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Biomedical subjects

V Mishra

Publications and source records attributed to V Mishra.

At least 37 records · Page 2Linked to original sources

Ligand directed macrophage targeting of amphotericin B loaded liposomes.

Two types of ligand anchored multilamellar liposomes (MLVs) containing amphotericin B (Amp B) were prepared. The MLVs consisting of soya phosphatidylcholine (PC) and cholesterol (Chol) were coated with O-palmitoyl mannan (OPM). Similarly, the MLVs with the same Amp B content consisting of soya PC, Chol and phosphatidylethanolamine (PE) were prepared and covalently anchored with p-aminophenyl-mannopyranoside (PAM). The surface modified MLVs and their plain counterparts were characterised for size, shape, lamellarity, entrapment efficiency and ligand density. The stability in serum and in vivo bio-distribution in albino rats were also determined. It was observed that extent of accumulation of liposomal Amp B in macrophage rich organs, particularly liver, spleen and lungs was significantly high when compared against the free drug. The rates and extent of accumulation were found to increase further on ligand anchoring. In either of the cases, the macrophagic uptake of ligand anchored liposomes was inhibited significantly on pre-injection of hydrolysed mannan, being suggestive of receptor mediated uptake of ligand anchored liposomes. Comparison of biodistruibution pattern of ligand anchored MLVs revealed that PAM linked liposomes exhibited a higher hepato-splenic accumulation where as drug accumulation in lungs was highest in the case of OPM coated liposomes. It was thus observed that mannopyranoside is a specific ligand for targeting bioactives to the macrophages of liver and spleen while OPM could preferentially negotiate the targeting of bioactives to the alveolar macrophages.

Amphotericin B↗

Controlled and targeted drug delivery strategies towards intraperiodontal pocket diseases.

Advances in the understanding of the aetiology, epidemiology, pathogenesis and microbiology of periodontal pocket flora have revolutionized the strategies for the management of intraperiodontal pocket diseases. Intra-pocket, sustained release, drug delivery devices have been shown to be clinically effective in the treatment of periodontal infections. Several degradable and non-degradable devices are under investigation for the delivery of antimicrobial agents into the periodontal pocket including non-biodegradable fibres, films (biodegradable and non-biodegradable), bio-absorbable dental materials, biodegradable gels/ointments, injectables and microcapsules. With the realization that pocket bacteria accumulate as biofilms, studies are now being directed towards eliminating/killing biofilm concentrations rather than their planktonic (fluid phase) counterparts. Intraperiodontal pocket drug delivery has emerged as a novel paradigm for the future research. Similarly, bioadhesive delivery systems are explored that could significantly improve oral therapeutics for periodontal disease and mucosal lesions. A strategy is to target a wide range of molecular mediators of tissue destruction and hence arrest periodontal disease progression. Research into regenerating periodontal structures lost as a result of disease has also shown substantial progress in the last 25 years.

Biofilms↗

Need for bringing in a change in biochemistry curriculum to make it clinically oriented?

OBJECTIVES: This study was conducted to (a) assess the views of medical students and doctors regarding relevance of biochemistry training, (b) explore if they have any suggestion to bring in any improvement in contents of biochemistry curriculum and mode of teaching. METHODS: In 1997-98, a structured questionnaire was filled up by 114 medical students and 118 doctors. RESULTS: As many as 62/114 (55%) medical students and 40/118 (34%) doctors believed that it is not important to remember minute details of biochemical reactions (p value < 0.0001). Among medical students, 108/110 (98.2%) agree that a clinician should be invited to seminars for developing skills of interpretation of laboratory investigations; whilst 110/118 (93.2%) doctors expressed similar view, p value ns. Approximately 92% responders favored that departments biochemistry and physiology should co-ordinate on the topics of common interest in order to save time and effort. What is the most informative and effective way of teaching biochemistry?' in response to this question only 0.9% responders opted lecture as the best option. Seminars with active participation of medical students was preferred by 93.2% responders. About 6.9% responders reckoned that symposium prepared by a more than one teacher. In response to the question whether it is possible to cover pre-clinical subjects in 12 months so as to allow spiral mode of curriculum, 73% of all the responders agreed that it would be good idea, there was no difference of opinion among the doctors and medical students. On the other hand, 27% were strongly opposed to this suggestion. CONCLUSIONS: We suggest that there is a need to modify the contents, methods of teaching, and curriculum organization of training in clinical biochemistry. How best the curriculum can be made problem oriented needs to be debated among medical educationists.

Biochemistry↗

Self-Preservation of the Drop Size Distribution Function and Variation in the Stability Ratio for Rapid Coalescence of a Polydisperse Emulsion in a Simple Shear Field

Coalescence of oil-in-water emulsion droplets in a simple shear flow produced by a Couette device is considered. A phase Doppler anemometer was used to measure the droplet size distribution as a function of time for shear rates ranging from 55 to 213 s-1 and for sodium chloride salt concentrations from 0.095 to 0.6 M. The initial droplet size distribution was log-normal. During the coalescence process, the size distribution was self-preserving in accordance with D. L. Swift and S. K. Friedlander's analysis [J. Colloid Sci. 19, 621 (1964)]. In the limiting case of negligible repulsive force due to the electric double layer, the calculated stability ratios, corrected for droplet polydispersity, agree well with the theoretical analyses of G. R. Zeichner and W. R. Schowalter [AIChE J. 23, 243 (1977)] and D. L. Feke and W. R. Schowalter [J. Fluid Mech. 133, 17 (1983)] for the case of solid particle aggregation. The good agreement between the stability ratios for the case of coalescence of droplets in the present study and those for aggregation of solid particles indicates that resistance to film deformation and thinning present in the case of coalescence is not important compared with the collision process. Copyright 1998 Academic Press. Copyright 1998Academic Press

Journal Article↗

Anticonvulsant activity of thioureido derivatives of acetophenone semicarbazone.

A series of thioureido derivatives of acetophenone semicarbazone were synthesized and evaluated for anticonvulsant activity. Some compounds provided significant protection against maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) induced seizures. The compound (2e) was the most active compound in the series with a dose of 30 mg kg-1 and ED50 23.5 mg kg-1 and equipotent to phenytoin ED50 23.2 mg kg-1. The toxicity of the compounds was assessed by determination of their approximate TD50 and LD50 values in order to have a better assessment of their pharmacological profile and protective index.

Acetophenones↗

Synthesis of aryl semicarbazone of 4-aminoacetophenone and their anti-HIV activity.

The thioureido derivative of 4-aminoacetophenone aryl semicarbazone have been prepared. These derivatives have been characterised on the basis of different physicochemical evidences. The anti-HIV-1 (HTLV-IIIB) and -HIV-2 (ROD) activity and cytotoxicity of the compounds were tested. The compound VII and VIII showed maximum protection among the series.

Acetophenones↗

Anisotropy of an 192iridium high dose rate source measured with a miniature ionization chamber.

The anisotropy of a high dose rate (HDR) 192Ir source was measured in air and in water using a miniature (0.147 cm3) ionization chamber. Measurements were made at a distance of 5 cm from the source center at polar angles from 10 degrees-170 degrees. The anisotropy was found to be less pronounced in water, and the anisotropy is asymmetric about the transverse axis. The results agree with previous ionization chamber and TLD measurements to within +/- 4%. Mean anisotropy factors were determined at each angle from all existing data at 5 cm distance, and compared to published Monte Carlo calculations, and to the values used in the microSelectron HDR brachytherapy planning system (BPS). The Monte Carlo photon transport code appears to systematically underestimate the anisotropy factor by up to 4% in the forward direction and overestimate it by up to 3% in the backward direction. The mean anisotropy factors also indicate that the BPS systematically underestimates the anisotropy factor by up to 3% in the forward direction, and overestimates it by up to 15% in the backward direction. However, the 15% difference occurs at 180 degrees where it is not likely to be clinically significant.

Air↗

Quantitative evaluation of radiochromic film response for two-dimensional dosimetry.

Radiochromic film (RCF) is attractive as a thin, high resolution, 2D planar dosimeter. We have studied the uniformity, linearity, and reproducibility of a commercially supplied RCF system (model MD-55). Forty 12 cm long strips of RCF were exposed to uniform doses of 6 MV x rays. Optical density (OD) distributions were measured by a helium-neon scanning laser (633 nm) 2D densitometer and also with a manual densitometer. All film strips showed 8%-15% variations in OD values independent of densitometry technique which are evidently due to nonuniform dispersal of the sensor medium. A double exposure technique was developed to solve this problem. The film is first exposed to a uniform beam, which defines a pixel-by-pixel nonuniformity correction matrix. The film is then exposed to the unknown dose distribution, rescanned, and the net OD at each pixel corrected for nonuniformity. The double exposure technique reduces OD/unit dose variation to a 2%-5% random fluctuation. RCF response was found to deviate significantly from linearity at low doses (40% change in net OD/Gy from 1 to 30 Gy); a finding not previously reported. To study the tradeoff between statistical noise and spatial resolution, OD was averaged over blocks of adjacent 50 microns pixels (ranging from 1 x 1 to 10 x 10 pixels). Reproducibility, defined as the standard deviation of repeated single-pixel measurements on separate film pieces, was 2% at 30 Gy for a resolution of 0.25 mm. With careful correction for nonlinearity and nonuniformity, RCF is a promising quantitative 2D dosimeter for radiation oncology applications.

Absorptiometry, Photon↗

A secondary air kerma strength standard for Yb-169 interstitial brachytherapy sources.

Ytterbium-169 (169Yb) is a promising new intermediate low-energy isotope for interstitial implantation. To date, no air kerma strength (SK) standard for this source exists that can serve as a sound foundation for comparing various dose measurements and theoretical calculations. We have solved this problem by adapting the free air measurement technique of Goetsch et al, originally developed for 192Ir. Using a 100 cm3 spherical ion chamber with NIST traceable external beam calibrations in a free air geometry, we have measured the air kerma strength of six different source batches (two type 6 batches, three type 8 batches, and one experimental high-intensity source). Room scatter corrections, derived from an empirical fit to the data (following Goetsch et al) and/or directly by Monte Carlo simulation, yielded identical results with a reproducibility of 1%. The ratio [SK/Avendor] of measured SK to the vendor's contained activity assay averaged 1.554 cGy cm2 mCi-1 h-1 (0.0420 microGy m2 MBq-1 h-1), in conflict with the expected value of 1.34 (0.0362), derived from Monte Carlo calculations. The measured [SK/Avendor] for the type 8 seeds varies by as much as 10% whereas the SK/dose calibrator reading ratio varies by no more than 0.3%, suggesting that the reproducibility of Avendor is relatively poor. These discrepancies may help explain the variation (as large as 28%) in published dose rate constants for 169Yb.

Air↗

Experimental validation of Monte Carlo dose calculations about a high-intensity Ir-192 source for pulsed dose-rate brachytherapy.

Despite widespread use of high-intensity Ir-192 remotely afterloaded sources, no published measured or calculated dose-rate tables for currently used source designs are available. For a pulsed dose-rate Ir-192 source, both transverse axis (0.5-10 cm) and two-dimensional polar dose-rate profiles (1.5, 3, and 5 cm) were measured with thermoluminescent dosimetry in a solid water phantom. Dose rates were normalized to measured air-kerma strength, and the source geometry was verified by pinhole autoradiography and transmission radiography. At each measurement point, dose rates were calculated by a Monte Carlo photon transport (MCPT) code, which realistically modeled the experimental phantom, source, and detector geometry. Agreement between MCPT absolute dose-rate calculations and measurements averaged 3% and was less than 5%, demonstrating that Monte Carlo simulation is an accurate and powerful tool for two-dimensional dosimetric characterization of high activity Ir-192 sources.

Brachytherapy↗

Instrumentation and dosimeter-size artifacts in quantitative thermoluminescence dosimetry of low-dose fields.

Thermoluminescence dosimetry is extensively used for quantitative dose measurements in various irradiation fields such as dosimetry of brachytherapy sources. In this application, small doses on the order of 0.5 cGy must be accurately measured, which requires careful control of instrumentation, energy-dependence, and nonlinearity of detector response. Several investigators have observed the presence of some undesirable signals when the thermoluminescent dosimeters (TLDs) were read without any nitrogen gas flow in the TLD reader. Others have indicated that the "prereadout" annealing technique is the same as the "preirradiation" technique for doses above 10 cGy, but they have not extended their study to lower doses. The goal of this study is to investigate dependence of sensitivity and linearity of the TLD response to the flow of nitrogen gas in the TLD reader at low dose level, annealing technique, and TLD size. The effect of nitrogen flow sensitivity and linearity of two different sizes of lithium fluoride TLD-100 chips has been studied. Our data indicate a large standard deviation of TLD sensitivity, up to a factor of 2, when TLDs were read without nitrogen gas flow in the TLD reader. In addition, a large deviation from linearity was observed for doses below 5 cGy. When the reading-chamber was purged with nitrogen gas, dispersion of the responses of the TLDs that were exposed to the same dose fell to within 5%. At precision levels of 2% and 5%, the low dose limits are 1 cGy and 0.5 cGy, respectively, for large chips and 15 cGy and 1 cGy for small chips, if TLDs are read with nitrogen gas flow in the TLD reader.(ABSTRACT TRUNCATED AT 250 WORDS)

Artifacts↗

Dosimetric characteristics, air-kerma strength calibration and verification of Monte Carlo simulation for a new Ytterbium-169 brachytherapy source.

PURPOSE: Ytterbium-169 (169Yb) is a promising new isotope for brachytherapy with a half life of 32 days and an average photon energy of 93 KeV. It has an Ir-192-equivalent dose distribution in water but a much smaller half-value layer in lead (0.2 mm), affording improved radiation protection and customized shielding of dose-limiting anatomic structures. The goals of this study are to: (a) experimentally validate Monte Carlo photon transport dose-rate calculations for this energy range, (b) to develop a secondary air-kerma strength standard for 169Yb, and (c) to present essential treatment planning data including the transverse-axis dose-rate distribution and dose correction factors for a number of local shielding materials. METHODS AND MATERIALS: Several interstitial 169Yb sources (type 6) and an experimental high dose-rate source were made available for this study. Monte-Carlo photon-transport (MCPT) simulations, based upon validated geometric models of source structure, were used to calculate dose rates in water. To verify MCPT predictions, the transverse-axis dose distribution in homogeneous water medium was measured using a silicon-diode detector. For use in designing shielded applicators, heterogeneity correction factors (HCF) arising from small cylindrical heterogeneities of lead, aluminum, titanium, steel and air were measured in a water medium. Finally, to provide a sound experimental basis for comparing experimental and theoretical dose-rate distributions, the air-kerma strength of the sources was measured using a calibrated ion chamber. To eliminate the influence of measurement artifacts on the comparison of theory and measurement, simulated detector readings were compared directly to measured diode readings. The final data are presented in the format endorsed by the Interstitial Collaborative Working Group. RESULTS: The in-air calibration revealed that the air-kerma strength per unit activity (mCi), as quoted by the vendor, varied from 1.30 to 1.57 cGy.cm2/mCi.h depending on seed design. The maximum difference between measured and MCPT-simulated absolute diode readings on the transverse axis was less than 2%, indicating that MCPT accurately predicts dose rate in medium for brachytherapy sources in this energy range. Comparison of measured and simulated HCFs for each of the 16 different cylindrical heterogeneities demonstrated 1-3% agreement. The HCFs vary by as much as 200% with respect to distance and by as much as 48% as a function of disk diameter, showing that HCF is strongly dependent on heterogeneity location and lateral dimensions as well as thickness. The dose-rate constant for water medium was found to be 1.225 cGy/h per kerma unit air-strength and 1.962 cGy/h per unit mCi as measured by the vendor. CONCLUSION: Monte Carlo simulation is an accurate and powerful tool for dosimetric characterization of brachytherapy sources in this energy range. Thin lead foils produce shielding factors comparable to standard shielded applicators for 137Cs. Meaningful theoretical absolute dose calculations in brachytherapy require accurately implemented air-kerma strength standards.

Brachytherapy↗

A comparative study of dosimetric properties of Plastic Water and Solid Water in brachytherapy applications.

In this study the dosimetric properties of Plastic Water and Solid Water phantom materials are evaluated using Monte Carlo photon transport simulations. In particular, their water-equivalence with respect to absorption and attenuation of photons in the brachytherapy energy range are examined. For the given chemical compositions of the materials, the linear attenuation coefficients were calculated for photons of 1 keV-2 MeV. Moreover, absorbed doses to water in each phantom material were calculated at distances of 0.5-12.0 cm from point sources of 20 keV to 60Co gamma rays. These results show that at low photon energies (below 100 keV), there are substantial differences (up to a factor of 5) between the absorbed dose in Plastic Water and that in liquid water. The differences decrease as photon energy increases, and they become insignificant at 60Co gamma rays, as claimed by the manufacturer. In contrast, calculations show that the difference in absorbed dose in Solid Water from that in liquid water, over the entire range of photon energies employed in this study, is less than 25%. The results of this study demonstrate the necessity of careful dosimetric evaluation of a new phantom material, before its clinical application, particularly in energy ranges outside those referred to by the manufacturer.

Biophysical Phenomena↗