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Biomedical subjects

G K Shiu

Publications and source records attributed to G K Shiu.

32 records · Page 2Linked to original sources
PubMed1984

Brain-stem auditory evoked potentials in rats with high-dose pentobarbital.

Brain-stem auditory evoked potentials (BAEPs) are relatively resistant to alteration by barbiturate drugs, but the effects of the high doses that are used clinically to produce deep barbiturate coma for the treatment of intracranial hypertension and postischemic anoxic encephalopathy on BAEPs are unknown. We gave high-dose pentobarbital infusions to mechanically ventilated rats while recording serial BAEPs from the scalp. Pentobarbital progressively suppressed and then abolished all peaks. First the later waves, then all but the first wave, and finally all waves were abolished at intravenous doses of 120, 220, and 260 mg/kg, respectively, in addition to the initial anesthetic dose of 60 mg/kg i.p. The changes were at least partially reversible; peaks returned in reverse order of their disappearance. Peak latencies increased with dose. The results show a significant effect of pentobarbital on BAEPs in the rat, suggesting that BAEPs may be useful in assessing the depth of and recovery from barbiturate coma.

Animals↗
PubMed1983

Free fatty acid accumulation in the pathogenesis and therapy of ischemic-anoxic brain injury.

Energy depletion and lactate are at plateau levels within five minutes of complete ischemic-anoxia in the brain; however, irreversible brain injury has not occurred in this time. Brain free fatty acids (FFA) rise sharply during the first five minutes of ischemic-anoxia, but then continue to rise during the following hour without plateauing. Barbiturate anesthesia preischemia attenuates the FFA rise. Other agents which also attenuate the FFA increase include, among others, phenytoin and Innovar. The Ca2+ antagonists flunarizine and gallopamil also attenuated FFA rise, but were not as effective as pentobarbital during ischemia. Protective effects of Ca2+ antagonists may be more important during recirculation than during ischemia.

Animals↗
PubMed1983

Dose of thiopental, pentobarbital, and phenytoin for maximal therapeutic effects in cerebral ischemic anoxia.

Recent interest in pharmacotherapy for various cerebral insults with potentially dangerous drugs, such as barbiturate anesthetics, has created a need to determine the lowest or optimal dose resulting in maximal therapeutic effects. Our earlier studies suggested that whole brain free fatty acid (FFA) accumulation during complete global ischemia reflects the evolution of brain damage. Various drugs effective in ameliorating ischemic brain injury were also effective in attenuating FFA accumulation. The degree of attenuation by a given drug at various doses may indicate the optimal dose. We studied the attenuation of whole brain FFAs (i.e., 20:4, 18:0, 18:1, and 16:0) by 15-120 mg/kg of thiopental or pentobarbital, or 50-300 mg/kg of phenytoin or ketamine intraperitoneal (IP), during 10-min decapitation ischemia in rats. Plasma and brain drug levels were measured except ketamine. Maximal attenuation of FFAs occurred at pentobarbital, thiopental, and phenytoin doses of 15, 30, and 150 mg/kg IP reducing total FFA by 18, 22, and 31%, respectively. These results indicate that maximal therapeutic effects are obtained at subanesthetic doses of barbiturates and at the anticonvulsant dose of phenytoin.

Animals↗
PubMed1983

Reassessment of brain free fatty acid liberation during global ischemia and its attenuation by barbiturate anesthesia.

We previously reported that whole-brain free fatty acids (FFA) rose almost linearly for up to 1 h after decapitation of unanesthetized rats and was significantly attenuated by pentobarbital anesthesia. However, our values for total FFA and arachidonic, stearic, oleic, and palmitic acids were severalfold higher than those obtained by previous investigators. Based upon the suggestion that this may be due to FFAs released from di- and triglycerides in the quantitation of FFAs, we have now analyzed and improved our procedures for TLC separation of FFA and reassessed the accumulation of FFA in whole brain during decapitation ischemia in unanesthetized and pentobarbital-anesthetized rats. FFA levels in whole brain after 0.5 min of ischemia were one-half to one-fourth the levels previously reported after 1 min of ischemia. The rise in FFA between 0.5 and 60 min of ischemia was 9-fold for total FFA, and between 7 and 12-fold for each of the FFAs quantitated. Pentobarbital significantly attenuated the rise of all FFAs with, however, greater effects on oleic and palmitic acids than previously reported.

Anesthesia↗
PubMed1982

Attenuation of brain free fatty acid liberation during global ischemia: a model for screening potential therapies for efficacy?

Whole brain free fatty acids (FFA) continue to rise appreciably even 1 h after decapitation, which may reflect the evolution of ischemic brain injury at least during global ischemia. If so, the attenuation of FFA liberation by various drugs may reflect their efficacy in ischemic brain injury. Rats were pretreated with either 0.9% NaCl (controls), ketamine, halothane, lofentanil, etomidate, Y-9179, R41-468, Innovar-Vet, pentobarbital, thiopental, or phenytoin and decapitated 15 to 30 min thereafter. The brains were kept normothermic for 10 min until they were frozen in liquid nitrogen. Whole brain FFAs were quantitated gy gas-liquid chromatography. After 10 min of ischemia in controls, total FFAs and arachidonic, stearic, oleic, and palmitic acids increased by 8- to 10-fold. The drugs, in order of decreasing effectiveness in attenuating FFA liberation, fell into the following three groups: (1) phenytoin, thiopental, pentobarbital, and Innovar-Vet; (2) R41-468, Y-9179, and etomidate; and (3) lofentanil, halothane and ketamine. The three groups reduced total FFAs by about 23%, 13%, and 8%, respectively. The effectiveness of drugs in attenuating FFA liberation appears to correlate with their efficacy in ischemic brain injury. However, a cause and effect relationship between FAA liberation and the evolution of ischemic brain injury must be established before accurate predictions of efficacy can be made by this method. The limitations of the proposed method of evaluation are discussed.

Anesthetics↗
PubMed1981

Barbiturate attenuation of brain free fatty acid liberation during global ischemia.

To find a biochemical basis for the increased tolerance of the brain to anoxia during barbiturate anesthesia, we studied whole-brain free fatty acids (FFA) at various times after decapitation of awake and pentobarbital-anesthetized rats. Post-decapitation, the brains were kept at 37 degrees C for 1 to 60 min before freezing in liquid N2. Nonischemic brains were frozen in liquid N2, using a rapid sampling technique. Whole-brain arachidonic, stearic, oleic, linoleic, and palmitic acids were quantitated by gas-liquid chromatography. In unanesthetized, nonischemic brain, total FFA was 1226 +/- 121 nmol/g brain (n = 12) and was unaffected by pentobarbital anesthesia (1126 +/- 86 nmol/g brain, n = 11), except for a reduction in arachidonic acid. Total FFA in unanesthetized and pentobarbital-anesthetized rats transiently declined between 0 and 1 min of ischemia, and then rose linearly for up to 60 min, with consistently lower values in pentobarbital-treated rats, the greatest attenuation being that of arachidonic and stearic acid liberation. Brain FFA liberation during global ischemia is the first known biochemical variable directly correlated with the duration (i.e., severity) of global ischemia. The attenuation of brain FFA liberation and especially of arachidonic and stearic acids may be the biochemical basis of barbiturate attenuation of ischemic brain injury.

Animals↗
PubMed1979

Rapid high-performance liquid chromatographic determination of bleomycin A2 in plasma.

A rapid and specific method for the determination of bleomycin A2 is described. A 50-microliter aliquot of 20% trichloroacetic acid was added to 200 microliter of plasma. The sample was vortexed and centrifuged, and 50 microliter of the clear supernate was injected into a liquid chromatograph equipped with a microparticulate reversed-phase column and a fixed wavelength detector. Elution was carried out using methanol-acetonitrile-0.0085 M heptanesulfonic acid-acetic acid. A linear calibration curve was found in the 0.05-5 microgram/ml range with an estimated precision of +/-6% (CV). Preliminary pharmacokinetic data in the rabbit also are reported.

Animals↗
PubMed1977

Rapid GLC determination of therapeutic plasma glycerin levels.

A new rapid and inexpensive method for the determination of therapeutic plasma glycerin concentrations is described. In this method, acetic anhydride and pyridine are added to 15 microliter of plasma. After brief incubation and centrifugation, an aliquot of the supernate is injected directly onto the 3% OV-1 column. A linear calibration curve was found in the 0.05--3-mg/ml range, with the precision of the assay estimated to be +/-5.5% (RSD). The method was used to determining preliminary pharmacokinetic data in the rabbit.

Acetylation↗
PubMedDate not supplied

High performance liquid chromatographic analysis of six conjugated and unconjugated estrogens in serum.

Six estrogens-estrone, equilin, estradiol, sodium estrone sulphate, sodium equilin sulphate and sodium 17-alpha-dihydroequilin sulphate in dog serum were successfully separated and quantified by a high performance liquid chromatographic method developed in our laboratories. The mobile phase was optimized by studying the effects of an organic modifier (acetonitrile) and an ion pairing reagent (tetrabutylammonium hydroxide). The serum sample work-up procedure was designed to recover both conjugated and unconjugated estrogens. The optimum method involved acetonitrile to precipitate serum proteins/peptides and extract estrogens. Residues were reconstituted in 50% acetonitrile in water for injection. The detection limits for these six estrogens via UV detection ranged from 0.5 to 5 ng on-column with a signal-to-noise ratio (S/N) of 10 for a 20 microL injection and via fluorescence 0.1 ng on-column for 17-beta-estradiol. Validation data are included for all six estrogens.

Acetonitriles↗
PubMedDate not supplied

Reduced bioavailability of moisture-exposed carbamazepine resulting in status epilepticus.

A 28-year-old man with seizures well controlled with carbamazepine (CBZ) and valproate (VPA) developed generalized convulsive status epilepticus three days after his CBZ tablets became wet during a rainstorm while he was camping out. He continued the CBZ but avoided ingesting obviously disintegrating tablets. The VPA was not exposed to excessive moisture. Previous random CBZ blood levels had been in the range of 9-13 micrograms/ml; at the time of admission to the emergency room the level had decreased to 3.8 micrograms/ml. The VPA level did not change significantly from baseline. The moisture-exposed CBZ tablets were of expected weight but were swollen and enlarged. Analysis of these tablets by USP paddle method 2 demonstrated a mean dissolution of 16% at 60 min as compared with > 80% for fresh CBZ tablets. After final dissolution of the moisture-exposed CBZ tablets, normal quantities of active drug were noted. We propose that poor dissolution of moisture-exposed CBZ tablets results in reduced bioavailability. We urge caution in the packaging and storage of CBZ to avoid exposure to moisture.

Adult↗