Effect of daily loperamide administration on gastrointestinal myoelectric activity

The objective of this study was to determine the effect of daily administration of loperamide on gastrointestinal myoelectric activity. Six dogs were randomly administered three regimens–placebo, low dose loperamide (0.10–0.15 mg/kg/day, p.o.), and high dose loperamide (0.30–0.36 mg/kg/day, p.o.)–for one week each. Using surgically implanted bipolar electrodes, gastrointestinal myoelectric activity was recorded on at least 2 fed and 2 fasted experimental days for each regimen. In the fasted state, low dose loperamide decreased MMC cycle length, initiated intestinal amyogenesia in 40% of experiments, but did not induce vomiting. High-dose loperamide in the fasted state did not change MMC cycle length, but induced vomiting in 50% of experiments and initiated intestinal amyogenesia in 43% of experiments. The rate of occurrence of the myoelectric carrelates of giant migrating contractions (GMCs) and retrograde giant contractions (RGCs) increased with loperamide administration at both doses, as did the rate of occurrence of fed state MMCs. We conclude that daily oral administration of loperamide results in: (1) a dose-dependent effect on MMC cycle length; (2) intestinal amyogenesia; (3) an increase in frequency of vomiting at higher doses; and (4) an increase in incidence of GMCs and RGCs.     

High‐resolution manometry changes our views of gastrointestinal motility

High‐resolution manometry using catheters with 36 solid‐state sensors spaced 1 cm apart has already become an established technique for esophageal manometry where it has replaced water‐perfused and station pull‐through manometry. Spatiotemporal plots with color coding of pressure have greatly facilitated the analysis of esophageal peristalsis. Although suitable for the length of the esophagus, the solid‐state catheter is insufficient for the study of longer segments of the gastrointestinal tract. A new technique with fiber‐optic sensors has made it possible to construct catheters with 72–144 sensors. Studies of colonic motility have revealed that the most common motor pattern of the colon is a peristaltic contraction that travels 7–10 cm in the retrograde direction. Earlier studies using low‐resolution manometry with 7–45 cm between sensors led us to erroneous conclusions regarding direction and frequency of contractions and they largely missed both antegrade and retrograde contractions traveling short distances. Fiber‐optic high‐resolution manometry holds promise for greatly improving our understanding of gut motor physiology and hopefully also our understanding of patients with symptoms of disordered gut motility.     

Magnetic resonance imaging to evaluate gastrointestinal function

Magnetic resonance imaging of gastrointestinal (GI) function has advanced substantially in the last few years. The ability to obtain high resolution images of the undisturbed bowel with tunable tissue contrast and using no ionizing radiation are clear advantages, particularly for children and women of reproductive age. Barriers to diffusion in clinical practice so far include the need to demonstrate clinical value and the burden of data processing. Both difficulties are being addressed and the technique is providing novel insights into both upper and lower GI disorders of function at an ever increasing rate.     

The effect of sildenafil on oesophageal motor function in healthy subjects and patients with nutcracker oesophagus

Type 5 phosphodiesterase terminates the action of nitric oxide (NO) induced 3',5'-cyclic monophosphate (cGMP). Sildenafil inhibits this phosphodiesterase, increases cellular cGMP concentrations and enhances NO-induced smooth muscle relaxation. We investigated the effect of sildenafil on the oesophageal motor function of healthy subjects and patients with nutcracker oesophagus. Eight healthy volunteers and nine patients with nutcracker oesophagus participated in this study. The participants underwent oesophageal manometries on two separate days after either 20 mL of distilled water or 0.8 mg kg-1 sildenafil dissolved in 20 mL of water was infused into the stomach. Lower oesophageal sphincter (LOS) resting pressure, the duration of LOS relaxation and the amplitudes of oesophageal pressure waves were examined before, and 7.5, 15, 30 and 60 min after either placebo or sildenafil. In both healthy subjects and patients with nutcracker oesophagus, sildenafil decreased resting LOS pressure and the amplitude of peristaltic pressure waves at 3, 8 and 13 cm above LOS. Sildenafil also prolonged the duration of LOS relaxation. It had no effect on the velocity of peristalsis or the amplitude of peristaltic pressure waves 18 cm above LOS. Sildenafil may be considered as an alternative treatment in nutcracker oesophagus although there are several limitations to be overcome.     

Innervation of the monotreme gastrointestinal tract: A study of peptide and catecholamine distribution

The distribution of neurons and endocrine cells containing various peptides or catecholamines was examined in the digestive tracts of the echidna (Tachyglossus aculeatus) and the platypus (Ornithorhynchus anatinus). Comparisons were made with published studies in other species in order to obtain a broader view of the phylogenetic distribution and possible functions of gut peptides and catecholamines. Further comparisons between the echidna and platypus were made in light of their different dietary features and gut histology. The distribution of neurons and axons containing catecholamines or various peptides resembled that in other species (such as the frequent appearance of axons containing substance P and vasoactive intestinal peptide in the intestinal mucosa, and axons containing substance P or enkephalins in the circular muscle). In both species, the stomach histologically resembles the esophagus, being aglandular and lined with stratified squamous epithelium. Innervation of these two organs was similar but not identical, with a greater array of peptides found in the gastric muscle. The intestinal mucosa was densely innervated in both species. The platypus small intestine is unusual in having a thick and deeply folded mucosa (but no villi), in which the superficial epithelium is absent or incomplete at many sites; many axons travel close to these luminal surfaces. Many (putative noradrenergic) axons associated with blood vessels contained neuropeptide Y, but there was no evidence for intrinsic catecholamine-containing neurons. Somatostatin and cholecystokinin were present in some endocrine cells, but unlike many mammals, absent in neuronal tissue. These studies have shown that there are many strong similarities between monotremes and other mammals in the distribution and array of peptides found within nervous and endocrine tissues of the digestive tract. However, numerous small differences of the echidna and platypus innervation may be correlated with their different digestive structures. © 1993 Wiley-Liss, Inc.     

The neurobiological mechanisms of physical exercise in methamphetamine addiction

Methamphetamine (METH) is the primary drug within amphetamine‐type stimulants which are the second most abused group of drugs worldwide. There is no pharmacological treatment addressed specifically to METH addiction, and behavioral therapy is shadowed by poor long‐term recovery and relapse. Therefore, novel approaches to manage METH addiction are an urgent need. This review aims to describe the current state of physical exercise use on methamphetamine addiction management. The following searching terms in PubMed were used: (“physical exercise” OR “exercise”) AND “methamphetamine.” Relevant references from key publications and gray literature were also reviewed to identify additional citations for inclusion. Original investigation regarding physical exercise and methamphetamine addiction (clinical data) or neurobiological mechanisms of physical exercise in animal models of methamphetamine administration (preclinical data) was included. Overall, METH users demonstrated improvements, including better fitness and emotional measures, lower relapse rates, and sustained abstinence when compared to nonexercised individuals. The neurobiological mechanisms of physical exercise in METH users seem to reflect an interplay of several agents, including neurochemicals, oxidative stress, neurogenesis, gliogenesis, and blood‐brain barrier as disclosed by preclinical data. Exercise‐based interventions alone or as a conjoint therapy may be a useful tool for managing METH addiction.     

Combined effect of repetitive transcranial magnetic stimulation and physical exercise on cortical plasticity

Physical exercise can minimize dysfunction and optimize functional motor recovery after stroke by modulating cortical plasticity. However, the limitation of physical exercise is that large amounts of time and effort are necessary to significantly improve motor function, and even then, substantial exercise may not be sufficient to normalize the observed improvements. Thus, interventions that could be used to strengthen physical exercise-induced neuroplasticity may be valuable in treating hemiplegia after stroke. Repetitive transcranial magnetic stimulation seems to be a viable strategy for enhancing such plasticity. As a non-invasive cortical stimulation technique, repetitive transcranial magnetic stimulation is able to induce longterm plastic changes in the motor system. Recently, repetitive transcranial magnetic stimulation was found to optimize the plastic changes caused by motor training, thereby enhancing the long-term effects of physical exercise in stroke patients. Therefore, it is believed that the combination of repetitive transcranial magnetic stimulation and physical exercise may represent a superior method for restoring motor function after stroke.     

The effects of physical exercise on depressive symptoms among the aged: a systematic review

OBJECTIVE: To determine the effects of physical exercise on depression or depressive symptoms among the aged. METHOD: A literature search covering various medical databases was conducted to identify randomised controlled trials (RCT's) about the effects of exercise treatments on depression or depressive symptoms among the aged. The studies were classified according to the baseline depression status of participants and assessed in relation to allocation concealment, blinding at outcome assessment, follow-up and whether intention to treat analysis was used. Studies meeting the inclusion criteria were accepted. RESULTS: Exercise was effective in treating depression among those suffering from minor or major depression and in reducing depressive symptoms among those with a high amount of depressive symptoms at baseline. However, both the allocation concealment and the blinding method were adequately described in only four studies. Furthermore, intention-to-treat analysis was conducted in half of the studies and some follow-up information after the intervention has been published for five studies. CONCLUSIONS: Physical exercise may be efficient in reducing clinical depression and depressive symptoms in the short-term among the aged suffering from depression or a high amount of depressive symptoms. More well controlled studies are needed.     

Effects of physical exercise on Autism Spectrum Disorders: A meta-analysis

It is generally agreed that regular physical exercise promotes physical and mental health, but what are the benefits in people with Autism Spectrum Disorders (ASD)? This meta-analysis evaluates 16 behavioural studies reporting on a total of 133 children and adults with various variants of the syndrome who were offered structured physical activities either in an individual or a group context. The effects on social and motor deficiencies, two of the three primary symptom clusters of ASD, were normalized to afford a quantitative evaluation. Results pertaining to communication deficits were insufficient to permit classification. All activity programmes yielded significant progress on the measures assessed, but the individual programmes elicited significantly more improvement than the group interventions in the motor and, more surprisingly, also in the social domain. Although overall sample sizes were small, the combined results do permit the tentative conclusion that in terms of motor performance and social skills children and adults with ASD benefit most from individual exercise interventions. Further research of the impact of individual and group interventions on communication deficits in particular as well as studies gauging the extent to which exercise effects depend on ASD symptom severity are warranted.     

The effects of moderate exercise on chronic stress-induced intestinal barrier dysfunction and antimicrobial defense

The purpose of this study was to examine the effect of moderate exercise on repeated restraint stress (RRS)-induced intestinal barrier dysfunction and explore possible mechanisms in a mouse model. Male Balb/c mice (6 weeks) were randomized into 7 groups: CON functioned as controls with no intervention; RRS was subjected to 6 h per day RRS for 7 consecutive days; RRS+SWIM received 30 min per day of swimming prior to RRS; CON+SWIM only received 30 min per day of swimming; and the other groups received one session of 30 min swimming prior to sacrifice at 1-, 3- and 6 h recovery. Intestinal permeability was quantified with FITC-dextran. Bacterial translocation was determined by quantification of bacterial colony forming units (CFUs) in cultured mesenteric lymph nodes (MLN), and with fluorescence in situ hybridization (FISH). Antimicrobial related gene expression at baseline and 1 h after one session of 30 min swimming was tested by quantitative real-time polymerase chain reaction (Q-PCR) in small intestinal segments. Protein expression of 5 genes with statistically significant increase was measured at baseline, and 1-, 3- and 6 h post-swimming using enzyme-linked immunosorbent assay (ELISA). Thirty minutes per day of swimming before RRS attenuated bacterial translocations and maintained intestinal permeability. Gene expression and protein levels for four antimicrobial peptides (α-defensin 5, β-defensin 1, RegIIIβ and RegIIIγ) were significantly increased after one 30 min swimming session. In conclusion, moderate exercise attenuated chronic stress-induced intestinal barrier dysfunction in mice, possibly due to augmentation of antimicrobial responses in the small intestine.     

Rolling out physical exercise and energy homeostasis: Focus on hypothalamic circuitries

Energy balance is the fine regulation of energy expenditure and energy intake. Negative energy balance causes body weight loss, while positive energy balance promotes weight gain. Modern societies offer a maladapted way of life, where easy access to palatable foods and the lack of opportunities to perform physical activity are considered the roots of the obesity pandemic. Physical exercise increases energy expenditure and, consequently, is supposed to promote weight loss. Paradoxically, physical exercise acutely drives anorexigenic-like effects, but the mechanisms are still poorly understood. Using an evolutionary background, this review aims to highlight the potential involvement of the melanocortin system and other hypothalamic neural circuitries regulating energy balance during and after physical exercise. The physiological significance of these changes will be explored, and possible signalling agents will be addressed. The knowledge discussed here might be important for clarifying obesity aetiology as well as new therapeutic approaches for body weight loss.     

The effect of fibrinogen genotype on fibrinogen levels after strenuous physical exercise

We have examined the effect of two beta-fibrinogen gene promoter polymorphisms (-455G>A and -854G>A) on the fibrinogen response to severe exercise in a group of male army recruits undergoing basic training. Fibrinogen was measured pre-training and again serially after severe 48 h final military exercise (FME). Out of 884 subjects, 762 completed training of whom 250 were selected for post-FME study. Fibrinogen levels (g/l) were significantly elevated over baseline levels 2, 48 and 96 h after FME, representing increases of 15.7%, 3.4% and 7.6% (p <0.005; p = 0.05 and p <0.005 respectively), with higher levels in -455A allele carriers than genotype -455GG: 3.17+/-0.05 vs. 2.94+/-0.05 (p <0.001), 2.86+/-0.05 vs. 2.60+/-0.05 (p <0.0005) and 2.98+/-0.06 vs. 2.69+/-0.06 (p <0.0005) at 2, 48 and 96 h respectively. There was no effect of the -854G>A polymorphism on fibrinogen, even after taking into account beta-fibrinogen -455 genotype. Thus the fibrinogen -455G>A polymorphism influences fibrinogen levels following exercise. The effect of genotype might be clinically relevant at times of hyperfibrinogenaemia such as following an acute inflammatory response.     

Effect of physical exercise on mortality in patients with Parkinson''s disease

Public health nurses visited and followed up for more than one year 438 patients with Parkinson's disease living in Osaka. The follow-up period averaged 4.1 years, during which 71 deaths were observed. The patients were classified according to the degree of physical exercise they performed, and the ratios of observed to expected deaths were calculated. The exercising group showed the lowest ratio of 1.68 (1.45 for patients able to walk independently, and 1.89 for those could not) while all patients exhibited a ratio of 2.47. Multivariate analysis using Cox's proportional hazard model, adjusted for age, sex, walking ability and duration of disease at study entry, showed that, compared with the exercising group, the non-exercising patients had a hazard ratio of 1.83.     

有氧运动对男性慢性精神分裂症患者认知功能的影响

背景精神分裂症的治疗方式以药物治疗及物理治疗为主,但均存在不良反应,影响治疗依从性及疗效。既往研究结果显示,有氧运动有助于改善阿尔茨海默病患者及抑郁障碍患者的认知功能。目前,国内对有氧运动改善精神分裂症患者认知功能的研究存在不足。目的 探讨有氧运动对男性慢性精神分裂症患者认知功能的影响,为精神分裂症患者的治疗提供参考。方法 选取2022年12月—2023年4月在芜湖市第四人民医院住院的76例男性慢性精神分裂症患者为研究对象,采用随机数字表法分为研究组（n=36）和对照组（n=40）。两组均接受常规药物治疗,研究组在此基础上接受为期8周、每周5次、每次60 min的有氧运动干预。于干预前后,采用MATRICS共识认知成套测验（MCCB）和Stroop色词测验（SCWT）分别评定患者的认知功能和执行功能。结果 干预后,研究组MCCB的连线测验用时短于对照组,空间广度测验及迷宫测验评分均高于对照组（Z=-2.070、-2.306、-2.375,P均<0.05）,重复测量方差分析结果显示,干预后,两组患者霍普金斯词语学习测验评分的时间主效应有统计学意义（F=39.067,P<0.0...     

Serum homocysteine and physical exercise in patients with Parkinson's disease

Background: Hyperhomocysteinemia is a major risk factor for cerebral and peripheral vascular diseases, as well as cortical and hippocampal injury, including an increased risk of dementia and cognitive impairment. Elevated serum homocysteine (Hcy) concentrations are common in patients with Parkinson's disease (PD) who have been treated with levodopa; however, physical exercises can help reduce Hcy concentrations. The aim of the present study was to compare serum Hcy levels in patients with PD who partook in regular physical exercises, sedentary PD patients, and healthy controls. Methods: Sixty individuals were enrolled in the present study across three groups: (i) 17 patients who did not partake of any type of exercise; (ii) 24 PD patients who exercised regularly; and (iii) 19 healthy individuals who did not exercise regularly. All participants were evaluated by Hoehn and Yahr scale, the Unified Parkinson’s Disease Rating Scale (UPDRS) and Schwab and England scale (measure daily functionality). The serum levels of Hcy were analyzed by blood samples collected of each participant. An analysis of variance and a Tukey’s post hoc test were applied to compare and to verify differences between groups. Pearson’s correlation and stepwise multiple regression analyses were used to consider the association between several variables. Results: Mean plasma Hcy concentrations in individuals who exercised regularly were similar to those in the healthy controls and significantly lower than those in the group that did not exercise at all (P= 0.000). In addition, patients who did not exercise were receiving significantly higher doses of levodopa than those patients who exercised regularly (P= 0.001). A positive relationship between levodopa dose and Hcy concentrations (R²= 0.27; P= 0.03) was observed in patients who did not exercise, but not in those patients who exercised regularly (R²= 0.023; P= 0.15). Conclusions: The results of the present study suggest that, even with regular levodopa therapy, Hcy concentrations in PD patients who exercise regularly are significantly lower than in patients who do not exercise and are similar Hcy concentrations in healthy controls.     

Effect of eccentric versus concentric exercise training on mitochondrial function

Introduction: The effect of eccentric (ECC) versus concentric (CON) training on metabolic properties in skeletal muscle is understood poorly. We determined the responses in oxidative capacity and mitochondrial H₂O₂ production after eccentric (ECC) versus concentric (CON) training performed at similar mechanical power. Methods: Forty‐eight rats performed 5‐ or 20‐day eccentric (ECC) or concentric (CON) training programs. Mitochondrial respiration, H₂O₂ production, citrate synthase activity (CS), and skeletal muscle damage were assessed in gastrocnemius (GAS), soleus (SOL) and vastus intermedius (VI) muscles. Results: Maximal mitochondrial respiration improved only after 20 days of concentric (CON) training in GAS and SOL. H₂O₂ production increased specifically after 20 days of eccentric ECC training in VI. Skeletal muscle damage occurred transiently in VI after 5 days of ECC training. Conclusions: Twenty days of ECC versus CON training performed at similar mechanical power output do not increase skeletal muscle oxidative capacities, but it elevates mitochondrial H₂O₂ production in VI, presumably linked to transient muscle damage. Muscle Nerve 50 : 803–811, 2014     

Effect of naloxone on somatostatin inhibition of arginine vasopressin response to physical exercise in normal men

To establish whether somatostatin (SRIH) and/or endogenous opioids play a role in the control of arginine-vasopressin (AVP) response to physical exercise, eight healthy men underwent four bicycle-ergometer tests until exhaustion: exercise control test; exercise plus SRIH, naloxone or SRIH plus naloxone. Serum AVP levels, physiological and biochemical variables were measured during tests. Physiological and biochemical variables were similar in all tests. During control test exercise significantly increased serum AVP levels, with a peak value 4.1 times higher than baseline. The AVP response to exercise was similar in the presence of naloxone, whereas it was significantly reduced by SRIH (AVP peak was only 2.8 times higher than baseline). When SRIH and naloxone were given together, the exercise-induced AVP rise was comparable to that observed in the control test. Results indicate a somatostatinergic involvement in the regulation of the AVP response to physical exercise. Furthermore, naloxone-sensitive endogenous opioids appear to play a role in the mechanism underlying SRIH inhibitory action, but not in mediation of the AVP response to physical exercise.     

自愿适量运动对脑的有益作用及其生物学机制

本文综述了在人和动物方面有关自愿适量运动有益于脑作用的研究,包括改善心理状态和认知功能、增强心理幸福感、降低老年痴呆症发生危险度和发挥抗抑郁及抗焦虑药的作用等。运动对脑的作用机制包含上游和下游两方面：上游途径主要涉及投射到海马的几种神经递质系统的功能增强,其中包括去甲肾上腺素、5-羟色胺、乙酰胆碱和γ-氨基丁酸;下游途径主要涉及脑源性神经营养因子的表达提高和神经元发生的增强;其中,激活β受体介导的去甲肾上腺素能神经的传递被认为是运动导致脑源性神经营养因子表达增强的前提,上述过程在细胞内的可能信号转导机制主要涉及G-蛋白偶联受体-促分裂原活化蛋白激酶-磷脂酰肌醇（-3）激酶等细胞信号转导通路的交互及正反馈调控。