Biomedical subjects
R Rattan
Publications and source records attributed to R Rattan.
Krabbe disease: psychosine-mediated activation of phospholipase A2 in oligodendrocyte cell death.
Globoid cell leukodystrophy (Krabbe disease) is an inherited neurological disorder caused by the pathogenomic accumulation of psychosine (galactosylsphingosine), a substrate for the deficient enzyme galactocerebroside beta-galactosidase. This study underscores the mechanism of action of psychosine in the regulation of oligodendrocyte cell death via the generation of lysophosphatidylcholine (LPC) and arachidonic acid (AA) by the activation of secretory phospholipase A2 (sPLA2). There was a significant increase in the level of LPC, indicating a phospholipase A2 (PLA2)-dependent pathobiology, in the brains of Krabbe disease patients and those of twitcher mice, an animal model of Krabbe disease. In vitro studies of the treatment of primary oligodendrocytes and the oligodendrocyte MO3.13 cell line with psychosine also showed the generation of LPC and the release of AA in a dose- and time-dependent manner, indicating psychosine-induced activation of PLA2. Studies with various pharmacological inhibitors of cytosolic phospholipase A2 and sPLA2 and psychosine-mediated induction of sPLA2 enzymatic activity in media supernatant suggest that psychosine-induced release of AA and generation of LPC is mainly contributed by sPLA2. An inhibitor of sPLA2, 7,7-dimethyl eicosadienoic acid, completely attenuated the psychosine-mediated accumulation of LPC levels, release of AA, and generation of reactive oxygen species, and blocked oligodendroyte cell death, as evident from cell survival, DNA fragmentation, and caspase 3 activity assays. This study documents for the first time that psychosine-induced cell death is mediated via the sPLA2 signaling pathway and that inhibitors of sPLA2 may hold a therapeutic potential for protection against oligodendrocyte cell death and resulting demyelination in Krabbe disease.
Rho/ROCK pathway as a target of tumor therapy.
This study emphasizes the importance of Rho/ROCK pathway in lovastatin-induced apoptosis as replenishment with exogenous isoprenoid, geranylgeranylpyrophosphate (GGPP), resulted in inhibition of apoptosis in cultured tumor cells. Treatment of C6 glioma cells with Toxin B and exoenzyme C3 resulted in cell death suggesting the role of geranylgeranylated protein(s) in the survival of glioma cells. Relative apoptotic death observed in cells transfected with dominant negative constructs of RhoA, Rac, and cdc42 imply Rho A as playing the major role in cell survival. Furthermore, the inhibition of Rho A kinase (ROCK), a direct downstream effector of Rho A, by Y-27632 or dominant negative of ROCK, induced apoptosis in glioma cells. These findings indicate that RhoA/ROCK pathway is involved negatively in the regulation of glioma cell death pathway. Moreover, in vivo studies of lovastatin treatment in animals implanted with C6 glioma cell tumors also resulted in smaller tumor size and induced apoptosis in the tumor tissue. The implantation of stably transfected C6 glioma cells with expression vector of C3 exoenzyme, dominant negative of RhoA and ROCK, resulted in significant smaller tumor mass, further establishing the importance of geranylgeranylated proteins, specifically RhoA and its downstream effecter ROCK, in cell survival and tumor genesis.
Performance of a pediatric ambulatory anesthesia program--a developing country experience.
BACKGROUND: The aim of this study was to evaluate the performance of a pediatric ambulatory anesthesia program in a tertiary care teaching hospital in a developing country. METHODS: Data on all pediatric patients (<16 years of age) scheduled to have elective day-care surgery during a 1 year period from January 1999 to December 1999 were collected retrospectively. An audit form was used to determine the specialty of the procedures, anesthesia techniques, postoperative analgesia, perioperative complications, unplanned admissions and outcomes with respect to morbidity and mortality. RESULTS: A total of 763 pediatric ambulatory surgical procedures were performed during the year of 1999. The procedures included general surgery, ENT, orthopedic and plastic surgery. The most common procedure was inguinal hernia repair followed by umbilical hernia repair, adenotonsillectomy and circumcision and 96% of the patients had general anesthesia. There were only three unplanned admissions (0.4%); one for a surgical reason and two for anesthetic reasons. There was no serious morbidity or mortality in any patient. CONCLUSIONS: Performance of pediatric day-care anesthesia has been good in our day-care unit and we have a successful ambulatory surgery program, despite the limitations of a developing country.
Comparing lecture and e-learning as pedagogies for new and experienced professionals in dentistry.
OBJECTIVE: To evaluate the relative effectiveness of e-learning versus lecture learning in VDPs and trainers. DESIGN: Experimental comparison of two groups' learning retention. SETTING: VDPs and trainers from two regions were assessed by independent researchers. METHOD: One region's VDPs and trainers received e-learning; another's received a traditional one hour lecture. Retention and understanding were tested and compared. Personal preference was assessed in group interviews. RESULTS: Significantly greater retention for the trainees occurred from lecturing rather than e-learning, and for the trainers e-learning was significantly more successful than lecturing. CONCLUSIONS: Small numbers in this study preclude wide generalisation. However, the results point to the benefits of face-to-face interaction for inexperienced staff, and the benefits of the speed and manageability of e-learning for busy, more experienced staff. The need for a discussion facility to be incorporated into ICT innovations to CPD (via, for example, online 'chatrooms') is also highlighted, with the potential of greatly enhancing e-learning efficacy.
'Complications of pin placement. A survey of 429 cases'.
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'A comparison of fibreoptic transillumination with bitewing radiographs'.
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What about the reluctant patients.
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