53 research outputs found

    Review: apoptotic mechanisms in bacterial infections of the central nervous system

    Get PDF
    In this article we review the apoptotic mechanisms most frequently encountered in bacterial infections of the central nervous system (CNS). We focus specifically on apoptosis of neural cells (neurons and glia), and provide first an overview of the phenomenon of apoptosis itself and its extrinsic and intrinsic pathways. We then describe apoptosis in the context of infectious diseases and inflammation caused by bacteria, and review its role in the pathogenesis of the most relevant bacterial infections of the CNS

    Receptor tyrosine kinases play a significant role in human oligodendrocyte inflammation and cell death associated with the Lyme disease bacterium Borrelia burgdorferi

    No full text
    Abstract Background In previous studies, human oligodendrocytes were demonstrated to undergo apoptosis in the presence of Borrelia burgdorferi under an inflammatory milieu. Subsequently, we determined that the MEK/ERK pathway played a significant role in triggering downstream inflammation as well as apoptosis. However, the identity of receptors triggered by exposure to B. burgdorferi and initiating signaling events was unknown. Methods In this study, we explored the role of several TLR and EGFR/FGFR/PDGFR tyrosine kinase pathways in inducing inflammation in the presence of B. burgdorferi, using siRNA and/or inhibitors, in MO3.13 human oligodendrocytes. Cell death and apoptosis assays were also carried out in the presence or absence of specific receptor inhibitors along with the bacteria to determine the role of these receptors in apoptosis induction. The expression pattern of specific receptors with or without B. burgdorferi was also determined. Results TLRs 2 and 5 had a minimal role in inducing inflammation, particularly IL-6 production. Rather, their effect was mostly inhibitory, with TLR2 downregulation significantly upregulating CXCL8, and CXCL (1,2,3) levels, and TLR5 likely having a similar role in CXCL8, CXCL(1,2,3), and CCL5 levels. TLR4 contributed mostly towards CCL5 production. On the other hand, inhibition of all three EGF/FGF/PDGF receptors significantly downregulated all five of the inflammatory mediators tested even in the presence of B. burgdorferi. Their inhibition also downregulated overall cell death and apoptosis levels. The expression pattern of these receptors, as assessed by immunohistochemistry indicated that the PDGFRβ receptor was the most predominantly expressed receptor, followed by FGFR, although no significant differences were discernible between presence and absence of bacteria. Interestingly, inhibition of individual EGFR, FGFR, or PDGFR receptors did not indicate an individual role for any of these receptors in the overall downregulation of pathogenesis. Contrarily, suppression of FGFR signaling alone in the presence of bacteria significantly upregulated inflammatory mediator levels indicating that it might control an inhibitory pathway when triggered individually. Conclusions Unlike TLRs, EGF/FGF/PDGF receptors collectively play a significant role in the inflammation and apoptosis of human oligodendrocytes as mediated by B. burgdorferi. It is likely that these three receptors need to be triggered simultaneously to achieve this effect

    Ultrasonic velocity and absorption studies on drug release pattern from different ethylcellulose bases

    No full text
    152-154<span style="font-size:14.0pt;line-height: 115%;font-family:" times="" new="" roman";mso-fareast-font-family:fd884270-identity-h;="" color:black;mso-ansi-language:en-in;mso-fareast-language:en-in;mso-bidi-language:="" hi"="" lang="EN-IN">Ultrasonic velocity and absorption studies have been carried out in the drug sparfloxacin added to different, bases viz .. ethylcellulose : poly ethylene glycol (EC:PEG), ethylcellulose : hydroxy propyl methyl cellulose (EC:HPMC) and ethyl cellulose : eudrajit (EC: EUD). The elastic properties of the different bases with and without drug are estimated and an overall view about the drug release pattern is given.</span

    Multimedia Chemistry in Tamil for 10 th Standard Students

    No full text
    An attractive Multimedia contents in chemistry has been developed in both Tamil and English for 10 th standard students. The chapters covered in this work are Periodic Classifications

    The FGF/FGFR system in the microglial neuroinflammation with Borrelia burgdorferi: likely intersectionality with other neurological conditions

    No full text
    Abstract Background Lyme neuroborreliosis, caused by the bacterium Borrelia burgdorferi affects both the central and peripheral nervous systems (CNS, PNS). The CNS manifestations, especially at later stages, can mimic/cause many other neurological conditions including psychiatric disorders, dementia, and others, with a likely neuroinflammatory basis. The pathogenic mechanisms associated with Lyme neuroborreliosis, however, are not fully understood. Methods In this study, using cultures of primary rhesus microglia, we explored the roles of several fibroblast growth factor receptors (FGFRs) and fibroblast growth factors (FGFs) in neuroinflammation associated with live B. burgdorferi exposure. FGFR specific siRNA and inhibitors, custom antibody arrays, ELISAs, immunofluorescence and microscopy were used to comprehensively analyze the roles of these molecules in microglial neuroinflammation due to B. burgdorferi. Results FGFR1-3 expressions were upregulated in microglia in response to B. burgdorferi. Inhibition of FGFR 1, 2 and 3 signaling using siRNA and three different inhibitors showed that FGFR signaling is proinflammatory in response to the Lyme disease bacterium. FGFR1 activation also contributed to non-viable B. burgdorferi mediated neuroinflammation. Analysis of the B. burgdorferi conditioned microglial medium by a custom antibody array showed that several FGFs are induced by the live bacterium including FGF6, FGF10 and FGF12, which in turn induce IL-6 and/or CXCL8, indicating a proinflammatory nature. To our knowledge, this is also the first-ever described role for FGF6 and FGF12 in CNS neuroinflammation. FGF23 upregulation, in addition, was observed in response to the Lyme disease bacterium. B. burgdorferi exposure also downregulated many FGFs including FGF 5, 7, 9, 11, 13, 16, 20 and 21. Some of the upregulated FGFs have been implicated in major depressive disorder (MDD) or dementia development, while the downregulated ones have been demonstrated to have protective roles in epilepsy, Parkinson’s disease, Alzheimer’s disease, spinal cord injury, blood–brain barrier stability, and others. Conclusions In this study we show that FGFRs and FGFs are novel inducers of inflammatory mediators in Lyme neuroborreliosis. It is likely that an unresolved, long-term (neuro)-Lyme infection can contribute to the development of other neurologic conditions in susceptible individuals either by augmenting pathogenic FGFs or by suppressing ameliorative FGFs or both

    Assessment of Population Exposure to Coarse and Fine Particulate Matter in the Urban Areas of Chennai, India

    No full text
    Research outcomes from the epidemiological studies have found that the course (PM10) and the fine particulate matter (PM2.5) are mainly responsible for various respiratory health effects for humans. The population-weighted exposure assessment is used as a vital decision-making tool to analyze the vulnerable areas where the population is exposed to critical concentrations of pollutants. Systemic sampling was carried out at strategic locations of Chennai to estimate the various concentration levels of particulate pollution during November 2013–January 2014. The concentration of the pollutants was classified based on the World Health Organization interim target (IT) guidelines. Using geospatial information systems the pollution and the high-resolution population data were interpolated to study the extent of the pollutants at the urban scale. The results show that approximately 28% of the population resides in vulnerable locations where the coarse particulate matter exceeds the prescribed standards. Alarmingly, the results of the analysis of fine particulates show that about 94% of the inhabitants live in critical areas where the concentration of the fine particulates exceeds the IT guidelines. Results based on human exposure analysis show the vulnerability is more towards the zones which are surrounded by prominent sources of pollution

    Development of Eco-Friendly Cutting Fluid for Machining of AISI 1010 Steel in Automotive Industry

    No full text
    In spite of better performance, the disposal of used petroleum-based cutting fluids threatens our environment. Thus, it is essential to develop eco-friendly cutting fluids for performing machining operations in industries. The main contribution of this paper is to develop an eco-friendly cutting fluid for the plain turning of AISI 1010 steel which is used in the automotive industry. In the present work, boric acid (H3BO3) was mixed with the neem seed. Neem seed oil is easily available in many countries including India. The effectiveness of the proposed cutting fluid was evaluated by conducting different tests as per the standards. The mean biodegradability value of the developed cutting fluid is 97% which is better than other cutting fluids. The average cutting force required by the proposed cutting fluid is only 127.2 N which is much less than the cutting force requirements of dry machining and conventional cutting fluids. The average surface roughness of the machined component using the proposed cutting fluid is 122.9 µm. The mean flank wear of the tool is only 289 µm. The flash point of the proposed cutting fluids is more than 250 °C which is better than the conventional cutting fluids. The fire point of the neem oil-based cutting fluids is 300 °C. The results of the stability test and the microhardness test revealed the effectiveness of the proposed cutting fluids. The results obtained in this work are superior to several other cutting fluids reported in the existing literature. Hence, it is suggested to replace the existing petroleum-based metal cutting fluid with this eco-friendly cutting fluid in the automotive industry in Hosur, India
    corecore