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Biomedical subjects

R Bhat

Publications and source records attributed to R Bhat.

At least 91 records · Page 5Linked to original sources

Disposition of vitamin E in the eye.

To study the effect of exogenous vitamin E on its plasma and eye tissue levels, we administered 100 mg/kg of dl-alpha-tocopherol either by intravenous, intramuscular, or oral routes in 3-day-old newborn kittens. Controls did not receive the drug. alpha-Tocopherol levels in the plasma, retina, choroid, and vitreous were analyzed by high-performance liquid chromatography at selected intervals following drug administration. Our results showed that after intravenous administration of vitamin E, the retinal alpha-tocopherol levels increased 300 and 500% the baseline value at 2 and 4 h, respectively. By contrast, comparable retinal levels were achieved at 24 h following intramuscular administration and 72 h following oral administration. In the intravenous group high retinal levels were maintained up to 168 h, while in the intramuscular and oral groups retinal levels continued to increase up to 192 h. Irrespective of route of administration, the retinal concentration of alpha-tocopherol remained high even when the plasma levels were declining; plasma levels did not reflect retinal levels at any time. Following exogenous vitamin E administration, alpha-tocopherol levels increased both in the choroid (4 to 6 times the control) and in the vitreous (1.5 to 4 times the control). Significant differences in tocopherol levels were also seen between the eyes in the same animal in all groups. Our studies suggest a single dose of vitamin E by intravenous, intramuscular, or oral routes increases retinal levels from 3 to 5 times the control levels. However, peak retinal levels are achieved earlier by parenteral than by the oral route.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Purification and properties of two DNA ligases from human placenta.

Two DNA ligase activities have been separated, purified, and characterized. The resolution of the two enzymes from crude extracts was initially achieved through Polymin P precipitation. The ligation activity precipitating with the nucleic acids on treatment with Polymin P is designated as DNA ligase I, and an activity remaining in the supernatant fraction, as DNA ligase II. DNA ligase I and II are ATP and Mg2+-dependent enzymes with pH optima of 7.8 and 8.0 and isoelectric points of 6.9 and 7.6, respectively. The purified I and II DNA ligase activities have molecular weights of 83,000 and 89,000, respectively. Both activities are inhibited by dATP and inorganic pyrophosphate. However, in the presence of optimum rATP levels, dATP stimulates DNA ligase II activity, whereas DNA ligase I is inhibited under the same conditions. Both activities are DNA specific and ligation follows reaction steps similar to those described for the Escherichia coli DNA ligase.

Adenosine Triphosphate↗

Effect of tolazoline on renal function in newborn puppies.

Tolazoline is used in pulmonary hypertension and hypoperfusion syndrome during the neonatal period. Some of the side effects of tolazoline are hypotension, bleeding disorders and renal dysfunction. The present study was designed to investigate the effect of hypoxia and tolazoline on renal function in newborn puppies. The data in normal animals administered tolazoline alone did not reveal any statistically significant changes in blood pressure or in renal function. In the hypoxia group changes in renal function were noticed in spite of normal blood pressure. When tolazoline was administered to the hypoxic animals, a marked decrease in blood pressure resulted. Indeed, changes in renal function were more profound in the hypoxic animals receiving tolazoline than in hypoxic animals not receiving tolazoline, even though some of the renal functional values did not reach statistical significance.

Animals↗

Serum, retinal, choroidal vitreal vitamin E concentrations in human infants.

Vitamin E is being used as an antioxidant in preterm neonates in an attempt to decrease the severity of retinopathy of prematurity. However, its efficacy may depend on many factors, a major one being its concentration in the retina. There is very little information available on the alpha-tocopherol levels in the human eye tissue. The present study was carried out to determine the total alpha-tocopherol levels in the retina, choroid, and vitreous and to compare the retinal levels with the serum levels obtained at the time of death. Thirteen whole eye donations were available during the past 22 months for the study. The data from this small number of cases showed that retinal levels of alpha-tocopherol were higher than choroidal and vitreal levels; higher serum levels were associated with higher retinal levels; and both serum and retinal alpha-tocopherol levels were lower in the unsupplemented (group A) infants. Further studies on pharmacokinetics of vitamin E in human newborns and its distribution are needed.

Administration, Oral↗

Tissue pH monitoring by a disposable sensor in critically ill neonates.

Using a new disposable polymer sensor, tissue pH was continuously monitored successfully in 33 critically ill neonates. Tissue pH correlated well with the arterial pH at wide pH ranges [n = 476; r = .84; y = 0.46 + (0.94)x]. Tissue pH changes accurately reflected the arterial pH during both respiratory and metabolic acidosis and alkalosis. During severe metabolic acidosis (arterial pH less than 7.10) tissue pH was lower than arterial pH. No complications were encountered during or after monitoring. Compared with earlier studies using a glass electrode, this electrode reflects a marked technologic improvement because of its ease of application, longevity of use, disposability, and decreased risk of complications in small preterm infants. Unlike transcutaneous oxygen and carbon dioxide sensors, this device is invasive but is not heated and does not require frequent site changes.

Acid-Base Imbalance↗

Uptake of taurocholate by freshly isolated hepatocytes from fetal and newborn rabbits.

During early postnatal maturation a significant increase in the rate constant of translocation (Michaelis-Menten constant; Km) for taurocholate uptake occurs in isolated rabbit hepatocytes. This age-dependent change is related to a decrease in the efficiency of uptake for taurocholate and is probably associated with changes in the receptor or its microenvironment within the plasma membrane. Cholic acid conjugates (taurocholic and glycocholic acids) are the predominant bile acids found in the premature and neonatal human. It is therefore of interest that in the fetal and neonatal rabbit we have found a developmentally dependent alteration of taurocholic acid transport.

Animals↗

Transcutaneous oxygen and carbon dioxide monitoring in sick neonates using a combined sensor.

Using a combined O2-CO2 sensor, we evaluated the effect of cathode size and membrane thickness and incorporation of correction factor upon transcutaneous O2-CO2 readings. The present studies were carried out in three phases in newborns less than a week of age. The data from these studies indicate that a combined O2-CO2 sensor with a smaller cathode, Teflon membrane and with a built-in correction factor can accurately reflect arterial O2 and CO2 tension and can replace the present two heated sensors.

Carbon Dioxide↗

Bovine surfactant (surfactant TA) therapy in immature baboons with hyaline membrane disease.

As a prelude to clinical trials with a bovine surfactant (surfactant TA), in human infants with hyaline membrane disease, pulmonary and hemodynamic changes following its instillation in premature baboons were investigated. Baboons, delivered by cesarean section at 141 +/- 3.5 days (mean +/- SD, 77% gestation), were provided with intensive care. At 2 hours of age in one group (n = 10), 100 mg/kg of surfactant TA (reconstituted bovine surfactant, Tokyo Tanabe Co., Tokyo) was instilled into the lungs. Sequential measurements and monitoring of pulmonary and hemodynamic variables were carried out in these ten baboons and in a control group of five baboons for 16 hours, at which time the experiments were electively terminated. At birth, the pulmonary compliance, findings of chest radiographs, ratio of arterial PO2 to alveolar PO2, and respirator variables needed to maintain normal blood gas and acid base status were identical in both groups and indicative of severe hyaline membrane disease. Following surfactant instillation, the treated group demonstrated a rapid increase in PO2 with significantly improved ratio of arterial PO2 to alveolar PO2 (from a mean +/- SD pretreatment value of 0.21 +/- 0.11 to 0.45 +/- 0.11 by 16 hours). Pulmonary compliance improved similarly (from pretreatment value of 0.18 +/- 0.06 mL/cm H2O/kg to 0.27 +/- 0.09 mL/cm H2O/kg). Significant reduction in respirator support variables could be achieved in all treated animals; however, in the control animals, the pulmonary status worsened as evidenced by increasing mean airway pressure and respirator variables to keep normal blood gas and acid base status, thus worsening compliance. At autopsy, pulmonary pressure-volume curves were significantly different with large hysteresis obtained in the surfactant-treated group. Although no deleterious effect on hemodynamics was noted in surfactant TA-treated animals, a large patent ductus arteriosus was demonstrated by aortography. Increased lung blood flow, probably due to a large patent ductus arteriosus flow, was demonstrated by radiolabeled microsphere technique. The physiologic significance and clinical relevance of these findings in premature baboons treated with surfactant TA are discussed.

Animals↗

Intravenous indomethacin and changes of renal function in premature infants with patent ductus arteriosus.

Selected parameters of renal function were studied in premature infants with a significant patent ductus arteriosus who were treated with intravenous indomethacin according to a specific protocol. Urine volume, glomerular filtration rate, urine sodium, and the fractional excretion of sodium were analyzed in 17; osmolar, sodium, and free water clearances in 8; and indomethacin pharmacokinetics in 7 premature infants. All renal function parameters analyzed decreased during indomethacin therapy: urine volume and glomerular filtration rate returned to normal, while urine sodium, fractional excretion of sodium, and the osmolar, sodium, and free water clearances remained low 24 hours after cessation of therapy. The water retention, shown by the reduced free water clearance, had no apparent deleterious effects, probably because of the infants' low fluid intake. Indomethacin pharmacokinetic parameters (clearance, area under the curve) may account in part for the variability of the fractional excretion of sodium, glomerular filtration, and urine flow rate.

Ductus Arteriosus, Patent↗

Colloid osmotic pressure in infants with hyaline membrane disease.

Colloid osmotic pressure (COP) was measured serially in 81 critically ill neonates with hyaline membrane disease (HMD) during the first five days of life, and these changes were correlated with the birth weight, gestational age, serum protein level, clinical status, and outcome. Colloid osmotic pressure correlated better with the total protein level (n = 81; r = 0.54) than with birth weight (r = 0.23) and gestational age (r = 0.31; n = 81). Seventy-one of 81 neonates survived. Among the survivors, COP increased significantly by day 5, whereas changes in the total protein level were not significant during the same period. Colloid osmotic pressure decreased significantly in nine of ten nonsurvivors (mean +/- SE, 11 +/- 0.5 to 8 +/- 0.55 mm Hg), whereas the total protein level did not show a similar change. Thus, COP cannot be accurately predicted by measuring serum protein during acute illness. Serial measurement of COP was a better prognostic indicator than the total protein level in infants with HMD.

Birth Weight↗

Age-related difference in cerebral perfusion pressure response to acute hypoxia in neonatal puppies.

Acute hypoxia is known to increase cerebral blood flow and intracranial pressure in the fetus and newborn. The combined effects of these changes on cerebral perfusion pressure are unknown. We investigated cerebral perfusion pressure changes in newborn puppies of two age groups (group I, mean age 28 days, group II, mean age 11 days) during acute, severe hypoxia. The results indicate that (1) in both groups the intracranial pressure increases within seconds following the onset of hypoxia; (2) the mean arterial blood pressure drops almost precipitantly in older animals, whereas in group II, the blood pressure is maintained near baseline values up to 4 min, and (3) because of differences in blood pressure responses the cerebral perfusion pressure falls dramatically in group I, whereas in younger animals normotensive response to hypoxia helps maintain the cerebral perfusion pressure for a longer period. We conclude that in young animals early normotensive response to hypoxia assures adequate transmural pressure for the perfusion of brain which may be a built-in protective factor.

Acute Disease↗

Nerve damage in leprosy-a teased fibre study of sciatic nerves in experimental mice.

The extent of nerve damage was assessed in the sciatic nerves of CBA/J mice with experimental leprosy by the teased single fibre preparations. Morphological changes in the fibres were observed upto 15 months of infection and compared with control animals of the same age groups. During 4 to 9 months period, the fibres showed paranodal enlargements, widening of the Schmidt-Lantermann incisures, paranodal and whole segmental demyelination. In addition, fragmentation of axons with the formation of myelin ovoids in the schwann tubes was also observed in animals with 9 to 15 months of infection. While segmental demyelination was predominant early in infection, axonal degeneration was more evident in advanced infection. These findings may possibly, explain the underlying mechanism of nerve damage in human leprosy.

Animals↗