Gastrointestinal carcinoid tumors: cellular biology, molecular expression and physiopathological consequences of an enigmatic neoplasia

Gastrointestinal carcinoid tumors arise from cells of the diffuse neuroendocrine system localized in the digestive trace and represent more than 70% of all carcinoid tumors in humans. The present article reviews the following topics: 1) The biological profile of these tumors (histopathology, cytokine markers, metabolic alterations, storage of neuroamines and hormonal proteins, cytodynamic behavior, and biological behavior according to embryological origin). 2) The etiological circumstances (exceptional hereditary factors, association of gastric carcinoid tumors with autoimmune gastritis, little-known exogenous factors). 3) Pathogenic aspects (persistent mitogenesis of endocrine cells associated with hypergastrinemia, inactivation of some putative tumor suppressor genes, the doubtful participation of oncogenes, autocrine action of some cellular growth-stimulating proteins). 4) The repercussions of certain physiopathological events (peritumoral desmoplastic reaction causing the "mass effect" on the digestive tube, the "kidnapping" of dietary tryptophan by tumoral cells toward an abnormal metabolic pathway; the easy metastatic dissemination coexisting with low tumoral aggressivity, and the release into the bloodstream of stored secretory products leading to "carcinoid syndrome" and some endocrine hyperfunction syndromes. Finally, it should be remembered that gastrointestinal carcinoid tumors represent only a proportion of the neoplasms classified as neuroendocrine tumors.     

Changes in Macrophage Phenotype after Infection of Pigs with Haemophilus parasuis Strains with Different Levels of Virulence

Haemophilus parasuis is a colonizer of healthy piglets and the etiological agent of Glässer''s disease. Differences in virulence among strains of H. parasuis have been widely observed. In order to explore the host-pathogen interaction, snatch-farrowed colostrum-deprived piglets were intranasally infected with 4 strains of H. parasuis: reference virulent strain Nagasaki, reference nonvirulent strain SW114, field strain IT29205 (from a systemic lesion and virulent in a previous challenge), and field strain F9 (from the nasal cavity of a healthy piglet). At different times after infection, two animals of each group were euthanized and alveolar macrophages were analyzed for the expression of CD163, CD172a, SLA I (swine histocompatibility leukocyte antigen I), SLA II, sialoadhesin (or CD169), and CD14. At 1 day postinfection (dpi), virulent strains induced reduced expression of CD163, SLA II, and CD172a on the surfaces of the macrophages, while nonvirulent strains induced increased expression of CD163, both compared to noninfected controls. At 2 dpi, the pattern switched into a strong expression of CD172a, CD163, and sialoadhesin by the virulent strains, which was followed by a steep increase in interleukin 8 (IL-8) and soluble CD163 in serum at 3 to 4 dpi. The early increase in surface expression of CD163 induced by nonvirulent strains went along with higher levels of IL-8 in serum than those induced by virulent strains in the first 2 days of infection. Alpha interferon (IFN-α) induction was observed only in animals infected with nonvirulent strains. Overall, these results are compatible with a delay in macrophage activation by virulent strains, which may be critical for disease production.     

The tumor suppressor SirT2 regulates cell cycle progression and genome stability by modulating the mitotic deposition of H4K20 methylation

The establishment of the epigenetic mark H4K20me1 (monomethylation of H4K20) by PR-Set7 during G₂/M directly impacts S-phase progression and genome stability. However, the mechanisms involved in the regulation of this event are not well understood. Here we show that SirT2 regulates H4K20me1 deposition through the deacetylation of H4K16Ac (acetylation of H4K16) and determines the levels of H4K20me2/3 throughout the cell cycle. SirT2 binds and deacetylates PR-Set7 at K90, modulating its chromatin localization. Consistently, SirT2 depletion significantly reduces PR-Set7 chromatin levels, alters the size and number of PR-Set7 foci, and decreases the overall mitotic deposition of H4K20me1. Upon stress, the interaction between SirT2 and PR-Set7 increases along with the H4K20me1 levels, suggesting a novel mitotic checkpoint mechanism. SirT2 loss in mice induces significant defects associated with defective H4K20me1–3 levels. Accordingly, SirT2-deficient animals exhibit genomic instability and chromosomal aberrations and are prone to tumorigenesis. Our studies suggest that the dynamic cross-talk between the environment and the genome during mitosis determines the fate of the subsequent cell cycle.     

From the Cover: Contrasting drivers of diversity in hosts and parasites across the tropical Andes

Geographic turnover in community composition is created and maintained by eco-evolutionary forces that limit the ranges of species. One such force may be antagonistic interactions among hosts and parasites, but its general importance is unknown. Understanding the processes that underpin turnover requires distinguishing the contributions of key abiotic and biotic drivers over a range of spatial and temporal scales. Here, we address these challenges using flexible, nonlinear models to identify the factors that underlie richness (alpha diversity) and turnover (beta diversity) patterns of interacting host and parasite communities in a global biodiversity hot spot. We sampled 18 communities in the Peruvian Andes, encompassing ∼1,350 bird species and ∼400 hemosporidian parasite lineages, and spanning broad ranges of elevation, climate, primary productivity, and species richness. Turnover in both parasite and host communities was most strongly predicted by variation in precipitation, but secondary predictors differed between parasites and hosts, and between contemporary and phylogenetic timescales. Host communities shaped parasite diversity patterns, but there was little evidence for reciprocal effects. The results for parasite communities contradicted the prevailing view that biotic interactions filter communities at local scales while environmental filtering and dispersal barriers shape regional communities. Rather, subtle differences in precipitation had strong, fine-scale effects on parasite turnover while host–community effects only manifested at broad scales. We used these models to map bird and parasite turnover onto the ecological gradients of the Andean landscape, illustrating beta-diversity hot spots and their mechanistic underpinnings.

Turnover in community composition across space, or “beta diversity,” reflects eco-evolutionary processes that determine range limits of species (1–3). These processes include adaptive specialization on particular habitats, barriers to dispersal, and interactions among species (4–6). Antagonistic interactions between hosts and parasites may have an underappreciated effect on turnover (7), as evidenced by the sensitivity of host populations to novel parasites. For example, introductions of avian malaria (Plasmodium relictum) and avian pox (Avipoxvirus) led to extinctions or range contractions for dozens of endemic Hawaiian honeycreeper species (8). Introduced parasites have also driven shifts in community composition when competing hosts differ in susceptibility to infection (9). While these cases highlight extreme impacts of parasites on host communities, it remains unclear whether host–parasite interactions generally drive turnover in continental faunas, whether such effects are reciprocal or unidirectional, and whether these interactions also impact diversity patterns at regional scales or over evolutionary time.A persistent challenge in studying the factors that underlie community assembly is that turnover is dynamic and exhibits nonlinear variation over space and time (10). As a result, different processes may underlie turnover, depending on the scale at which the community is defined (11–13). For instance, numerous studies have asserted that adaptive specialization on abiotic conditions and barriers to dispersal drive regional turnover patterns while biotic interactions filter communities locally (2, 14). Still, the spatial scales of these various processes are uncertain (11, 15, 16), and empirical tests are complicated by the fact that potential drivers of turnover tend to be spatially autocorrelated (17).To determine the drivers and scale of community turnover in complex systems, we need appropriate, nonlinear analytical tools. Generalized dissimilarity models (GDMs) are an extension of matrix regression that provides two notable innovations: 1) GDMs can incorporate various biotic and abiotic predictors into a single model, and 2) GDMs explicitly model the curvilinear relationship between community dissimilarity and ecological or geographic distance (4, 10, 18). This modeling framework is better suited than linear matrix regression to identifying key factors underlying turnover in complex environments (19–21). In addition, by incorporating phylogenetic measures of community diversity and similarity, we can use GDMs to test how drivers of turnover have varied over evolutionary time (22). Comparing “phylogenetic turnover” to species turnover allows us to distinguish deep-time processes that may restrict the ranges of clades from contemporary processes that may constrain the range limits of individual species (2). For example, evolutionary conservation of traits may exclude entire clades from certain habitats, leading to strong phylogenetic turnover over ecological gradients (3). Alternatively, if traits that underpin environmental associations are evolutionarily labile, species turnover will be higher than phylogenetic turnover and better predicted by ecological variation.The tropical Andes provide an ideal natural laboratory for investigating community turnover in response to biotic and abiotic changes in the environment. Habitable elevational gradients spanning more than 5,000 vertical meters encompass rapid changes in vegetation structure, temperature, atmospheric pressure, ultraviolet (UV) exposure, and precipitation (23, 24). The Andean cordillera generates broad orographic precipitation, but its complex topography also creates a patchwork of rain shadows. Rain-shadowed slopes and valleys fragment the ranges of humid and dry-adapted species, particularly those occurring at higher elevations (25–29). Environmental change across elevational gradients of the Andes is exceptionally rapid compared to change along axes parallel to the cordillera. As a result, spatial distance and environmental difference are decoupled. Pairs of communities separated by the same geographic distance may have similar or contrasting environments. In this way, this landscape provides the opportunity to pinpoint environmental effects on community turnover and distinguish them from the effects of dispersal limitation.The Andes are a global hot spot for species richness and turnover, evolutionary distinctness, and small-ranged species (30–33). Species interactions are thought to be particularly important in shaping Andean community turnover: For example, Andean birds are often highly specialized on particular habitats and resources (13, 34), and competitive exclusion is thought to further limit and reinforce range boundaries (7, 35–37). However, parasitism has received less attention as a driver of turnover compared to competition (35, 37) and bird–plant mutualisms (36, 38, 39). One important group that could affect bird turnover is the hemosporidians (Apicomplexa: Haemosporida), a diverse clade of vector-borne parasites in the genera Haemoproteus, Parahaemoproteus, Plasmodium, and Leucocytozoon (40, 41). These parasites can reduce the fitness of their hosts, even in low-level chronic infections (42), and are thought to have the potential to shape avian biogeographic patterns (40, 43). Hemosporidian communities in turn are thought to be influenced to varying degrees by host community, climate, and barriers to dispersal (44–51), but improved modeling frameworks with new data are needed to reciprocally test the causes of host and parasite turnover across biodiverse, tropical landscapes.In this study, we identified and compared the drivers of diversity in interacting bird and hemosporidian communities of the Peruvian Andes. First, we tested whether similar or different drivers affect host and parasite turnover; second, we tested how drivers of turnover vary with spatial scale; and third, we tested how drivers of turnover have changed over evolutionary time. Then, we used a complementary modeling approach to identify sources of variation in species richness among host and parasite communities, respectively. We used these models to map host and parasite turnover and richness to identify hot spots for faunal overlap and transition, critical zones for biodiversity study and protection.     

Laparoscopic management of intra-abdominal infections: Systematic review of the literature

AIM: To investigate the role of laparoscopy in diagnosis and treatment of intra abdominal infections.METHODS: A systematic review of the literature was performed including studies where intra abdominal infections were treated laparoscopically.RESULTS: Early laparoscopic approaches have become the standard surgical technique for treating acute cholecystitis. The laparoscopic appendectomy has been demonstrated to be superior to open surgery in acute appendicitis. In the event of diverticulitis, laparoscopic resections have proven to be safe and effective procedures for experienced laparoscopic surgeons and may be performed without adversely affecting morbidity and mortality rates. However laparoscopic resection has not been accepted by the medical community as the primary treatment of choice. In high-risk patients, laparoscopic approach may be used for exploration or peritoneal lavage and drainage. The successful laparoscopic repair of perforated peptic ulcers for experienced surgeons, is demonstrated to be safe and effective. Regarding small bowel perforations, comparative studies contrasting open and laparoscopic surgeries have not yet been conducted. Successful laparoscopic resections addressing iatrogenic colonic perforation have been reported despite a lack of literature-based evidence supporting such procedures. In post-operative infections, laparoscopic approaches may be useful in preventing diagnostic delay and controlling the source.CONCLUSION: Laparoscopy has a good diagnostic accuracy and enables to better identify the causative pathology; laparoscopy may be recommended for the treatment of many intra-abdominal infections.     

Accreditation of processes in hepatology

The Spanish Association for the Study of the Liver decided in 2006 to develop a project to assess the quality of the professionals, processes and medical units dealing with the management of patients with liver diseases in Spain. The current article reports the criteria proposed to assess the quality and the accreditation of the processes in hepatology. The processes considered include most patients with liver diseases and the accreditation system designed is highly specific. This document, together with a previous one published in gastroenterología y hepatología concerning the accreditation of the professionals and a third document dealing with the accreditation of liver units that will be published soon, form the basis of the quality assessment of hepatology in our country.