Astrocytes are specialized glial cells that outnumber neurons by over fivefold. They contiguously tile the entire central nervous system (CNS) and exert many essential complex functions in the healthy CNS. Astrocytes respond to all forms of CNS insults through a process referred to as reactive astrogliosis, which has become a pathological hallmark of CNS structural lesions. Substantial progress has been made recently in determining functions and mechanisms of reactive astrogliosis and in identifying roles of astrocytes in CNS disorders and pathologies. A vast molecular arsenal at the disposal of reactive astrocytes is being defined. Transgenic mouse models are dissecting specific aspects of reactive astrocytosis and glial scar formation in vivo. Astrocyte involvement in specific clinicopathological entities is being defined. It is now clear that reactive astrogliosis is not a simple all-or-none phenomenon but is a finely gradated continuum of changes that occur in context-dependent manners regulated by specific signaling events. These changes range from reversible alterations in gene expression and cell hypertrophy with preservation of cellular domains and tissue structure, to long-lasting scar formation with rearrangement of tissue structure. Increasing evidence points towards the potential of reactive astrogliosis to play either primary or contributing roles in CNS disorders via loss of normal astrocyte functions or gain of abnormal effects. This article reviews (1) astrocyte functions in healthy CNS, (2) mechanisms and functions of reactive astrogliosis and glial scar formation, and (3) ways in which reactive astrocytes may cause or contribute to specific CNS disorders and lesions.

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Astrocytes: biology and pathology

Important progress has been made in the management of Helicobacter pylori infection and in this fifth edition of the Maastricht Consensus Report, key aspects related to the clinical role of H. pylori were re-evaluated in 2015. In the Maastricht V/Florence Consensus Conference, 43 experts from 24 countries examined new data related to H. pylori in five subdivided workshops: (1) Indications/Associations, (2) Diagnosis, (3) Treatment, (4) Prevention/Public Health, (5) H. pylori and the Gastric Microbiota. The results of the individual workshops were presented to a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in the various clinical scenarios.

https://gut.bmj.com/content/gutjnl/66/1/6.full.pdf

Management of Helicobacter pylori infection—the Maastricht V/Florence Consensus Report

Hypoxia, a characteristic feature of locally advanced solid tumors, has emerged as a pivotal factor of the tumor (patho-)physiome since it can promote tumor progression and resistance to therapy. Hypoxia represents a “Janus face” in tumor biology because (a) it is associated with restrained proliferation, differentiation, necrosis or apoptosis, and (b) it can also lead to the development of an aggressive phenotype. Independent of standard prognostic factors, such as tumor stage and nodal status, hypoxia has been suggested as an adverse prognostic factor for patient outcome. Studies of tumor hypoxia involving the direct assessment of the oxygenation status have suggested worse disease-free survival for patients with hypoxic cervical cancers or soft tissue sarcomas. In head & neck cancers the studies suggest that hypoxia is prognostic for survival and local control. Technical limitations of the direct O2 sensing technique have prompted the use of surrogate markers for tumor hypoxia, such as hypoxia-related endogenous proteins (e.g., HIF-1α, GLUT-1, CA IX) or exogenous bioreductive drugs. In many—albeit not in all—studies endogenous markers showed prognostic significance for patient outcome. The prognostic relevance of exogenous markers, however, appears to be limited. Noninvasive assessment of hypoxia using imaging techniques can be achieved with PET or SPECT detection of radiolabeled tracers or with MRI techniques (e.g., BOLD). Clinical experience with these methods regarding patient prognosis is so far only limited. In the clinical studies performed up until now, the lack of standardized treatment protocols, inconsistencies of the endpoints characterizing the oxygenation status and methodological differences (e.g., different immunohistochemical staining procedures) may compromise the power of the prognostic parameter used.

Hypoxia in cancer: significance and impact on clinical outcome

Although gastric adenocarcinoma is associated with the presence of Helicobacter pylori in the stomach, only a small fraction of colonized individuals develop this common malignancy. H. pylori strain and host genotypes probably influence the risk of carcinogenesis by differentially affecting host inflammatory responses and epithelial-cell physiology. Understanding the host-microbial interactions that lead to neoplasia will improve cancer-targeted therapeutics and diagnostics, and provide mechanistic insights into other malignancies that arise within the context of microbially initiated inflammatory states.

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Helicobacter pylori and gastrointestinal tract adenocarcinomas

Recent studies have suggested that the intestinal microbiome plays an important role in modulating risk of several chronic diseases, including inflammatory bowel disease, obesity, type 2 diabetes, cardiovascular disease, and cancer. At the same time, it is now understood that diet plays a significant role in shaping the microbiome, with experiments showing that dietary alterations can induce large, temporary microbial shifts within 24 h. Given this association, there may be significant therapeutic utility in altering microbial composition through diet. This review systematically evaluates current data regarding the effects of several common dietary components on intestinal microbiota. We show that consumption of particular types of food produces predictable shifts in existing host bacterial genera. Furthermore, the identity of these bacteria affects host immune and metabolic parameters, with broad implications for human health. Familiarity with these associations will be of tremendous use to the practitioner as well as the patient.

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Influence of diet on the gut microbiome and implications for human health.

Aim To examine the impact of gut microbiota on non alcoholic fatty liver disease (NAFLD) pathogenesis. Data synthesis Emerging evidence suggests a strong interaction between gut microbiota and liver. Receiving approximately 70% of its blood supply from the intestine, the liver represents the first line of defence against gut-derived antigens. Intestinal bacteria play a key role in the maintenance of gut–liver axis health. Disturbances in the homeostasis between bacteria- and host-derived signals at the epithelial level lead to a break in intestinal barrier function and may foster “bacterial translocation”, defined as the migration of bacteria or bacterial products from the intestinal lumen to mesenteric lymph nodes or other extraintestinal organs and sites. While the full repertoire of gut-derived microbial products that reach the liver in health and disease has yet to be explored, the levels of bacterial lipopolysaccharide, a component of the outer membrane of Gram-negative bacteria, are increased in the portal and/or systemic circulation in several types of chronic liver diseases. Derangement of the gut flora, particularly small intestinal bacterial overgrowth, occurs in a large percentage (20–75%) of patients with chronic liver disease. In addition, evidence implicating the gut–liver axis in the pathogenesis of metabolic liver disorders has accumulated over the past ten years. Conclusions Complex metabolic diseases are the product of multiple perturbations under the influence of triggering factors such as gut microbiota and diet, thus, modulation of the gut microbiota may represent a new way to treat or prevent NAFLD.

Gut--liver axis: the impact of gut microbiota on non alcoholic fatty liver disease.

State of the Art: Gastric can- cer (GC) is still a major health problem world- wide due to its frequency, poor prognosis and limited treatment options. At present prevention is likely to be the most effective means of reduc- ing the incidence and mortality from this dis- ease. The most important etiological factors im- plicated in gastric carcinogenesis are diet and Helicobacter pylori (H. pylori) infection. High intake of salted, pickled or smoked foods, as well as dried fish and meat and refined carbohy- drates significantly increased the risk of develop- ing GC while fibers, fresh vegetables and fruit were found to be inversely associated with GC risk. Epidemiological investigations (retrospective, case-control and prospective) and several meta- analyses have demonstrated that concurrent or previous H. pylori infection is associated with an increased risk of GC in respect to uninfected peo- ple. H. pylori colonizes gastric mucosa where it induces a complex inflammatory and immune re- action that on time leads to a severe mucosal damage i.e., atrophy, intestinal metaplasia (IM) and dysplasia. The risk of GC is closely related to the grade and extension of gastric atrophy, IM and dysplasia. Perspectives and Conclusions: Today a plausi- ble program for GC prevention means: (1) a correct dietary habit since childhood increasing vegeta- bles and fruit intake, (2) a decrease of H. pylori spread improving family and community sanitation and hygiene, (3) a search and treat H. pylori strate- gy in offspring of GC, (4) a search and treat H. py- lori strategy in patients with chronic atrophic gas- tritis and intestinal metaplasia (IM), (5) a careful en- doscopic and histologic follow-up if precancerous lesions persist irrespective of H. pylori eradication.

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Risk factors in gastric cancer.

The harmful use of alcohol is a worldwide problem. It has been estimated that alcohol abuse represents the world's third largest risk factor for disease and disability; it is a causal factor of 60 types of diseases and injuries and a concurrent cause of at least 200 others. Liver is the main organ responsible for metabolizing ethanol, thus it has been considered for long time the major victim of the harmful use of alcohol. Ethanol and its bioactive products, acetaldehyde-acetate, fatty acid ethanol esters, ethanol-protein adducts, have been regarded as hepatotoxins that directly and indirectly exert their toxic effect on the liver. A similar mechanism has been postulated for the alcohol-related pancreatic damage. Alcohol and its metabolites directly injure acinar cells and elicit stellate cells to produce and deposit extracellular matrix thus triggering the "necrosis-fibrosis" sequence that finally leads to atrophy and fibrosis, morphological hallmarks of alcoholic chronic pancreatitis. Even if less attention has been paid to the upper and lower gastrointestinal tract, ethanol produces harmful effects by inducing: (1) direct damaging of the mucosa of the esophagus and stomach; (2) modification of the sphincterial pressure and impairment of motility; and (3) alteration of gastric acid output. In the intestine, ethanol can damage the intestinal mucosa directly or indirectly by altering the resident microflora and impairing the mucosal immune system. Notably, disruption of the intestinal mucosal barrier of the small and large intestine contribute to liver damage. This review summarizes the most clinically relevant alcohol-related diseases of the digestive tract focusing on the pathogenic mechanisms by which ethanol damages liver, pancreas and gastrointestinal tract.

Alcoholic disease: Liver and beyond

Background

: The treatment of angiodysplasia and watermelon stomach, vascular abnormalities implicated in gastrointestinal bleeding of obscure origin, is a major clinical problem.



Aim

: To determine the efficacy of octreotide in patients with long-standing gastrointestinal bleeding due to acquired angiodysplasia and watermelon stomach, resistant to previous treatments and not suitable for surgery because of old age and/or concomitant disorders.



Patients and methods

: We treated 17 patients (seven had isolated angiodysplasia, seven had multiple upper and lower gastrointestinal angiodysplasia, and three had watermelon stomach) with octreotide (0.1 mg subcutaneous t.d.s. for 6 months). Six of the patients had liver cirrhosis, one had Glanzmann-type platelet derangement, two had cardiovascular diseases and one had chronic uraemia.



Results

: Octreotide treatment stopped bleeding in 10 patients. A transient improvement was observed in four, who needed subsequent cyclical retreatment to correct low haemoglobin levels. No effect was observed in three, probably due to the severity of the concomitant disorders.



Conclusions

: Octreotide is a safe drug that may be useful to control the recurrent gastrointestinal bleeding due to acquired angiodysplasia and watermelon stomach, especially in patients who are not candidates for surgery due to old age and/or concomitant disorders.

https://onlinelibrary.wiley.com/doi/pdf/10.1046/j.1365-2036.1999.00647.x

The efficacy of octreotide therapy in chronic bleeding due to vascular abnormalities of the gastrointestinal tract.

Background and aims Antimicrobial drug resistance is a major cause of the failure of Helicobacter pylori eradication and is largely responsible for the decline in eradication rate. Quadruple therapy has been suggested as a first-line regimen in areas with clarithromycin resistance rate >15%. This randomised trial aimed at evaluating the efficacy of a levofloxacin-containing sequential regimen in the eradication of H pylori -infected patients in a geographical area with >15% prevalence of clarithromycin resistance versus a clarithromycin-containing sequential therapy. Methods 375 patients who were infected with H pylori and naive to treatment were randomly assigned to one of the following treatments: (1) 5 days omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by 5 days omeprazole 20 mg twice daily + clarithromycin 500 mg twice daily + tinidazole 500 mg twice daily; or (2) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 250 mg twice daily + tinidazole 500 mg twice daily; or (3) omeprazole 20 mg twice daily + amoxicillin 1 g twice daily followed by omeprazole 20 mg twice daily + levofloxacin 500 mg twice daily + tinidazole 500 mg twice daily. Antimicrobial resistance was assessed by the E-test. Efficacy, adverse events and costs were determined for each group. Results Eradication rates in the intention-to-treat analyses were 80.8% (95% CI, 72.8% to 87.3%) with clarithromycin sequential therapy, 96.0% (95% CI, 90.9% to 98.7%) with levofloxacin-250 sequential therapy, and 96.8% (95% CI, 92.0% to 99.1%) with levofloxacin-500 sequential therapy. No differences in prevalence of antimicrobial resistance or incidence of adverse events were observed between groups. Levofloxacin-250 therapy was cost-saving compared with clarithromycin sequential therapy. Conclusion In an area with >15% prevalence of clarithromycin resistant H pylori strains, a levofloxacin-containing sequential therapy is more effective, equally safe and cost-saving compared to a clarithromycin-containing sequential therapy.

https://gut.bmj.com/content/gutjnl/59/11/1465.full.pdf

Alba Rocco

Papers

Gut--liver axis: the impact of gut microbiota on non alcoholic fatty liver disease.

Risk factors in gastric cancer.

Alcoholic disease: Liver and beyond

The efficacy of octreotide therapy in chronic bleeding due to vascular abnormalities of the gastrointestinal tract.

Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial