Supraorbital transcutaneous neurostimulation has sedative effects in healthy subjects

Background

Transcutaneous neurostimulation (TNS) at extracephalic sites is a well known treatment of pain. Thanks to recent technical progress, the Cefaly^® device now also allows supraorbital TNS. During observational clinical studies, several patients reported decreased vigilance or even sleepiness during a session of supraorbital TNS. We decided therefore to explore in more detail the potential sedative effect of supraorbital TNS, using standardized psychophysical tests in healthy volunteers.

Methods

We performed a double-blind cross-over sham-controlled study on 30 healthy subjects. They underwent a series of 4 vigilance tests (Psychomotor Vigilance Task, Critical Flicker Fusion Frequency, Fatigue Visual Numeric Scale, d2 test). Each subject was tested under 4 different experimental conditions: without the neurostimulation device, with sham supraorbital TNS, with low frequency supraorbital TNS and with high frequency supraorbital TNS.

Results

As judged by the results of three tests (Psychomotor Vigilance Task, Critical Flicker Fusion Frequency, Fatigue Visual Numeric Scale) there was a statistically significant (p < 0.001) decrease in vigilance and attention during high frequency TNS, while there were no changes during the other experimental conditions. Similarly, performance on the d2 test was impaired during high frequency TNS, but this change was not statistically significant.

Conclusion

Supraorbital high frequency TNS applied with the Cefaly^® device decreases vigilance in healthy volunteers. Additional studies are needed to determine the duration of this effect, the underlying mechanisms and the possible relation with the stimulation parameters. Meanwhile, this effect opens interesting perspectives for the treatment of hyperarousal states and, possibly, insomnia.

     

The sedative effects of hops (Humulus lupulus), a component of beer, on the activity/rest rhythm

The hop (Humulus lupulus), a component of beer, is a sedative plant whose pharmacological activity is due principally to its bitter resins, especially to the α-acid component 2-methyl-3-buten-2-ol. The mechanism of action of the resin of hop consists of increasing the activity of the neurotransmitter γ-aminobutyric (GABA), inhibiting the central nervous system (CNS). Objectives: To analyze in an experimental model of diurnal animal the sedative effect of hop, a component of beer, on the activity/rest rhythm. Methods: Experiments were performed with common quail (Coturnix coturnix) similar to humans in the sleep-wake rhythm, isolated in 25 × 25 × 25 cm methacrylate cages, with food and water ad libitum, in a room with artificial ventilation (22 ± 1 °C) and a lighting cycle of 12L/12D (n = 5). The doses administered, close to the content of non-alcoholic beer, were 1, 2 and 11 mg extract of hop as one capsule per day, at 18:00 h for one week. A control group received capsules only with a methylcellulose excipient and a basal group received no treatment. The chronobiological analysis of the animals' activity captured and logged by the software DAS24 was performed using the Ritme computer program (cosinor methods). Results: With the dose of 2 mg, there was a statistically significant (p < 0.05) reduction of the arithmetic mean nocturnal activity (23 ± 3.0) with respect to the basal (38.56 ± 2.79), control (38.1 ± 2.8) and other doses groups 1 mg (52.04 ± 3.65) and 11 mg (47.47 ± 5.88). This dose of 2 mg, similar to the concentration in beer, was more effective in reducing nocturnal activity than the other doses of 1 and 11 mg, as well as preserving the circadian activity/rest rhythm. Conclusion: The concentration of 2 mg of hop extract effectively decreased nocturnal activity in the circadian activity rhythm. On the basis of this investigation, administration of non-alcoholic beer would be recommended due to its hop content and consequent sedative action, which would be an aid to nocturnal sleep.     

Effects of moderate beer consumption on first-line immunity of healthy adults

Moderate alcohol consumption has shown to induce benefits on host specific (cell-mediated and humoral) immune system, but there is scarce literature regarding first-line immune responses. The aim of this study was to investigate differences in non-specific immunity after alcohol abstention and moderate beer consumption in healthy adults. After a 30 day-alcohol abstemious period, 57 healthy volunteers were submitted to a daily moderate consumption of beer (330 mL for women and 660 mL for men, respectively) during the following 30 days. White blood cell counts and phagocytic and oxidative burst activity were evaluated at three points: a) basal, b) abstemious, c) after moderate consumption of beer. Absolute values of leukocytes, neutrophils, lymphocytes and basophiles (x10(9)/L) increased significantly in women from point b to point c (6.34 +/- 1.26 vs. 7.27 +/- 1.97, 3.43 +/- 0.88 vs. 4.13 +/- 1.53, 2.14 +/- 0.50 vs. 2.38 +/- 0.63, and 0.05 +/- 0.02 vs. 0.06 +/- 0.03, respectively; p < 0.05) as well as basophils in men (0.05 +/- 0.03 vs. 0.06 +/- 0.03). A significant increase of oxidative burst capacity was also observed after the moderate consumption of beer in both women (33.90 +/- 19.00 vs. 48.86 +/- 21.83) and men (27.39 +/- 18.13 vs. 39.25 +/- 24.53). In healthy adults, after 30 days of moderate beer consumption the parameter describing the non-specific immunity improved when compared to the basal situation. For several of these parameters, the response is more enhanced in women.     

Body fat distribution has no effect on serum visfatin levels in healthy female subjects

Obesity is the presence of either abnormal absolute amount or relative proportion of body fat. Contrary to gluteal obesity, visceral obesity is associated with different metabolic alterations including insulin resistance (IR). A relatively new adipocytokine visfatin is shown to be expressed predominantly in visceral fat and exhibit insulin-mimicking effects in rodents. It is still unclear whether serum visfatin levels are associated with increased total or visceral fat mass in humans. The aim of our study was to investigate the relation between visfatin and obesity parameters namely body mass index (BMI) and waist circumference (WaC) and IR in healthy female subjects. Eighty one female subjects ?20 years of age, having no diagnosis of glucose intolerance or diabetes, hypertension and dyslipidemia were chosen. The patients were divided into four groups according to their BMI and WaC values. Serum visfatin and HOMA-IR levels did not differ among groups. No correlation was detected between serum visfatin levels and obesity and metabolic parameters. In conclusion, we demonstrated that body fat distribution did not affect serum visfatin levels in healthy female subjects. Further studies are needed to clarify the exact factors influencing and determining serum visfatin levels and its clinical reflections.     

The role of lager beer yeast in oxidative stability of model beer

Aims: In this study, we investigated the relationship between the ability of lager brewing yeast strains to tolerate oxidative stress and their ability to produce oxidative stable model beer. Methods and Results: Screening of 21 lager brewing yeast strains against diamide and paraquat showed that the oxidative stress resistance was strain dependent. Fermentation of model wort in European Brewing Convention tubes using three yeast strains with varying oxidative stress resistances resulted in three model beers with different rates of radical formation as measured by electron spin resonance in forced ageing experiments. Interestingly, the strain with the lowest oxidative stress resistance and lowest secretion of thioredoxin, as measured by Western blotting, resulted in the highest uptake of iron, as measured by inductively coupled plasma‐mass spectrometry, and the slowest formation of radicals in the model beers. Conclusions: A more oxidative stable beer is not obtained by a more‐oxidative‐stress‐tolerant lager brewing yeast strain, exhibiting a higher secretion of thioredoxin, but rather by a less‐oxidative‐stress‐tolerant strain, exhibiting a higher iron uptake. Significance and Impact of the Study: To obtain lager beers with enhanced oxidative stability, yeast strains should be screened for their low oxidative stress tolerance and/or high ability to take up iron rather than for their high oxidative stress tolerance and/or high ability to secrete thioredoxin.     

睫状神经营养因子基因多态性在中国汉族女性人群中的分布

目的:研究 CNTF基因多态性在我国健康汉族人群体中的分布情况.方法:采用自行建立的口腔上皮细胞法提取核DNA,并对CNTF基因多态性进行分析;卡方检验群体代表性.结果:所选群体等位基因、基因型频率符合Hardy-Weinberg平衡.结论:CNTF基因多态性分布在一定程度上体现出人种差异.     

芹菜素对雌性大鼠生殖轴的影响

目的：探讨芹菜素在10-9mol/L浓度时对雌性大鼠生殖功能的影响。方法：应用侧脑室注射方法观察芹菜素对雌性大鼠生殖轴激素含量的影响。在侧脑室注射后第3天取血浆,采用放免技术测定血浆中促性腺激素释放激素（GnRH）、卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇（E2）、孕酮（P）的含量。结果：在给药后第3天血浆中促性腺激素释放激素（GnRH）、卵泡刺激素（FSH）、黄体生成素（LH）的含量增加而雌二醇（E2）、孕酮（P）的含量降低,差异有显著性。结论：芹菜素抑制雌二醇（E2）合成中芳香化酶的活性实现对雌二醇（E2）、孕酮（P）分泌的抑制。芹菜素通过影响雌激素受体而使下丘脑的促性腺激素释放激素（GnRH）和腺垂体的卵泡刺激素（FSH）、黄体生成素（LH）分泌增加。     

左炔诺孕酮和炔雌醚复合不育剂（EP-1）对雌性东方田鼠生殖的影响

  本文在实验室条件下通过一次性灌胃的方式研究了左炔诺孕酮-炔雌醚复合不育剂（EP-1）对雌性东方田鼠激素、生殖系统、胎仔数、受孕率的影响及药效持续时间,旨在检验其应用于野外东方田鼠不育控制的价值。结果表明,各浓度EP-1灌胃均能显著提高雌性东方田鼠的子宫系数,使子宫形态发生变化,对卵巢组织造成损伤,影响卵泡和黄体的发育,但是对雌二醇含量和子宫长度没有明显影响;60mg/kg EP-1灌胃能显著提高促卵泡刺激素含量和卵巢系数,而10mg/kg、30mg/kg EP-1灌胃对二者没有明显影响。室内繁殖实验表明,各浓度EP-1灌胃均能不同程度延迟初次怀孕时间,并降低试鼠的怀孕率和胎仔数,但抗生育作用具有可逆性且与药物浓度相关,10mg/kg、30mg/kg和60mg/kg剂量组生殖系统恢复时间分别为16 d、38 d和52 d。     

Temperature profiles, and the effect of sleep on them, in relation to morningness-eveningness in healthy female subjects

There were 15 healthy female subjects, differing in their position on the “morningness-eveningness” scale, studied for 7 consecutive days, first while living a sedentary lifestyle and sleeping between midnight and 08:00 and then while undergoing a “constant routine.” Rectal temperature was measured at regular intervals throughout this time, and the results were subjected to cosinor analysis both before and after “purification” for the effects of physical activity. Results showed that there was a phase difference in the circadian rhythm of core temperature that was associated with the morningness score, with calculations that “morning types” would be phased earlier than “evening types” by up to about 3h. This difference in phase (which was also statistically significant when the group was divided by a median split into a “morning group” and an “evening group”) could not be attributed to effects of waking activity and existed in spite of the subjects keeping the same sleep-wake schedule. Moreover, it persisted when the subjects' data had been purified and when the data were obtained from the constant routine. That is, there was an endogenous component to this difference in phase of the core temperature. The morning group also showed a greater fall of core temperature during sleep; this was assessed in two ways, the main one being a comparison of constant routine and nychthemeral data sets after correction for any effects of activity. Even though the morning group was sleeping at a later phase of their circadian temperature rhythm than was the evening group, neither group showed a fall of temperature due to sleep that varied with time elapsed since the temperature acrophase. It is concluded that another factor that differs between morning and evening types is responsible for this difference. (Chronobiology International, 18(2), 227-247, 2001)     

Evaluation of adverse effects in tamoxifen exposed healthy female dogs

Background

Hypertension and proteinuria are medical complications associated with the multisystemic effects of long-term hypercortisolism in dogs with hyperadrenocorticism (HAC).

Methods

This study investigated the relationships among adrenocorticotropic hormone (ACTH)-stimulation test results, systemic blood pressure, and microalbuminuria in clinically-healthy dogs (n = 100), in dogs affected with naturally occurring pituitary-dependent (PDH; n = 40), or adrenal-dependent hyperadrenocorticism (ADH; n = 30).

Results

Mean systemic blood pressure was similar between clinically healthy dogs and dogs with HAC (p = 0.803). However the incidence of hypertension was highest in dogs with ADH (p = 0.017), followed by dogs with PDH, with the lowest levels in clinically healthy dogs (p = 0.019). Presence of microalbuminuria and albuminuria in clinically healthy dogs and dogs affected with HAC was significantly different (p < 0.001); incidences of albuminuria followed the same pattern of hypertension; highest incidence in dogs with ADH, and lowest level in clinically healthy dogs; but microalbuminuria showed a different pattern: clinically healthy dogs had highest incidences and dogs with ADH had lowest incidence. The presence of albuminuria was not associated with blood pressure values, regardless of whether dogs were clinically healthy or affected with ADH or PDH (p = 0.306).

Conclusions

Higher incidence of hypertension and albuminuria, not microalbuminuria was seen in dogs affected with HAC compared to clinically healthy dogs; incidence of hypertension and albuminuria was significantly higher in dogs affected with ADH compared to PDH. However, presence of albuminuria was not correlated with systemic blood pressure.     

The effect of exercise intensity on hematuria in healthy male runners

The purpose of this study were: (1) to establish the prevalence of exercise-induced hematuria in a group of otherwise healthy male runners (n = 70), and (2) to investigate the role of exercise intensity in those runners who exhibited exercise-related hematuria (n = 10) by evaluating the effect of running and cycling at high and low intensities. The identified and recruited subjects participated in four different exercise protocols: (1) a 60-min treadmill run (RUN) at 90% of anaerobic threshold (Th_ae), (2) a 60-min leg cycle ergometer ride (BIKE) at 90% of Th_ae, (3) a 3×400-m sprint (SPRINT), each followed by 4 min of rest or light walking, and (4) 3×60-Wingate leg cycle ergometry tests, each followed by 4 min of rest or light cycling. The study employed a 3×4 (time by protocol) within-subjects design and dependent variables were measured before exercise, 4 min after, and 1 h after exercise, and included measurements of hematuria, proteinuria, urinary pH, serum haptoglobin concentration, serum creatine phosphokinase activity, plasma lactate concentration, and hemoglobin. The 400-m sprint at maximal effort significantly increased both hematuria and proteinuria (P < 0.01). Post-exercise hematuria for the SPRINT protocol was significantly different than that for the BIKE (P < 0.01) and RUN (P < 0.01) protocols. Due to the significant increase in hematuria and proteinuria following the SPRINT protocol, it was concluded that exercise-related changes in renal function were associated with weight-bearing exercise intensity rather than non-weight-bearing exercise duration. Accepted: 30 April 1998     

The effect of leg preference on postural stability in healthy athletes

In research regarding postural stability, leg preference is often tested and controlled for. However, leg preference may vary between tasks. As athletes are a group of interest for postural stability testing, we evaluated the effect of five leg preference tasks categorization (step up, hop, ball kick, balance, pick up) on single-leg postural stability of 16 field hockey athletes. The ‘center of pressure speed’ was calculated as the primary outcome variable of single-leg postural stability. Secondary variables were ‘mean length of the GRF vector in the horizontal plane’, ‘mean length of the ankle angular velocity vector’, and ‘mean length of the hip angular velocity vector’, as well as the separate outcomes per degree of freedom. Results showed that leg preference was inconsistent between leg preference tasks. Moreover, the primary and secondary variables yielded no significant difference between the preferred and non-preferred legs, regardless of the applied leg preference task categorization (p>0.05). The present findings do not support the usability of leg preference tasks in controlling for bias of postural stability. In conclusion, none of the applied leg preference tasks revealed a significant effect on postural stability in healthy field hockey athletes.     

The effect of high dose digoxin on cytokines in healthy dogs

BACKGROUND: Tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta are pro-inflammatory cytokines, causing myocardial dysfunction and a negative inotropic effect. The drugs used to treat heart failure affect the production of cytokines. Digoxin, on which this study was focused, is one of the drugs for the treatment of heart failure. AIM: The present study was designed to examine the early effects of high doses of digoxin on the production of cytokines in healthy dogs. METHODS: Digoxin was given parenterally to dogs at 0.15 mg/kg. IL-1beta and TNF-alpha production and levels of digoxin in the serum were measured 0, 12, 24, 48, and 72 h following administration of digoxin. RESULTS: As the levels of serum digoxin taken at 12, 24, 48, and 72 h of administration were considered significantly high compared with preceding values (p < 0.001), no notable change in serum IL-1beta and TNF-alpha levels was observed. CONCLUSIONS: These results suggest that high doses of digoxin do not cause a significant cytokine production in heart muscle in the early phase.     

The effect of territory quality on female preference in Metriaclima zebra

The cichlid fishes of Lake Malawi are an excellent model group with which to study adaptive radiation and speciation; due to the vast number of individual species, large variation in feeding adaptations and behaviours, and relatively recent divergence are found. Males of many cichlid species will obtain and defend lek‐like territories, where they court potential mates in addition to foraging for food. Aspects of territory quality warrant investigation because of the relationship between reproductive success and territory defence success. In this study, we tested whether the presence of a small or large food resource had any effect on the preference of a gravid female for a potential mate. The results of this experiment suggest that the presence of a large food resource increases the attractiveness of a male to a potential mate. This may suggest that the presence of food alone may not be the most important factor, or there may be a threshold amount over which females are attracted. These results indicate that certain aspects of territory quality such as habitat type or proximity to a food resource may play a role in both intersexual and intrasexual selection mechanisms: perhaps even driving and possibly accelerating the speciation of certain lineages of cichlid fishes.