Intracellular inflammatory signalling cascades in human monocytic cells on challenge with phytohemagglutinin and 2,4,6-trinitrophenol.

Phytohemagglutinin (PHA) is a plant mitogen that can agglutinate human leukocytes and erythrocytes. PHA is mainly derived from red kidney beans and can act as an exogenous pyrogen. When entering into the blood circulation, exogenous pyrogens principally interact with monocytes and macrophages and induce the release of pro-inflammatory cytokines. Monocytes and macrophages are the cells that fight against foreign invaders and acts as a primary line of immune defence. Similar to PHA, the chemical 2,4,6-trinitrophenol (TNP) also acts as an exogenous pyrogen. The study focused on the in vitro interaction of PHA and TNP with the human monocyte/macrophage cell model THP-1. The exposure and associated change in cellular morphology, organelle function, mechanism of cell death, inflammatory signalling and expression of inflammation-related genes were analyzed in different time periods. It was observed that PHA and TNP induce dose and time-dependent toxicity to monocytes/macrophages where the mechanism of cell death was different for PHA and TNP. Both PHA and TNP can evoke immune signalling with increased expression of inflammatory genes and associated activation of intracellular signalling cascades.

Toxicity of dextran stabilized fullerene C60 against C6 Glial cells.

Elevated application potential of fullerene C60 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 C60 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 C60 nanoparticles (Dex-C60) forms uniform suspension in water and was stable up to 72 h. The C6 glial cell-Dex-C60 interactions indicated that the Dex-C60 nanoparticles penetrate deeper into the cells and cause dose dependent toxic response. The result of the study recommended that Dex-C60 nanoparticles should undergo intensive risk assessment before biomedical applications and should take proper safety measure to avoid its entry to the environment.

Cytoskeletal synchronization of CHO cells with polymer functionalized fullerene C60.

Recent developments in the field of fullerene C60 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 C60 (Dex-C60) on Chinese Hamster Ovary cells. The results showed that the cell viability was not affected by Dex-C60 treatment even at higher concentrations. Treatment of Dex-C60 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-C60 can be a potential candidate for various biomedical applications.

Bio-interactions and risks of engineered nanoparticles.

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.

Pyrogens, a polypeptide produces fever by metabolic changes in hypothalamus: Mechanisms and detections.

Fever is one of the cardinal symptoms of onset of an infection or inflammation and is the common clinical indicator for medical consultation in mammalian host worldwide. Simply, fever manifested with elevation of body temperature from normal physiological range represents adaptive response of immune system on challenge with an infectious and non-infectious circumstance. Fever usually initiated in the periphery as a result of interaction of immune cells with exogenous or endogenous pyrogens. Peripheral pyrogenic signals gain access to the central nervous system via humoral and neural route. Humoral pathway was initiated with production of pyrogenic cytokines and prostaglandins from immune cells of blood as well as liver, transmitted directly to pre-optic area of hypothalamus through the circumventricular organ of brain. On the other hand an alternative pathway was initiated by the same cytokines indirectly via stimulating the vagal sensory neurons result in pyrogenic fever; so-called neuronal pathway. If the magnitude of pyrogens associated fever is very high, it will lead to severe illness ranging from septic shock to death. So it is necessary to evaluate the presence of pyrogens in implants, medical devices, drugs and biological materials to ensure safety in biomedical applications and therapeutics. Classification, route of administration, mechanism of action and detection of pyrogens and associated products are the major subject of this review.