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Biomedical subjects

S B Rao

Publications and source records attributed to S B Rao.

At least 19 recordsLinked to original sources
PubMed1993

Halomethane-chlordecone (CD) interactive hepatotoxicity--current concepts on the mechanism.

Why is a low dose of toxic chemical nontoxic? What makes a larger dose of the same chemical toxic? Extensive work done to understand the mechanism of halomethane hepatotoxicity and its potentiation by chlorinated insecticide, chlordecone has resulted in the understanding of these basic tenets of toxicology. Studies suggest that ordinarily a small dose of halomethane causes limited liver injury which is accompanied by stimulated tissue repair enabling complete recovery from injury before manifestation. A large dose of halomethane becomes toxic due to suppressed tissue repair, which permits injury to progress in an unchecked fashion. Exposure to very low levels of chlordecone results in highly exaggerated toxicity of ordinarily nontoxic doses of halomethane because of suppressed hepatocellular regeneration and restoration, permitting the progression of liver injury ultimately resulting in liver failure and animal mortality. This concept is further supported by the observation that, while exposure to even high levels of phenobarbital and subsequent low nontoxic doses of halomethane results in greater level of initial liver injury, tissue repair is not completely suppressed; it is slightly postponed by 24 hr, but then much higher rate of tissue repair ensures and consequently enables the animals to completely recover from liver injury and survive. Thus, whether initiation of tissue repair processes occurs or not is the critical determinant in the ultimate manifestation of hepatotoxicity and its end result of either animal death or recovery and survival. Currently understood 'Mechanisms of toxicity' adequately explain only how toxic injury begins. These mechanisms do not permit us to predict the ultimate outcome of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Magnetic resonance imaging in full-term infants with repetitive focal seizures.

We report two full-term infants who developed repetitive focal seizures within the first 48 hours of life. Neither infant had predisposing factors and there were no abnormalities on a computed tomography (CT) scan performed on day 2 of life. Magnetic resonance imaging (MRI) performed during the second week of life showed a focal hemorrhagic infarction in both patients. We conclude that either an MRI or a contrast-enhanced CT scan should be obtained within 1 week in patients in whom the initial imaging technique failed to reveal a focal lesion, at which time a cerebral infarction can be diagnosed with greater sensitivity.

Brain↗
PubMed1992

Plasticity in the barrel cortex of the adult mouse: effects of chronic stimulation upon deoxyglucose uptake in the behaving animal.

We investigated experience-dependent regulation of neuronal activity in the whisker-to-barrel pathway of the adult mouse using the autoradiographic deoxyglucose (DG) method. Animals were placed in the Lausanne whisker stimulator, and three of their whisker follicles were passively stimulated for a period of 1, 2, or 4 d. After this period, mice received a dose of DG and were placed in a cage containing a pile of wooden sticks. Mice that underwent the same procedure except the passive stimulation served as controls. Patterns of stimulus-dependent DG uptake were studied in the somatosensory cortex and in the trigeminal sensory brainstem complex. DG uptake in the barrels corresponding to the passively stimulated whiskers was lower than in controls. This decrease was present throughout the radial extent of a barrel column and was observed in all passively stimulated animals. Quantitative analysis confirmed these observations and, furthermore, showed a statistically significant decrease in DG uptake in barrels neighboring the passively stimulated ones. In half of the animals, the brainstem nuclei showed a decreased DG uptake in the representation of the passively stimulated whiskers, whereas in the other animals the pattern of DG uptake was as in controls. We propose that the signs of cortical plasticity are due to a mechanism that operates in layer IV and functions as a gate for peripheral sensory activity to enter cortical circuitry.

Animals↗
PubMed1990

Keratinization of rat vaginal epithelium--V. Modulation of intracellular calcium by estradiol.

Changes in the calcium levels under the influence of estradiol were investigated in rat vaginal epithelial cells (VEC). After single estradiol injection, the immature rats showed 1.5-fold increase in Ca2+ levels within 15 min when compared to control animals. Progesterone priming brought calcium levels well below control values throughout the experimental period (up to 12 h). Ca2+ levels in serum did not show any appreciable change. Localization of calcium in VEC with electron microscopy showed aggregates of calcium oxalate on the inner nuclear membrane, nucleolus, mitochondria and keratohyaline granules. After 15 min of estradiol priming, maximum electron density was seen on all these cell organelles mentioned above, however, by 30 min the electron density was reduced considerably and did not increase during the experimental period (up to 12 h).

Animals↗
PubMed1990

Perturbations in polyamines and related enzymes following chlordecone-potentiated bromotrichloromethane hepatotoxicity.

The mechanism by which chlordecone (CD) amplifies the hepatotoxicity of halomethanes such as CCl4, CHCl3, and BrCCl3 has been a subject of intense study. Recent work has shown that suppression of hepatocellular regeneration leads to accelerated progression of liver injury leading to complete hepatic failure due to an unusual interaction between individually nontoxic low-dose combination of CD and CCl4. Since polyamines are involved in cell division, their levels reflect the extent to which there is suppression of hepatocellular regeneration during CD and CCl4 interaction. The present studies were designed to investigate the polyamine levels and associated enzymes in livers of rats treated with BrCCl3 alone or CD and BrCCl3 low-dose combination in order to confirm whether the sequence of events of hepatotoxicity is similar to that seen in CCl4 toxicity or that seen during CD and CCl4 interaction. The extent of liver toxicity in rats fed 10 ppm chlordecone (CD) for 15 days prior to the injection of a single low dose of BrCCl3 (15 microL/kg body weight) or after exposure to a high dose of BrCCl3 (80 microL/kg body weight) without CD pretreatment, was similar 6 and 24 hr later as assessed by plasma transaminase levels. There was also an increase in transaminase levels, in rats exposed to a single low dose of BrCCl3 alone (15 microL/kg body weight) but this increase was far below the high-dose exposure alone or the combination treatment. Hepatic levels of ornithine decarboxylase, S-adenosylmethionine decarboxylase, N1-acetylputrescine, N1-acetylspermidine, putrescine, spermidine, and spermine at the end of 24 hr increased after exposure to a low dose of BrCCl3 alone as compared to exposure to a high dose alone or the low-dose combination of CD and BrCCl3. Liver spermidine N1-acetyltransferase was elevated at 2, 6, and 24 hr after exposure to a high dose of BrCCl3 alone as compared to treatment with a low-dose combination of CD and BrCCl3 suggesting decreased synthesis of this enzyme, in spite of a greater need as seen from liver transaminase levels. In general, it was observed that there is significant elevation in some polyamines and related enzymes during toxicity of a low dose of BrCCl3 which seemed to stabilize within 24 hr. This was not observed with the other two groups of rats exposed either to BrCCl3 high dose alone or the low-dose combination of CD and BrCCl3.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetyltransferases↗
PubMed1990

Sarcoidosis. Report of two cases with oral involvement.

Sarcoidosis is a multisystem granulomatous disease in which pulmonary involvement is the most characteristic feature. Even though extrapulmonary manifestations occur infrequently in the area of the head and neck an occasional patient will have oral involvement. As we will demonstrate in these case reports, sarcoidosis should be included in the differential diagnosis of oral and perioral papular lesions noted on examinations of the head and neck.

Adult↗
PubMed1990

Comparative evaluation of sequestration of polyamines by perfused rabbit and rat lungs.

Differences were observed in the sequestration of polyamines putrescine, spermidine and spermine by isolated, ventilated, perfused rat and rabbit lungs, former being able to accumulate more polyamines compared to the latter. Steady state equilibrium was reached earlier for spermine in rat. Isolated ventilated lungs were perfused with harmaline and ouabain, inhibitors known to inhibit the sodium pump at a maximum concentration of 1 mM for rabbit lungs and 0.4 and 0.2 mM for rat lungs, respectively. They did not affect the uptake of polyamines by rat lung but decreased the uptake of putrescine by rabbit lung. Decreased sodium (50 meq/L) in the perfusate increased the uptake of spermine and spermidine by rabbit lung but again showed no effect with rat lung. However, the uptake of polyamines by isolated ventilated rat and rabbit lungs perfused for 60 min with these compounds was linear over the entire range of high concentrations studied. These results suggest that the major uptake process of polyamines by intact lungs of both animal species is primarily by simple diffusion. HPLC analysis of the perfusate and lungs from both animal species post-perfusion indicated no detectable metabolites of the polyamines.

Animals↗
PubMed1990

Immunoelectrophoresis of mycobacterial antigens.

Polyvalent antiserum to culture filtrate of H37 Ra M. tuberculosis was raised in rabbits. Monospecific antiserum was raised against M. tuberculosis antigen-5, prepared from the culture filtrates by immunoabsorbent affinity chromatography. On immunoelectrophoresis, antigen-5 demonstrated single precipitin arc against polyvalent and monospecific antisera. The culture filtrate antigen demonstrated multiple precipitin arcs against polyvalent antiserum and single precipitin are against monospecific antiserum. Antigen-5 could be isolated and characterized from the culture filtrate of H37 Ra M. tuberculosis. Immunoelectrophoresis could be one of the method to characterize the mycobacterial antigens prepared in the laboratory.

Animals↗
PubMed1989

Protective role of fructose 1,6-bisphosphate during CCl4 hepatotoxicity in rats.

Rats were injected intraperitoneally with CCl4 (2.5 ml/kg body wt.) and the hepatotoxicity was compared with that of rats receiving the same dose of CCl4 and an intraperitoneal injection of fructose 1,6-bisphosphate (2 g/kg body wt.). A 50-70% decrease in plasma aspartate aminotransferase and alanine aminotransferase activities was observed in the latter treatment, indicating a protective role of the sugar bisphosphate in CCl4 hepatotoxicity. The protection was accompanied by elevated hepatic activities of ornithine decarboxylase at 2, 6 and 24 h, S-adenosylmethionine decarboxylase at 6 h, and spermidine N1-acetyltransferase at 2 h. The increase in the enzymes involved in polyamine metabolism was shown in our previous work [Rao, Young & Mehendale (1989) J. Biochem. Toxicol. 4, 55-63] to correlate with increased polyamine synthesis or interconversion, which was related to the extent of hepatocellular regeneration. The hepatic contents of fructose 1,6-bisphosphate and ATP significantly decreased after CCl4 treatment, and administration of the sugar bisphosphate increased hepatic ATP. Fructose 1,6-bisphosphate, an intermediary metabolite of the glycolytic pathway, may decrease CCl4 toxicity by increasing the ATP in the hepatocytes. The ATP generated is useful for hepatocellular regeneration and tissue repair, events which enable the liver to overcome CCl4 injury.

Acetyltransferases↗
PubMed1989

Hepatic polyamines and related enzymes following chlordecone-potentiated carbon tetrachloride toxicity in rats.

Chlordecone potentiation of the hepatotoxic and lethal effects of CCL4 has been well established. Recent studies have shown that the suppression of hepatocellular regeneration results in an accelerated progression of liver injury leading to complete hepatic failure. Since polyamines are involved in cell division, these studies were designed to investigate the polyamine levels and associated enzymes in the livers of rats treated with a low-dose combination of CD and CCl4. For comparison, a large toxic dose of CCl4 was also employed. The extent of liver toxicity in rats fed 10 parts per million chlordecone (CD) for 15 days and subsequently injected with a single dose of CCl4 (100 microL/kg body weight) or a high dose of CCL4 alone (2.5 mL/kg body weight) was similar 6 and 24 hr later as assessed by plasma transaminase levels. There was significant elevation in liver ornithine decarboxylase, S-adenosylmethionine decarboxylase, and putrescine at 24 hr and spermidine N1-acetyltransferase, N1-acetylputrescine, putreanine, putrescine, and N1-acetylspermidine at 6 hr in rats treated with the high dose of CCl4 alone compared to the combination treatment. Spermidine levels decreased up to 6 hr and then increased up to 24 hr for both treatments. Spermine continuously decreased up to 24 hr for the CD and CCl4 low-dose combination treatment compared to rats treated with a high dose of CCl4 alone. Spermidine levels were lower than in controls and rose towards control value between 6 and 24 hr after the combination treatment and the high dose of CCl4. Results indicate that the CD and CCl4 low-dose combination treatment increased liver toxicity, resulting in compromised polyamine metabolism that is coincidental with suppressed hepatocellular regeneration, which leads to an accelerated progressive phase of liver injury and culminates in complete hepatic failure.

Adenosylmethionine Decarboxylase↗
PubMed1989

Protection from chlordecone (Kepone)-potentiated CCl4 hepatotoxicity in rats by fructose 1,6-diphosphate.

1. The extent of liver injury assessed as elevation of plasma transaminases was decreased 40-50% by administration of fructose 1,6-diphosphate to rats receiving the highly hepatotoxic combination of chlordecone and CCl4. 2. This protection was accompanied by significantly higher sustenance of ATP levels in the liver. 3. Polyamine synthesis as well as interconversion were stimulated in favor of maintaining higher levels of polyamines. 4. These events are consistent with the concept that suppressed hepatocellular regeneration which leads to progression of otherwise limited injury observed in chlordecone potentiation of CCl4 hepatotoxicity is due to lack of cellular energy.

Acetyltransferases↗
PubMed1989

Localization of intracellular zinc under conditions of altered permeability control of the plasma membrane.

Intracellular zinc was located as electron dense granules associated with the plasma membrane, endoplasmic reticular membranes, mitochondrial membranes, nuclear membranes and chromatin in Zajdela ascitic hepatoma and AK5 macrophage ascitic tumour cells. The quantity of intracellular zinc estimated by atomic emission spectrometer was different in the two cell lines. However, after loss of permeability control by the plasma membrane, involving glutaraldehyde and heat-shock treatments, the quantity of intracellular zinc was increased to almost the same extent in both cases.

Animals↗
PubMed1988

Passive sequestration of putrescine, spermidine and spermine by rat lungs.

The pulmonary uptake and accumulation of the three polyamines putrescine, spermidine and spermine by isolated ventilated and perfused rat lungs was investigated using 0.1, 1 or 5 mM concentrations of these compounds. The lung uptake of putrescine for all concentrations was greater than that of spermidine and spermine, but all three showed concentration-dependent linear uptake. A significant uptake of all three polyamines was also observed when incubated separately with rat lung slices for 60 min. Harmaline (0.4 mM), ouabain (0.2 mM) and perfusate with decreased Na+ (50 mEq/l) did not affect the uptake of any of the three polyamines by isolated perfused rat lungs or rat lung slice incubations. HPLC analysis of the whole lung or slices and media after perfusion or incubation studies, respectively, with polyamines did not reveal the presence of any metabolites. Likewise, the analysis of the lung homogenate incubated at 37 degrees C for 60 min with polyamines did not show any metabolites, confirming the absence of detectable pulmonary metabolism. These findings indicate a significant accumulation of polyamines in the rat lungs, accumulation predominantly occurring via simple diffusion, at variance with the reported active polyamine uptake process in the lung.

Animals↗
PubMed1988

Effect of orally administered neomycin on uterine growth in young mice and rats.

Neomycin has been widely used as a gut antibiotic in preconditioning animals for the experimental evaluation of biomaterials and biomedical devices. As a chance observation during a routine conditioning process, it was noticed that orally administered neomycin retarded uterine growth in growing mice and rats. Body weights and the weights of liver and spleen were uneffected, although there was a marginal increase in the kidneys' weight. This finding is consistent with the theory that a change induced in intestinal flora activity mediated a uterotrophic influence of dietary fiber.

Animals↗
PubMed1987

Meningiomas in childhood.

The clinical presentation and pathological characteristics of 18 histologically verified meningiomas in the paediatric age group are reviewed. There was a 1:1 sex ratio. Two children presented with seizures. The majority were supratentorial in location and large in size. In 4 patients, the meningiomas showed sarcomatous changes, while in 6 patients they were cystic.

Adolescent↗
PubMed1986

Absence of diamine oxidase activity from rabbit and rat lungs.

To study the presence of diamine oxidase (DAO) activity in any tissue with putrescine as the substrate, it is necessary to use inhibitors to block all pathways that could further metabolize gamma-aminobutyraldehyde, which is the product of enzyme reaction. It is also necessary to inhibit any enzyme that may convert putrescine into higher polyamines. By this approach it was observed that lung tissue of both rat and rabbit exhibited no DAO activity. DAO activity was observed in the rat and rabbit intestine, the former showing 3 times as much activity as the latter. The other potential pathways of putrescine metabolism are of no consequence in the rat and rabbit intestine and lungs.

Amine Oxidase (Copper-Containing)↗