on many factors like size, shape, surface chemistry, dose, duration and the biological milieu. In this account, we reviewed physico-chemical properties of graphene that plays a key role in toxicity prediction. We also detailed some examples of the in vitro and in vivo toxicity studies that have been published so far. The potential environmental risk associated with these carbon materials is also addressed, in order to avoid unintentional leaching of these materials into surface water., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Graphene and its derivatives have garnered significant scientific interest and have potential use in nano-electronics as well as biomedicine. However the undesirable biological consequence, especially upon inhalation of the particle, requires further investigations. This study aimed to elucidate the nano-biointeractions of PEGylated reduced graphene oxide (PrGO) and reduced graphene oxide (rGO) with that of lung alveolar epithelial cells (A549). Both nanomaterials showed dose dependent decrease in cell viability and alteration of cell morphology after 24h. Upon intracellular uptake of PrGO, it elicited oxidative stress mediated apoptosis in the cells by inducing ROS, loss of mitochondrial membrane potential (MMP) and inflammatory response by NF-κB activation. Conversely, rGO was found to scavenge ROS efficiently except at high dose after 24h. It was found that ROS at high dose of rGO prompted loss of MMP. rGO was found to adhere to the cell membrane, where it is assumed to bind to cell surface Toll like receptors (TLRs) thereby activating NF-κB mediated inflammatory response. All these events culminated in an increase in apoptosis of A549 cells after 24h of rGO exposure. It was also noticed that both the nanomaterials did not initiate lysosomal pathway but instead activated mitochondria mediated apoptosis. This study highlights the possible adverse toxic effect of PrGO and rGO upon inhalation and persistence of these particles in the lungs. Further research is required to comprehend the biological response of PrGO and rGO so as to advance its biomedical application and safety., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Zinc oxide nanoparticles (ZnO NPs) are one of the widely used nanoparticles with spectrum of application, in the areas like daily care products, sensors, antibacterial agents, and biomedical sector. With extensive application the risk of exposure at occupational and consumer level also increases. Huge amount of data are available on the biointeraction of ZnO NPs. Though the toxicity of ZnO NPs is attributed to particle dissolution inside the cellular compartments and their ability to generate the reactive oxygen species, the ambiguity prevails over the exact mechanism of toxicity. The in vivo studies on different animal models and humans suggest different level of toxicity in these organisms. However the synthetic route, physiochemical properties of the nanoparticle, mode of exposure and nature of the test system often influences these studies. Hence the study results vary and sometimes contradict on one another. The current review focuses on the interaction of ZnO NPs with different organ systems. It also points to the factors to be considered while undertaking such studies in order to ensure reliability of the results.

Adipose Derived Mesenchymal Stem Cells, multipotent stem cells isolated from adipose tissue, present close resemblance to the natural in vivo milieu and microenvironment of bone tissue and hence widely used for in bone tissue engineering applications. The present study evaluates the compatibility of tissue engineered hydroxyapatite burr hole button device (HAP-BHB) seeded with Rabbit Adipose Derived Mesenchymal Stem Cells (ADMSCs). Cytotoxicity, oxidative stress response, apoptotic behavior, attachment, and adherence of adipose MSC seeded on the device were evaluated by scanning electron and confocal microscopy. The results of the MTT (3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium bromide) assay indicated that powdered device material was noncytotoxic up to 0.5 g/mL on cultured cells. It was also observed that oxidative stress related reactive oxygen species production and apoptosis on cell seeded device were similar to those of control (cells alone) except in 3-day period which showed increased reactive oxygen species generation. Further scanning electron and confocal microscopy indicated a uniform attachment of cells and viability up to 200 μm deep inside the device, respectively. Based on the results, it can be concluded that the in-house developed HAP-BHB device seeded with ADMSCs is nontoxic/safe compatible device for biomedical application and an attractive tissue engineered device for calvarial defect regeneration.

Iron oxide nanoparticles have attracted enormous interest as potential therapeutic agents. The purpose of this study was to examine the in vitro hematological toxicity and in vivo immune response toward previously synthesized and characterized dextran stabilized iron oxide nanoparticles (DIONPs) developed for hyperthermia application. Peripheral whole blood from human volunteers was used to investigate hemolysis, platelet aggregation, lymphocyte proliferation and cytokine mRNA expression induced by DIONPs in vitro. In the concentration range of 0.008-1 mg/ml, DIONPs did not induce relevant levels of hemolysis or platelet aggregation. Assessment of lymphocyte function showed significant suppression of the proliferation activity of T-lymphocytes in cultures stimulated with the mitogen phytohemagglutinin (PHA). In addition, inhibition of PHA-induced cytokine mRNA expressions was also seen. However, systemic administration of DIONPs resulted in enhanced proliferation of mitogen-stimulated spleen derived lymphocytes and secretion of IL-1β at day 7 post exposure. In conclusion, our results demonstrate that immune response is influenced variably by nanoparticles and its degradation milieu. Further investigation of the observed immunosuppressive effects of DIONPs in immune stimulated animal models is required to assess the functional impact of such a response., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Zinc oxide nanoparticles (ZnO NPs) are widely used in cosmetic industries and have also found important applications in electrical and chemical industries. It is well documented that inhaled ZnO NPs can reach the brain through the olfactory neuronal pathway and can interfere with the brain zinc homeostasis. Most of the studies focus on the toxicity of ZnO NPs on neuronal cells and microglia. Not much work is available on the bio interaction of ZnO NPs with astrocytes, the major cells involved in brain homeostasis. Therefore, this study focuses on the interaction of ZnO NPs with rat C6 glial cells. The results of this study reveal that the nanoparticles are taken up by the astrocytes and induce a time and dose dependent toxicological response which is indicated by the nanoparticle uptake studies and cell viability assays. Also the results of DCFH-DA (2',7'-dichlorofluorescein diacetate) assay show that the ZnO NPs induce strong oxidative stress in cells at 3 and 6h. However, at 24h the reactive oxygen species (ROS) detected in the nanoparticles treated groups were same as that of control. The mode of cell death induced by ZnO NPs was apoptosis as revealed by the nuclear condensation studies, live dead assay using acridine orange/ethidium bromide and apoptosis detection kit. This study, which explores the interaction of ZnO NPs with astrocytes, concludes that the persistence of particle can continue to have a damaging effect on the astrocytes. And hence the time of exposure and particle clearance by the system should be evaluated more thoroughly to prevent the health hazards due to these particles., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Multifunctional nanomaterial-based probes have had key impacts on high-resolution and high-sensitivity bioimaging and therapeutics. Typically, NIR-absorbing metal sulfide-based nanocrystals (NCs) are highly assuring due to their unique optical properties. Yet, their in vivo behavior remains undetermined, which in turn undermines their potential bioapplications. Herein, we have examined the application of PEGylated Cu2S NCs as tumor contrast optical nanoprobes as well as investigated the short- and long-term in vivo compatibility focusing on anti-oxidant defense mechanism, genetic material, immune system, and vital organs. The studies revealed an overall safe profile of the NCs with no apparent toxicity even at longer exposure periods. The acquired observations culminate into a set of primary safety data of this nanomaterial and the use of PEGylated Cu2S NCs as promising optical nanoprobes with immense futuristic bioapplications.

Polysaccharides that show finest bioactivities and physicochemical properties are always promising for bionanoscience applications. Mauran is such a macromolecule extracted from halophilic bacterium, Halomonas maura for biotechnology and nanoscience applications. Antioxidant properties of MR/CH nanoparticles were studied using biochemical assays to prove the versatility of these test nanoparticles for biomedical applications. Here, we demonstrate the prospects of extremophilic polysaccharide, mauran based nanoparticles for scavenging reactive oxygen species in both in vitro and ex vivo conditions. 5-fluorouracil loaded MR/CH nanoparticles were tested for anticancer proliferation and compared their therapeutic efficiency using breast adenocarcinoma and glioma cells. Fluorescently labeled nanoparticles were employed to show the cellular uptake of these nanocarriers using confocal microscopic imaging and flow cytometry., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers (IL-1α, IL-1β, IL-8 and TNF-α) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.

With the recent advancement in nanoscience and nanotechnology, there is a growing demand for assessment of the toxicological effects of nano materials to humans and other biological systems. And a predictive toxicology approach that uses in vitro screening assays in conjunction with in vivo study results are widely employed in nano safety evaluation. In recent years stem cells have gained wide attention in the scientific community owing to their potential benefits for various applications in health care systems. Stem cells are undifferentiated cells that have high replicative potential and multilineage differentiation capacity. And therefore, stem cells could be exploited for developing in vitro model systems to study nanomaterials interaction with the biological systems and a potential tool to predict toxicity in humans. The details provided in this article will give an overview of optimizing stem cell technology in predicting the toxicity of nano materials the essential features of the article.

In this study, dextran coated ferrite nanoparticles (DFNPs) of size <25 nm were synthesized, characterized, and evaluated for cytotoxicity, immunotoxicity, and oxidative stress by in vitro and in vivo methods. Cytotoxicity was performed in vitro using splenocytes with different concentrations of DFNPs. Gene expression of selected cytokines (IL-1, IL-10, and TNF β) secretion by splenocytes was evaluated. Also, 100 mg of DFNPs was injected intraperitoneally to 18 albino mice for immunological stimulations. Six animals each were sacrificed at the end of 7, 14, and 21 days. Spleen was subjected to immunotoxic response and liver was analyzed for antioxidant parameters (lipid peroxidation, reduced glutathione, glutathione peroxidase, superoxide dismutase, and glutathione reductase). The results indicated that DFNPs failed to induce any immunological reactions and no significant alternation in antioxidant defense mechanism. Also, mRNA expression of the cytokines revealed an increase in IL-10 expression and subsequent decreased expression of IL-1 and TNF β. Eventually, DNA sequencing of liver actin gene revealed base alteration in nonconserved regions (10-20 bases) of all the treated groups when compared to control samples. Hence, it can be concluded that the DFNPs were nontoxic at the cellular level and nonimmunotoxic when exposed intraperitoneally to mice.

Engineered nanoparticles are developed for various applications in industrial, electrical, agricultural, pharmaceutical and medical fields due to their unique properties. Nanoparticles such as TiO(2) and ZnO are widely used in cosmetics for UV protection. The toxicological investigations of ZnO NPs are highly recommended because of the increasing use in various industrial and consumer products. The toxic potential of ZnO NPs was assumed to be caused by the release of free Zn+ ions in the medium. Many of the in vivo studies suggest the toxic nature of ZnO NPs, the in vitro studies are certainly important to elucidate the mechanism of toxicity. This study examined the toxicity of ZnO NPs with the average size of 6-8 nm on the isolated mice bone marrow mesenchymal stem cells. The study focuses on the cytotoxicity and oxidative stress-mediated cellular responses upon exposure to ZnO NPs. The results indicated that the exposure to ZnO NPs significantly affects cellular viability in a dose-dependent manner. Formation of reactive oxygen species (ROS) was found to be the mechanism of cellular toxicity. The release of Zn(+) ions from the nanoparticles, due to the instability of ZnO NPs in the acidic compartment of lysosomes, also increases the ROS generation. In addition to increased ROS production, damage of lysosomal membrane and the activation of executioner caspase-3 and caspase-7 were observed, which eventually ends in apoptosis.

Mesenchymal stem cells or multipotent progenitor cells isolated from bone marrow presents close resemblance to the natural in vivo milieu and hence preferred more than the conventional cell culture systems to predict the toxicological behavior of bio-nano interaction. The objective of the present study is to evaluate the molecular toxicity of hydroxyapatite nanoparticles (HANPs) using mouse bone marrow mesenchymal stem cells (BMSCs). In-house synthesized HANPs (50 nm) were used to study the cytotoxicity, nano particle uptake, effect on cyto skeletal arrangement, oxidative stress response and apoptotic behavior with the confluent BMSCs as per standard protocols. The results of the MTT assay indicated that HANPs does not induce cytotoxicity up to 800 μg/mL. It was also observed that oxidative stress related apoptosis and reactive oxygen species (ROS) production following nanoparticle treatment was similar to that of control (cells without treatment). Hence it can be concluded that the in-house synthesized HANPs are non-toxic/safe at the molecular level suggesting that the HANPs are compatible to BMSCs. Further, the in vitro BMSCs cell culture can be used as a model for evaluating the preliminary toxicity of nanomaterials., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The study focused on the interfacing of dextran coated ferrite nanomaterials (DFNM) with the cellular system and delayed hypersensitivity on Guinea pigs. In vitro study investigated the cytotoxic potential of DFNM on L929 cells, effect on antioxidant enzymes and Lipid peroxides (LPO) production on rat brain homogenates. DFNM was also repeatedly exposed topically to Guinea pigs for the evidence of skin sensitization and toxicity at the molecular level. Biochemical and hematological parameters were estimated. Liver and brain of Guinea pigs were homogenized and evaluated for the induction of LPO, glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and 8-hydroxyl-2-deoxyguanosine (8-OHdG). The results of the study demonstrated that there was no significant alternation in the level of antioxidant defense enzymes, LPO, hematological, biochemical or oxidative stress related DNA damage. Hence, it can be concluded that the synthesized DFNM was non-skin irritant or non-toxic at the molecular level under the laboratory conditions., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The aim of the study was to evaluate the cells-nanoparticle interactions and molecular toxicity after delayed hypersensitivity in Guinea pigs, exposed to hydroxyapatite nanoparticles (HANP). The study focuses on synthesizing and characterizing HANPs and gaining an insight into the cytotoxicity, molecular toxicity, hypersensitivity and oxidative stress caused by them in vitro and in vivo. HANP was synthesized by chemical method and characterized by standard methods. Cytotoxicity was assessed on L929 cells by MTT assay and in vitro studies were carried out on rat liver homogenate. In vivo study was carried out by topical exposure of Guinea pigs with HANP, repeatedly, and evaluating the skin sensitization potential, blood parameters, oxidative stress in liver and brain and DNA damage (8-hydroxyl-2-deoxyguanosine: 8-OHdG) in liver. The results of the study indicated that there was no cytotoxicity (up to 600μg/mL) and oxidative damage (up to 100μg/mL), when exposed to HANPs. It was also evident that, there was no skin sensitization and oxidative damage when HANP were exposed to Guinea pigs., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Mauran (MR), a highly polyanionic sulfated exopolysaccharide was extracted from moderately halophilic bacterium; Halomonas maura and characterized using X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy. Purified MR was evaluated for antioxidant defense mechanisms under in vitro conditions using L929, mouse fibroblast cell line and mice liver homogenate. It was demonstrated that MR could impart protective effect against oxidative stress in both cells and tissue up to a concentration of 500 μg, which is found to be safe under laboratory conditions. Various enzymatic and non-enzymatic parameters of antioxidant mechanisms were evaluated and concluded that MR has the tendency to maintain a balance of antioxidative enzymes with in the test systems studied. Also, hemocompatibility assay performed revealed that MR has a lesser hemolytic index and exhibited a prolonged clotting time, which shows both antihemolytic, and antithrombogenic nature respectively. Furthermore, absorption studies performed using fluorescent-labeled MR confirmed that MR accumulated within the cell cytoplasm neither induced cellular lysis nor affected the cell integrity., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Oxidative stress is involved in diverse biological phenomenon, and is caused by the imbalance between reactive oxygen species (ROS) and antioxidant defense system. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) is the most critical biomarker in the estimation of ROS-induced DNA damage. This investigation focuses on the effect of fibrin glue on lipid peroxidation (LPO), antioxidant enzymes and oxidative DNA damage (both in vitro and in vivo). The blood biochemical parameters of the implanted animals and in vitro chromosomal aberrations were also studied. Fibrin glue was applied on the calvarial defect made on the anesthetized rats for an observation period of 4, 12, 26 and 52 weeks. At the end of the observation period, animals were anesthetized; blood was collected for serum analysis and was sacrificed. Brain was collected for the detection of 8-OHdG using competitive ELISA and liver was collected for analyzing the antioxidant enzymes and LPO. The results of this study suggest that the effect of fibrin glue on rat brain (in vivo and in vitro) and mice liver (in vitro) did not make any significant influence on LPO and antioxidant defense system. Similarly, there was no change observed in the expression of 8-OHdG. Serum constituents of implanted rats were observed to be within the normal range. The normal karyotype obtained indicates that the physiological saline extract of fibrin glue does not induce any chromosomal anomalies. Hence, it was concluded that the fibrin glue material does not have any potential to produce oxidative stress, alterations in the C-8 position of guanine and chromosomal anomalies.

The present study was carried out to evaluate the effect of HAP-EVA, fibrin glue, HA-BG, Latex and Dental material on oxidative stress related mtDNA damage by in vitro and in vivo methods. In vivo studies of these biomaterials were carried out by implanting biomaterials (five materials) on animals for period of 1, 4, 12, 26 and 52 weeks. At the end of observations, animals were anesthetized, sacrificed and tissues surrounding the implanted materials were collected. Brain, bone and muscles were used for the extraction of mtDNA. Similarly mtDNA was extracted from the homogenate of fresh brain, bone and muscles on exposure to the physiological saline extract of all the above five biomaterials (In vitro). The extracted mtDNA were subjected to analyse the presence of 8-OHdG. The results of study indicated that there was no significant increase in the level of 8-OHdG and thereby does not influence on the GC-TA transversions.

Iron oxide nanoparticles are one of the most important genres of nanoparticles with promise. Dextran, a stable biocompatible coating agent was employed in the synthesis of iron oxide nanoparticles in the presence of urea. The morphology of nanoparticles was confirmed by dynamic light scattering and transmission electron microscopy. These particles were also assessed for cytotoxicity, cellular uptake and cell adhesion in vitro using murine fibroblast cell line. The synthesized nanoparticles were superparamagnetic, possessed spherical shape with narrow size distribution and were found to be biocompatible and non-toxic. This study serves as a background for using DIONPs in further in vitro and in vivo studies with a long term goal of using it in biological applications., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Pyrogens are heterogeneous group of fever-inducing substances derived from Gram-positive and Gram-negative bacteria, fungi, and viruses. They incite immune response by producing endogenous pyrogens such as prostaglandins and other proinflammatory cytokines like IL-1β, IL-6, and TNF-α. The present study was to analyze the influence of cryopreservation in IL-1β release, a marker for inflammatory response from human lymphocytes, in response to exogenous pyrogenic stimulants. Lymphocytes isolated from pooled blood of multiple healthy individuals were cryopreserved in DMSO and glycerol for periods of 7, 14, 30, and 60 days and were challenged with LPS and LTA in vitro. The inflammatory cytokine, IL-1β release, was measured by ELISA method. It was observed that the release of IL-1β increases instantaneously after the initiation of incubation and reaches a maximum at 3 to 5 hours and then gradually decreases and gets stabilized for both pyrogens. Moreover it was also observed that the effect of cryoprotectants, DMSO (10%) and glycerol (10%), showed almost similar results for short-term storage, but DMSO-preserved lymphocytes yielded a better viability for long-term storage. Thus, the isolated cryopreserved lymphocytes system can be a promising approach for the total replacement/alteration to animal experimentation for pyrogenicity evaluation.

Aim: To detect the interleukin -1β levels from single and pooled isolated human lymphocytes in response to lipolysaccharide and lipoteichoic acid., Materials and Methods: Blood collected from healthy individuals (O +ve, A +ve, B +ve, and AB +ve) were subjected to gradient centrifugation to isolate lymphocytes. Different lymphocyte concentrations were used for in vitro pyrogen assay. Lymphocytes isolated were challenged with 5 EU of Gram negative (LPS) and 1 μg/μl of Gram positive (LTA) pyrogens in vitro and the inflammatory cytokine, Interleukin 1β (IL-1β) release was measured by Sandwich ELISA method., Results: The results indicated that the release of IL-1β increases immediately after the initiation of incubation and reaches a maximum at 4 to 6th hour and then stabilizes for both the pyrogens. Furthermore, IL-1β release by 5 EU of LPS and 1 μg/μl of LTA is dependent on lymphocytes concentration. It was also observed that the difference in blood group did not interfere with the IL-1β release., Conclusion: The isolated lymphocyte system can be used as an alternative to the in vivo rabbit pyrogen assay.