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R Upton

Publications and source records attributed to R Upton.

25 records · Page 2Linked to original sources
PubMed1995

Methamphetamine and ethanol interactions in humans.

OBJECTIVE: Methamphetamine and ethanol are commonly used together. We examined the effects of intravenous methamphetamine (30 mg), oral ethanol (1 gm/kg), and the combination of methamphetamine (30 mg) and ethanol (1 gm/kg). METHODS: Eight methamphetamine and ethanol users were studied in a double-blind, double-placebo, within-subject, balanced Latin-square design. Ethanol was administered in six drinks over 30 minutes. Methamphetamine was injected 60 minutes after the first drink was begun. Cardiovascular, subjective, and neuropsychologic effects of the drug combinations were measured for 6 hours. Methamphetamine and amphetamine in plasma and urine were measured by capillary gas chromatography for 48 hours. Data were analyzed by repeated-measures ANOVA. RESULTS: Compared with methamphetamine alone, the combination increased heart rate but decreased systolic blood pressure. The net cardiovascular effect was an increase in rate pressure product, an index of cardiac work and myocardial oxygen consumption. The combination diminished the subjective effects of ethanol while not affecting the subjective effects of methamphetamine. Methamphetamine pharmacokinetics were not altered by the concurrent administration of ethanol, with the exception of lowering the apparent volume of distribution at steady state for methamphetamine. CONCLUSIONS: As a potent sympathomimetic drug with alpha-agonist-like effects, methamphetamine increased systolic blood pressure, with minimal change in heart rate. The concurrent administration of methamphetamine and ethanol increased cardiac work, which could produce more adverse cardiovascular effects than either drug taken alone. The increased perceived global intoxication may explain the popularity of this drug combination.

Administration, Oral↗
PubMed1995

A method for frequent measurement of sedation and analgesia in sheep using the response to a ramped electrical stimulus.

A method for the frequent, precise measurement of the analgesic and sedative (or anesthetic) effects of drugs after bolus administration to sheep was developed. A ramped pulsed DC electrical stimulus was delivered to the hind limb of sheep via subcutaneous needles by use of a peripheral nerve stimulator modified to allow control of current ramp rate and pulse frequency, and limb withdrawal was used as an endpoint. The optimal stimulus pattern was found to be a pulse frequency of 20 Hz, with a 5-sec ramp time and measurement intervals of 30 sec. The effects of a range of analgesic and sedative drugs on the threshold current to produce limb withdrawal were examined. Administration of the sedative/anesthetic drugs propofol and thiopentone intravenously and of the analgesic xylazine both intravenously and intramuscularly resulted in a reproducible dose-dependent rise in the threshold current required to produce limb withdrawal. Administration of the opioids alfentanil and pethidine produced agitation, making measurements unreliable. It is concluded that this device allows repeated reproducible measurements of analgesia and sedation to be made in sheep at a frequency sufficient to characterize the initial effects of analgesic and sedative drugs, particularly after intravenous administration.

Analgesics↗
PubMed1995

Biosynthetic origin of mycobacterial cell wall arabinosyl residues.

Designing new drugs that inhibit the biosynthesis of the D-arabinan moiety of the mycobacterial cell wall arabinogalactan is one important basic approach for treatment of mycobacterial diseases. However, the biosynthetic origin of the D-arabinosyl monosaccharide residues themselves is not known. To obtain information on this issue, mycobacteria growing in culture were fed glucose labeled with 14C or 3H in specific positions. The resulting radiolabeled cell walls were isolated and hydrolyzed, the arabinose and galactose were separated by high-pressure liquid chromatography, and the radioactivity in each sugar was determined. [U-14C]glucose, [6-3H]glucose, [6-14C]glucose, and [1-14C]glucose were all converted to cell wall arabinosyl residues with equal retention of radioactivity. The positions of the labeled atoms in the arabinose made from [1-14C]glucose and [6-3H]glucose were shown to be C-1 and H-5, respectively. These results demonstrated that the arabinose carbon skeleton is formed via the nonoxidative pentose shunt and not via hexose decarboxylation or via triose condensations. Since the pentose shunt product, ribulose-5-phosphate, is converted to arabinose-5-phosphate as the first step in 3-keto-D-manno-octulosonic acid biosynthesis by gram-negative bacteria, such a conversion was then searched for in mycobacteria. However, cell-free enzymatic analysis using both phosphorous nuclear magnetic resonance spectrometry and colorimetric methods failed to detect the conversion. Thus, the conversion of the pentose shunt intermediates to the D-arabino stereochemistry is not via the expected isomerase but rather must occur via novel metabolic transformations.

Arabinose↗
PubMed1994

An ultrasonic Doppler venous outflow method for the continuous measurement of cerebral blood flow in conscious sheep.

A pulsed ultrasonic Doppler venous outflow method was developed for the continuous measurement of global cerebral blood flow (CBF) in conscious sheep. The sheep were prepared under anesthesia with a "suture down"-style ultrasonic flow probe on the dorsal sagittal sinus placed via a trephine hole. Angiographic and dye studies showed that the dorsal sagittal sinus at the point of placement of the probe collected the majority of the blood from the cerebral hemispheres. Studies of the blood velocity profile across the sinus showed that the dimensions of the dorsal sagittal sinus changed minimally with changes in CBF in vivo. The velocity measurements were calibrated under anesthesia against an in vivo direct venous outflow method. Control CBF values for six sheep ranged from 31 to 53 ml/min for the area of brain described above; for two sheep in which the weight of the brain was determined, this gave total CBF values of approximately 34 and 30 ml min-1 100 g-1. The CBF measured varied in the expected manner with changes in the end-tidal CO2 concentration in expired breath and showed transient reductions with the barbiturate thiopentone and transient increases with the opiate alfentanil. It is concluded that the method is simple and accurate.

Alfentanil↗
PubMedDate not supplied

Quantitative analysis of flavonol glycosides in Ginkgo biloba: a comparison of two analytical methods.

A comparison of testing methods for constituents of Ginkgo biloba was performed as part of the process for determining which of the many available analytical methods was most appropriate for inclusion in the American Herbal Pharmacopoeia (AHP). Three primary methods were reviewed: those adopted by the European Pharmacopoeia, the National Science Foundation-Institute for Nutraceutical Advancement (NSF-INA) and the United States Pharmacopeia. Methods were compared by evaluating sample preparation and hydrolysis, precision and methods of total flavonol glycoside calculation by two independent laboratories. The AHP adopted the method of NSF-INA for inclusion in the AHP monograph owing to observed superiority of this method in terms of precision, glycoside calculation, ease of sample preparation and chromatographic parameters.

Chromatography, High Pressure Liquid↗