Quality of life, depression, and psychosocial characteristics of patients awaiting liver transplants.

BACKGROUND: The identification of the psychological issues that impair the quality of life and the adherence to treatment in transplant candidates are important. OBJECTIVE: This study evaluated the presence of symptoms of depression and the quality of life of liver transplant candidates. METHODS: One hundred liver transplant candidates underwent a psychological analysis using the following instruments: the short form-36 (SF-36) quality of life questionnaire, the Beck depression inventory (BDI), and Structured Interviews for liver transplant candidates. RESULTS: Seventy-three (73%) of the patients were males. Interestingly, 63% of the patients were in a domestic partnership. At the time of the evaluation, 55 patients were not working due to illness, 27 patients were actively working, and 11 patients were retired. Importantly, fears related to the transplant (e.g., fear the surgery and of death) were identified in 38% of the patients. The data from this study demonstrated a significant negative correlation between depressive scores (BDI) and seven of the eight areas of quality of life (SF-36), such as functional capacity (r = .317, P = .0013), social aspects (r = -.469, P < .0001), economic aspects (r = -.319, P = .0012), and mental health (r = -.3832, P < .0001). CONCLUSION: The data indicated that the psychological aspects related to transplants require psychological intervention because they can affect the recuperation process, the quality of life, and the adherence to treatment for potential transplant patients.

Dendritic cell are able to differentially recognize Sporothrix schenckii antigens and promote Th1/Th17 response in vitro.

Sporotrichosis is a disease caused by the dimorphic fungus Sporothrix schenckii. The main clinical manifestations occur in the skin, however the number of systemic and visceral cases has increased, especially in immunocompromised patients. Dendritic cells (DCs) are highly capable to recognize the fungus associated data and translate it into differential T cells responses both in vivo and in vitro. Although, the mechanisms involved in the interaction between DCs and S. schenckii are not fully elucidated. The present study investigated the phenotypic and functional changes in bone marrow dendritic cells (BMDCs) stimulated in vitro with the yeast form of S. schenckii or exoantigen (ExoAg) and its ability to trigger a cellular immune response in vitro. Our results demonstrated that the live yeast of S. schenckii and its exoantigen, at a higher dose, were able to activate BMDCs and made them capable of triggering T cell responses in vitro. Whereas the yeast group promoted more pronounced IFN-γ production rather than IL-17, the Exo100 group generated similar production of both cytokines. The exoantigen stimulus suggests a capability to deviate the immune response from an effector Th1 to an inflammatory Th17 response. Interestingly, only the Exo100 group promoted the production of IL-6 and a significant increase of TGF-ß, in addition to IL-23 production. Interestingly, only Exo100 group was capable to promote the production of IL-6 and a significant increase on TGF-ß, in addition with IL-23 detection. Our results demonstrated the plasticity of DCs in translating the data associated with the fungus S. schenckii and ExoAg into differential T cell responses in vitro. The possibility of using ex vivo-generated DCs as vaccinal and therapeutic tools for sporotrichosis is a challenge for the future.

Exposure to Mycobacterium avium decreases the protective effect of the DNA vaccine pVAXhsp65 against Mycobacterium tuberculosis-induced inflammation of the pulmonary parenchyma.

This work investigated the effect of previous Mycobacterium avium exposure on the protective ability of the DNA vaccine pVAXhsp65 against inflammation in the pulmonary parenchyma. BALB/c mice were presensitized with heat-killed M. avium and then immunized with three doses of pVAXhsp65 prior to challenge with Mycobacterium tuberculosis. M. avium sensitization induced high levels of spontaneous IL-5 production that were concomitant with a positive delayed-type hypersensitivity reaction; antigen-specific IFN-γ production was also observed upon splenocyte stimulation. Prior exposure to M. avium resulted in altered cytokine and antibody production induced by immunization with pVAXhsp65; instead of a Th1 response, vaccinated mice previously exposed to M. avium developed a strong Th2 response. This switch to a Th2 response coincided with the loss of the anti-inflammatory effect of pVAXhsp65 vaccination previously observed in the pulmonary parenchyma of mice infected with M. tuberculosis. These results suggest that exposure to environmental mycobacteria can modulate immune responses induced by mycobacterial vaccines other than bacillus Calmette-Guérin.

Patients undergoing liver transplantation: psychosocial characteristics, depressive symptoms, and quality of life.

BACKGROUND: Liver transplantation is the treatment of choice for patients with end-stage liver diseases to improve social rehabilitation and quality of life. Our objective was to evaluate the psychosocial characteristics, depressive symptoms, and quality of life among patients undergoing liver transplantation. MATERIALS AND METHODS: Patients underwent individual assessments using a semidirected interview. Beck's Depression Inventory and SF-36 Quality of Life Questionnaire. The signal test was used with a significance level set at .05. RESULTS: The characteristics of the sample (n = 30) were compatible with literature data for gender (n = 20 men), age (mean age, 51.96 years), education (elementary and middle school), and etiology (viral hepatitis). A significant number of patients were not able to maintain their professional activities: prior to transplantation (n = 18) and after transplantation (n = 13) due to the adverse effects of immunosuppressants (n = 9). The analysis indicated a significant quality of life improvement after transplantation for the following domains: functional capacity (P = .047), physical aspects (P = .024), pain (P = .001), overall health status (P = .003), and social aspects (P = .021). Significant depressive symptoms (n = 6) were experienced before and after the surgery. CONCLUSIONS: The data indicated a significant quality of life improvement after liver transplantation. Occupational activity and surgery time had a positive influence on these results. The frequency of depressive symptoms was similar before and after transplantation, correlating with less favorable quality of life scores. The results indicated the need to provide regular psychosocial assessment and follow-up in all stages of therapy.

Immune modulation induced by tuberculosis DNA vaccine protects non-obese diabetic mice from diabetes progression.

We have described previously the prophylactic and therapeutic effect of a DNA vaccine encoding the Mycobacterium leprae 65 kDa heat shock protein (DNA-HSP65) in experimental murine tuberculosis. However, the high homology of this protein to the corresponding mammalian 60 kDa heat shock protein (Hsp60), together with the CpG motifs in the plasmid vector, could trigger or exacerbate the development of autoimmune diseases. The non-obese diabetic (NOD) mouse develops insulin-dependent diabetes mellitus (IDDM) spontaneously as a consequence of an autoimmune process that leads to destruction of the insulin-producing beta cells of the pancreas. IDDM is characterized by increased T helper 1 (Th1) cell responses toward several autoantigens, including Hsp60, glutamic acid decarboxylase and insulin. In the present study, we evaluated the potential of DNA-HSP65 injection to modulate diabetes in NOD mice. Our results show that DNA-HSP65 or DNA empty vector had no diabetogenic effect and actually protected NOD mice against the development of severe diabetes. However, this effect was more pronounced in DNA-HSP65-injected mice. The protective effect of DNA-HSP65 injection was associated with a clear shift in the cellular infiltration pattern in the pancreas. This change included reduction of CD4(+) and CD8(+) T cells infiltration, appearance of CD25(+) cells influx and an increased staining for interleukin (IL)-10 in the islets. These results show that DNA-HSP65 can protect NOD mice against diabetes and can therefore be considered in the development of new immunotherapeutic strategies.

Immune regulatory effect of pHSP65 DNA therapy in pulmonary tuberculosis: activation of CD8+ cells, interferon-gamma recovery and reduction of lung injury.

A DNA vaccine based on the heat-shock protein 65 Mycobacterium leprae gene (pHSP65) presented a prophylactic and therapeutic effect in an experimental model of tuberculosis. In this paper, we addressed the question of which protective mechanisms are activated in Mycobacterium tuberculosis-infected mice after immune therapy with pHSP65. We evaluated activation of the cellular immune response in the lungs of infected mice 30 days after infection (initiation of immune therapy) and in those of uninfected mice. After 70 days (end of immune therapy), the immune responses of infected untreated mice, infected pHSP65-treated mice and infected pCDNA3-treated mice were also evaluated. Our results show that the most significant effect of pHSP65 was the stimulation of CD8+ lung cell activation, interferon-gamma recovery and reduction of lung injury. There was also partial restoration of the production of tumour necrosis factor-alpha. Treatment with pcDNA3 vector also induced an immune stimulatory effect. However, only infected pHSP65-treated mice were able to produce significant levels of interferon-gamma and to restrict the growth of bacilli.

Synthesis, antimycobacterial activities and cytotoxicity on V79 of 3-[4'-Y-(1,1'-biphenyl)-4-yl]-N,N-dimethyl-3-(4-X-phenyl)-2-propen-1-amine derivatives.

The derivatives of 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl)-N,N-dimethyl-2-propen-1-amine (5a-m) were synthesised through a Friedel-Crafts acylation followed by Wittig reaction. The effects of the compounds on standard strains of Mycobacterium sp. (ATCC) and M. tuberculosis isolated from clinical specimens were evaluated. Also the toxicity was determined on V79 cells line using neutral red uptake (NRU), nucleic acid content (NAC) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction to measure the cellular viability.

Antimycobacterial activity of 4'-bromo-[1,1'-biphenyl]-4-yl 4-x-phenylmethanone derivatives, and their acute toxicity and cytotoxicity.

The antimycobacterial activity of nine biphenyl methanone (BPM) derivatives against standard strains of Mycobacterium kansasii, M. avium and M. malmoense was determined by colorimetric assay in microplates with the dye Alamar Blue. Acute toxicity of these compounds was also analyzed by determination of CO2 concentration in a respirometric assay using Escherichia coli. The compounds showed weak antimycobacterial activity with a minimal inhibitory concentration (MIC) over 0.038 mmol l-1 and no toxicity was found in E. coli up to 400 mmol l-1. No cytotoxicity was observed on V79 cells up to 0.35 mmol l-1 with 7 of the BPM derivatives, with two exceptions (X = SO2CH3, NO2) that showed some toxicity. The greatest antimycobacterial activity was observed with the SO2CH3 derivative and the application of Principal Component Analysis (PCA) showed a relationship between structure and antimycobacterial activity of the compounds. Two descriptors, nucleophilic superdelocalizability of carbon atom and pi-hydrophobic constant, were necessary to describe this relationship.

Frontoethmoidal mucocele with intracranial extension: a case report.

Mucoceles with intracranial extension are often reported by otolaryngologists and neurosurgeons. The authors present a case of a large frontoethmoidal mucocele with intracranial and intraorbital extension exerting a mass effect on the anterior cranial fossa. The patient experienced spontaneous drainage of the mucocele without evidence of recurrence of the lesion after a one-year period, suggesting that mucoceles, regardless of size, can be treated with conservative procedures such as functional endoscopic sinus surgery.