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ABSTRACTChlamydophila pneumoniaeis a pathogen that is involved in acute and chronic respiratory infections and that is associated with asthma and coronary artery diseases. In this study, we evaluated the effects of PEX, a noncatalytic metalloproteinase fragment with integrin-binding activity, against experimental infections caused by C. pneumoniae. Moreover, we investigated the relationships between C. pneumoniaeand αvβ3integrin functions in order to explain the possible mechanism of action of PEX both in vitro and in vivo. For the in vitro experiments, HeLa cells were infected with C. pneumoniaeand treated with either PEX or azithromycin. The results obtained with PEX were not significantly different (P> 0.05) from those achieved with azithromycin. Similar results were also obtained in a lung infection model. Male C57BL/J6 mice inoculated intranasally with 106inclusion-forming units of C. pneumoniaewere treated with either PEX or azithromycin plus rifampin. Infected mice treated with PEX showed a marked decrease in C. pneumoniaecounts versus those for the controls; this finding did not differ significantly (P> 0.05) from the results observed for the antibiotic-treated group. Integrin αvβ3plays an important role in C. pneumoniaeinfection. Blockage of integrin activation led to a significant inhibition of C. pneumoniaeinfection in HeLa cells. Moreover, CHODHFRαvβ3-expressing cells were significantly (P< 0.001) more susceptible to C. pneumoniaeinfection than CHODHFRcells. These results offer new perspectives on the treatment of C. pneumoniaeinfection and indicate that αvβ3could be a promising target for new agents developed for activity against this pathogen.

ABSTRACTThe in vitro and in vivo antichlamydial activities of dexamethasone and beclomethasone alone and in combination with an antibiotic were tested. In vitro, dexamethasone and beclomethasone decreased the number of inclusion-forming units versus the control number (P< 0.001). The combination of glucocorticoids with azithromycin, telithromycin, or levofloxacin was more active than antibiotics used alone (P< 0.001). The combination, tested in a murine Chlamydophila pneumoniaeinfection model, produced similar results.

We compared the diagnostic accuracy of a new immunological marker of celiac sprue (CS), the antijejunum antibody (JAB), with that of antigliadin (AGA) and antiendomysium (EmA) antibodies. One hundred untreated adults with biopsy-proven CS, 52 healthy controls, and 57 patients with inflammatory bowel disease, lymphoma of the small bowel, Whipple's disease, and irritable bowel syndrome were investigated. Only JAB and EmA were detected at a similar titer in all patients with untreated CS but in no controls (100 sensitivity and specificity). Sensitivity of AGA was, respectively, 55 for IgA and 78 for Ig class, with a 100 and 82 specificity. The differences in frequencies between both EmA and JAB with IgA and IgG AGA were highly significant. We conclude that JAB and EmA provide a reliable noninvasive screening test for clinically significant gluten- sensitive enteropathy. The lower cost of IgA-JAB is a major advantage, owing to the different availability of the lower third of the esophagus and jejunum from primates. The sensitivity and specificity of the two tests are almost identical, but we find interpreting EmA easier than JAB especially when the titer is low.

We studied 47 adults (21 men, 26 women), with biopsy-proven celiac sprue and anti-endomysin antibody (EmA) positivity while untreated, to evaluate the usefulness of both serologic markers of celiac sprue [i.e., immunoglobulin A (IgA)-EmA and total Ig-anti-gliadin (AGA) antibodies] and of a detailed dietary inquiry in predicting the mucosal pattern after gluten withdrawal. A second biopsy was repeated 8-30 months after beginning a gluten-free diet, along with EmA and AGA determinations and the dietary inquiry. Both EmA and AGA were appraised by indirect immunofluorescence on monkey esophagus and rat kidney, respectively. Intestinal biopsy was graded according to Cooke's criteria. After gluten withdrawal, intestinal mucosa reverted to normal in only nine patients. Both EmA and AGA showed high positive but low negative predictive values on intestinal histologic outcome. The positive predictive value of admission of dietary lapses was 100%, whereas the negative predictive value was 39.1%. Neither serologic markers nor dietary inquiries are to be regarded as reliable predictors of intestinal outcome after a gluten-free diet. Biopsy remains the best means of ascertaining mucosal recovery.

Compliance with medications is very important in the management of many gastrointestinal disorders in inflammatory bowel disease (IBD), controlled trials have shown the benefit of prophylactic medical treatment in lowering the risk of recurrences. Our aim was to appraise the association between current psychiatric disorders and medication adherence in an unselected consecutive group of outpatients with IBD. In 85 unselected consecutive outpatients with IBD, a professional structured diagnostic interview and a psychiatric assessment, by the Structured Clinical Interview for Diagnostic and Statistical Manual-III-Reviewed, were carried out. In a stepwise regression analysis, compliance, as dependent variable, correlated positively with disease duration and inversely with both disease severity and presence of psychiatric disorders. In patients with IBD, preventive liaison psychiatry interventions seem indicated.

Acquired hemophilia A is a rare and serious autoimmune disease. Morbidity and mortality are associated with advanced age, comorbidities, toxicity of treatment and bleeding severity. Treatment goals are control of the bleeding and eradication of the inhibitor, while treating the underlying condition if it is present.To describe the baseline characteristics of acquired hemophilia A patients and to assess the response to treatment.Between November 1991 and April 2013, 27 patients were diagnosed with acquired hemophilia A (mean age 59, range 21-86; 18 women - 66%) in the Departamento de Hemostasia y Trombosis. Five patients were lost from follow-up. APTT mixing studies with normal plasma (1:1) and time-temperature dependent effect on the APTT were performed for a-FVIII diagnosis. Whenever possible, inhibitor activity was titrated by Bethesda method at diagnosis (BU/mL). Medical records were reviewed to evaluate the initial symptoms, underlying diseases, treatments and outcome.The mean follow-up was 86 weeks (range 1-640). Underlying etiologies included: idiopathic 70.4%, postpartum 14.8%, malignancy 11.1%, autoimmune disease 3.7%. All patients had bleeding at diagnosis. The most frequent sites of bleeding were: muscular 32%, soft tissue 18%, urinary tract 9%, gastrointestinal tract 6%; being from multiple sites in 9%. At diagnosis, the mean value for FVIII was 6% (range 1-40), and inhibitor titer 220 BU/mL (range 2.2-1173). Initial therapeutic scheme included glucocorticoids in 97% of the patients, 13 in monotherapy (mean age 53 years ± 19), 13 with cyclophosphamide (63 years ± 18) (p= ns), and human immunoglobulin in 1 patient. This last patient died after 1 week of diagnosis due to uncontrolled gastrointestinal bleeding (previous to the era of rVIIa). As a second-line therapy, rituximab was used in 3 patients.Sixty-three (63%) patients achieved complete response (CR) (inhibitor titer < 0.6 BU/mL without bleeding episodes), and 23% achieved partial response (PR) (reduction in inhibitor titer > 50% without bleeding episodes), without differences between monotherapy or combined. Overall, women responded more frequently than men (93.3% vs. 71.4%, p= ns). All patients that received rituximab achieved CR.In this study, the overall response rate was higher than 80%. In most cases, the disease has a prolonged course like other autoimmune diseases, with remissions and relapses.No relevant conflicts of interest to declare.

Acquired hemophilia A is a rare and serious autoimmune disease. Morbidity and mortality are associated with advanced age, comorbidities, toxicity of treatment and bleeding severity. Treatment goals are control of the bleeding and eradication of the inhibitor, while treating the underlying condition if it is present.

BACKGROUND: Infection with different genotypes of virulent Helicobacter pylori strains (cytotoxin-associated gene A [CagA]-and/or vacuolating cytotoxin A [VacA]-positive) can play a role in the development of atrophic gastritis, duodenal ulcer (DU) and gastric cancer (GC).OBJECTIVE: To determine whether patients with GC and H pylori-negative histological staining had previously been infected with H pylori CagA- and/or VacA-positive virulent strains.METHODS: Twenty-three GC patients with a mean (± SD) age of 68.14±9.8 years who tested H pylori-negative on histological staining took part in the study. Three control groups were included. The first group comprised 19 patients with past H pylori infection and DUs eradicated 10 years earlier, with a mean age of 58±18.2 years. H pylori-negative status for this group was determined every year with Giemsa staining, and follow-up testing occured 120±32 months (mean ± SD) after therapy. The subsequent control groups included 20 asymptomatic children, with a mean age of 7±4.47 years, and with H pylori-negative fecal tests; the final group contained 30 patients without clinical symptoms of H pylori infection, with a mean age of 68±11.6 years, who tested H pylori-negative by histological staining.RESULTS: Prevalence of CagA and VacA seropositivity, respectively was 82.6% and 73.91% in GC patients; 84.2% and 84.2% in H pylori-negative DU patients; 25% and 5% in H pylori-negative children; and 36.6% and 16.6% in the patients without clinical symptoms on histological staining. CagA and VacA antibody positivity was not significantly different between GC patients and patients with DUs that had been eradicated 10 years earlier. Significant positivity was found between the children’s group and the H pylori-negative (with past DUs) group (P<0.001). A statistically significant difference was found in age between groups (P<0.03).CONCLUSIONS: Patients with GC, even when H pylori-negative at the time of the present study, may have been infected by H pylori before the onset of the disease, as confirmed by CagA and VacA seropositivity. These data reinforce the hypothesis that H pylori may be a direct carcinogenic agent of GC.