Oralmucositis (OM) is a common complication of treatments for head and neck cancer, par- ticularly radiotherapy with or without chemotherapy. OM is characterised by oral erythema, ulceration, and pain. The aim of this study was to evaluate the effect of azilsartan (AZT), an angiotensin II receptor antagonist, on 5-fluorouracil (5-FU)-induced oralmucositis (OM) in Syrian hamsters. OM was induced by the intraperitoneal administration of 5-FU on experi- mental days 1 (60mg/Kg) and 2 (40mg/Kg). Animals were pretreated with oral AZT (1, 5, or 10 mg/kg) or vehicle 30 min before 5-FU injection and daily until day 10. Experimental treatment protocols were approved by the Animal Ethics Committee Use/CEUA (Number 28/2012) of the UFRN. Macroscopic analysis and cheek pouch samples were removed for histopathologic analysis. Myeloperoxidase (MPO), Malonyldialdehyde (MDA), interleukin-1 beta (IL-1β), interleukin-10 (IL-10), and tumour necrosis factor-alpha (TNF-α) were ana- lysed by Enzyme Linked Immuno Sorbent Assay (ELISA). Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), keratinocyte growth factor (KGF), and transforming growth factor (TGF)-α were measured by immunohistochemistry. Analysis of variance followed by Bonferroni’s test was used to calculate the means of intergroup differ- ences (p 0.05). Treatment with 1 mg/kg AZT reducedlevels MPO (p<0.01), MDA (p<0.5) and histological inflammatory cell infiltration, andincreased the presence of granulation tis- sue. AZT treatment at 1 mg/kg reduced the TNF-α (p<0.05) andIL-1β (p<0.05) levels, in- creased the cheek pouch levels of IL-10 (p<0.01), andupregulatedVEGF, FGF, KGF, andTGF-α. Administration of AZT at higher doses (5 and10 mg/kg) did not significantly reverse
Oralmucositis (OM) is an important side effect of cancer treatment, characterized by ulcera- tive lesions in the mucosa of patients undergoing radiotherapy or chemotherapy, which has marked effects on patient quality of life and cancer therapy continuity. Considering that few protocols have demonstrated efficacy in preventing this side effect, the aim of this study was to examine the effect of dexamethasone (DEX) on OM induced by 5-fluorouracil (5-FU) in hamsters by studying signaling pathways. OM was induced in hamsters by 5-FU followed by mechanical trauma (MT) on day 4. On day 10, the animals were euthanized. The experi- mental groups included saline, MT, 5-FU, and DEX (0.25, 0.5, or 1 mg/kg). Macroscopic, histopathological, and immunohistochemical analyses as well as immunofluorescence experiments were performed on the oral mucosa of the animals. The oral mucosal samples were analyzed by enzyme-linked immunosorbent assays, and quantitative real-time poly- merase chain reaction (qPCR). DEX (0.5 or 1 mg/kg) reduced inflammation and ulceration of the oral mucosa of hamsters. In addition, DEX (1 mg/kg) reduced the cytokine levels of tumor necrosis factor (TNF)- α, interleukin (IL)-1β, and macrophage migration inhibitory fac- tor (MIF). DEX (1 mg/kg) also reduced the immunoexpression of cyclooxygenase (COX)-2, matrix metalloproteinase (MMP)-2, transforming growth factor (TGF)- β, MIF, Smad 2/3, Smad 2/3 phosphorylated and NF κB p65 in the jugal mucosa. Finally, DEX (1 mg/kg) increased interleukin-1 receptor-associated kinase 3 (IRAK-M), glucocorticoid-induced leu- cine zipper (GILZ), and mitogen-activated protein kinase (MKP1) gene expression andreduced NFκB p65 and serine threonine kinase (AKt) gene expression, relative to the 5-FU group. Thus, DEX improved OM induced by 5-FU in hamsters.
There are five phases in OM pathogenesis. The initiation phase involves the initial injury to cells by radiotherapy and/or chemotherapy. This injury may be induced directly via DNA dam- age or (more commonly) indirectly via reactive oxygen species. The consequent activation of various enzymes and transcription factors eventually leads to the upregulation of genes coding for inflammatory cytokines, such as tumour necrosis factor (TNF)-α, interleukin (IL)-1β, andIL-6, which target the submucosa and basal epithelium. The resulting inflammation and tissue damage lead to ulceration and subsequent bacterial colonisation, further feeding a vicious cycle of inflammatory cytokine-mediated damage. The final healing phase involves signalling via the extracellular matrix, resulting in epithelial proliferation, epithelialisation, and reestablishment of the mucosal barrier .
Cytokines in vitreous fluid and serum are presented in percent of samples with detectable cyto- kine (percent detectable, %) andin cytokine level (mean ± standard deviation, pg/ml) for each group. Cytokines with values below limits of detection were graded as negative and the levels were assigned a numerical value of 0 pg/ml for statistical analysis. Percent detectable were com- pared by Pearson's chi-squared test. Since the levels of cytokines were not normally distributed, the statistical comparisons of cytokine levels were performed using nonparametric test (Wil- coxon signed-rank test for two groups, and Steel-Dwass multiple comparison test for three groups). Pearson’s correlation coefficient test was used to examine the correlation between vit- reous levels of cytokines. A P value of 0.05 was considered significant.
the phagocytic cells are committed to a more Th1-biased phenotype during drug-induced clearance of parasitaemia and release of parasite metabolites, such as haemozoin, which is a known inducer of pro-inflammatory responses via signalling through Toll-like receptors 9 (Coban et al. 2005). Nonetheless, before the initiation of antimalarial treatment, a notably high IL-10 concentration that mark- edly decreased with the resolution of parasitaemia was ob- served and this down regulation of the Th2 response dis- criminated the successfully treated malaria patients. IL-10 has a number of effects andIL-10 inhibited IL-6, IFN-γ andTNF-α secretion and function inanin vitro malaria model when anti-IL-10 antibody was produced. Another plausible cause for the increase in several cytokine levels between the acute and convalescent phases could be the diminished suppressive effect by IL-10 on other cytokines such as pro-inflammatory cytokines, as well as a reduced systemic inflammatory response due to all haematological alterations returning to references values. IL-10 perturba- tions appear to have the most significant inhibitory effect on other cytokine concentrations. In this endemic area, we were unable to rule out concomitant intestinal para- site infections with organisms such as helminths, which potentially influenced the results (Hartgers & Yazdanba- khsh 2006). An association of IL-10levels with parasi- taemia has also been reported in Plasmodium knowlesi and P. vivax infections. Moreover, IL-10levelsin both P. vivax and P. knowlesi patients were elevated, but were not associated with markers of disease severity (Cox-Singh et al. 2011). In contrast, the IFNγ/IL-10 ratio has been suc-
Dendrobium officinale is a member of Orchidales Dendrobium plants, and is one of the precious traditional Chinese medicines in China (Li et al., 2008). It has the effect of nourishing Yin, clearing heat, reinforcing stomach fluid, and moistening lung (Lin et al., 2010). A variety of active ingredients have been isolated from Dendrobium officinale, including alkaloids, polysaccharides, sesquiterpenes, phenanthrene quinones, bibenzyls, fluorenones, steroids, phenols and volatile oils (Lv et al., 2013). The polysaccharide is the main component of Dendrobium officinale, which has immune-regulating (Liu et al., 2011), anti-oxidant (Luo et al., 2016), anti-tumor (Bao, 2008), antibacterial (Lei, 2011) and anti-hypoglycemic activity (Chen et al., 2003). Gastric cancer is one of the common malignant tumors, with high mortality (Leylabadlo et al., 2016). With the change of modern lifestyle, the incidence of gastric cancer is increasing year by year, which poses a great threat to people’s health. The occurrence and development of gastric cancer is a process of carcinogenesis caused by multiple factors, multiple stages and polygenic variations (Eom et al., 2012). The single resection can be applied for gastric cancer, but the cure is only limited for early-stage gastric cancer without any metastasis. For early-stage gastric cancer with metastasis or advanced-stage gastric cancer, the medical treatment occupies an important position (Lepage et al., 2010). SGC-7901 cell line is one kind of
Sixty SD rats (240±30 g; Zhejiang Experimental Animal Center, Hangzhou, China) were randomly divided into sham operation group, model group, and low-, middle- and high-dose baicalin group, 12 rats in each group. In the sham operation group, the abdomen was cut open, with mildly rubbing the pancreas and turning over the intestinal canal for 5 min, followed by abdominal closure. In other 4 groups, the SAP model was established. After abdominal incision, 5% sodium taurocholate (Sigma-Aldrich Corp., MO, USA) was injected retrogradely into bile duct, with dose of 0.1 ml/100 g body weight, followed by abdominal closure. In low-, middle- and high-dose baicalin groups, after 5 min from SAP modeling, 5% baicalin injection (Shaanxi Saide Science and Technology Development Co., Ltd., Xi’an, China) was injected through the tail vein (2 ml/h), with dose of 0.1, 0.2 and 0.4 ml/100 g, respectively. The sham operation andmodel groups were injected with equal amount of physiological saline.
Five-μm thick frozen sections of mouse aortas were applied for staining or immunostaining for TLR4 (1:100 dilution), macrophages (macrophage marker [MOMA-2], 1:200 dilution; Abcam; catalog number: ab33451; rat monoclonal antibody), VSMCs (α-smooth muscle actin [α- SMA], 1:400 dilution; Sigma-Aldrich; catalog number: A2547; mouse monoclonal antibody) and elastin degradation (Verhoeff-Van Gieson [VVG] staining). Isotype IgG control (Calbio- chem, San Diego, CA) slides were provided as negative controls to confirm the specificity of respective primary antibodies in mouse AAA specimens (S6 Fig). All sections used for compar- ison were located at the maximal expansion of the infra-renal aorta and approximately at a similar distance from the renal arteries. These slides were visualized with a Carl Zeiss upright microscope. Digital images were acquired using a digital camera and were analyzed using Ima- geJ software. VSMC content, as represented by the intensity of α-SMA staining, was deter- mined using HistoQuest software (TissueGnostics, Vienna, Austria), an automated image analysis system for quantification of protein expression . Elastin fragmentation and macro- phage counts were evaluated blindly by 2 independent observers. For each mouse, the intensity of α-SMA staining and numbers of elastin breaks and macrophages were measured in 3 serial 5-μm sections and the data were then averaged. The mean value from 6 mice in each group was presented.
On day 37, after evaluation of motor function, animals were euthanized with high doses of 2% xylazine (0.1 ml/g) and10% ketamine (0.22 ml/g) intraperitoneally. 6 rats were perfused with saline followed by 4% paraformaldehyde (PFA). The spine was carefully dissected and the spinal cord was removed. A piece of spinal cord, measuring 1cm, was dissected to perform the histological analysis. The main lesion produced in our study was located at the center of the piece. Tissue sections with a thickness of 5 mm were kept inan oven for 1 hour to fix the cuts. Immunodetection was performed using appropriate antibodies as follows: rabbit anti-IL-1 β, and anti-TNF-α (Abcam). For each reaction a negative control was used in the absence of primary antibody. The results were obtained by optical microscope (Nikon Eclipse 50i) and a digital camera (DS-5M-L1, Nikon, NY, USA) coupled. The scanned images were transferred to a computer and the intensity of staining was determined using the ImageJ 1.36b program NIH (National Institutes of Health, Maryland, USA).
30% of patients undergo remission following the ﬁrst antidepressant treatment, and approximately 50% of patients do not respond to monoaminergic antidepressants (Krishnan and Nestler, 2008). Thus, other systems appear to be involved in the pathophysiology of MDD. Several studies have shown that the immune system plays an important role in the pathophysiology of MDD, as well as in thera- peutic responses to antidepressant drugs (Abelaira et al., 2014; R eus et al., 2015a; Mocking et al., 2017). This theory is sustained by the ﬁnding that patients with inﬂammatory diseases, such as diabetes, cardiovascular diseases, asthma and metabolic diseases, have a high prevalence of MDD (Fenton and Stover, 2006; Maes et al., 2011; Ceretta et al., 2012a,b). Moreover, patients with MDD have elevated peripheral levels of pro-inﬂammatory cytokines, such as inter- leukin-1 b (IL-1 b ), interleukin-6 (IL-6), and tumour necrosis factor- a (TNF- a ) (Lindqvist et al., 2017). Increasedlevels of inﬂammatory mediators in the periphery and central nervous system (CNS) are associated with more vulnerability to stress and MDD (M enard et al., 2017). Inan inﬂammatory state, brain resident cells, such as neurons, microglia, and astrocytes, receive mediators that signal to increase the expression of genes associated with inﬂammation and neuro- endocrine signaling impairment (M enard et al., 2017).
Quanto ao perfil de citocinas sintetizado por camundongos infestados sucessivamente com carrapatos R. sanguineus, observou-se primeiramente uma proliferação celular inibida quando suas células eram estimuladas in vitro com Con-A, e que essa supressão estava restrita a células obtidas dos linfonodos situados próximos ao sítio de fixação dos carrapatos, sugerindo uma regionalização da resposta a carrapatos. As células dos linfonodos regionais de camundongos re-infestados (no sexto dia de infestação) sintetizaram reduzidos níveis de citocinas associadas com linfócitos do tipo Th1, ou seja, IL-2, IFN-γ e IL- 12. Por outro lado, produziram elevados níveis de citocinas associados com linfócitos Th2, ou seja, IL-4, IL-10 e TGF-β (FERREIRA & SILVA, 1999).
CD40 . As an example, downstream signalling through the IL-3/IL3R pathway induces growth and extends survival in HL cells . Paracrine signals may arise from non-malignant tumor-infiltrating cells in HL microenvironment (e.g., eosinophils, mast cells, neutrophils and macrophages) . The nuclear factor-kappa B (NF-kB) and Janus Kinase-signal transducer and activator of transcription (JAK-STAT) pathways have been identified as important modulators in HL . Activation of the NF-kB pathway, which is involved in the expression of multiple anti-apoptotic factors and pro- inflammatory cytokines, reduces the expression of CD99, a marker associated with HRS cells phenotype . This cell surface receptor is involved in Tcell adhesion, leukocyte migration, and Tcell caspase-independent cell death, playing also a role in the induction on human thymocytes of Tcell receptor (TCR) and Major histocompatibility complex Class I and II molecules expression. It has been reported that CD99 deficiency leads to the arrest of MHC Class I molecules at the Golgi complex, impairing their transport to the cell surface, which constitutes one of the most frequent immune escape mechanisms adopted by cancer cells ..Some authors identified candidate-circulating biomarkers for HL, with prognostic and/or predictive response to therapy values. These molecules act at HL site and modulate disease outcome [30-32]. Furthermore, it was found that before treatment, HL patients have increasedlevels of serum interleukin 6 (IL-6) and YKL-40, both facts correlated with disease progression stage .
Inicialmente, a infecção por Schistosoma mansoni em camundongos induz a resposta imune do tipo-1 e, com o inicio da postura dos ovos do parasito há uma mudança na resposta, tornando-se predominantemente do tipo-2. As citocinas de perfil Th2 são essenciais para formação do granuloma e para o desenvolvimento da fibrose associada à esquistossomose. A produção de citocinas da resposta inata, como IL-33 e sua ligação ao receptor ST2 estimula a produção precoce de IL-13 e IL-5, que auxilia a diferenciação da resposta do tipo-2, mas sua participação na esquistossomose não é conhecida. Assim, objetivou-se avaliar a participação da ativação da via IL-33/ST2 na evolução da infecção e na formação e modulação do granuloma induzido pela retenção de ovos de S. mansoni. Camundongos deficientes (ST2 -/- ) e controles Balb/c não deficientes (WT) foram infectados com 25 cercárias de S. mansoni/camundongo e avaliados após 8 semanas (fase aguda) e 14 semanas (fase crônica). A carga parasitária foi estimada através da recuperação de vermes no sistema porta-hepático, número de ovos retidos no fígado e nas fezes. A concentração sérica de IgE total e os níveis de IgM, IgG total e o subtipo IgG1 parasito reativas foram estimados por ELISA. Alterações hepáticas foram avaliadas pela quantificação de citocinas (IL-4, IL-5, IL-10, IL-13, IL-17, TNF-α e TGF- β), pela infiltração celular, medida através da atividade de Peroxidase de Eosinófilo (EPO), mieloperoxidase (MPO) e N-acetilglicosaminidase (NAG), pela deposição de colágeno e avaliação histopatológica. A função hepática foi determinada pelos níveis séricos de aspartato aminotransferase (AST) e alanina aminotransferase (ALT). Resultados mostraram que a recuperação dos vermes adultos, número de ovos retidos no fígado e ovos nas fezes foram semelhantes
Signiicant immune effects of other antipsychotic drugs in FEP patients have been reported (see Tourjman et al., 2013). These previous studies found a signiicant decrease of IL-6, IL-4, andIL-27 after antipsychotic treatment in FEP (Kubistova et al., 2012; Borovcanin et al., 2013), but not of TNF-α (Kubistova et al., 2012). In a recent meta-analysis (Tourjman et al., 2013), 23 studies were included showing that antipsychotics may have anti-inlammatory effects. However, none of the cytokine levelsreduced after risperidone treatment in our study were signii- cant in this meta-analysis. These differences may be explained by differences in study samples and antipsychotic agents, such as FEP patients treated with risperidone in our study versus chronic patients treated with different antipsychotics in the meta-analysis. In another meta-analysis, Miller et al. (2011) concluded that some cytokines (IL-1β, IL-6, andTGF-β) may be state markers for the acute phase of schizophrenia, while other immune markers (IL-12, IFN-β, TNF-β, and sIL-2R) may be trait markers. However, in our sample, we did not ind any cytokine that could function as a trait marker because all cytokines that were initially increasedin FEP were normalized after risperi- done treatment.
Besides prediabetes and type 2 diabetes, CB overactivation has been associated with other pathologies that occur with cardiometabolic comorbidities, such as obstructive sleep apnea (OSA) [27,28]. OSA is a potentially serious sleep disorder characterized by repetitive episodes of complete or partial nocturnal breathing obstructions and by altered hypoxic ventilatory responses [27,29–31], being also associated with several metabolic and cardiovascular abnormalities [32–34]. The consensus is that CB overactivation due to chronic intermittent hypoxia (CIH) is involved in the genesis of OSA-mediated hypertension and insulin resistance through an increase in sympathetic nervous system activity [10,27,29,30,35]. One of the risk factors contributing to the development of OSA is obesity and, in fact, it is estimated that 40% of obese individuals have OSA and that approximately 70% of individuals with OSA are obese [36,37]. In addition, in middle-aged men with OSA, it was observed that there is an association with visceral obesity, inflammation, hyperinsulinemia, and hyperleptinemia . Obesity is also known to be present in 90% of type 2 diabetes patients andin 85–99% of metabolic syndrome patients, being a risk factor for the development of these diseases [38,39] due to adipose tissue dysfunction. White adipose tissue is the main lipid storage depot in humans, being critically important in buffering the dietary fat influx entering the circulation by suppressing the release of non-esterified fatty acids into the circulation and by increasing the clearance of triacylglycerols . Apart from the decrease in lipid storage and the release of free fatty acids into the circulation, promoting thereby whole-body insulin-resistance, adipose tissue plays a crucial role in the development of metabolic diseases, due to its critical immune and endocrine functions. Adipose tissue is an active endocrine organ that secretes several humoral factors named adipokines, such as leptin and adiponectin, that exhibit important systemic metabolic effects, from food intake to glucose tolerance [41–43]. Along with the production of specialized adipokines, such as leptin and adiponectine, adipose tissue also secretes proinflammatory cytokines that contribute to the low-level systemic inflammation that is involved in adipose tissue dysfunction and systemic metabolic abnormalities [43,44].
TUKMACHI, 2000; LANGEVIN, et al., 2001; LANGEVIN et al., 2001; SHERMAN et al., 2002). In fact, few reports concerning the effect of acupuncture on inflammatory models are available, although clinical trials claim the success of acupuncture in the treatment of pruritic dermatosis, bronchial asthma, carpal tunnel syndrome, rheumatoid arthritis and other inflammatory disorders in humans and animals (SCOGNAMILLO-SZABÓ & BECHARA, 2001). However, these observations are limited by methodological considerations such as small sample size, placebo effects and lack of control groups (STREITBERGER & KLEINHENZ, 1998; CASIMIRO et al., 2002, MCCARNEY et al., 2004). Therefore, research on the use of acupuncture in experimentally induced inflammatory process will bring new perspectives towards investigations in this area, including on the mechanisms of action of such technique.
In SOT patients, the severity of infection has been as- sociated with the level of immunosuppression (Husain et al. 2001). Studies by Pappas et al. (2001) have shown that the type of immunosuppressive treatment(s) administered to this group influences their susceptibility to CNS-asso- ciated cryptococcosis, responses to antifungal treatments, and likely fatality. Another study by Saha et al. (2007) pro- vided serological evidence that the majority of cryptococ- cal infections in these patients were due to reactivation of pre-transplantation infections. Individuals with circulating antibodies against Cryptococcus prior to organ transplan- tation acquired cryptococcosis sooner than those without previous exposure to the pathogen, and were more likely to develop CM. Disease progression in this subset was also dependent on the type of organ transplanted, although transmission of infection from organ donor to recipient has rarely been observed (Singh et al. 2009).
Although known relatively recently, AIDS and hepatitis C virus (HCV) have emerged as two of the most important and prevalent diseases in the world, by generating high morbidity and mortality and great social and financial impact, even in most developed countries (1,2) . Since the first reports in 1981, it is estimated that approximately 65 million people became infected with human immunodeficiency virus (HIV), and of those, about 25 million have already died (1) . Regarding HCV, it is estimated that about 180 million people or about 3% of world population is infected, while 130 million are at high risk of developing cirrhosis and/or hepatocellular carcinoma (2) . HCV is responsible for 50% to 76% of all new cases of liver cancer and two thirds of liver transplants in developed countries (2) . The prevalence of HCV in people living with HIV/AIDS (PLWHA) varies widely, depending mainly on the mode of HIV acquisition, but as a rule, is much higher than in the general population. Because the two viruses share the same transmission mechanisms, this relationship can be very high, as seen in drug users (91%) or Blood transfusion (71%), or even lower (7%) and those which has only sexual risk factor, not very effective route for HCV transmission (3) .
to the Institute of Cardiology “Niska Banja” in Nis (Serbia, Southeast Europe, geographic latitude 43°N and longitude 22°E) were taken into consideration. The characteristics of donors are defined in Table 1. Systolic blood pressure higher than 140 mmHg, diastolic blood pressure higher than 90 mmHg, or use of antihypertensive therapy was considered as hypertension. Coronary heart disease included history of myocardial infarction, coronary insufficiency or angina. The conditions known to influence the VD status were considered as exclusion criteria: previous gastrectomy, intestinal malabsorption, history of chronic liver disease, significant increase of liver enzymes, or biochemical evidence of hepatic dysfunction, current use of antiepileptic drugs or supplements containing vitamin D. The study was approved by the ethics committee of the Institute of cardiology and rehabilitation “Niska banja,” conducted according to the Declaration of Helsinki Principles and all patients gave written informed consent.
Desequilíbrios na produção de prostaglandinas (PGs) secretadas durante os ciclos menstruais, principalmente as do tipo F2α e E2, têm sido associados à ocorrência de dismenorreia e sangramento uterino excessivo. Dependendo da magnitude dessas disfunções, o uso de anti-inflamatórios não hormonais continua sendo indicado para bloquear a síntese de PGs e controlar o quadro clínico. Entretanto, como esse tipo de opção terapêutica apresenta resultados variáveis e pode produzir efeitos colaterais que restringem sua utilização, o emprego da fitoterapia vem sendo proposto como alternativa terapêutica. Trabalhos e relatos têm mostrado que o limão Taiti (Citrus latifolia) atua de forma eficaz no controle da menorragia não estrutural e da dismenorreia. Embora as formas de atuação não sejam conhecidas, a inibição da cascata de produção dos ácidos araquidônicos é uma das possibilidades que merece ser investigada. Deste modo, para contribuir com a elucidação dos mecanismos de ação, propomos estudar o efeito do suco do limão Taiti na produção de PGs e de citocinas envolvidas nas vias de síntese das PGs em mulheres saudáveis durante a menstruação. Para isso, voluntárias na fase do menacme foram divididas de forma aleatória em três grupos e tratadas a partir do início da menstruação por dois dias consecutivos com Limão (G1, n=15) ou Meloxicam (G2, n=14) e comparadas com grupo Controle (G3, n=13) formado por participantes que não sofreram qualquer tipo de intervenção. Para isso, amostras de fluído menstrual e sangue periférico foram coletadas no segundo dia da menstruação para dosagem de PGE2, PGF2α, IL-1β, TNF-α e IL-6 com o propósito de avaliar o efeito uterino e sistêmico da citroterapia. Além disso, foram realizadas cultura de células a partir de sangue total, estimuladas (24h) ou não com LPS, para medir os efeitos do limão Taiti