Dileep Nair - Academia.edu (original) (raw)
Papers by Dileep Nair
AJP: Cell Physiology, 2010
Intestinal smooth muscle cells are normally quiescent, but in the widely studied model of trinitr... more Intestinal smooth muscle cells are normally quiescent, but in the widely studied model of trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat, the onset of inflammation causes proliferation that leads to increased cell number and an altered phenotype. The factors that drive this are unclear and were studied in primary cultures of circular smooth muscle cells (CSMC) from the rat colon. While platelet-derived growth factor (PDGF)-AA, fibroblast growth factor (FGF), and epidermal growth factor (EGF) were ineffective, PDGF-BB and insulin-like growth factor-1 (IGF-1) caused significant increase in [3H]thymidine incorporation, bromodeoxyuridine uptake, and increased CSMC number, with PDGF-BB (≥0.2 nM) substantially more effective than IGF-1. Surprisingly, CSMC lacked expression of PDGF receptor-β (PDGF-Rβ) upon isolation but by 4 days in vitro, CSMC gained expression of PDGF-Rβ as shown by quantitative PCR, Western blot analysis, and immunocytochemistry; these CSMC responded t...
…, 2008
Background Many commonly used anesthetic agents produce a dose-dependent amplitude reduction and ... more Background Many commonly used anesthetic agents produce a dose-dependent amplitude reduction and latency prolongation of evoked responses, which may impair diagnosis of intraoperative spinal cord injury. Dexmedetomidine is increasingly used as an adjunct for general anesthesia. Therefore, the authors tested the hypothesis that dexmedetomidine does not have a clinically important effect on somatosensory and transcranial motor evoked responses. Methods Thirty-seven patients were enrolled and underwent spinal surgery with instrumentation during desflurane and remifentanil anesthesia with dexmedetomidine as an anesthetic adjunct. Upper- and lower-extremity transcranial motor evoked potentials and somatosensory evoked potentials were recorded during four defined periods: baseline without dexmedetomidine; two periods with dexmedetomidine (0.3 and 0.6 ng/ml), in a randomly determined order; and a final period 1 h after drug discontinuation. The primary outcomes were amplitude and latency of P37/N20, and amplitude, area under the curve, and voltage threshold for transcranial motor evoked potential stimulation. Results Of the total, data from 30 patients were evaluated. Use of dexmedetomidine, as an anesthetic adjunct, did not have an effect on the latency or amplitude of sensory evoked potentials greater than was prespecified as clinically relevant, and though the authors were unable to claim equivalence on the amplitude of transcranial motor evoked responses due to variability, recordings were made throughout the study in all patients. Conclusion Use of dexmedetomidine as an anesthetic adjunct at target plasma concentrations up to 0.6 ng/ml does not change somatosensory or motor evoked potential responses during complex spine surgery by any clinically significant amount.
American Journal of Physiology-gastrointestinal and Liver Physiology, 2010
Hyperplasia of smooth muscle contributes to the thickening of the intestinal wall that is charact... more Hyperplasia of smooth muscle contributes to the thickening of the intestinal wall that is characteristic of inflammation, but the mechanisms of growth control are unknown. Nitric oxide (NO) from enteric neurons expressing neuronal NO synthase (nNOS) might normally inhibit intestinal smooth muscle cell (ISMC) growth, and this was tested in vitro. In ISMC from the circular smooth muscle of the adult rat colon, chemical NO donors inhibited [ 3 H]thymidine uptake in response to FCS, reducing this to baseline without toxicity. This effect was inhibited by the guanylyl cyclase inhibitor ODQ and potentiated by the phosphodiesterase-5 inhibitor zaprinast. Inhibition was mimicked by 8-bromo (8-Br)-cGMP, and ELISA measurements showed increased levels of cGMP but not cAMP in response to sodium nitroprusside. However, 8-Br-cAMP and cilostamide also showed inhibitory actions, suggesting an additional role for cAMP. Via a coculture model of ISMC and myenteric neurons, immunocytochemistry and image analysis showed that innervation reduced bromodeoxyuridine uptake by ISMC. Specific blockers of nNOS (7-NI, NAAN) significantly increased [ 3 H]thymidine uptake in response to a standard stimulus, showing that nNOS activity normally inhibits ISMC growth. In vivo, nNOS axon number was reduced threefold by day 1 of trinitrobenzene sulfonic acidinduced rat colitis, preceding the hyperplasia of ISMC described earlier in this model. We conclude that NO can inhibit ISMC growth primarily via a cGMP-dependent mechanism. Functional evidence that NO derived from nNOS causes inhibition of ISMC growth in vitro predicts that the loss of nNOS expression in colitis contributes to ISMC hyperplasia in vivo.
AJP: Cell Physiology, 2010
Intestinal smooth muscle cells are normally quiescent, but in the widely studied model of trinitr... more Intestinal smooth muscle cells are normally quiescent, but in the widely studied model of trinitrobenzene sulfonic acid (TNBS)-induced colitis in the rat, the onset of inflammation causes proliferation that leads to increased cell number and an altered phenotype. The factors that drive this are unclear and were studied in primary cultures of circular smooth muscle cells (CSMC) from the rat colon. While platelet-derived growth factor (PDGF)-AA, fibroblast growth factor (FGF), and epidermal growth factor (EGF) were ineffective, PDGF-BB and insulin-like growth factor-1 (IGF-1) caused significant increase in [3H]thymidine incorporation, bromodeoxyuridine uptake, and increased CSMC number, with PDGF-BB (≥0.2 nM) substantially more effective than IGF-1. Surprisingly, CSMC lacked expression of PDGF receptor-β (PDGF-Rβ) upon isolation but by 4 days in vitro, CSMC gained expression of PDGF-Rβ as shown by quantitative PCR, Western blot analysis, and immunocytochemistry; these CSMC responded t...
…, 2008
Background Many commonly used anesthetic agents produce a dose-dependent amplitude reduction and ... more Background Many commonly used anesthetic agents produce a dose-dependent amplitude reduction and latency prolongation of evoked responses, which may impair diagnosis of intraoperative spinal cord injury. Dexmedetomidine is increasingly used as an adjunct for general anesthesia. Therefore, the authors tested the hypothesis that dexmedetomidine does not have a clinically important effect on somatosensory and transcranial motor evoked responses. Methods Thirty-seven patients were enrolled and underwent spinal surgery with instrumentation during desflurane and remifentanil anesthesia with dexmedetomidine as an anesthetic adjunct. Upper- and lower-extremity transcranial motor evoked potentials and somatosensory evoked potentials were recorded during four defined periods: baseline without dexmedetomidine; two periods with dexmedetomidine (0.3 and 0.6 ng/ml), in a randomly determined order; and a final period 1 h after drug discontinuation. The primary outcomes were amplitude and latency of P37/N20, and amplitude, area under the curve, and voltage threshold for transcranial motor evoked potential stimulation. Results Of the total, data from 30 patients were evaluated. Use of dexmedetomidine, as an anesthetic adjunct, did not have an effect on the latency or amplitude of sensory evoked potentials greater than was prespecified as clinically relevant, and though the authors were unable to claim equivalence on the amplitude of transcranial motor evoked responses due to variability, recordings were made throughout the study in all patients. Conclusion Use of dexmedetomidine as an anesthetic adjunct at target plasma concentrations up to 0.6 ng/ml does not change somatosensory or motor evoked potential responses during complex spine surgery by any clinically significant amount.
American Journal of Physiology-gastrointestinal and Liver Physiology, 2010
Hyperplasia of smooth muscle contributes to the thickening of the intestinal wall that is charact... more Hyperplasia of smooth muscle contributes to the thickening of the intestinal wall that is characteristic of inflammation, but the mechanisms of growth control are unknown. Nitric oxide (NO) from enteric neurons expressing neuronal NO synthase (nNOS) might normally inhibit intestinal smooth muscle cell (ISMC) growth, and this was tested in vitro. In ISMC from the circular smooth muscle of the adult rat colon, chemical NO donors inhibited [ 3 H]thymidine uptake in response to FCS, reducing this to baseline without toxicity. This effect was inhibited by the guanylyl cyclase inhibitor ODQ and potentiated by the phosphodiesterase-5 inhibitor zaprinast. Inhibition was mimicked by 8-bromo (8-Br)-cGMP, and ELISA measurements showed increased levels of cGMP but not cAMP in response to sodium nitroprusside. However, 8-Br-cAMP and cilostamide also showed inhibitory actions, suggesting an additional role for cAMP. Via a coculture model of ISMC and myenteric neurons, immunocytochemistry and image analysis showed that innervation reduced bromodeoxyuridine uptake by ISMC. Specific blockers of nNOS (7-NI, NAAN) significantly increased [ 3 H]thymidine uptake in response to a standard stimulus, showing that nNOS activity normally inhibits ISMC growth. In vivo, nNOS axon number was reduced threefold by day 1 of trinitrobenzene sulfonic acidinduced rat colitis, preceding the hyperplasia of ISMC described earlier in this model. We conclude that NO can inhibit ISMC growth primarily via a cGMP-dependent mechanism. Functional evidence that NO derived from nNOS causes inhibition of ISMC growth in vitro predicts that the loss of nNOS expression in colitis contributes to ISMC hyperplasia in vivo.