Heme in intestinal epithelial cell turnover, differentiation, detoxification, inflammation, carcinogenesis, absorption and motility

The gastrointestinal tract is lined by a simple epithelium that undergoes constant renewal involving cell division, differentiation and cell death. In addition, the epithelial lining separates the hostile processes of digestion and absorption that occur in the intestinal lumen from the aseptic environment of the internal milieu by defensive mechanisms that protect the epithelium from being breached. Central to these defensive processes is the synthesis of heme and its catabolism by heme oxygenase (HO). Dietary heme is also an important source of iron for the body which is taken up intact by the enterocyte. This review describes the recent literature on the diverse properties of heme/HO in the intestine tract. The roles of heme/HO in the regulation of the cell cycle/ apoptosis, detoxification of xenobiotics, oxidative stress, inflammation, development of colon cancer, heme-iron absorption and intestinal motility are specifically examined.     

Evidence for a role of mitogen-activated protein kinases in the treatment of experimental acute pancreatitis

Acute pancreatitis(AP) is an inflammatory disease characterized by acute inflammation and necrosis of the pancreatic parenchyma. AP is often associated with organ failure, sepsis, and high mortality. The pathogenesis of AP is still not well understood. In recent years several papers have highlighted the cellular and molecular events of acute pancreatitis. Pancreatitis is initiated by activation of digestive enzymes within the acinar cells that are involved in autodigestion of the gland, followed by a massive infiltration of neutrophils and macrophages and release of inflammatory mediators, responsible for the local and systemic inflammatory response. The hallmark of AP is parenchymal cell necrosis that represents the cause of the high morbidity and mortality, so that new potential therapeutic approaches are indispensable for the treatment of patients at high risk of complications. However, not all factors that determine the onset and course of the disease have been explained. Aim of this article is to review the role of mitogen-activated protein kinases in pathogenesis of acute pancreatitis.     

Indexed in SCI Medline

正Asian Pacific Journal of Tropical Medicine(APJTM)is an international journal of tropical medicine that is edited by International Federation of Tropical Medicine(IFTM)and published by Elsevier.It is the only journal of tropical medicine included by SCI,Medline in China.It indicates APJTM has become one of the top international journals.Since the first issue in March 2008,it has been included by 12 international databases:     

Indexed in SCI Medline

正Asian Pacific Journal of Tropical Medicine(APJTM)is an international journal of tropical medicine that is edited by International Federation of Tropical Medicine(IFTM)and published by Elsevier.It is the only journal of tropical medicine included by SCI,Medline in China.It indicates APJTM has become one of the top international journals.Since the first issue in March 2008,it has been included by 12 international databases:     

Indexed in SCI Medline

正Asian Pacific Journal of Tropical Medicine(APJTM)is an international journal of tropical medicine that is edited by International Federation of Tropical Medicine(IFTM)andl published by Elsevier.It is the only journal of tropical medicine included by SCI,Medline in China.It indicates APJTM has become one of the top international journals.Since the first issue in March 2008,it has been included by 12 international databases:     

Indexed in SCI Medline

正Asian Pacific Journal of Tropical Medicine(APJTM)is an international journal of tropical medicine that is edited by International Federation of Tropical Medicine(IFTM)and published by Elsevier.It is the only journal of tropical medicine included by SCI,Medline in China.It indicates APJTM has become one of the top international journals.Since the first issue in March 2008,it has been included by 12 international databases:     

Indexed in SCI Medline

正Asian Pacific Journal of Tropical Medicine (APJTM) is an international journal of tropical medicine that is edited by International Federation of Tropical Medicine (IFTM) and published by Elsevier. It is the only journal of tropical medicine included by SCI, Medline in China. It indicates APJTM has become one of the top international journals.Since the first issue in March 2008, it has been included by 12 international databases:     

Indexed in SCI Medline

正Asian Pacific Journal of Tropical Medicine(APJTM)is an international journal of tropical medicine that is edited by International Federation of Tropical Medicine(IFTM)and published by Elsevier.It is the only journal of tropical medicine included by SCI,Medline in China.It indicates APJTM has become one of the top international journals.Since the first issue in March 2008,it has been included by 12 international databases:     

Indexed in SCI Medline

正Asian Pacific Journal of Tropical Medicine(APJTM)is an international journal of tropical medicine that is edited by International Federation of Tropical Medicine(IFTM)and published by Elsevier.It is the only journal of tropical medicine included by SCI,Medline in China.It indicates APJTM has become one of the top international journals.Since the first issue in March 2008,it has been included by 12 international databases:     

Indexed in SCI Medline

正Asian Pacific Journal of Tropical Medicine(APJTM)is an international journal of tropical medicine that is edited by International Federation of Tropical Medicine(IFTM)and published by Elsevier.It is the only journal of tropical medicine included by SCI,Medline in China.It indicates APJTM has become one of the top international journals.Since the first issue in March 2008,it has been included by 12 international databases:     

Combined multichannel intraluminal impedance and manometry testing

Oesophageal manometry has been considered the "gold standard" test for the evaluation of oesophageal motility. Oesophageal manometry allows physicians to assess peristalsis by using informations about the shape, amplitude and duration of the oesophageal contraction, but it does not offer direct information about bolus transit through the oesophagus. Recent studies demonstrate that combined impedance-manometry provides important additional information about oesophageal motility as compared to conventional manometry such as: (1) monitoring of bolus transport patterns without the use of radiation, (2) calculation of bolus transit parameters, (3) evaluation of bolus clearance and (4) investigation of the relationships between bolus transit and LES relaxation. These changes could potentially improve diagnostic accuracy of oesophageal motility testing, advancing both clinical and basic research. This review focuses on current aspects of the novel technology of combined impedance-manometry for oesophageal motility testing.     

Impedance characteristics of normal oesophageal motor function

OBJECTIVE: To obtain detailed data about the correlation between oesophageal peristalsis and bolus transport for clinical oesophageal motility testing. METHODS: Oesophageal motility testing was performed in 25 healthy subjects by using the newly developed technique of concurrent impedancometry and manometry. Parameters of oesophageal motility and bolus transport as well as the correlation between transit and motility were analysed after swallowing saline or yogurt. RESULTS: Detailed data about bolus transport and oesophageal motility could be obtained during a single investigation step. Air was observed in front of the bolus in 76% of the swallows. Resting baseline impedance was significantly higher in the oesophagus than in the stomach (2832+/-118 Omega vs 688+/-119 Omega). The deglutitive impedance gradient was 222+/-26 Omega for saline and 482+/-38 Omega for yogurt. Bolus propagation velocity and bolus transit time as impedance parameters of bolus transport discriminated fluid from semisolid bolus (4.0+/-0.1 cm/s vs 3.2+/-0.1 cm/s and 9.9+/-0.2 s vs 11.5+/-0.2 s, for saline vs yogurt), while contraction wave amplitude as a manometry parameter of oesophageal motor function did not (91.4+/-7.5 mmHg vs 80.7+/-9.4 mmHg, for saline vs yogurt). There was a poor correlation between bolus propagation velocity and contraction wave amplitude. CONCLUSIONS: Impedance parameters of normal oesophageal motor function have been characterized. Impedancometry and manometry provide different but complementary data about oesophageal motor function. Concurrent impedancometry and manometry allows detailed monitoring of oesophageal motility and bolus transit, which may open new perspectives for comprehensive oesophageal motility testing.     

New esophageal function testing (impedance,Bravo pH monitoring,and high-resolution manometry): Clinical relevance

Esophageal testing aims to quantify gastroesophageal reflux or characterize esophageal motility. Reflux monitoring traditionally has been based on the detection of acidic reflux by a transnasal catheter that measures esophageal pH. Recently there have been two major developments in this field: the wireless Bravo pH capsule (Medtronic, Inc., Minneapolis, MN), which allows catheter-free monitoring, and impedance-pH measurement, a catheter-based technique that enables detection of acidic and nonacidic reflux. The assessment of esophageal motility has relied on conventional manometry for many years. Two new proedures also recently became available to assess esophageal motility: high-resolution manometry, which uses many closely spaced pressure sensors and provides spatiotemporal plots of esophageal pressure changes, and impedance manometry, a test that directly measures bolus transit and provides conventional manometric data. The advantages, disadvantages, and clinical importance of these new esophageal tests are discussed in this review.     

Esophageal impedance recording: Clinical utility and limitations

Multichannel intraluminal impedance (MII) is a new technique available for the evaluation of esophageal bolus transit and reflux similar to barium swallow, but without the hazards of radiation exposure. Combined MII and pH monitoring (MII-pH) allows evaluation of the nature and pH of the refluxate and the proximal extent of a reflux event. Thus, MII-pH is useful in evaluation of nonacid reflux in patients with persistent typical or atypical symptoms of gastroesophageal reflux disease that are refractory to acid suppression therapy. Additionally, combined MII and esophageal manometry (MII-EM) affords concurrent assessment of esophageal function (bolus transit) and motility. Therefore, it provides a more complete esophageal function test than esophageal manometry alone. The few limitations of impedance monitoring include the complexity of interpreting the tracings and the lack of data in the diseased population. However, continued improvements in the software and increasing studies in different patient populations will aid in overcoming these limitations.     

Multiple intraluminal electrical impedancometry for recording of upper gastrointestinal motility: current results and further implications

This review focuses on current aspects of the novel technology of multiple intraluminal electrical impedance measurement. It presents methodological features, summarizes current results, and discusses potential implications for further research. The impedance technique assesses a bolus transport and its associated peristalsis. Validation studies showed a good analogy between physically deduced impedance characteristics and characteristics derived from cineradiography and manometry. From the impedance tracings, it is possible to distinguish between resting states, bolus transit, and wall contraction. Characteristics of a peristaltic wave can be obtained. In human studies, esophageal and small intestinal peristaltic patterns can quantitatively and qualitatively be assessed. A high resolution recording of bolus movements with interesting details of transport and mixing can be obtained. On the basis of several prior characterized impedance tracings duodenal contractile patterns have been classified, and the interdigestive and postprandial states characterized. For reflux evaluation the impedance technique was especially useful for the detection of nonacid gastroesophageal reflux, which is not detectable by pH monitoring. In summary, the main impact of the impedance technique is its capability to characterize esophageal and intestinal chyme transport. Important data on luminal chyme transport have been obtained. This technique is developing into an interesting investigative tool to complement standard techniques for study of upper GI motility, in particular for basic research.     

Technology review: Esophageal impedance monitoring

Intraluminal impedance monitoring is a new technique that can be used to detect the flow of liquids and gas through hollow viscera. In combination with manometry, it is used for esophageal function testing and while manometry provides information on contractile activity, impedance provides information on esophageal bolus transit. This is especially useful in patients with nonobstructive dysphagia. However, impedance monitoring appears to be less suitable for the evaluation of patients with achalasia. When used in combination with esophageal pH monitoring, impedance monitoring makes gastroesophageal reflux monitoring more complete because it allows recognition of both acidic and weakly acidic reflux episodes. The results of several studies suggest that impedance-pH monitoring is useful in the evaluation of patients with PPI-resistant typical reflux symptoms, chronic unexplained cough, excessive belching, and rumination.     

Axial force measurement for esophageal function testing

The esophagus serves to transport food and fluid from the pharynx to the stomach. Manometry has been the ＂golden standard＂ for the diagnosis of esophageal motility diseases for many decades. Hence, esophageal function is normally evaluated by means of manometry even though it reflects the squeeze force （force in radial direction） whereas the bolus moves along the length of esophagus in a distal direction. Force measurements in the longitudinal （axial） direction provide a more direct measure of esophageal transport function. The technique used to record axial force has developed from external force transducers over in-vivo strain gauges of various sizes to electrical impedance based measurements. The amplitude and duration of the axial force has been shown to be as reliable as manometry. Normal, as well as abnormal, manometric recordings occur with normal bolus transit, which have been documented using imaging modalities such as radiography and scintigraphy. This inconsistency using manometry has also been documented by axial force recordings. This underlines the lack of information when diagnostics are based on manometry alone. Increasing the volume of a bag mounted on a probe with combined axial force and manometry recordings showed that axial force amplitude increased by 130% in contrast to an increase of 30% using manometry. Using axial force in combination with manometry provides a more complete picture of esophageal motility, and the current paper outlines the advantages of using this method.     

How to Optimally Apply Impedance in the Evaluation of Esophageal Dysmotility

The utilization of impedance technology has enhanced our understanding and assessment of esophageal dysmotility. Esophageal high-resolution manometry (HRM) catheters incorporated with multiple impedance electrodes help assess esophageal bolus transit, and the combination is termed high-resolution impedance manometry (HRIM). Novel metrics have been developed with HRIM—including esophageal impedance integral ratio, bolus flow time, nadir impedance pressure, and impedance bolus height—that augments the assessment of esophageal bolus transit. Automated impedance-manometry (AIM) analysis has enhanced understanding of the relationship between bolus transit and pressure phenomena. Impedance-based metrics have improved understanding of the dynamics of esophageal bolus transit into four distinct phases, may correlate with symptomatic burden, and can assess the adequacy of therapy for achalasia. An extension of the use of impedance involves impedance planimetry and the functional lumen imaging probe (FLIP), which assesses esophageal biophysical properties and distensibility, and could detect patterns of esophageal contractility not seen on HRM. Impedance technology, therefore, has a significant impact on esophageal function testing in the present day.     

Combined multichannel intraluminal impedance and manometry clarifies esophageal function abnormalities: study in 350 patients

BACKGROUND: Combined multichannel intraluminal impedance and esophageal manometry (MII-EM) is a technique that uses an FDA-approved device allowing simultaneous evaluation of bolus transit (MII) in relation to pressure changes (EM). METHODS: During a 9-month period, beginning from July 2002 through March 2003, we prospectively performed combined MII-EM on all patients referred for esophageal function testing. Each patient received 10 liquid and 10 viscous swallows. Manometric findings were reported based on criteria described by Spechler and Castell for liquid swallows. MII findings were reported as having normal bolus transit if >/=80% (8/10) of liquid and >/=70% (7/10) of viscous swallows had complete bolus transit. RESULTS: Three-hundred fifty studies were evaluated from patients with a variety of symptoms having the following manometric diagnoses: normal manometry (125), achalasia (24), scleroderma (4), ineffective esophageal motility (IEM) (71), distal esophageal spasm (DES) (33), nutcracker esophagus (30), hypertensive lower esophageal sphincter (LES) (25), hypotensive LES (5), and poorly relaxing LES (33). None of the patients with achalasia and scleroderma had normal bolus transit. Fifty-one percent of patients with IEM and 55% of patients with DES had normal bolus transit while almost all (more than 95%) patients with normal esophageal manometry, nutcracker esophagus, poorly relaxing LES, hypertensive LES, and hypotensive LES had normal bolus transit. Dysphagia occurred most often in patients with incomplete bolus transit on MII testing. CONCLUSION: Esophageal body pressures primarily determine bolus transit with isolated LES abnormalities appearing to have little effect on esophageal function. MII clarifies functional abnormalities in patients with abnormal manometric studies.     

Impedance detected abnormal bolus transit in patients with normal esophageal manometry. Sensitive indicator of esophageal functional abnormality?

SUMMARY. When used in combination with manometry, multichannel intraluminal impedance better characterizes the established manometric abnormalities into those with and without associated transit defects. However, the significance of the finding of normal manometry and abnormal impedance is not known. The objective of this study is to evaluate the clinical relevance of abnormal impedance associated with normal manometry during esophageal function testing in patients with a variety of esophageal symptoms. All patients referred for esophageal function testing during a 27‐month period underwent combined multichannel intraluminal impedance and esophageal manometry studies including 10 liquid and 10 viscous swallows in supine position. From 576 patients with normal esophageal body manometry we identified 158 patients (27%) with abnormal impedance. The primary symptom in these 158 patients was compared to that in 146 consecutive patients with normal manometry and normal impedance selected from the original 576 patients. Abnormal bolus transit was found with viscous, liquid and both type swallows in 60%, 19% and 21% of the patients respectively. Of patients with abnormal bolus transit, 23% presented with dysphagia compared to 10% of normal transit patients (p = 0.0035). In conclusion, abnormal impedance even in patients with normal manometry may be a sensitive indicator of esophageal functional abnormality as represented by the symptom of dysphagia in these patients. Abnormal transit was more frequently identified with viscous than liquid swallows. Prospective studies to further clarify impedance detected transit defects in patients with normal manometry and the role of viscous swallows in diagnostic testing are warranted.