Alpha-1-antitrypsin deficiency (carrier) as possible risk factor for development of colonic diverticula. A multicentre prospective case-control study: the ALADDIN study.

AIM: Connective tissue changes due to ageing or diseases leading to changes in the colonic wall are one theory for the development of diverticula. Alpha-1-antitrypsin (A1AT), a protease inhibitor that protects connective tissue, possibly plays a role in the aetiology of diverticulosis. The aim of this study was to explore associations between the development of diverticula and A1AT deficiency. METHODS: This was a multicentre prospective case-control study. A total of 221 patients aged ≥ 60 years with acute abdominal pain undergoing abdominal CT were included and analysed. Patients with diverticula were defined as the research group, patients without diverticula as controls. Genotype analysis for A1AT deficiency was performed. RESULTS: Twenty-six of 221 (11.8%) patients were diagnosed with (being a carrier of) A1AT deficiency. A non-significant difference in prevalence between patients with and without diverticula was found, 20 (13.9%) of 144 vs 6 (7.8%) of 77, respectively, with a crude OR of 1.9 (95% CI 0.7-5.0; P = 0.186) and after adjustment for confounders an adjusted OR of 1.5 (95% CI 0.5-4.0; P = 0.466). A non-significant difference in 30-day mortality rate from acute diverticulitis between A1AT deficient patients (or carriers) and those without was observed: two (22.2%) of nine patients with A1AT deficiency vs 1 (1.8%) of 55 without. CONCLUSION: We found no convincing evidence that A1AT deficiency plays a role in the aetiology of diverticulitis, although deficient patients and carriers had a higher mortality when experiencing diverticulitis. Diverticulitis is a multifactorial disease and larger numbers may be needed to explore the role of A1AT deficiency among other contributing factors.

Prevalence of alpha-1-antitrypsin deficiency carriers in a population with and without colonic diverticula. A multicentre prospective case-control study: the ALADDIN study.

PURPOSE: The underling pathophysiological mechanisms that cause the formation of colonic diverticula (diverticulosis) remain unclear. Connective tissue changes due to ageing that cause changes in collagen structure of the colonic wall is one theory. Alpha-1-antitrypsin (A1AT) is a protease inhibitor known to protect connective tissue in other organs. Associations between (carriers of) A1AT deficiency and the development of colonic diverticula will be the main focus of this study. METHODS: A multicentre prospective case-controlled study. In total, 230 patients ≥ 60 years with acute abdominal pain undergoing an abdominal computed tomography (CT) will be included. The research group consists of patients with diverticulosis and/or diverticulitis; controls are patients without diverticula (0 to ≤ 5 diverticula). Genotype analysis for A1AT deficiency will be performed. RATIONALE: Hypothetically, connective tissue changes, in particular related to (carriers of) A1AT deficiency, can contribute to the development of diverticula and diverticulitis. We expect to find a higher prevalence of A1AT carriers in patients with diverticulosis compared to patients without diverticulosis. Having diverticulosis does not affect the general health of these individuals per se, when asymptomatic. Once an association is found, present findings can be the basis for a second study to assess the risk of developing acute diverticulitis and its disease course in carriers of A1AT deficiency. Because a large cohort is needed in the latter, we shall first perform a pilot study to investigate the likelihood of the primary hypothesis. TRIAL REGISTRATION: Netherlands Trial register, NTR6251, NL55016.094.15.

Enhancement of coral calcification via the interplay of nickel and urease.

Corals are the main reef builders through the formation of calcium carbonate skeletons. In recent decades, coral calcification has however been impacted by many global (climate change) and local stressors (such as destructive fishing practices and changes in water quality). In this particular context, it is crucial to identify and characterize the various factors that promote coral calcification. We thus performed the first investigation of the effect of nickel and urea enrichment on the calcification rates of three coral species. These two factors may indeed interact with calcification through the activity of urease, which catalyzes the hydrolysis of urea to produce inorganic carbon and ammonia that are involved in the calcification process. Experiments were performed with the asymbiotic coral Dendrophyllia arbuscula and, to further assess if urea and/or nickel has an indirect link with calcification through photosynthesis, results were compared with those obtained with two symbiotic corals, Acropora muricata and Pocillopora damicornis, for which we also measured photosynthetic rates. Ambient and enriched nickel (0.12 and 3.50 µg L-1) combined with ambient and enriched urea concentrations (0.26 and 5.52 µmol L-1) were tested during 4 weeks in aquaria. We demonstrate in the study that a nickel enrichment alone or combined with a urea enrichment strongly stimulated urea uptake rates of the three tested species. In addition, this enhancement of urea uptake and hydrolysis significantly increased the long-term calcification rates (i.e. growth) of the three coral species investigated, inducing a 1.49-fold to 1.64-fold increase, respectively for D. arbuscula and P. damicornis. Since calcification was greatly enhanced by nickel in the asymbiotic coral species - i.e. in absence of photosynthesis - we concluded that the effect of increased urease activity on calcification was mainly direct. According to our results, it can be assumed that corals in some fringing reefs, benefiting from seawater enriched in nickel may have advantages and might be able to use urea more effectively as a carbon and nitrogen source. It can also be suggested that urea, for which hotspots are regularly measured in reef waters may alleviate the negative consequences of thermal stress on corals.

Photophysiology and daily primary production of a temperate symbiotic gorgonian.

Gorgonians are one of the most important benthic components of tropical and temperate areas, and play a fundamental role as ecosystem engineers. Although global warming and pollution increasingly threaten them, the acquisition of nutrients, which is a key process in fitness and stress resistance, has been poorly investigated in such species. This study has thus used an advanced in situ incubation chamber for the first time with gorgonians, to assess the daily acquisition of nutrients and the photophysiology of the Mediterranean symbiotic species, Eunicella singularis. The xanthophyll cycle was assessed in parallel. This work has revealed that E. singularis presents a different functioning than the Mediterranean symbiotic corals. This gorgonian indeed relies on both autotrophy and heterotrophy in summer to optimize its energetic budget, while corals mainly shift to autotrophy for their respiratory needs and tissue growth. In addition, although E. singularis lives in the same depths/locations, and harbours the same symbiont genotype than the corals, the photosynthetic performances of their respective symbionts are significantly different. Indeed, E. singularis acquired 2-3 times less autotrophic carbon from its symbionts than corals, but maintained a positive carbon budget by reducing respiration rates, and by presenting maximal photosynthetic rates throughout the day, suggesting a very efficient light utilization. Almost no photoinhibition was observed under very high light levels, because of the induction of a xanthophyll photoprotection process. These results help understanding why gorgonians often dominate many benthic ecosystems.

Serum response of hepatocyte growth factor, insulin-like growth factor-I, interleukin-6, and acute phase proteins in patients with colorectal liver metastases treated with partial hepatectomy or cryosurgery.

BACKGROUND/AIMS: The aim of the study was to compare the serum response of regeneration factors and acute phase proteins in patients treated with partial hepatectomy or cryosurgery. METHODS: The responses of serum hepatocyte growth factor (HGF), insulin-like growth factor-I (IGF-I) (free and total), interleukin-6 (IL-6) and the acute phase proteins, C-reactive protein (CRP) and serum amyloid A (SAA) were examined in patients with colorectal liver metastases treated with partial hepatectomy (n = 14) or cryosurgery (n = 10). RESULTS: In both groups, IL-6 peak levels at the end of the operation were followed by peak levels at day 1 for HGF and CRP. SAA peak levels occurred on day 1 (hepatectomy group) and on day 4 (cryo group). The total HGF, IGF-I, and IL-6 responses were comparable in both groups. CRP and SAA responses were higher in the patients treated with cryosurgery than in patients after hepatectomy. Free IGF-I trough levels were lower in partial hepatectomy patients than in cryosurgery patients. CONCLUSIONS: In patients with colorectal liver metastases the responses of the regenerating factors HGF, IGF-I, and IL-6 are comparable to those in patients treated with partial hepatectomy. Upregulation of acute phase protein production is higher in patients after cryosurgery than in patients after partial hepatectomy.