Institute of Nuclear Medicine and Allied Sciences

Delhi, India

Institute of Nuclear Medicine and Allied Sciences

Delhi, India
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Ganapathi R.,Institute of Nuclear Medicine and Allied Sciences | Manda K.,Institute of Nuclear Medicine and Allied Sciences
International Journal of Radiation Oncology Biology Physics | Year: 2017

Purpose To investigate long-term changes in behavioral functions of mice after exposure to low-dose prenatal radiation at an early organogenesis stage. Methods and Materials Pregnant C57BL/6J mice were irradiated (20 cGy) at postcoitus day 5.5. The male and female offspring were subjected to different behavioral assays for affective, motor, and cognitive functions at 3, 6, and 12 months of age. Behavioral functions were further correlated with the population of CA1 and CA3 pyramidal neurons and immature neurons in hippocampal dentate gyrus. Results Prenatally exposed mice of different age groups showed a sex-specific pattern of sustained changes in behavioral functions. Male mice showed significant changes in anxiety-like phenotypes, learning, and long-term memory at age 3 months. At 6 months of age such behavioral functions were recovered to a normal level but could not be sustained at age 12 months. Female mice showed an appreciable recovery in almost all behavioral functions at 12 months. Patterns of change in learning and long-term memory were comparable to the population of CA1 and CA3 pyramidal neurons and doublecortin-positive neurons in hippocampus. Conclusion Our finding suggests that prenatal (early organogenesis stage) irradiation even at a lower dose level (20 cGy) is sufficient to cause potential changes in neurobehavioral function at later stages of life. Male mice showed relatively higher vulnerability to radiation-induced neurobehavioral changes as compared with female. © 2017 Elsevier Inc.


Gandhi S.,Institute of Nuclear Medicine and Allied Sciences | Chandna S.,Institute of Nuclear Medicine and Allied Sciences
Cancer and Metastasis Reviews | Year: 2017

The disease-free survival following radiotherapy is often limited by the development of second/secondary cancers. This significant impediment to effective cancer treatment implicated even in the modern-day radiotherapy needs to be countered effectively. Critical analysis reveals that besides achieving effective tumor control, radiotherapy elicits certain cellular and systemic inflammatory events in tumor infiltrate, which remain relatively stable and tend to facilitate “in-field” or “out of field” oncogenesis in due course of time. Acute pro-inflammatory cytokines generated as a result of radiation-induced oxidative insult and DNA damage induce genetic instability that contributes to tumor heterogeneity and plasticity. The reverberating crosstalks between radiation-targeted tumor and its microenvironment in turn initiate inflammatory loops that feedback the immune system to manifest as systemic consequences. An “inflammatory switchover” within the tumor microenvironment is thus induced by cumulative radiation exposure, initiating pro-tumor events that can severely limit the outcome of radiotherapy. Various pro-survival tumorigenic pathways activated as a result regulate radiation-induced hypoxia, ECM remodeling, angiogenesis/vasculogenesis, and immune suppression/evasion within the tumor microenvironment. NF-κB, HIF and STAT are identified as central regulating mediators among others that orchestrate inflammatory switchover from apoptosis-mediated tumor surveillance to radiation-induced carcinogenesis. Radiation-induced interleukins stimulate recruited macrophages and endothelial cells to promote intravasation, which is further aided by release of chemokines favoring extravasation and secondary site lesions. We hence propose that delineating the inflammatory signaling network emanating from irradiation of complex tumor tissue is critical for devising suitable therapeutic strategies to prevent post-radiotherapy second cancers or metastasis. [Figure not available: see fulltext.] © 2017 Springer Science+Business Media, LLC


Haridas S.,Institute of Nuclear Medicine and Allied Sciences | Kumar M.,Institute of Nuclear Medicine and Allied Sciences | Manda K.,Institute of Nuclear Medicine and Allied Sciences
Physiology and Behavior | Year: 2013

Melatonin, a neurohormone, is known to regulate several physiological functions, especially the circadian homeostasis, mood and behavior. Chronic exposure to stress is involved in the etiology of human affective disorders, and depressed patients have been reported to show changes in the circadian rhythms and nocturnal melatonin concentration. The present study was conducted to evaluate a possible beneficial action of chronic night-time melatonin treatment against chronic mild stress (CMS) induced behavioral impairments. As expected in the present study, the stress exposed mice showed reduced weight gain, hedonic deficit, cognitive deficits and decreased mobility in behavioral despair test. Interestingly, CMS exposed mice showed less anxiety. Chronic night-time melatonin administration significantly ameliorated the stress-induced behavioral disturbances, especially the cognitive dysfunction and depressive phenotypes. In conclusion, the present findings suggest the mitigating role of melatonin against CMS-induced behavioral changes, including the cognitive dysfunctions and reaffirm its potential role as an antidepressant. © 2013 Elsevier Inc.


Manda K.,Institute of Nuclear Medicine and Allied Sciences | Reiter R.J.,University of Texas Health Science Center at San Antonio
Progress in Neurobiology | Year: 2010

Cognitive health of an organism is considered to be maintained by the capacity of hippocampal precursors to proliferate and differentiate. Environmental stressors including irradiation have been shown to inhibit neurogenesis and are associated with the onset of cognitive impairments. Over the last two decades, much evidence has been gathered showing that enhanced free radical levels and an impaired antioxidant pool are important factors underlying the pathophysiological mechanisms in a variety of neurocognitive and neurodegenerative ailments. Since oxidative stress is reported to be implicated in impaired neurogenesis, it is likely that antioxidants such as melatonin and its metabolites could restore or minimize cellular death in the hippocampal dentate gyrus. The present review summarizes the recent studies documenting the protective role of melatonin against radiation-induced impairment of neurogenesis and cognitive functions. © 2009 Elsevier Ltd.


Ghosh S.,Natural Radiation Response Mechanisms Group | Kumar A.,Natural Radiation Response Mechanisms Group | Tripathi R.P.,Institute of Nuclear Medicine and Allied Sciences | Chandna S.,Natural Radiation Response Mechanisms Group
Carcinogenesis | Year: 2014

Radiotherapy exposes certain regions of solid tumours to low sublethal doses of γ-radiation that may cause secondary malignancies. Therefore, evaluating low-dose-γ-radiation-induced alterations in tumorigenic potential and understanding their mechanisms could help in improving radiotherapy outcome. Limited studies have indicated connexin (Cx) up-regulation by low doses, whereas Cxs are independently shown to alter cell migration in unirradiated cells. We investigated low-dose-γ-radiation-induced alterations in Cx43 expression and cell prol iferation/migration/invasion in various tumour cell lines, along with the putative molecular pathways such as p38 and extracellular signal-regulated kinase-1/2 (ERK-1/2)-mitogen-activated protein kinases (MAPKs). Interestingly, a narrow range of low doses (10-20 cGy) enhanced Cx43 expression and also selectively induced glioma cell migration without altering cell proliferation, accompanied by sustained activation of p38 and up-regulation of p21waf1/cip1, whereas the lowest (5 cGy) dose induced cell proliferation coupled with enhanced p-ERK1/2, proliferating cell nuclear antigen and p-H3 levels without inducing cell migration. Most importantly, low-dose-γ-radiation-induced cell migration and p38 activation was strongly inhibited by knocking down Cx43 expression, thereby demonstrating latter's upstream role, whereas the knock-down had no effect on ERK-1/2 or cell proliferation. Silencing Cx43 caused near-complete inhibition of radiation-induced cell migration/invasion in all tumour cell lines (U87, BMG-1, A549 and HeLa), whereas no cell migration/invasiveness was induced in the γ-irradiated primary VH10 or transformed AA8 fibroblasts. Our study demonstrates for the first time that low-dose γ-radiation induces p38-MAPK mediated cell migration selectively in tumour cells. Further, this effect is regulated by Cx43, which could thus be an important mediator in radiation-induced secondary malignancies and/or metastasis. © The Author 2013. Published by Oxford University Press. All rights reserved.


Anuranjani,Institute of Nuclear Medicine and Allied Sciences | Bala M.,Institute of Nuclear Medicine and Allied Sciences
Redox Biology | Year: 2014

Whole body exposure to low linear energy transfer (LET) ionizing radiations (IRs) damages vital intracellular bio-molecules leading to multiple cellular and tissue injuries as well as pathophysiologies such as inflammation, immunosuppression etc. Nearly 70% of damage is caused indirectly by radiolysis of intracellular water leading to formation of reactive oxygen species (ROS) and free radicals and producing a state of oxidative stress. The damage is also caused by direct ionization of biomolecules. The type of radiation injuries is dependent on the absorbed radiation dose. Sub-lethal IR dose produces more of DNA base damages, whereas higher doses produce more DNA single strand break (SSBs), and double strand breaks (DSBs). The Nrf2-ARE pathway is an important oxidative stress regulating pathway. The DNA DSBs repair regulated by MRN complex, immunomodulation and inflammation regulated by HMGB1 and various types of cytokines are some of the key pathways which interact with each other in a complex manner and modify the radiation response. Because the majority of radiation damage is via oxidative stress, it is essential to gain in depth understanding of the mechanisms of Nrf2-ARE pathway and understand its interactions with MRN complex, HMGB1 and cytokines to increase our understanding on the radiation responses. Such information is of tremendous help in development of medical radiation countermeasures, radioprotective drugs and therapeutics. Till date no approved and safe countermeasure is available for human use. This study reviews the Nrf2-ARE pathway and its crosstalk with MRN-complex, HMGB1 and cytokines (TNF-α, IL-6, IFN-γ etc.). An attempt is also made to review the modification of some of these pathways in presence of selected antioxidant radioprotective compounds or herbal extracts. © 2014 The Authors.


Dutta A.,Institute of Nuclear Medicine and Allied Sciences
Cellular and molecular biology (Noisy-le-Grand, France) | Year: 2012

The current study was aimed to determine the stability, serum protein binding ability, biodistribution, antioxidant potential and tissue toxicity status of a novel radioprotective formulation (G-002M) from Podophyllum hexandrum. G-002M is the combination of a flavonoid, a lignan and its glucoside isolated from P. hexandrum rhizome that exhibit high radioprotective potential. Stability of G-002M tagged with 99mTc was observed in vitro and with mice serum till 24 hr of incubation. The formulation was investigated for its antioxidant status and its bioavailability and toxicity in different organs of mice. Biodistribution study of 99mTc-G-002M revealed its uptake by all the vital organs of mice. Higher absorbed dose was observed in lungs, liver, jejunum and kidney. Maximum retention of G-002M in kidney revealed that G-002M was excreted predominantly through renal route. G-002M was also observed to have high free radical scavenging and total reducing properties. Histopathological observations showed no significant alterations in tissue morphology of lungs, liver, jejunum and kidney by G-002M administration. The data conclusively demonstrate that high stability, multi organ availability, longer retention and non-toxic behavior of G-002M might help in exhibiting strong protective potential against lethal radiation.


Mishra K.,Institute of Nuclear Medicine and Allied Sciences | Ojha H.,Institute of Nuclear Medicine and Allied Sciences | Chaudhury N.K.,Institute of Nuclear Medicine and Allied Sciences
Food Chemistry | Year: 2012

Applications of antioxidants are increasing due to their multiple roles in minimising harmful effects of oxidative stress. 2,2-diphenyl-1-picrylhydrazyl (DPPH -) radical scavenging assay is routinely practiced for the assessment of antiradical properties of different compounds. A detailed literature survey revealed use of different materials and methods for DPPH - assay by different investigators resulted in variation in the values of reference standards and measured parameters of new antioxidants. In the present work a detailed kinetic study of antioxidants has been performed and comprehensive results in terms of effective concentration which scavenges 50% radical (EC 50), antioxidant reducing power (ARP), stoichiometry and second order rate constant (k 2) values have been reported with DPPH - assay. Importance of selection of appropriate reference compounds and kinetic calculations are suggested. Few case studies of standard antioxidants have been discussed to emphasise the utilisation of appropriate methodology and reference compounds. © 2011 Elsevier Ltd. All rights reserved.


D'Souza M.M.,Institute of Nuclear Medicine and Allied Sciences
Nuclear Medicine Communications | Year: 2012

BACKGROUND: 18F-fluorodeoxyglucose ( 18F-FDG) has limited specificity in the evaluation of intracranial lesions as it is taken up by inflammatory and granulomatous lesions as well. C-methionine is known to have a higher specificity in tumor detection, delineation, and differentiation of benign from malignant lesions. However, its uptake in granulomatous lesions remains unclarified. OBJECTIVE: The aim of this study was to explore the value of C-methionine PET/CT and 18F-FDG in the evaluation of intracranial tuberculomas. METHODS: C-methionine PET/CT followed by 18F-FDG PET/CT study was performed on 12 patients with intracranial tuberculomas. The diagnosis was confirmed for all cases on histopathological evaluation and/or follow-up. Quantitative analysis was performed for all cases by measuring the lesion-to-normal gray matter uptake ratio. RESULTS: A high lesion-to-normal gray matter uptake ratio was observed on both C-methionine (1.8±0.38) and 18F-FDG scans (1.64±0.26) in all newly diagnosed cases. Lesion detection and delineation was superior on C-methionine PET/CT. In addition, C-methionine appeared to be a more sensitive indicator for assessing early therapeutic response and incomplete therapeutic response in intracranial tuberculomas. There was complete concordance in the number and sites of lesions detected on C-methionine PET/CT and radiological imaging modalities (namely, CT and MRI). CONCLUSION: This preliminary study suggests that in newly diagnosed, untreated intracranial tuberculomas, C-methionine, like 18F-FDG, may have limited specificity in distinguishing it from a neoplastic lesion. However, it may play an important role in assessing the response to antitubercular treatment. Further studies are warranted to explore the potential of C-methionine in this regard. Copyright © Lippincott Williams & Wilkins.


Tripathi M.,Institute of Nuclear Medicine and Allied Sciences
Clinical nuclear medicine | Year: 2011

We report a case of a 60-year-old woman, diagnosed as a case of non Hodgkins lymphoma (NHL), referred for F-18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) following 6 cycles of chemotherapy to evaluate response to therapy. The scan revealed a curvilinear pattern of FDG accumulation in the midline extending anteroposteriorly, just adjacent to the inner table of the skull on the fused PET/CT images with no corresponding abnormality on the low-dose CT. Because this site anatomically corresponded to that of the sagittal sinus, an MRI and magnetic resonance venography was advised which confirmed the presence of sagittal sinus tumor deposits. This case highlights the pattern of sagittal sinus tumor thrombosis on FDG PET/CT and the possibility of its occurrence in NHL.

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