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Biomedical subjects

R Ramanathan

Publications and source records attributed to R Ramanathan.

At least 73 records · Page 4Linked to original sources
PubMed1994

Effects of gamma-linolenic acid, flavonoids, and vitamins on cytotoxicity and lipid peroxidation.

Gamma linolenic acid (GLA), a polyunsaturated fatty acid, promoted lipid peroxidation in Raji lymphoma suspension cultures, in a dose (10 microM-100 microM) and time-dependent (4 h-48 h) manner. The increase in lipid peroxidation could be correlated to an increase in cytotoxicity. The plant flavonoids (quercetin, luteolin, butein, rutin) and the fat-soluble components (retinol, retinoic acid, alpha-tocopherol) by themselves did not affect lipid peroxidation in Raji cells. Quercetin, luteolin, retinol, and alpha-tocopherol were able to inhibit cell proliferation significantly. Although GLA only decreased the cytotoxicity of retinol-treated cells, the latter compound was able to block the prooxidative action of GLA by scavenging the free radicals induced by it. Quercetin at 50 and 100 microM exerted equipotent superoxide anion scavenging effects, but at the higher concentration it had no effect on lipid peroxidation. Although the bioactive test compounds are well known natural antioxidants, interestingly, our data showed that their potent cytotoxic actions do not involve free radicals or lipid peroxidation reactions.

Cell Death↗
PubMed1992

Cytotoxic effect of plant polyphenols and fat-soluble vitamins on malignant human cultured cells.

In vitro studies showed that several flavonoids, tannic acid, gallic acid and fat-soluble vitamins inhibited HeLa and Raji lymphoma cell growth. The inhibition trend exhibited by these compounds was similar for both cell lines, and their growth was inhibited dose dependently. Butein, (10 microM), the most potent anti-proliferative agent, exerted 30% growth inhibition and was more effective on HeLa cells. Retinol (100 microM) inhibited cell proliferation completely. Tannic acid was twice as potent as its monomer gallic acid. From structure-activity consideration, the C2,3-double bond of the flavonoid molecule was important for activity. Flavonoid aglycones were more effective than their corresponding glycosides in suppressing cell growth.

Cell Division↗
PubMed1991

Physiological pharmacokinetic modeling of inhaled trichloroethylene in rats.

The pharmacokinetics of trichloroethylene (TCE) was characterized during and following inhalation exposures of male Sprague-Dawley rats. The blood and exhaled breath TCE time-course data were used to formulate and assess the accuracy of predictions of a physiologically based pharmacokinetic (PB-PK) model for TCE inhalation. Fifty or 500 ppm of TCE was inhaled by unanesthetized rats of 325-375 g for 2 hr through a miniaturized one-way breathing valve. Repetitive samples of the inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently during and for 3 hr following the exposures and analyzed for TCE by headspace gas chromatography. Respiratory rates and volumes were continuously monitored and used in conjunction with the pharmacokinetic data to delineate uptake and elimination profiles. Levels of TCE in the exhaled breath attained near steady-state soon after the beginning of exposures, and were then directly proportional to the inhaled concentration. Exhaled breath levels of TCE in rats were similar in magnitude to values previously published for TCE inhalation exposures of humans. Levels of TCE in the blood of the 50 ppm-exposed animals also rapidly approached near steady-state, but blood levels in the 500 ppm-exposed animals rose progressively, reaching concentrations 25- to 30-fold higher than in the 50 ppm group during the second hour of exposure. The 10-fold increase in inhaled concentration resulted in an 8.7-fold increase in cumulative uptake, or total absorbed dose. These findings of nonlinearity indicate that metabolic saturation ensued during the 500 ppm exposure. The PB-PK model was characterized as blood flow-limited with TCE eliminated unchanged in the exhaled breath and by saturable liver metabolism. The uptake and elimination profiles were accurately simulated by the PB-PK model for both the 50 and 500 ppm TCE exposure levels. Such a model may be quite useful in risk assessments in predicting internal (i.e., systemically absorbed) doses of TCE and other volatile organics under a variety of exposure scenarios.

Administration, Inhalation↗
PubMed1990

Effect of mechanical ventilation and barotrauma on pulmonary clearance of 99mtechnetium diethylenetriamine pentaacetate in lambs.

We studied the effect of positive pressure mechanical ventilation on the pulmonary clearance (k) of 99mtechnetium diethylenetriamine pentaacetate (99mTc-DTPA) in lambs. Twelve lambs were anesthetized and ventilated with air at 25 breaths/min and with end expiratory airway pressure at 2 cm H2O for a minimum period of 8 h. Four lambs received normal pressure ventilation with peak airway pressure at 17 +/- 3 cm H2O and eight received high pressure ventilation with peak airway pressure at 41 +/- 2 cm H2O. Three 99mTc-DTPA clearance studies were done in each lamb; at the start and after 4 and 8 h of mechanical ventilation. All clearance measurements were made at normal peak airway pressure 16 +/- 3 cm H2O. Baseline clearance rate, k, (n = 12) was 1.2 +/- 0.5% (SD). During normal pressure ventilation, k increased from 1.0 +/- 0.5 to 2.2 +/- 0.8% after 4 h and to 2.7 +/- 0.8% after 8 h. During high pressure ventilation, k increased from 1.4 +/- 0.4 to 3.6 +/- 1.3% after 4 h and to 4.8 +/- 1.2% after 8 h. To see if 8 h of mechanical ventilation was associated with other evidence of lung epithelial injury, we determined the movement of I125 labeled albumin from the interstitium into the airspace, lung water content, lung histology, and lung lavage constituents in the lambs at the end of the study. All variables were similar between ventilated and four unventilated lambs, except the percentage of alveolar macrophages recovered by lavage, which was more in the ventilated lambs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

The uptake and elimination of 1,1,1-trichloroethane during and following inhalation exposures in rats.

The pharmacokinetics of 1,1,1-trichloroethane (TRI) was studied in male Sprague-Dawley rats in order to characterize and quantify TRI uptake and elimination oby direct measurements of the inhaled and exhaled compound. Fifty or 500 ppm TRI was inhaled for 2 hr through a one-way breathing valve by unanesthetized rats of 325-375 g. Repetitive samples of the separate inhaled and exhaled breath streams, as well as arterial blood, were collected concurrently both during and following TRI inhalation and analyzed for TRI by gas chromatography. Respiratory rates and volumes were continuously monitored during and following exposure and were used in conjunction with the pharmacokinetic data to characterize profiles of uptake and elimination. TRI was very rapidly absorbed from the lung, in that substantial levels were present in arterial blood at the first sampling time (i.e., 2 min). Blood and exhaled breath concentrations of TRI increased rapidly after the initiation of exposure, approaching but not reaching steady state during the 2-hr exposures. The blood and exhaled breath concentrations were directly proportional to the exposure concentration during the exposures. Percentage uptake of TRI decreased 30-35% during the first hour of inhalation, diminishing to approximately 45-50% by the end of the exposure. Total cumulative uptake in the 50 and 500 ppm groups over the 2-hr inhalation exposures was determined to be 6 and 48 mg/kg body wt, respectively. By the end of the exposure period, 2.1 and 20.8 mg, respectively, of inhaled TRI was eliminated from rats inhaling 50 and 500 ppm TRI. A physiological pharmacokinetic model for TRI inhalation was utilized to predict blood and exhaled breath concentrations for comparison with observed experimental values. Overall, values predicted by the physiological pharmacokinetic model for TRI levels in the blood and exhaled breath were in close agreement with measured values both during and following TRI inhalation.

Administration, Inhalation↗
PubMed1989

Oral toxicity of 1,2-dichloropropane: acute, short-term, and long-term studies in rats.

The objective of this investigation was to characterize the acute and short- and long-term toxic potency of orally administered 1,2-dichloropropane (DCP). In the acute and short-term studies, male rats of 250-300 g were gavaged with 0, 100, 250, 500, or 1000 mg DCP/kg in corn oil once daily for up to 10 consecutive days. Although ingestion of DCP caused body weight loss and CNS depression, few other toxic effects were manifest 24 hr after a single dose of the chemical. Morphological changes were limited to liver centrilobular cells in 500 and 1000 mg/kg rats. Similarly, elevated activity of some serum enzymes occurred only at these two highest dose levels. Hepatic nonprotein sulfhydryl (NPS) levels were decreased and renal NPS levels increased at 24 hr. In the short-term study resistance developed to DCP hepatotoxicity over the 10 consecutive days of exposure, as reflected by progressively lower serum enzyme levels and by decreases in the severity and incidence of toxic hepatitis and periportal vacuolization. Nucleolar enlargement in hepatocytes, however, was observed at all dosage levels at 5 and 10 days. There were a number of manifestations of hemolytic anemia, including erythrophagocytosis in the liver, splenic hemosiderosis and hyperplasia of erythropoietic elements of the red pulp, renal tubular cell hemosiderosis, and hyperbilirubinemia. Urinalyses and histopathology revealed no evidence of nephrotoxicity. In the long-term study, male rats initially weighing 180-200 g were gavaged five times weekly for up to 13 weeks with 0, 100, 250, 500, or 750 mg DCP/kg. As over one-half the 750 mg/kg group died within 10 days, the survivors were sacrificed. Histopathological changes in the 750 mg/kg animals included mild hepatitis and splenic hemosiderosis, as well as adrenal medullary vacuolization and cortical lipidosis, testicular degeneration and a reduction in sperm, and increased number of degenerate spermatogonia in the epididymis in some members of the group. Similar testicular and epididymal degenerative change also were observed in some 500 mg/kg animals after 13 weeks of dosing. There was a progressive increase in the number of deaths in the 500 mg/kg group, such that more than 50% were dead by 13 weeks. No deaths occurred in the 100 or 250 mg/kg groups. The DCP dosage regimen also produced a dose-dependent decrease in body weight gain. DCP exhibited very limited hepatotoxic potential and no apparent nephrotoxic potential in the long-term study. Slight elevations in serum ornithine-carbamyltransferase activity, periportal vacuolization, and active fibroplasia in the liver were seen in the 500 mg/kg animals.

Administration, Oral↗
PubMed1989

Effect of hematocrit on microvascular pressures in 3- to 5-wk-old rabbit lungs.

To examine the effects of blood hematocrit (Hct) and apparent viscosity on the pulmonary microcirculation, we studied 30 isolated, perfused 3- to 5-wk-old rabbits with varying perfusate Hct. We partitioned total vascular resistance by measuring pulmonary artery and left atrial pressures and by micropuncture the pressures in the subpleural microcirculation in 20-40 microns diameter arterioles, 20-40 microns venules, and 250-300 microns venules. To prevent active vasomotion and changes in vessel geometry, we paralyzed the vasculature with papaverine hydrochloride. We studied four groups of lungs: group I (n = 7) with low Hct (17.8 +/- 2.4%); group II (n = 9) with medium Hct (46.8 +/- 8.2%); group III (n = 6) with high Hct (74.4 +/- 5.8%); and group IV (n = 8) with both low and high Hct perfusates. Lungs were perfused at constant flow (80 +/- 4 ml.kg body wt-1.min-1) in zone 3, airway and venous pressures being 6 and 8 cmH2O, respectively. We found that in lungs perfused with low Hct, approximately 52% of the total resistance was in arteries, approximately 25% in microvessels, and approximately 21% in small veins, with very little resistance in large veins. With an increase in perfusate hematocrit and apparent viscosity, total pulmonary vascular resistance increased mainly because of an increase in resistance in arteries and small veins, with little change in resistance in microvessels and large veins.

Animals↗
PubMed1988

Effect of cell substrate on antioxidant enzyme activities in cultured renal glomerular epithelium.

The activities of three antioxidant enzymes, superoxide dismutase, catalase, and glutathione peroxidase, were monitored in isolated guinea pig glomeruli and primary or subcultured glomerular epithelial cells. Cell injury was assessed by morphologic studies and by measurement of cellular lipid peroxidation (levels of malondialdehyde). Antioxidant enzyme activities were very different in cultured cells than in parent glomeruli. The possible effect of culture substrates (tissue culture plastic, bovine corneal endothelial [BCE] cell basement membrane, and PF-HR-9 endodermal cell basement membrane) on antioxidant enzyme status, cell morphology, and lipid peroxidation was also assessed. Glomerular epithelial cells cultured on the BCE cell basement membrane substrate survived longer and showed less lipid peroxidation than cells cultured on plastic or the HR-9 substrate. Cells cultured on a plastic substrate had substantially less glutathione peroxidase activity than cells cultured on either BCE or HR-9 basement membranes.

Animals↗
PubMed1987

Effects of metaproterenol on pulmonary mechanics, oxygenation, and ventilation in infants with chronic lung disease.

Changes in pulmonary resistance, dynamic compliance, tidal volume, and transcutaneous PO2 and PCO2 after nebulized administration of metaproterenol were evaluated in eight newborn infants (birth weight 650 to 1060 g, gestational age 25 to 28 weeks) with chronic lung disease receiving mechanical ventilation. The infants were monitored continuously before and for 15 minutes after nebulization of metaproterenol during 3 consecutive days at mean age 34 days. There were significant increases in compliance, tidal volume, and tcPO2, and significant decreases in pulmonary resistance and tcPCO2. These data show that bronchospasm contributes significantly to the high pulmonary resistance in preterm infants with chronic lung disease and that metaproterenol is beneficial in the therapy of infants with chronic lung disease requiring mechanical ventilation.

Blood Gas Monitoring, Transcutaneous↗
PubMed1987

Blood cultures in neonates with percutaneous central venous catheters.

We compared the results of 74 pairs of blood cultures obtained simultaneously every two weeks from a peripheral vein and a percutaneously inserted central venous catheter in 38 newborns. Three babies (7.9%) had bacteraemia. In two of these the central catheter was colonised 48 hours beforehand.

Blood↗
PubMed1987

Pulse oximetry in very low birth weight infants with acute and chronic lung disease.

With improved survival of very low birth weight infants, the incidence of bronchopulmonary dysplasia has significantly increased. Pulse oximetry appears to be an adequate alternative to transcutaneous PO2, for continuous arterial oxygen saturation (SaO2) monitoring in neonates; however, its usefulness has not been very well documented in very low birth weight infants. We studied 68 patients with birth weight less than 1,250 g; 44 neonates had respiratory distress syndrome and 24 had bronchopulmonary dysplasia. Using a Nellcor N-100 pulse oximeter, we compared transcutaneous oxygen saturation with simultaneous arterial samples analyzed for SaO2 (range 78% to 100%) using an IL 282 co-oximeter. Fetal hemoglobin was measured in 66 patients. We also evaluated the accuracy of transcutaneous PO2 in reflecting arterial PO2 in patients with bronchopulmonary dysplasia. Over a wide range of PO2, PCO2, pH, heart rate, BP, hematocrit, and fetal hemoglobin, linear regression analysis revealed a close correlation between pulse oximeter values and co-oximeter measured SaO2 in patients with acute (r = .88, Y = 19.41 + 0.79X) and chronic (r = .90, Y = 9.72 + 0.92X) disease. Regression analysis of transcutaneous v arterial PO2 in infants with bronchopulmonary dysplasia showed an r value of .78. In addition, in these patients with chronic disease, the mean difference between pulse oximeter SaO2 and co-oximeter measured SaO2 was 2.7 +/- 1.9% (SD); whereas the mean difference between transcutaneous and arterial PO2 was -14 +/- 10.7 mm Hg. Our findings indicate that pulse oximetry can be used reliably in very low birth weight infants with acute and chronic lung disease, for SaO2 values greater than 78%.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1986

Pulse oximetry for continuous oxygen monitoring in sick newborn infants.

We studied 54 neonates with acute cardiorespiratory illness and 21 infants with bronchopulmonary dysplasia, to evaluate the accuracy of a nonheated pulse oximeter in predicting arterial oxygen saturation (SaO2). We also studied the accuracy of transcutaneous oxygen tension (tcPO2) in estimating arterial oxygen tension (PaO2) in infants with bronchopulmonary dysplasia. We compared pulse oximeter SaO2 with simultaneously measured SaO2 (range 78% to 100%) using a co-oximeter. Over a wide range of values for heart rate, blood pressure, hematocrit, PO2, PCO2, and pH, linear regression analysis revealed a close correlation between in vivo pulse oximeter readings and in vitro SaO2 measurements in patients with acute (r = 0.86, Y = 29.64 + 0.68X) and chronic (r = 0.91, Y = 6.29 + 0.96X) disease. Regression analysis of tcPO2 versus PaO2 showed an r value of 0.76 in infants with bronchopulmonary dysplasia. In these patients the mean difference between pulse oximeter SaO2 and in vitro SaO2 was 2.9% +/- 1.8% (SD), whereas the mean difference between tcPO2 and PaO2 was -14.5 +/- 11.1 mm Hg. Fetal hemoglobin ranged from 4.3% to 95%. We conclude that pulse oximetry is an appropriate alternative to tcPO2 for continuous oxygen monitoring in newborn infants with acute cardiorespiratory illnesses and chronic lung disease.

Acute Disease↗
PubMed1986

In vitro activation and resultant binding of benzo[a]pyrene to DNA by microsomes from rats fed corn and menhaden oils.

Dietary unsaturated fat is required for maximum induction of the hepatic mixed function oxidases (MFO) responsible for activating carcinogens to forms that may bind covalently to DNA. The aim of this study was to assess the influence of dietary fat type and content on the activities of some enzymes involved in activation and detoxification of the carcinogen benzo[a]pyrene (B[a]P). Modification of these changes by pretreatment with phenobarbital (PB) was also evaluated. Male rats were fed diet devoid of fat or containing 20% corn oil (CO) or 20% menhaden fish oil (MO) for 4 days. PB induced soluble glutathione S-transferase, a detoxifying enzyme, only in rats fed dietary fats. Microsomes from rats fed both types of dietary fat had increased levels of cytochrome P-450 (P-450) and PB induced P-450 only in rats fed these fats. Although ethoxycoumarin O-dealkylase was significantly elevated in the MO group, the induction by PB was not dependent on dietary fat type or level. Dietary fat increased microsome-catalyzed in vitro binding of [3H]-B[a]P to calf thymus DNA, especially in response to PB. Menhaden oil depressed B[a]P hydroxylation and PB treatment depressed this activity to the greatest extent in rats fed this diet. When calculated as B[a]P metabolized per unit of P-450, PB seems to induce a P-450 in fat fed animals having lower affinity and capacity for B[a]P hydroxylation and activation than in rats fed the fat-free diet.

7-Alkoxycoumarin O-Dealkylase↗
PubMed1986

Prospective evaluation of percutaneous central venous silastic catheters in newborn infants with birth weights of 510 to 3,920 grams.

With improved neonatal survival, especially of very low birth weight infants, our efforts should be directed toward reduction of morbidity. Sick preterm infants require total parenteral nutrition for prolonged periods of time due to extreme prematurity and feeding intolerance. However, the use of surgically placed Broviac catheters has been associated with a high complication rate. A prospective study of 53 percutaneous central venous Silastic catheterizations for administration of total parenteral nutrition was performed in 45 newborn infants. At the time of catheter insertion, 37 babies weighted less than 1,500 g and 19 weighed less than 1,000 g. Percutaneous central venous catheters were placed successfully the first time in 50 of 55 attempts. In three babies, insertion was successful on second attempt. The catheters remained in place for 25.4 +/- 16.7 days ([mean +/- SD] range two to 80 days). In babies weighing less than 1,000 g, the catheters remained in place for a longer period of time (34.0 +/- 18.0; range 12 to 80 days). Sixty-six percent of the catheters were removed electively. There were four cases of bacteremia (7.5%), and the overall incidence of mechanical complications was 26.4%. We conclude that percutaneous central venous catheters can be used safely and effectively in newborn infants for prolonged administration of total parenteral nutrition, especially in neonates weighing less than 1,000 g.

Birth Weight↗