Time course of effects of brief inhalations of nitrous oxide in normal volunteers

Nitrous oxide is commonly used (abused) recreationally by inhaling it in a bolus form (i.e. single or several breaths). The time course of the psychoactive effects of nitrous oxide, via this mode of inhalation, has not been adequately characterized and thus formed the basis for this study. Twelve healthy volunteers participated in four sessions, using a randomized, cross-over, placebo-controlled design. In each session one of the following four measures were assessed: self-reported strength of drug effects, mood, memory and psyckomotor performance. Within sessions, subjects were exposed to four different concentrations of nitrous oxide in a randomized fashion: 0% (oxygen-placebo), 40%, 60% and 80%. At each concentration, or “trial”, subjects took four deep breaths of the gas. Peak drug effects, as reported by our subjects, occurred within 30 seconds after the last inhalation of nitrous oxide, persisted for about a minute, and then gradually subsided to near-baseline levels by 5 minutes post-inhalation. Certain aspects of mood were briefly affected by nitrous oxide, generally in a dose-related fashion with increases in visual analog scale ratings of “anxious”, “stimulated”, “coasting (spaced out)”, “lightheaded”, “confused”, and “high”. Free recall of words that had been presented between 30 and 60 seconds post-inhalation was significantly reduced after 80% nitrous oxide, relative to oxygen-placebo. There was a trend towards psychomotor impairment (Concentration x time: p – 0.08), as measured by the Digit Symbol Substitution Test, with peak decrements in performance (about a minute after inhalation) being greater after 80% nitrous oxide than after 0% nitrous oxide. Our results suggest that there arc acute, albeit brief, adverse effects of inhaling bolus concentrations of nitrous oxide.     

Reduction of variability of exhaled nitric oxide in healthy volunteers

Exhaled nitric oxide (eNO) is elevated in patients with asthma in contrast to healthy subjects, although the variability is high. In this study, we tried to reduce the variability of eNO in healthy subjects.We measured eNO using ERS guidelines with a fixed exhalation flow of 250 ml/s in 117 (72 women, 45 men) non-smoking healthy subjects and correlated this to antropometric data and standard lung function measurements. Using a model previously defined by Hyde et al., we selected parameters that were likely to have a high correlation with eNO. ENO was log-normally distributed. The normal values for eNO are significantly (P < 0.001) different for men and women: in women mean ln eNO levels (SD) were 1.49 (0.34), in men 1.74 (0.41) (back-transformed value 4.43 resp. 5.73 ppb). Using multiple regression analysis, only In D(m,CO), InTLC and In sG(aw) showed a significant positive correlation with In eNO in men, although only 20% of the variability of eNO could be explained. In women no correlation was observed and only 5% ofthe variability was explained. The high variability of eNO could only partly be explained in men, which makes the use of reference equations not very helpful.     

Hemodynamic, hormonal, and renal effects of short-term adrenomedullin infusion in healthy volunteers

The actions of adrenomedullin (ADM), a 52-amino acid peptide, are not well defined in man. We, therefore, studied eight normal volunteers aged 1832 yr in a placebo-controlled crossover study. On the 2 study days, subjects received, in random order, ADM in "low" and "high" dose (2.9 pmol/kg x min and 5.8 pmol/kg x min for 2 h each) or vehicle (hemaccel) infusion on day 4 of a metabolic diet (Na+ 80 mmol/day, K+ 100 mmol/day). Achieved plasma ADM levels were in the pathophysiological range, and plasma cAMP values rose 5 pmol/L during the higher dose. Compared with time-matched vehicle infusion, high-dose ADM increased peak heart rate by 10 beats per minute (P < 0.05) and lowered diastolic (by 5 mm Hg, P < 0.01) blood pressure. Cardiac output increased in both phases of ADM (low dose, 7.6 L/min; high dose, 10.2 L/min; vehicle, 6 L/min; P < 0.05 for both). Despite a 2-fold rise in PRA during high-dose ADM (P < 0.01), aldosterone levels were unaltered. Norepinephrine levels increased by 50% during high-dose ADM (P < 0.001), but epinephrine levels were unchanged. Plasma PRL levels increased during high-dose ADM (P = 0.014). ADM had no significant effect on urine volume and sodium excretion. Infusion of ADM to achieve pathophysiological plasma levels produced significant hemodynamic effects, stimulated renin but inhibited the aldosterone response to endogenous angiotensin II, and activated the sympathetic system and PRL without altering urine sodium excretion in normal subjects.     

Pramiracetam effects on scopolamine-induced amnesia in healthy volunteers

Pramiracetam has been evaluated for its potential antiamnesic properties in scopolamine-induced amnesia in healthy volunteers. Two groups of twelve males, 18-42 and 55-65 years old, respectively, were randomly assigned to oral treatment with pramiracetam (600 mg twice a day) or with placebo for 10 consecutive days. On day 11 each subject was injected intramuscularly with scopolamine hydrobromide (0.5 mg). Before scopolamine injection and then 1, 3 and 6 h after it, subjects were administered the following psychometric tests: simple and choice visual reaction times, digit symbol substitution test, Rey's 15 words test for short and long term verbal memory. Scopolamine significantly impaired episodic memory and selective attention tests in both scopolamine and placebo groups. Instead visuo-motor and incidental learning measures were unaffected. Pramiracetam, when compared to placebo, was able to partially reduce the amnesic effects induced by scopolamine both in young and old subjects.     

Effects of magnesium oxide on the lipid profile of healthy volunteers

Elevated serum cholesterol is a risk factor in the development of coronary artery disease. Magnesium has been reported to decrease total serum cholesterol, low density lipoprotein, and very low density lipoprotein, and increase high density lipoprotein. A randomized, double-blind, placebo-controlled, crossover study was completed to determine if supplemented magnesium, in the form of magnesium oxide, would produce changes in the lipid profile. Fifty normal volunteers received placebo or magnesium oxide, 400 mg capsules, twice a day for 60 days, then switched to the alternate treatment. Weight, height, blood pressure, serum potassium, serum magnesium, and a lipid profile were determined initially and after each treatment. Analysis of variance (ANOVA), comparing the mean of each component of the lipid profile at baseline and after each treatment, showed no significant difference. In conclusion, supplemental magnesium oxide did not produce statistically significant changes in the lipid profile in this group of healthy volunteers.     

胰岛素口腔喷雾剂在正常人口腔粘膜的吸收和生物学效应

目的　研究胰岛素口腔喷雾剂 (华中科技大学药物研究所制备 )在正常人体的吸收情况以及生物学效应。方法　 13名健康受试者 (男 11,女 2 ) ,年龄 ( 2 4.2± 2 .3 )岁 ,体重指数为 ( 2 0 .7± 2 .0 )kg/m2 ,接受正常血糖胰岛素钳夹试验。经 2h平衡后 ,给予胰岛素口腔喷雾剂 10喷 ( 4 0单位胰岛素 ) ,分别于给药后 0、15、3 0、45、60、75、90、10 5、12 0、15 0、180、2 40、3 0 0和 3 60min取血测血清胰岛素水平 ,同时记录每5min的葡萄糖输注率 ,以计算药代动力学和药效动力学参数。结果　每例均有 3个明显的“血液浓度”峰值Cmax(mU/L) :12 .2± 6.8,15 .2± 6.3和 16.5± 8.1;其达峰时间TCmax(min)分别为 45 .0± 17.7,12 8.8±2 6.7和 2 70 .0± 42 .4。葡萄糖处置率ΔGIR也有一致表现 ,ΔGIRmax(mg·kg-1·min-1)为 2 .75± 1.97、4.40± 1.99和 4.3 8± 1.45 ,TΔGIRmax(min)为 79.2± 3 0 .9、170 .0± 42 .9和 2 81.5± 3 5 .6。结论　胰岛素口腔喷雾剂起效时间约在给药后 1h ,作用时间达 4h以上。     

植物雌激素对血压的影响

目的研究大豆饮食中所含的植物雌激素对健康人血压、血脂谱的影响。方法213名健康受试者(男性108人,绝经后女性105人),年龄50-75岁,随机、双盲接受特定大豆蛋白饮食(试验组)或酪蛋白安慰剂(安慰剂组)干预,为期3个月。建立多变量模型以评价治疗效果。结果饮食干预后,仅在试验组受试者尿液中植物雌激素含量增高。试验组血压较安慰剂组下降明显[收缩压(-7.5±1.2)mm Hg比(-3.6±1.1)mm Hg,P<0.01;舒张压(-4.3±0.8)mm Hg比(-1.9±0.7)mm Hg,P<0.05;平均压(-5.5±1.0)mm Hg比(-0.9±1.0)mm Hg,P<0.008]。试验组血脂水平较安慰剂组有显著改变(P<0.001),其中试验组低密度脂蛋白胆固醇/高密度脂蛋白胆固醇比值显著下降[(-0.33±0.10) mmol/L比(0.04±0.10) mmol/L,P<0.05],甘油三酯水平也有显著下降[(-0.20±0.05)mmol/L比(-0.01±0.05)mmol/L,P<0.05],而脂蛋白(a)水平升高(±95%可信区间)[42(17-67)mg/L比4(-22-31)mg/L,P<0.05]。两组中总胆固醇和低密度脂蛋白胆固醇水平均下降,高密度脂蛋白胆固醇水平升高。副作用的发生率两组相似,并且都没有观察到男性激素水平发生改变。结论在正常血压男性和绝经后女性人群中,大豆饮食对血压和血脂水平有改善作用。     

The effects of self-administered alcohol-induced 'hangover' in a naturalistic setting on psychomotor and cognitive performance and subjective state

AIMS: To examine in as naturalistic a setting as possible whether having an alcohol-induced 'hangover' impairs psychomotor and cognitive performance. PARTICIPANTS AND DESIGN: The sample consisted of 71 male and female social drinkers who were tested twice, once at baseline and once after exposure to the study condition. They were randomized into a control group who returned for testing on a prearranged date (n = 33), and a group who were instructed to make arrangements to return the day after a self-determined heavy drinking session (n = 38). Of the 'hangover' group, 13 participants still had a blood alcohol concentration of >1 mg/100 ml at the time of testing and these were analysed separately. All participants were students. MEASUREMENTS: Psychomotor performance was assessed by means of a battery of psychomotor tasks, rate of information processing was tested by the Speed and Capacity of Language Processing Test (SCOLP) and subjective state was assessed by questionnaire measures. FINDINGS: All participants in the 'hangover' group reported subjective and physical symptoms of hangover on the second testing session. Performance was significantly impaired on the hits-key components of the vigilance task, was less accurate on the primary and secondary reaction time tasks and showed greater dispersion in range of ability for participants in the 'acute and hangover' compared to 'control'. Probe memory revealed no significant group effect. Ratings of subjective state revealed significant group differences for the variables 'ability to drive', 'concentrate' and 'react quickly' as well as 'tiredness'. There were no group differences for performance on the SCOLP. CONCLUSION: Hangover had negative effects on self-reported subjective and physical state and subtle effects on performance.     

Acute effects of angiotensin II on fibrinolysis in healthy volunteers.

Recent studies have suggested that angiotensin II may inhibit fibrinolysis. In order to further test this hypothesis, we investigated the acute effects of angiotensin II (intravenous infusion of 10 ng/kg per min over 15-20 min) on fibrinolytic function in 18 healthy men. Time-controls (n=11) and control experiments with a placebo infusion (n = 13) were also performed. The activities of plasmin activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA), as well as t-PA antigen levels, were determined in plasma before, during and 60 min after the infusion of angiotensin II. Angiotensin II caused a clear-cut elevation in blood pressure; heart rate and plasma noradrenaline levels tended to decrease during the infusion but increased afterwards, indicating reflexogenic adjustments. Plasma t-PA activity and antigen levels increased by 81+/-11 and 14+/-3%, respectively, during angiotensin II infusion (both P < 0.001), whereas t-PA activity was unchanged and t-PA antigen decreased (P < 0.05) in placebo experiments. PAI-1 activity decreased similarly in time-controls and during angiotensin infusion (P < 0.001). Thus, short-term infusion of angiotensin II enhances fibrinolysis by elevating plasma t-PA. It is not clear whether this is a direct angiotensin-receptor-mediated effect or if it is related to the hemodynamic effects of the infusion.     

Short term cardiovascular effects of aldosterone in healthy male volunteers.

Clinical evidence of rapid, nongenomic aldosterone effects in the cardiovascular system has been provided by clinical studies; an increase in systemic vascular resistance (SVR) was shown by invasive techniques within 3 min after injection of aldosterone. Here, we study the dose dependency and the later course of the rapid aldosterone effects by noninvasive techniques. In 12 healthy male volunteers, SVR and heart rate variability were determined by impedance cardiography and digital electrocardiography, respectively, for 8 h after the injection of 0.05 or 0.5 mg aldosterone in a double blind, placebo-controlled, 3-fold cross-over study. No significant differences were observed for baseline values among the three treatments. The area under the curve of SVR during the first 45 min after injection was significantly different between the periods with the highest areas under the curve seen after the injection of 0.5 mg aldosterone (mean +/- SD, 40.4 +/- 12.8 vs. 36.8 +/- 10.3 for 0.05 mg aldosterone and 36.8 +/- 10.4 for placebo; P = 0.05). Individual comparisons showed significant differences at 6 and 30 min between placebo and the 0.5 mg aldosterone period (P < 0.05), with values for the 0.05 mg aldosterone period similar to those for the placebo period. From 330-390 min, opposite changes occurred; SVR was depressed during the 0.05 mg (P < 0.05) and 0.5 mg aldosterone periods compared with that during the placebo period. These delayed effects may reflect an increased vagal tone in the aldosterone groups, as demonstrated by higher values of the time domain parameter of heart rate variability pNN50. This study provides further evidence for clinically detectable rapid cardiovascular aldosterone effects in vivo obtained by noninvasive techniques. The data are consistent with the view of aldosterone as a rapid modulator of cardiovascular responses acting through nongenomic mechanisms.     

Gastritis and Campylobacter pylori in healthy, asymptomatic volunteers

A high prevalence of histologic gastritis in asymptomatic individuals has been reported in the literature. The studies have been poorly controlled for gastritis risk factors. We evaluated 20 healthy, asymptomatic volunteers free of known risk factors for gastritis with endoscopy, mucosal biopsy, culture, and gastric pH determination. The prevalence of gastritis on histologic examination was found to be 20%. There was no relationship between the presence of macroscopic findings at endoscopy and the presence of histologic gastritis. In all instances where histologic gastritis was documented, Campylobacter pylori was observed in the gastric mucus. Mucosal tissue invasion by C pylori was not observed. The presence of gastritis and C pylori was associated with fasting hypochlorhydria. Follow-up evaluation was performed eight to 13 months after the initial endoscopic evaluation in three of the volunteers with positive test results. Persistence of C pylori and gastritis was observed. These findings suggest that histologic gastritis is common in healthy, asymptomatic individuals and is strongly associated with the presence of C pylori.     

Gallbladder motility in healthy volunteers: effects of age, gender, body mass index, and hair color

BACKGROUND/AIMS: Ultrasonographic determination of gallbladder motility is sparsely performed in clinical practice as the examination is considered to be time consuming and there is uncertainty about a number of parameters possibly influencing the results. The aims of this study were a) to establish normal values for a simple ultrasonographic test and b) to evaluate the influence of different parameters on gallbladder motility. METHODOLOGY: In 62 systematically age- and sex-matched healthy volunteers, ultrasonographic measurements of gallbladder volume (ellipsoid method, planimetry and sum-of-cylinders method) were performed fasting and 5, 10, 20, 30, 40, 50, 60, 70 and up to 75 min after stimulation with a standardized high-caloric liquid meal. RESULTS: Using the ellipsoid method, gallbladder fasting volume (V0) reached a mean value (+/- SD) of 24.6 +/- 10.0 mL with an ejection fraction of 65.9 +/- 19.1%. Age, gender and hair color did not influence parameters of gallbladder contraction. Body mass index showed a weak correlation with V0 but not with ejection fraction. There was a highly significant correlation between the ellipsoid method and longitudinal planimetry and the sum-of-cylinders method, respectively. CONCLUSIONS: Ultrasonographic measurement of gallbladder motility in healthy volunteers shows a very wide scattering of normal values. In the interpretation of gallbladder emptying, age, gender and body mass index do not have to be considered. Determination of gallbladder motility may be performed by a rather simple approach with oral stimulation and ellipsoid method or longitudinal planimetry as easily applicable ultrasonographic measurements.     

Effect of an inducible nitric oxide synthase inhibitor on differential flow-exhaled nitric oxide in asthmatic patients and healthy volunteers

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, particularly airway epithelial cells, and its increased concentration in asthma is likely to derive from inducible NO synthase (iNOS) expressed in inflamed airways. To evaluate whether an increased bronchial flux of NO (ie, airway wall NO flux [Jno] in picoliters per second) produced in the large airways is due to an enzyme overexpression, we administered a relatively selective iNOS inhibitor, aminoguanidine, by nebulization in a double-blind, placebo-controlled manner in asthmatic and healthy subjects and also investigated whether the same concentration of inhibitor has any effect on NO produced in the peripheral lungs (ie, alveolar NO concentration [Calv] in parts per billion [ppb]) or on the diffusing capacity of NO (Dno) [in picoliters per second(-1) per ppb(-1)) in the airways. Aminoguanidine administration resulted in a significant reduction in Jno compared with administration of the saline solution control in eight healthy subjects and in eight patients with asthma but caused no significant changes in Calv or in Dno in either group. No rise in BP, fall in FEV(1), or adverse effects were observed in either group. These results indicate that iNOS from larger airways is the predominant source of elevated large airway-derived NO in patients with asthma, and that exhaled NO from peripheral lungs is not affected by a nebulized iNOS inhibitor and, therefore, is more likely to be derived form constitutive forms of NO synthase.     

Prevalence peptic lesion in asymptomatic, healthy volunteers

Aim. To investigate the presence of lesions of the upper gastrointestinal tract of asymptomatic, healthy volunteers undergoing clinical pharmacology studies.Material and Methods. A series of 53 volunteers (45 male, 23 Helicobacter pylori negative and 30 Helicobacter pylori positive) underwent upper gastrointestinal endoscopy. Helicobacter pylori status was assessed using two methods (rapid urease test and histology) from antral and corpus biopsies.Results. Peptic lesions were found in 24 (45%) subjects: erosive oesophagitis, gastric/duodenal ulcers and gastric/duodenal erosions were found in 23%, 9% and 36% of these volunteers, respectively. Helicobacter plyori-positive subjects had significantly (p<0.05) more gastroduodenal lesions than Helicobacter pylori negative individuals (12/30 vs 3/23). The presence of peptic ulcers and erosive oesophagitis was similar in Helicobacter pylori-positive and -negative individuals.Conclusions. The possibility that peptic lesions might exist in otherwise asymptomatic, asymptomatic, healthy individuals cannot be ruled out. Helicobacter pylori-positive individuals have a significantly higher incidence of gastric and duodenal lesions than Helicobacter pylori negative subjects.