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Biomedical subjects

R Nath

Publications and source records attributed to R Nath.

At least 181 records · Page 10Linked to original sources

Effect of vitamin A deficiency on oxalate uptake by rat intestinal brush border membrane vesicles (BBMV) and its contribution towards urolithiasis.

The intestinal uptake of [14C]oxalate, [14C]glyoxylate, and [14C]glycolate are studied in brush border membrane vesicles (BBMV) isolated from vitamin A-deficient and pair-fed control rats. The data obtained indicate that oxalate and its precursors are transported across the BBMV by passive diffusion. The intestinal uptake of glyoxylate and glycolate remains unaltered in vitamin A deficiency, while uptake rate of oxalate was significantly increased (p less than 0.01) in vitamin A-deficient rats as compared to pair-fed controls. In conclusion, the results indicate that vitamin A deficiency leads to hyperabsorption of oxalate through the gut.

Animals↗

Effects of a perfluorochemical emulsion on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation.

The effects of the combination of a perfluorochemical emulsion (Fluosol DA, 20%) and carbogen (95% O2, 5% CO2) on the response of BA1112 rat rhabdomyosarcomas to continuous low-dose-rate irradiation were examined. Tumors were irradiated locally in unrestrained, unanesthetized rats at a dose rate of 0.98 Gy/h, using a specially designed 241Am irradiator system. Cell survival was measured using a colony formation assay. The tumor cell survival curves were fitted to linear relationships of the form ln S = - alpha D, where alpha for air-breathing rats was 0.104 +/- 0.005 Gy-1, as compared to 0.137 +/- 0.009 Gy-1 for rats treated with Fluosol plus carbogen. The increase in the slope of the survival curve produced by the treatment with Fluosol and carbogen was highly significant with a P value of 0.0015. The radiosensitization factor for the combination of Fluosol/carbogen plus continuous low-dose-rate irradiation was 1.32 +/- 0.11. Slightly less radiosensitization was observed with continuous low-dose-rate irradiation than in previous experiments using acute high-dose-rate irradiation. The diminished sensitization with Fluosol/carbogen during continuous low-dose-rate irradiation probably reflects the intrinsically lower oxygen enhancement ratio (OER) of low-dose/low-dose-rate irradiation, reoxygenation of the tumors during the prolonged treatment times used for continuous low-dose-rate irradiation, and the decrease in the levels of circulating perfluorochemicals during the 30-h irradiations. More importantly, the significant level of radiosensitization observed in the experiments with continuous low-dose-rate irradiation suggests that hypoxic cells persist in BA1112 tumors during continuous low-dose-rate irradiations and that the response of these tumors to continuous low-dose-rate irradiation can be improved by adjunctive treatments which oxygenate these radioresistant hypoxic tumor cells.

Americium↗

Iododeoxyuridine radiosensitization by low- and high-energy photons for brachytherapy dose rates.

The dependence of iododeoxyuridine (IUdR) radiosensitization on photon energy and dose rate in the range of interest to brachytherapy was investigated by irradiating Chinese hamster cells in vitro under aerobic conditions. The radiosensitization produced by 10(-5) and 10(-4) M IUdR for 28-keV (average) photons from 125I, 60-keV photons from 241Am, and 830-keV (average) photons from 226Ra was measured at nominal dose rates of 0.17, 0.30, 0.57, and 0.73 Gy/h. Radiosensitization factors for IUdR were essentially independent of dose rate from 0.30 to 0.73 Gy/h for all cases except for 10(-4) M IUdR plus 241Am, in which case the radiosensitization factor increased from 2.5 +/- 0.2 to 3.0 +/- 0.1. In all cases, the radiosensitization factor decreased significantly as the dose rate was lowered from 0.30 to 0.17 Gy/h e.g., the radiosensitization factor for 241Am dropped to 1.9 +/- 0.2 at a dose rate of 0.17 Gy/h. Moreover, at 0.17 Gy/h the radiosensitization factors were essentially the same for all three photon energies. As the dose rate increased from 0.17 to 0.73 Gy/h, the difference between the radiosensitization factors for the three photon energies became larger; radiosensitization factors for 241Am were higher than those for 226Ra and 125I. In temporary brachytherapy the tumor is irradiated at the higher dose rate of about 0.50-0.70 Gy/h, while the normal tissues are irradiated at lower dose rates; the dose rate dependence of the radiosensitization factor may therefore lead to an improvement in the therapeutic ratio for brachytherapy in combination with IUdR.

Americium↗

Metal inhibition of calmodulin activity in monkey brain.

Studies were conducted to investigate the effect of vanadium (V5+), cadmium (Cd2+), mercury (Hg2+), aluminium (Al3+), lead (Pb2+) and manganese (Mn2+) ions on calmodulin (CaM)-related Ca2+-ATPase activity in rhesus monkey (Macaca mulatta) brain (RMB). The cerebral cortex of RMB was dissected and homogenized in 10% sucrose buffer, and synaptic plasma membranes (SPM) were prepared. Ca2+-ATPase activity was determined by the inorganic phosphate method. Different concentrations of metal ions were incubated with RMB fractions containing endogenous CaM and RMB fractions without CaM. The results show that no metal ion inhibited the basal enzyme but that they showed a profound inhibition of total Ca2+-ATPase containing CaM. The order of potency of metals was Hg greater than Cd greater than Pb greater than Mn greater than Al greater than V. Exogenous addition of CaM restored the metal-inhibited enzyme activity to near the normal level. The basal enzyme, when reconstituted with CaM, showed sensitivity to metal ions. These data, presented for the first time in non-human primate brain, indicate that the metal ions inhibit CaM activity in RMB.

Animals↗

The loss of circadian rhythmicity of urinary solute excretion in idiopathic stone formers.

Circadian rhythmicity in urinary volume and excretion of creatinine, calcium, oxalate, uric acid and phosphate was studied in 15 idiopathic stone formers and in 17 control subjects who were age-matched, related adult males, living in the same house and engaged in similar occupations to those of the stone patients, but who had no clinically obvious stone disease. Three-hourly urine samples were collected and creatinine, calcium, oxalate, uric acid and inorganic phosphate were estimated. The time series of data were analysed by cosinor rhythmometry. Circadian rhythmicity has been described in urinary volume and urinary excretion of creatinine, calcium, oxalate, uric acid and inorganic phosphate in normal subjects, but it was not detected in the stone formers. The control subjects exhibited a circadian rhythmicity only in urinary volume and creatinine excretion. Thus they occupied a position midway between healthy adults, who exhibit circadian rhythmicity in all of the above parameters, and the stone formers, who appear to have lost it altogether.

Adult↗

Effect of cadmium on lipid peroxidation and antioxidant enzymes in undernourished weanling rat brain.

The effect of early postnatal cadmium exposure on lipid peroxidation and antioxidant enzymes in undernourished weanling rat brain has been studied. The results suggest that undernutrition makes the weanling rat brain more susceptible to the neurotoxic effects of cadmium. Cadmium at a low dose of 1 mg/kg body weight did not produce any changes in lipid peroxidation and antioxidant enzymes in normal weanling rat brain, but caused a significant increase in lipid peroxidation and markedly decreased the activities of antioxidant enzymes like glutathione peroxidase, superoxide dismutase and catalase when subjected to undernutrition.

Animal Nutritional Physiological Phenomena↗

Comparative study of the circadian rhythmicity in the urinary concentration of glycosaminoglycans in patients of calcium oxalate nephrolithiasis and in healthy adults.

Glycosaminoglycans (GAGs) are potent inhibitors of calcium oxalate crystallisation and/or crystal aggregation. Urinary concentration of GAGs has been shown to vary during 24 h; therefore, circadian rhythmicity in urinary concentration of GAGs was investigated in 33 healthy male adults in the age group of 20-40 years and in 27 male patients of a similar age group with calcium nephrolithiasis. Three-hourly urine samples were collected for 24 h beginning from 00.00 h for estimation of urinary concentration of GAGs. The data of each patient was analysed by single cosinor rhythmometry and population mean-cosinor rhythmometry was then applied to each group. Twenty-four-hour urinary excretion of GAGs was significantly less in renal calculus patients (16.867 +/- 5.89 mumol) than in healthy subjects (22.588 +/- 5.32 mumol; p less than 0.001). A statistically validated circadian rhythm in urinary concentration of GAGs was demonstrated in both the groups. However, the amplitude-acrophase test revealed a significant difference between the two groups (F2,57 = 8.305; p less than 0.001); the amplitude was 2.354 mumol/l in patients with nephrolithiasis, whereas the amplitude was 7.028 mumol/l in healthy adults. The mesor test also revealed a significant difference in the 3-hour urinary concentration of GAGs between the two groups (18.536 mumol/l in healthy adults vs. 9.728 mumol/l in patients with nephrolithiasis). Thus in patients with nephrolithiasis, not only is the 24-hour urinary excretion of GAGs significantly low but the 3-hourly urinary concentration of GAGs is also significantly decreased as compared to healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative study of 24-hour urinary excretion of glycosaminoglycans by renal stone formers and healthy adults.

In order to find out the possible aetiological factors for urolithiasis in North-Western India, an endemic region for urinary calculi, we studied the 24-hour urinary excretion of glycosaminoglycans (GAGs), inhibitors of calcium oxalate crystallisation and/or crystal aggregation, in 58 healthy adults and in 100 stone formers. GAGs were colorimetrically estimated in urine in terms of glucuronic acid content after precipitation of GAGs by cetyl pyridinium chloride. The 24-hour urinary excretion of GAGs was significantly less in stone formers as compared to healthy adults (15.32 +/- 6.94 vs. 22.44 +/- 5.54 mumol/day; p less than 0.001). There was no significant difference in the 24-hour urinary excretion of GAGs between male and female stone formers, or between male and female healthy adults. There was no correlation between age and 24-hour urinary excretion of GAGs in any of the groups. In conclusion, 24-hour urinary excretion of GAGs is significantly less both in male and in female stone formers. The 24-hour urinary excretion of GAGs is not related to age or sex in both healthy adults as well as in stone formers.

Adult↗

Asplenia syndrome.

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Consanguinity↗

Effect of diclofenac-Na on 24-hour urinary excretion of creatinine, calcium, uric acid and glycosaminoglycans in adult patients with recurrent calcium oxalate nephrolithiasis.

Non-steroidal anti-inflammatory drugs (NSAID viz. indomethacin, flurbiprofen) decrease urinary calcium excretion in male Sprague-Dawley rats. Indomethacin decreases significantly the urinary calcium excretion in hypercalciuric patients. These observations encouraged the use of NSAID in the treatment of nephrolithiasis with encouraging initial results. However, NSAID (indomethacin and naproxen) retard both glycosaminoglycans (GAGs) synthesis and degradation thereby causing a significant reduction in the urinary excretion of GAGs, known to be potent inhibitors of calcium oxalate crystallization. Therefore, the effect of another NSAID, diclofenac-Na (50 mg t.i.d. for 4 weeks) was studied on 31 recurrent calcium oxalate nephrolithiasis patients who were not hypercalciuric or hyperuricosuric. The 24-h urinary excretion of creatinine, calcium and uric acid remained unchanged at 2 weeks and 4 weeks of therapy. However, after treatment of 2 weeks and 4 weeks, there was a significant decrease in the 24-h urinary excretion of GAGs (from 17.04 +/- 7.39 mumol to 11.54 +/- 7.02 and 12.7 +/- 6.2 mumol, respectively), and urinary concentration of GAGs (from 10.77 +/- 7.09 mumol/l to 6.03 +/- 5.00 mumol/l and 7.35 +/- 4.81 mumol/l, respectively). Thus diclofenac-Na (50 mg t.i.d.) did not reduce urinary excretion of calcium but significantly lowered the urinary excretion and concentration of GAGs in normocalciuric nephrolithiasis patients, an observation which cautions against the use of diclofenac-Na in prevention of nephrolithiasis in this group of patients.

Adult↗

Relative biological effectiveness of 241Am relative to 192Ir for continuous low-dose-rate irradiation of BA1112 rat sarcomas.

Sealed sources of 241Am have been developed for intracavitary irradiation of gynecological cancers. Relative to conventional isotopes (that is, 226Ra, 137Cs, 192Ir), 241Am allows for better shielding of dose-limiting normal tissues in the patient. In addition, the long half-life of 241Am (432 years) makes it an attractive isotope both for clinical use and for long-term radiobiology studies. Using a previously developed in vivo applicator system, BA1112 sarcomas on WAG/Rij Y rats were irradiated using 241Am or 192Ir at three different dose rates. Following in vivo treatment of the sarcomas with graded doses of radiation, cell survival curves were determined using an in vitro colony formation assay. The slopes of the resulting cell survival curves were observed to increase significantly as the dose rate increased from 0.30 to 0.60 Gy/h, then to decrease slightly as the dose rate increased from 0.60 to 0.95 Gy/h. The relative biological effectiveness (RBE) of 241Am relative to 192Ir was observed to increase linearly with increasing dose rate; the RBEs were 0.96 +/- 0.009, 1.09 +/- 0.12, and 1.17 +/- 0.11 at dose rates of 0.30, 0.60, and 0.95 Gy/h, respectively.

Americium↗

Reproducibility of two in vivo tests of platelet function.

We correlated repeat determinations of platelet aggregate ratios (PAR) and plasma beta-thromboglobulin (BTG) in the right and left arms of thirty-four subjects in order to measure test reproducibility and to evaluate the effects of venipuncture. The reproducibility of PAR on the same blood samples was relatively low but similar to that obtained when the right arm and left arm values were compared, thus indicating little variation secondary to venipuncture. For BTG, the reproducibility on identical blood samples was quite high, but fell significantly when plasma samples from the two sides were correlated. This finding and increased BTG values when obvious blood collection problems occurred, indicated that plasma BTG levels are quite sensitive to venipuncture technique.

Humans↗

Development of an 241Am applicator for intracavitary irradiation of gynecologic cancers.

Sealed sources of 241Am that emit primarily 60 keV photons produce relative dose distributions in water comparable to those from 137Cs or 226Ra sources and can produce dose rates of up to 100 cGy/hr at 1 cm in water. Also, 241Am gamma rays can be effectively shielded by thin layers of high atomic number materials (HVL is 1/8th mm of lead) placed on the applicator or inside some body cavities (for example, hypaque in bladder, barium sulphate in rectum). These properties of 241Am sources open a new approach to optimizing intracavitary irradiation of various cancers by allowing a reduction in dose and volume of irradiated critical organs or by increasing tumor doses. The relative ease with which highly effective shielding is achievable with 241Am sources would allow the design and fabrication of partially shielded applicators which can produce asymmetric dose distributions to allow unidirectional irradiation of localized lesions. Design and dosimetry characteristics of a gynecological applicator containing 241Am sources are presented. The applicator consists of a 2, 3, or 4 segment vaginal plaque (loaded with 2 and 5 Ci 241Am sources) and a tandem made up of a single 8 Ci 241Am source. Dose rates at 2 cm from the plaques are 42.0, 47.4, 58.3 and 56.7 cGy/hr for 5-5, 5-4-5, 5-5-5, and 5-4-4-5 Ci plaques, respectively. The 5-4-5 Ci plaque in combination with the 8 Ci tandem produces dose rates of 60.0 and 22.8 cGy/hr to points A and B, respectively. Surface dose rates on the plaque applicators are 143, 124, 142 and 132 cGy/hr for 5-5, 5-4-5, 5-5-5 and 5-4-4-5 Ci applicators, respectively. The shielding effect of a 0.5 mm thick lead foil on one side of the 5-4-5 Ci applicator is found to be a factor of 16.8; for example, the dose rate at 2 cm from the unshielded side is 42.0 cGy/hr compared to a dose rate of 2.5 cGy/hr at 2 cm from the shielded side. Initial clinical experience with this applicator in the treatment of recurrent gynecological lesions is also presented.

Americium↗

On the choice of phantom material for the dosimetry of 192Ir sources.

Dosimetric characteristics of polystyrene, solid water, and polymethylmethacrylate were examined and compared to water to determine the suitability of these solid materials for the dosimetry of 192Ir. Ionization charge measured in each of the four media as a function of depth and depth-dose curves calculated by Monte Carlo simulation show that the three solids are equivalent to each other and to water under full scattering conditions. Photon energy spectra generated from the Monte Carlo simulation show little variation for the different media. Mass energy absorption coefficients and exposure-to-dose conversion factors were calculated as a function of depth for these spectra. Measured tissue attenuation factors are in excellent agreement with Meisberger's "selected" values. The radial dose function, which describes the change in dose with distance in phantom exclusive of the inverse square law, was calculated from the tissue attenuation factor and found to be in significant disagreement with Dale's Monte Carlo values. The reason for this discrepancy is discussed.

Brachytherapy↗

Oxalate uptake in intestinal and renal brush-border membrane vesicles (BBMV) in vitamin B6-deficient rats.

Acute, subclinical, and chronic pyridoxine deficiency did not modify the oxalate influx in rat intestinal BBMV but elevated the oxalate reabsorption by renal tubular cells. The Na+ and K+ ions did not affect oxalate uptake in either intestinal or renal BBMV. Although thiol group blocking agents did not affect intestinal uptake of oxalate they significantly altered oxalate translocation across the renal tubular cells. Following pyridoxine deficiency the rat kidneys appear to be more specific for inducing oxalate lithiasis as compared to oxalate influx through the intestine.

Animals↗

Molecular aspects, physiological function, and clinical significance of metallothioneins.

Metallothioneins (MTs) are well-characterized low molecular weight, heat-stable cytosolic proteins with exceptional high content of cysteinyl sulfur and are known to bind heavy metals like cadmium (Cd), zinc (Zn), and copper (Cu). Since these proteins are induced on exposure to heavy metals, it is now accepted that they have a detoxifying role during heavy metal toxicity. It has also been suggested that the primary function of Mt is in the homeostasis of the essential metals Zn and Cu. Recently, a role MT in selenium metabolism in primates has been established. Further, MT has gained considerable importance in the clinical disorders related to trace metal metabolism.

Amino Acid Sequence↗

Influence of the variation of energy spectra with depth in the dosimetry of 192Ir using LiF TLD.

Absolute dose measurements around low activity seeds used in brachytherapy are difficult to perform with ionisation chambers. The physical size of the chamber does not allow good resolution close to the seeds and the ionisation current generated is very low. Small thermoluminescent dosimeters (TLDs) overcome these problems but the energy dependence of their response should be considered. In this work, dose in polystyrene was measured at several distances from the high activity 192Ir source (370 GBq) of a remote afterloading device using an ionisation chamber and LiF TLD chips. These data show that over a range of 1-10 cm from the source the sensitivity of LiF varies by up to 8.5%. This is attributed to the higher response of LiF to the lower photon energies, and to the shift of the photon spectrum to lower energies with increasing depth. The sensitivity of LiF to 192Ir was also calculated by weighting the energy-dependent response of LiF by the Monte Carlo calculated photon spectra. The calculations give a similar change in sensitivity with distance from the source.

Brachytherapy↗