Effect Of Single Oral Dose Research Articles

Effect of vitamin A supplementation on diarrhoea and acute respiratory tract infection in children

To determine the effect of a massive single oral dose of vitamin A (200,000 IU) supplementation on diarrhoea and acute respiratory infection (ARI), a double-blind placebo controlled trial involving 174 children under six years of age (excluding infants) was carried out in a Calcutta slum community. Ninety-one children received vitamin A supplementation (experimental group) and 83 children received a placebo (control group). All the children were followed up for six months by active fortnightly surveillance for occurrence of diarrhoea or ARI and their duration. There was no statistically significant difference in the incidence of diarrhoeal episodes or ARI. However, there was a significant difference (p < 0.05) in the average duration of diarrhoea per episode (2.1 vs. 3 days) between the experimental and control groups. Possible beneficial effects of a single oral dose of vitamin A supplementation on the incidence of diarrhoea and ARI could not be demonstrated in the present study.

In vitro and in vivo reversible and irreversible inhibition of rat glutathione S-transferase isoenzymes by caffeic acid and its 2- S-glutathionyl conjugate

The reversible and irreversible inhibition of glutathione S-transferases (GST) by caffeic acid [3-(3,4-dihydroxyphenyl)-2-propenoic acid] was studied in vitro using purified rat isoenzymes, and in vivo in male Wistar (WU) rats. The concentrations of caffeic acid that inhibited reversibly 50% of the activity of different GST isoenzymes towards 1-chloro-2,4-dinitrobenzene (CDNB) (I 50 values) were 58 (GST 4-4), 360 (GST 3-3) and 470 μ m (GST 7-7), and higher than 640 μ m for GST isoenzymes of the α class (GST 1-1 and 2-2). The major glutathione conjugate of caffeic acid, 2- S-glutathionylcaffeic acid (2-GSCA), was a much more potent reversible inhibitor of GST, with I 50 values of 7.1 (GST 3-3), 13 (GST 1-1), 26 (GST 4-4), 36 (GST 7-7) and more than 125 μ m (GST 2-2). On the other hand, caffeic acid was a much more efficient irreversible inhibitor of GST than 2-GSCA. In this respect, GST 7-7 was by far the most sensitive enzyme. The remaining activity towards CDNB (expressed as percentage of control) after incubating 1.25 μ m-GST with 100 μ m-caffeic acid for 6 hr at 37°C was 34 (GST 2-2), 24 (GST 1-1), 23 (GST 4-4), 10 (GST 3-3) and 5% (GST 7-7). Almost no irreversible inhibition of GST 1-1 and 3-3 occurred during incubation with 2-GSCA. Incubation of caffeic acid with liver microsomes from dexamethasone-induced rats catalysed the oxidation of caffeic acid about 18 times more effectively as compared with the spontaneous oxidation, as determined by the formation of GSH conjugates from caffeic acid. In vivo, the effect of single oral doses of caffeic acid (50–500 mg/kg body weight) on the cytosolic GST activity towards CDNB was studied 18 hr after dosing in the liver, kidney and intestinal mucosa. A marginal but significant linear relationship was found between the amount of caffeic acid dosed and the irreversible inhibition of GST activity in the liver, with a maximum of about 14% inhibition in the highest dose group. This inhibition coincided with a small decrease in the μ-class GST subunits, which was only significant for GST subunit 4.

In vivo evaluation of nylon-coated diclofenac-resin complexes

Nylon-coated ion exchange resins containing sodium diclofenac were prepared by an interfacial polycondensation method. The in vitro release rate of sodium diclofenac from the coated and uncoated resins was determined using a continous-flow apparatus. The study showed that drug release from these formulations was slower than from a commercial sustained-release formulation of sodium diclofenac (Dolotrén Retard R), and that release from coated resins with low crosslinking exhibited first order kinetics indicating membrane-controlled release, whereas more highly crosslinked coated resins complied with Bhaskar et al.'s model of particle diffusion-controlled drug release. When the effects of single oral doses of five formulations were compared in rabbits, there were no statistically significant differences with respect to C max and AUC 0–24 h, but significantly t max was reached more slowly by the coated resins with low crosslinking than by the other formulations.

A comparison of the effects of single doses of amoxapine and amitriptyline on autonomic functions in healthy volunteers

We have studied the effects of single oral doses of amoxapine (100 mg and 200 mg), amitriptyline (50 mg and 100 mg), and placebo on some autonomic functions in ten healthy volunteers, using a balanced double-blind crossover design. Amitriptyline significantly reduced salivation and it significantly attenuated both miosis evoked by locally applied pilocarpine and sweat secretion evoked by locally applied carbachol. Amoxapine did not significantly alter any of these measures. Neither treatment significantly altered the pupillary light reflex (latency, amplitude, or 75% recovery time). Resting pupil diameter was significantly reduced by the higher dose of amoxapine but was not affected by the other treatments. The higher dose of amoxapine significantly increased supine systolic blood pressure, but did not affect heart rate or diastolic blood pressure; amitriptyline had no effect on any of these cardiovascular measures. These results confirm the antimuscarinic effects of amitriptyline in man, but provide no evidence for antimuscarinic effects of amoxapine.

Stereoselective features of (R)‐ and (S)‐atenolol: Clinical pharmacological, pharmacokinetic, and radioligand binding studies

In a randomized, double-blind, cross-over study in 12 healthy volunteers, the effects of single oral doses of 100 mg rac-atenolol were compared during exercise to those of equal amounts of the optically pure enantiomers, i.e., 50 mg (R)- and 50 mg (S)-atenolol. The mean rate pressure product decreased with rac-atenolol (-37%; P < 0.01) and half-dosed (S)-atenolol (-35%; P < 0.01) to the same extent, whereas (R)-atenolol caused no effect. Radioligand binding studies in beta-adrenergic receptors of the guinea pig heart yielded a eudismic ratio of 46 for (S)- to (R)-atenolol. The mean AUCs, maximal plasma concentrations, and plasma half-lives of the enantiomers were similar regardless of whether they were administered as optically pure enantiomers or as racemic mixture. On the other hand, the AUC of (R)-atenolol was 1.08-fold greater (P < 0.01) than that of the (S)-enantiomer. The reason for this finding remains unclear. We conclude that only (S)-atenolol, but not (R)-atenolol, contributes to the beta-blocking effect of currently used rac-atenolol since the same effect can be elicited with the (S)-enantiomer alone.

Acute effects of the novel antidepressant venlafaxine on cognitive event-related potentials (P300), eye blink rate and mood in young healthy subjects

Venlafaxine is a novel non-tricyclic antidepressant, which preclinically has demonstrated serotonin, norepinephrine, and dopamine reuptake inhibiting effects. In this study acute effects of single oral doses of placebo, 12.5 mg, 25 mg, and 50 mg venlafaxine on event-related potentials (ERPs), eye blink rate and mood were studied in 16 healthy subjects. ERPs were investigated in an auditory odd-ball paradigm before as well as 3 h after each drug intake. In addition to 17 EEG leads, vertical and horizontal EOGs were recorded. After EOG minimization and visual artefact rejection the peak latencies of the spatial average were determined by an automatic procedure. The applied methods of data acquisition, artefact processing, objective component determination and statistical analysis were successful in describing acute effects of venlafaxine on ERPs in normals. N1 and P2 latencies were not affected. An increase in P2 amplitude in the relevant central and frontal regions was seen, reflecting some effect on automatic information processing. Stimulus evaluation time was not affected, as P300 latency remained unchanged. P300 amplitude was not affected at the relevant central and parietal region. Blink rate was not changed. By means of the adjective checklist a dose-dependent decrease of "extroversion" and "high spirits" and an increase of "introversion" was observed. Our findings suggest that venlafaxine affects human information processing less than would be expected from the more centrally inhibiting classical antidepressants.

Effects of the prodrug loperamide oxide, loperamide, and placebo on jejunal motor activity

This crossover, double-blind study investigated the effects of single oral doses of the prodrug loperamide oxide, which is reduced gradually to loperamide in the intestine, and loperamide on jejunal motor activity in 12 fasting healthy men. Five minutes after a phase III of the migrating motor complex (MMC), 2 mg loperamide oxide, 4 mg loperamide oxide, 4 mg loperamide, or placebo were administered. Thereafter, motor activity 10-30 cm abroad the ligament of Treitz was recorded with five catheter orifices at 3-cm intervals over 4 hr. Number of contractions and area under curve increased significantly with 4 mg loperamide and 4 mg loperamide oxide, the increases with loperamide oxide occurring more gradually. Placebo and 2 mg loperamide oxide had no discernible effects. With both 4 mg loperamide and 4 mg loperamide oxide, phase I of the MMC was slightly prolonged and phase II and the time from drug administration to the onset of the first phase III slightly shortened. The percentage of aborally propagated contractions in phase II increased with all active treatments, whereas the occurrence of phases III was not altered.

Acute neurobehavioural toxicity of trichothecene T-2 toxin in the rat.

The acute effects of single oral doses, 0.4 and 2.0 mg/kg, of trichothecene T-2 mycotoxin on behaviour, motor performance and nociception were studied in male Wistar rats. Both doses are sublethal and did not cause overt acute signs of intoxication. In the open field test, 2.0 mg/kg of T-2 toxin increased motionlessness and decreased sniffing (P less than 0.05) 4 hr after the administration. The higher dose shortened step-through latencies in the test trial of the 24-hr passive avoidance test (two-way shuttle box). The exponential data analysis showed that, in those rats that did not learn to avoid the dark (unsafe) compartment of the box, the retention after 2.0 mg/kg of T-2 toxin was only 25% of that in controls (P less than 0.001). T-2 toxin had no effect on motor coordination in the rotarod test and in the bridge walking test 7-8 hr after administration. T-2 toxin had no effect on nociception in the hot place test 8.5 hr after administration. The results suggest that T-2 toxin has some inactivating effects on behaviour of rats, and it seems to cause an impairment in the passive avoidance test at dose 2.0 mg/kg.

Comparison of the cardiovascular effects of nifedipine and nicardipine in the presence of atenolol

A placebo controlled double blind crossover study was performed in 12 healthy volunteers to compare the cardiovascular effects of single oral doses of nifedipine (5, 10 and 15 mg) and nicardipine (20 and 30 mg) in the presence of atenolol 100 mg. Haemodynamic measurements were made by transthoracic electrical bioimpedance cardiography (TEBC) 2 h following drug administration during passive tilting, graded bicycle exercise (30-150 W) and recovery from exercise. In the absence of calcium channel blockade, atenolol reduced mean blood pressure, heart rate, and cardiac index, and increased stroke volume, peripheral resistance, pre-ejection period, and ventricular ejection time, particularly during and after exercise. In comparison with atenolol alone, addition of nifedipine or nicardipine reduced peripheral resistance but did not produce significant changes in stroke volume, cardiac output, dZ/dt [max], pre-ejection period (PEP). Ventricular ejection time (VET), PEP/VET, or Heather index at any point in the experiment. Similar reductions in peripheral resistance were produced by nifedipine 10 mg and nicardipine 20 and 30 mg. These apparently equivalent doses of nifedipine and nicardipine had similar effects on stroke volume, cardiac index, PEP/VET and Heather index. Thus the increases in ventricular performance previously demonstrated in association with nifedipine and nicardipine therapy were not observed in the presence of beta-adrenoceptor blockade. Under these conditions no important differences have been observed in the cardiovascular effects of these two calcium channel blockers.

A comparison of the sensitivities of adaptive tracking, eye movement analysis, and visual analog lines to the effects of incremental doses of temazepam in healthy volunteers

The effects of single oral doses of 5, 10, and 20 mg temazepam were evaluated with the adaptive tracking test, analysis of smooth-pursuit and saccadic eye movements, and visual analog lines in a placebo-controlled, double-blind, crossover experiment with 12 healthy volunteers. Pharmacodynamic testing was performed until 10 hours and pharmacokinetics were evaluated until 24 hours. Temazepam, 20 mg, caused effects in all tests, with peak effects occurring at 30 minutes. The 10 mg dose caused effects on saccadic eye movements and subjective scores of alertness, whereas 5 mg temazepam was detected only by analysis of saccadic eye movements. Linear relationships between plasma concentrations and effects were found in nine subjects for saccadic peak velocity and eight subjects for subjective scores of alertness. The results of this study demonstrate manifest differences in the sensitivities of performance tests and stress the importance of validation of methods when effects of drugs on human performance are studied.

Effect of azelastine and ketotifen on the bronchial and skin responses to platelet‐activating factor in humans

In a randomized, double-blind placebo-controlled study we investigated the effect of single oral doses of 8 mg azelastine and 2 mg ketotifen on the immediate response to platelet-activating factor (PAF) inhalation and to increasing doses of PAF injected intradermally. Bronchial provocation with 100 micrograms of PAF resulted in marked bronchoconstrictor responses, but neither azelastine nor ketotifen had any significant effect on these responses. Intradermal injection of PAF (100, 200 and 400 ng) resulted in a dose-related weal and flare response. Azelastine and ketotifen both caused significant reductions in this response (P less than 0.002-P less than 0.01). There was no significant difference between the effect of the two drugs.

Peripheral antihistamine and central sedative effects of single and continuous oral doses of cetirizine and hydroxyzine

The peripheral histamine-inhibiting and central sedative effects of single oral doses (SOD) and of repeated administration for one week (steady state, SS), of 20 mg hydroxyzine HCL and 10 mg cetirizine have been assessed in 12 healthy volunteers, in a double-blind placebo-controlled cross-over study. Peripheral H1-receptor antagonism was estimated as the reduction in the area of the flare and the duration of the itch after intradermal injection of histamine 0.1 and 1.0 micrograms. CNS effects were assessed by a battery of computerized neuropsychological tests and seven visual analogue scales. Drug compliance was ascertained by plasma level determinations. Cetirizine 10 mg (SOD) produced a more pronounced peripheral effect than 20 mg hydroxyzine, whereas hydroxyzine but not cetirizine, showed a significant sedative action in the relevant rating scales. These effects vanished during steady state, suggesting adaptation to the initial sedative effect of hydroxyzine in most of the subjects. No sedative effect of cetirizine was demonstrated. There was no impairment at group level in the neuropsychological tests after the SOD or SS treatment. However, six subjects who showed sedation in the analogue ratings after hydroxyzine, displayed significantly impaired performance after hydroxyzine SOD. The findings are discussed in relation to the individual characteristics of the study groups.

Effects of Diuretics on Outputs and Flows of Urine and Urinary Solutes in Healthy Subjects

The effects of single oral doses of common formulations of diuretics (i.e. formulations on the market or designed to be marketed) on 24-hour diuresis and natriuresis in healthy subjects are considered as a measure of the renal excretory potency of diuretics. Common formulations of distal tubular diuretics (e.g. hydrochlorothiazide 25mg, xipamide 10mg and 20mg) are more potent diuretics and natriuretics than common formulations of loop diuretics [e.g. furosemide (frusemide) 40mg, torasemide 2.5, 5 and 10mg]. Indeed, some common formulations of loop diuretics, such as torasemide 2.5, do not increase 24-hour diuresis or natriuresis in healthy subjects. 24-hour kaliuresis and magnesiuresis are elevated by common formulations of distal tubular diuretics, but they are only slightly increased or (more usually) not affected by common formulations of loop diuretics, when single doses are administered to healthy individuals. Common formulations of loop diuretics have lower diuretic and natriuretic potency and lower kaliuretic and magnesiuretic effects than common formulations of distal tubular diuretics, because the pronounced elevations in urinary excretions caused by loop diuretics during the first 6 hours after dosing are followed by rebounds, with respect to post-placebo excretions, between 6 and 24 hours after dosing. These rebounds, which affect the urinary flows of fluid, chloride, sodium, potassium and magnesium, do not occur after administration of common formulations of distal tubular diuretics, at least during the first 24 hours after administration of single doses to healthy subjects. The time courses of urinary excretions after loop diuretics are dose dependent. Higher doses produce more rapid changes in the urinary flows of fluid, chloride, sodium, potassium and magnesium than lower doses, to the extent that single administration of torasemide 2.5 or 5mg to healthy subjects is followed by urinary fluid and solute flows whose time courses resemble those after administration of hydrochlorothiazide 25mg.

The cardiovascular effects of oral nifedipine and nicardipine: A double-blind comparison in healthy volunteers using transthoracic bioimpedance cardiography

The cardiovascular effects of single oral doses of nifedipine (5 and 10 mg) and nicardipine (20 and 30 mg) were compared in a placebo controlled double-blind crossover study involving 8 healthy male volunteers. Two hours following drug administration stroke volume and cardiac index were measured non-invasively using transthoracic electrical bioimpedance cardiography during passive tilting, graded bicycle exercise, and recovery from exercise. Two separate experiments were performed in the absence of active drug to allow the reproducibility of the measurements to be assessed. Coefficients of variation (within experiment/between experiments) for cardiac index were 7.0%/19.9% at rest and 11.5%/9.3% at 180 W exercise. Both nifedipine and nicardipine increased stroke volume and cardiac index and reduced total peripheral resistance (mean blood pressure/cardiac index) at all times in the experiment. Reductions in peripheral resistance were similar for nifedipine 10 mg and nicardipine 20 mg but in these doses slightly larger increases in heart rate were produced by nifedipine, and in stroke volume and cardiac index with nicardipine. The study shows that the cardiovascular effects of nifedipine and nicardipine can be detected using impedance cardiography which is a simple, safe, and inexpensive technique. The differences between the effects of the two drugs were small. Although some were of statistical significance and are consistent with a less marked cardiodepressant effect for nicardipine, the clinical importance of these observations is uncertain. Further studies to examine the effect of oral nifedipine and nicardipine in patients with impaired ventricular function may be helpful in clarifying this tissue.

Effects of single doses of quinapril and atenolol on autonomic nervous function and exercise capacity in healthy volunteers

The effects of single oral doses of the angiotensin converting enzyme (ACE) inhibitor quinapril (CI-906) 40 mg and the cardioselective beta-adrenoceptor blocker atenolol 100 mg on sympathetic and parasympathetic function and on exercise capacity have been studied in 8 healthy young men. The trial followed a double-blind, placebo controlled, randomized cross-over design, with at least one week between treatments. Blood pressure (BP) and heart rate (HR) at rest were slightly reduced by atenolol but were not affected by quinapril. Atenolol impaired the sympathetically mediated increases in HR and BP caused by standing, immersion of the hand into melting ice, the Valsalva manoeuvre and isometric forearm exercise. Quinapril did not influence those responses nor the vagally mediated bradycardia of the diving reflex. Atenolol, however, augmented the vagal bradycardia, presumably by sympathetic inhibition. In a dynamic bicycle ergometer test with a stepwise increasing work load, exercise performance was decreased by atenolol but not by quinapril. Inhibition of the renin-angiotensin system by quinapril was shown by a marked decrease in serum ACE activity and a several-fold increase in plasma renin activity (PRA). Atenolol produced a moderate reduction in PRA. Before or during exercise, plasma noradrenaline and adrenaline were not influenced by either drug. The results indicate that, unlike the atenolol-induced beta-adrenoceptor blockade, ACE inhibition by a single dose of quinapril had no clear effect on autonomic nervous function or exercise capacity.

Experimental oral toxicity of domoic acid in cynomolgus monkeys ( Macaca fascicularis) and rats. : Preliminary investigations

A recent outbreak of marine food poisoning in humans was attributed to the consumption of blue mussels ( Mytilus edulis L.) contaminated with domoic acid (DA) that was produced by the diatom Nitzchia pungens. The clinical and morphological effects of single oral doses of extracts of mussels contaminated with DA or of DA isolated from toxic mussels were investigated in small groups (one to six) of cynomolgus monkeys ( Macaca fascicularis; 0.5–10 mg DA/kg body weight) and of Sprague-Dawley rats (60 to 80 mg DA/kg body weight). Control animals were either given saline or were not treated. To test whether monosodium glutamate, present in the food consumed by some affected humans, and dimethylsulphoxide, suspected of being present in the plankton, enhanced the response, monosodium glutamate (at 0.25% of mussel extract bolus) or dimethylsulphoxide (at 1 g per bolus) were co-administered to two (one each) of the DA-treated monkeys. DA-treated monkeys developed transient excitation characterized by vomiting. DA-treated rats showed withdrawal followed by hyperexcitation and death (in one case). Mild to moderate central nervous system lesions consistent with neuroexcitation were present in both monkeys and rats. The addition of monosodium glutamate and dimethylsulphoxide had no significant effect on the appearance and severity of central nervous system clinical signs and lesions. The wide variations in the response of test animals to orally administered DA were attributed to the protective effect of vomiting, and to suspected incomplete or slow gastro-intestinal absorption of the toxic agent. The results reinforce the view that DA is an emetic and that under appropriate conditions may also inflict excitotoxic central nervous system damage.

The effects of propranolol or atenolol on the cardiovascular responses to central hypovolaemia in Europeans and Bengalees.

1. The effects of single oral doses of propranolol (80 mg), or atenolol (100 mg) on resting heart rate, blood pressure, forearm blood flow and forearm vascular resistance and on responses to central hypovolaemia, were compared with those of placebo in nine healthy European and nine healthy Bengalee volunteers, in a double-blind, three-period, cross-over study. 2. Atenolol induced a significant reduction in resting systolic blood pressure (SBP) in Europeans but not in Bengalees, although the bradycardic effects of atenolol were similar in both groups. Atenolol did not have any significant effect on forearm blood flow (FBF) or forearm vascular resistance (FVR) in either group. In the presence of propranolol (80 mg) there were no statistically significant falls in BP but there were significant bradycardias, falls in FBF and rises in FVR that were similar in Europeans and Bengalees. 3. In the presence of placebo Europeans exhibited significant falls in diastolic blood pressure (DBP) during lower body negative pressure (LBNP) of 20 and 30 mm Hg. Bengalees did not show falls in DBP during LBNP. However, there were no significant differences between DBP responses in Europeans and Bengalee subjects. Both Bengalees and European subjects showed similar reductions in FBF and FVR during LBNP of 30 mm Hg. 4. In the presence of propranolol, significant changes in forearm blood flow and forearm vascular resistance were evident in Bengalee subjects during LBNP of 20 mm Hg and 30 mm Hg, whereas in the Europeans significant changes in those variables did not occur at any level. The changes in FBF and FVR during LBNP of 20 and 30 mm Hg in Bengalee and European subjects were significantly different.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracardial Effects of Oral Ibopamine versus Furosemide in Patients with Mild or Moderate Heart Failure

Ibopamine is a novel oral dopamine analogue with vasodilatory, positive inotropic and diuretic effects. In a double-blind, randomized study, the drug was investigated in 12 patients (mean age 49 +/- 10 years, 8 male, 4 female) with mild or moderate heart failure (NYHA classes II:8 patients, III:4 patients). Effects of single oral doses of 200 mg ibopamine, of 40 mg furosemide and of 200 mg ibopamine + 40 mg furosemide were compared in each patient at 3-day intervals. 1 h after administration, systolic and diastolic blood pressure increased from 120 +/- 11 to 124 +/- 9 and from 76 +/- 5 to 81 +/- 6 mm Hg in the ibopamine group. During 4 h after drug ingestion, urinary flow was significantly raised from 124 +/- 81 to 228 +/- 166 ml/2 h in the ibopamine group (p less than 0.05), while the administration of furosemide (with or without ibopamine) resulted in several folds increases of urinary flow. After ibopamine, the 2-h creatinine clearance rose from 123 +/- 73 to 131 +/- 85 ml/min (not significant). Sodium and potassium excretion remained essentially unchanged by ibopamine, while effects of furosemide were several folds of those of ibopamine. Plasma renin activity was lowered to 65% by ibopamine (p less than 0.01). No additive effects of ibopamine in the presence of furosemide were observed for all parameters tested. These results indicate that ibopamine has smaller renal effects than furosemide with regard to water diuresis and kaliuresis. These effects of ibopamine could reflect direct changes of renal function or secondary effects of neurohumoral origin. Ibopamine does not produce undesirable renal side effects, but affects the neurohumoral status favourably. This drug, thus, could be useful as an adjuvant therapy in mild heart failure.

Behavioral performance effects of nifedipine in normotensive baboons: Single dosing

The effects of single oral doses of the calcium channel blocker nifedipine were assessed on performance of a simultaneous color match-to-sample task in three normotensive baboons. Both accuracy of color matching, and speed and latency of response were measured 30 min after administration of 0.10, 0.34, 0.57, and 1.7 mg/kg and vehicle, with each dose tested on three occasions in randomized order. Systolic and diastolic blood pressures also were measured after testing sessions. Maximal decreases in systolic blood pressure (mean of three subjects = −4.56 mmHg) were obtained after ingestion of the 0.57 mg/kg dose. Nifedipine produced dose-related changes in choice reaction times with a trend toward increased reaction times of approximately 5% obtained at 0.34 and 1.7 mg/kg. A reversal of effect was noted at 0.57 mg/kg such that smaller changes in reaction times were obtained, suggesting a lack of correlation between blood pressure and behavioral performance changes. These results indicate that nifedipine administered in single doses to patients with hypertensive crisis is unlikely to produce large impairments in these aspects of sensory and motor functioning.

Effect of Single Oral Doses of Ascorbic Acid on Body Temperature in Healthy Guinea Pigs

A series of experiments were conducted to examine the effect of single oral doses of ascorbic acid on body temperature in healthy guinea pigs. Fifteen male guinea pigs (approximately 200 g) were fed a nonpurified diet designed for rabbits (a scorbutogenic diet) ad libitum and received orally 2 mg L-ascorbic acid/100 g body wt daily. After acclimation, rectal temperatures were recorded hourly following five separate ascorbate dosage treatments: 0 (control dosage), 2, 10 or 50 mg ascorbic acid/100 g body wt, or 50 mg ascorbic acid and 0.07 mg indomethacin/100 g body wt. Mean body temperature was significantly elevated (P less than 0.05) after 1 h in animals receiving either the 10 or 50 mg dosage (+ 0.27 +/- 0.05 and + 0.41 +/- 0.07 degree C, respectively) compared to that in animals receiving the 2 mg dosage (-0.07 +/- 0.05 degree C), the recommended daily intake for guinea pigs. Changes in body temperature of animals receiving the 50 mg dosage plus indomethacin did not differ significantly from those reported with the 2 mg dosage. Thus, a single oral dose of ascorbic acid at levels 5-25 times the recommended intake, can elevate body temperature significantly in healthy guinea pigs, a phenomenon which is inhibited by indomethacin administration.