Ghrelin: integrative neuroendocrine peptide in health and disease

OBJECTIVE: Ghrelin is a novel gastric hormone recognized in 1999 as a mediator of growth hormone release. Since growth hormone is anabolic, an important function of ghrelin may be to coordinate energy needs with the growth process. Newly discovered biologic roles of ghrelin imply that it may have other important physiological functions as well. This is a review of recent clinically relevant, yet less well-known, physiologic actions of ghrelin. SUMMARY BACKGROUND DATA: Ghrelin has profound orexigenic, adipogenic, and somatotrophic properties, increasing food intake and body weight. Secreted predominantly from the stomach, ghrelin is the natural ligand for the growth hormone secretagogue receptor in the pituitary gland, thus fulfilling criteria of a brain-gut peptide. The brain-gut axis is the effector of anabolism by regulating growth, feeding, and metabolism via vagal afferents mediating ghrelin signaling. However, the wide tissue distribution of ghrelin suggests that it may have other functions as well. METHODS: Systematic literature review of all PubMed citations between 1999 and August 2003 focusing on clinically relevant biochemical and physiological characteristics of ghrelin. RESULTS: Ghrelin is an important component of an integrated regulatory system of growth and metabolism acting via the vagus nerve, and is implicated in a variety of altered energy states such as obesity, eating disorders, neoplasia, and cachexia. It also enhances immune responses and potentially down-regulates anti-inflammatory molecules. Ghrelin's role as a brain-gut peptide emphasizes the significance of afferent vagal fibers as a major pathway to the brain, serving the purpose of maintaining physiologic homeostasis. CONCLUSIONS: The discovery of ghrelin has increased our understanding of feeding regulation, nutritional homeostasis, and metabolic processes. Further characterization of ghrelin's functions will likely generate new pharmacological approaches to diagnose and treat different disease entities including those related to the over-nutrition of obesity and the catabolic response to surgical trauma.     

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胃肠肽类激素是指传统的激素和许多可通过旁分泌神经分泌、自分泌和外分泌等方式 ,介导细胞间信息传递 ,发挥激素和局部递质效应的胃肠肽。　　胃肠肽类激素对胃肠道运动功能的调控形式为兴奋和(或 )抑制 ,即促进和 (或 )抑制作用。胰岛素和胰高糖素虽属胃肠肽类激素 ,但由于其功能特殊 ,故不在此讨论。1　兴奋型胃肠肽类激素1 1　胃动素 (ｍｏｔｉｌｉｎ)　　胃动素是由 2 2个氨基酸组成的多肽。主要存在于十二指肠和近端空肠粘膜内分泌细胞中 ,胃底、胃窦、远端小肠粘膜以及中枢、外周和胃肠道壁内神经系统中也有胃动素存在。人类胃动素基…     

Gastrointestinal neuromuscular pathology in alpers disease

Alpers disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration. Intestinal dysmotility is a frequent symptom, but it is often overshadowed by other clinical manifestations. The onset and progression of Alpers disease vary; however, most patients die during childhood, often before a specific diagnosis has been established. The gastrointestinal neuromuscular pathology of 4 patients, obtained largely from postmortem specimens, showed distinctive eosinophilic cytoplasmic granules in a subset of enteric ganglia and patchy atrophy of small intestinal muscularis externa. The cytoplasmic inclusions corresponded to abnormal mitochondria, which have been reported previously in another mitochondrial disorder (mitochondrial neurogastrointestinal encephalomyopathy) but not in Alpers disease. Recognition of these distinctive light microscopic findings, in an appropriate clinical setting, should prompt the evaluation of an underlying primary mitochondriopathy.     

Patterns of gastroesophageal reflux in health and disease.

Twenty-four pH monitoring the distal esophagus quantitates gastroesophageal reflux in a near physiologic setting by measuring the frequency and duration of acid exposure to the esophageal mucosa. Fifteen asymptomatic volunteers were studies with 24-hour pH and esophageal manometry. The normal cardia was more competent supine than in the upright position. Physiologic reflux was unaffected by age, rarely occurred during slumber, and was the rule after alimentation. One hundred symptomatic pateitns with an abnormal 24-hour pH record (2 S.D. above the mean of controls) could be divided into three patterns of pathological reflux: those who refluxed only in the upright position (9), only in the supine position (37), and in both positions (54). Upright differed from supine refluxers by excessive aerophagia causing reflux episodes by repetitive belching. Compared to controls, they had excessive post-prandial reflux, lower DES pressure, and less DES exposed to the positive pressure of the abdomen. Supine differed from upright refluxers by having a higher incidence of esophagitis and an inability to clear the esophagus of acid after a supine reflux episode. Compared to controls, they had only a lower DES pressure. Combined refluxers had a higher incidence of esophagitis than supine refluxers. Stricture (15%) was seen only in this group. They were similar to supine refluxers in their inability to clear a supine reflux episode. Compared to controls, they had a lower DES pressure and less DES exposed to the positive pressure of the abdomen. Forty of the 100 patients had an antireflux procedure (4 upright, 8 supine, 28 combined). The most severe postoperative flatus and abdominal distention was seen in the upright refluxers. It is concluded that minimal reflux is physiological. Patients with pathological reflux all have lower DES pressure. Patients with upright reflux have less of their DES exposed to the positive pressure environment of the abdomen. Patients with supine reflux have an inability to clear the esophagus of reflux acid and are prone to develop esophagitis. Patients with both upright and supine reflux have the most severe disease and are at risk in developing strictures. In patients with only upright reflux, aerophagia and delayed gastric emptying may be an important etiological factor.     

Endocytic trafficking of CFTR in health and disease.

The cystic fibrosis transmembrane conductance regulator (CFTR) is a Cl-selective anion channel expressed in epithelial tissues. Mutations in CFTR lead to the genetic disease cystic fibrosis (CF). Within each epithelial cell, CFTR interacts with a large number of transient macromolecular complexes, many of which are involved in the trafficking and targeting of CFTR. Understanding how these complexes regulate the trafficking and fate of CFTR, provides a singular insight not only into the patho-physiology of cystic fibrosis, but also provides potential drug targets to help cure this debilitating disease.     

Gastrointestinal graft-versus-host disease in man. A clinicopathologic study of the rectal biopsy.

Evaluation of the diagnostic utility of the rectal biopsy in graft-versus-host disease (GVHD), using the crypt abscess as a major diagnostic criterion, was based on 52 patients who had received marrow allografts for leukemia or aplastic anemia. Thirty-six of these patients had acute GVHD by skin biopsy criteria. These 36 patients demonstrated a strong association of the rectal crypt abscess with severity of clinical GVHD. High stool volume also correlated strongly with the crypt abscess. Patients without clear evidence of GVHD usually had normal rectal histology. Serial studies showed a good correlation of rectal biopsy results with the clinical course of acute GVHD. Patients with chronic GVHD had rectal mucosal damage only during the acute phase. Rectal ileal and cecal disease accurately. The rectal biopsy is a useful adjunct to serial skin biopsies in the diagnosis of GVHD in man.     

Connective tissues in health and disease. The Aberdeen experience.

Connective tissues have primarily a mechanical function within the body. How each tissue derives its mechanical properties from its composition and structure and how these properties are maintained by the cells are still poorly understood. Some principles that may provide a unifying basis for the material properties of these tissues as materials is described. Given this understanding current studies in Aberdeen are investigating the ways in which cells may regulate these properties in response to mechanical stimuli.     

Atrial natriuretic peptide in stable and decompensated chronic obstructive pulmonary disease.

BACKGROUND--Plasma levels of atrial natriuretic peptide (ANP) are elevated in patients with chronic obstructive pulmonary disease (COPD) and may have a role in preventing oedema formation in these patients. METHODS--Plasma ANP levels were measured in 60 patients with COPD and these measurements were related to pulmonary haemodynamics, response to treatment during exacerbations, and clinical patterns of the stable disease. RESULTS--Plasma ANP levels did not correlate significantly with right atrial or pulmonary arterial pressures but did correlate significantly with both the right ventricular end diastolic volume and right ventricular wall volume measured by magnetic resonance imaging. Oxygen (2 1/min by nasal prongs for 30 minutes) did not change the mean pulmonary arterial pressure or the level of plasma ANP. In 20 patients with an acute exacerbation of COPD plasma ANP levels were higher in those with oedema (302 (185) pg/ml) than in those without oedema (87 (43) pg/ml). Oxygen given for one hour had no effect on plasma levels of ANP. However, plasma ANP levels fell over the first three days during treatment in those with oedema, the fall correlating with the change in body weight. In a further 20 stable patients with hypoxic COPD, those with hypercapnia and previous episodes of oedema had higher levels of plasma ANP (120 (50) pg/ml) than normocapnic patients with no previous oedema (54 (15) pg/ml). CONCLUSIONS--The level of ANP is high in the plasma of patients with COPD, particularly during exacerbations in those with oedema. The association of a high plasma ANP level and volume overload is shown by the fall in ANP levels with treatment of the oedema, and the correlation between levels of ANP and right ventricular end diastolic or wall volumes.     

Gastrointestinal manifestations of chronic granulomatous disease

OBJECTIVE: Chronic granulomatous disease is a rare clinical entity characterized by recurrent infective and inflammatory complications. Patients are usually assigned to specialist centres, but nonspecialist clinicians may be required to treat these patients in the emergency setting. This review serves as a management guide to those clinicians who are faced with patients presenting with gastrointestinal manifestations of chronic granulomatous disease. METHODS: This review is based on a literature search (Medline and NLM PubMed) with manual cross-referencing of all articles related to gastrointestinal chronic granulomatous disease. RESULTS: Gastrointestinal tract involvement is present in most affected patients. Clinical presentation can mimic common surgical complications such as colitis, perianal sepsis, gastric outlet obstruction and liver abscess. A history of recurrent infections during childhood is common. Management involves haematological, microbiological, endoscopic and radiological investigations. Treatment modalities include early aggressive empirical antimicrobial therapy for sepsis, immunomodulation for inflammatory complications and surgical drainage of abscesses. CONCLUSION: Early involvement of a centre with immunological expertise combined with aggressive management of complications significantly improves morbidity and mortality from this rare condition.