Antiplatelet Effect of Clopidogrel Can Be Reduced by Calcium-Channel Blockers

Purpose

Clopidogrel is metabolized by the hepatic cytochrome P450 (CYP) system into its active thiol metabolite. CYP3A4 is involved in the metabolism of both clopidogrel and dihydropyridine calcium channel blockers (CCBs). A few reports have suggested an inhibitory interaction between CCBs and clopidogrel. Accordingly, the aim of this study was to determine the effect of CCBs on the antiplatelet activity of clopidogrel by serial P2Y12 reaction unit (PRU) measurements.

Materials and Methods

We assessed changes in antiplatelet activity in patients receiving both clopidogrel and CCBs for at least 2 months prior to enrollment in the study. The antiplatelet activity of clopidogrel was measured by VerifyNow P2Y12 assay in the same patient while medicated with CCBs and at 8 weeks after discontinuation of CCBs. After discontinuation of the CCBs, angiotensin receptor blockers were newly administered to the patients or dosed up for control of blood pressure.

Results

Thirty patients finished this study. PRU significantly decreased after discontinuation of CCBs (238.1±74.1 vs. 215.0±69.3; p=0.001). Of the 11 patients with high post-treatment platelet reactivity to clopidogrel (PRU≥275), PRU decreased in nine patients, decreasing below the cut-off value in seven of these nine patients after 8 weeks. Decrease in PRU was not related to CYP2C19 genotype.

Conclusion

CCBs inhibit the antiplatelet activity of clopidogrel.     

Adjunctive Cilostazol versus High Maintenance Dose of Clopidogrel in Patients with Hyporesponsiveness to Chronic Clopidogrel Therapy

Purpose

Whether addition of cilostazol is superior to increasing dose of clopidogrel in patients with hyporesponsiveness to chronic clopidogrel therapy is unknown.

Materials and Methods

We studied 73 patients with hyporesponsiveness to clopidogrel on standard dual antiplatelet therapy for more than 2 weeks. Clopidogrel hyporesponsiveness was defined as percent inhibition of P2Y12 reaction units (PRU) <30% on VerifyNow P2Y12 assay. Patients were randomly assigned to increased dose of clopidogrel (aspirin 100 mg+clopidogrel 150 mg daily: group A, n=38) or to receiving additional cilostazol (aspirin 100 mg+clopidogrel 75 mg+cilostazol 100 mg bid daily: group B, n=35).

Results

Baseline percent inhibition of PRU and PRU was similar between 2 groups (13.0±10.2% versus 11.8±9.7%, p=0.61, and 286.3±54.7 versus 295.7±53.7, p=0.44, respectively). At follow-up, percent inhibition of PRU was higher and PRU was lower significantly in group B than in group A (38.5±17.9% versus 28.3±16.6%, p=0.02, and 207.3±68.2 versus 241.3±76.7, p=0.050, respectively). Among those still showing hyporesponsiveness to clopidogrel at follow-up (21 patients in group A, 10 patients in group B), 12 patients completed further crossover study. Compared to the baseline, magnitude of change in percent inhibition of PRU and PRU showed an improved tendency after the crossover (from 2.7±8.7% to 15.8±18.4%, p=0.08, and from -18.6±58.0 to -61.9±84.3, p=0.08).

Conclusion

Adjunctive cilostazol improved clopidogrel responsiveness better than the higher maintenance dose of clopidogrel in hyporesponsive patients with chronic clopidogrel therapy.     

Pharmacogenetics of glucocorticoid replacement could optimize the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

INTRODUCTION:

21-hydroxylase deficiency is an autosomal recessive disorder that causes glucocorticoid deficiency and increased androgen production. Treatment is based on glucocorticoid replacement; however, interindividual variability in the glucocorticoid dose required to achieve adequate hormonal control has been observed.

OBJECTIVE:

The present study aimed to evaluate the association between polymorphic variants involved in glucocorticoid action and/or metabolism and the mean daily glucocorticoid dose in 21-hydroxylase deficiency patients.

METHODS:

We evaluated 53 patients with classical forms of 21-hydroxylase deficiency who were receiving cortisone acetate. All patients were between four and six years of age and had normal androgen levels.

RESULTS:

The P450 oxidoreductase A503V, HSD11B1 rs12086634, and CYP3A7*1C variants were found in 19%, 11.3% and 3.8% of the patients, respectively. The mean±SD glucocorticoid dose in patients with the CYP3A7*1C and wild-type alleles was 13.9±0.8 and 19.5±3.2 mg/m²/d, respectively. We did not identify an association between the P450 oxidoreductase or HSD11B1 allelic variants and the mean glucocorticoid dose.

CONCLUSION:

Patients carrying the CYP3A7*1C variant required a significantly lower mean glucocorticoid dose. Indeed, the CYP3A7*1C allele accounted for 20% of the variability in the cortisone acetate dose. The analysis of genes involved in glucocorticoid metabolism may be useful in the optimization of treatment of 21-hydroxylase deficiency.     

Core temperature and sweat responses in professional women's tennis players during tournament play in the heat

Context:

Tennis is often played in hot, humid environments, intensifying the thermoregulatory strain placed on the athletes. As a safety measure, some tennis organizations allow for a 10-minute break in play between the second and third sets when environmental conditions are extreme. However, the actual effect of these breaks in reducing core temperature is unknown.

Objective:

To determine change in core temperature after a 10-minute break in play and assess fluid balance in professional female tennis players during tournament matches in the heat.

Design:

Cross-sectional study.

Setting:

A Women''s Tennis Association Tour–sanctioned outdoor tournament on hard courts under hot conditions (30.3°C ± 2.3°C).

Patients or Other Participants:

Seven professional tennis players.

Main Outcome Measure(s):

Change in core temperature after a 10-minute break in tournament play, fluid intake, and sweat losses during match play.

Results:

Core temperature was reduced from 38.92°C to 38.67°C (change of −0.25°C ± 0.20°C) when a break was taken (P  =  .02). Mean sweat rate during match play was 2.0 ± 0.5 L/h. During that time, mean fluid intake was 1.5 ± 0.5 L/h, resulting in a 1.2% ± 1.0% reduction in body mass.

Conclusions:

Female professional tennis players are subjected to high heat loads during match play in hot environments. However, a 10-minute break in play decreased core temperature in 6 of 7 players by an average of 0.25°C, indicating that the break provides practical benefits in the field. Furthermore, although mean sweat rate in this group of female tennis players was high, most athletes were still able to minimize mass loss to less than 2% of their prematch weight.     

Core-temperature sensor ingestion timing and measurement variability

Context:

Telemetric core-temperature monitoring is becoming more widely used as a noninvasive means of monitoring core temperature during athletic events.

Objective:

To determine the effects of sensor ingestion timing on serial measures of core temperature during continuous exercise.

Design:

Crossover study.

Setting:

Outdoor dirt track at an average ambient temperature of 4.4°C ± 4.1°C and relative humidity of 74.1% ± 11.0%.

Patients or Other Participants:

Seven healthy, active participants (3 men, 4 women; age  =  27.0 ± 7.5 years, height  =  172.9 ± 6.8 cm, body mass  =  67.5 ± 6.1 kg, percentage body fat  =  12.7% ± 6.9%, peak oxygen uptake [V̇o_2peak]  =  54.4 ± 6.9 mL•kg⁻¹•min⁻¹) completed the study.

Intervention(s):

Participants completed a 45-minute exercise trial at approximately 70% V̇o_2peak. They consumed core-temperature sensors at 24 hours (P1) and 40 minutes (P2) before exercise.

Main Outcome Measure(s):

Core temperature was recorded continuously (1-minute intervals) using a wireless data logger worn by the participants. All data were analyzed using a 2-way repeated-measures analysis of variance (trial × time), Pearson product moment correlation, and Bland-Altman plot.

Results:

Fifteen comparisons were made between P1 and P2. The main effect of time indicated an increase in core temperature compared with the initial temperature. However, we did not find a main effect for trial or a trial × time interaction, indicating no differences in core temperature between the sensors (P1  =  38.3°C ± 0.2°C, P2  =  38.3°C ± 0.4°C).

Conclusions:

We found no differences in the temperature recordings between the 2 sensors. These results suggest that assumed sensor location (upper or lower gastrointestinal tract) does not appreciably alter the transmission of reliable and repeatable measures of core temperature during continuous running in the cold.     

Temperature Increases in the Human Achilles Tendon During Ultrasound Treatments With Commercial Ultrasound Gel and Full-Thickness and Half-Thickness Gel Pads

Context:

Although originally manufactured for use in diagnostic imaging of internal structures, 2-cm-thick gel pads are also used as conducting media for therapeutic ultrasound over areas with bony prominences. Research on the ability of these pads to conduct enough energy to adequately heat tissues has provided mixed results. However, this research has mainly been performed on the triceps surae muscle, an area over which gel pads are not typically used. We wondered how much heating might be produced if a thinner pad was used over a tendon.

Objective:

To compare temperature rises in the human Achilles tendon during ultrasound treatments using ultrasound gel, a 2-cm-thick pad, and a 1-cm-thick pad.

Design:

Cross-sectional study.

Setting:

University therapeutic modality laboratory.

Patients or Other Participants:

Forty-eight healthy volunteers (24 women, 24 men).

Intervention(s):

We inserted a rigid thermocouple 1 cm deep into the Achilles tendon. Ultrasound was delivered at the following settings: 3 MHz, continuous, 1 W/cm², 10 minutes.

Main Outcome Measure(s):

Temperature was recorded every 30 seconds for 10 minutes.

Results:

Temperature increased the most in the ultrasound gel group (increase  =  13.3°C, peak  =  42°C). The 1-cm-thick pad resulted in higher tendon temperature (increase  =  9.3°C, peak  =  37.8°C) than the 2-cm-thick pad (increase  =  6.5°C, peak  =  4.8°C). The 1-cm pad produced approximately 30% more heating than the 2-cm pad (SE  =  0.72, P < .03).

Conclusions:

The thinner pad transmitted ultrasound more efficiently than the thicker pad. Thus, a gel pad of less than 1-cm thickness might be useful for superficial areas, such as the hands and ankles.     

Post-resistance exercise hypotension in patients with intermittent claudication

OBJECTIVE:

To verify the acute effects of resistance exercise on post‐exercise blood pressure in patients with intermittent claudication.

METHODS:

Eight patients randomly underwent two experimental sessions: a session of resistance exercise (R: 6 exercises, 3 sets of 12, 10 and 8 reps with a perceived exertion of 11 to 13 on the 15‐grade Borg scale) and a control session (C: resting on exercise machines).

RESULTS:

Before and for 60 min following an intervention, auscultatory blood pressure was measured while subjects rested in a sitting position. After the C session, systolic, diastolic and mean blood pressures did not change from the pre‐intervention values, while these values decreased significantly after the R session throughout the entire recovery period (greatest decreases  =  ‐14±5, ‐6±5, and ‐9±4 mmHg, respectively, P < 0.05).

CONCLUSION:

After a single bout of resistance exercise patients with intermittent claudication exhibited reduced systolic, diastolic and mean blood pressures, suggesting that acute resistance exercise may decrease cardiovascular load in these patients.     

Response of Thermocouples Interfaced to Electrothermometers When Immersed in 5 Water Bath Temperatures

Context:

Thermocouples and electrothermometers are used in therapeutic modality research. Until recently, researchers assumed that these instruments were valid and reliable.

Objective:

To examine 3 different thermocouple types in 5°C, 15°C, 18.4°C, 25°C, and 35°C water baths.

Design:

Randomized controlled trial.

Setting:

Therapeutic modality laboratory.

Intervention(s):

Eighteen thermocouple leads were inserted through the wall of a foamed polystyrene cooler. The cooler was filled with water. Six thermocouples (2 of each model) were plugged into the 6 channels of the Datalogger and 6 randomly selected channels in the 2 Iso-Thermexes. A mercury thermometer was immersed into the water and was read every 10 seconds for 4 minutes during each of 6 trials. The entire process was repeated for each of 5 water bath temperatures (5°C, 15°C, 18.4°C, 25°C, 35°C).

Main Outcome Measure(s):

Temperature and absolute temperature differences among 3 thermocouple types (IT-21, IT-18, PT-6) and 3 electrothermometers (Datalogger, Iso-Thermex calibrated from −50°C to 50°C, Iso-Thermex calibrated from −20°C to 80°C).

Results:

Validity and reliability were dependent on thermocouple type, electrothermometer, and water bath temperature (P < .001; modified Levene P < .05). Statistically, the IT-18 and PT-6 thermocouples were not reliable in each electrothermometer; however, these differences were not practically different from each other. The PT-6 thermocouples were more valid than the IT-18s, and both thermocouple types were more valid than the IT-21s, regardless of water bath temperature (P < .001).

Conclusions:

The validity and reliability of thermocouples interfaced to an electrothermometer under experimental conditions should be tested before data collection. We also recommend that investigators report the validity, the reliability, and the calculated uncertainty (validity + reliability) of their temperature measurements for therapeutic modalities research. With this information, investigators and clinicians will be better able to interpret and compare results and conclusions.     

Alcohol alters sensory processing to respiratory stimuli in healthy men and women during wakefulness

Study Objectives:

Alcohol can cause sleep-disordered breathing in healthy men, increase O₂ desaturation in men who snore, and worsen obstructive sleep apnea (OSA) severity in men with OSA. These findings are less consistent among women, and the underlying mechanisms are incompletely understood. Respiratory-load sensory processing, which underpins upper-airway and respiratory responses to increased breathing load, is potentially impaired by alcohol. Using respiratory-related evoked potentials (RREPs) during wakefulness, this study aimed to test the hypothesis that alcohol impairs respiratory-load sensory processing and to explore potential sex differences.

Design:

Within-subjects cross-over design in men versus women.

Setting:

Sleep physiology laboratory.

Participants:

Twenty healthy individuals (9 women) aged 18 to 38 years.

Interventions:

Within each subject, RREP waveform components were generated by ∼60 brief early-inspiratory negative-pressure pulses (−13 cm H₂O mask pressure, 200 ms) before and after acute alcohol administration (1.5 mL/kg body weight). Choanal and epiglottic pressures were recorded to monitor stimulus magnitude and upper-airway resistance.

Measurements and Results:

The latency of several RREP waveform components increased after the administration of alcohol (ΔN1 = 11 ± 5 ms, ΔN2 = 6 ± 3 ms, ΔP3 = 26 ± 10 ms), and P2 amplitude decreased (3.4 ± 1.5 μV vs 1.2 ± 0.8 μV). There were no changes in P1 latency or amplitude. During relaxed breathing, nasal resistance increased after alcohol ingestion (1.38 ± 0.16 vs 1.86 ± 0.18 cm H₂O·l^-1·s^-1), but pharyngeal and supraglottic resistances remained unchanged. RREP waveform components and upper-airway resistance measures were not different in men versus women before or after alcohol ingestion.

Conclusions:

These data demonstrate that alcohol alters sensory processing of respiratory neural information, but not early neural transmission (P1), to a similar extent in healthy men and women. Altered sensory processing to respiratory stimuli, as well as nasal congestion, may be important mechanisms contributing to alcohol-related sleep disordered breathing.

Citation:

Eckert DJ; Elgar NJ; McEvoy RD; Catcheside PG. Alcohol alters sensory processing to respiratory stimuli in healthy men and women during wakefulness. SLEEP 2010;33(10):1389-1395.     

The Inhibitory Activity of the Extracts of Popular Medicinal Herbs on CYP1A2, 2C9, 2C19 and 3A4 and the Implications for Herb-Drug Interaction

Background

Studies have suggested an increasing practice of concurrent herb-drug consumption. One of the major clinical risks of such concomitant herb-drug use is pharmacokinetic herb-drug interaction (HDI). This is brought about by the ability of phytochemicals to inhibit or induce the activity of metabolic enzymes. The aim of this study was to investigate the potential of the crude aqueous extracts of three popular medicinal herbs used in South Africa to inhibit major cytochrome P450 (CYP) enzymes.

Materials and Methods

The extracts of Bowiea volubilis, Spirostachys africana and Tulbaghia violacea were incubated with human liver microsomes (HLM) to monitor the phenacetin O-deethylation, diclofenac 4′-hydroxylation, S-mephenytoin 4′-hydroxylation and testosterone 6β-hydroxylation as respective probe reactions for CYP1A2, CYP2C9, CYP2C19 and CYP3A4. The inhibitory activity, where observed, was profiled against the extract concentration.

Results

Extracts of Bowiea volubilis inhibited the metabolic activity of CYP1A2 and CYP3A4 with IC₅₀ values of 92.3 ± 5.5 µg/mL and 8.1 ± 0.6 µg/mL respectively. Similar observation with Spirostachys africana showed inhibitory activity against CYP1A2 and CYP3A4 with respective IC₅₀ values of 14.3 ± 0.6 µg/mL and 47.4 ± 2.4 µg/mL. Tulbaghia violacea demonstrated relatively weak inhibitory activity against CYP1A2 (767.4 ± 10.8 µg/mL) and CYP2C9 (921 ± 15.3 µg/mL).

Conclusion

The results suggest the potential for HDI between the herbs and the substrates of the affected enzymes, if sufficient in vivo concentration is attained.     

Tibiofemoral Joint Positioning for the Valgus Stress Test

Context:

Recommendations on the positioning of the tibiofemoral joint during a valgus stress test to optimize isolation of the medial collateral ligament (MCL) from other medial joint structures vary in the literature. If a specific amount of flexion could be identified as optimally isolating the MCL, teaching and using the technique would be more consistent in clinical application.

Objective:

To determine the angle of tibiofemoral joint flexion between 0° and 20° that causes a difference in the slope of the force-strain line when measuring the resistance to a valgus force applied to the joint.

Design:

Cross-sectional study.

Setting:

University research laboratory.

Patients or Other Participants:

Twelve healthy volunteers (6 men, 6 women: age  =  26.4 ± 5.6 years, height  =  170.9 ± 8.4 cm, mass  =  75.01 ± 14.6 kg).

Intervention(s):

Using an arthrometer, we applied a valgus force, over a range of 60 N, to the tibiofemoral joint in 0°, 5°, 10°, 15°, and 20° of flexion.

Main Outcome Measure(s):

Force-strain measurements were obtained for 5 positions of tibiofemoral joint flexion.

Results:

As knee flexion angle increased, slope values decreased (F_4,44  =  17.6, P < .001). The slope at full extension was not different from that at 5° of flexion, but it was different from the slopes at angles greater than 10° of flexion. Similarly, the slope at 5° of flexion was not different from that at 10° of flexion, but it was different from the slopes at 15° and 20° of flexion. Further, the slope at 10° of flexion was not different from that at 15° or 20° of flexion. Finally, the slope at 15° of flexion was not different from that at 20° of flexion.

Conclusions:

When performing the manual valgus stress test, the clinician should fully extend the tibiofemoral joint or flex it to 5° to assess all resisting medial tibiofemoral joint structures and again at 15° to 20° of joint flexion to further assess the MCL.     

Cold-Water Immersion and the Treatment of Hyperthermia: Using 38.6��C as a Safe Rectal Temperature Cooling Limit

Context:

Cold-water immersion is recommended for the immediate field treatment of exertional heat stroke. However, concerns exist over potential overcooling of hyperthermic individuals during cold-water immersion.

Objective:

To evaluate the recommendation that removing previously hyperthermic individuals from a cold-water bath at a rectal temperature (T_re) of 38.6°C would attenuate overcooling.

Design:

Controlled laboratory study.

Setting:

University research laboratory.

Patients or Other Participants:

Participants included 6 men and 4 women (age  =  22 ± 3 years, height  =  172 ± 10 cm, mass  =  67.8 ± 10.7 kg, body fat percentage  =  17.1% ± 4.5%, maximum oxygen consumption  =  59.3 ± 8.7 mL·kg⁻¹·min⁻¹).

Intervention(s):

After exercising at an ambient temperature of 40.0°C for 38.5 ± 9.4 minutes, until T_re reached 39.5°C, participants were immersed in a 2.0°C circulated water bath until T_re decreased to either 37.5°C or 38.6°C. Subsequently, participants were removed from the water bath and recovered for 20 minutes at an ambient temperature of 25°C.

Main Outcome Measure(s):

Rectal and esophageal temperatures were measured continuously during the immersion and recovery periods.

Results:

Because of the experimental design, the overall time of immersion was greater during the 37.5°C trial (16.6 ± 5.7 minutes) than the 38.6°C trial (8.8 ± 2.6 minutes) (t₉  =  −4.740, P  =  .001). During the recovery period after cold-water immersion, both rectal (F_1,9  =  50.540, P < .001) and esophageal (F_1,6  =  20.365, P  =  .007) temperatures remained greater in the 38.6°C trial than in the 37.5°C trial. This was evidenced by low points of 36.47°C ± 0.70°C and 37.19°C ± 0.71°C for rectal temperature (t₉  =  2.975, P  =  .016) and of 35.67°C ± 1.27°C and 36.72°C ± 0.95°C for esophageal temperature (t₆  =  3.963, P  =  .007) during the recovery period of the 37.5°C and 38.6°C trials, respectively.

Conclusions:

Immersion for approximately 9 minutes to a rectal temperature cooling limit of 38.6°C negated any risk associated with overcooling hyperthermic individuals when they were immersed in 2°C water.     

Exercise training prevents diastolic dysfunction induced by metabolic syndrome in rats

OBJECTIVE:

High fructose consumption contributes to the incidence of metabolic syndrome and, consequently, to cardiovascular outcomes. We investigated whether exercise training prevents high fructose diet-induced metabolic and cardiac morphofunctional alterations.

METHODS:

Wistar rats receiving fructose overload (F) in drinking water (100 g/l) were concomitantly trained on a treadmill (FT) for 10 weeks or kept sedentary. These rats were compared with a control group (C). Obesity was evaluated by the Lee index, and glycemia and insulin tolerance tests constituted the metabolic evaluation. Blood pressure was measured directly (Windaq, 2 kHz), and echocardiography was performed to determine left ventricular morphology and function. Statistical significance was determined by one-way ANOVA, with significance set at p<0.05.

RESULTS:

Fructose overload induced a metabolic syndrome state, as confirmed by insulin resistance (F: 3.6±0.2 vs. C: 4.5±0.2 mg/dl/min), hypertension (mean blood pressure, F: 118±3 vs. C: 104±4 mmHg) and obesity (F: 0.31±0.001 vs. C: 0.29±0.001 g/mm). Interestingly, fructose overload rats also exhibited diastolic dysfunction. Exercise training performed during the period of high fructose intake eliminated all of these derangements. The improvements in metabolic parameters were correlated with the maintenance of diastolic function.

CONCLUSION:

The role of exercise training in the prevention of metabolic and hemodynamic parameter alterations is of great importance in decreasing the cardiac morbidity and mortality related to metabolic syndrome.     

The Role of Oxidative Stress and Lipid Peroxidation in Ventricular Remodeling Induced by Tobacco Smoke Exposure after Myocardial Infarction

OBJECTIVE:

To evaluate the roles of oxidative stress and lipid peroxidation in the ventricular remodeling that is induced by tobacco smoke exposure after myocardial infarction.

METHODS:

After induced myocardial infarction, rats were allocated into two groups: C (control, n=25) and ETS (exposed to tobacco smoke, n=24). After 6 months, survivors were submitted to echocardiogram and biochemical analyses.

RESULTS:

Rats in the ETS group showed higher diastolic (C = 1.52 ± 0.4 mm², ETS = 1.95 ± 0.4 mm²; p=0.032) and systolic (C = 1.03 ± 0.3, ETS = 1.36 ± 0.4 mm²/g; p=0.049) ventricular areas, adjusted for body weight. The fractional area change was smaller in the ETS group (C = 30.3 ± 10.1 %, ETS = 19.2 ± 11.1 %; p=0.024) and E/A ratios were higher in ETS animals (C = 2.3 ± 2.2, ETS = 5.1 ± 2.5; p=0.037). ETS was also associated with a higher water percentage in the lung (C = 4.8 (4.3–4.8), ETS = 5.5 (5.3–5.6); p=0.013) as well as higher cardiac levels of reduced glutathione (C = 20.7 ± 7.6 nmol/mg of protein, ETS = 40.7 ± 12.7 nmol/mg of protein; p=0.037) and oxidized glutathione (C = 0.3 ± 0.1 nmol/g of protein, ETS = 0.9 ± 0.3 nmol/g of protein; p=0.008). No differences were observed in lipid hydroperoxide levels (C = 0.4 ± 0.2 nmol/mg of tissue, ETS = 0.1 ± 0.1 nmol/mg of tissue; p=0.08).

CONCLUSION:

In animals exposed to tobacco smoke, oxidative stress is associated with the intensification of ventricular remodeling after myocardial infarction.     

Cooling the neck region during exercise in the heat

Context:

Cooling the neck region can improve the ability to exercise in a hot environment. It might improve performance by dampening the perceived level of thermal strain, allowing individuals to override inhibitory signals.

Objective:

To investigate whether the enhanced ability to exercise in a hot environment observed when cooling the neck region occurs because of dampening the perceived level of thermal strain experienced and the subsequent overriding of inhibitory signals.

Design:

Crossover study.

Setting:

Walk-in environmental chamber.

Patients or Other Participants:

Eight endurance-trained, nonacclimated men (age  =  26 ± 2 years, height  =  1.79 ± 0.04 m, mass  =  77.0 ± 6.2 kg, maximal oxygen uptake [V̇O_2max]  =  56.2 ± 9.2 mL·kg⁻¹·min⁻¹) participated.

Intervention(s):

Participants completed 4 running tests at approximately 70% V̇O_2max to volitional exhaustion: 2 familiarization trials followed by 2 experimental trials (cooling collar [CC] and no collar [NC]). Trials were separated by 7 days. Familiarization and NC trials were performed without a collar and used to assess the test variability.

Main Outcome Measure(s):

Time to volitional exhaustion, heart rate, rectal temperature, neck skin temperature, rating of perceived exertion, thermal sensation, and feeling scale (pleasure/displeasure) were measured.

Results:

Time to volitional exhaustion was increased by 13.5% ± 3.8% (CC  =  43.15 ± 12.82 minutes, NC  =  38.20 ± 11.70 minutes; t₇  =  9.923, P < .001) with the CC, which reduced mean neck skin temperature throughout the test (P < .001). Participants terminated exercise at identical levels of perceived exertion, thermal sensation, and feeling scale, but the CC enabled participants to tolerate higher rectal temperatures (CC  =  39.61°C ± 0.45°C, NC  =  39.18°C ± 0.7°C; t₇  =  −3.217, P  =  .02) and heart rates (CC  =  181 ± 6 beats/min, NC  =  178 ± 9 beats/min; t₇  =  −2.664, P  =  .03) at the point of termination.

Conclusions:

Cooling the neck increased the time taken to reach volitional exhaustion by dampening the perceived levels of thermal strain.     

Association of CYP2C19*2 and *3 Genetic Variants with Essential Hypertension in Koreans

Purpose

The cytochrome P450 2C19 (CYP2C19) metabolizes arachidonic acid to produce epoxyicosanoid acids, which are involved in vascular tone and regulation of blood pressure. Recent findings suggest that CYP2C19 gene might be considered as a novel candidate gene for treatment of cardiovascular disease. The aim of the present study was to evaluate the association between two variants, CYP2C19^*2 (681G>A) and CYP2C19^*3 (636G>A) and the development of essential hypertension (EH) in Koreans.

Materials and Methods

We carried out an association study in a total of 1190 individuals (527 hypertensive subjects and 663 unrelated healthy controls). The CYP2C19 polymorphisms were genotyped using the SNaPShot™ assay.

Results

The distribution of alleles and genotypes of CYP2C19^*3 showed significant difference between hypertensive patients and normal controls (p=0.011 and p=0.013, respectively). Logistic regression analysis indicated that the CYP2C19^*3 (636A) allele carriers were significantly associated with EH [odds ratio, 0.691; 95% confidence interval (CI), 0.512-0.932, p=0.016], in comparison to wild type homozygotes (CYP2C19^*1/^*1). Neither genotype nor allele distribution of CYP2C19^*2 polymorphism showed significant differences between hypertensive and control groups (p>0.05).

Conclusion

Our present findings strengthen the evidence of an association between CYP2C19 gene polymorphism and EH prevalence. In particular, the CYP2C19^*3 defective allele may contribute to reduced risk for the development of EH.     

Short Insulin Tolerance Test Can Determine the Effects of Thiazolidinediones Treatment in Type 2 Diabetes

Purpose

The short insulin tolerance test is a simple and reliable method of estimating insulin sensitivity. This study was designed to compare the insulin sensitizing effects of thiazolidinediones (TZDs) on the degree of insulin resistance, determined by a short insulin tolerance test (Kitt) in type 2 diabetic patients.

Patients and Methods

Eighty-three subjects (mean age = 57.87 ± 10.78) with type 2 diabetes mellitus were enrolled and received daily one dose of rosiglitazone (4 mg) or pioglitazone (15 mg). The mean follow-up duration was 25.39 ± 9.66 months. We assessed insulin sensitivity using HOMA-IR and the short insulin tolerance test before and after TZDs treatment.

Results

When we compared patients'' characteristics before and after TZDs treatment, the mean fasting glucose level was significantly decreased (183.27 ± 55.04 to 137.35 ± 36.42 mg/dL, p < 0.001) and the mean HbA1C level was significantly decreased (9.24 ± 1.96 to 8.11 ± 1.39%, p < 0.001). Also, Kitt values were significantly increased (2.03 ± 1.14 to 2.67 ± 0.97%/min, p = 0.003), whereas HOMA-IR was significantly decreased (2.98 ± 0.68 to 1.04 ± 0.24, p < 0.05). When classifying insulin resistance by Kitt values, insulin resistant subjects'' values were increased (< 2.5 %/min; 1.51 ± 0.53%/min to 2.63 ± 0.88, p < 0.001), whereas the values decreased in insulin sensitive subjects (≥ 2.5%/min; 3.50 ± 0.75%/min to 2.75 ± 1.12%/min, p = 0.002).

Conclusion

The glucose lowering effects of TZDs by improving insulin resistance could be determined by using Kitt. However, Kitt may be a beneficial tool to determine TZDs'' effects only when patients'' Kitt values are less than 2.5%/min.     

Normative and Critical Criteria for Iliotibial Band and Iliopsoas Muscle Flexibility

Context:

The Ober and Thomas tests are subjective and involve a “negative” or “positive” assessment, making them difficult to apply within the paradigm of evidence-based medicine. No authors have combined the subjective clinical assessment with an objective measurement for these special tests.

Objective:

To compare the subjective assessment of iliotibial band and iliopsoas flexibility with the objective measurement of a digital inclinometer, to establish normative values, and to provide an evidence-based critical criterion for determining tissue tightness.

Design:

Cross-sectional study.

Setting:

Clinical research laboratory.

Patients or Other Participants:

Three hundred recreational athletes (125 men, 175 women; 250 in injured group, 50 in control group).

Main Outcome Measure(s):

Iliotibial band and iliopsoas muscle flexibility were determined subjectively using the modified Ober and Thomas tests, respectively. Using a digital inclinometer, we objectively measured limb position. Interrater reliability for the subjective assessment was compared between 2 clinicians for a random sample of 100 injured participants, who were classified subjectively as either negative or positive for iliotibial band and iliopsoas tightness. Percentage of agreement indicated interrater reliability for the subjective assessment.

Results:

For iliotibial band flexibility, the average inclinometer angle was −24.59° ± 7.27°. A total of 432 limbs were subjectively assessed as negative (−27.13° ± 5.53°) and 168 as positive (−16.29° ± 6.87°). For iliopsoas flexibility, the average inclinometer angle was −10.60° ± 9.61°. A total of 392 limbs were subjectively assessed as negative (−15.51° ± 5.82°) and 208 as positive (0.34° ± 7.00°). The critical criteria for iliotibial band and iliopsoas flexibility were determined to be −23.16° and −9.69°, respectively. Between-clinicians agreement was very good, ranging from 95.0% to 97.6% for the Thomas and Ober tests, respectively.

Conclusions:

Subjective assessments and instrumented measurements were combined to establish normative values and critical criterions for tissue flexibility for the modified Ober and Thomas tests.