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Research paper thumbnail of Present perspectives on flaviviral chemotherapy

Drug Discovery Today - DRUG DISCOV TODAY, 2008

Flaviviruses are a group of arboviruses under the family of Flaviviridae. Flaviviruses are global... more Flaviviruses are a group of arboviruses under the family of Flaviviridae. Flaviviruses are global pathogens, some of which cause neurotrophic disorders from mild febrile illness to lethal encephalitis while others cause severe hemorrhagic fever. These viruses are endemic to many parts of the world and periodic outbreaks take thousands of lives. With globalization of the world accompanied by gradual shift in global climate, the viruses are emerging in newer areas and we are in a point of exigency to decipher new drugs to combat these emerging threats. Although extensive research has taken place and vaccines for few of these viral diseases are available, still no chemotherapeutic agent has been found to deliver an absolute cure to flaviviral infections. It is important to assess the present status of flavivirus drug research and delve deep into the avenues of flavivirus drug discovery. This review outlines the chemotherapeutic agents explored till date, and highlights perspectives on a possible future breakthrough – at least to ameliorate if not to abrogate the diseases.

Research paper thumbnail of Tobacco carcinogen induces microglial activation and subsequent neuronal damage

Journal of Neurochemistry, 2009

4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific procarcinogen. We have i... more 4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific procarcinogen. We have investigated whether NNK causes inflammatory upheaval in the brain by activation of resident microglia and astrocyte and result in bystander neuronal damage. We have carried out the work in both in vitro and in vivo models. We have found that treatment with NNK causes significant activation of mouse microglial (BV2) cell line as evident by increase in reactive oxygen species and nitric oxide level. Western blot analysis has showed increase in proinflammatory signaling proteins, proinflammatory effector proteins, and other stress-related proteins. Interestingly, increased levels of proinflammatory cytokines like interleukin (IL)-6, tumor necrosis factor-α, monocyte chemoattractant protein 1 (MCP1), and IL-12p70 are also detected. Work from our in vivo studies has demonstrated similar increase in proinflammatory signaling and effector molecules along with the proinflammatory cytokine levels, following NNK treatment. Immunohistochemical staining of the brain sections of NNK-treated mice reveals massive microglial and astrocyte activation along with distinct foci of neuronal damage. Both in vitro and in vivo results provide strong indication that NNK causes significant upheaval of the inflammatory condition of brain and inflicts subsequent neuronal damage.

Research paper thumbnail of Present perspectives on flaviviral chemotherapy

Drug Discovery Today - DRUG DISCOV TODAY, 2008

Flaviviruses are a group of arboviruses under the family of Flaviviridae. Flaviviruses are global... more Flaviviruses are a group of arboviruses under the family of Flaviviridae. Flaviviruses are global pathogens, some of which cause neurotrophic disorders from mild febrile illness to lethal encephalitis while others cause severe hemorrhagic fever. These viruses are endemic to many parts of the world and periodic outbreaks take thousands of lives. With globalization of the world accompanied by gradual shift in global climate, the viruses are emerging in newer areas and we are in a point of exigency to decipher new drugs to combat these emerging threats. Although extensive research has taken place and vaccines for few of these viral diseases are available, still no chemotherapeutic agent has been found to deliver an absolute cure to flaviviral infections. It is important to assess the present status of flavivirus drug research and delve deep into the avenues of flavivirus drug discovery. This review outlines the chemotherapeutic agents explored till date, and highlights perspectives on a possible future breakthrough – at least to ameliorate if not to abrogate the diseases.

Research paper thumbnail of Tobacco carcinogen induces microglial activation and subsequent neuronal damage

Journal of Neurochemistry, 2009

4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific procarcinogen. We have i... more 4-Methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) is a tobacco-specific procarcinogen. We have investigated whether NNK causes inflammatory upheaval in the brain by activation of resident microglia and astrocyte and result in bystander neuronal damage. We have carried out the work in both in vitro and in vivo models. We have found that treatment with NNK causes significant activation of mouse microglial (BV2) cell line as evident by increase in reactive oxygen species and nitric oxide level. Western blot analysis has showed increase in proinflammatory signaling proteins, proinflammatory effector proteins, and other stress-related proteins. Interestingly, increased levels of proinflammatory cytokines like interleukin (IL)-6, tumor necrosis factor-α, monocyte chemoattractant protein 1 (MCP1), and IL-12p70 are also detected. Work from our in vivo studies has demonstrated similar increase in proinflammatory signaling and effector molecules along with the proinflammatory cytokine levels, following NNK treatment. Immunohistochemical staining of the brain sections of NNK-treated mice reveals massive microglial and astrocyte activation along with distinct foci of neuronal damage. Both in vitro and in vivo results provide strong indication that NNK causes significant upheaval of the inflammatory condition of brain and inflicts subsequent neuronal damage.

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