Fractalkine (C-X3-C motif chemokine ligand 1) as a potential biomarker for depression and anxiety in colorectal cancer patients.

Fractalkine, a unique chemokine of the CX3C subfamily, is involved in the pathogenesis of different types of cancer and also in non-immune mechanisms associated with psychiatric disorders. The aim of the present study was to investigate whether there is a correlation between anxiety, depression and fractalkine serum levels in colorectal cancer (CRC) patients in different stages of antitumor therapy. Four groups of patients undergoing treatment (n=20 per group) were evaluated: Patients with CRC who did not undergo surgical resection of the tumor; patients who underwent resection and who did not start adjuvant therapy; patients undergoing chemotherapy for ~3 months; and patients who had completed adjuvant chemotherapy regimen for ~6 months. The control group was composed of 20 healthy volunteers free of any psychiatric or immune system disease. Depression and anxiety were evaluated using the Hospital Anxiety and Depression Scale (HADS) and serum levels of fractalkine were measured by cytometric bead array. Clinically relevant levels of anxiety and/or depression were observed in all of the CRC patients at the different stages of antitumor therapy. Elevated serum levels of fractalkine were identified in the CRC patients in the pre-surgery (P<0.001) and pre-chemotherapy (P<0.001) groups, but reduced upon chemotherapy (P<0.05). Furthermore, a positive correlation was observed between fractalkine levels and the HADS scores in the CRC patients at different stages of antitumor therapy. These results demonstrate a link between fractalkine, depression and anxiety in CRC patients indicating that this chemokine is involved in the pathophysiology of these comorbidities. An improved understanding of the molecular mechanisms involved in these psychological disorders will allow the design of novel therapeutic strategies to assist in alleviating such symptoms in cancer patients. Therefore, fractalkine may present as a relevant biomarker for depression and anxiety in CRC patients.

Modelo de parkinson por lesão unilateral induzida pela 6-hidroxidopamina: análises comportamentais e imunohistoquímicas / Parkinson model for unilateral injury induced by 6-hydroxidopamine: behavioral and immunohistochemistry analysis

Introdução: A doença de Parkinson é uma doença neurodegenerativa crônica complexa que afeta o sistema dopaminérgico e atinge cercade 3% da população mundial acima de 50 anos. Clinicamente, a doença de Parkinson não é diagnosticada antes da manifestação dessasdifi culdades locomotoras, o que contribuiu para o diagnóstico tardio da doença e a dominância de modelos animais de estudos baseadosnessas características. Embora o uso de modelos animais seja limitado em diversos aspectos, devido às diferenças genéticas, anatômicase funcionais entre murinos e humanos, muito do nosso conhecimento a respeito da patofi siologia da doença é devido ao uso destasferramentas. Objetivos: Estabelecer modelo de estudo da doença de Parkinson, reprodutível e validado por testes comportamentais eimuno-histoquímicos. Método: O modelo murino de lesão unilateral induzida pela 6-hidroxidopamina (6-OHDA) foi realizado por meio decirurgia estereotáxica para administração intracranicana, no feixe medial do encéfalo anterior (MFB). A toxina foi infundida a uma taxade 1uL/min, e a cânula foi deixada no lugar por 3 min antes da retirada. Para limitar os danos nos neurônios noradrenérgicos, cloridratode desipramina (10 mg/kg, i.p) foram administrados 30 min antes da injeção de 6-OHDA. Os animais controles foram submetidos aomesmo procedimento estereotáxico, mas com solução salina...

Introduction: Parkinson's disease is a complex chronic neurodegenerative disease, damaging the dopaminergic system and affectingabout 3% of the world population over 50 years. Clinically, Parkinson's disease is not diagnosed prior to the manifestation of theselocomotor diffi culties, thus contributing to the late disease diagnosis and to the dominance of animal models of studies based on thesecharacteristics. Although the use of animal models is limited in several aspects due to genetic, anatomical and functional differencesbetween murine and human, much of our knowledge about the pathophysiology of the disease is due to the use of these tools.Objectives: To establish Parkinson's disease study models, reproducible and validated by behavioral and immunohistochemical tests.Method: The murine model of unilateral lesion induced by 6-hydroxydopamine (6-OHDA) was performed by stereotactic surgery forintracranial administration in the medial bundle of the forebrain (MFB). The toxin was infused at a rate of 1µL/ min, and the cannulawas left in place for 3 min prior to withdrawal...

Introducción: La enfermedad de Parkinson es una enfermedad neurodegenerativa crónica compleja que afecta al sistema dopaminérgicoy alcanza cerca del 3% de la población mundial por encima de 50 años. Clínicamente, la enfermedad de Parkinson no se diagnostica antesde la manifestación de esas difi cultades locomotoras, lo que contribuyó al diagnóstico tardío de la enfermedad y la dominación de modelosanimales de estudios basados en esas características. Aunque el uso de modelos animales es limitado en diversos aspectos, debido a las...

Heterogeneity of mast cells and expression of Annexin A1 protein in a second degree burn model with silver sulfadiazine treatment.

Mast cells (MCs) participate in all stages of skin healing and one of their mediators is the Annexin A1 protein (AnxA1), linked to inflammation, proliferation, migration and apoptosis processes, but not studied in thermal burns yet. Therefore, our objectives were to evaluate the behavior of MCs and AnxA1 in a second degree burn model, treated or not with silver sulfadiazine 1% (SDP 1%) and associated to macrophages quantification and cytokines dosages. MCs counts showed few cells in the early stages of repair but increased MCs in the final phases in the untreated group. The normal skin presented numerous tryptase-positive MCs that were reduced after burning in all analyzed periods. Differently, few chymase-positive MCs were observed in the early stages of healing, however, increased chymase-positive MCs were found at the final phase in the untreated group. MCs also showed high immunoreactivity for AnxA1 on day 3 in both groups. In the tissue there was a strong protein expression in the early stages of healing, but in the final phases only in the SDP treated animals. TNF-α, IL-1ß, IL-6, IL-10 and MCP-1 levels and macrophages quantification were increased in inflammation and reepithelialization phases. Reduced IL-1ß, IL-6 and IL-10 levels and numerous macrophages occurred in the treated animals during tissue repair. Our results indicate modulation in the profile of MCs and AnxA1expression during healing by the treatment with SDP 1%, pointing them as targets for therapeutic interventions on skin burns.

Humoral immune responses against the malaria vaccine candidate antigen Plasmodium vivax AMA-1 and IL-4 gene polymorphisms in individuals living in an endemic area of the Brazilian Amazon.

BACKGROUND: Several studies have recently demonstrated that the immune responses against malaria is governed by different factors, including the genetic components of the host. The IL-4 gene appears to be a strong candidate factor because of its role in the regulation of the Th2 response. The present study investigated the role of IL-4 polymorphisms in the development of IgG antibodies against PvAMA-1 and the IL-4 levels in individuals infected with Plasmodium vivax in a malaria endemic area in the Brazilian Amazon. METHODS: The study sample included 83 patients who were diagnosed with P. vivax infection using thick smear and confirmed by nested-PCR. The IL-4 -590C>T and IL-4 -33C>T polymorphisms were genotyped by PCR-RFLP, and the intron 3 VNTR was genotyped by PCR. A standardised ELISA protocol was used to measure the total IgG against PvAMA-1. The cytokine/chemokine levels were measured using a Milliplex multiplex assay (Millipore). All of the subjects were genotyped with 48 ancestry informative markers to determine the proportions of African, European and Amerindian ancestry using STRUCTURE software. RESULTS: Of the 83 patients, 60 (73%) produced IgG antibodies against PvAMA-1. A significant decrease in the percentage of respondents was observed among the primo-infected individuals. No significant differences were observed in the frequencies of genotypes and haplotypes among individuals who were positive or negative for IgG antibodies against PvAMA-1. Furthermore, no significant correlation was observed between the IL-4 polymorphisms, antibody levels, IL-4 levels, and parasitemia. CONCLUSIONS: This study indicated that the polymorphisms identified in the IL-4 gene are not likely to play a role in the regulation of the antibody response against PvAMA-1 and IL-4 production in vivax malaria.