Search

Multiple sclerosis is an autoimmune treatable but not curable disease. There are a multiplicity of medications for multiple sclerosis therapy, including a class entitled disease-modifying drugs that are mainly indicated to reduce the number and severity of disease relapses. Not all patients respond well to these therapies, and minor to severe adverse effects have been reported. Vitamin D, called sunshine vitamin, is being studied as a possible light at the end of the tunnel. In this review, we recapitulated the similar immunopathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis, the immunomodulatory and neuroprotective potential of vitamin D and the state-of-art concerning its supplementation to multiple sclerosis patients. Finally, based on our and other groups’ experimental findings, we analyzed the need to consider the relevance of the route and the different time-point administration aspects for a more rational indication of this vitamin to multiple sclerosis patients.

The COVID-19 pandemic was triggered by the coronavirus SARS-CoV-2, whose peak occurred in the years 2020 and 2021. The main target of this virus is the lung, and the infection is associated with an accentuated inflammatory process involving mainly the innate arm of the immune system. Here, we described the induction of a pulmonary inflammatory process triggered by the intranasal (IN) instillation of UV-inactivated SARS-CoV-2 in C57BL/6 female mice, and then the evaluation of the ability of vitamin D (VitD) to control this process. The assays used to estimate the severity of lung involvement included the total and differential number of cells in the bronchoalveolar lavage fluid (BALF), histopathological analysis, quantification of T cell subsets, and inflammatory mediators by RT-PCR, cytokine quantification in lung homogenates, and flow cytometric analysis of cells recovered from lung parenchyma. The IN instillation of inactivated SARS-CoV-2 triggered a pulmonary inflammatory process, consisting of various cell types and mediators, resembling the typical inflammation found in transgenic mice infected with SARS-CoV-2. This inflammatory process was significantly decreased by the IN delivery of VitD, but not by its IP administration, suggesting that this hormone could have a therapeutic potential in COVID-19 if locally applied. To our knowledge, the local delivery of VitD to downmodulate lung inflammation in COVID-19 is an original proposition.

Abstract Multiple sclerosis is an autoimmune disease that affects the myelinated central nervous system (CNS) neurons and triggers physical and cognitive disabilities. Conventional therapy is based on disease-modifying drugs that control disease severity but can also be deleterious. Complementary medicines have been adopted and evidence indicates that yeast supplements can improve symptoms mainly by modulating the immune response. In this investigation, we evaluated the therapeutic potential of Saccharomyces cerevisiae and its selenized derivative (Selemax) in experimental autoimmune encephalomyelitis (EAE). Female C57BL/6 mice submitted to EAE induction were orally supplemented with these yeasts by gavage from day 0 to day 14 after EAE induction. Both supplements determined significant reduction in clinical signs concomitantly with diminished Th1 immune response in CNS, increased proportion of Foxp3+ lymphocytes in inguinal and mesenteric lymph nodes and increased microbiota diversity. However, Selemax was more effective clinically and immunologically; it reduced disease prevalence more sharply, increased the proportion of CD103+ dendritic cells expressing high levels of PD-L1 in mesenteric lymph nodes and reduced the intestinal inflammatory process more strongly than S. cerevisiae. These results suggest a clear gut-brain axis modulation by selenized S. cerevisiae and suggest their inclusion in clinical trials.

Mast cells are immune cells of the myeloid lineage that are found throughout the body, including the central nervous system. They perform many functions associated with innate and specific immunity, angiogenesis, and vascular homeostasis. Moreover, they have been implicated in a series of pathologies (e.g., hypersensitivity reactions, tumors, and inflammatory disorders). In this review, we propose that this cell could be a relevant therapeutic target in multiple sclerosis, which is a central nervous system degenerative disease. To support this proposition, we describe the general biological properties of mast cells, their contribution to innate and specific immunity, and the participation of mast cells in the various stages of multiple sclerosis and experimental autoimmune encephalomyelitis development. The final part of this review is dedicated to an overview of the available mast cells immunomodulatory drugs and their activity on multiple sclerosis and experimental autoimmune encephalomyelitis, including our own experience related to the effect of ketotifen fumarate on experimental autoimmune encephalomyelitis evolution.

Candidiasis may affect the central nervous system (CNS), and although Candida albicans is predominant, non-albicans Candida species can also be associated with CNS infections. Some studies have suggested that Candida infections could increase the odds of multiple sclerosis (MS) development. In this context, we investigated whether systemic infection by non-albicans Candida species would affect, clinically or immunologically, the severity of experimental autoimmune encephalomyelitis (EAE), which is an animal model used to study MS. For this, a strain of C. glabrata, C. krusei, and C. parapsilosis was selected and characterized using different in vitro and in vivo models. In these analysis, all the strains exhibited the ability to form biofilms, produce proteolytic enzymes, and cause systemic infections in Galleria mellonella, with C. glabrata being the most virulent species. Next, C57BL/6 mice were infected with strains of C. glabrata, C. krusei, or C. parapsilosis, and 3 days later were immunized with myelin oligodendrocyte glycoprotein to develop EAE. Mice from EAE groups previously infected with C. glabrata and C. krusei developed more severe and more prevalent paralysis, while mice from the EAE group infected with C. parapsilosis developed a disease comparable to non-infected EAE mice. Disease aggravation by C. glabrata and C. krusei strains was concomitant to increased IL-17 and IFN-γ production by splenic cells stimulated with fungi-derived antigens and with increased percentage of T lymphocytes and myeloid cells in the CNS. Analysis of interaction with BV-2 microglial cell line also revealed differences among these strains, in which C. krusei was the strongest activator of microglia concerning the expression of MHC II and CD40 and pro-inflammatory cytokine production. Altogether, these results indicated that the three non-albicans Candida strains were similarly able to reach the CNS but distinct in terms of their effect over EAE development. Whereas C. glabrata and C. Krusei aggravated the development of EAE, C. parapsilosis did not affect its severity. Disease worsening was partially associated to virulence factors in C. glabrata and to a strong activation of microglia in C. krusei infection. In conclusion, systemic infections by non-albicans Candida strains exerted influence on the experimental autoimmune encephalomyelitis in both immunological and clinical aspects, emphasizing their possible relevance in MS development.

Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the central nervous system (CNS). The persistent inflammation is being mainly attributed to local oxidative stress and inflammasome activation implicated in the ensuing demyelination and axonal damage. Since new control measures remain necessary, we evaluated the preventive and therapeutic potential of a beta-selenium-lactic acid derivative (LAD-βSe), which is a source of organic selenium under development, to control experimental autoimmune encephalomyelitis (EAE) that is an animal model for MS. Two EAE murine models: C57BL/6 and SJL/J immunized with myelin oligodendrocyte glycoprotein and proteolipid protein, respectively, and a model of neurodegeneration induced by LPS in male C57BL/6 mice were used. The preventive potential of LAD-βSe was initially tested in C57BL/6 mice, the chronic MS model, by three different protocols that were started 14 days before or 1 or 7 days after EAE induction and were extended until the acute disease phase. These three procedures were denominated preventive therapy −14 days, 1 day, and 7 days, respectively. LAD-βSe administration significantly controlled clinical EAE development without triggering overt hepatic and renal dysfunction. In addition of a tolerogenic profile in dendritic cells from the mesenteric lymph nodes, LAD-βSe also downregulated cell amount, activation status of macrophages and microglia, NLRP3 (NOD-like receptors) inflammasome activation and other pro-inflammatory parameters in the CNS. The high Se levels found in the CNS suggested that the product crossed the blood-brain barrier having a possible local effect. The hypothesis that LAD-βSe was acting locally was then confirmed by using the LPS-induced neurodegeneration model that also displayed Se accumulation and downmodulation of pro-inflammatory parameters in the CNS. Remarkably, therapy with LAD-βSe soon after the first remitting episode in SJL/J mice, also significantly downmodulated local inflammation and clinical disease severity. This study indicates that LAD-βSe, and possibly other derivatives containing Se, are able to reach the CNS and have the potential to be used as preventive and therapeutic measures in distinct clinical forms of MS.

Multiple sclerosis (MS) is a progressive disease of the central nervous system (CNS) that involves damage to the myelin sheath surrounding axons. MS therapy is based on immunomodulatory drugs that reduce disease recurrence and severity. Vitamin D is a hormone whose immunomodulatory ability has been widely demonstrated, including in experimental autoimmune encephalomyelitis (EAE), which is an animal model of CNS inflammation. In this study, we evaluated the potential of very early intervention with the active form of vitamin D (1,25-dihydroxyvitamin D3) to control neuroinflammation during EAE development. EAE was induced in C57BL/6J mice and 1,25-dihydroxyvitamin D3 administration began 1 day after disease induction. This procedure decreased prevalence, clinical score, inflammation, and demyelination. It also reduced MHCII expression in macrophages and microglia as well as the level of oxidative stress and messenger RNA (mRNA) expression for NLRP3, caspase-1, interleukin (IL)-1β, CX3CR1, CCL17, RORc and Tbx21 at the CNS. Otherwise, mRNA expression for ZO-1 increased at the lumbar spinal cord. These effects were accompanied by the stabilization of blood-spinal cord barrier permeability. The results of this study indicate that early intervention with 1,25-dihydroxyvitamin D3 can control the neuroinflammatory process that is the hallmark of EAE and MS immunopathogenesis and should thus be explored as an adjunct therapy for MS patients.

Abstract Background The injection of mesenchymal stem cells (MSCs) directly into the bone of osteoporotic (OP) patients for rapid recovery has been studied worldwide. Scaffolds associated with MSCs are used to maintain and avoid cell loss after application. A unique heterologous fibrin sealant (HFS) derived from snake venom was evaluated for the cytotoxicity of its main components and as a three-dimensional biological scaffold for MSCs to repair a critical femur defect in osteoporotic rats. Methods The cytotoxicity of HFS was assessed using a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazoliumbromide (MTT) assay and transmission electron microscopy. The cells were cultured, characterized by flow cytometry and differentiated into the osteogenic lineage. Two-month-old rats underwent ovariectomy to induce OP. After 3 months, a 5 mm critical bone defect was made in the distal end of the rat femurs and filled with HFS; HFS + MSCs; and HFS + MSCs D (differentiated into the osteogenic lineage) to evaluate the effects. An injury control group (injury and no treatment) and blank control group (no injury and no treatment) were also included. The animals were observed at days 14 and 28 by microtomographic (micro-CT) analyses, histologic and biochemical analysis, as well as scanning electron microscopy. Results The results revealed that one of the compounds of HFS, the thrombin-like enzyme extracted from snake venom, had no cytotoxic effects on the MSCs. OP was successfully induced, as demonstrated by the significant differences in the levels of 17β-estradiol, Micro-CT analyses and alkaline phosphatase between the ovariectomized (OVX) and non-ovariectomized (NOVX) groups. The histological data revealed that at 14 days after surgery in both the OVX and NOVX animals, the HFS + CTMs and HFS + CTMsD showed a higher formation of bone cells at the site in relation to the control group (without treatment). Collagen formation was evidenced through bone neoformation in all treated and control groups. No morphological differences in the femurs of the NOVX and OVX animals were observed after the surgical procedure. Scanning electron microscopy (SEM) confirmed the histological analysis. Conclusions The new HFS composed of two non-toxic components for MSCs showed capacity to promote the recovery of the bone lesions in OVX and NOVX animals at 14 days after surgery. In addition, the HFS enabled the differentiation of MSCs into MSCs D in the group treated with HFS + MSCs. Using the MSCs and/or MSCs D together with this biopharmaceutical could potentially enable significant advances in the treatment of osteoporotic fractures. Future clinical trials will be necessary to confirm these results.

Fibrin scaffold fits as a provisional platform promoting cell migration and proliferation, angiogenesis, connective tissue formation and growth factors stimulation. We evaluated a unique heterologous fibrin biopolymer as scaffold to mesenchymal stem cells (MSCs) to treat a critical-size bone defect. Femurs of 27 rats were treated with fibrin biopolymer (FBP); FBP + MSCs; and FBP + MSC differentiated in bone lineage (MSC-D). Bone repair was evaluated 03, 21 and 42 days later by radiographic, histological and scanning electron microscopy (SEM) imaging. The FBP + MSC-D association was the most effective treatment, since newly formed Bone was more abundant and early matured in just 21 days. We concluded that FBP is an excellent scaffold for MSCs and also use of differentiated cells should be encouraged in regenerative therapy researches. The FBP ability to maintain viable MSCs at Bone defect site has modified inflammatory environment and accelerating their regeneration.

Multiple sclerosis (MS) is an inflammatory and demyelinating disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely employed to evaluate new strategies to control MS, including procedures to induce immunological tolerance. Considering that skin exposure to protein antigens can induce tolerance and that vitamin D analogs conserve immunomodulatory potential and are less toxic, we investigated the efficacy of epicutaneous application of a myelin oligodendrocyte glycoprotein peptide (MOG35–55) associated with paricalcitol (PARI) on EAE development. Three and 11 days after EAE induction, C57BL/6 mice were treated with an occlusive patch containing MOG plus PARI. Clinical parameters were daily assessed, whereas immunological and histological evaluations were performed during the acute EAE phase. MOG and MOG + PARI significantly controlled disease development reducing weight loss and clinical score. Moreover, MOG and MOG + PARI reduced the inflammatory process and preserved the myelin sheath in the CNS. High percentages of Foxp3+ regulatory T cells (Tregs) and lower MHCII fluorescence intensity in dendritic cells in draining lymph nodes were concomitantly observed. MOG + PARI association was, however, more efficient being able to reduce disease incidence and clinical scores more significantly than MOG or PARI alone. This experimental group also displayed a higher ratio between mRNA expression for Foxp3 and RORc and a higher percentage of Foxp3+ cells in the CNS. Modulation of activation markers observed in microglial cells eluted from EAE treated mice were confirmed by in vitro studies with the BV-2 microglial cell line. The results show that MOG + PARI association applied by an epicutaneous route controlled EAE development. Protective involved mechanisms include mainly a higher proportion of Tregs and also a direct immunomodulatory effect of PARI on microglial cells.

Experimental autoimmune encephalomyelitis (EAE) is a demyelinating pathology of the central nervous system (CNS) used as a model to study multiple sclerosis immunopathology. EAE has also been extensively employed to evaluate potentially therapeutic schemes. Considering the presence of an immune response directed to heat shock proteins (hsps) in autoimmune diseases and the immunoregulatory potential of these molecules, we evaluated the effect of a previous immunization with a genetic vaccine containing the mycobacterial hsp65 gene on EAE development. C57BL/6 mice were immunized with 4 pVAXhsp65 doses and 14 days later were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein (MOG35–55) emulsified in Complete Freund’s Adjuvant. Vaccinated mice presented significant lower clinical scores and lost less body weight. MOG35–55 immunization also determined less inflammation in lumbar spinal cord but did not change CD4+CD25+Foxp3+ T cells frequency in spleen and CNS. Infiltrating cells from the CNS stimulated with rhsp65 produced significantly higher levels of IL-10. These results suggest that the ability of pVAXhsp65 vaccination to control EAE development is associated with IL-10 induction.

This study was undertaken to evaluate the prophylactic potential of proteoglycan (PG) administration in experimental arthritis. Female BALB/c retired breeder mice received two (2xPG50 and 2xPG100 groups) or three (3xPG50 group) intraperitoneal doses of bovine PG (50 μg or 100 μg) every three days. A week later the animals were submitted to arthritis induction by immunization with three i.p. doses of bovine PG associated with dimethyldioctadecylammonium bromide adjuvant at intervals of 21 days. Disease severity was daily assessed after the third dose by score evaluation. The 3xPG50 group showed significant reduction in prevalence and clinical scores. This protective effect was associated with lower production of IFN-γ and IL-17 and increased production of IL-5 and IL-10 by spleen cells restimulated in vitro with PG. Even though previous PG administration restrained dendritic cells maturation this procedure did not alter the frequency of regulatory Foxp3+ T cells. Lower TNF-α and IL-6 levels and higher expression of ROR-γ and GATA-3 were detected in the paws of protected animals. A delayed-type hypersensitivity reaction confirmed specific tolerance induction. Taken together, these results indicate that previous PG inoculation determines a specific tolerogenic effect that is able to decrease severity of subsequently induced arthritis.

Background: Recently, various biostimulation′s effects of low energy laser irradiation have been reported. The present study was designed to examine the effects of low-energy laser irradiation on alveolar bone remodelling during orthodontic tooth movement and finally on formation of new keratinized gingiva. Materials and Methods: 22 patients and 27 teeth in vestibular mucosal without keratinized gingiva were selected. Every patient was treated with self ligating appliances. In every orthodontic session the patient was treated with Diode laser biostimulation. At the moment of debonding, 27 teeth involved in the research were evaluated in terms of quality and quantity of attached gingiva. BOP and CAL loss were investigated. Results: Every tooth considered at the end of orthodontic treatment showed an attached gingiva around the crown: The average of keratinized gingiva at the end of the study was 3.10 mm and the mean increasing at each month was 0,49 mm. Conclusions: The combination between self ligating appliances and laser′s biostimulation could improve the differentiation of periodontal ligaments stem cells in fibroblasts, able to promote attached gingiva around the crown of the teeth erupted in oral vestibular mucosa.

Ferruccio Rossi-Landi locates in communication the backbone of the material and immaterial production, anticipating some central issues of the current phase of the capitalist form. At the center of rossilandian theory is the interpretation of goods as messages and messages as commodities, based on a homology between the linguistic sphere and the economic sphere. The advantage of a homological study of social phenomena is in homology ability to translate into a semiotics of social sign systems and incorporate within it the economy as a field of semiotics. Being a branch of semiotics, the economy is therefore one of the social sciences and humanities. The inclusion of economic science in this area makes Rossi-Landi proposal extremely timely especially in view of a rethinking of today's general economic structures.

Experimental autoimmune encephalomyelitis (EAE) is mediated by CD4+ Th1 cells that mainly secrete IFN-γ and TNF-α, important cytokines in the pathophysiology of the disease. Spontaneous remission is, in part, attributed to the down regulation of IFN-γ and TNF-α by TGF-β. In the current paper, we compared weight, histopathology and immunological parameters during the acute and recovery phases of EAE to establish the best biomarker for clinical remission. Female Lewis rats were immunised with myelin basic protein (MBP) emulsified with complete Freund's adjuvant. Animals were evaluated daily for clinical score and weight prior to euthanisation. All immunised animals developed the expected characteristics of EAE during the acute phase, including significant weight loss and high clinical scores. Disease remission was associated with a significant reduction in clinical scores, although immunised rats did not regain their initial weight values. Brain inflammatory infiltrates were higher during the acute phase. During the remission phase, anti-myelin antibody levels increased, whereas TNF-α and IFN-γ production by lymph node cells cultured with MBP or concanavalin A, respectively, decreased. The most significant difference observed between the acute and recovery phases was in the induction of TNF-α levels in MBP-stimulated cultures. Therefore, the in vitro production of this cytokine could be used as a biomarker for EAE remission.

More sensitive methodologies are necessary to improve strongyloidiasis diagnosis. This study compared the sensitivities of the McMaster modified technique and polymerase chain reaction (PCR) assays, both performed in faecal samples. Lewis rats were subcutaneously infected with 4,000, 400 or 40 infective third-stage larvae, considered as high, moderate or low infection, respectively. Seven days later, they were euthanized to count adult nematodes recovered from the small intestine. Stool samples were used to count the number of eggs per gram (EPG) of faeces and to detect parasite DNA by PCR performed with a species and a genus primer pair. The sensitivity of these assays depended upon parasite burden and the primer specificity. All assays presented 100% sensitivity at the highest parasite load. In the moderate infection, EPG and PCR with the genus primer maintained 100% specificity, whereas PCR sensitivity with the species primer decreased to 77.7%. In low infection, the sensitivity was 60% for EPG, 0% for PCR with the species primer and 90% for PCR done with the genus primer. Together, these results suggest that PCR with a genus primer can be a very sensitive methodology to detect Strongyloides venezuelensisin faeces of Lewis rats infected with very low parasite burden.

Malnutrition may be a consequence of energy deficit or micronutrient deficiency. It is considered the most relevant risk factor for illness and death, particularly in developing countries. In this review we described the magnitude of this problem, as well as its direct effect on the immune system and how it results in higher susceptibility to infections. A special emphasis was given to experimental models used to investigate the relationship between undernutrition and immunity. Malnutrition is obviously a challenge that must be addressed to health authorities and the scientific community.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the brain and spinal cord that is mediated by CD4+ T lymphocytes specific to myelin components. In this study we compared development of EAE in Lewis rats from two colonies, one kept in pathogen-free conditions (CEMIB colony) and the other (Botucatu colony) kept in a conventional animal facility. Female Lewis rats were immunized with 100 µl of an emulsion containing 50 µg of myelin, associated with incomplete Freund's adjuvant plus Mycobacterium butyricum. Animals were daily evaluated for clinical score and weight. CEMIB colony presented high EAE incidence with clinical scores that varied from three to four along with significant weight losses. A variable disease incidence was observed in the Botucatu colony with clinical scores not higher than one and no weight loss. Immunological and histopathological characteristics were also compared after 20 days of immunization. Significant amounts of IFN-gamma, TNF-alpha and IL-10 were induced by myelin in cultures from CEMIB animals but not from the Botucatu colony. Significantly higher levels of anti-myelin IgG1 were detected in the CEMIB colony. Clear histopathological differences were also found. Cervical spinal cord sections from CEMIB animals showed typical perivascular inflammatory foci whereas samples from the Botucatu colony showed a scanty inflammatory infiltration. Helminths were found in animals from Botucatu colony but not, as expected, in the CEMIB pathogen-free animals. As the animals maintained in a conventional animal facility developed a very discrete clinical, and histopathological EAE in comparison to the rats kept in pathogen-free conditions, we believe that environmental factors such as intestinal parasites could underlie this resistance to EAE development, supporting the applicability of the hygiene hypothesis to EAE.

Multiple sclerosis (MS) is an inflammatory/autoimmune disease of the central nervous system (CNS) mainly mediated by myelin specific T cells. It is widely believed that environmental factors, including fungal infections, contribute to disease induction or evolution. Even though Candida infection among MS patients has been described, the participation of this fungus in this pathology is not clear. The purpose of this work was to evaluate the effect of a Candida albicans infection on experimental autoimmune encephalomyelitis (EAE) that is a widely accepted model to study MS. Female C57BL/6 mice were infected with C. albicans and 3 days later, animals were submitted to EAE induction by immunization with myelin oligodendrocyte glycoprotein. Previous infection increased the clinical score and also the body weight loss. EAE aggravation was associated with expansion of peripheral CD4+ T cells and production of high levels of TNF-α, IFN-γ IL-6, and IL-17 by spleen and CNS cells. In addition to yeast and hyphae, fungus specific T cells were found in the CNS. These findings suggest that C. albicans infection before EAE induction aggravates EAE, and possibly MS, mainly by CNS dissemination and local induction of encephalitogenic cytokines. Peripheral production of encephalitogenic cytokines could also contribute to disease aggravation.

Experimental autoimmune encephalomyelitis (EAE) is an animal model to study multiple sclerosis (MS). Considering the tolerogenic effects of active vitamin D, we evaluated the therapeutic effect of myelin oligodendrocyte glycoprotein (MOG) associated with active vitamin D in EAE development. EAE was induced in female C57BL/6 mice by immunization with MOG emulsified with Complete Freund's Adjuvant plus Mycobacterium tuberculosis. Animals also received two intraperitoneal doses of Bordetella pertussis toxin. One day after immunization, mice were treated with 0,1 μg of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) every other day during 15 days (on days 1, 3, 5, 7, 9, 11, 13 and 15). MOG (150 μg) was co-administered on days 3 and 11. The administration of 1,25(OH)2D3 or MOG determined significant reduction in EAE incidence and in clinical scores. When MOG was associated with 1,25(OH)2D3 the animals did not develop EAE. Spleen and central nervous system (CNS) cell cultures from this group produced less IL-6 and IL-17 upon stimulation with MOG in comparison to the EAE control group. In addition, this treatment inhibited dendritic cells maturation in the spleen and reduced inflammatory infiltration in the CNS. The association of MOG with 1,25(OH)2D3 was able to control EAE development.

Experimental autoimmune encephalomyelitis (EAE) is an artificially induced demyelination of the central nervous system (CNS) that resembles multiple sclerosis in its clinical, histopathological, and immunological features. Activated Th1 and Th17 cells are thought to be the main immunological players during EAE development. This study was designed to evaluate peripheral and local contribution of IL-17 to acute and chronic EAE stages. C57BL/6 mice were immunized with MOG plus complete Freund’s adjuvant followed by pertussis toxin. Mice presented an initial acute phase characterized by accentuated weight loss and high clinical score, followed by a partial recovery when the animals reached normal body weight and smaller clinical scores. Spleen cells stimulated with MOG produced significantly higher levels of IFN-γ during the acute period whereas similar IL-17 levels were produced during both disease stages. CNS-infiltrating cells stimulated with MOG produced similar amounts of IFN-γ but, IL-17 was produced only at the acute phase of EAE. The percentage of Foxp3+ Treg cells, at the spleen and CNS, was elevated during both phases. The degree of inflammation was similar at both disease stages. Partial clinical recovery observed during chronic EAE was associated with no IL-17 production and presence of Foxp3+ Treg cells in the CNS.

A prime-boost strategy conserving BCG is considered the most promising vaccine to control tuberculosis. A boost with a DNA vaccine containing the mycobacterial gene of a heat shock protein (pVAXhsp65) after BCG priming protected mice against experimental tuberculosis. However, anti-hsp65 immunity could worsen an autoimmune disease due to molecular mimicry. In this investigation, we evaluated the effect of a previous BCG or BCG/pVAXhsp65 immunization on experimental autoimmune encephalomyelitis (EAE) development. Female Lewis rats were immunized with BCG or BCG followed by pVAXhsp65 boosters. The animals underwent EAE induction and were daily evaluated for weight loss and clinical score. They were euthanized during recovery phase to assess immune response and inflammatory infiltration at the central nervous system. Previous immunization did not aggravate or accelerate clinical score or weight loss. In addition, this procedure clearly decreased inflammation in the brain. BCG immunization modulated the host immune response by triggering a significant reduction in IL-10 and IFN-γ levels induced by myelin basic protein. These data indicated that vaccination protocols with BCG or BCG followed by boosters with pVAXhsp65 did not trigger a deleterious effect on EAE evolution.

Aim of this study is analyze the effects of dental occlusion on postural stability in patients with previous whiplash and normal occlusion. Materials and methods: 36 adult patients with previous whiplash and normal occlusion (good alignment, 1 st class or mild 2 nd class deep bite for mandibular retrusion) were selected. The patients were suffering from masticatory muscles pain caused by clenching during sleep. Exclusion criteria: use of psych drugs. To simulate the conditions of sleep (with a reduction of proprio-and esteroceptive inputs for postural management performed by CNS), we used postural Romberg analysis (feet together, closed eyes)on stabilometric platform changing occlusal parameters only, under the following conditions: 1) in occlusal rest position, 2) in centric occlusion, 3) in clenching, 4) with occlusal disengage with cotton rolls and 5) in clenching on cotton rolls. Time of each test: 15 seconds. It was performed a statistical analysis with T-test comparing between them the mean of all tests. Results: stabilometry data (postural ball and ellipse) show better postural performances in centric occlusion and clenching in centric occlusion, and a worsening in all tests with occlusal disengage (with statistically significant difference - p

24 patients are selected and 30 teeth in vestibular mucosae, without keratinized gingiva. No active periodontal disease (no BOP and gingival recessions). No BOP and CAL loss at the start of the orthodontic treatment. Every patient was treated with self ligating appliances (Time2/Time3, American Orthodontics). In every orthodontic session (each 30 days as average) the patient was treated with Nd: Yag laser biostimulation, for 90 seconds, with 320 micron fiber section, on utilizing the Biostimulating machine paremeters. No termical effects were produced by lasers applications. At the moment of debonding, 30 teeth involved in the research were evaluated in terms of quality and quantity of attached gingiva. BOP and CAL loss were also investigated. Every tooth considerated, at the end of orthodontic treatment showed a attached gingiva around the crown: the average of keratinized gingiva at the end of the study was 2,7 mm and the mean increasing at each month was 0,45 mm. The combination between self ligating appliances and laser's biostimulation could improve the differentiation of periodontal ligaments stem cells in fibroblasts, able to promote attached gingiva around the crown of the teeth erupted in oral vestibular mucosae.

IntroductionMicronutrient deficiency is observed in heart failure patients. Taurine, for example, represents 50% of total free amino acids in the heart, and in vivo studies have linked taurine deficiency with cardiomyopathy.MethodsThirty-four male Wistar rats (body weight = 100 g) were weighed and randomly assigned to one of two groups: Control (C) or taurine-deficient (T (-)). Beta-alanine at a concentration of 3% was added to the animals' water to induce taurine deficiency in the T (-) group. On day 30, the rats were individually submitted to echocardiography; morphometrical and histopathological evaluation and metalloproteinase activity, oxidative stress and inflammation evaluation were performed. Tissue samples were collected to determine the taurine concentration in the heart.ResultsTaurine deficiency led to decreases in: ventricular wall thickness, left ventricle dry weight, myocyte sectional area, left ventricle posterior wall thickness and ventricular geometry. With regard to heart function, the velocity of the A wave, the ratio between the E and A wave, the ejection fraction, fractional shortening and cardiac output values were decreased in T (-) rats, suggesting abnormal diastolic and systolic function. Increased fibrosis, inflammation and increased activation of metalloproteinases were not observed. Oxidative stress was increased in deficient animals.ConclusionsThese data suggest that taurine deficiency promotes structural and functional cardiac alterations with unique characteristics.

Cellular immunity is critical for protection against tuberculosis, but its integrity is compromised during undernutrition. The present study was designed to evaluate if the attenuated mycobacterium BCG is a safe vaccine for undernourished individuals. An experimental model of undernutrition was established by subjecting BALB/c mice to dietary restriction. These animals received 70% of the amount of food consumed by the healthy control group and exhibited physiological alterations compatible with malnutrition, including body weight loss, reduced levels of triglycerides and glucose, and reduced lymphocyte numbers. Undernourished mice were immunized with BCG, and the mycobacterial loads in lymph nodes, spleen, liver, lungs, and thymus were determined. A much higher proportion of undernourished mice exhibited bacterial dissemination to the lymph nodes, spleen and liver. In addition, only undernourished animals had bacteria in the lungs and thymus. Concomitant with higher mycobacterial loads and more widespread BCG dissemination in undernourished mice, production of TNF-α, IFN-γ, and IL-10 was also diminished in these mice. Taken together, these results indicate that BCG infection is more severe in undernourished mice. Whether a similar phenomenon exists in undernourished children or not remains to be thoroughly investigated.

O objetivo do presente estudo foi comparar a produção de IFN- , IL-12 e IL-4 entre camundongos jovens (5, 12 e 19 dias de idade) e adultos (30 dias de idade). As avaliações foram feitas por estimulação, in vitro, de células esplênicas com Concanavalina A (ConA) , Staphylococcus aureus (S. aureus) e lipopolissacarídeo (LPS). Diferentes concentrações de cada estímulo foram testadas e os sobrenadantes das culturas foram coletados após 48 horas de incubação e as concentrações de IFN- , IL-12 e IL-4 determinadas por ELISA. Células de camundongos jovens e adultos produziram níveis igualmente elevados de IFN- após estímulo com ConA. Somente animais adultos produziram IFN- em resposta ao estímulo com S. aureus. Em culturas estimuladas com LPS, a produção desta citocina foi baixa e similar nos animais jovens e significativamente elevada nos animais adultos. Somente células de animais adultos estimuladas com S. aureus foram capazes de produzir IL-12. O único estímulo capaz de induzir níveis detectáveis de IL-4 foi ConA, sendo que estes níveis foram mais elevados nos animais com 12 e 19 dias de idade em comparação com animais neonatos e adultos. A diminuição das doses ótimas dos estímulos não mudou o perfil de produção de cada citocina nos animais jovens. Estes resultados permitem concluir que a idade afeta a produção de citocinas: ocorre maior produção de IL-4 em camundongos jovens e maior produção de IL-12 e IFNem animais adultos. Estas informações são importantes devido ao papel destas citocinas na polarização das respostas imunes nos sentidos Th1 e Th2.

Abstract Background Staphylococcus aureus methicillin-resistant (MRSA) has been frequently isolated from endotracheal and lung puncture aspirates in malnourished children with pneumonia. In this work we evaluated the susceptibility of undernourished BALB/c mice and its ability to mount a protective immunity against MRSA with emphasis on the lung involvement. Results BALB/c mice submitted to a 20% dietary restriction during 20 days presented a significant decrease in body weight, lymphocyte number and also atrophy in thymus and intestinal epithelium. Determination of bacterial load by the number of colony forming units (CFU) indicated a similar susceptibility whereas the findings of Gram stain clearly suggested a higher amount of bacteria in the lungs of normal mice than in the undernourished ones. Immunization reduced bacterial growth in the lungs of normal mice but not in the undernourished ones. Histopathological analysis showed that inflammation appeared in the lungs from normal mice only after infection and that immunization prevented this pulmonary inflammatory process. On the other hand, undernourished mice presented lung inflammation even before infection. In addition, the degree of this inflammatory process did not change with infection or previous immunization. Conclusion Our results indicated that lung injury during MRSA infection is prevented by previous immunization in well nourished but not in undernourished mice.