The findings of this study indicate that the recommendations of the International Society of Urological Pathology are a valuable refinement of the standard Gleason grading system.

Mucosal immunization is advantageous over other routes of antigen delivery because it can induce both mucosal and systemic immune responses. Our goal was to develop a mucosal delivery vehicle based on bacteria generally regarded as safe, such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as a proof of concept. We demonstrate that an oral vaccine based on live recombinant Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi infection. Our method of expressing vaccine antigens in L. plantarum induces both systemic and mucosal immunity after oral administration. This platform technology can be applied to design oral vaccine delivery vehicles against several microbial pathogens.Lactic acid bacteria are naturally associated with mucosal surfaces, particularly the gastrointestinal tract, and are also indigenous to food-related habitats, including plants, wine, milk, and meat. These gram-positive bacteria include both important pathogens, e.g., several Streptococcus species, and extremely valuable nonpathogenic species that have been used since ancient times for food and feed fermentation (11,37,58). The host is highly adapted to the presence of commensal intestinal bacteria (36). There is evidence that some strains of lactic acid bacteria have a favorable influence on physiologic and pathological processes of the host due to their specific health-promoting probiotic characteristics that relate to modulation of the immune system (15,36,41). Some strains of lactic acid bacteria polarize the naïve immune system by skewing it toward Th1 responses (41, 56).There have been a number of reports of oral vaccine candidates established from genetically modified pathogenic bacteria, such as Salmonella and Listeria species (1, 2, 30, 45, 52), or commensal bacteria, such as Lactococcus lactis and Lactobacillus species (27,31,32,60). The latter are food-grade bacteria that have GRAS status (generally regarded as safe). While both pathogenic and commensal bacteria have advantages and disadvantages as mucosal delivery vehicles, lactic acid bacteria are preferable in terms of safety and a lower risk of side effects (27,47). Presentation of antigens on the surface of lactobacilli is attractive for vaccine design, especially because the peptidoglycan layer of some strains appears to exhibit natural immuno-adjuvanticity (33,35,44,46). Thus, these species are excellent candidates for the development of safe mucosal delivery vehicles of prophylactic and therapeutic molecules. Of the Lactobacillus strains previously used for vaccine delivery, we chose L. plantarum because there is evidence that this strain is a better agent for vaccination with tetanus toxin fragment C (TTFC) than L. casei or L. lactis (22,53).Lyme disease is the most prevalent vector-borne infectious disease in the United States. A vaccine administered via needle inoculation and based on outer surface protein A (OspA) has proved effective in preventing Borrelia burgdorferi infection in animals and humans (7,10,(16)(17)...

SummaryCrohn's disease (CD) is characterized by inflammation and an aetiology that is still unknown. Hypertrophy of mesenteric fat is a reflection of disease activity, as this fat covers the entire length of the affected area. Adipocytes synthesize leptin and adiponectin, adipocytokines responsible for pro-and anti-inflammatory effects. Therefore, we evaluated serum levels of adiponectin and leptin, as well as mesenteral expression of adiponectin in active CD and those in remission. Sixteen patients with ileocaecal CD followed at the Outpatient Clinic, Coloproctology Unit of University of Campinas Clinical Hospital, participated in the study. Analysis of serum adiponectin and leptin by enzyme-linked immunosorbent assay was performed in patients with active CD (ACD group), remission CD (RCD group) and in six healthy controls. Ten patients with active ileocaecal CD (FCD group) and eight patients with non-inflammatory disease selected for surgery were also studied. The specimens were snap-frozen and the expression of adiponectin was determined by immunoblot of protein extracts. Serum C-reactive protein levels were higher in the ACD group when compared to the others and no difference of body mass index was observed between the groups. Serum adiponectin was lower in the ACD group when compared to control, but no differences were seen when comparing the ACD and RCD groups. Mesenteric adiponectin expression was lower in the FCD group when compared to the FC group. Serum leptin was similar in all groups. The lower levels of serum and mesenteric adiponectin in active CD suggest a defective regulation of anti-inflammatory pathways in CD pathogenesis.

Early diagnosis of Lyme disease (LD) is critical to successful treatment. However, current serodiagnostic tests do not reliably detect antibodies during early infection. OspC induces a potent early immune response and is also one of the most diverse proteins in the Borrelia proteome. Yet, at least 70% of the amino acid sequence is conserved among all 21 known OspC types. We performed a series of comprehensive seroprofiling studies to select the OspC types that have the most crossreactive immunodominant epitopes. We found that proteins belonging to seven OspC types detect antibodies from all three infected host species regardless of the OspC genotype of the infecting strain. Although no one OspC type identifies all seropositive human samples, combinations of as few as two OspC proteins identified all patients that had anti-OspC antibodies.

In the absence of erythema migrans, the basis for diagnosis of Lyme disease is the demonstration of an antibody response against Borrelia burgdorferi in an appropriate clinical setting. The C6 enzyme-linked immunosorbent assay, based on the IR6 region of VlsE, has become widely used in both the United States and Europe. We mapped the antigenic epitopes of IR6 to a shorter sequence that is equivalent in sensitivity and specificity to the full-length IR6 25-residue peptide. In addition, we observed significant differences in sensitivity between serum panels (60 to 100%), indicating that the selection of the serum panels can shape the apparent overall sensitivity of the assay. Contrary to prior reports, the assay sensitivity is greater when the IR6 peptide is derived from the sequence of the same infecting Borrelia genospecies. Using our North American panels and the two panels obtained from European Lyme disease patients, we determined that the IR6 assay that is based on a single genospecies of Borrelia spp. is not optimal for use as a universal diagnostic assay for Lyme disease.

Inflammatory myofibroblastic tumor (IMT) of the stomach is extremely rare and its prognosis is unpredictable. We present a 37-year-old woman with a gastric IMT. She presented epigastric pain since 2 months, anemia and weight loss associated. Physical examination showed cutaneous pallor and mild abdominal tenderness in the epigastrium. Abdominal ultrasonography showed a tumor near the pancreas and the CT scan revealed that the lesion was arising from the stomach. Upper endoscopy showed a submucosal lesion of approximately 7.5 cm located in the posterior wall of the gastric body such as a gastrointestinal stromal tumor (GIST). The patient underwent a subtotal gastrectomy and Billroth I reconstruction. The histopathological and immunohistochemical analysis revealed an IMT that originated from the gastric wall.

Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.

BackgroundCrohn’s disease (CD) is associated with complex pathogenic pathways involving defects in apoptosis mechanisms. Recently, mesenteric adipose tissue (MAT) has been associated with CD ethiopathology, since adipose thickening is detected close to the affected intestinal area. However, the potential role of altered apoptosis in MAT of CD has not been addressed.AimsTo evaluate apoptosis in the intestinal mucosa and MAT of patients with CD.MethodsSamples of intestinal mucosa and MAT from patients with ileocecal CD and from non-inflammatory bowel diseases patients (controls) were studied. Apoptosis was assessed by TUNEL assay and correlated with the adipocytes histological morphometric analysis. The transcriptional and protein analysis of selected genes and proteins related to apoptosis were determined.ResultsTUNEL assay showed fewer apoptotic cells in CD, when compared to the control groups, both in the intestinal mucosa and in MAT. In addition, the number of apoptotic cells (TUNEL) correlated significantly with the area and perimeter of the adipose cells in MAT. Transcriptomic and proteomic analysis reveal a significantly lower transcript and protein levels of Bax in the intestinal mucosa of CD, compared to the controls; low protein levels of Bax were found localized in the lamina propria and not in the epithelium of this tissue. Furthermore, higher level of Bcl-2 and low level of Caspase 3 were seen in the MAT of CD patients.ConclusionThe defective apoptosis in MAT may explain the singular morphological characteristics of this tissue in CD, which may be implicated in the pathophysiology of the disease.