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Gupta H.,Institute of Nuclear Medicine and Allied Sciences | Velpandian T.,All India Institute of Medical Sciences | Jain S.,National Institute of Pharmaceutical Education and Research
Journal of Drug Targeting | Year: 2010

Poor bioavailability (<1%) of drugs from conventional eye drops is mainly due to the various precorneal loss factors which include rapid tear turnover, systemic drug absorption through naso-lachrymal duct, transient residence time of the drug solution in the cul-de-sac and the relative impermeability of the drugs to corneal epithelial membrane. The present study describes the formulation and evaluation of chitosan and gellan gum based novel in-situ gel system activated by dual physiological mechanisms. Chitosan (a pH-sensitive polymer) in combination with gellan gum (an ion-activated polymer) were used as gelling agent. Timolol maleate, the drug which is frequently used for glaucoma therapy was used as model drug to check the efficacy of the formulation. The developed formulation was characterized for various in vitro parameters, for example, clarity, gelation pH, isotonicity, sterility, viscosity, transcorneal permeation profile, and ocular irritation. Ocular retention was studied by gamma scintigraphy and a significant increase in retention time was observed. The formulation was also found to be nonirritant and well tolerable. The developed system can be a viable alternative to conventional eye drops for the treatment of various ocular diseases and is suitable for clinical application. © 2010 Informa UK 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.

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.

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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