Human and rodent interferon-γ as a growth factor for Trypanosoma brucei

An example for the bidirectional exchange of activating signals between a pathogen and immunocompetent cells in the host is presented. Trypanosoma brucei, which include subspecies that cause African sleeping sickness, secrete a molecule that triggers lymphocytes to produce interferon (IFN)-γ. We now report that proliferation of T. brucei is stimulated in axenic cultures by IFN-γ. The growth-enhancing effect on the pathogen is inhibited by anti-IFN-γ receptor (R) antibodies and does not occur after exposure to other cytokines, i.e. IFN-α, IFN-β and tumor necrosis factor (TNF)-α. While rodent-pathogenic T. brucei strains are stimulated by rat IFN-γ, human pathogenic strains are more potently stimulated by human IFN-γ. Rat and human IFN-γ can partially block each others effects. Mice with disrupted IFN-γ genes have reduced parasitemia and prolonged survival, while the outcome is reversed in mice that lack the IFN-γR gene.     

Outcome of Judet's quadricepsplasty for knee contractures and the effect of local infiltration of epinephrine on reducing blood loss

Objective: To evaluate the effectiveness of Judet''s quadricepsplasty for treatment of knee contractures and to identify the effect of local infiltration of epinephrine on blood loss associated with this procedure.Methods: A retrospective cohort study was conducted in which all cases of knee contractures managedwith Judet''s quadricepsplasty from 1st January 2009 to 31st December 2013 were included and weredivided into two groups. The epinephrine group included patients who were infiltrated with dilutedepinephrine (1:400,000) along with xylocaine, around the operative field 15 min prior to the incisiontime, while the control group did not receive any infiltration. Judet''s outcome, blood loss, drop in hemoglobin and required blood transfusion were noted for all patients and compared between both groups.Results: Most common preceding pathology identified for the development of knee contractures wasperiarticular fracture while ilizarov application was the most common etiology. Both groups were found similar in all preoperative characteristics except preoperative flexion contracture (p=0.02). All functional outcome measures including Judet''s outcome were similar in both groups. In contrast, duration of surgery (p=0.01), blood loss (p=0.02), drop in hemoglobin (p=0.01) and number of transfusions (p=0.03) were significantly reduced in epinephrine group.Conclusion: Judet''s quadricepsplasty is a useful procedure to increase the range of motion of rigid knees and local infiltration of epinephrine is effective in decreasing the amount of subsequent blood loss and transfusion requirements.     

Intrathoracic gastric fistula after bariatric surgery: a systematic review and pooled analysis

Even in the hands of highly experienced bariatric surgeons, perioperative complications are inevitable. Of these, leaks and fistulas are amongst the scariest complications. Intrathoracic gastric fistulas (ITGF) can be associated with serious morbidity, mostly when cases are misdiagnosed or detected with delay. This is a systematic review of the literature to investigate the clinical and surgical outcomes of morbidly obese adult patients with a confirmed diagnosis of ITGF following bariatric surgery. A pooled analysis of 25 articles, encompassing 76 patients with post-bariatric ITGF, showed that the clinical outcome depends on the initial presentation, timing of the diagnosis in relation to symptom onset, and prompt and effective treatment. Any septic or unstable patient must undergo urgent surgical intervention, while stable patients might tolerate a step-up approach and watchful waiting for nonsurgical treatment. Among those who undergo surgery, treatment failure and the mortality rate are substantially high. Contingent upon a prompt management strategy, patients with postbariatric ITGF can generally have a favorable outcome in the long term.     

African trypanosomes activate human fetal brain cells to proliferation and IFN-gamma production

We addressed the host-parasite interplay and the immunopathogenetic events occurring in the central nervous system (CNS) during human African trypanosomiasis. Human first trimester forebrain cells were stimulated with a trypanosome lymphocyte-triggering factor (TLTF) and studied for their immune response as exemplified by cell proliferation and IFN-gamma production. TLTF induced proliferation of human first trimester forebrain cells and IFN-gamma production at the mRNA and protein levels. Astrocytes are the major producers of IFN-gamma in response toTLTE These data illustrated for the first time a direct effect of a parasite factor on human brain cells. TargetingTLTF during the course of the disease may be considered in preventing the deadly neurological complications of human African trypanosomiasis. NeuroReport     

Chemokines are produced in the brain early during the course of experimental African trypanosomiasis

African trypanosomiasis is characterized by progressive central nervous system (CNS) involvement. Using single and double immunohistochemistry, we evaluated the induction of alpha- and beta-chemokines in brains of Sprague-Dawley rats infected with Trypanosoma brucei brucei (T. b. brucei) and identified their cellular source. The results showed high production of MIP-2, RANTES and MIP-1alpha and to a lower extend MCP-1 in infected animals compared to controls. MIP-2, RANTES and MIP-1alpha were produced early by astrocytes and microglia and later by macrophages and T-cells. These findings suggest that chemokines may contribute to the immunopathogenesis that occurs in the CNS early during infections.     

Modulation of early immune responses and suppression of Trypanosoma brucei brucei infections by surgical denervation of the spleen

OBJECTIVE: To examine critical interactions between the nervous system and the immune system during experimental African trypanosomiasis. METHODS AND RESULTS: Inoculation of Trypanosoma brucei brucei resulted in early interferon (IFN)-gamma production, elevated corticosterone and prostaglandin E(2) (PGE(2)) levels and increased splenocyte proliferation, as measured by enzyme-linked immunospot assay, radioimmunoassay and thymidine incorporation assay, respectively. Splenic denervation suppressed IFN-gamma, corticosterone and PGE(2) production, enhanced splenocyte proliferation, and significantly reduced parasitemia and prolonged rat survival. CONCLUSIONS: Our data show substantial effects of the nervous system on early immune responses that may influence the outcome of this disease. These effects were not dependent on cytokine inhibitory mediators such as prostaglandins or stress hormones. More investigations are required to understand the evident neural control over the immune system during infectious challenges, which may assist in novel therapeutic approaches.     

Effect of triclosan on interferon-gamma production and major histocompatibility complex class II expression in human gingival fibroblasts

BACKGROUND, AIMS: The effect of triclosan (2,4,4'-trichloro-2'-hydroxyl-diphenyl ether) on the production of interferon-gamma (IFN-gamma) and the expression of major histocompatibility complex (MHC) class II antigen was studied in human gingival fibroblasts isolated from 4 individuals. METHODS/RESULTS: All cell lines demonstrated high IFN-gamma production in 24-h cultures of human gingival fibroblasts stimulated by phytohemagglutinin (PHA) (5 microg/ml). Human gingival fibroblasts showed a high expression of MHC class II when stimulated with 500 and 1,000 pg/ml rIFN-gamma in 7-day cultures. Treatment of the cells with triclosan (0.5 microg/ml) reduced both IFN-gamma production and MHC class II expression in human gingival fibroblast cultures. Similar inhibitory effects on IFN-gamma production and MHC class II expression were observed when the anti-inflammatory agent dexamethazone (1 microM) was used. CONCLUSION: The present study further supports the view that the agent has an anti-inflammatory effect in addition to its antibacterial capacity.     

Susceptibility of Bovans chicks to low dietary levels of Ammi visnaga and Artemisia herba-alba

Ammi visnaga seeds and Artemisia herba-alba shoots were fed to 7-d-old Bovans chicks at 2% and 10% of diet for 9 w. The 10% A visnaga seed was toxic but not lethal to chicks and caused a consistently reduced body weight gain, inefficient feed utilization, enterohepatonephropathy, anemia, and alterations of serum aspartate transaminase and creatine kinase activities and cholesterol, total lipid and uric acid concentrations. The depression in growth and damage to vital organs of chicks fed 10% A herba-alba shoots 2% A visnaga seed, or 2% A herba-alba shoots were less marked.     

Dose-dependent liver tissue repair in chloroform plus thioacetamide acute hepatotoxicity

The objective of this study was to test whether a binary mixture (BM) of chloroform (CHCl(3)) and thioacetamide (TA) causes a dose-dependent liver injury and an opposing tissue repair. Liver injury was assessed by plasma alanine aminotransferase (ALT) and histopathology. Tissue repair was measured by [(3)H-CH(3)]-thymidine ((3)H-T) incorporation into hepatonuclear DNA and PCNA over a time course of 0-72h. Male Sprague-Dawley (S-D) rats received six- and five-fold dose ranges of TA and CHCl(3), respectively. ALT levels and (3)H-T incorporation were in complete agreement with corresponding microscopic observations, and only ALT elevation and (3)H-T incorporation data are presented here. Liver injury observed after exposure to BM was no different than addition of injuries caused by individual compounds. Tissue repair was prompt and adequate, leading to recovery from injury and animal survival. Tissue repair is dose-dependent and plays central role in the hepatotoxic outcome.     

Splenic denervation suppresses mRNA gene expression and protein production of IL-1beta and IL-6 by peritoneal macrophages in both Trypanosoma brucei brucei-infected and non-infected rats

OBJECTIVE: To test the hypothesis that the nervous system participates in modulating the immune response during experimental African trypanosomiasis caused by Trypanosoma brucei brucei. METHODS AND RESULTS: Using in situ hybridization and immunochemistry, we studied the effects of splenic sympathectomy on mRNA gene expression and protein production of IL-1beta and IL-6 in splenic and peritoneal macrophages (PMPhi) of Sprague-Dawley rats infected with T. brucei brucei and non-infected rats. The enhancements of mRNA gene expression and production of IL-1beta and IL-6 by peritoneal macrophages were significantly suppressed by the splenic sympathectomy in both infected and non-infected rats. CONCLUSIONS: Our data indicate a probably stimulatory role of the sympathetic nervous system during the host immune response in both normal and T. brucei brucei-infected rats.