Deciphering the influence of paraimmunobiotic bifidobacteria on the innate antiviral immune response of bovine intestinal epitheliocytes by transcriptomic analysis.

Previously, we reported that the non-viable immunomodulatory Bifidobacterium infantis MCC12 and Bifidobacterium breve MCC1274 strains (paraimmunobiotic bifidobacteria) were able to increase the protection against rotavirus infection in bovine intestinal epithelial (BIE) cells. In order to gain insight into the influence of paraimmunobiotic bifidobacteria on the innate antiviral immune response of BIE cells, their effect on the transcriptomic response triggered by Toll-like receptor 3 (TLR3) activation was investigated. By using microarray technology and qPCR analysis, we obtained a global overview of the immune genes involved in the innate antiviral immune response in BIE cells. Activation of TLR3 by poly(I:C) in BIE cells significantly increased the expression of interferon (IFN)-α and IFN-ß, several interferon-stimulated genes, cytokines, and chemokines. It was also observed that both paraimmunobiotic bifidobacteria differently modulated immune genes expression in poly(I:C)-challenged BIE cells. Most notable changes were found in genes involved in antiviral defence (IFN-ß, MX1, OAS1X, MDA5, TLR3, STAT2, STAT3), cytokines (interleukin (IL)-6), and chemokines (CCL2, CXCL2, CXCL6) that were significantly increased in bifidobacteria-treated BIE cells. B. infantis MCC12 and B. breve MCC1274 showed quantitative and qualitative differences in their capacities to modulate the innate antiviral immune response in BIE cells. B. breve MCC1274 was more efficient than the MCC12 strain to improve the production of type I IFNs and antiviral factors, an effect that could be related to its higher ability to protect against rotavirus replication in BIE cells. Interestingly, B. infantis MCC12 showed a remarkable anti-inflammatory effect. The MCC12 strain was more efficient to reduce the expression of inflammatory cytokines and chemokines (IL-16, IL-20, CX3CL1) when compared with B. breve MCC1274. These results provided valuable information for the deeper understanding of the antiviral immune response of intestinal epithelial cells as well as the host-paraimmunobiotic interaction in the bovine host.

Lactobacillus fermentum UCO-979C beneficially modulates the innate immune response triggered by Helicobacter pylori infection in vitro.

Helicobacter pylori infection is associated with important gastric pathologies. An aggressive proinflammatory immune response is generated in the gastric tissue infected with H. pylori, resulting in gastritis and a series of morphological changes that increase the susceptibility to cancer development. Probiotics could present an alternative solution to prevent or decrease H. pylori infection. Among them, the use of immunomodulatory lactic acid bacteria represents a promising option to reduce the severity of chronic inflammatory-mediated tissue damage and to improve protective immunity against H. pylori. We previously isolated Lactobacillus fermentum UCO-979C from human gastric tissue and demonstrated its capacity to reduce adhesion of H. pylori to human gastric epithelial cells (AGS cells). In this work, the ability of L. fermentum UCO-979C to modulate immune response in AGS cells and PMA phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1 (human monocytic leukaemia) macrophages in response to H. pylori infection was evaluated. We demonstrated that the UCO-979C strain is able to differentially modulate the cytokine response of gastric epithelial cells and macrophages after H. pylori infection. Of note, L. fermentum UCO-979C was able to significantly reduce the production of inflammatory cytokines and chemokines in AGS and THP-1 cells as well as increase the levels of immunoregulatory cytokines, indicating a remarkable anti-inflammatory effect. These findings strongly support the probiotic potential of L. fermentum UCO-979C and provide evidence of its beneficial effects against the inflammatory damage induced by H. pylori infection. Although our findings should be proven in appropriate experiments in vivo, in both H. pylori infection animal models and human trials, the results of the present work provide a scientific rationale for the use of L. fermentum UCO-979C to prevent or reduce H. pylori-induced gastric inflammation in humans.

Incidence of proximal femur fractures in Marilia, Brazil.

SETTING: Three general hospitals in the town of Marília that have an orthopaedic and traumatologic unit. Marília is a Municipality with 161.000 inhabitants in the middle-east of São Paulo State, Brazil. PATIENTS/PARTICIPANTS: All inpatients, living in Marília-SP, aged 20 years or more, with a diagnosis of proximal femur fracture (WHO, International Classification of Diseases, 9th.ed., code 820), in the period of January 01, 1994 and December 31, 1995. MAIN OUTCOME MEASURES: The incidence rates of the proximal femur fractures in Marília-SP. Secondary Measurements: mean-age of the occurrence (male and female), in-hospital mortality, hospitalar costs to S.U.S. (Government Health System), the average length of hospital stay, seasonality, mean-interval between admission and surgical procedure, type of fracture: transcervical and pertrochanteric, content validity of S.I.H.-S.U.S data base report on proximal femur fractures, when compared with hospital registrations. OBJECTIVE: To determine the incidence (crude, age-specific and age-adjusted) of fractures of the proximal femur in Marília-SP, Brazil, in 1994 and 1995. DESIGN: Retrospective cohort study. RESULTS: The crude incidence rate was 4.96/10,000 inhabitants/year in 1994 and 5.51/10,000 inhabitants/year in 1995; the age-specific incidence rate increased from 0.25/10,000 inhabitants 20-49 years/year to 100.27/10,000 inhabitants 70 years or more/year in 1995 among women; the age-adjusted incidence rate was 29.48/10,000 inhabitants 60 years or more/year in 1994, and 35.83/10,000 inhabitants 60 years or more/year in 1995. CONCLUSION: The crude incidence rate of the proximal femur fractures in Marília-SP, Brazil was 4.96 / 10,000 inhabitants in 1994 and 5.51/10,000 inhabitants in 1995. It was significantly greater among women (7.2/10,000 inhabitants in 1994 and 8.6/10,000 inhabitants in 1995) and among the elderly, 70 year-old or more (female: 90.21/10,000 inhabitants in 1994 and 100.27/10,000 inhabitants in 1995; male: 25.46/10,000 inhabitants in 1994 and 45.66/10,000 inhabitants in 1995).

Evidence based medicine is the conscientious, explicit, and judicious use of current evidence in making decisions about the care of individual patients.

The 2nd U.K. Workshop on Evidence Based Health Care, London, 11th-16th February 1996, with Dr. Trisha Greenhalgh (UCLMS) as co-ordinator, and Prof. David Sackett (Oxford), as orientator, constituted an important meeting to disseminate EBHC in UK and Europe. "Evidence Based Medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individuals patients" (Sackett, 1996). The methodology utilized was Problem-Based Learning (PBL), with small groups sessions with tutor and co-tutor as facilitators of the discussion process. The participants have been demonstrated that it's possible to teach EBHC using different strategies, approaches and resources. This Workshop was an excellent opportunity not only to share and receive informations about Clinical Epidemiology, Biostatistics and EBHC, but also to participate in a "learning to learn" active process to understand how to teach and learn EBHC.