People with tuberculosis are associated with a subsequent risk of depression.

BACKGROUND: There is some evidence that the prevalence of depression in patients with tuberculosis (TB) is higher than those in the general population. However, the incidence of depression after Mycobacterium tuberculosis infection remains unknown. Our aim was to assess the association between TB and the subsequent risk of depression. METHODS: We conducted a retrospective cohort study using data from the National Health Insurance (NHI) system of Taiwan. The TB cohort included 9020 patients who were newly diagnosed and recruited between 2000 and 2010. Each patient was randomly frequency-matched for age, sex and the year of index date with four people without TB from the general population. The newly diagnosed depression was followed up until the end of 2011. The relative risks of depression were estimated using Cox proportional hazard models after adjusting for age, sex, index year and comorbidities. RESULTS: The overall incidence rate of depression was 1.54-fold higher in the TB cohort as compared with the controlled cohort (8.15 vs. 5.29 per 1000 person-years, 95% confidence interval [CI]=1.45-1.64). Stratified analyses by gender, age group, monthly income and comorbidities revealed that the adjusted hazard ratio (HR) of depression was higher in males as well as individuals older than 65 years with a low monthly income and comorbidities. CONCLUSION: People who have been diagnosed with TB have a significantly higher risk of developing depression compared with those in the general population. We should pay more attention to this group of individuals and ensure that they are offered appropriate support.

Interleukin-4 enhances trafficking and functional activities of GM-CSF-stimulated mouse myeloid-derived dendritic cells at late differentiation stage.

Mouse bone marrow-derived dendritic cells (BMDCs) are being employed as an important model for translational research into the development of DC-based therapeutics. For such use, the localization and specialized mobility of injected BMDCs within specific immune tissues are known to define their immunity and usefulness in vivo. In this study, we demonstrate that IL-4, a key driving factor for in vitro propagation and differentiation of BMDCs, when added during a late culture stage can enhance the in vivo trafficking activity of granulocyte-macrophage colony-stimulating factor (GM-CSF)-induced BMDCs. It suggests that the temporal control of IL-4 stimulation during the in vitro generation of DCs drastically affects the DC trafficking efficiency in vivo. With this modification of IL-4 stimulation, we also show that much less cytokine was needed to generate BMDCs with high purity and yield that secrete a high level of cytokines and possess a good capacity to induce proliferation of allogeneic CD4+ T cells, as compared to the conventional method that uses a continuous supplement of GM-CSF and IL-4 throughout cultivation. These results provide us with an important know-how for differentiation of BMDCs from myeloid stem cells, and for use of other immune cells in related medical or stem cell applications.

Clinical presentations, prognostic factors, and mortality in patients with Aeromonas sobria complex bacteremia in a teaching hospital: a 5-year experience.

BACKGROUND AND PURPOSE: Bacteremia due to Aeromonas sobria complex is an uncommon clinical presentation, associated with a high mortality rate. This retrospective study reviewed the clinical manifestations and prognostic factors of A. sobria complex bacteremia. METHODS: From September 2001 to August 2006, all adult patients with A. sobria complex bacteremia treated at a tertiary medical center in Taiwan were included. Antibiotic susceptibility was tested by disc diffusion method. RESULTS: Of 33 patients with A. sobria complex bacteremia, 66.7% were men and 72.0% were older than 50 years. Most patients (72.7%) had community-acquired infection. The commonest associated conditions were liver cirrhosis (42.4%) and neoplasm (30.3%). With the exception of diarrhea, the clinical manifestations were similar to those of other Aeromonas spp. Secondary bacteremia occurred in 51.5% of patients, most of whom had either biliary tract infection (47%) or peritonitis (23.5%) as the major infection focus. Monomicrobial bacteremia was recorded in 23 patients. All isolates were susceptible to gentamicin, amikacin, ceftazidime, cefepime, and ciprofloxacin; 90.9% were susceptible to aztreonam and piperacillin-tazobactam, 87.9% to imipenem, and 78.8% to trimethoprim-sulfamethoxazole. The mortality rate was 39.4% and nearly 50% of deaths occurred within 96 h of admission. Hypotension, impaired renal function, and liver cirrhosis were significantly associated with a high mortality rate. CONCLUSIONS: A. sobria complex bacteremia usually occurs in patients with liver cirrhosis or neoplasm. In patients with A. sobria complex bacteremia, a secondary infection focus should be considered. Adequate antibiotics should be given early, especially to patients with hypotension and impaired renal function.

Genomics and proteomics of immune modulatory effects of a butanol fraction of echinacea purpurea in human dendritic cells.

BACKGROUND: Echinacea spp. extracts and the derived phytocompounds have been shown to induce specific immune cell activities and are popularly used as food supplements or nutraceuticals for immuno-modulatory functions. Dendritic cells (DCs), the most potent antigen presenting cells, play an important role in both innate and adaptive immunities. In this study, we investigated the specific and differential gene expression in human immature DCs (iDCs) in response to treatment with a butanol fraction containing defined bioactive phytocompounds extracted from stems and leaves of Echinacea purpurea, that we denoted [BF/S+L/Ep]. RESULTS: Affymetrix DNA microarray results showed significant up regulation of specific genes for cytokines (IL-8, IL-1beta, and IL-18) and chemokines (CXCL 2, CCL 5, and CCL 2) within 4 h after [BF/S+L/Ep] treatment of iDCs. Bioinformatics analysis of genes expressed in [BF/S+L/Ep]-treated DCs revealed a key-signaling network involving a number of immune-modulatory molecules leading to the activation of a downstream molecule, adenylate cyclase 8. Proteomic analysis showed increased expression of antioxidant and cytoskeletal proteins after treatment with [BF/S+L/Ep] and cichoric acid. CONCLUSION: This study provides information on candidate target molecules and molecular signaling mechanisms for future systematic research into the immune-modulatory activities of an important traditional medicinal herb and its derived phytocompounds.

Immunomodulatory effects of phytocompounds characterized by in vivo transgenic human GM-CSF promoter activity in skin tissues.

To investigate the immunomodulatory activities of phytocompounds for potential therapeutics, we devised an in vivo, transgenic, human cytokine gene promoter assay using defined epidermal skin cells as test tissue. Test compounds were topically applied to mouse skin before or after gene gun transfection, using a cytokine gene promoter-driven luciferase reporter. Croton oil, an inflammation inducer, induced transgenic GM-CSF and TNF-alpha promoter activities in skin epidermis 6-fold and 3.4-fold, respectively; however, it produced a less than 1.5-fold and 1.7-fold change in IL-1beta and IL-18 promoter activity, respectively. The phytocompound shikonin drastically inhibited inducible GM-CSF promoter activity. However, a fraction of Dioscorea batatas extract significantly increased the GM-CSF promoter activity in normal and inflamed skin. Shikonin suppressed the transcriptional activity of GM-CSF promoter by inhibiting the binding of TFIID protein complex (TBP) to TATA box. Our results demonstrate that this in vivo transgenic promoter activity assay system is cytokine gene-specific, and highly responsive to pro-inflammatory or anti-inflammatory stimuli. Currently it is difficult to profile the expression and cross-talk of various types of cytokines in vivo. This investigation has established a bona fide in vivo, in situ, immune tissue system for research into cytokine response to inflammation.

Modulatory effects of Echinacea purpurea extracts on human dendritic cells: a cell- and gene-based study.

Echinacea spp. are popularly used as an herbal medicine or food supplement for enhancing the immune system. This study shows that plant extracts from root [R] and stem plus leaf [S+L] tissues of E. purpurea exhibit opposite (enhancing vs inhibitory) modulatory effects on the expression of the CD83 marker in human dendritic cells (DCs), which are known as professional antigen-presenting cells. We developed a function-targeted DNA microarray system to characterize the effects of phytocompounds on human DCs. Down-regulation of mRNA expression of specific chemokines (e.g., CCL3 and CCL8) and their receptors (e.g., CCR1 and CCR9) was observed in [S+L]-treated DCs. Other chemokines and regulatory molecules (e.g., CCL4 and CCL2) involved in the c-Jun pathway were found to be up-regulated in [R]-treated DCs. This study, for the first time, demonstrates that E. purpurea extracts can modulate DC differentiation and expression of specific immune-related genes in DCs.

Comparative studies of the capsid precursor polypeptide P1 and the capsid protein VP1 cDNA vectors for DNA vaccination against foot-and-mouth disease virus.

BACKGROUND: Foot-and-mouth disease virus (FMDV) causes a severe livestock disease, and the virus is an interesting target for virology and vaccine studies. MATERIALS AND METHODS: Here we evaluated comparatively three different viral antigen-encoding DNA sequences, delivered via two physical means (i.e., gene gun delivery into skin and electroporation delivery into muscle), for naked DNA-mediated vaccination in a mouse system. RESULTS: Both methods gave similar results, demonstrating commonality of the observed DNA vaccine effects. Immunization with a cDNA vector expressing the major viral antigen (VP1) alone routinely failed to induce the production of anti-VP1 or neutralizing antibodies in test mice. As a second approach, the plasmid L-VP1 that produces a transgenic membrane-anchored VP1 protein elicited a strong antibody response, but all test mice failed in the FMDV challenge experiment. In contrast, for mice immunized with the viral capsid precursor protein (P1) cDNA expression vector, both neutralizing antibodies and 80-100% protection in test mice were detected. CONCLUSIONS: This strategy of using the whole capsid precursor protein P1 cDNA for vaccination, intentionally without the use of virus-specific protease or other encoding genes for safety reasons, may thus be employed as a relevant experimental system for induction or upgrading of effective neutralizing antibody response, and as a convenient surrogate test system for DNA vaccination studies of FMDV and presumably other viral diseases.