化学刺激引起的两种大鼠内脏高敏感性模型的建立

目的本文采用两种化学刺激建立两种新的大鼠内脏高敏感性肠易激综合征(IBS)模型。方法采用成年大鼠,经肠道连续6d给予冰醋酸或芥末油刺激后,进行直肠扩张,评估肠道敏感性,记录胃肠电频率、峰电位、峰峰值和面积,检测血清5-HT含量。结果与对照组相比,冰醋酸模型肠敏感性(P<0.05)、胃肠电频率(P<0.01)均升高;芥末油模型肠敏感性(P<0.01),胃肠电频率(P<0.01)、峰电位(P<0.05)、峰峰值(P<0.01)、峰面积(P<0.01),血清5-HT含量(P<0.05)均有变化,提示模型组敏感性增高。与模型组比较,反证药物组肠敏感性、胃肠电及血清5-HT含量均有一定恢复。结论通过对成年大鼠肠道进行化学刺激,成功建立了新的大鼠内脏高敏感性IBS模型。

肠易激综合征发病机制研究新进展

综述了肠易激综合征(irritable bowel syndrome,IBS)的流行病学情况和近年来对其病因和发病机制的认识,指出目前研究IBS的前提假设是该病起于胃肠动力学的改变和以内脏传入神经传递变化为主导的心理异常,但近年来研究显示IBS 的发病与内脏高敏性异常有关,并从脑一肠轴方面进行了一些研究。至今该病的病因和发病机理尚未明确,传统西药的治疗仅旨在缓解排便习惯改变出现的症状,效果不很理想。近年来,许多学者的研究发现中医学的整体观更有利于对IBS病因和发病机制的认识,中药在改善IBS症状方面有一定的优势,值得进一步研究。

Liver in systemic disease

Potential causes of abnormal liver function tests include viral hepatitis,alcohol intake,nonalcoholic fatty liver disease,autoimmune liver diseases,hereditary diseases,hepatobiliary malignancies or infection,gallstones and drug-induced liver injury.Moreover,the liver may be involved in systemic diseases that mainly affect other organs.Therefore,in patients without etiology of liver injury by screening serology and diagnostic imaging,but who have systemic diseases,the abnormal liver function test results might be caused by the systemic disease.In most of these patients,the systemic disease should be treated primarily.However,some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.

Can probiotics benefit children with autism spectrum disorders?

Children with autism are commonly affected by gastrointestinal problems such as abdominal pain, constipation and diarrhea. In recent years, there has been a growing interest in the use of probiotics in this population, as it hypothetically may help to improve bowel habits and the behavioral and social functioning of these individuals. The gut microbiome plays an important role in the pathophysiology of organic as well as functional gastrointestinal disorders. Microbial modification with the use of antibiotics, probiotics, and fecal transplantation have been effective in the treatment of conditions such as recurrent Clostridium difficile infection, pouchitis, and irritable bowel syndrome. The present review presents a number of reported clinical, immunological and microbiomerelated changes seen in children with autism compared to normally developed children. It also discusses gut inflammation, permeability concerns, and absorption abnormalities that may contribute to these problems. Most importantly, it discusses evidence, from human and animal studies, of a potential role of probiotics in the treatment of gastrointestinal symptoms in children with autism.

Gastrointestinal hormone abnormalities and G and D cells in functional dyspepsia patients with gastric dysmotility

AIM: To investigate the relationship between gastric dysmotility,gastrointestinal hormone abnormalities, and neuroendocrine cells in gastrointestinal mucosa in patients with functional dyspepsia (FD).METHODS: Gastric emptying was assessed with solid radiopaque markers in 54 FD patients, and the patients were divided into two groups according to the results, one with delayed gastric emptying and the other with normal gastric emptying. Seventeen healthy volunteers acted as normal controls. Fasting and postprandial plasma levels and gastroduodenal mucosal levels of gastrointestinal hormones gastrin, somatostatin (SS) and neurotensin (NT)were measured by radioimmunoassay in all the subjects.G cells (gastrin-producing cells) and D cells (SS-producing cells) in gastric antral mucosa were immunostained with rabbit anti-gastrin polyclonal antibody and rabbit anti-SS polyclonal antibody, respectively, and analyzed quantitatively by computerized image analysis.RESULTS: The postprandial plasma gastrin levels, the fasting and postprandial plasma levels and the gastric and duodenal mucosal levels of NT were significantly higher in the FD patients with delayed gastric emptying than in those with normal gastric emptying and normal controls. The number and gray value of G and D cells and the G cell/D cell number ratio did not differ significantly between normal controls and the FD patients with or without delayed gastric emptying.CONCLUSION: Our findings suggest that the abnormalities of gastrin and NT may play a role in the pathophysiology of gastric dysmotility in FD patients, and the abnormality of postprandial plasma gastrin levels in FD patients with delayed gastric emptying is not related to the changes both in the number and gray value of G cells and in the G cell/D cell number ratio in gastric antral mucosa.

Functional oesophago-gastric junction imaging

Despite its role in disease there is still no definitive method to assess oesophago-gastric junction competence （OGJ）. Traditionally the OGJ has been assessed using manometry with lower oesophageal sphincter pressure as the indicator. More recently this has been shown not to be a very reliable marker of sphincter function and competence against reflux. Disorders such as gastro-oesophageal reflux disease and to a lesser extend achalasia still effects a significant number of patients. This review looks at using a new technique known as impedance planimetry to profile the geometry and pressure in the OGJ during distension of a bag. The data gathered can be reconstructed into a dynamic representation of OGJ action. This has been shown to provide a useful representation of the OGJ and to show changes to the competence of the OGJ in terms of compliance and distensibility as a result of endoluminal therapy.

Wireless capsule endoscopy in the investigation of patients with chronic renal failure and obscure gastrointestinal bleeding (preliminary data)

AIM： To investigate the role of wireless capsule endoscopy （WCE） in detection of small bowel （SB） pathology in patients with chronic renal failure （CRF） and obscure bleeding. METHODS： Consecutive CRF patients with obscure bleeding were prospectively studied. Patients with normal renal function and obscure bleeding, investigated during the same period with WCE, were used for the interpretation of results. RESULTS： Seventeen CRF patients （11 overt, 6 occult bleeding） and 51 patients （33 overt, 18 occult bleeding） with normal renal function were enrolled in this study. Positive SB findings were detected in 70.6% of CRF patients and in 41.2% of non-CRF patients （P〈0.05）. SB angiodysplasia was identified in 47% of CRF patients and in 17.6% of non-CRF patients. Univariate logistic regression revealed CRF as a significant predictive factor for angiodysplasia （P〈0.05）. Therapeutic measures were undertaken in 66% of the patients with the positive findings. CONCLUSION： According to our preliminary results, SB angiodysplasia was found in an increased prevalence among CRF patients with obscure bleeding. WCE is useful in diagnosis of gastrointestinal pathologies and in planning appropriate therapeutic intervention and, therefore, should be included in the work-up of this group of patients.

Novel mechanisms in functional dyspepsia

Functional dyspepsia （FD） is a highly prevalent but heterogeneous disorder in which multiple pathogenetic mechanisms are involved. Although there are many studies that have investigated various pathophysiologic mechanisms, the underlying casual pathways associated with FD remain obscure. The currently proposed pathophysiologic mechanisms associated with FD include genetic susceptibility, delayed as well as accelerated gastric emptying, visceral hypersensitivity to acid or mechanical distention, impaired gastric accommodation, abnormal fundic phasic contractions, abnormal antroduodenal motility, acute and chronic infections, and psychosocial comorbidity. A greater understanding of the abnormalities underlying FD may lead to improved management. The aim of this editorial is to provide a critical overview of current pathophysiologic concepts in functional dyspepsia.

Acute liver failure is frequent during heat stroke

Acute liver failure （ALF） is relatively frequent during heat stroke （HS）. This risk must be emphasized, because its inddence is higher than is usually thought. In a recent study by Weigand et al, two cases were reported in which liver failure was the leading symptom. We have confirmed their conclusion in a study of 25 cases of HS with ALF, compared with 25 other cases without ALE Moreover, we observed that hypophosphatemia on admission could predict occurrence of ALF during HS. As for clinical and other biological parameters, phosphatemia should be monitored for at least 3 d in all cases of HS, even when it is thought to be mild.

Hemorrhagic Fever with Renal Syndrome Complicated by Orchitis

Hemorrhagic fever with renal syndrome (HFRS) is a disease caused by viruses of the family Bunyaviridae,genus Hantavirus.HFRS from Dobrava virus (DOBV) is a seldom reported disease in Albania.Clinically HFRS is manifested as mild,moderate,or severe.Therefore,the number of cases of Hantavirus' infection may be underestimated,and should be included in the differential diagnosis of many acute infections,hematologic diseases,acute abdominal diseases and renal diseases complicated by acute renal failure.We report here an atypical presentation of HFRS from Dobrava virus complicated by orchitis with a positive outcome.

Relationship between gastrointestinal and extra-gastrointestinal symptoms and delayed gastric emptying in functional dyspeptic patients

AIM: Delayed gastric emptying and an enlarged fasting gastric antrum are common findings in functional dyspepsia but their relationship with gastrointestinal (GI), and the frequently associated extra-GI symptoms remains unclear.This study evaluated the relationship between GI and extra-GI symptoms, fasting antral volume and delayed gastric emptying in functional dyspepsia.METHODS: In 108 functional dyspeptic patients antral volume and gastric emptying were assessed with ultrasonography (US). Symptoms were assessed with standardized questionnaire. The association of symptoms and fasting antral volume with delayed gastric emptying was estimated with logistic regression analysis.RESULTS: Delayed gastric emptying was detected in 39.8% of the patients. Postprandial drowsiness (AOR 11.25; 95%CI 2.75-45.93), nausea (AOR 3.51; 95%CI 1.19-10.32), fasting antral volume (AOR 1.93; 95%CI 1.22-3.05), were significantly associated with delayed gastric emptying. Symptoms, mainly the extra-GI ones as postprandial drowsiness and nausea, combined with fasting antral volume predicted the modality of gastric emptying with a sensitivity and specificity of 78%.CONCLUSION: In functional dyspeptic patients, (1) an analysis of fasting antral volume and of symptoms can offer valuable indication on the modality of gastric emptying,and (2) it seems appropriate to inquire on postprandial drowsiness that showed the best correlation with delayed gastric emptying.

Hepatotoxicity of NONI juice: Report of two cases

NONI juice (Morinda citrifolia) is an increasingly popular wellness drink claimed to be beneficial for many illnesses.No overt toxicity has been reported to date. We present two cases of novel hepatotoxicity of NONI juice. Causality of liver injury by NONI juice was asses-sed. Routine laboratory tests and transjugular or percutaneous liver biopsy were performed. The first patient underwent successful liver transplantation while the second patient recovered spontaneously after cessation of NONI juice.A 29-year-old man with previous toxic hepatitis associated with small doses of paracetamol developed sub-acute hepatic failure following consumption of 1.5 L NONI juice over 3 wk necessitating urgent liver transplantation. A 62-year-old woman without evidence of previous liver disease developed an episode of self-limited acutehepatitis following consumption of 2 L NONI juice for over 3 mo. The most likely hepatotoxic components of Morinda citrifolia were anthraquinones. Physicians should be aware of potential hepatotoxicity of NONI juice.

Nodular lymphoid hyperplasia: A marker of low-grade inflammation in irritable bowel syndrome?

AIM To evaluate the prevalence of nodular lymphoid hyperplasia(NLH) in adult patients undergoing colonoscopy and its association with known diseases. METHODS We selected all cases showing NLH at colonoscopy in a three-year timeframe, and stratified them into symptomatic patients with irritable bowel syndrome(IBS)-type symptoms or suspected inflammatory bowel disease(IBD), and asymptomatic individuals undergoing endoscopy for colorectal cancer screening.Data collection included medical history and final diagnosis. As controls, we considered all colonoscopies performed for the aforementioned indications during the same period.RESULTS One thousand and one hundred fifty colonoscopies were selected. NLH was rare in asymptomatic individuals(only 3%), while it was significantly more prevalent in symptomatic cases(32%). Among organic conditions associated with NLH, the most frequent was IBD, followed by infections and diverticular disease. Interestingly, 31% of IBS patients presented diffuse colonic NLH. NLH cases shared some distinctive clinical features among IBS patients: they were younger, more often female, and had a higher frequency of abdominal pain, bloating, diarrhoea, unspecific inflammation, self-reported lactose intolerance and metal contact dermatitis. CONCLUSION About 1/3 of patients with IBS-type symptoms or suspected IBD presented diffuse colonic NLH, which could be a marker of low-grade inflammation in a conspicuous subset of IBS patients.

PPARs： diverse regulators in energy metabolism and metabolic diseases

The nuclear receptor PPARs are fundamentally important for energy homeostasis. Through their distinct yet overlapping functions and tissue distribution, the PPARs regulate many aspects of energy metabolism at the transcriptional level. Functional impairment or dysregulation of these receptors leads to a variety of metabolic diseases, while their ligands offer many metabolic benefits. Studies of these receptors have advanced our knowledge of the transcriptional basis of energy metabolism and helped us understand the pathogenic mechanisms of metabolic syndrome.

EFFECTS OF ALCOHOL INTAKE ON PENILE STRUCTURE AND FUNCTION IN RATS

Objective To investigate the effects of alcohol intake on penile structure and function in rats. Methods Thirty adult male Wistar rats were randomly divided into two groups: control group and alcohol intake group. They were administered with 2 mL of normal saline and 40% alcohol solution respectively through gastric tubes every day. Three months later, the animal model of alcohol intake was evaluated by modified Nayagida's method, and the effects of alcohol on the rats were studied by sexual behavior, the number of apomorphine-induced penile erection, level of testosterone in the sera, and the content of penile smooth muscle. Results The scores of animal model of alcohol intake evaluated by Nayagida's method were 0.66±2.05 in the control group and 9.26±5.50 in the alcohol intake group(P<0.05), which indicated that an animal model of alcohol intake was successfully established. Sexual behavior, the number of apomorphine-induced penile erection, testosterone level in the sera, and the content of penile smooth muscle of the alcohol intake group were all statistically different as compared with the control group(P<0.05). Conclusion Alcohol intake induces sexual dysfunction in rats, which may be due to the decline of testosterone level in the sera and decline of penile smooth muscle.

Study on the Effect of Simvastatin on Left Ventricular Mass and Endothelial Function and the Relationship between Their Changes in the Patients with Essential Hypertension

Objective:To study the effect of Simvastatin on the left ventricular mass and endothelial function and to investigate the relationship between their changes in the patients with essential hypertension(EH). Methods: 50 patients with hypertension without severe complication were divided into two groups in a randomized,controlled and single blind trial.Group I(n=25)were given Simvastatin and hydragogue for 12 weeks while Group Ⅱ were given hydragogue during the same time.We detected the left ventricular mass and the brachial artery dilatation induced by reactive hyperemia(DIRH)or nitroglycerin(DING)respectively with ultrasonography in all patients before and after treatment.25 normal subjects without any treatment were taken as the control. Results:The left ventricular mass index(LVMI)was higher in the two groups of patients[(133.61±31.02)g/m 2;(118.04±39.62)g/m 2]than that in the control(88.79±22.73)g/m 2 before treatment(P<0.01,0.000 1,respectively)while the blood pressure was higher.The DIRH was lower in the two groups of patients(5.93±2.24)%;(6.54±3.16)%than that in the control(13.09±2.99)%,P<0.000 1.There was no significantly differences in age,serum concentrations of total cholesterol,triglyceride,sugar,blood pressure or the DING between two groups of patients and the control(P>0.05).And there was no significant difference in the all variables between group Ⅰ and group Ⅱ before treatment.After treatment the LVMI decreased[(133.61±31.02)g/m 2 VS(91.07±16.01)g/m 2,P<0.01]and the DTRH increased[(5.93±2.24)% VS(13.53±2.38)%,P<0.01]in the patients of group Ⅰ while there was no significant change in LVMI and DIRH in the patients of group Ⅱ.The blood pressure in the two groups of patients was decreased to the normal.Compared with group Ⅱ,the changes of LVMI and DIRH was higher in patients of group Ⅰ though the serum concentrations of total cholesterol,triglyceride or sugar were not significantly different.No significant change in serum concentrations oftotal cholesterol,triglyceride or sugar was found during treatment in the two groups of patients.Analysis showed that the LVMI correlated with DIRH and the change of LVMI correlated better with the change of DIRH(r=-0.56;0.69,P<0.000 1,respectly). Conclusions: The increase of left ventricular mass was related with endothelial dysfunction in essential hypertension.Being independent of the changes of serum concentrations of total cholesterol,triglyceride or sugar and blood pressure,Simvastatin could inhibit the increase of left ventricular mass and improve endothelial function.

Neurogenic bowel dysfunction in patients with spinal cord injury, myelomeningocele, multiple sclerosis and Parkinson’s disease

Exciting new features have been described concerning neurogenic bowel dysfunction,including interactions between the central nervous system,the enteric nervous system,axonal injury,neuronal loss,neurotransmission of noxious and non-noxious stimuli,and the fields of gastroenterology and neurology.Patients with spinal cord injury,myelomeningocele,multiple sclerosis and Parkinson's disease present with serious upper and lower bowel dysfunctions characterized by constipation,incontinence,gastrointestinal motor dysfunction and altered visceral sensitivity.Spinal cord injury is associated with severe autonomic dysfunction,and bowel dysfunction is a major physical and psychological burden for these patients.An adult myelomeningocele patient commonly has multiple problems reflecting the multisystemic nature of the disease.Multiple sclerosis is a neurodegenerative disorder in which axonal injury,neuronal loss,and atrophy of the central nervous system can lead to permanent neurological damage and clinical disability.Parkinson's disease is a multisystem disorder involving dopaminergic,noradrenergic,serotoninergic and cholinergic systems,characterizedby motor and non-motor symptoms.Parkinson's disease affects several neuronal structures outside the substantia nigra,among which is the enteric nervous system.Recent reports have shown that the lesions in the enteric nervous system occur in very early stages of the disease,even before the involvement of the central nervous system.This has led to the postulation that the enteric nervous system could be critical in the pathophysiology of Parkinson's disease,as it could represent the point of entry for a putative environmental factor to initiate the pathological process.This review covers the data related to the etiology,epidemiology,clinical expression,pathophysiology,genetic aspects,gastrointestinal motor dysfunction,visceral sensitivity,management,prevention and prognosis of neurogenic bowel dysfunction patients with these neurological diseases.Embryological,morphological and experimental studies on animal models and humans are also taken into account.

Targeting voltage-gated sodium channels for treatment for chronic visceral pain

Voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability,and their abnormal activity is related to several pathological processes,including cardiac arrhythmias,epilepsy,neurodegenerative diseases,spasticity and chronic pain.In particular,chronic visceral pain,the central symptom of functional gastrointestinal disorders such as irritable bowel syndrome,is a serious clinical problem that affects a high percentage of the world population.In spite of intense research efforts and after the dedicated decade of pain control and research,there are not many options to treat chronic pain conditions.However,there is a wealth of evidence emerging to give hope that a more refined approach may be achievable.By using electronic databases,available data on structural and functional properties of VGSCs in chronic pain,particularly functional gastrointestinal hypersensitivity,were reviewed.We summarize the involvement and molecular bases of action of VGSCs in the pathophysiology of several organic and functionalgastrointestinal disorders.We also describe the efficacy of VGSC blockers in the treatment of these neurological diseases,and outline future developments that may extend the therapeutic use of compounds that target VGSCs.Overall,clinical and experimental data indicate that isoform-specific blockers of these channels or targeting of their modulators may provide effective and novel approaches for visceral pain therapy.

Molecular mechanisms of insulin resistance in chronic hepatitis C

It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV)genotype 1,in contrast to hepatic steatosis, which is associated with genotype 3 infection.Apart from the well-described complications of diabetes,IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma.More recently,it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined.This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.

Adult hereditary fructose intolerance

Hereditary fructose intolerance(HFI) is an underrecognized,preventable life-threatening condition.It is an autosomal recessive disorder with subnormal activity of aldolase B in the liver,kidney and small bowel.Symptoms are present only after the ingestion of fructose,which leads to brisk hypoglycemia,and an individual with continued ingestion will exhibit vomiting,abdominal pain,failure to thrive,and renal and liver failure.A diagnosis of HFI was made in a 50-year-old woman on the basis of medical history,response to fructose intolerance test,demonstration of aldolase B activity reduction in duodenal biopsy,and molecular analysis of leukocyte DNA by PCR showed homozygosity for two doses of mutant gene.HFI may remain undiagnosed until adult life and may lead to disastrous complications following inadvertent fructose or sorbitol infusion.Several lethal episodes of HFI following sorbitol and fructose infusion have been reported.The diagnosis can only be suspected by taking a careful dietary history,and this can present serious complications.