Double-blind Crossover Manner Research Articles

Home-Based Double-Blind, Placebo-Controlled Challenges for Diagnosis of Delayed Gluten/Milk Hypersensitivity in Children

Delayed hypersensitivity to gluten and milk protein is frequently reported but may be difficult to diagnose. We aimed to explore if a method of home-based double-blind placebo-controlled food challenges (H-FC) can identify and reduce unnecessary elimination diets in children. We included 73 of 92 children aged 1 to 17 years referred to a tertiary allergy clinic from 2011 to 2021 due to self-reported, delayed symptoms to gluten or milk. The children were randomized to H-FC, receiving gluten/milk protein or placebo for 5 to 7 days in a double-blind crossover manner, separated by 3 washout weeks. Patients/parents recorded symptoms using standardized forms. Two crossover periods were used from 2011 to 2016 and 3 periods from 2017 to 2021. A positive challenge required significantly more symptoms during the active period versus the placebo period. After the challenge, reintroduction of milk/gluten was assessed by a follow-up interview. The primary outcome was the proportion of children with a positive challenge. The children, with a mean age of 11 years, had followed a strict gluten-free or milk-protein-free diet for a median duration of 24 months (range: 3-180 months). A positive challenge was observed in 18 of 73 children (25%), more often using 2 (35%) compared with 3 challenge periods (12%). At follow-up, 44 of 55 (80%) children with a negative challenge had successfully reintroduced milk/gluten. H-FC may be an effective method in avoiding unnecessary elimination diets in children. Only 25% of the challenges were positive, and 80% of the children with negative challenges succeeded in reintroducing the food. Three challenge periods may be necessary to reduce false-positive outcomes.

Nocturnal sodium oxybate increases the anterior cingulate cortex magnetic resonance glutamate signal upon awakening.

Clinical guidelines recommend sodium oxybate (SXB; the sodium salt of γ-hydroxybutyrate) for the treatment of disturbed sleep and excessive daytime sleepiness in narcolepsy, yet the underlying mode of action is elusive. In a randomised controlled trial in 20 healthy volunteers, we aimed at establishing neurochemical changes in the anterior cingulate cortex (ACC) following SXB-enhanced sleep. The ACC is a core neural hub regulating vigilance in humans. At 2:30 a.m., we administered in a double-blind cross-over manner an oral dose of 50 mg/kg SXB or placebo, to enhance electroencephalography-defined sleep intensity in the second half of nocturnal sleep (11:00 p.m. to 7:00 a.m.). Upon scheduled awakening, we assessed subjective sleepiness, tiredness and mood and measured two-dimensional, J-resolved, point-resolved magnetic resonance spectroscopy (PRESS) localisation at 3-Tesla field strength. Following brain scanning, we used validated tools to quantify psychomotor vigilance test (PVT) performance and executive functioning. We analysed the data with independent t tests, false discovery rate (FDR) corrected for multiple comparisons. The morning glutamate signal (at 8:30 a.m.) in the ACC was specifically increased after SXB-enhanced sleep in all participants in whom good-quality spectroscopy data were available (n=16; pFDR < 0.002). Further, global vigilance (10th-90th inter-percentile range on the PVT) was improved (pFDR < 0.04) and median PVT response time was shorter (pFDR < 0.04) compared to placebo. The data indicate that elevated glutamate in the ACC could provide a neurochemical mechanism underlying SXB's pro-vigilant efficacy in disorders of hypersomnolence.

Duodenal acidification induces gastric relaxation and alters epithelial barrier function by a mast cell independent mechanism

Duodenal hyperpermeability and low-grade inflammation in functional dyspepsia is potentially related to duodenal acid exposure. We aimed to evaluate in healthy volunteers the involvement of mast cell activation on the duodenogastric reflex and epithelial integrity during duodenal acidification. This study consisted of 2 parts: (1) Duodenal infusion of acid or saline during thirty minutes in a randomized, double-blind cross-over manner with measurement of intragastric pressure (IGP) using high resolution manometry and collection of duodenal biopsies to measure epithelial barrier function and the expression of cell-to-cell adhesion proteins. Mast cells and eosinophils were counted and activation and degranulation status were assessed. (2) Oral treatment with placebo or mast cell stabilizer disodiumcromoglycate (DSCG) prior to duodenal perfusion with acid, followed by the procedures described above. Compared with saline, acidification resulted in lower IGP (P < 0.01), increased duodenal permeability (P < 0.01) and lower protein expression of claudin-3 (P < 0.001). Protein expression of tryptase (P < 0.001) was increased after acid perfusion. Nevertheless, an ultrastructural examination did not reveal degranulation of mast cells. DSCG did not modify the drop in IGP and barrier dysfunction induced by acid. Duodenal acidification activates an inhibitory duodenogastric motor reflex and, impairs epithelial integrity in healthy volunteers. However, these acid mediated effects occur independently from mast cell activation.

The Effect of a 12-Week Beta-hydroxy-beta-methylbutyrate (HMB) Supplementation on Highly-Trained Combat Sports Athletes: A Randomised, Double-Blind, Placebo-Controlled Crossover Study.

The aim of this study was to verify the effect of beta-hydroxy-beta-methylbutyrate (HMB) supplementation on physical capacity, body composition and the value of biochemical parameters in highly-trained combat sports athletes. Forty-two males highly-trained in combat sports were subjected to 12 weeks of supplementation with HMB and a placebo in a randomized, placebo controlled, double-blind crossover manner. Over the course of the experiment, aerobic and anaerobic capacity was determined, while analyses were conducted on body composition and levels of creatine kinase, lactate dehydrogenase, testosterone, cortisol and lactate. Following HMB supplementation, fat-free mass increased (p = 0.049) with a simultaneous reduction of fat mass (p = 0.016) in comparison to placebo. In turn, after HMB supplementation, the following indicators increased significantly in comparison to the placebo: the time to reach ventilatory threshold (p < 0.0001), threshold load (p = 0.017) and the threshold HR (p < 0.0001), as well as anaerobic peak power (p = 0.005), average power (p = 0.029), maximum speed (p < 0.001) and post-exercise lactate concentrations (p < 0.0001). However, when compared to the placebo, no differences were observed in blood marker levels. The results indicate that supplying HMB promotes advantageous changes in body composition and stimulates an increase in aerobic and anaerobic capacity in combat sports athletes.

Is Skin-Touch Sham Needle Not Placebo? A Double-Blind Crossover Study on Pain Alleviation.

It remains an open question whether placebo/sham acupuncture, in which the needle tip presses the skin, can be used as a placebo device for research on pain. We compare the analgesic effect of the skin-touch placebo needle with that of the no-touch placebo needle, in which the needle tip does not touch the skin, in a double-blind crossover manner including no-treatment control in 23 healthy volunteers. The subjects received painful electrical stimulation in the forearm before and during needle retention to the LI 4 acupoint and after the removal of the needle and rated pain intensity using a visual analogue scale. We found no significant difference in analgesic effects among the skin-touch placebo needle, no-touch placebo needle, and no-treatment control at every point before, during, and after the treatments (p > 0.05). The results indicate that the skin-touch placebo needle can be used as a placebo device in clinical studies on pain.

Effect of intravenous tropisetron on modulation of pain and central hypersensitivity in chronic low back pain patients

The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2 mg, and tropisetron 5 mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

Aspirin and clopidogrel treatment impair nitric oxide biosynthesis by platelets

Aspirin and clopidogrel are used therapeutically for their anti-platelet effects. We examined the effects of aspirin and clopidogrel on basal and β-adrenoceptor (β-AR)-mediated platelet nitric oxide (NO) synthesis in healthy subjects and patients with coronary heart disease (CHD). Healthy subjects ( n = 19) were randomized in a double-blind cross-over manner to receive aspirin or clopidogrel, each at 75 mg daily, for 14 days. Patients ( n = 17) of similar age with CHD, taking aspirin, were randomized double-blind to either continue on aspirin 75 mg daily or to receive clopidogrel 75 mg daily for 14 days. NO synthase (NOS) activity was measured from l-[ 3H]arginine to l-[ 3H]citrulline conversion, and cGMP was determined by radioimmunoassay, in platelets basally and following incubation with isoproterenol or albuterol (each at 10 −5 mol/L). In healthy subjects, aspirin did not affect basal NOS activity or cGMP in platelets, but suppressed the normal increase in both by isoproterenol and albuterol. Clopidogrel suppressed platelet NOS activity and cGMP both basally and in response to β-AR agonists. In platelets from CHD patients, clopidogrel suppressed basal and β-AR-stimulated NOS activity and cGMP as compared with aspirin. Platelet NOS activity and cGMP were lower in CHD subjects pre-randomization compared with healthy subjects both pre-randomization and post-aspirin. We conclude that chronic aspirin treatment suppresses β-AR-stimulated but not basal platelet NO synthesis, as previously described, whereas chronic clopidogrel treatment suppresses both, with resultant functional consequences. Moreover, CHD may itself be associated with decreased platelet NO biosynthesis.

MILDRONATE EFFECT ON ENDOTHELIUM-DEPENDENT VASODILATION IN PATIENTS WITH CHRONIC HEART FAILURE: DOUBLE BLIND CROSSOVER STUDY

Aim. To study effect of mildronate on stream-dependent vasodilation in patients with chronic heart failure (CHF). Material and methods . 30 patients with CHF taking standard therapy (diuretic, ACE inhibitor, β- blocker) as well as 30 healthy volunteers have been examined. Test of reactive hyperemia (RH) of brachial artery (BA) was performed in all patients. RH test was performed in patients with CHF in double blind crossover manner before and after infusion of NaCl-isotonic solution (placebo) or mildronate 1000 mg in NaCl-isotonic solution. Results. Increase in BA diameter (%∆D) in patients with CHF was less than this in control group (p&lt;0,01) during RH test. After mildronate infusion increase in %∆D during RH phase was observed (from 8,6+0,8 to 14,4+0,9%, р&gt;&lt;0,001). After placebo infusion BA diameter did not change significantly (from 9,3+0,7 to 10,4+0,8%, p&gt;0,05). Conclusion. Mildronate improves endothelium-dependent vasodilation in patients with stable CHF.

Dietary Medium- and Long-chain Triacylglycerols Accelerate Diet-Induced Thermogenesis in Humans

This study investigated the effects of a liquid meal containing medium- and long-chain triacylglycerols (MLCT) on diet-induced thermogenesis (DIT) and was conducted in double-blind cross-over manner. Twenty subjects participated in this examination. The subjects consumed the liquid meal, which was made with 14 g of canola oil (LCT, long-chain triacylglycerols) or MLCT containing about 12% medium-chain fatty acids (MCFA). Oxygen consumption and carbon dioxide production were measured by indirect calorimetry. Resting energy expenditure (REE) was determined based on there parameters, applying the equation of Weir. Increase in DIT after ingesting the liquid meal with MLCT during 6h was significantly greater than with LCT (P<0.05). The results suggest that the substitution of MLCT for cooking oil is useful to control body weigh and fat in subjects.

Failure of Protein to Improve Time Trial Performance when Added to a Sports Drink

Recent studies have reported that adding approximately 2% protein to a carbohydrate sports drink increased cycle endurance capacity compared with carbohydrate alone. However, the practical implications of these studies work are hampered by the following limitations: (a) the rate of carbohydrate ingestion was less than what is considered optimal for endurance performance, and (b) the performance test (exercise time to fatigue) did not mimic the way in which athletes typically compete (i.e., a race in which a fixed distance or set amount of work is performed as quickly as possible). We tested the hypothesis that adding 2% protein to a 6% carbohydrate drink (CHO-PRO) would improve 80-km cycling time trial performance, as compared with a 6% carbohydrate drink (CHO) and a nonenergetic sweetened placebo (PLAC). Ten trained male cyclists (24 +/- 2 yr; VO2peak = 63 +/- 2 mL.kg(-1).min(-1); mean +/- SE) performed an 80-km laboratory time trial (TT) on three occasions separated by 7 d. In a double-blind crossover manner, subjects ingested CHO-PRO, CHO, or PLAC at a rate of 250 mL every 15 min with no temporal, verbal, or physiological feedback. Time to complete the TT was 4.4% lower (P < 0.002) during CHO (135 +/- 9 min) and CHO-PRO (135 +/- 9) compared with PLAC (141 +/- 10), with no difference between CHO and CHO-PRO (P = 0.92). Ingesting 6% carbohydrate at a rate of 1 L.h(-1) (60 g.h(-1)) improved an 80-km TT performance in trained male cyclists. However, adding 2% protein to a 6% carbohydrate drink provided no additional performance benefit during a task that closely simulated the manner in which athletes typically compete.

Pharmacodynamic study of procaterol hydrochloride dry powder inhaler: Evaluation of pharmacodynamic equivalence between procaterol hydrochloride dry powder inhaler and procaterol hydrochloride metered-dose inhaler in asthma patients in a randomized, double-dummy, double-blind crossover manner

Therapeutic equivalence between procaterol hydrochloride dry powder inhaler (Meptin DPI) and procaterol hydrochloride metered-dose inhaler (Meptin MDI), the currently marketed formulation, was assessed in 16 patients with bronchial asthma. The study was conducted in a randomized, double-dummy, double-blind crossover manner, using forced expiratory volume in the first second (FEV1) as an index of bronchodilatory effect. In Period I, the patients received 20 mcg of either Meptin DPI or Meptin MDI, and then crossed over in Period II after a washout interval of 3--28 days. Pharmacodynamic equivalence was accessed using AUC (FEV1)/h and peak FEV1 as indices, and the data were analyzed by analysis of variance (ANOVA). Factors used for the analysis were the treatment group and/or carryover effect, patients within each group, period, and treatment. The 90% confidence intervals for the differences between the two treatments were --0.0995 to --0.0204 (L) for mean AUC (FEV1)/h and --0.102 to --0.022 (L) for mean peak FEV1, both within the acceptance criteria of --0.15 to 0.15 (L). Meptin DPI was therefore assessed as being equivalent to the current Meptin MDI.

Pharmacodynamic equivalence study of CFC-free and CFC-containing procaterol hydrochloride metered-dose inhalers

Equivalence between a CFC-free procaterol hydrochloride metered-dose inhaler using HFA-227 as a propellant (Meptin [HFA]) and a CFC-containing procaterol hydrochloride metered-dose inhaler (Meptin [CFC]) was assessed in 28 patients with bronchial asthma. The study was conducted in a randomized, double-dummy, double-blind crossover manner, using forced expiratory volume in the first second (FEV1) as an index of bronchodilatory effect. In Period I, the patients received 20 microg of either Meptin [HFA] or Meptin [CFC] and then crossed over in Period II after a washout interval of 3-28 days. Pharmacodynamic equivalence was assessed using AUC (FEV1)/h and peak FEV1 as indices, and the data was analyzed by analysis of variance. Factors used for the analysis were the treatment group and/or carryover effect, patients within each group, period, and treatment. The 90% confidence intervals for the differences between the two treatments were -0.0507 to 0.0039 (L) for mean AUC (FEV1)/h and -0.056 to 0.026 (L) for mean peak FEV1, both within the acceptance criteria of -0.15 to 0.15 (L). Meptin [HFA] was therefore assessed as being equivalent to the current Meptin [CFC].

EFFECTS OF SUBLINGUAL ANDROSTENEDIOL-CYCLODEXTRIN ON SERUM SEX HORMONES IN YOUNG MEN

The effectiveness of orally ingested androstenediol in raising serum testosterone concentrations may be limited by hepatic breakdown of the ingested androgens. Since substances administered sublingually avoid first-pass hepatic catabolism, we evaluaated the acute hormonal response to sublingual cyclodextrin-androstenediol intake in young men. Eight experienced male weight lifters (22.9 ± 1.2 y) consumed either 20 mg androstenediol in a sublingual cyclodextrin tablet (DIOL) or placebo (PL) separated by at least one week in a randomized, double blind crossover manner. Blood samples were collected before supplementation and at 30 min intervals for 3 h following supplementation. Serum hormone concentrations did not change in PL. Serum androstenedione concentrations increased (P < 0.05) in DIOL from 60 to 180 min and peaked at 125% above basal 150 min after intake. Serum free testosterone concentrations were increased in DIOL from 30 to 180 min (P < 0.05), and peaked at 118% above basal 60 min after intake. Serum estradiol concentrations were increased (P < 0.05) from 30–180 min in DIOL and peaked at 71% above basal 180 min after intake.TableThese data indicate that sublingual cyclodextrin androstenediol intake increases serum androstenedione, free testosterone, and estradiol concentrations. -Funded in part by the Graduate Student Senate at Iowa State University-

Pulmonary function response to EDTA, an additive in nebulized bronchodilators

Background: Some nebulized bronchodilator solutions contain additives, such as EDTA, benzalkonium chloride (BAC), or both. Objective: Although BAC-induced bronchoconstriction has been well documented in patients with asthma, there is no information on the effects of EDTA on FEV1 when inhaled in the amounts that would be administered during emergency department treatment of asthma. Methods: Eighteen subjects with stable asthma and airway responsiveness to methacholine were randomly assigned to inhale up to four 600-μg nebulized doses of EDTA, BAC (positive control), and normal saline (placebo) in a double-blind crossover manner on separate days. FEV1 was measured 15 minutes after each dose. Treatments were repeated every 20 minutes until FEV1 decreased by 20% or greater or a maximum of 4 doses were administered. Results: Mean ± SD maximum percent decrease in FEV1 was 1.8% ± 5.8% after EDTA, 16.6% ± 13.9% after BAC, and 3.6% ± 8.2% after placebo (P < .001); there was no significant difference between EDTA and placebo. Conclusion: The amount of EDTA contained in maximum recommended doses of nebulized bronchodilators does not induce bronchospasm. In contrast, BAC induces clinically important bronchospasm, which could decrease the efficacy of a bronchodilator during an emergency. (J Allergy Clin Immunol 2001;107:68-72.)

Helicobacter Pylori produces tetrahydroharman from alcohol and tryptamine

The activation of 5-hydroxytryptamine-3 (5-HT-3) receptors in spinal cord can enhance intrinsic spinal mechanisms of central hypersensitivity, possibly leading to exaggerated pain responses. Clinical studies suggest that 5-HT-3 receptor antagonists may have an analgesic effect. This randomized, double-blind, placebo-controlled crossover study tested the hypothesis that the 5-HT-3 receptor antagonist tropisetron attenuates pain and central hypersensitivity in patients with chronic low back pain. Thirty patients with chronic low back pain, 15 of whom were women (aged 53 ± 14 years) and 15 men (aged 48 ± 14 years), were studied. A single intravenous injection of 0.9% saline solution, tropisetron 2 mg, and tropisetron 5 mg was administrated in 3 different sessions, in a double-blind crossover manner. The main outcome was the visual analogue scale (VAS) score of spontaneous low back pain before, and 15, 30, 60, and 90 minutes after drug administration. Secondary outcomes were nociceptive withdrawal reflexes to single and repeated electrical stimulation, area of reflex receptive fields, pressure pain detection and tolerance thresholds, conditioned pain modulation, and area of clinical pain. The data were analyzed by analysis of variance and panel multiple regressions. All 3 treatments reduced VAS scores. However, there was no statistically significant difference between tropisetron and placebo in VAS scores. Compared to placebo, tropisetron produced a statistically significant increase in pain threshold after single electrical stimulation, but no difference in all other secondary outcomes was found. A single-dose intravenous administration of tropisetron in patients with chronic low back pain had no significant specific effect on intensity of pain and most parameters of central hypersensitivity.

Does Sucralfate Prevent Short-Term NSAID Induced Damage to the Gastroduodenal Mucosa?

The objective of the study was to assess whether sucralfate can prevent or diminish short-term nonsteroidal anti-inflammatory drug (NSAID)-induced damage in the stomach and duodenum. Sixteen healthy subjects were randomly treated for 7 days with sucralfate 2 g b.d. or placebo in a double-blind cross-over manner. Naproxen 500 mg b.d. was given on days 3-7. Gastrointestinal endoscopy was performed before and after each treatment period. Mucosal damage was measured by counting erosions, submucosal hemorrhages or ulcers on a fixed point scale of 0-4 for stomach and duodenum separately. The mean posttreatment injury score in the stomach was 2.13 +/- 1.51 and 2.0 +/- 0.97 for the placebo and sucralfate periods, respectively (p = 0.72). The possibility of type II error was 7%. In the duodenum, the injury score was 1.69 +/- 1.08 and 1.06 +/- 0.93 for the placebo and sucralfate periods, respectively (p = 0.08). The possibility of type II error was 37%. Sucralfate has no efficacy as a prophylactic agent against short-term NSAID-induced gastroduodenal injury.

The Effect of Triazolam on the Arousal Response to Airway Occlusion during Sleep in Normal Subjects

The purpose of this study was to assess the effect of triazolam (0.25 mg) on the arousal response to airway occlusion during nonrapid eye movement sleep in normal subjects. Six male subjects (mean age +/- SD, 28.1 +/- 7.1 yr) had their arousal response tested by occluding a mask covering the nose with the mouth sealed. After an adaptation night, subjects were studied on two consecutive nights. They ingested triazolam (0.25 mg) or placebo one-half hour before bedtime in a randomized double-blind crossover manner. Mask occlusion was performed 1 to 4 h after triazolam/placebo ingestion while the subjects breathed a mixture of air and oxygen adjusted to produce an arterial oxygen saturation of 98%. The maximal deflections in airway pressure were measured at a supraglottic location during airway occlusion to reflect the degree of inspiratory effort. The time to arousal (mean +/- SEM) was significantly longer on triazolam nights (32.0 +/- 5.2 versus 22.6 +/- 3.2 s, p < 0.01). The maximal airway suction pressure preceding arousal was higher on triazolam nights (26.5 +/- 2.0 cm H2O versus 20.0 +/- 1.2 cm H2O, p < 0.02). Conversely, the rate of increase in inspiratory effort (maximal pressure) during occlusion was not decreased by triazolam. We conclude that triazolam prolongs the time to arousal following airway occlusion by increasing the arousal threshold.

Rapid Onset of Action of Inhaled Formoterol in Asthmatic Patients

Twelve patients with stable asthma (mean age, 39 years; asthma duration, 11 years; mean forced expiratory volume in 1 s, 65 percent of predicted; and reversibility, 31 percent) were studied in a double-blind crossover trial. The patients were studied during three test days. Airway resistance and specific airway conductance (Raw and SGaw) were measured using a body plethysmograph and pulse rate, blood pressure, tremor, and subjective effects were recorded before and 1, 3, 5, 10, 15, 30, 60, and 120 min after the test doses. A baseline Raw variability of +/- 20 percent was allowed between the test days. Formoterol 12 micrograms, 24 micrograms, and terbutaline 500 micrograms were given in a spacer (Nebulator) in a randomized double-blind crossover manner as two puffs with a 30-s interval in between. The effect of formoterol 12 micrograms on Raw was significantly better than terbutaline after 3, 5, 10, 60, and 120 min. Formoterol 24 micrograms was significantly better than terbutaline as soon as 3 min after inhalation and at every point in time after that. Formoterol 24 micrograms tended to be better than formoterol 12 micrograms but the differences were not significant at any point in time. All three treatments were well-tolerated. No differences were observed for pulse rate, blood pressure, tremor, or palpitations. The overall onset of bronchodilatation after formoterol 12 and 24 micrograms was faster than after terbutaline 500 micrograms. The tolerability of formoterol was good.

Cardiacβ 2-adrenoceptors and the inotropic response to exercise in man

To find out what role, if any, beta 2-adrenoceptors play in cardiac contractility, the heart rate, stroke volume and cardiac output of twelve healthy male and female volunteers (aged 18-28 years) were studied at rest (standing) and during two stages of treadmill exercise, 2 h after ingestion of propranolol (100 mg) or atenolol (100 mg) or a placebo, on different occasions, in a double-blind crossover manner. Cardiac output was measured by a carbon dioxide-rebreathing method. Atenolol and propranolol caused equal reductions in heart rate at rest, and in heart rate and cardiac output during exercise (p less than 0.001, two-way analysis of variance). Neither atenolol nor propranolol had any significant effect on resting cardiac output, resting stroke volume or stroke volume during exercise. Since atenolol (100 mg) has been shown to be beta 1-adrenoceptor-selective, we conclude that cardiac inotropic function during exercise is largely beta 1-adrenoceptor-mediated with little or no beta 2-adrenoceptor involvement.

Effects of a Sodium-Potassium Ion-Exchanging Seaweed Preparation in Mild Hypertension

A nonpharmacological approach in the treatment of mild hypertension is often advocated. In an attempt to decrease sodium and increase potassium intake, sixty-two middle-aged patients with mild hypertension were given a potassium loaded ion-exchanging sodium-adsorbing potassium-releasing seaweed preparation (seaweed fiber, SF). The mean blood pressure (MBP), evaluated in a double-blind crossover manner with four weeks familiarization and wash-out periods, showed a significant decrease after four weeks on 12 and 24 g/day SF but not on 6 g/day or placebo treatment. Systolic blood pressure during submaximal exercise decreased on all three SF doses. The decrease in MBP appeared to be significantly higher in sodium-sensitive (11.2 mm Hg, P less than .001) than in sodium-insensitive (5.7 mm Hg, P less than .05) patients and was in salt-sensitive patients significantly correlated to the increase in plasma renin activity (PRA). The urinary sodium excretion decreased, the urinary potassium increased and the sodium/potassium urinary excretion ratio decreased, indicating that the decrease of MBP was dependent on the decreased intestinal absorption of sodium and increased absorption of potassium released from the seaweed preparation. A sodium-potassium ion-exchanging seaweed preparation is an effective means of decreasing sodium and increasing potassium intake, and may be used for antihypertensive treatment in mild hypertension.