Anti-tissue transglutaminase antibodies from celiac patients are responsible for trophoblast damage via apoptosis in vitro.

OBJECTIVES: The association between maternal celiac disease (CD) and both reduced fertility and increased risk of adverse pregnancy-related events has been long documented. However, no evidences are available regarding the pathogenic mechanisms of this link. The aim of this study was to determine whether anti-tissue transglutaminase (anti-tTG) antibodies are involved in the damage of trophoblastic cells in vitro. METHODS: Human primary trophoblastic cells, isolated from term placenta, were exposed to anti-tTG immunoglobulin G (IgG) antibodies, both commercially available and separated from sera of three untreated celiac women. The ability of anti-tTG antibodies to bind to trophoblastic cells, invasiveness of placental cells through a layer of extracellular matrix, and the activity of cellular matrix metalloprotease (MMP) and cellular apoptosis were evaluated, as indicators of trophoblast damage, by TdT-mediated dUTP digoxigenin nick end labeling (TUNEL) and annexin V expression. RESULTS: Anti-tTG IgG showed a specific dose- and time-dependent binding to human trophoblast. In addition, trophoblastic cells, after being exposed to anti-tTG IgG antibodies, both commercially available and separated from sera of celiac women, showed an impaired invasiveness, a decreased activity of cellular MMP, and a greater percentage of TUNEL positivity and annexin V positivity. CONCLUSIONS: We showed that the binding of anti-tTG antibodies to trophoblast might represent a key mechanism by which the embryo implantation and pregnancy outcome are impaired in untreated celiac pregnant women. Because healthy trophoblast development is essential for placental and fetal development, these data provide a novel mechanism for CD-induced infertility, early pregnancy loss, and intrauterine growth retardation.

Chest ultrasonography in lung contusion.

STUDY OBJECTIVE: Despite the high prevalence of chest trauma and its high morbidity, lung contusion (LC) often remains undiagnosed in the emergency department (ED). The present study investigates the possible clinical applicability of chest ultrasonography for the diagnosis of LC in the ED in comparison to radiography and CT. MATERIALS AND METHODS: One hundred twenty-one patients admitted to the ED for blunt chest trauma were investigated using ultrasonography by stage III longitudinal scanning of the anterolateral chest wall to detect LC. Data were retrospectively collected in an initial series of 109 patients (group 1) and prospectively in the next 12 patients (group 2). All patients who presented with pneumothorax were excluded. After the ultrasound study, all patients were submitted to chest radiography (CXR) and CT. The sonographic patterns indicative of LC included the following: (1) the alveolointerstitial syndrome (AIS) [defined by increase in B-line artifacts]; and (2) peripheral parenchymal lesion (PPL) [defined by the presence of C-lines: hypoechoic subpleural focal images with or without pleural line gap]. RESULTS: The diagnosis of LC was established by CT scan in 37 patients. If AIS is considered, the sensitivity of ultrasound study was 94.6%, specificity was 96.1%, positive and negative predictive values were 94.6% and 96.1%, respectively, and accuracy was 95.4%. If PPL is alternatively considered, sensitivity and negative predictive values drop to 18.9% and 63.0%, respectively, but both specificity and positive predictive values increased to 100%, with an accuracy of 65.9%. Radiography had sensitivity of 27% and specificity of 100%. CONCLUSIONS: Chest ultrasonography can accurately detect LC in blunt trauma victims, in comparison to CT scan.

The role of H. pylori infection in diabetes.

Helicobacter pylori [H. pylori], one of the most common chronic infections worldwide, is the main etiologic agent of gastritis, peptic ulcer and gastric cancer. Patients with diabetes mellitus are often affected by chronic infections. Many studies have evaluated the prevalence of H. pylori infection in diabetic patients and the possible role of this condition in their metabolic control. Some studies found a higher prevalence of the infection in diabetic patients and a reduced glycaemic control, while others did not support any correlation between metabolic control and H. pylori infection. There are only a few studies on the eradication rate of H. pylori in diabetic patients. Most of these papers concluded that standard antibiotic therapy allows a significantly lower H. pylori eradication rate than is observed in control groups matched for sex and age. Changes in the microvasculature of the stomach with a possible reduction of antibiotic absorption, the presence of gastroparesis and the frequent use of antibiotics for recurrent bacterial infections with the development of resistant strains could be some of the mechanisms underlying this phenomenon. A quadruple therapy may be used as the second line approach with a good eradication rate, even if an antibiotic selected according to a specific H. pylori antibiogram is considered the gold standard in these patients. As regards the gastrointestinal symptoms of H. pylori infected individuals, many studies showed that they are as frequent in patients with type 1 diabetes as in the general population. The incidence of H. pylori recurrence after 12 months follow-up is significantly higher in type 1 diabetic subjects when compared to controls. Reduced lymphocyte activity, neutrophil dysfunction with failure of chemotaxis and a possible reservoir of H. pylori in dental plaque may explain the higher rate of re-infection in these patients.

Cardiopulmonary bypass in man: role of the intestine in a self-limiting inflammatory response with demonstrable bacterial translocation.

BACKGROUND: Cardiopulmonary bypass provokes a systemic inflammatory reaction that, in 1% to 2% of all cases, leads to multiorgan disfunction. The aim of this study was to evaluate the possible role of the intestine in the pathogenesis and development of this reaction. METHODS: Eleven selected patients scheduled for elective coronary artery bypass graft surgery were enrolled in a open, prospective clinical study. Gastric tonometry, chromium-labeled test and double sugar intestinal absorption tests, polymerase chain reaction microbial DNA test, and measurement of cytokines and transcriptional factor (nuclear factor kappaB) activation were performed. RESULTS: During the postoperative period, gastric pH remained stable (range,7.2 to 7.3). The partial pressure for carbon dioxide gradient between the gastric mucosa and arterial blood increased significantly (from 1 to 23 mm Hg), peaking in the sixth postoperative hour. Interleukin 6 increased significantly over basal levels, peaking 3 hours after cardiopulmonary bypass (96.3 versus 24 pg/mL). Nuclear factor kappaB never reached levels higher than those observed after lipopolysaccharide stimulation. Escherichia coli translocation was documented in 10 patients: in eight cases from removal of aortic cross-clamps and in two cases from the first postoperative hour. With respect to basal value (6.4%), the urine collection revealed a significant increase in excretion of the radioisotope during the first 24 hours after surgery (39.1%), although there were no significant variations with the double sugar test. CONCLUSIONS: The results obtained showed a correlation between the damage of the gastrointestinal mucosa, subsequent increased permeability, E coli bacteremia, and the activation of a self-limited inflammatory response in the absence of significant macrocirculatory changes and postoperative complications.