Síndrome de tako-tsubo con severa acalasia / Tako-tsubo cardiomyopathy triggered by severe achalasia

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Increased proteasome-mediated degradation of occludin in irritable bowel syndrome.

OBJECTIVES: Proteasome-mediated protein degradation may contribute to the regulation of intestinal inflammation. At the same time, low-grade inflammation and increased intestinal permeability seem to be involved in the pathophysiology of irritable bowel syndrome (IBS). Thus, we aimed to evaluate proteasome composition and activities in colonic mucosa of IBS patients and its putative pathogenic role. METHODS: Proteasome activities and proteasome subunit expression were measured in colonic mucosa of IBS, Crohn's disease (CD), and control patients by fluorometric assays and western blot, respectively. Expression of inhibitor of kappa B factor (IkappaB alpha) and occludin, a tight junction protein, was also evaluated in colonic biopsies. The degradation of recombinant occludin incubated with protein extracts from colonic mucosa was evaluated in the presence or absence of proteasome inhibitor, MG132. RESULTS: Proteasome trypsin-like activity was increased in IBS patients compared with CD and controls, whereas chymotrypsin-like activity was upregulated in CD patients only. Caspase-like activity was reduced both in IBS and CD patients. IkappaB alpha expression was similar between IBS and controls. In contrast, occludin expression was lower in IBS than in controls, but occludin mRNA level was similar. Protein extracts from IBS patients but not from controls degraded recombinant occludin (20% over 160 min), which was blocked by MG132. Although mast cell number was increased in IBS patients, no correlation was found between this number and proteasome alterations. CONCLUSIONS: Our study shows that proteasome alterations are present in the colonic mucosa of IBS patients and may contribute to the pathophysiology of IBS by increasing occludin degradation.

Severe ulcerative colitis: present medical treatment strategies.

A total of 15-19% of ulcerative colitis patients have a severe attack at some time during their illness. As a consequence of its high associated mortality and morbidity rates, a close collaboration between gastroenterologists and surgeons in their management is mandatory, in order to define, as best as possible, the timing of surgery (i.e., colectomy) when patients fail to respond to medical treatment or worsen despite optimal medical treatment. The first step in medical treatment consists of using intravenous corticosteroids as they have been demonstrated to reduce drastically the mortality rates. However, at 1 year approximately 25% of patients become corticosteroid dependent and 30% require colectomy, which can consistently affect their quality of life. Therefore, intravenous ciclosporin has been proposed as a rescue therapy, with a further improvement of short-term efficacy and reduction of surgery requirement. Nevertheless, its use is associated with a risk of toxicity and intravenous ciclosporin is not easy to use in non-specialised centres. In addition, long-term studies suggest that colectomy is often only delayed and relapse frequent. Consequently, some authors evaluate the potential use of infliximab. Available data are encouraging, reporting a significant short-term reduction in colectomy rate. Nevertheless, additional trials are required to better define the more effective and safe treatment option(s), for both the short- and long-term, in this patient setting; a question addressed in ongoing trials.

[Nutritional therapy in inflammatory bowel disease]. / Traitements nutritionnels au cours des MICI: où en est-on?

Protein-energy malnutrition and specific nutrient deficiencies are common in inflammatory bowel diseases (IBD), more particularly in Crohn's disease. In adults, the use of artificial nutrition is indicated in the event of malnutrition, short bowel syndrome, or IBD refractory to all other treatments. In children, enteral nutrition has a place as first-line treatment to avoid side effects of corticosteroids on growth. The use, as a therapeutic tool, of specific nutrients (n-3 fatty acids, glutamine, antioxydant vitamins and minerals, TGF-beta, probiotics...) seems interesting at the pathophysiological level. Nevertheless, these nutrients are still under evaluation and there are not enough available studies to recommend them in clinical routine. A very promising solution is the use of probiotics for the treatment of refractory pouchitis.

Semi-elemental formula or polymeric formula: is there a better choice for enteral nutrition in acute pancreatitis? Randomized comparative study.

BACKGROUND: Jejunal nutrition is recommended during acute pancreatitis. The use of semi-elemental formulas presents several theoretical advantages over polymeric formulas, but their clinical value has been poorly documented. Our aim was to evaluate in patients with acute pancreatitis the effect of enteral nutrition by a semi-elemental formula compared with a polymeric formula. METHODS: A randomized prospective pilot study, stratified according to severity, was performed in 30 consecutive patients with acute pancreatitis requiring jejunal nutrition. The semi-elemental group received 35 kcal/kg/d of Peptamen (n = 15), and the polymeric group received the same quantity of Sondalis-Iso (n = 15). Tolerance was evaluated after 7 days of enteral nutrition (D7) on visual analog scale (VAS), stool frequency, and 24-hour steatorrhea/creatorrhea. Outcome was evaluated by weight loss, length of hospital stay, and infection rate. RESULTS: Results were calculated as mean +/- SEM, t-test, or chi2. Patients of the 2 groups were comparable in terms of age, gender, and severity. Tolerance was good in both groups (semi-elemental vs polymeric: VAS, 7.4 +/- 0.6 vs 7.1 +/- 0.6, not significant (NS); number of stools per 24 hours, 1.7 +/- 0.4 vs 1.8 +/- 0.4, NS). Steatorrhea and creatorrhea were lower than normal in both groups. In semi-elemental group, the length of hospital stay was shorter (23 +/- 2 vs 27 +/- 1, p = .006) and weight loss was less marked (1 +/- 1 vs 2 +/- 0, p = .01). One patient in semi-elemental group and 3 patients in polymeric group developed an infection (NS). CONCLUSIONS: Semi-elemental and polymeric nutrition are very well tolerated in patients with acute pancreatitis. Nutrition with a semi-elemental formula supports the hypothesis of a more favorable clinical course than nutrition with a polymeric formula, but this conclusion needs to be established in larger adequately powered clinical trials.

Protease-activated receptors: potential therapeutic targets in irritable bowel syndrome?

Protease-activated receptors (PARs) are a family of four G-protein-coupled receptors (PAR-1 to PAR-4) activated by the proteolytic cleavage of their N-terminal extracellular domain. This activation first involves the recognition of the extracellular domain by proteases, such as thrombin, but also trypsin or tryptase which are particularly abundant in the gastrointestinal tract, both under physiological circumstances and in several digestive diseases. Activation of PARs, particularly of PAR-1 and -2, modulates intestinal functions, such as gastrointestinal motility, visceral nociception, mucosal inflammatory response, and epithelial functions (intestinal secretion and permeability). As these physiological properties have been shown to be altered in various extents and combinations in different clinical presentations of irritable bowel syndrome, PARs appear as putative targets for future therapeutic intervention in these patients.

Fulminant hepatitis during self-medication with hydroalcoholic extract of green tea.

Despite an ancient reputation for potential phytotherapeutic effects and innocuity, traditional herbal medicine has previously been implicated in severe adverse events. Exolise is an 80% ethanolic dry extract of green tea (Camellia sinensis) standardized at 25% catechins expressed as epigallocatechin gallate, containing 5-10% caffeine. It has been available in France, Belgium, Spain and the United Kingdom since 1999, as an adjuvant therapy for use in weight loss programmes. In various studies, green tea has to date been considered useful for its potential hepatic protective properties. In this study, we report a case of fulminant hepatitis during self-medication with Exolise, requiring liver transplantation.

[Disseminated strongyloidiasis associated with pulmonary fibrosis and gastrointestinal bleeding]. / Anguillulose maligne associée à une fibrose pulmonaire et une hémorragie digestive.

Strongyloidiasis is a parasitic disease that can be lethal in immunosuppressed patients especially if lung fibrosis is associated, which has been rarely reported. We report the case of a patient treated with corticosteroids for pulmonary fibrosis who developed disseminated strongyloidiasis revealed by massive gastrointestinal bleeding. Diagnosis was based on histological analysis of gastrointestinal biopsies and broncho-alveolar lavage. Treatment improved digestive features as well as respiratory function.