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Biomedical subjects

R Nath

Publications and source records attributed to R Nath.

At least 199 records · Page 11Linked to original sources

Effects of continuous low dose-rate irradiation: computer simulations.

The effects of continuous low dose-rate irradiation are studied with a computer model that incorporates cell kinetics and the accumulation and repair of radiation damage. This theoretical approach independently explores the effects on survival curves of a phase block, inherited damage and proliferation by dying cells. The computer model is a Monte Carlo simulation which follows the evolution in time of the family trees of a growing cell population under continuous irradiation. The model uses as input the measured phase-specific survival curves for acute exposures and the cell kinetic parameters to generate survival curves for continuous low dose-rate irradiations. Cell survival curves for Chinese hamster lung cells (V79) for dose rates ranging from 15 to 500 cGy/h have been generated using various model assumptions. The model shows that for these cells a G2 block will maximize cell killing for an optimum dose rate near 75 cGy/h. The effect on survival curves of inherited damage, as well as that of the proliferation by dying cells, is shown to increase monotonically with decreasing dose rates, and to be quite large at low dose rates.

Animals↗

A study of central neurotransmitter mechanisms in morphine-induced 'Straub reaction' in mice: role of central dopamine receptors.

1. The role of putative neurotransmitters was investigated in morphine-induced Straub reaction (SR) in albino mice. 2. Apomorphine (15 mg/kg) was also effective in inducing SR. However, in a smaller dose (0.2 mg/kg) it blocked SR induced by morphine. 3. Morphine-induced SR was potentiated by tranylcypromine, reserpine (acute effect), imipramine and L-dopa and blocked by reserpine (chronic effect), alpha-methyldopa, pimozide, chlorpromazine, haloperidol and metoclopramide. Prazosin and clonidine partially blocked morphine SR in high doses. 4. Propranolol, yohimbine, cyproheptadine and atropine were ineffective in blocking morphine SR. 5. The results indicate that morphine SR is mediated through release of DA in the CNS which excites central D2 receptors. Activation of central alpha 1-adrenoceptors might also play a minor role.

Animals↗

Chronological variation in chemical composition of urinary calculi between 1965-68 and 1982-86 in north western India.

The chemical composition of 210 urinary calculi either spontaneously passed or surgically removed during January 1965-December 1968 was compared with the chemical composition of 1338 urinary calculi received during July 1982-June 86. The proportion of vesical calculi had significantly decreased from 30.48% (n = 64) during 1965-68 to 8.37% (n = 112), during 1982-86 (p less than 0.001). During 1965-68, magnesium was present in 16%, ammonium in 31% and urate in 33% of vesical calculi. But during 1982-86, the percentage of vesical calculi containing magnesium and ammonium was nil (p less than 0.001), but 76.8% of vesical calculi contained urate (p less than 0.001). Similarly, during 1965-68, 35.6% of renal calculi containing magnesium, 20% contained ammonium, 13.6% contained carbonate and urate was present in 32.2% of renal calculi. In contrast during 1982-86, magnesium was detected in only 0.24% of renal calculi (p less than 0.001), ammonium in 0.16% (p less than 0.001) and carbonate in 3.9% (p less than 0.001) but 57.4% of renal calculi contained urate (p less than 0.001).

Adolescent↗

A comparative study of the diuretic, natriuretic, and kaluretic effects of furosemide when administered at 07:00 h and at 19:00 h.

Furosemide (0.5 mg/kg, i.v.) was administered to 31 healthy, day-active adults (Group 1) at 07:00 h (study 1) and urine output during the next 2 h was collected. Urine volume, urinary sodium, potassium and creatinine were determined. After 60 h, furosemide (0.5 mg/kg, i.v.) was administered at 19:00 h (study 2) and urine output during the subsequent 2 h (19:00 h to 21:00 h) was collected for estimation of urine volume, sodium, potassium and creatinine. Twenty-two healthy, day-active adults (Group 2) who constituted the control group underwent study 1 and study 2 and received 2 ml of normal saline instead of furosemide. There was no significant difference in urinary volume, urinary sodium, potassium and creatinine excretion between study 1 and study 2 in the control subjects (Group 2). In contrast, administration of furosemide at 07:00 h (study 1) resulted in greater diuresis (247.1 +/- 202.07 ml), more marked sodium excretion (42.66 +/- 29.06 mmol), increased potassium excretion (5.14 +/- 4.014 mmol), and greater creatinine excretion (0.415 +/- 0.414 mmol) as compared to study 2. In conclusion, the diuretic, natriuretic and kaluretic effects of furosemide are greater when administered at 07:00 h than at 19:00 h. Therefore, in clinical practice, the time of administration of furosemide can be so chosen as to achieve a greater diuresis or to prevent a marked loss of sodium.

Adult↗

Role of metallothionein in metal detoxification and metal tolerance in protein calorie malnutrition and calcium deficient monkeys (Macaca mulatta).

A monkey model has been set up for protein calorie malnutrition and calcium deficiency. Oral exposure of 5ppm Cd/kg body wt./day for 24 weeks led to increased excretion of Cd, metallothionein (MT) and zinc. Rehabilitation of PCM monkeys for one year resulted in gradual reduction and finally complete disappearance of urinary metallothionein. During Cd exposure, the accumulation of Cd and induction of MT was significantly higher in liver, kidney and intestine. MT was also induced in heart, lung and testis of Cd exposed PCM and calcium deficient monkeys. Metallothionein from liver has been resolved into three isoforms, viz MTa, MTb and MTc on DEAE-Sephadex A 25 ion exchange column. MTc is the major isoform in Cd-treated, normal and protein calorie malnourished monkeys whereas MTb is the major isoprotein in the cadmium treated calcium deficient monkeys. The iso-metallothioneins varied in their metal composition in the nutritional stress conditions and showed different capacities to reactivate apo-enzymes viz. alkaline phosphatase, ceruloplasmin, superoxide dismutase and glutathione peroxidase. Thus, metallothionein plays a key role in metal metabolism during cadmium toxicity under nutritional stress conditions.

Alkaline Phosphatase↗

Isolation and characterization of a metallothionein-like protein from monkey brain.

A cadmium-binding protein from monkey brain has been isolated, purified and characterized. The absorption spectrum of this protein indicates the presence of Cu-Zn thionein in the normal monkey brain which has a strong affinity to bind cadmium. On cadmium exposure the protein sequestered most of the cadmium which entered the brain. The apparent molecular weight of this protein as determined on a gel filtration column calibrated with marker proteins has been found to be in the range of 11,500-12,000 Da. The ratio of absorbance at 254 nm/280 nm is more than 1 indicating the presence of cadmium-mercaptide bonds, which was further confirmed by the presence of 15 cysteine residues. Polyacrylamide gel electrophoresis of the protein shows 3 bands indicating the presence of 3 isometallothionein forms. Unlike hepatic or renal thioneins, the cadmium-binding protein in brain is not inducible following administration of cadmium. However, when antibodies raised against hepatic metallothionein were cross-reacted with brain Cd-binding protein, a line of identity was observed, indicating the 2 proteins are immunologically identical and share a high degree of structural similarity.

Animals↗

Enhancement of IUdR radiosensitization by low energy photons.

The effect of the photon energy on the radiosensitization produced by iododeoxyuridine (IUdR) was examined using Chinese hamster cells in vitro. Radiosensitization by IUdR was considerably higher for 60 keV photons from 241Am sources than for the 860 keV photons (average energy) from 226Ra sources, under continuous low dose rate conditions applicable to intracavitary brachytherapy (a dose rate of 0.57 Gy/hr). Also, IUdR radiosensitization was higher for 250 kV X rays than for 4 MV X rays under the acute exposure conditions used in external beam radiation therapy (dose rates of 1 to 2 Gy/min). These data support the hypothesis that photons with energies just greater than 32.2 keV, the K-absorption edge of iodine, are more effective in causing cell damage than are photons of other energies, because their absorption results in the production of Auger electron cascades and therefore in the production of high linear energy transfer (LET) radiations.

Americium↗

Dosimetry studies on prototype 241Am sources for brachytherapy.

Sealed sources of 241Am emit primarily 60 keV photons which, because of multiple Compton scattering, produce dose distributions in water that are comparable to those from 226Ra or 137Cs. However, americium gamma rays can be shielded by thin layers of high atomic number materials since the half value layer thickness is only 1/8th of a mm of lead for americium gamma rays as compared to a value of 12 mm for 226Ra gamma rays. This may allow effective in vivo shielding of critical organs, for example; the bladder can be partially shielded by hypaque solution, and the rectum and sigmoid colon by barium sulfate. In addition, the exposure to medical personnel involved in intracavitary application and patient care may be reduced substantially by the use of relatively thin lead aprons and light weight, portable shields. To investigate the feasibility of 241Am sources for intracavitary irradiation, dosimetry studies on prototype 241Am sources have been performed and a computer model for the determination of dose distributions around encapsulated cylindrical sources of 241Am has been developed and tested. Results of dosimetry measurements using ionization chambers, lithium fluoride thermoluminescent dosimeters, a scanning scintillation probe, and film dosimetry, confirm theoretical predictions that these sources can deliver dose rates adequate for intracavitary irradiation. Further dosimetry measurements in simulated clinical situations using lead foils and test tubes filled with hypaque or barium sulfate, confirm the predicted effectiveness of in vivo shielding which can be readily achieved with 241Am sources.

Americium↗

Development of an 241Am applicator for continuous low-dose-rate irradiation of the rat sarcoma BA1112.

An 241Am applicator for continuous low-dose-rate irradiation of the rat sarcoma BA1112 has been developed. The irradiator consists of two disc sources, each containing 800 mCi of 241Am, an isotope which emits primarily 60 keV photons. The disc sources are held in a specially-designed light-weight helmet which surrounds the tumor on the head of the rat. Dose distributions produced by these sources have been measured using an ionization chamber, thermoluminescent dosimeters and Fricke dosimeter. A computerized treatment planning system has been modified to compute dose distributions from 241Am sources, to optimize the design of this applicator. Computed and measured dose distributions for several values of separation between the 241Am discs are presented. A survival curve for cells from tumors irradiated in vivo with this applicator has been determined by an in vitro colony formation technique. The mean lethal dose DO was found to be 720 cGy for an average tumor dose rate of 95 +/- 7 cGy/hr. The major advantages of the 241Am applicator in comparison with the 192Ir applicator used previously for continuous low-dose-rate studies are: a considerably smaller half value layer thickness and the longer half life of the radionuclide. These features make it more suitable for long-term tumor cure studies because of the lower whole body dose to the animal, the availability of relatively constant dose-rate irradiators for many years, the decreased shielding requirements for the animal care facility and the diminished exposure to laboratory personnel involved with the implants on the animals.

Americium↗

Oxalate metabolism in thiamine-deficient rats.

Male weanling rats were maintained on a thiamine-deficient diet for 4 weeks, and compared with ad libitum and pair-fed controls. Thiamine deficiency led to slow growth and finally a decrease in body weight. Liver and kidney weights of the deficient rats were low, but appropriate to the body weight. Thiamine deficiency also caused a significant decrease in erythrocyte transketolase levels. The decarboxylation of glyoxylate both via the glyoxylate oxidation cycle and alpha-ketoglutarate:glyoxylate (alpha-KG:GA) carboligase was significantly lower in the liver and kidney mitochondria, leading to accumulation of glyoxylate in the tissues and its excretion in the urine. Part of the accumulated glyoxylate is converted to oxalate, causing hyperoxaluria.

Aldehyde-Ketone Transferases↗

Effects of norepinephrine on the dog common carotid, coronary and renal arteries: in vitro studies.

The effects of norepinephrine were studied on segments of the common carotid, left circumflex and renal arteries of dogs with the endothelium intact and removed. Norepinephrine induced a dose-dependent increase in tension in segments of the renal and carotid artery but did not produce any effect on the coronary artery. Although the absence of endothelium did not affect the magnitude of the norepinephrine-induced vasoconstriction of the renal artery, it elicited a more pronounced response in the carotid artery in which the endothelium was removed. Our data suggest that the vascular response to norepinephrine is dependent upon the specific arterial bed and, secondly, that the endothelium plays a determinant role in the magnitude of the response of the carotid artery.

Animals↗

Purification and characterization of metallothionein from liver of cadmium exposed rhesus monkeys (Macaca mulatta).

Metallothionein (MT) a low molecular weight, Cd-binding, cysteine rich, cytosolic protein has been isolated, purified and characterized from cadmium exposed Rhesus monkeys maintained on protein calorie malnourished (PCM) diet. Metallothionein was resolved into three isoforms i.e. MTa, MTb and MTc. The ratio of Cd, Zn and Cu varied in these isometallothioneins. MTc was the major isometallothionein. U.V. Spectra of MTc revealed the presence of mercaptide bonds and absence of aromatic amino acids. These observations were further confirmed by amino acid analysis of MTc which demonstrated high cysteine content (22.6) followed by serine, glycine and lysine. The molecular weight of MTc as determined by gel filtration and amino acid analysis was 13,000 and 6398 daltons respectively. This demonstrates that MTc is a nonglobular ellipsoid polypeptide. MTc showed a unique property of binding selenium. Monkey liver metallothionein was immunologically identical with human metallothionein. All the characteristics of MTc obtained in the present study reveal a similarity between monkey and human metallothionein probably due to closer phylogenetic relationship between the two species.

Amino Acids↗

Inhibition of calcium oxalate monohydrate (COM) crystal growth by pyrophosphate, citrate and rat urine.

An assay system for the measurement of the rate of Calcium Oxalate Monohydrate (COM) seed crystal growth in a metastable solution of calcium chloride and sodium oxalate containing traces of 14C-oxalic acid was used to assess the inhibitory activity of pyrophosphate (10(-5) M-10(-4) M), citrate (10(-4) M-10(-3) M) and urines of normal and pyridoxine deficient rats. Both pyrophosphate and citrate were strong inhibitors of COM crystal growth and caused a 50% decrease in crystal growth rate at 1.50 X 10(-5) M and 2.85 X 10(-4) M respectively. Normal rat urine strongly inhibited the COM crystal growth, while pyridoxine deficient animals showed a significant (p less than 0.01) decrease in mean inhibitory activity as compared to pair-fed controls. A lowered urinary inhibitory potential accompanied with hyperoxaluria and hypercalciuria, which is known to be associated with pyridoxine deficiency, may be a contributory risk of calcium oxalate crystallization and stone formation.

Animals↗

Effect of cadmium on lipid composition of the weanling rat brain.

The effect of early postnatal cadmium exposure (cadmium injected at dose levels of 1 and 2 mg cadmium/kg body weight on 3rd, 10th and 17th day after birth) on various lipid fractions of the weanling rat brain was studied. The results suggest that cadmium treatment (a dose of only 2 mg Cd/kg) results in an appreciable decrease in myelin-specific lipids like nonesterified cholesterol, ethanolamine-containing lipids, cerebrosides and sulfatides leading to hypomyelination. The lower dose of cadmium (1 mg Cd/kg) did not have any significant effect.

Animals↗