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Biomedical subjects

R Nath

Publications and source records attributed to R Nath.

At least 145 records · Page 8Linked to original sources
PubMed1993

New Directions in Radionuclide Sources for Brachytherapy.

Brachytherapy continues to play an important role in the management of cancers of several sites, including the head and neck, brain, uterine cervix, endometrium, and prostate. The physical advantages of brachytherapy result from a superior localization of dose to the tumor volume. In brachytherapy, as radiation is continuously delivered over a period of time, repair of sublethal and potentially lethal damage, proliferation, and other cell kinetic effects modify the response of tumor and normal tissues, resulting in complex dose rate effects that also influence the therapeutic ratio for brachytherapy. There are two different forms of brachytherapy. There are two different forms of brachytherapy: intracavitary irradiation using radioactive sources that are placed in body cavities in close proximity to the tumor, and interstitial brachytherapy using radioactive seeds implanted directly into tumor volume. Intracavitary radiation is always temporary and usually takes about 1 to 4 days. On the other hand, interstitial brachytherapy can be temporary or permanent. Radioactive sources emtting higher energy photons have better tissue penetration but are more difficult to shield for radiation protection purposes than sources emitting lower energy photons. Longer-lived radioactive sources can be used several times in different patients, which reduces their effective cost compared with shorter-lived radioisotopes. However, for permanent implants, shorter-lived radionuclides can provide higher initial dose rate, which may have biological advantages in some cases. These characteristics of various forms of brachytherapy dictate the choice of radioactive sources for a specific treatment. Recently, a number of new radionuclide sources have been developed, making a wide variety of half-lives and photon energies available to the brachytherapy community. Conventional sources for brachytherapy in the United States are cesium 137, iridium 192, iodine 125, and gold 198. The physical characteristics of these sources and of the newly developed sources, americium 241, palladium 103, samarium 145, and ytterbium 169, are described.

Journal Article↗
PubMed1993

Lipid peroxidation and antioxidant defense enzymes in various regions of adult rat brain after co-exposure to cadmium and ethanol.

Effect of cadmium (1 mg/kg body weight) and ethanol (2 g/kg body weight) exposure, alone as well as in combination, on essential trace metal homeostasis, lipid peroxidation and antioxidant defense enzymes in various regions of the adult rat brain was investigated. It was observed that cadmium when administered along with ethanol accumulated significantly in corpus striatum (3.5 fold) and cerebral cortex (3.0 fold) compared to the cadmium treated group. The ethanol induced accumulation of cadmium led to significant depletion in the levels of essential trace metals like zinc and copper in these regions of the brain. Further, cadmium or ethanol alone did not show any significant effect on lipid peroxidation and antioxidant defense enzymes in any of the regions of the adult brain but when given in combination, caused a significant increase in lipid peroxidation and markedly decreased the activities of antioxidant defense enzymes like glutathione peroxidase, superoxide dismutase and catalase particularly in corpus striatum and cerebral cortex. Structural alterations produced by increased lipid peroxidation after cadmium and ethanol co-exposure may have profound effect on the activities of membrane bound enzymes and hence may lead to functional impairment. The results of the present study imply that ethanol renders the adult brain more susceptible to the neurotoxic effects of cadmium. Corpus striatum and cerebral cortex are more vulnerable to the toxic effects of cadmium under the influence of ethanol than other regions of the brain.

Animals↗
PubMed1993

Antioxidant enzymes in RBCs as a biological index of age related macular degeneration.

The present study was undertaken to assess the levels of antioxidant enzymes in red blood cells of subjects with age-related macular degeneration and age-matched controls. The results obtained show a significant decrease in activities of superoxide dismutase (p < 0.001) and glutathione peroxidase (p < 0.001) as compared to the controls. A good correlation (r = -0.99) was also observed between age and decreased activity of antioxidant enzymes in controls, and also correlated well with age-related macular degeneration. In conclusion, oxidative stress as assessed by antioxidant enzymes is more pronounced in subjects with age-related macular degeneration as compared to age-matched controls.

Aged↗
PubMed1993

The predictive value of the relative lens position in primary angle-closure glaucoma.

The relative lens position has been considered to be an important determinant in primary angle-closure glaucoma, but its predictive value needs to be assessed. Therefore, in this tertiary-care center-based case-control study, 70 cases and an equal number of controls were investigated to analyze this association. It was found that, after controlling for age, sex, and refractive error, the relative lens position and anterior chamber depth had a strong association with the disease in separate logit models (P < .01). The predictability of the separate logit models with the relative lens position and anterior chamber depth was found to be statistically significant (-2 x maximized logarithmic likelihood, 93.94 and 19.39, respectively, P < .01). Because the relative lens position represents a composite measure from a set of variables, it can be used as a significant predictive alternative to anterior chamber depth in the genesis of this disease.

Adult↗
PubMed1993

A comparative study of erythrocyte oxalate flux rate and urinary oxalate excretion in hyperoxaluric rats.

The present study was carried out to investigate the relation between erythrocyte oxalate flux rate and the pathogenesis of calcium oxalate renal stone disease having hyperoxaluria as the main risk factor. Male albino rats were made hyperoxaluric by feeding them diets viz. vitamin B6 deficient, vitamin B6 deficient + 51.7% galactose or fructose (serving as a sole source of carbohydrate), along with their respective pair-fed controls for 4 weeks. After 28 days of feeding, oxalate excretion was in the order of vitamin B6 deficient + galactose > galactose control > vitamin B6 deficient + fructose > vitamin B6 deficient > fructose control/vitamin B6 control. Whereas, transmembrane oxalate flux rate was in the order of vitamin B6 deficient > vitamin B6 deficient + galactose > vitamin B6 deficient + fructose > vitamin B6 control > galactose control > fructose control. No significant correlation (r = 0.304) was found between the urinary oxalate excretion and erythrocyte oxalate flux rates of various groups of rats. The study indicates that increase in oxalate excretion does not concomitantly increase the transmembrane oxalate flux in red blood cells.

Alanine Transaminase↗
PubMed1993

Anterior chamber depth and lens thickness in primary angle-closure glaucoma: a case-control study.

Anterior chamber depth and lens thickness have been considered as important biometric determinants in primary angle-closure glaucoma (PACG). In a tertiary care centre-based case-control study, 70 patients and equal number of controls were investigated to analyse the strength of association and predictability of anterior chamber depth (ACD) and lens thickness (LT) in the disease. Mean (+/- S.D.) ACD and LT in the cases and the controls were found to be 2.28 +/- 0.19, 2.87 +/- 0.10; 4.57 +/- 0.34 and 4.13 +/- 0.19 mm respectively. Two sample t test demonstrated statistically significant difference in the ACD and LT between the cases and the controls (Difference being -0.59, 0.44; 95% confidence interval of the difference: -0.64, -0.53 and 0.34, 0.53 respectively, P < 0.01). Logistic regression analysis demonstrated statistically significant protective effect of ACD over PACG (P < 0.01). The odds ratio corresponding to an increase of 0.01 mm in ACD and LT were computed as 0.83 and 1.11 respectively.

Anterior Chamber↗
PubMed1993

Oxalate metabolism in magnesium-deficient rats.

Male weanling rats were maintained on magnesium-deficient diet for 30 d and compared with pair-fed control rats fed magnesium-supplemented diet. Magnesium deficiency led to slow growth and finally to a significant decrease in body weight (P < 0.001) accompanied by a significant hypomagnesaemia, hypomagnesuria and hyperoxaluria (P < 0.001 in each case) in experimental rats as compared to the control rats. Magnesium deficiency altered the glyoxylate metabolism in the liver and kidney mitochondria by significantly decreasing glyoxylate oxidation (by 26 per cent in liver and 17 per cent in kidney) and activity of alpha-ketoglutarate:glyoxylate carboligase enzyme (by 35 per cent in liver and 27 per cent in kidney) in the experimental animals. A significant increase in the specific activities of glycolic acid oxidase (P < 0.001) and glycolic acid dehydrogenase (P < 0.01) and a significant decrease in alanine transaminase (P < 0.01) was also observed in magnesium-deficient rats. No change in liver and kidney lactate dehydrogenase was observed. Thus magnesium deficiency in rats leads to accumulation of glyoxylate in the tissues, a part of which is converted into oxalate, thereby promoting hyperoxaluria.

Aldehyde-Ketone Transferases↗
PubMed1993

Recent advances in measurement of oxalate in biological materials.

Hyperoxaluria is the predominant risk factor in urinary stone disease. A specific, accurate and reliable oxalate assay for urine and plasma is very important for both the diagnosis and efficient management of patients. A review of the advantages and disadvantages of various methods of oxalate determination is presented and is followed by the authors' recommendations.

Carboxy-Lyases↗
PubMed1993

Intestinal absorption of calcium and oxalate in magnesium-deficient rats.

To examine the contribution of exogenous calcium and oxalate in magnesium deficiency, intestinal absorption of both calcium and oxalate was studied by preparing brush border membrane vesicles (BBMV). Purity of the BBMV was ascertained biochemically by enrichment of the marker enzyme alkaline phosphatase by 14-fold with a concomitant 90 per cent decrease in the basolateral marker enzyme Na+/K(+)-ATPase in the purified membrane preparation as compared to the respective homogenate in both the groups. Uptake studies were carried out by a rapid filtration technique. The kinetics were studied by measuring the rate of influx as a function of concentration (0.1-1.0 mM). BBMV from both the groups showed a linear positive relationship between the uptake rate and the concentration for both calcium and oxalate, thereby demonstrating that calcium and oxalate are transported through intestinal microvillus membrane by a simple passive diffusion process. However, the rate of uptake of calcium and oxalate was significantly higher in the magnesium-deficient group as compared to the pair-fed control group, as shown by the increase in the slope line for both calcium and oxalate (for calcium, control = 3.88, deficient = 5.86; for oxalate, control = 4.41, deficient = 7.20). Analysis of the lipid composition of the BBM revealed a significant decrease in the cholesterol content (P < 0.01) with a concomitant increase in the triglycerides (P < 0.01) and total fatty acid content (P < 0.001) in the magnesium-deficient group. Thus the results indicate that, although the mechanism of translocation of calcium and oxalate in the intestine is similar in the two groups, magnesium deficiency leads to hyperabsorption of both the ligands through alterations in the lipid composition of the membrane, thereby increasing the risk of stone formation.

Animals↗
PubMed1992

ZK98299--a new antiprogesterone: biochemical characterization of steroid binding parameters in the calf uterine cytosol.

We have examined steroid binding characteristics of a newly synthesized antisteroid, ZK98299 [onapristone, 11 beta-(4-dimethylaminophenyl)-17 alpha-hydroxy-17 beta-(3-hydroxypropyl)- 13 alpha-methyl-4,9-gonadien-3-one], in the calf uterus cytosol and compared the nature of this interaction with the binding of progesterone receptor (PR) agonist R5020 [promegestone, 17,21-dimethylpregna-4,9-diene-3,20-dione]. In the freshly prepared cytosol, [3H]ZK98299 interacted specifically with a macromolecule: the binding was abolished in the presence of excess progestins (R5020 and progesterone) and the antiprogesterone ZK98299. The high affinity (Kd = 2.5 nM) interaction between [3H]ZK98299 and PR was temperature- and time-dependent, reaching an optimum by 2-3 h at 0 degrees C, and was facilitated by 20 mM Na2MoO4. Under nontransforming conditions, [3H]ZK98299-receptor complexes sedimented as 8 S species in 8-30% linear glycerol gradients. Upon salt or thermal transformation, there was a loss of the 8 S form, with only a small fraction of total complexes (5-7%) binding to DNA-cellulose. In contrast, transformed [3H]R5020-receptor complexes exhibited a greater extent of binding (25-55%) to DNA-cellulose. [3H]ZK98299-receptor complexes could be resolved into two ionic species over DEAE-Sephacel following incubation of the complexes at 0 or 23 degrees C. [3H]ZK98299 binding was sensitive to sulfhydryl group modification as beta-mercaptoethanol increased the extent of steroid binding. Although treatment with iodoacetamide (IA) abolished [3H]R5020 binding, there was a significant (nearly twofold) increase in the [3H]ZK98299 binding. The results of this study point to similarities and differences between the steroid binding properties of the uterine PR occupied by R5020 and ZK98299: both steroids appear to bind the same 8 S receptor but exhibit differential DNA binding and sensitivity to IA. The reported antagonist properties of ZK98299 may, therefore, be explained on the basis of a distinct receptor conformation induced by the antisteroid.

Animals↗
PubMed1992

Effect of ethanol on the distribution of cadmium between the cadmium metallothionein- and non-metallothionein-bound cadmium pools in cadmium-exposed rats.

In an attempt to assess the effect of ethanol on cadmium accumulation, metallothionein (MT) synthesis, Cd-binding capacity and lipid peroxidation, rats were administered either Cd, ethanol or their combination for a period of 4 weeks. A significant increase in Cd accumulation was observed in all the organs of rats under study co-exposed to Cd and ethanol as compared to only Cd-treated rats. Increased MT levels in response to Cd were associated with a marked alteration in the distribution of Cd amongst the two pools of intracellular Cd i.e. Cd bound to MT (Cd-MT) and Cd not bound to MT (non-MT-Cd). Higher levels of non-MT-Cd were observed in liver, kidney and heart of Cd+ethanol-exposed rats as compared to only Cd-exposed rats. Lesser binding of 109Cd to the protein peak was observed in Cd+ethanol-exposed rats than the Cd-treated rats when hepatic supernatants from all the groups were chromatographed on Sephadex G-75 columns, suggesting that ethanol has a redistributing effect on Cd amongst the two pools. A marked increase in lipid peroxidation was observed which was linear to the increase in non-MT-Cd levels. A positive correlation between non-MT-Cd levels and lipid peroxidation was observed in liver, kidney and heart suggesting that non-MT-Cd levels are more crucial and toxicologically more important than total Cd levels.

Animals↗
PubMed1992

Development of a shielded 241Am applicator for continuous low dose rate irradiation of rat rectum.

This paper describes the development of sources, applicators, and techniques that can be used to irradiate rat rectums with continuous irradiation at dose rates of interest in brachytherapy, either with the full circumference of the rectum irradiated, or with half of the circumference shielded from the radiation. The system uses encapsulated 241Am sources, to irradiate rat rectum with 60 keV photons continuously at a dose rate of up to 50 cGy/hr. Details of the design and fabrication of the 241Am sources, the rectal applicator, the dosimetry of the system, and the protocols for preparing and irradiating the rats, and for detecting early rectal injury using histological examination of irradiated rectum are presented. Highly effective shielding (attenuation factors as low as 0.04) of half of the circumference of the rat rectum was achievable. Unidirectional 241Am irradiators for intracavitary brachytherapy offer a unique tool for examining the effects of shielding a portion of the circumference of the rat rectum, on the radiation tolerance of the rectum.

Americium↗
PubMed1992

A comparison of radial dose functions for 103Pd, 125I, 145Sm, 241Am, 169Yb, 192Ir, and 137Cs brachytherapy sources.

Recently, encapsulated sources of 103Pd (21 keV average), 145Sm (41 keV average), 241Am (60 keV), and 169Yb (93 keV average) have been introduced as alternatives to conventional brachytherapy sources of 125I Model 6711 (27 keV average), 125I Model 6702 (28 keV average), 192Ir (369 keV average), and 137Cs (662 keV). To illustrate the dependence of the penetrating ability of photons from brachytherapy sources as a function of photon energy, a comparison of their radial dose functions is presented. Using the ITS Monte Carlo simulation code for photon-electron transport, the radial dose functions were calculated for monoenergetic photon sources with energies in the range of 30 keV to 1 MeV. Also, similar calculations were performed using the photon spectra emitted by the encapsulated brachytherapy sources. To verify the accuracy of Monte Carlo calculations, comparisons are made with our new measured data for 241Am and existing experimental and theoretical data from other investigators. A comparison of radial dose functions indicates that for 241Am, 169Yb, 192Ir and 137Cs sources radial dose functions are close to unity for distances up to 10 cm, for 145Sm the radial dose function drops to about 0.4 at 10 cm, and for 125I and 103Pd it drops precipitously to less than 0.20 at 7 cm. At 5 cm, the measured radial dose functions for 103Pd, 125I Model 6711, 125I Model 6702, 145Sm, 241Am, and 192Ir have values of 0.09, 0.34, 0.38, 0.86, 1.12, and 0.97, respectively. While all of these radioisotopes provide adequate penetrating power for interstitial brachytherapy, only the radioisotopes emitting photons with energies greater than about 40 keV can provide adequate depth dose (that is, small or no tissue attenuation) for intracavitary irradiation. Our criterion for choice of minimum photon energy suitable for intracavitary irradiation is that the radial dose function at 5 cm should not be less than 0.90. Also, note that photons with energies around 80 keV exhibit maximum penetrating ability in solid water for distances up to 5 cm.

Americium↗
PubMed1992

Some treatment planning considerations for 103Pd and 125I permanent interstitial implants.

Sealed sources of palladium-103 (103Pd), which decay with a half life of 17 days and emit on average 21 keV photons, are now in clinical use for permanent implants. For seed implantation of prostatic cancer, 103Pd implants are usually planned to deliver 115 Gy to full decay at an initial dose rate of 19.7 cGy/hr whereas 125I implants are usually planned to deliver 160 Gy at an initial dose rate of 7.72 cGy/hr. Because of the lower energy of photons emitted by 103Pd compared to the 125I sources (27 keV average energy), the tissue attenuation is more severe for 103Pd sources. The radial dose function drops more steeply with distance from the 103Pd sources compared to the 125I sources, raising a concern about the possibility of cold spots in the tumors implanted with 103Pd sources. To investigate this issue, a detailed analysis of the dependence of dose uniformity as a function of seed spacing for 125I and 103Pd sources in various cubic and spherical configurations was carried out. Using the measured single source dosimetry data as input, dose distributions for a variety of cubic and spherical implants were generated on a computerized treatment planning system. This study indicates that relative dose distributions for 125I and 103Pd implants with the same geometric configuration and number of seeds are very similar inside the implanted volume for implants. Dose uniformity within a target volume implanted with 103Pd seeds is also very similar to that for 125I. To expedite clinical implementation of 103Pd, an atlas of dose distributions for 103Pd implants has been produced for various seed configurations, seed spacings, and target volumes. Using 125I implants as a guideline, clinical procedures for planning of 103Pd implants have been developed. It was found that the total source strength implanted divided by the dimension of the implant can be expressed as an exponential function of implant size, resulting in a simple method for estimating the strength of seeds necessary in an implant. Also, the air kerma strength of 103Pd seeds is about 3.3 times that of 125I sources in an implant with the same geometric configuration and number of seeds, provided treatment doses of 115 Gy and 160 Gy are chosen for 103Pd and 125I implants, respectively.

Brachytherapy↗
PubMed1992

Urinary excretion of inorganic pyrophosphate by normal subjects and patients with renal calculi in north-western India and the effect of diclofenac sodium upon urinary excretion of pyrophosphate in stone formers.

24 h urinary pyrophosphate excretion was studied in 20 normal healthy subjects and 75 idiopathic stone formers from north-western regions of India. The mean 24-hour urinary excretion of pyrophosphate was significantly low in stone formers (50.67 +/- 2.16 mumol/24 h) as compared to that of normal subjects (71.46 +/- 5.46 mumol/24 h) (p less than 0.01). Diclofenac sodium, a non-steroidal anti-inflammatory agent, was administered 50 mg thrice daily for 1 week to 18 stone formers and 24-hour urinary pyrophosphate excretion was studied before and after drug therapy. The 24-hour urinary excretion of pyrophosphate increased from 54.32 +/- 21.40 to 78.31 +/- 28.03 mumol subsequent to diclofenac sodium therapy (p less than 0.01).

Adult↗
PubMed1992

Effect of cadmium on tissue glutathione and glutathione peroxidase in rats: influence of selenium supplementation.

Administration of cadmium (2.5 mg/kg, sc on alternate days for 3 weeks) to male albino rats led to significant accumulation of cadmium and metallothionein in the liver and kidneys. The activity of glutathione peroxidase was significantly decreased whereas, the concentration of glutathione was increased in these organs. Glycine-l-14C incorporation studies showed enhanced synthesis of glutathione in kidney but not in the liver. Selenium supplementation (1 mg/kg/day orally) failed to prevent these cadmium-induced changes, although it resulted in very high accumulation of selenium in these organs indicating the formation of cadmium-selenium complex.

Animals↗
PubMed1992

Transient thermal and mechanical response of water subject to ionizing radiation.

The ultrafast transient (10(-14) to 10(-12)S) thermal and mechanical response of water subject to ionizing radiations of different linear energy transfers has been investigated in order to understand the initial events which lead to cell mutation and lethality. Based on computational fluid dynamics, the production of a "thermal spike" around the trajectory of a charged particle and subsequent diffusion of deposited heart are calculated for particles with linear energy transfer (LET) of 4, 40, and 400 keV/microns. A radiation damage region (that is, the so-called "thermal core") is identified, and the transient behavior of the thermal core is studied. The local and transient environment has a dimension of nanometers, a scale which is of critical interest in understanding mechanisms of radiation damage in cells. The radius of the thermal core, Dd, at temperatures (or internal energy density) of up to 1,000 K, is observed to increase with LET, L, as Dd (in nanometers) = C4.L (in keV/microns)0.6, where, for example, C4 = 0.50 for T = 800 degrees C.

Energy Transfer↗