Pandit B. Vidyasagar

Biologic Evaluation of a Novel 188Re-Labeled Porphyrin in Mice Tumor Model

The aim of this study was to develop a (188)Re-labeled porphyrin-based tumor-specific agent and to evaluate its biologic behavior, including tumor-regressing effectiveness, in mouse tumor models for possible use in achieving targeted cancer radiotherapy. (188)Re was obtained from an alumina-column-based (188)W-(188)Re generator constructed in-house. The compound, 5,10,15,20-tetrakis[3,4-bis(carboxymethyleneoxy)phenyl]porphyrin, was synthesized and labeled with (188)ReO(4)(-). (188)Re-labeled porphyrin complex was produced with a radiochemical purity of approximately 98% with reasonably good in vitro stability (>24 hours at 4 degrees C). Swiss mice bearing thymic lymphoma and fibrosarcoma were used as tumor models. The biodistribution studies revealed satisfactory tumor retention (2.07% +/- 0.80% injected activity per g) with insignificant activities in blood (0.53%), liver (0.26%) and kidney (0.04%) at 24 hours. The radiolabeled conjugate treatment increased the average tumor-doubling time and decreased the average specific growth rate substantially in thymic lymphoma, compared to fibrosarcoma tumor. (188)Re-labeled 5,10,15,20-tetrakis[3,4 bis(carboxymethyleneoxy)phenyl] porphyrin has specific affinity toward the fibrosarcoma and thymic lymphoma tumors in mice. Thymic lymphoma was found to be more sensitive to the radionuclide complex, compared to fibrosarcoma. The (188)Re-labeled porphyrin complex showed promising results and warrants further investigations.

Analysing the effects of surface distribution of pores in cell electroporation for a cell membrane containing cholesterol

This paper presents a model and numerical analysis of transmembrane potential, m, induced in a biological cell membrane under the influence of an externally applied electric field (i.e. electroporation). This model differs from the established models in two distinct ways. Firstly, it incorporates the presence of cholesterol (~20% mole fraction) in the membrane. Secondly, it considers the dependence of pore distribution on the variation of m from one region of the cell to the other. Formulation is based on the role of membrane tension and electrical forces in the formation of pores in a cell membrane, which is considered as an infinitesimally thin insulator. The model has been used to explore the creation and evolution of pores and to determine the number and size of pores as a function of the applied electric field (magnitude and duration). Results show that the presence of cholesterol enhances poration by changing the membrane tension. Analyses indicate that the number of pores and average pore radii differ significantly from one region of the cell to the other. While some regions undergo rapid and dense poration, others may remain unaffected. The method can be a useful tool for a more realistic prediction of pore formation in cells subjected to electroporation.

Determination of peak parameters for thermoluminescence glow curves obtained from spinach thylakoid preparations, using mathematical models based on general order kinetics

Abstract Thermoluminescence (TL) bands obtained from spinach thylakoid preparations were analysed by computer-assisted models. The use of mathematical models, based on the general order kinetics of TL peaks, results in acceptable values of peak parameters such as the activation energy (E), frequency factor (S), entropy (ΔS) and free energy of activation (FE). Earlier workers, such as Tatake et al. (Photochem. Photobiol., 33 (1981) 243–250), have reported comparatively higher values of the activation energy and frequency factor for the peaks obtained at higher temperatures, namely peaks IV and V. The model used by them was based on the Randall-Wilkins first-order kinetics theory. De Vault et al. (Proc. Natl. Acad. Sci. USA, 80 (1983) 983–987; Photosynth. Res., 24 (1990) 175–181) have attempted to justify the high E and S values by postulating temperature-dependent equilibria between two or more carriers acting as traps. However, their postulation results in abnormally high values even for lower temperature peaks. Contrary to these results, it was observed that the use of general order kinetics models results in lower E and S values. Thus it is evident that the non-consideration of the retrapping of electrons is the reason for the abnormally large activation energy and frequency factor values observed by earlier workers. A comparison of the results reported previously and those obtained in this work is presented.

Studies on Efficacy of a Novel 177Lu-Labeled Porphyrin Derivative in Regression of Tumors in Mouse Model

OBJECTIVE The aim of the present study was to develop a (177)Lu-labeled porphyrin derivative having favorable characteristics for use in targeted radiotherapy of cancer and to evaluate its biological behavior in mouse tumor models with respect to its effectiveness in tumor regression. Owing to the inherent affinity of porphyrins to accumulate in the tumors, suitably modified porphyrin derivative was chosen as the vehicle for the targeted delivery of the radionuclide. (177)Lu was preferred as the radionuclide of choice due to its suitable nuclear decay characteristics [E(β(max)) = 497 keV, Eγ = 208 keV (11%), 113 keV (6.4%)], comparatively longer half-life (6.73 d) and ease of production in adequate quantity and sufficiently high specific activity using medium flux research reactors. METHODS A novel porphyrin analogue, 5,10,15,20-tetrakis[4-carboxymethyleneoxyphenyl]porphyrin was synthesized inhouse and coupled with a macrocyclic bi-functional chelating agent, namely p-amino-benzyl-1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid. The porphyrin-BFCA conjugate was labeled with (177)Lu and the biological behavior of the radiolabeled conjugate was studied by biodistribution and imaging in Swiss mice bearing either fibrosarcoma or thymic lymphoma tumors. Effectiveness of the agent in controlling the growth of tumor volumes was also studied by administering various doses of the radiolabeled preparation in the mouse tumor models. RESULTS (177)Lu-labeled porphyrin-BFCA conjugate was prepared with high radiochemical purity ( > 99%) and adequate invitro stability. Biodistribution and imaging studies revealed good uptake and retention of the agent in the tumors with encouraging tumor to blood and tumor to muscle ratios at various post-administration time points. Tumor regression studies showed that the administration of the agent increased the average tumor doubling time and decreased the average specific growth rate substantially in both the types of tumors. However, thymic lymphoma was found to be more sensitive to the radiolabeled conjugate compared to fibrosarcoma. CONCLUSION Preliminary biological evaluation and tumor regression studies carried out in two different tumor models in Swiss mice exhibited the promising nature of (177)Lu-labeled porphyrin-BFCA conjugate as an agent for targeted tumor therapy. However, further detailed investigations are warranted to evaluate the true potential of the developed agent.

Effects of Hypergravity on the Chlorophyll Content and Growth of Root and Shoot During Development in Rice Plants

Earlier Studies On Hypergravity Effects Showed Modification In The Metabolism Of Cell Wall Components, Promotion Of Metaxylem Development And Decrease In Extensibility Of Secondary Cell Walls In Arabidopsis Thaliana (Tamaoki Et Al. 2006; Nakabayashi Et Al. 2006). In The Present Study, The Effects Of Hypergravity On Rice Seeds Which Were Exposed To Hypergravity Conditions And Grown Under Normal Gravity Have Been Studied. Rice Seeds (Prh-10 Obtained From National Seeds Corporation, Govt. Of India) Were Suspended In Water In A Test Tube And Were Exposed To Hypergravity Ranging From 500–3,000 G For 10 Min. Seeds Exposed To Hypergravity Were Grown On 0.8% Agar Under Ambient Conditions And Light Intensity Of 1,250 Lux For 16 H Per Day. Seeds Unexposed To Hypergravity Grown Under The Same Conditions Acted As Control. Length Of Roots And Shoots Were Measured. Chlorophyll Was Extracted On The Fifth Day And Absorption And Fluorescence Spectra Were Recorded In Both Control And Hypergravity Samples. The Cross Parts Of The Roots Were Obtained And Studied Under The Microscope. The Results Obtained Showed That The Chlorophyll Content Was Less In The Samples Exposed To Hypergravity. The Roots Showed Changes In The Diameter Of Cells At The Core. To The Best Of Our Knowledge, Such Type Of Study Has Been Reported For The First Time.

FBX aqueous chemical dosimeter for measurement of virtual wedge profiles

We investigated the ferrous sulfate–benzoic acid–xylenol orange (FBX) aqueous chemical dosimeter for measurement of virtual (dynamic) wedge profiles on a linear accelerator. The layout for irradiation of the FBX‐filled tubes mimicked a conventional linear detector array geometry. A comparison of the resulting measurements with film‐measured profiles showed that, in the main beam region, the difference between the FBX system and the film system was within ±2% and that, in the penumbra region, the difference varied from ±1mm to ±2.5mm in terms of positional equivalence, depending on the size of the dosimeter tubes. We thus believe that the energy‐independent FBX dosimetry system can measure virtual wedge profiles with reasonable accuracy at reasonable cost. However, efficiency improvement is required before this dosimetry system can be accepted into routine practice. PACS numbers: 87.53.‐j, 87.53.Dq, 87.53.Mr, 87.53.Xd, 87.66.Ff

Analysis of thermoluminescence glow curves obtained from diethylpyrocarbonate-treated spinach thylakoid preparations using the general order kinetics model

Abstract The general order kinetics model was applied for the fitting and analysis of thermoluminescence (TL) glow curves obtained from diethylpyrocarbonate (DEPC)-treated chloroplast samples in order to understand the mechanism of TL dynamics. Incubation of thylakoids for 15 min in the presence of DEPC resulted in a reduction in the intensity of the B band at around 30°C, with a concomitant enhancement of the Q band at 10°C. This enhanced peak has a value for the order of kinetics much greater than that of the control peak, indicating that histidine modification by DEPC at photosystem II (PSII) acceptor sites increases the retrapping probability. DEPC also brought about a shift in the peak temperature of the charged A band from − 30 to − 15°C. The order of kinetics for the shifted peak remained unchanged. Since this peak is explained as a DEPC effect on the donor side of PSII, the unchanged order of kinetics indicates that retrapping events are not dominant on the donor side. The mathematical analysis of the TL peaks thus supports an earlier interpretation and provides further information on the kinetics of retrapping during TL peak formation.

LIFE AND GRAVITY

All organisms on earth have evolved at unit gravity and thus are probably adapted to function optimally at 1 g. However, with the advent of space exploration, it has been shown that organisms are capable of surviving at much less than 1 g, as well as at greater than 1 g. Organisms subjected to increased g levels exhibit alterations in physiological processes that compensate for novel environmental stresses, such as increased weight and density-driven sedimentation. Weight drives many chemical, biological, and ecological processes on earth. Altering weight changes these processes. The most important physiological changes caused by microgravity include bone demineralization, skeletal muscle atrophy, vestibular problems causing space motion sickness, cardiovascular deconditioning, etc. Manned missions into space and significant concerns in developmental and evolutionary biology in zero and low gravity conditions demand a concentrated research effort in space-medicine, physiology and on a larger scale — gravitational biophysics. Space exploration is a new frontier with long-term missions to the moon and Mars not far away. Research in these areas would also provide us with fascinating insights into how gravity has shaped our evolution on this planet and how it still governs some of the basic life processes. Understanding the physiological changes caused by long-duration microgravity remains a daunting challenge. The present concise review deals with the effects of altered gravity on the biological processes at the cellular, organic and systemic level which will be helpful for the researchers aspiring to venture in this area. The effects observed in plants and animals are presented under the classifications such as cells, plants, invertebrates, vertebrates and humans.

Sci‐AM Fri ‐ 03: Radio‐electro therapy of murine fibrosarcoma: In vivo study

Radiation therapy and chemotherapy are important modalities of cancertreatment. However, there are several limitations due to the development of radio‐resistance and chemoresistance of cancer cells. This requires the development of new protocols for improved cancer therapy. The present study is an attempt to modify radiation damage by using the electric pulses (electroporation) using murine fibrosarcoma as a model system. Electroporation is a membrane phenomenon that involves the enhanced permeability of the cell membrane by application of the electric pulses of high voltage and short duration. In the present study the fibrosarcoma tumors have been treated with Co 60 gamma radiation and/or electroporation (both monophasic and biphasic pulses separately). The tumor growth kinetics shows considerable growth delays in case of tumorstreated with combination modality. On 7th day of treatment the average tumor volume of the treatment groups Electroporation (monophasic), Radiation, and combination of both were 85%, 80% and 51% of that of control respectively. Similarly, the treatments with Electroporation with biphasic pulses in combination with radiation also resulted in considerable tumor growth delay as compared to the control. The study reveals that the combination of radiation with electroporation has produced enhanced cytotoxicity in tumor cells and that the monophasic pulses were more effective than the biphasic pulses in modulating the radiation‐induced toxicity.

Conserved Oligopeptides in the Rubisco Large Chains

The evolution of intelligent behavior observed in metazoan species requires a steady and sufficient supply of energy. Photosynthesis assumes the important role in the evolutionary mechanism in this respect. Since the basic mechanism of photosynthesis has remained unchanged in the evolutionary pathway, the study of the molecular evolution of the photosynthetic proteins has gained importance. Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) catalyses the first step in the CO2 assimilation in Photosynthesis. RuBisCO exists as dimmer in case of prokaryotic autotrophs as revealed by the crystallographic structure in case of bacteria Rhodospirilium rubrum (Schinder et al 1986). It exists as a multimeric protein in case of the higher vascular plants viz Spinach (Chapman et al 1988) and Tobacco (Chapman MS et al 1987). In the present study amino acid sequence analysis of the RuBisCO large chains have been carried out using bioinformatics protocols.