Effect of Disulfiram on Cognition, Subjective Response, and Cortical-Event-Related Potentials in Nonalcoholic Subjects

The effect of 0.5 g of disulfiram per day for 2 wk on a battery of cognitive and cortical-event-related potential tasks was studied in healthy, nonalcoholic volunteers.     

Two Types of Hypotensive Effect of Beta-Blocking Agents

In anesthetized and immobilized rats, an hour-long continuous intravenous injection of dl-propranolol (PR; 3 mg/kg), pindolol (PI; 1 mg/kg), oxprenolol (OX; 3 mg/kg) or atenolol (AT; 3 mg/kg) invariably resulted in moderate hypotension. When the drug-induced hypotension was plotted against the control arterial pressure (AP), two types of correlation were found. The hypotension induced by PR or PI, both known to accumulate in the brain at a high concentration was positively correlated to the control AP, whereas the hypotension produced by OX or AT, both known to penetrate the blood-brain-barrier poorly, was not. To test the hypothesis that the observed difference was attributable to the presence or lack of sympathoinhibitory action of the drug, the effect of these agents on the renal nerve activity (RNA) was examined. PR or PI diminished the tonic and reflexly evoked RNA, when the evoked RNA was elicited by sciatic nerve stimulation. No such changes were induced by OX or AT. These results demonstrate a modulatory role of sympathoinhibitory effect of beta-blocking agents in their hypotensive action.     

Left Ventricular Structure and Diastolic Function in Subjects with Two Hypertensive Parents

Purpose : To examine the influence of (i) strong predisposition to essential hypertension and (ii) insulin sensitivity and plasma levels of cardiomyotrophic hormones on echocardiographic parameters of left ventricular structure and function. Methods : 26 normotensive subjects (age 18-35) with bi-parental hypertension and 26 matched controls with normotensive parents. Families with non-insulin-dependent diabetes or morbid obesity were excluded. (i) Echocardiography; (ii) plasma concentrations of renin, angiotensin-II, aldosterone, epinephrine and norepinephrine; (iii) euglycaemic, hyperinsulinemic clamp study. Results (means ±SD): Hypertension-prone subjects vs controls had (i) higher resting systolic (117.0 ±14.0 vs 107.1 ±11.9 mmHg), and 24-h diastolic blood pressure (77.9 ±7.1 vs 72.9 ±7.2 mmHg), (ii) higher relative wall thickness (RWT) (0.39 ±0.09 vs 0.34 ±0.06). They had similar left vetricular mass index, diastolic function parameters, insulin sensitivity and plasma concentrations of cardiomyotrophic hormones. The increased RWT was not attributable to any other factor than the systolic blood pressure. Conclusion : In a carefully selected group of subjects with two hypertensive parents compared to a control group, the only echocardiographic change demonstrated was an increased RWT. This remodelling was attributable to a higher systolic blood pressure in the hypertension-prone subjects, but not to insulin sensitivity or a selection of cardiomyotrophic hormones.     

Two Latex Tests for Australia Antigen in Subjects with and without Hepatitis1

Abstract. With latex particles coated with guinea pig or rabbit antibodies to Australia (Au) antigen, one third of Au-positive acute hepatitis sera gave weak agglutination patterns similar to the nonspecific reaction of 10% of normal sera. More than 10% were negative and the rest caused strong agglutination. After Au antigen had ceased to be detectable by complement fixation (CF) in 23 patients, 9 to 16 still were positive with the latex tests. This is due to rheumatoid factor (RF) or a similar factor appearing during hepatitis, since (a) the latex test was 32-fold less sensitive than CF for the specific detection of Au antigen; (b) 10 out of 10 latex-positive CF-negative hepatitis sera were positive in the RF test; and (c) 20 out of 20 Au-CF-negative sera from rheumatoid arthritis patients without hepatitis were positive in the latex-Au test. In the present form, latex tests are unacceptable for use on patients' sera due to lack of specificity and sensitivity. Qualified use on the healthy population seems acceptable, but only under certain conditions. Parallel results, with quantitative rather than qualitative differences, were obtained with 2 latex tests of different sources and composition.     

Gender Effects on Airway Closure in Normal Subjects

The present study was designed to examine age and gender differences with respect to the duration of laryngeal closure, the onset of laryngeal closure in relation to the first cricopharyngeal opening, and the duration of cricopharyngeal opening for six different groups: normal younger men and women (22–29 years), normal middle-aged men and women (45–53 years), and normal older men and women (81–94 years) (10 subjects in each group for a total of 60 subjects). Data were collected by means of videofluoroscopic studies. During swallows of liquid barium, results indicated that normal older subjects had longer cricopharyngeal opening than younger subjects (P = 0.044). Results also revealed that the mean duration of laryngeal closure was significantly longer in women than in men (P = 0.013). The onset of laryngeal closure was significantly earlier in women than in men (P = 0.006). Also, bolus volume effects were observed for both the duration of laryngeal closure (P < 0.0001) and cricopharyngeal opening (P < 0.0001). During liquid barium swallows there was a linear increase in both the duration of laryngeal closure and cricopharyngeal opening.     

Autonomic Effects of Nebivolol versus Atenolol in Healthy Subjects

Summary Purpose Nitric oxide may stimulate sympathoinhibitory reflexes. Nebivolol is a ₁ selective adrenergic receptor antagonist with ancillary vasodilating properties by modulating nitric oxide secretion. We investigated whether nebivolol affects autonomic function differently compared with atenolol, another selective ₁-blocker without vasorelaxant actions.Methods: Fourteen healthy volunteers (9 men, 5 women; 25 ± 3.7 years) received single oral doses of 5 mg nebivolol, 50 mg atenolol, and 100 mg atenolol, each taken for a 2-week period. Heart rate variability (HRV) measurements in time- (SDNN; rMSSD; pNN50) and frequency-domain (low frequency-LF; high frequency-HF; LF/HF ratio) were used to study the autonomic effects of the three regimens on the same patients from serial 24-hour ECGs.Results: Both nebivolol and atenolol, the 50 mg dose as well as the 100 mg dose, produced similar decreases in heart rate compared with baseline throughout the 24-h period (from 82 ± 9 beats/min to 72 ± 7 beats/min, 69 ± 9, and 68 ± 8 beats/min, respectively, p < 0.001). Overall, the administration of each -blocker led to directionally similar increases in the HRV variables, which were most significant following 100 mg atenolol. Nebivolol and the 50 mg dose of atenolol produced similar increases in rMSSD and pNN50 during the entire 24-h period, and in HF power, particularly during the nighttime (p < 0.05). However, the coefficient of HF variance resulted in similar values after either -blocker regimen. The LF/HF ratio was most reduced throughout the 24-h period following 100 mg atenolol (p < 0.001), and to a similar extent decreased in the nighttime following nebivolol and atenolol 50 mg (p < 0.01).Conclusions: Nebivolol 5 mg exerts similar effects on time and frequency domain indexes of HRV as 50 mg atenolol. Nebivolol attenuates sympathetic tone, but does not appear to promote vagal activity more than atenolol.     

Effects of Caloric Restriction and Fenfluramine on Weight Loss and Personality Profiles of Patients with Long Standing Obesity

Summary: Fifty consecutive patients who were referred to a special clinic for weight reduction were 49% in excess of their ideal body weight and had been obese for an average of 19 years. Sixtyfour percent exhibited a personality disorder on psychological testing and almost all patients had had at least one previous unsuccessful attempt at weight reduction. They had a good understanding of dietetics, but made the dietitian's task difficult by grossly understating their caloric intake. With detailed dietary instruction and regular super-vision there was no improvement in the patients' concepts of nutrition, four patients reduced to an ideal body weight, 24 defaulted after losing an average of 2.9 kg and 22 were given fenfluramine (120 mg/day) when their weights became static after an average loss of 3.4 kg. Addition of fenfluramine to the therapeutic regime for three months caused a significant and progressive loss of weight, but failed to causeanychanges in mood as measured by psychological testing. After a further three months on fenfluramine most patients ceased losing weight despite large increases in the dose. Thus, many patients neither required nor benefitted from the services of a dietitian, they could not be motivated to adhere to a low calorie diet, and those who received fenfluramine eventually became resistant to its anorectic effects.     

Response Localization of the Pharmacological Agents Histamine and Salbutamol Along the Respiratory System by Forced Oscillations in Asthmatic Subjects

The bronchodilating effect of 1 mg and 0.4 mg salbutamol on the impedance of the respiratory system was studied in 25 asthmatic subjects after histamine-induced bronchoconstriction. Histamine caused an increase of respiratory resistance (R_rs) at lower frequencies and a frequency dependence of R_rs. Respiratory reactance (X_rs) decreased at all frequencies after histamine challenge. These changes can be explained by peripheral airway obstruction. Impedance measurements performed 5 min after inhalation of 1 mg and 0.4 mg salbutamol showed a decrease of R_rs values at lower frequencies, a disappearance of the frequency dependence of R_rs, and a significant increase of X_rs values. No significant differences in absolute changes of R_rs and X_rs are observed between the salbutamol regimens. These changes after inhalation of salbutamol can be explained by supposing a predominant action on the peripheral airways.     

Suppression of Ethanol Intake in Chickens by Fenfluramine and Dietary Tryptophan

Two groups of 10-week-old White Leghorn cockerels were fed a commercial grower diet with or without an L-tryptophan (0.5%) supplement. After a 24-hr water deprivation and 13 to 14 hr without food, the birds were randomly injected with 0 (saline) 4, 8, or 12 mg of fenfluramine/kg body weight. Thirty minutes after injections, water or a 5% ethanol solution was offered, no choice, to the birds and fluid consumption as well as skin and rectal temperature before and after fluid availability were measured. The ethanol solution in otherwise untreated animals was consumed in similar amounts as water was. Fenfluramine (8 mg/kg) significantly reduced ethanol consumption and tryptophan further significantly reduced ethanol intake. At 12 mg/kg fenfluramine, both water and ethanol intake were sharply reduced. Ethanol decreased body temperature, an effect that was reversed by both tryptophan alone and fenfluramine + tryptophan in a dose-dependent manner. These observations are discussed in reference to the effects of central serotonergic manipulations and ethanol consumption.     

miR-448在溃疡性结肠炎组织中的表达水平及意义

目的探讨miR-448在溃疡性结肠炎(UC)组织中的表达水平及意义。方法选取2015年7月至2017年7月宣城市人民医院收治的67例UC患者(UC组)作为研究对象,另选取同期在该院行结肠息肉切除术的60例受试者作为对照组。采用实时荧光定量PCR(real-time PCR)法检测miR-448的相对表达量,并分析其与UC疾病活动度及患者预后的关系。结果UC组的miR-448相对表达量高于对照组,差异有统计学意义(P<0.05)。缓解期组的miR-448相对表达量低于轻度组、中度组及重度组,轻度组低于中度组及重度组,中度组低于重度组,差异均有统计学意义(P均<0.05)。67例UC患者随访期间的预后不良发生率为41.79%。预后不良组的miR-448相对表达量高于预后良好组,差异有统计学意义(P<0.05)。miR-448评估UC患者预后的受试者工作特征曲线下面积(AUC)、敏感度和特异度分别为0.854、75.00%和92.31%。多因素Logistic回归分析结果显示,肛周病变、miR-448与UC患者的预后密切相关。结论miR-448与UC疾病活动度及预后关系密切,检测miR-448相对表达量有助于评估患者的预后情况。     

Comparison of the Effects of β-Adrenergic Agents on Pineal Serotonin N-Acetyltransferase Activity and Melatonin Content in Two Species of Hamsters

The nighttime rise in pineal melatonin levels can be blocked by administration of the β-adrenergic receptor antagonist, propranolol, in both Syrian hamsters and rats. Although the administration of β-adrenergic receptor agonists such as norepinephrine or isoproterenol stimulates pineal melatonin production in the rat, these drugs are without apparent effect on indole production in the Syrian hamster. To determine whether this lack of stimulatory effect in the Syrian hamster is characteristic of this species, a comparison of the effects of norepinephrine and isoproterenol on pineal serotonin N-acetyltransferase activity and melatonin content was conducted. In contrast to their lack of effect in the Syrian hamster, norepinephrine and isoproterenol stimulated pineal serotonin N-acetyltransferase activity and melatonin content in the Djungarian hamster. Hourly injection of norepinephrine during a continuation of light into the normal dark period stimulated increases in the activity of serotonin N-acetyltransferase and melatonin content in the Djungarian hamster but was without effect on these pineal parameters in the Syrian hamster.     

Iron Absorption: Effects of Sugars and Reducing Agents

The effect of the iron-chelating sugars, fructose, glucose and galactose, oniron absorption in rats has been examined. Fructose has an effect in increasing iron absorption. Glucose and galactose have no effect on iron absorption.These findings suggest that the metabolism of fructose is responsible forchanging iron absorption in the rat since it is metabolized during its absorption, while glucose and galactose are not.

Pyruvate and lactate, the final products of glycolysis, also increase ironabsorption in the rat. The effects of lactate and hydroquinone on iron absorption are additive, suggesting independent actions. The effects of cysteineand hydroquinone on iron absorption are additive, suggesting independentactions of these two reducing agents in increasing iron absorption. Alternativehypotheses are offered in explanation of these observations.

Submitted on December 20, 1963 Accepted on February 25, 1964     

Effects of Sildenafil on Esophageal Motility of Normal Subjects

Sildenafil shows an intense and prolonged inhibitory effect on the smooth muscle cells of corpus cavernosum arterioles by blocking phosphodiesterase type 5 that inactivates the nitric oxide-stimulated cyclic guanosine monophosphate. We investigated if this inhibitory effect is also displayed on smooth muscle cells of the esophagus. In 16 normal subjects (9 men and 7 women, mean age 34 years, range 22–56) esophageal motility was recorded by means of a low-compliance manometric system with side holes for the esophageal body and a sleeve for the lower esophageal sphincter (LES). After a basal period of 60 min, a tablet of sildenafil 50-mg ground and dissolved in water was infused in the stomach in eight subjects (group A) and a placebo tablet in the other eight subjects (group B), randomly and in a double-blind manner; the recording continued for another 60 min. LES tone and postdeglutitive residual pressure, as well as amplitude, propagation velocity, and onset latency of contractions were measured each minute, the values averaged every 5 min, and the mean of the entire basal and postinfusion periods was calculated. The postinfusion values were compared with the basal values in each group and with the corresponding values of the other groups. The percent variations of postinfusion values with respect to basal values were also compared. Sildenafil induced a statistically significant decrease of LES tone, residual pressure, wave amplitude, and propagation velocity and a significant increase of onset latency of pressure waves in comparison with the values of the basal period and placebo. The inhibitory effect reached its maximum 10–15 min after the infusion and lasted about 1 hr. In conclusion, sildenafil markedly inhibits the motor activity of the esophageal musculature by decreasing LES pressure, wave amplitude, and propagation velocity and increasing the onset latency of pressure waves.     

Effects of Apple Consumption on Plasma and Erythrocyte Antioxidant Parameters in Elderly Subjects

The effects of apple consumption on plasma and erythrocyte antioxidant parameters of elderly subjects were investigated in this study. Fifteen elderly subjects (mean age 71.86 ± 4.17) participated in the study. They consumed an apple a day for 1 month. Before and after this period, fasting blood samples were obtained, and oxidant (malondialdehyde [MDA]) and antioxidant (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and antioxidant potential [AOP]) parameters were studied. MDA and AOP levels were studied in plasma, and SOD, GSH-Px, and CAT activities and MDA levels were measured in the erythrocytes. In the erythrocytes, GSH-Px and SOD activities were found to be higher (p < .001 and p < .01), but MDA levels were lower in the second samples relative to the first ones. In the plasma, AOP value was found to be higher in the second samples relative to first ones (p < .001). No differences were found, however, between the routine blood parameters such as total cholesterol, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, high-density-lipoprotein cholesterol, and triglyceride levels. The results show that consumption of apple leads to significant increases in the activities of some antioxidant enzymes and in the antioxidant potential values of the blood, and that decreases oxidation reactions in the body in significant amount. It is quite possible that reduced peroxidation processes owing to consumption of this fruit may play a part in some of their beneficial effects in the elderly subjects.     

Intestinal Effects of Sulfate in Drinking Water on Normal Human Subjects

Uncontrolled observations implicate sulfate indrinking water at concentrations exceeding 500-700mg/liter as a cause of diarrhea, but controlled studieshave not been reported. We conducted a controlled study in normal adults to determine the effectof various drinking water sodium sulfate concentrationson bowel function. Ten healthy subjects were given aconstant diet and fluid intake. Fluid consisted of 36 ml/kg/day of drinking water of variousknown sulfate concentrations and 500 ml of other fluid.In a dose-ranging study, four subjects received drinkingwater with sulfate concentrations of 0, 400, 600, 800, 1000, and 1200 mg/liters for sixconsecutive two-day periods. In a single-dose study, sixother subjects received water with sulfateconcentrations of 0 and 1200 mg/liter for twoconsecutive six-day periods. Stool mass, frequency, and consistencyand mouth-to-anus appearance time of colored markerswere measured. In the dose-ranging study, the onlysignificant linear trend was decreasing mouth-to-anus appearance time with increasing sulfateconcentrations. In the single-dose study, 1200 mg/litersulfate caused a significant but clinically mildincrease in mean stool mass per six-day pool from 621 gto 922 g (P = 0.03). When all 10 subjects wereused to compare effects of 0 mg/liter and 1200 mg/litersulfate, significant differences in stool consistency (P= 0.02) and transit time (P = 0.03) were observed. None of the subjects reported diarrhea orpassed more than three stools per day. In 10 normaladult subjects, sulfate in drinking water at aconcentration of 1200 mg/liter, which is higher thanreported to occur in US municipal water sources, causeda measurable but clinically insignificant increase instool mass and decrease in stool consistency andappearance time, but no change in stool frequency and no complaint of diarrhea.