Intestinal epithelial cells synthesize glucocorticoids and regulate T cell activation

Glucocorticoids (GCs) are important steroid hormones with widespread activities in metabolism, development, and immune regulation. The adrenal glands are the major source of GCs and release these hormones in response to psychological and immunological stress. However, there is increasing evidence that GCs may also be synthesized by nonadrenal tissues. Here, we report that the intestinal mucosa expresses steroidogenic enzymes and releases the GC corticosterone in response to T cell activation. T cell activation causes an increase in the intestinal expression of the steroidogenic enzymes required for GC synthesis. In situ hybridization analysis revealed that these enzymes are confined to the crypt region of the intestinal epithelial layer. Surprisingly, in situ-produced GCs exhibit both an inhibitory and a costimulatory role on intestinal T cell activation. In the absence of intestinal GCs in vivo, activation by anti-CD3 injection resulted in reduced CD69 expression and interferon-gamma production by intestinal T cells, whereas activation by viral infection led to increased T cell activation. We conclude that the intestinal mucosa is a potent source of immunoregulatory GCs.     

Hepatitis B virus infection in Haemodialysis Centres from Santa Catarina State, Southern Brazil. Predictive risk factors for infection and molecular epidemiology

Background

Patients under haemodialysis are considered at high risk to acquire hepatitis B virus (HBV) infection. Since few data are reported from Brazil, our aim was to assess the frequency and risk factors for HBV infection in haemodialysis patients from 22 Dialysis Centres from Santa Catarina State, south of Brazil.

Methods

This study includes 813 patients, 149 haemodialysis workers and 772 healthy controls matched by sex and age. Serum samples were assayed for HBV markers and viraemia was detected by nested PCR. HBV was genotyped by partial S gene sequencing. Univariate and multivariate statistical analyses with stepwise logistic regression analysis were carried out to analyse the relationship between HBV infection and the characteristics of patients and their Dialysis Units.

Results

Frequency of HBV infection was 10.0%, 2.7% and 2.7% among patients, haemodialysis workers and controls, respectively. Amidst patients, the most frequent HBV genotypes were A (30.6%), D (57.1%) and F (12.2%). Univariate analysis showed association between HBV infection and total time in haemodialysis, type of dialysis equipment, hygiene and sterilization of equipment, number of times reusing the dialysis lines and filters, number of patients per care-worker and current HCV infection. The logistic regression model showed that total time in haemodialysis, number of times of reusing the dialysis lines and filters, and number of patients per worker were significantly related to HBV infection.

Conclusions

Frequency of HBV infection among haemodialysis patients at Santa Catarina state is very high. The most frequent HBV genotypes were A, D and F. The risk for a patient to become HBV positive increase 1.47 times each month of haemodialysis; 1.96 times if the dialysis unit reuses the lines and filters ≥ 10 times compared with haemodialysis units which reuse < 10 times; 3.42 times if the number of patients per worker is more than five. Sequence similarity among the HBV S gene from isolates of different patients pointed out to nosocomial transmission.     

Electronic MEMS for triggered delivery

Implantable electronic devices such as pacemakers and neural implants are often used for electrical stimulation. The usage of microfabrication techniques to produce microelectromechanical systems (MEMS) has allowed engineers to address a wider range of clinical indications. A new direction in the area of MEMS technology is the goal of achieving pulsatile drug delivery. The digital capabilities of MEMS may allow greater temporal control over drug release compared to traditional polymer-based systems, while the batch-processing techniques used in the microelectronics industry can lead to greater device uniformity and reproducibility than is currently available to the pharmaceutical industry. A repertoire of structures, including microreservoirs, micropumps, valves, and sensors, is being developed that will provide a strong foundation for the design of integrated, responsive MEMS for drug delivery.     

High-throughput crystallization: polymorphs, salts, co-crystals and solvates of pharmaceutical solids

The concepts of high-throughput (HT) screening and combinatorial synthesis have been integrated into the pharmaceutical discovery process, but are not yet commonplace in the pharmaceutical development arena. Emerging strategies to speed pharmaceutical development and capture solid form diversity of pharmaceutical substances have resulted in the emergence of HT crystallization technologies. The primary type of diversity often refers to polymorphs, which are different crystal forms of the same chemical composition. However, diverse salt forms, co-crystals, hydrates and solvates are also amenable to study in HT crystallization systems. The impact of form diversity encompasses issues of stability and bioavailability, as well as development considerations such as process definition, formulation design, patent protection and regulatory control. This review highlights the opportunities and challenges of HT crystallization technologies as they apply to pharmaceutical research and development.     

Immunization with the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins induces long-term duration cross-reactive antibodies with heart functional and structural alterations in young and aged mice

The R13 peptide sequence (EEEDDDMGFGLFD) that corresponds to the C-terminal region of Trypanosoma cruzi ribosomal P1 and P2 proteins differs from the eukariotic P concensus sequence EESDDDMGFGLFD (H13) only in a nonconservative amino acid substitution. The immunization of BALB/c mice with R13 synthetic peptide coupled to a carrier protein (OVA) induces specific (anti-R13) and autoreactive (anti-H13 and anti-heart) antibodies as well as heart functional alterations. Since aged human and experimental animals are impaired in their responses to most foreign antigens but they produce greater amounts of autoantibodies, in this work we used aged mice as an experimental model able to exaggerate the autoimmune component of the R13-induced response in case it was present. We studied whether these antibodies generated in the absence of the parasite would induce pathological changes in heart tissues. The levels of antibodies against R13 (foreign antigen) and H13 (autoantigen) studied comparatively in 2- and 12-month-old mice 10 days after the third immunization with R13 coupled to OVA were, as we expected for a foreign antigen, higher in almost all sera from 2-month-old mice tested than in sera from 12-month-old mice. Besides, these specific and cross-reactive antibody response remain elevated as long as 150 days post third immunization. In addition, the isotype pattern that recognizes R13 and the self-sequence H13 showed no differences between sera from young and aged mice. Moreover, when ECG traces were obtained from immunized mice, the heart functional alterations observed at 10 days continued at 80 and 150 days after the third immunization, showing an association with the levels of antibodies. In addition, despite the fact that the heart tissue morphology showed no alterations 10 days post third immunization, several abnormalities in the tissue architecture were revealed at 80 and 150 days post third immunization. This report demonstrates the biological relevance of R13-induced cross-reactive antibodies in some of the electrophysiologic and histological changes found in T. cruzi-infected mammalians.     

ENDOTHELIAL CELL CULTURE AND SEEDING OF PROSTHETIC VASCULAR GRAFTS: AN EXPERIMENTAL STUDY

Current synthetic vascular prostheses do not acquire lining of vascular endothelium in humans or dogs. Endothelial seeding of vascular grafts has been proposed as a means of reducing the thrombogenicity of these grafts. We examined feasibility of cultivating endothelial cells (EC) by tissue culture technique and their subsequent seeding onto small diameter polytetra fluoroethylene (PTFE) grafts. Twenty adult dogs underwent common carotid artery interposition with 4 mm PTFE grafts. Ten dogs received seeded and the remaining ten received unseeded grafts. Grafts were removed at 4 and 12 weeks and their gross/morphological features compared. Cumulative patency rates for seeded grafts were 70% as compared to unseeded ones 30%. Seeded grafts were completely surfaced with a mono-layer of endothelium by 4 weeks. Small graft patency appears to be related to the establishment of an endothelial surface, the development of which is clearly facilitated by seeding with autogenous endothelium.KEY WORDS: Endothelial cell seeding, Vascular grafts     

Patient expectations of radiology in noninteractive encounters

Open-ended interviews with 107 patients documented specific patient expectations of radiologic procedures during which there was no direct radiologist-patient interaction. Patient expectations could be classified into those related to the facility and those related to interactions with radiology staff. Among facility-related expectations, waiting time far outweighed all other concerns. Interpersonal skills were the predominant expectation of radiology staff. The role of the radiologist in fulfilling patient expectations was less clear. Only 10% of unprompted patients cited the radiologist as a factor in their expectations. When patients were specifically prompted to discuss the radiologist's role, communication skills, accuracy of interpretation, and interpersonal skills were the predominant concerns.     

Perioperative Anti-Tumor Necrosis Factor Therapy Does Not Increase the Rate of Early Postoperative Complications in Crohn’s Disease

Background  

There have been numerous studies with conflicting results regarding the use of anti-tumor necrosis factor (TNF) therapy and its relationship to postoperative outcome in Crohn disease. The aim of our study was to examine the rate of postoperative morbidity in patients receiving anti TNF therapy in the perioperative period.