Morning Trials Research Articles

Resting State EEG Variability and Implications for Interpreting Clinical Effect Sizes.

Resting state electroencephalography (rsEEG) is widely used to investigate intrinsic brain activity, with the potential for detecting neurophysiological abnormalities in clinical conditions from neurodegenerative disease to developmental disorders. When interpreting quantitative rsEEG changes, a key question is: how much deviation from a healthy normal brain state indicates a clinically significant change? Here, we build on the existing rsEEG variability literature by quantifying how this baseline rsEEG range can be attributed to common but underinvestigated sources of variability: experiment day, time of day, and pre-recording exercise level. We found that even within individuals, frequency band powers and entropy measures can vary by 7% (sample entropy and relative alpha power) to 28% (absolute delta power). Absolute and relative delta power increased significantly after running, while relative theta power decreased significantly. Relative beta and gamma power were significantly higher in the afternoon compared to morning trials. Sample entropy and alpha power were relatively consistent. The coefficients of variability we found are similar to some clinical rsEEG effect sizes identified in prior literature, bringing into question the clinical significance of these effect sizes. Furthermore, time of day and activity level accounted for more rsEEG variability than experiment day, indicating the potential to reduce variability by controlling for these factors in repeated-measures studies.

A prenatal acoustic signal of heat affects thermoregulation capacities at adulthood in an arid-adapted bird

Understanding animal physiological adaptations for tolerating heat, and the causes of inter-individual variation, is key for predicting climate change impacts on biodiversity. Recently, a novel mechanism for transgenerational heat adaptation was identified in a desert-adapted bird, where parents acoustically signal hot conditions to embryos. Prenatal exposure to “heat-calls” adaptively alters zebra finch development and their thermal preferences in adulthood, suggesting a long-term shift towards a heat-adapted phenotype. However, whether such acoustic experience improves long-term thermoregulatory capacities is unknown. We measured metabolic rate (MR), evaporative water loss (EWL) and body temperature in adults exposed to a stepped profile of progressively higher air temperatures (Ta) between 27 and 44 °C. Remarkably, prenatal acoustic experience affected heat tolerance at adulthood, with heat-call exposed individuals more likely to reach the highest Ta in morning trials. This was despite MR and EWL reaching higher levels at the highest Ta in heat-call individuals, partly driven by a stronger metabolic effect of moderate activity. At lower Ta, however, heat-call exposed individuals had greater relative water economy, as expected. They also better recovered mass lost during morning trials. We therefore provide the first evidence that prenatal acoustic signals have long-term consequences for heat tolerance and physiological adaptation to heat.

Mental rotation performance and circadian chronotype in university students: a preliminary study

ABSTRACT The present study aimed to explore the influence of the chronotype on mental rotation performance in university students. Using the Morningness-Eveningness Questionnaire (MEQ), 24 healthy volunteers were categorized as either early chronotype (ECT) or late chronotype (LCT). Participants completed a chronometric mental rotation task with three-dimensional stimuli at different times of day (8 AM and 8 PM). ECT participants showed a shorter reaction time in the morning trial than in the evening (p = 0.003), whereas LCT participants showed a shorter reaction time (p = 0.001) and increased accuracy (p = 0.031) in the evening compared to the morning session. Additionally, the MEQ score was positively correlated with the difference in reaction time between morning and evening trials (r = −0.589, p = 0.002). Two-way analysis of variance revealed an interaction between time and chronotype for the parameter reaction time in the evening trials (F(1, 22) = 28.27, p < 0.001). LCT participants showed higher speed and increased accuracy during their optimal time compared to ECT participants. This study explored diurnal alterations of visual-spatial abilities assessed as mental rotation performance, and the possible implications for certain life skills such as sports, car driving, and manual labor are discussed.

The Impact Of Placebo Caffeine Dose On Cognitive Performance And Endurance Running In Recreational Athletes

PURPOSE: A caffeine-mediated dose-response placebo effect has previously been observed in trained cyclists. The current study aimed to determine if perceived caffeine dose influences cognitive and/or running performance in recreational athletes. METHODS: Twenty-nine healthy individuals (23.7±5 y (Mean±SD), 16 males) completed two morning trials (repeated measures design, separated by 1 week), involving a choice reaction time (CRT) test followed by a 10km performance run. Prior to the first trial, participants indicated their beliefs of caffeine’s effects on performance and any previous experience using caffeine as an ergogenic aid. On arrival to the testing facility, participants randomly received (and were told they were getting) “Low dose (100mg)” or “High dose (300mg)” of caffeine capsules (all contained placebo, (psyllium husk powder)) prior to commencing the CRT test (30min post capsule ingestion). Paired samples t tests were used to determine differences between trials and CRT latency (employing Ex-Gaussian analysis) and running performance using the entire participant sample and for the sub-groups exhibiting strong “beliefs” +/- prior experience. RESULTS: Perceived caffeine dose did not influence CRT (μ-, σ- and τ-components respectively, Low: 400±53ms vs High: 388±4ms; Low: 35±18ms vs High: 34±17ms; Low: 50±24ms vs High: 52±19ms, all p’s>0.05). Neither personal belief (n=9), nor belief + experience (n=6) influenced this effect. Furthermore, perceived caffeine dose did not influence run time (Low: 49.05±3.75 min vs High: 49.06±3.85 min, p=0.979). Personal belief (Low: 48.93±3.71 min vs High: 48.9±3.52 min, p=0.976), and belief + experience (Low: 48.68±1.87 min vs High: 49.55±1.75 min, p=0.386) did not influence this effect. CONCLUSIONS: Placebo effects of perceived caffeine-dose ingestion on cognitive and running performance were not observed in this study of recreationally active individuals, irrespective of individual’s prior beliefs or caffeine use.

Psychoacoustical Differentiation with Regard to the Perception of Pitch—A Comparison Between Musicians and Non-Musicians

Psychoacoustics is considered to be a category of psychophysics and is termed as the assessment of auditory or sound perception and deals with perception of sound among different human beings. Psychoacoustics is a very qualitative phenomenon and is often the reason for an individual to perceive the sound in different manner, as compared to another. This effect is more prominent in music wherein a given music bit may seem good to one, whereas, another may perceive it as bad. For this to happen, various attributes of sound play an important part, in the categorization based on psychoacoustical perception. The present work considered pitch as the varying attribute and provided a comparative assessment of sound, based on the variation of pitch in terms of Pitch Detection Threshold (PDTh) between trained musicians and non-musicians. 44 subjects of both conditioned and controlled set were considered for this study and were made to undergo the Pitch Detection Test (PDT) to assess their PDTh. Two trials were conducted, once in the morning and the other in the evening. The results provided substantial cue to conclude that the musicians had a better PDTh (6.83 dB) than the control set (31.31 dB). Also, the PDTh was better in the morning trials, as compared to their evening counterparts. This could be attributed to the professional training in music, due to which the conditioned set outperformed the control set of subjects. Such an analysis could aid in the assessment of auditory perceptive abilities and their improvement with music and hence indicate the plausible improvement in the auditory perception with music based raaga therapy. Further, more attributes such as intensity and frequency could be encompassed to provide stronger relationship between perception and learning, in this case being music training sessions, which could also work as therapy for certain auditory perceptive disorders.

Effects of Meal Timing on Postprandial Glucose Metabolism and Blood Metabolites in Healthy Adults

We examined the effects of meal timing on postprandial glucose metabolism, including the incretin response and metabolites in healthy adults. Nineteen healthy young men completed two trials involving blood collection in a fasting state and at 30, 60 and 120 min after meal provision in a random order: (1) morning (~0900 h) and (2) evening (~1700 h). The blood metabolome of eight participants was analyzed using capillary electrophoresis-mass spectrometry. Postprandial glucose concentrations at 120 min (p = 0.030) and glucose-dependent insulinotropic polypeptide concentrations (p = 0.005) at 60 min in the evening trials were higher than those in the morning trials. The incremental area under the curve values of five glycolysis, tricarboxylic acid cycle and nucleotide-related metabolites and 18 amino acid-related metabolites were higher in the morning trials than those in the evening trials (p < 0.05). Partial least-squares analysis revealed that the total metabolic change was higher in the morning. Our study demonstrates that a meal in the evening exacerbates the state of postprandial hyperglycemia in healthy adults. In addition, this study provides insight into the difference of incretion and blood metabolites between breakfast and dinner, indicating that the total metabolic responses tends to be higher in the morning.

Diurnal variation in the salivary melatonin responses to exercise: relation to exercise-mediated tachycardia

Salivary melatonin concentration is an established marker of human circadian rhythmicity. It is thought that melatonin is relatively robust to the masking effects of exercise. Nevertheless, the extent and even the direction of exercise-related change is unclear, possibly due to between-study differences in the time of day exercise is completed. Therefore, we aimed to compare melatonin responses between morning and afternoon exercise, and explore the relationships between exercise-related changes in melatonin and heart rate. At 08:00 and 17:00hours, seven male subjects (mean±SD age, 27±5years) completed 30min of cycling at 70% peak oxygen uptake followed by 30min of rest. Light intensity was maintained at ~150lx. Salivary melatonin (ELISA) and heart rate were measured at baseline, 15min during exercise, immediately post-exercise and following 30min recovery. Melatonin was ≈15pgml(-1) higher in the morning trials compared with the afternoon (P=0.030). The exercise-related increase in melatonin was more pronounced (P=0.024) in the morning (11.1±8.7pgml(-1)) than in the afternoon (5.1±5.7pgml(-1)). The slope of the heart rate-melatonin relationship was significantly (P=0.020) steeper in the morning (0.12pgml(-1)beats(-1)min(-1)) than in the afternoon (0.03pgml(-1)beats(-1)min(-1)). In conclusion, we report for the first time that the masking effect of moderate-intensity exercise on melatonin is approximately twice as high in the morning than the afternoon. The much steeper relationship between heart rate and melatonin changes in the morning raises the possibility that time of day alters the relationships between exercise-mediated sympathetic nervous activity and melatonin secretion.

Sources of Variability in Iso-Inertial Jump Assessments

This investigation aimed to quantify the typical variation for kinetic and kinematic variables measured during loaded jump squats. Thirteen professional athletes performed six maximal effort countermovement jumps on four occasions. Testing occurred over 2 d, twice per day (8 AM and 2 PM) separated by 7 d, with the same procedures replicated on each occasion. Jump height, peak power (PP), relative peak power (RPP), mean power (MP), peak velocity (PV), peak force (PF), mean force (MF), and peak rate of force development (RFD) measurements were obtained from a linear optical encoder attached to a 40 kg barbell. A diurnal variation in performance was observed with afternoon values displaying an average increase of 1.5-5.6% for PP, RPP, MP, PV, PF, and MF when compared with morning values (effect sizes ranging from 0.2-0.5). Day to day reliability was estimated by comparing the morning trials (AM reliability) and the afternoon trials (PM reliability). In both AM and PM conditions, all variables except RFD demonstrated coefficients of variations ranging between 0.8-6.2%. However, for a number of variables (RPP, MP, PV and height), AM reliability was substantially better than PM. PF and MF were the only variables to exhibit a coefficient of variation less than the smallest worthwhile change in both conditions. Results suggest that power output and associated variables exhibit a diurnal rhythm, with improved performance in the afternoon. Morning testing may be preferable when practitioners are seeking to conduct regular monitoring of an athlete's performance due to smaller variability.

Positive Relationship between Endogenous Melatonin and Core Temperature Responses to Exercise

At rest, circadian variation in the vaso-active substance, melatonin, is inversely related to that of core body temperature (Tcore). Although ingestion of exogenous melatonin has been reported to lower Tcore by approximately 0.2°C during subsequent exercise (Atkinson et al. 2005, J Pineal Res, 39, 353-9), the relationship between endogenous melatonin and Tcore has not been investigated during and after exercise at different times of the day. PURPOSE: To examine the relationship between exercise-related responses of salivary melatonin and Tcore measured at different sites in the morning and afternoon. METHODS: At 08:00 and 17:00 h, seven male subjects (mean±SD age: 27±5 y) completed 30 min of cycling at 70% peak oxygen uptake followed by 30 min recovery. Salivary melatonin levels were measured at baseline, 15 min into the exercise, immediately post-exercise and following 30 min recovery. Oesophageal (Tes), rectal (Trec), intestinal (Tit), and skin (Tskin) temperature were monitored during trials. Data were analysed using time of day × time general linear models and within-subjects correlation analysis. RESULTS: Melatonin was generally higher at 08:00 than 17:00 h (P=0.059) whilst Tcore was significantly lower during the morning trials compared to the afternoon (P=0.003). This difference was much smaller for Tes compared to Tit and Trec. Melatonin, Tcore and Tskin all increased with exercise but the standardised effects of exercise were smaller for melatonin (0.64-1.03) than for Tcore (2.23-5.26) and Tskin (2.22-4.18). The within-subject correlation between Tes and melatonin was 0.65 and 0.67 in the morning and afternoon respectively (P=0.001). Correlations between Tcore and melatonin were also positive for the other core temperature sites, irrespective of time of day. The correlation between Tskin and melatonin was 0.40 (P=0.065) in the morning and 0.65 (P=0.001) in the afternoon. CONCLUSION: These data indicate that, although circadian rhythms in endogenous melatonin and core temperature are inversely related at rest, exercise mediates a parallel acute increase in both variables. It seems that the effects of exercise are relatively more pronounced on core body temperature than on melatonin, adding weight to the notion that melatonin is a more stable marker of circadian timing.

Oral sensory and cephalic hormonal responses to fat and non-fat liquids in bulimia nervosa

Sensory evaluation of food involves endogenous opioid mechanisms. Bulimics typically limit their food choices to low-fat “safe foods” and intermittently lose control and binge on high-fat “risk foods”. The aim of this study was to determine whether the oral sensory effects of a fat versus a non-fat milk product (i.e., traditional versus non-fat half-and-half) resulted in different subjective and hormonal responses in bulimic women ( n = 10) compared with healthy women ( n = 11). Naltrexone (50 mg PO) or placebo was administered 1 h before, and blood sampling began 30 min prior to and 29 min after, a 3 min portion controlled modified sham-feeding trial. Following an overnight fast, three morning trials (fat, naltrexone; fat, placebo; and non-fat, placebo) were administered in a random double-blind fashion separated by at least 3 days. Overall, there were no differences between Fat and Non-Fat trials. Hunger ratings ( p < 0.001) and pancreatic polypeptide levels ( p < 0.05) were higher for bulimics at baseline. Bulimics also had overall higher ratings for nausea ( p < 0.05), fatty taste ( p < 0.01), and fear of swallowing ( p < 0.005). Bulimics had ∼ 40% higher total ghrelin levels at all time points ( p < 0.001). Hormones and glucose levels were not altered by the modified sham-feeding paradigm. Naltrexone, however, resulted in an overall increase in blood glucose and decrease in ghrelin levels in both groups ( p < 0.05, for both). These data suggest that bulimic women have different orosensory responses that are not influenced by opioid receptor antagonism, evident in hormonal responses, or dependent on the fat content of a similarly textured liquid.

Interaction effects of time of day and sub-maximal treadmill exercise on the main determinants of blood fluidity

The purpose of this study was to investigate the effects of time of day on responses of the main determinants of blood rheology to acute endurance exercise. Ten healthy male subjects (age, 26.9 +/- 5.5 yr) performed two bouts of running at 65% of VO2peak for 45 min on a motorised treadmill in the morning (08:00 h) and evening (20:00 h), which were followed by 30 min recovery. The two exercise trials were performed in two separate days with 7 days intervening. Haemorheological variables were measured before, immediately after exercise and after recovery. Haematocrit, haemoglobin and RBC count were increased significantly (p < 0.01) after 45 min running in both morning and evening trials and normalised following recovery, irrespective of time of day. Plasma viscosity increased significantly (F2,18 = 12.4, p < 0.01) following sub-maximal exercise in both trials and returned to pre-exercise level at the end of recovery. Baseline values (p < 0.05) but not responses of plasma viscosity to exercise were significantly affected by time of day. Neither a significant main effect of exercise nor a significant (p > 0.05) time-of-day effect was found for plasma proteins. It was concluded that sub-maximal running at 08:00 or 20:00 h does not induce different responses in the main determinant of blood rheology.

Oral sensory and cephalic hormonal responses to fat and non-fat liquids in bulimia nervosa

Sensory evaluation of food involves endogenous opioid mechanisms. Bulimics typically limit their food choices to low-fat safe foods and intermittently lose control and binge on high-fat risk foods. The aim of this study was to determine whether the oral sensory effects of a fat versus a non-fat milk product (i.e., traditional versus non-fat half-and-half) resulted in different subjective and hormonal responses in bulimic women (n=10) compared with healthy women (n=11). Naltrexone (50mg PO) or placebo was administered 1h before, and blood sampling began 30 min prior to and 29 min after, a 3 min portion controlled modified sham-feeding trial. Following an overnight fast, three morning trials (fat, naltrexone; fat, placebo; and non-fat, placebo) were administered in a random double-blind fashion separated by at least 3 days. Overall, there were no differences between Fat and Non-Fat trials. Hunger ratings (p<0.001) and pancreatic polypeptide levels (p<0.05) were higher for bulimics at baseline. Bulimics also had overall higher ratings for nausea (p<0.05), fatty taste (p<0.01), and fear of swallowing (p<0.005). Bulimics had approximately 40% higher total ghrelin levels at all time points (p<0.001). Hormones and glucose levels were not altered by the modified sham-feeding paradigm. Naltrexone, however, resulted in an overall increase in blood glucose and decrease in ghrelin levels in both groups (p<0.05, for both). These data suggest that bulimic women have different orosensory responses that are not influenced by opioid receptor antagonism, evident in hormonal responses, or dependent on the fat content of a similarly textured liquid.

Daytime Changes in Postural Stability and Repeatability of Posturographic Measurements

Daytime sleepiness correlates with sleep-related accidents, but convenient tests for occupational sleepiness monitoring are scarce. The effect of daytime on balance, on posturographic measurements, and on their repeatability was investigated in 30 healthy volunteers as part of our work to develop such a test. The daytime effect was assessed by measuring balance at 8:30 am, 10:30 am, and 1:30 pm. The repeatability was assessed with morning trials once a week for 1 month. The posturographic test was performed on a static force platform, and the balance was evaluated from a fractal dimension of sway, most common sway amplitude, and time interval for open-loop stance control. The balance worsened during the day, and it was possible to determine whether the measurement was performed in the morning or in the afternoon. The morning balance remained unchanged during the month-long test. Posturographic measurements are repeatable and have a circadian effect, which may be influenced by sleepiness.

Comparison of physiological responses to morning and evening submaximal running

The aim of this study was to assess the effect of time of day on physiological responses to running at the speed at the lactate threshold. After determination of the lactate threshold, using a standard incremental protocol, nine male runners (age 26.3 - 5.7 years, height 1.77 - 0.07 m, mass 73.1 - 6.5 kg, lactate threshold speed 13.6 - 1.6 km· h -1 ; mean - s ) completed a standardized 30 min run at lactate threshold speed, twice within 24 h (07:00- 09:00 h and 18:00-21:00 h). Core body temperature, heart rate, minute ventilation, oxygen uptake, carbon dioxide expired, respiratory exchange ratio and capillary blood lactate were measured at rest, after a warm-up and at 10, 20 and 30 min during the run. In addition, the rating of perceived exertion was reported every 10 min during the run. Significant diurnal variation was observed only for body temperature (36.9 - 0.9°C vs 37.3 - 0.3°C) and respiratory exchange ratio at rest (0.86 - 0.01 vs 0.89 - 0.07) ( P ≪ 0.05). Diurnal variation persisted for body temperature throughout the warm-up (37.1 - 0.2°C vs 37.5 - 0.3°C) and during exercise (36.2 - 0.6°C vs 38.6 - 0.4°C), but only during the warm-up for the respiratory exchange ratio (0.85 - 0.05 vs 0.87 - 0.02) ( P ≪ 0.05). The rating of perceived exertion was significantly elevated during the morning trial (12.7 - 0.9 vs 11.9 - 1.2) ( P ≪ 0.05). These findings suggest that, despite the diurnal variation in body temperature, other physiological responses to running at lactate threshold speed are largely unaffected. However, a longer warm-up may be required in morning trials because of a slower increase in body temperature, which could have an impact on ventilation responses and ratings of perceived exertion.

Reproducibility of diurnal variation in sub-maximal swimming.

Swimming training is characterised by the use of early morning and evening training sessions. The purpose of the present study was to investigate if the physiological and kinematic responses to swimming a typical training set are affected by time of day. Seven male collegiate swimmers (age 22 +/- 4 years; height 1.8 +/- 0.1 m; mass 82.1 +/- 4.1 kg) completed a standardised 600 m warm up followed by a 10 x 100 m sub-maximal freestyle set twice a day (06:30-08:00 h and 16:30-20:00 h) on three separate days. Swimming speed was controlled precisely throughout (limits of agreement multiplied/divided 1.00) using a new pacing device (Aquapacer, Challenge and Response, Inverurie, Scotland). Oral temperature (To), heart rate (HR), minute ventilation (VE), oxygen uptake (VO2), carbon dioxide expired (VCO2), respiratory exchange ratio (RER), capillary blood lactate (Bla), and glucose (BGL) were measured at rest and post exercise. Stroke rate (SR) and HR were measured during the first nine 100 m repetitions while rate of perceived exertion (RPE) was measured immediately after each 100 m. Significant diurnal variation was found at rest in To, HR, and VO2 on all three days and for VE and VCO2 on two of the days (P<0.05). During the training set no diurnal variation was evident in HR and SR responses or repetition times although RPE values were higher in morning trials compared to evening trials on two of the three days (P < 0.05). Post-exercise significant diurnal variation was found for To and blood glucose for two of the three days (P < 0.05). Therefore, although diurnal variation is evident at rest, there is no subsequent effect on physiological and kinematic responses during a sub-maximal training set following a standardised warm-up.

DIURNAL EFFECTS ON THERMOREGULATION AND TOLERANCE OF UNCOMPENSABLE HEAT STRESS

1537 This study examined whether the lower rectal temperature (Tre) in the morning hours would increase tolerance to uncompensable heat stress compared with trials conducted in the early afternoon. Nine males (34 y, 82 kg, 2.0 m2 surface area) performed a familiarisation trial and then 2 randomly ordered trials in the morning (0930h) and afternoon (1330h). The heat stress test consisted of intermittent walking at 3.5 km/h and seated rest at 40°C and 30% relative humidity while wearing nuclear, biological and chemical protective clothing. Initial Tre was significantly higher during the afternoon (37.1 ± 0.2°C) compared with the morning (36.8 ± 0.2°C) and these differences remained throughout the uncompensable heat stress such that final Tre was also significantly higher for the afternoon (39.2 ± 0.2°C) versus the morning (39.0 ± 0.3°C) trials. Metabolic rate, heart rate and the sweat production rate were similar during the morning and afternoon exposures. Since the rate of heat storage (100.6 ± 24 W/m2 and 96.5 ± 21.2 W/m2 for the morning and afternoon trials, respectively) and tolerance time (111 ± 22 and 107 ± 19 min for the morning and afternoon trials, respectively) were similar, calculated total heat storage also was similar for the morning (16.1 ± 2.9 kJ/kg) and afternoon heat stress exposures (15.1 ± 3.0 kJ/kg). It was concluded that trials conducted in the early afternoon were associated with an increased rectal temperature tolerated at exhaustion that offset the circadian influence on resting rectal temperature, and thus, maintained tolerance times similar to trials conducted in the morning.

A comparison of two assays to test the defensive behaviour of honey bees ((Apis mellifera)

SUMMARYThe reliability of a traditional leather-patch assay to measure the stinging behaviour of honey bees was compared with that of a temper detection apparatus developed to electronically measure and record defensiveness. Colonies were tested with the two different assays during morning and afternoon hours. The traditional assay was more reliable than the automated electronic assay. Afternoon trials were more reliable than morning trials. Significant variation was observed among colonies with both methods, suggesting that these assays may separate highly defensive from gentle colonies. However, variation among trials within colonies may result in misclassifying colonies with intermediate degrees of defensiveness. The need for the development of more reliable assays is stressed.

Time of day and processing strategies in narrative comprehension

We present two experiments investigating the different occurrence of comprehension strategies of written texts at different times of the day. Methods of inferential production (free recall, question answering, filling in) were adopted along with other methods reported in the literature (immediate recognition, immediate free recall, immediate cued recall). On the basis of the hypothesis that it is prevalently a maintenance strategy which is adopted in the morning vs. an elaborative strategy in the afternoon, it is suggested that recall of superficial linguistic information of the text is better in morning trials while inferential production is greater in afternoon trials. The results of both experiments on the whole agree with the predictions made.

Chronotherapy of Trichlormethiazide in Hypertensive Patients

Circadian influence of trichlormethiazide on serum electrolyte levels, lipid levels, and glucose levels were evaluated in 12 hypertensive patients. One tablet of trichlormethiazide (2 mg) was given once a day at 7:00 AM or 7:00 PM for 8 weeks. The study was done by a crossover design. Twenty-four-hour urine was collected, and fasting blood samples were obtained during the control period and at the end of each treatment period. The 24-hour urine level increased slightly after treatment with trichlormethiazide in the morning and evening trials. Urinary excretion of sodium also increased slightly in the morning trial and increased significantly in the evening trial. Serum concentrations of potassium and chloride decreased, and serum uric acid level increased after trichlor-methiazide treatment. No significant difference was observed in these parameters between morning and evening trials. Fasting blood glucose levels increased after trichlormethiazide treatment. The increment in blood glucose levels was greater in the evening trial than in the morning trial. These data indicate that the influence of trichlormethiazide on glucose tolerance might vary with its administration time.

Benzodiazepines and caffeine: effect on daytime sleepiness, performance, and mood

In a double-blind parallel group design, 80 young adult males were divided into eight treatment groups. Subjects received 15 or 30 mg flurazepam, 0.25 or 0.50 mg triazolam, or placebo at bedtime, and 250 mg caffeine or placebo in the morning for 2 treatment days. Two objective (Multiple Sleep Latency Test and lapses) and two subjective (Stanford Sleepiness Scale and Visual Analog Scale) measures of sleepiness, five performance tests, and two mood measures (Profile of Mood Scale and Visual Analog Mood Scale) were administered repeatedly on both days. Significant treatment effects were found for sleepiness but not for performance or mood. Early morning caffeine significantly antagonized next day hypnotic-induced drowsiness and enhanced alertness in the subjects who received bed-time placebo. Flurazepam, 30 mg, subjects were more sleepy than all other groups. Although not significantly different, the flurazepam, 30 mg, group demonstrated a trend toward poorer performance and a more negative mood than all other groups. Caffeine most improved performance of this group. In all groups, sleepiness was greatest and performance and mood poorest in early morning trials and caffeine was most effective at this time.