Factors that mediate colonization of the human stomach by Helicobacter pylori

Helicobacter pylori(H.pylori)colonizes the stomach of humans and causes chronic infection.The majority of bacteria live in the mucus layer overlying the gastric epithelial cells and only a small proportion of bacteria are found interacting with the epithelial cells.The bacteria living in the gastric mucus may act as a reservoir of infection for the underlying cells which is essential for the development of disease.Colonization of gastric mucus is likely to be key to the establishment of chronic infection.How H.pylori manages to colonise and survive in the hostile environment of the human stomach and avoid removal by mucus flow and killing by gastric acid is the subject of this review.We also discuss how bacterial and host factors may together go some way to explaining the susceptibility to colonization and the outcome of infection in different individuals.H.pylori infection of the gastric mucosa has become a paradigm for chronic infection.Understanding of why H.pylori is such a successful pathogen may help us understand how other bacterial species colonise mucosal surfaces and cause disease.     

Mycobacterial persistence requires the utilization of host cholesterol

A hallmark of tuberculosis is the ability of the causative agent, Mycobacterium tuberculosis, to persist for decades despite a vigorous host immune response. Previously, we identified a mycobacterial gene cluster, mce4, that was specifically required for bacterial survival during this prolonged infection. We now show that mce4 encodes a cholesterol import system that enables M. tuberculosis to derive both carbon and energy from this ubiquitous component of host membranes. Cholesterol import is not required for establishing infection in mice or for growth in resting macrophages. However, this function is essential for persistence in the lungs of chronically infected animals and for growth within the IFN-gamma-activated macrophages that predominate at this stage of infection. This finding indicates that a major effect of IFN-gamma stimulation may be to sequester potential pathogens in a compartment devoid of more commonly used nutrients. The unusual capacity to catabolize sterols allows M. tuberculosis to circumvent this defense and thereby sustain a persistent infection.     

American gastroenterological association consensus development conference on the use of biologics in the treatment of inflammatory bowel disease, June 21-23, 2006

The American Gastroenterological Association (AGA) convened a panel of gastroenterologists expert in the area of inflammatory bowel disease (IBD) that developed this consensus statement based on expert presentations of current scientific knowledge about IBD and through subsequent group discussion. This statement reflects the panel's assessment of medical knowledge available when written. Thus, readers should view this statement in the context of data that will accumulate after its creation. The opinions, conclusions, and recommendations expressed in this report are those of the consensus panel members and may or may not reflect the official opinion of the American Gastroenterological Association Institute. The conference upon which this report is based was funded through an unrestricted educational grant from Abbott Laboratories. Abbott Laboratories representatives did not attend the conference, nor did they participate in any way in the development of this report.     

New Insights in the Pathogenesis of High-Altitude Pulmonary Edema

High-altitude pulmonary edema is a life-threatening condition occurring in predisposed but otherwise healthy individuals. It therefore permits the study of underlying mechanisms of pulmonary edema in the absence of confounding factors such as coexisting cardiovascular or pulmonary disease, and/or drug therapy.There is evidence that some degree of asymptomatic alveolar fluid accumulation may represent a normal phenomenon in healthy humans shortly after arrival at high altitude. Two fundamental mechanisms then determine whether this fluid accumulation is cleared or whether it progresses to HAPE: the quantity of liquid escaping from the pulmonary vasculature and the rate of its clearance by the alveolar respiratory epithelium. The former is directly related to the degree of hypoxia-induced pulmonary hypertension, whereas the latter is determined by the alveolar epithelial sodium transport. Here, we will review evidence that, in HAPE-prone subjects, impaired pulmonary endothelial and epithelial NO synthesis and/or bioavailability may represent a central underlying defect predisposing to exaggerated hypoxic pulmonary vasoconstriction and, in turn, capillary stress failure and alveolar fluid flooding. We will then demonstrate that exaggerated pulmonary hypertension, although possibly a conditio sine qua non, may not always be sufficient to induce HAPE and how defective alveolar fluid clearance may represent a second important pathogenic mechanism.     

Physical and Chemical Characterisation of the Pigments of a 17th-Century Mural Painting in the Spanish Caribbean

The arrival of Spaniards in the Caribbean islands introduced to the region the practice of applying pigments onto buildings. The pigments that remain on these buildings may provide data on their historical evolution and essential information for tackling restoration tasks. In this study, a 17th-century mural painting located in the Cathedral of Santo Domingo on the Hispaniola island of the Caribbean is characterised via UV–VIS–NIR, Raman and FTIR spectroscopy, XRD and SEM/EDX. The pigments are found in the older Chapel of Our Lady of Candelaria, currently Chapel of Our Lady of Mercy. The chapel was built in the 17th century by black slave brotherhood and extended by Spaniards. During a recent restoration process of the chapel, remains of mural painting appeared, which were covered by several layers of lime. Five colours were identified: ochre, green, red, blue and white. Moreover, it was determined that this mural painting was made before the end of the 18th century, because many of the materials used were no longer used after the industrialisation of painting. However, since both rutile and anatase appear as a white pigment, a restoration may have been carried out in the 20th century, and it has been painted white.     

Adenomyoma of the main biliary tract: a real diagnostic trap. Two cases and a review of the literature

Adenomyoma of the biliary tract is a benign neoplasm but its clinical, radiological and intraoperative features can mimic pancreatic or biliary cancer. These similarities may yield to useless pancreatoduodenectomy. We report here two cases of adenomyoma treated by pancreatoduodenectomy. The analysis of these two cases and the review of literature show that radiological and pathological knowledge of this disease, associated with pre and intraoperative evaluation (echoendoscopy-guided biopsy, brushing and intraoperative biopsy) can achieve diagnosis and thus may avoid inappropriate resection. For asymptomatic patient, simple follow-up seems to be the rule. For symptomatic patient endoscopic resection or surgical segmentary resection where appropriate is recommended.     

A new concept of the anatomy of the anal sphincter mechanism and the physiology of defecation

A study, comprising dissection and microscopic examination of the pectinate area with special consideration to anal glands, was performed in 29 cadavers varying from fully mature neonatal deaths to 52 years of age. At the junction of the anal canal proper with the rectal neck, an “anorectal sinus” (a submucosal anal circumferential depression) was identified in 18 specimens; in 6 specimens, the anorectal sinus was replaced by a fibroepithelial band (“anorectal band”); in 5 specimens, the anorectal sinus was absent, and in 3 of the 5 specimens only scattered epithelial cells (“epithelial debris” of the anorectal sinus) were detected. These findings suggest that the anorectal sinus is an embryonic vestige which results from hindgut “invagination” by the proctodeum. Its persistence or partial obliteration would result in the formation of tubular structures which are considered by investigators as anal glands. The sinus may be completely obliterated or may leave behind a submucosal “anorectal band” or scattered “epithelial debris”. Evidence in favor of this new concept is put forward. The role of anorectal sinus, anorectal band, and epithelial debris in the genesis of some idiopathic anal lesions is discussed.     

Spontaneous free perforation of the small intestine in adults

Spontaneous free perforation of the small intestine is uncommon,especially if there is no prior history of visceral trauma.However,free,even recurrent,perforation may complicate a defined and established clinical disorder,such as Crohn’s disease.In addition,free perforation may be the initial clinical presentation of an occult intestinal disorder,such as a lymphoma complicating celiac disease,causing diffuse peritonitis and an acute abdomen.Initial diagnosis of the precise cause may be difficult,but now has been aided by computerized tomographic imaging.The site of perforation may be helpful in defining a cause(e.g.,ileal perforation in Crohn’s disease,jejunal perforation in celiac disease,complicated by lymphoma or collagenous sprue).Urgent surgical intervention,however,is usually required for precise diagnosis and treatment.During evaluation,an expanding list of other possible causes should be considered,even after surgery,as subsequent management may be affected.Free perforation may not only complicate an established intestinal disorder,but also a new acute process(e.g.,caused by different infectious agents)or a longstanding and unrecognized disorder(e.g.,congenital,metabolic and vascular causes).Moreover,new endoscopic therapeutic and medical therapies,including use of emerging novel biological agents,have been complicated by intestinal perforation.Recent studies also support the hypothesis that perforation of the small intestine may be genetically-based with different mutations causing altered connective tissue structure,synthesis and repair.     

Distal aortopulmonary septal defect,aortic origin of the right pulmonary artery,intact ventricular septum,patent ductus arteriosus and hypoplasia of the aortic isthmus: A newly recognized syndrome

The association of distal aortopulmonary septal defect, aortic origin of the right pulmonary artery, intact ventricular septum and Interruption or coarctation of the aortic isthmus has not previously been reported as a syndrome. This combination of anomalies was encountered in five new patients and was previously reported in three. Two patients have undergone surgery with successful results. In contrast to the sagittally oriented conventional proximal aortopulmonary septal defect, the patients in this series had a more distal type of defect, possibly representing a partial persistence of the common arterial trunk. The pulmonary arterial bifurcation may malattach to this undivided truncal segment and, as a result, the right pulmonary artery may be partially or completely shifted into the aorta. This abnormal right pulmonary arterial origin may lead to “steal” from the aortic flow during embryogenesis and to hypoplasia of the aortic arch. This concept is supported by the angiographic observation that the greater the rightward displacement of the right pulmonary artery, the greater the hypoplasia of the arch. The diagnostic angiographic sign is a strikingly high origin of the right pulmonary artery together with aortic arch hypoplasia or atresia. Closure of the aortopulmonary septal defect with implantation of the right pulmonary artery in the pulmonary trunk and repair of the aortic arch anomaly is the recommended surgical treatment.     

Oxygen deprivation and early myocardial contractile failure: a reassessment of the possible role of adenosine triphosphate.

The precise mechanism responsible for early contractile failure after the onset of myocardial anoxia or ischemia has attracted speculation and controversy. The simple and attractive hypothesis that adenosine triphosphate (ATP) deficiency is responsible for this failure has often been dismissed on the basis of claims that there is only a small reduction in cell ATP content at a time when contractile activity is severely reduced. The premise of this article is that the changes in cell ATP content and distribution that theoretically should occur after oxygen depletion may not have been adequately considered and that previous measurements of cell ATP content may not have been carried out at the correct time. Using an isolated rat heart preparation and high speed freeze-clamping techniques it has been possible to demonstrate that a substantial decrease in myocardial ATP and creatine phosphate content occurs after the onset of anoxia but before the onset of contractile failure. Thus, during the first 5 seconds of anoxia contractile activity remains constant whereas ATP decreases by 25 percent and creatine phosphate by 50 percent. Thereafter, contractile failure occurs and the rate of utilization of high energy phosphates declines with the cell content at a plateau or possibly increasing. These results are assessed in the light of the dynamic changes in energy metabolism occurring in early anoxia and suggest that ATP depletion in a specific cell compartment may be the primary trigger for early contractile failure.     

Differential effects of lipids and lyso-lipids on the mechanosensitivity of the mechanosensitive channels MscL and MscS

Mechanosensitive (MS) channels of small (MscS) and large (MscL) conductance are the major players in the protection of bacterial cells against hypoosmotic shock. Although a great deal is known about structure and function of these channels, much less is known about how membrane lipids may influence their mechanosensitivity and function. In this study, we use liposome coreconstitution to examine the effects of different types of lipids on MscS and MscL mechanosensitivity simultaneously using the patch-clamp technique and confocal microscopy. Fluorescence lifetime imaging (FLIM)-FRET microscopy demonstrated that coreconstitution of MscS and MscL led to clustering of these channels causing a significant increase in the MscS activation threshold. Furthermore, the MscL/MscS threshold ratio dramatically decreased in thinner compared with thicker bilayers and upon addition of cholesterol, known to affect the bilayer thickness, stiffness and pressure profile. In contrast, application of micromolar concentrations of lysophosphatidylcholine (LPC) led to an increase of the MscL/MscS threshold ratio. These data suggest that differences in hydrophobic mismatch and bilayer stiffness, change in transbilayer pressure profile, and close proximity of MscL and MscS affect the structural dynamics of both channels to a different extent. Our findings may have far-reaching implications for other types of ion channels and membrane proteins that, like MscL and MscS, may coexist in multiple molecular complexes and, consequently, have their activation characteristics significantly affected by changes in the lipid environment and their proximity to each other.     

Influence of environmental factors on the onset and course of inflammatory bowel disease

Numerous environmental factors have been linked with inflammatory bowel disease. These include smoking, diet, hygiene, drugs, geographical and psychosocial factors. These factors may either increase the risk of or protect against developing this condition and can also affect the course of illness in a positive or negative manner. A number of studies have examined the influence of environmental factors on inflammatory bowel diseases as a whole as well as on ulcerative colitis and Crohn's disease separately. As there are differences in the pathogenesis of ulcerative colitis and Crohn's disease, the effect of environmental factors on their onset and course is not always similar. Some factors have shown a consistent association, while reports on others have been conflicting. In this article we discuss the current evidence on the roles of these factors on inflammatory bowel disease, both as causative/protective agents and as modifiers of disease course.     

Role of the renin-angiotensin system in prostate cancer

Prostate cancer is highly prevalent in Western society, and its early stages can be controlled by androgen ablation therapy. However, the cancer eventually regresses to an androgen-independent state for which there is no effective treatment. The renin-angiotensin system (RAS), in particular the octapeptide angiotensin II, is now recognised to have important effects on growth factor signalling and cell growth in addition to its well known actions on blood pressure, fluid homeostasis and electrolyte balance. All components of the RAS have been recently identified in the prostate, consistent with the expression of a local RAS system in this tissue. This review focuses on the role of the RAS in the prostate, and the possibility that this pathway may be a potential therapeutic target for the treatment of prostate cancer and other prostatic diseases.     

Impairment of ghrelin synthesis in Helicobacter pyloricolonized stomach:New clues for the pathogenesis of H.pylori-related gastric inflammation

Ghrelin,the ligand of growth hormone secretagogue receptor 1a,takes part in several functions of the digestive system,including regulation of appetite,energy homeostasis,gastric acid secretion and motility.Ghrelin has also immunoregulatory properties and is supposed to inhibit some inflammatory pathways that can mediate gastric damage.Interestingly,ghrelin synthesis is reduced in the gastric mucosa of patients with Helicobacter pylori(H.pylori)infection,a worldwide condition inducing a T helper(Th)1/Th17 cell responsedriven gastritis,which may evolve towards gastric atrophy and cancer.In this article,we review the available data on the expression of ghrelin in H.pylori infection and discuss how the defective ghrelin synthesis may contribute to sustain the ongoing inflammatory response in this disease.     

Clinical management of inflammatory bowel disease in the organ recipient

There was estimated a higher incidence of de novo inflammatory bowel disease(IBD)after solid organ transplantation than in the general population.The onset of IBD in the organ transplant recipient population is an important clinical situation which is associated to higher morbidity and difficulty in the medical therapeutic management because of possible interaction between anti-reject therapy and IBD therapy.IBD course after liver transplantation(LT)is variable,but about one third of patients may worsen,needing an increase in medical therapy or a colectomy.Active IBD at the time of LT,discontinuation of 5-aminosalicylic acid or azathioprine at the time of LT and use of tacrolimusbased immunosuppression may be associated with an unfavorable outcome of IBD after LT.Anti-tumor necrosis factor alpha(TNFα)therapy for refractory IBD may be an effective and safe therapeutic option after LT.The little experience of the use of biological therapy in transplanted patients,with concomitant anti-rejection therapy,suggests there be a higher more careful surveillance regarding the risk of infectious diseases,autoimmune diseases,and neoplasms.An increased risk of colorectal cancer(CRC)is present also after LT in IBD patients with primary sclerosing cholangitis(PSC).Anannual program of endoscopic surveillance with serial biopsies for CRC is recommended.A prophylactic colectomy in selected IBD/PSC patients with CRC risk factors could be a good management strategy in the CRC prevention,but it is used infrequently in the majority of LT centers.About 30%of patients develop multiple IBD recurrence and 20%of patients require a colectomy after renal transplantation.Like in the liver transplantation,anti-TNFαtherapy could be an effective treatment in IBD patients with conventional refractory therapy after renal or heart transplantation.A large number of patients are needed to confirm the preliminary observations.Regarding the higher clinical complexity of this subgroup of IBD patients,a close multidisciplinary approach between an IBD dedicated gastroenterologist and surgeon and an organ transplantation specialist is necessary in order to have the best clinical management of IBD after transplantation.     

Mechanism of the interaction of hypertension and hypercholesterolemia in atherogenesis: The effects of antihypertensive agents

Any alteration in the balance between serum lipids, platelets, hemodynamic factors, and the blood vessel wall may lead to the development of atherosclerosis. Hypertension and hypercholesterolemia are two major risk factors that accelerate the development of coronary heart disease. The mechanisms of the interactions of these two risk factors are examined in this paper. First, hypertension may be associated with focal or generalized endothelial injury or dysfunction. The altered endothelial functional integrity may predispose to platelet aggregation and altered vessel wall interaction, which may stimulate proliferation and growth of vascular cells. Second, elevated serum cholesterol levels may accelerate lipid deposition and formation of atherosclerotic plaques. In hypertension the rate of clearance of lipoprotein from the vessel wall may be reduced. Third, the sympathetic nervous system may be involved in both the development of hypertension and the alterations of lipid metabolism. Adrenergic activation, which increases blood pressure may also adversely affect lipid metabolism. This is in part α₁-adrenoceptor mediated. Selective α₁-inhibitors have been found to prevent or reduce atherosclerosis in experimental animals. Selective α₁-inhibitors may act at a number of sites on lipoprotein metabolic pathways to favorably influence serum lipids. Taken together, the relationship between hypertension and atherosclerosis involves complex mechanisms. A complete understanding of the mechanisms is of obvious importance.     

The organic cation transporter-3 is a pivotal modulator of neurodegeneration in the nigrostriatal dopaminergic pathway

Toxic organic cations can damage nigrostriatal dopaminergic pathways as seen in most parkinsonian syndromes and in some cases of illicit drug exposure. Here, we show that the organic cation transporter 3 (Oct3) is expressed in nondopaminergic cells adjacent to both the soma and terminals of midbrain dopaminergic neurons. We hypothesized that Oct3 contributes to the dopaminergic damage by bidirectionally regulating the local bioavailability of toxic species. Consistent with this view, Oct3 deletion and pharmacological inhibition hampers the release of the toxic organic cation 1-methyl-4-phenylpyridinium from astrocytes and protects against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration in mice. Furthermore, Oct3 deletion impairs the removal of the excess extracellular dopamine induced by methamphetamine and enhances striatal dopaminergic terminal damage caused by this psychostimulant. These results may have far-reaching implications for our understanding of the mechanism of cell death in a wide range of neurodegenerative diseases and may open new avenues for neuroprotective intervention.