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R Nath

Publications and source records attributed to R Nath.

At least 163 records · Page 9Linked to original sources
PubMed1991

Effect of ethanol on cadmium-induced lipid peroxidation and antioxidant enzymes in rat liver.

We have investigated the effects of the intragastric administration of cadmium (10 mg/kg body weight) and ethanol (5.56 g/kg body weight) alone as well as in combination on hepatic lipid peroxidation, the antioxidant defense system, and the morphology of liver in rats. Cadmium given in combination with ethanol led to a marked increase in cadmium accumulation in liver compared to the level in rats treated only with cadmium. Further, cadmium and ethanol coexposure produced a more pronounced elevation in lipid peroxidation (L-px), which was associated with a significantly greater inhibition of antioxidant enzymes, glutathione peroxidase (GSH-px; EC 1.11.1.9), glutathione reductase (GR; EC 1.6.4.2) and superoxide dismutase (SOD; EC 1.15.1.1), than cadmium treatment alone. The levels of glutathione (GSH) and total thiols (TSH) also decreased significantly after cadmium and ethanol coexposure. On histopathological examination, it was observed that the livers of rats coexposed to cadmium and ethanol showed a marked degeneration of hepatocytes which was not seen in rats treated only with cadmium.

Animals↗
PubMed1991

ZK98299, a novel antiprogesterone that does not interact with chicken oviduct progesterone receptor.

Steroid antagonists, at receptor level, are valuable tools for elucidating the mechanism of steroid hormone action. We have examined and compared the interaction of avian and mammalian progesterone receptors with progestins; progesterone and R5020, and a newly synthesized antiprogesterone ZK98299. In the chicken oviduct cytosol, [3H]R5020 binding to macromolecule(s) could be eliminated with prior incubation of cytosol with excess radioinert steroids progesterone or R5020 but not ZK98299. Alternatively, [3H]ZK98299 binding in the chicken oviduct was not abolished in the presence of excess progesterone, R5020, or ZK98299. In the calf uterine cytosol, [3H]R5020 or [3H]ZK98299 binding was competeable with progesterone, R5020 and ZK98299 but not estradiol, DHT or cortisol. Furthermore, immunoprecipitation and protein A-Sepharose adsorption analysis revealed that in the calf uterine cytosol, the [3H]R5020-receptor complexes were recognized by anti-progesterone receptor monoclonal antibody PR6. This antibody, however, did not recognize [3H]ZK98299-receptor complexes. When phosphorylation of progesterone receptor was attempted in the chicken oviduct mince, presence of progesterone resulted in an increased phosphorylation of the known components A (79 kDa) and B (110 kDa) receptor proteins. Presence of ZK98299 neither enhanced the extent of phosphorylation of A and B proteins nor did it reverse the progesterone-dependent increase in the phosphorylation. The avian progesterone receptor, therefore, has unique steroid binding site(s) that exclude(s) interaction with ZK98299. The lack of immunorecognition of calf uterine [3H]ZK98299-receptor complexes, suggests that ZK98299 is either interacting with macromolecule(s) other than the progesterone receptor or with another site on the same protein. Alternatively, the antisteroid binds to the R5020 binding site but the complex adopts a conformation that is not recognized by the PRG antibodies.

Animals↗
PubMed1991

Oxalate binding to rat intestinal brush-border membrane in pyridoxine deficiency: a kinetic study.

Oxalate bound specifically to the intestinal brush-border membrane (BBM) of pyridoxine-deficient rats, but not to BBM of control rats. The binding of oxalate to intestinal BBM of pyridoxine-deficient rats was rapid, reversible, dependent on concentration of oxalate, temperature sensitive and competitively inhibited by oxalate analogues. Kinetic analysis of the oxalate binding data revealed induction of two distinct classes of receptor site for oxalate. The high-affinity oxalate binding sites, reached saturation at 60-70 nM oxalate, had a Kd of 24.29 nM and the number of binding sites were 30 pmoles (i.e., 1.8.10(13) molecules). The low-affinity oxalate binding sites, could not be saturated under experimental conditions upto 1 microM oxalate. It had a Kd of 487.5 nM and the number of binding sites were 156 pmoles (i.e., 9.4.10(13) molecules). The apparent energy of activation was 19 kcal/mol. The half-saturation concentration of inhibitor (IC50) of oxalate was 0.4.10(-5) M, while all other structural analogues of oxalate had higher IC50 values. Among the competitive inhibitors tested IC50 was in the following order, pyruvate greater than maleate greater than oxaloacetate greater than glyoxylate greater than parabonate greater than oxalate. These kinetic characteristics indicate involvement of a membrane protein in oxalate binding and transport in rat intestinal brush-border membrane in pyridoxine deficiency.

Alanine Transaminase↗
PubMed1991

Chronobiology of urinary citrate excretion amongst stone-formers and healthy males from north western India.

Urinary citrate excretion was estimated colorimetrically from urine samples collected every 3 h for 24 h from 25 healthy adult males (non-stone formers; mean age 39 +/- 7 years) and 25 male patients suffering from calcium nephrolithiasis (stone formers; mean age 41 +/- 6 years). The 24 h citrate excretion was 2.47 +/- 0.65 mmol in non-stone formers and 2.02 +/- 0.71 mmol in stone formers. This difference was not significant. However, cosinor rhythmometry revealed a significant circadian rhythmicity in urinary citrate excretion in the healthy males which was absent in the stone formers; the amplitude was 0.06 mmol in non-stone formers and 0.017 mmol in stone formers. The acrophase was located at 14:25 h in non-stone formers and at 23:30 h in stone formers.

Adult↗
PubMed1991

Sequential histopathologic alterations in Indian childhood cirrhosis treated with d-penicillamine.

Eight children who satisfied all the diagnostic criteria of classic Indian childhood cirrhosis were treated with d-penicillamine. Clinical recovery in a 3- to 12-month period was accompanied histopathologically by accentuation of micronodules with regression of hepatocytic degenerative changes, Mallory's hyaline, pericellular fibrosis, lobular inflammation, and disappearance of hepatocytic copper staining protein. The nodules in the posttreatment biopsies were so small as to be categorized as "micronodular cirrhosis." In one case clinical recovery was associated with an almost normal liver histology after passing through a micronodular phase. This report is the first documentation of the histologic sequence of changes in Indian childhood cirrhosis on d-penicillamine treatment.

Copper↗
PubMed1991

A simple technique for irradiation of recto-anal cancers with electrons using an internal anal shield.

A method of treating the primary site of recto-anal cancers using an en face electron beam in combination with an internal lead shield in the anus has been developed. Dose measurements using lithium fluoride thermoluminescent dosimetry indicate that the internal anal shield reduces the dose to the uninvolved anal wall by up to a factor of two while leaving the dose to the primary tumor site unaffected. Because the internal anal shield is placed in the anus during treatment, this system leads to a more precise daily positioning of the shield compared to the setup using an external shield alone. This technique has been used to treat two patients with anal cancer who tolerated the treatment well with no acute side effects. Both patients are now disease free, more than 30 months after their radiation treatment, without any treatment-related sequelae.

Aged↗
PubMed1991

A dosimetric analysis of Morris, Fletcher, and Henschke systems for treatment of uterine cervix carcinoma.

The role of intracavitary irradiation in the treatment of uterine cervix carcinoma is well established, and over the years a number of different systems for intracavitary irradiation have been developed. To compare the clinical efficacy of different systems and to develop guidelines for the design of applicators with new sources such as americium-241, we present a dosimetric comparison of three systems: (a) the Morris system, a modified Stockholm technique; (b) the Henschke system; and (c) the Fletcher system. Using a computerized planning system, dose distributions with different configurations of each system were calculated. For each case, doses to point A, B, and a set of reference points representing bladder and rectum were also calculated. Also, the 60 Gy reference volumes, as defined by ICRU Report No. 38, 1985, were calculated for six different treatment regimens. These treatment regimens employ widely different combinations of whole pelvis external beam dose, split pelvis external beam dose, and intracavitary irradiation dose to achieve similar clinical outcomes for the treatment of various stages of cervix carcinoma. From this analysis we observe the following: (a) The Morris system produces a higher dose rate to point A (70 to 90 cGy/hr) compared to the Fletcher or Henschke system (50 to 70 cGy/hr); (b) the doses to point B relative to point A dose are about the same for all three systems at 28 to 32%; (c) the doses to reference rectum and bladder points relative to point A dose for clinically equivalent configurations are about the same for Fletcher and Henschke systems (58-65%) not including the effects of shields in the vaginal ovoids, and somewhat higher for the Morris system (72-79%); (d) the volume treated to a given dose rate by each intracavitary system alone is about the same; and (e) the 60 Gy volume depends critically upon the external beam whole pelvis dose, rising steeply as the external beam whole pelvis dose approaches 30 Gy. Since different groups have used widely different prescriptions of external beam whole pelvis dose, ranging from 0 to 50 Gy depending upon stage, the 60 Gy volumes for these various dose prescriptions are strikingly different. Because the Morris system uses lower values for the external beam whole pelvis dose than the others, its 60 Gy volume for the advanced Stage IIB and IIIB is 2 to 4 times lower than others. This choice makes the Morris system more conservative than others, probably resulting in slightly lower cure rates for the advanced stage disease.

Brachytherapy↗
PubMed1991

Effect of ethanol on cadmium uptake and metabolism of zinc and copper in rats exposed to cadmium.

Effects of chronic administration of cadmium and ethanol, alone as well as in combination, on the uptake of cadmium and its interaction with other essential trace elements in various tissues of adult rats were investigated. Cadmium given in combination with ethanol led to a pronounced increase in cadmium absorption and accumulation in all the tissues studied relative to both non-exposed controls and rats treated with cadmium alone. Both cadmium and ethanol exhibited specific effects on copper and zinc levels of the tissues. These effects often were significantly altered when the animals were co-exposed to cadmium and ethanol. The results suggested that although both cadmium and ethanol individually pose a hazard to essential trace metal homeostasis of various organs, co-exposure can pose a major threat since animals exposed to ethanol absorb much more cadmium than their unexposed counterparts.

Absorption↗
PubMed1991

A method for determination of iododeoxyuridine substitution of thymidine using reversed-phase high-performance liquid chromatography.

An assay for thymidine substitution by iododeoxyuridine (IdUrd) using reversed-phase high-performance liquid chromatography (HPLC) has been developed. Three principal steps in this procedure are: extraction of DNA from cell or tissues, hydrolysis of DNA into deoxynucleosides and separation using HPLC. Approximately 1 microgram of DNA was recovered from 10(5) cells by phenol extraction, and subjected to hydrolysis into deoxynucleosides which required a three-stage DNA digestion using enzymes DNAse I. phosphodiesterase I and alkaline phosphatase. The deoxynucleosides were separated on the Microsorb C18 column with isocratic elution; 90-100% of the DNA was recovered as deoxynucleosides on the column. The method was used to determine quantitatively the percent IdUrd substitution of thymidine in Chinese hamster lung cells in vitro and BA1112 rhabdomyosarcoma in WAG/Rij rats perfused with IdUrd. It was possible to determine the thymidine substitution by IdUrd as small as 1% using a few micrograms of DNA. The close correspondence between the percent substitutions determined by HPLC and those determined by radioactive assay using [125I]-labelled IdUrd, confirmed the accuracy of our HPLC method. The HPLC analysis is especially suitable for the determination of percent IdUrd substitution of thymidine in tissue biopsies from animals used in in vivo experiments or humans undergoing radiation treatment.

Animals↗
PubMed1991

The effect of diclofenac sodium on urinary concentration of calcium, uric acid and glycosaminoglycans in traumatic paraplegics.

Non-steroidal anti-inflammatory drugs (NSAID) have been shown to decrease calcium excretion in the experimental animal, in human volunteers and in calcium stone formers. Paraplegics tend to be hypercalciuric during the first 2 years after their injury and this is said to be a predisposing factor for stone formation in these patients. The effect of the NSAID diclofenac sodium was studied in 12 traumatic paraplegics who had sustained their injury 1 to 6 months previously; 24-h urine samples collected before and 2 weeks and 4 weeks after oral diclofenac sodium 50 mg tds were analysed for calcium, uric acid, glycosaminoglycans (GAGs) and volume. There were no significant changes in urinary volume, uric acid and GAGs excretion. However, urinary calcium concentration and 24-h calcium excretion decreased significantly following 2 weeks' and 4 weeks' treatment with diclofenac sodium.

Adult↗
PubMed1991

Interaction of metals with brain calmodulin purified from normal and cadmium exposed rats.

Chronic exposure of cadmium (Cd) to rats (6 mg/kg body weight/day) led to a significant accumulation of Cd in brain and other organs. Calmodulin (CaM) isolated from brains of Cd exposed rats showed a decreased ability to stimulate CaM-dependent phosphodiesterase (PDE) as compared to that purified from unexposed animals. There was a dose dependent inhibition of CaM activity when CaM (from normal and Cd exposed rats) was incubated with different molar ratios of aluminium (Al3+), lead (Pb2+), manganese (Mn2+) and vanadium (V5+). Regression analysis of rat brain CaM activity versus varying metal ion concentration demonstrated negative slopes. However, CaM from the brains of Cd exposed rats was less sensitive to these metals in comparison to the normal rat brain CaM. These data suggest that CaM inhibition may be used as a biological marker of neurotoxicity and for elucidating the possible mechanism by which neurotoxic metals manifest toxic effects.

Animals↗
PubMed1991

Treatment of chronic pain by epidural spinal cord stimulation: a 10-year experience.

Epidural spinal cord stimulation by means of chronically implanted electrodes was carried out on 121 patients with pain of varied benign organic etiology. In 116 patients, the pain was confined to the back and lower extremities and, of these, 56 exhibited the failed-back syndrome. Most patients were referred by a pain management service because of failure of conventional pain treatment modalities. Electrodes were implanted at varying sites, dictated by the location of pain. A total of 140 epidural implants were used: 76 unipolar, 46 Resume electrodes, 12 bipolar, and six quadripolar. Patients were followed for periods ranging from 6 months to 10 years, with a mean follow-up period of 40 months. Forty-eight patients (40%) were able to control their pain by neurostimulation alone. A further 14 patients (12%), in addition to following a regular stimulation program, needed occasional analgesic supplements to achieve 50% or more relief of the prestimulation pain. Pain secondary to arachnoiditis or perineural fibrosis following multiple intervertebral disc operations, when predominantly confined to one lower extremity, seemed to respond favorably to this treatment. Uniformly good results were also obtained in lower-extremity pain secondary to multiple sclerosis. Pain due to advanced peripheral vascular disease of the lower limbs was well controlled, and amputation below the knee was delayed for up to 2 years in some patients. Pain due to cauda equina injury, paraplegic pain, phantom-limb pain, pure midline back pain without radiculopathy, or pain due to primary bone or joint disease seemed to respond less well. Patients who responded to preliminary transcutaneous electrical nerve stimulation generally did well with electrode implants. Notable complications included wound infection, electrode displacement or fracturing, and fibrosis at the stimulating tip of the electrode. Three patients in this series died due to unrelated causes. Epidural spinal cord stimulation has proven to be an effective and safe means of controlling pain on a long-term basis in selected groups of patients. The mechanism of action of stimulation-produced analgesia remains unclear; further studies to elucidate it might allow spinal cord stimulation to be exploited more effectively in disorders that are currently refractory to this treatment modality.

Chronic Disease↗
PubMed1991

In vivo effects of cadmium on calmodulin and calmodulin regulated enzymes in rat brain.

Effect of chronic cadmium (Cd) exposure and the influence of diethyldithiocarbamate (DDC) on Cd absorption was studied on the brain of young male Wistar rats. A significant amount of Cd accumulated in cerebral cortices of rats after 4 weeks of Cd (6 mg/kg body wt) exposure (through gastric intubation). The biological activity of calmodulin (CaM) decreased significantly (p less than 0.001) in the cerebral cortices of these animals in comparison to the control group. 3'-5' Phosphodiesterase and synaptic membrane Ca(2+)-Mg(2+) ATPase were also significantly affected (p less than 0.01 and p less than 0.001 respectively). However, Cd treatment did not alter synaptic membrane adenylate cyclase activity and DDC (9.2 mg/kg body wt, intraperitoneal) treatment along with Cd (6 mg/kg body wt) enhanced Cd accumulation in cerebral cortices of treated animals resulting in an increased inhibition of CaM and CaM dependent enzymes. These data suggest that Cd may be acting via binding to CaM and uncoupling it from its normal cellular control of calcium.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1990

Enhanced IUdR radiosensitization by 241Am photons relative to 226Ra and 125I photons at 0.72 Gy/hr.

The dependence of IUdR radiosensitization on photon energy was investigated by irradiating Chinese hamster cells in vitro under aerobic conditions at a dose rate of 0.72 Gy/hr which is typical of temporary brachytherapy implants. It had been observed previously that the IUdR radiosensitization with the 60 keV photons from 241Am is about 1.5 times greater than that with 830 keV (average) photons from 226Ra. It was hypothesized that the enhanced IUdR radiosensitization for 60 keV photons was a result of a larger production of Auger electron cascades from the filling of K-shell vacancies in the iodine atoms, which have a K-shell binding energy of 33.2 keV. Since most of the photons from a 125I source have energies below 33.2 keV, it would be expected that IUdR radiosensitization with 28 keV (average) photons from 125I and 830 keV (average) photons from 226Ra would both be smaller than the radiosensitization with the 60 keV photons from 241Am. To test this hypothesis we compared IUdR radiosensitization for 226Ra, 241Am, and 125I at 0.72 Gy/hr, using Chinese hamster lung cells in vitro. The measured survival curves led to RBEs of 1.20 +/- 0.10 and 1.30 +/- 0.11 for 241Am and 125I photons relative to 226Ra; to IUdR radiosensitization factors at a 10(-5) M concentration of 1.35 +/- 0.11, 1.67 +/- 0.09, and 1.47 +/- 0.08 for 226Ra, 241Am, and 125I, respectively; and to radiosensitization factors at a 10(-4) M concentration of 1.89 +/- 0.16, 3.04 +/- 0.13, and 2.48 +/- 0.17 for 226Ra, 241Am, and 125I, respectively. These results indicate that IUdR produces significant radiosensitization with all three isotopes (226Ra, 241Am, and 125I) for continuous low dose rate irradiations at 0.72 Gy/hr. Also, we observed greater radiosensitization with 241Am photons compared to 226Ra on the higher energy side and to 125I on the lower energy side. These findings support the concept that photon-induced Auger electrons produce a significant increase in IUdR radiosensitization when photons with energies just above the K-edge of the iodine atom are employed for continuous low dose rate irradiations. These findings suggest that regimens combining IUdR infusion with temporary brachytherapy implants using low energy photons in relatively quiescent sites such as brain tumors may have clinical potential, and indicate the need for rigorous preclinical evaluation of this approach.

Americium↗
PubMed1990

Deep brain stimulation for control of intractable pain in humans, present and future: a ten-year follow-up.

Deep brain stimulation with chronically implanted electrodes has provided satisfactory control of pain in patients with intractable chronic pain syndromes, which have been refractory to medication and other conventional modalities of management. In this series the authors present their experience with 48 patients who have been followed for periods ranging from 6 months to 10 years. Long-term pain control was achieved in 30 patients (63%). Both the periventricular gray and specific sensory thalamic nuclei have been used as targets. Our results indicate that there is an initial 2-year fall-off of pain control caused by idiopathic tolerance, with stable results thereafter, regardless of site of the implant. This is suggestive of some biochemical modification of tissues around the electrode. Patients with failed-back syndrome secondary to multiple disc operations fared well; those with pain secondary to progressive neurological disorders or cancer had only short-term pain relief, and those with thalamic pain, cauda equina injury, or phantom limb pain usually had a poor result. Deep brain stimulation, in selected patients, appears to provide long-term pain control safely with few side effects or complications.

Adult↗
PubMed1990

Comparative studies on the effect of vitamin A, B1 and B6 deficiency on oxalate metabolism in male rats.

The study was conducted to investigate the effect of vitamin A, B1 and B6 deficiency on oxalate metabolism in rats. A significant hyperoxaluria was the common observation in all the three vitamin deficiencies (vitamin B6 greater than vitamin A greater than vitamin B1). The activities of hepatic glycolate oxidase and glycolate dehydrogenase were markedly enhanced in vitamin-A- and vitamin-B6-deficient rats. However, lactate dehydrogenase levels remained unaltered in these deficiencies as compared to their respective pair-fed controls. Vitamin B1 deficiency of 4 weeks' duration could augment the activity of glycolate oxidase only, with no alterations in the glycolate dehydrogenase and lactate dehydrogenase levels. Intestinal oxalate uptake studies revealed increased bio-availability of oxalate from the gut in vitamin-A- and vitamin-B6-deficient rats. Thus, the results suggest the relative contribution of both exogenous as well as endogenous oxalate in the process of calculogenesis under various nutritional stress conditions in rat.

Animals↗