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Background: Identifying clinical characteristics and risk factors, comorbid conditions, and complications arising from SARS-CoV-2 infection is important to predict the progression to more severe forms of the disease among hospitalized individuals to enable timely intervention and to prevent fatal outcomes. The aim of the study is to assess the possible role of the neutrophil/lymphocyte ratio (NLR) as a biomarker of the risk of death in patients with comorbidities hospitalized with COVID-19 in a tertiary hospital in southern Brazil. Methods: This is a prospective cohort study on patients with SARS-CoV-2 infection admitted to a hospital in the metropolitan region of Porto Alegre from September 2020 to March 2022. Results: The sample consisted of 185 patients with associated comorbidities, namely, hypertension, diabetes mellitus, obesity, cardiovascular, pulmonary, and renal diseases, hospitalized with COVID-19. Of these, 78 died and 107 were discharged alive. The mean age was 66.5 years for the group that died and 60.1 years for the group discharged. Statistical analysis revealed that a difference greater than or equal to 1.55 in the NLR, from hospitalization to the 5th day, was associated with a relative risk of death greater than 2. Conclusions: Measuring a simple inflammatory marker such as NLR may improve the risk stratification of comorbid patients with COVID-19 and can be considered a useful biomarker. [ABSTRACT FROM AUTHOR]

Cryptosporidiosis is a major diarrheal disease with high mortality, primarily in young animals, and a zoonotic risk of infection. The molecular epidemiology patterns of Cryptosporidium isolates are still poorly understood in Egypt and other developing countries. The goal of this research was to better understand the genetic diversity of Cryptosporidium isolates in pre-weaned cattle calves in Egypt's Al- Sharkia governorate by examining the hemo-biochemical changes in infected calves. We used 100 diarrheal faecal samples to detect the presence of Cryptosporidium oocysts by Ziehl-Neelsen (ZN) staining. Twenty-two of the positive samples after staining were further verified using PCR targeting the Cryptosporidium oocyst wall protein (COWP) gene. We found that Cryptosporidium. Parvum (C. parvum) was the sole species identified using the polymorphic 60 kDa glycoprotein gene (GP60) locus. Sequencing GP60 locus samples revealed dominant circulation for subtype IIa of C. parvum in calves, unlike most previously reported sequences in Egypt. These sequences were 100% like those in Latin America (Brazil, KT948746 EPC30). Egypt imports cattle calves from Latin America, mainly Brazil, to overcome the deficiency in meat production, so it is more likely that the C. parvum sequences circulating in Egypt appear to be from different origins. Red Blood Cells (RBCs), Hemoglobin (Hb), Mean Corpuscular Hb (MCH), lymphocytes, and Total Iron Binding Capacity (TIBC) values were all significantly diminished in the infected calves than in the healthy ones, while Packed Cell Volume (PCV) and Mean Corpuscular Volume (MCV), neutrophil, eosinophil and monocytic percentages, Aspartate (Asp), and Glutamate Decarboxylase (GAD) values increased. Our study for the first time identified the presence of C. parvum isolates and changes in hemato-biochemical conditions in pre-weaned cattle calves in Al-Sharkia governorate, which may address the potential role of imported livestock in disease transmission. [ABSTRACT FROM AUTHOR]

Thalassophryne nattereri toadfish (niquim) envenomation, common in the hands and feet of bathers and fishermen in the north and northeast regions of Brazil, is characterized by local symptoms such as immediate edema and intense pain. These symptoms progress to necrosis that lasts for an extended period of time, with delayed healing. Wound healing is a complex process characterized by the interdependent role of keratinocytes, fibroblasts, and endothelial and innate cells such as neutrophils and macrophages. Macrophages and neutrophils are actively recruited to clear debris during the inflammatory phase of wound repair, promoting the production of pro-inflammatory mediators, and in the late stage, macrophages promote tissue repair. Our hypothesis is that injury caused by T. nattereri venom (VTn) leads to senescent wounds. In this study, we provide valuable information about the mechanism(s) behind the dysregulated inflammation in wound healing induced by VTn. We demonstrate in mouse paws injected with the venom the installation of γH2AX/p16Ink4a-dependent senescence with persistent neutrophilic inflammation in the proliferation and remodeling phases. VTn induced an imbalance of M1/M2 macrophages by maintaining a high number of TNF-α-producing M1 macrophages in the wound but without the ability to eliminate the persistent neutrophils. Chronic neutrophilic inflammation and senescence were mediated by cytokines such as IL-1α and IL-1β in a caspase-1- and caspase-11-dependent manner. In addition, previous blocking with anti-IL-1α and anti-IL-β neutralizing antibodies and caspase-1 (Ac YVAD-CMK) and caspase-11 (Wedelolactone) inhibitors was essential to control the pro-inflammatory activity of M1 macrophages induced by VTn injection, skewing towards an anti-inflammatory state, and was sufficient to block neutrophil recruitment and senescence. [ABSTRACT FROM AUTHOR]

The formation of microthrombi in lung autopsies indicates the involvement of NETs in the immunopathogenesis of severe COVID-19. Therefore, supplements inhibiting NET formation, in association with drugs with fewer adverse effects, should be a relevant strategy to attenuate the disease. Resveratrol (RESV) is a natural polyphenol with an important antiviral and antioxidant role. To modulate neutrophils from patients infected with SARS-CoV-2, we evaluated the in vitro effect of RESV on NET formation. Herein, we investigated 190 patients hospitalized with moderate, severe, and critical symptoms at Hospital das Clínicas, Brazil. We observed that neutrophilia in patients with severe COVID-19 infection is composed of neutrophils with activated profile able to release NET spontaneously. Notably, RESV decreased the neutrophil-activated status and the release of free DNA, inhibiting NET formation even under the specific PMA stimulus. At present, there is no evidence of the role of RESV in neutrophils from patients with COVID-19 infection. These findings suggest that adjunctive therapies with RESV may help decrease the inflammation of viral or bacterial infection, improving patient outcomes. [ABSTRACT FROM AUTHOR]

Cuphea genus (Lythraceae) popularly known in Brazil as "sete-sangrias", it's described as antimicrobial, anti-inflammatory, diuretic and antihypertensive mainly. Investigating the chemotactic ability plays an important role in the identification of new anti-inflammatory agents. Thus, this research aims to assay the antichemotactic activity of hydroethanolic extracts of C. calophylla, C. carthagenensis, C. glutinosa, and C. racemosa as well as the compounds miquelianin and myricitrin. The antichemotactic activity of the hydroethanolic extracts, miquelianin, and myricitrin were assayed at concentrations 0.001 to 10 µg/mL in the lipopolysaccharide-induced chemotaxis on rat polymorphonuclear neutrophils. All the assayed samples displayed antichemotactic activity with reduction of the neutrophil migration in the range of 4.46-100%, and an IC50 value in the range of 0.30-1.24 µg/mL. Thus, this study demonstrates that the extracts hydroethanolic of Cuphea species, miquelianin, and myricitrin display a significant antichemotactic activity. Therefore, in future studies, extracts from Cuphea spp. could be used as anti-inflammatory drugs. [ABSTRACT FROM AUTHOR]

Objective: Inflammation plays a crucial role in the initiation and progression of many cancers. This study aimed to investigate the utility of pretreatmentneutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), derived neutrophil-lymphocyte ratio (dNLR), and a combination of PLR and NLR in predicting the risk of death according to clinical staging in cervical cancer (CC) patients.Methods: A cohort study of women with CC, diagnosed and treated at a single cancer referral center in Brazil, from 2006 to 2009. A multivariate Cox regression analysis and ROC curve analysis accessed the predictive value of inflammatory response biomarkers in overall survival (OS). The median values of the biomarkers were used as cut-off points.Results: A total of 1,266 patients were included in the study, 76.0% with locally advanced disease. After adjusting for clinical variables, NLR > 2.57, PLR ≥ 146.70, dNLR ≥ 1.778 and PLR + NLR in combination had equivalent performance in predicting worse OS, but only among patients with locally advanced disease (adjusted Hazard Ratio [aHR] = 1.453, 95% Confidence Interval [CI] = 1.227-1.722; p < 0.001; aHR = 1.429; 95% CI = 1.209-1.688; p < 0.001; aHR = 1.486, 95% CI = 1.257-1.756, p < 0.001, aHR = 1.731; 95% CI = 1.411-2.123; p < 0.001, respectively).Conclusion: In conclusion, PLR, NLR, dNLR and PLR + NLR in combination presented equivalent performance in predicting OS in locally advanced CC patients. They are simple and readily available from routine blood tests, not entailing additional costs. PLR, NLR, dNLR and PLR + NLR in combination are strong prognostic biomarkers candidates in locally advanced CC and should be further explored in prospective trials. [ABSTRACT FROM AUTHOR]

Background: Neutrophils have been associated with lung tissue damage in many diseases, including tuberculosis (TB). Whether neutrophil count can serve as a predictor of adverse treatment outcomes is unknown. Methods: We prospectively assessed 936 patients (172 HIV-seropositive) with culture-confirmed pulmonary TB, enrolled in a multicenter prospective cohort study from different regions in Brazil, from June 2015 to June 2019, and were followed up to two years. TB patients had a baseline visit before treatment (month 0) and visits at month 2 and 6 (or at the end of TB treatment). Smear microscopy, and culture for Mycobacterium tuberculosis (MTB) were performed at TB diagnosis and during follow-up. Complete blood counts were measured at baseline. Treatment outcome was defined as either unfavorable (death, treatment failure or TB recurrence) or favorable (cure or treatment completion). We performed multivariable logistic regression, with propensity score regression adjustment, to estimate the association between neutrophil count with MTB culture result at month 2 and unfavorable treatment outcome. We used a propensity score adjustment instead of a fully adjusted regression model due to the relatively low number of outcomes. Results: Among 682 patients who had MTB culture results at month 2, 40 (5.9%) had a positive result. After regression with propensity score adjustment, no significant association between baseline neutrophil count (103/mm3) and positive MTB culture at month 2 was found among either HIV-seronegative (OR = 1.06, 95% CI = [0.95;1.19] or HIV-seropositive patients (OR = 0.77, 95% CI = [0.51; 1.20]). Of 691 TB patients followed up for at least 18 months and up to 24 months, 635 (91.9%) were either cured or completed treatment, and 56 (8.1%) had an unfavorable treatment outcome. A multivariable regression with propensity score adjustment found an association between higher neutrophil count (103/mm3) at baseline and unfavorable outcome among HIV-seronegative patients [OR= 1.17 (95% CI= [1.06;1.30]). In addition, adjusted Cox regression found that higher baseline neutrophil count (103/mm3) was associated with unfavorable treatment outcomes overall and among HIV-seronegative patients (HR= 1.16 (95% CI = [1.05;1.27]). Conclusion: Increased neutrophil count prior to anti-TB treatment initiation was associated with unfavorable treatment outcomes, particularly among HIV-seronegative patients. Further prospective studies evaluating neutrophil count in response to drug treatment and association with TB treatment outcomes are warranted. [ABSTRACT FROM AUTHOR]

Background. The Neutrophil-to-Lymphocyte Ratio (NLR) and the Platelet-to-Lymphocyte Ratio (PLR) are inflammatory biomarkers for several diseases, such as cancer and cardiovascular morbidities; however, there are currently few studies on kidney diseases. We aimed to evaluate nondialysis patients and determine the association of NLR and PLR with inflammation in these patients. Methods. A prospective cross-sectional study was conducted with 85 patients at different stages of chronic kidney disease (CKD), treated at the Kidney Disease Prevention Center of the University Hospital of the Federal University of Maranhão. This study included adult nondialysis patients diagnosed with CKD. The participants' blood samples were collected for a high-sensitivity C-reactive protein (hs-CRP) test and blood count. They were divided into two groups according to the presence or absence of inflammation based on the hs-CRP value (<0.5 mg/dL). NLR and PLR were calculated based on the absolute number of neutrophils, lymphocytes, and platelets and were compared between them and with hs-CRP. Statistical analysis was performed using the Stata software, with the Shapiro–Wilk, Mann–Whitney, Spearman's Correlation, and receiver operating characteristic curve tests. This study was approved by the local ethics committee. Results. The participants were categorized into two groups: with inflammation (n = 64) and without inflammation (n = 21). The mean age was 61.43 ± 14.63 y. The NLR and PLR values were significantly different between the groups with and without inflammation (p = 0.045 and p = 0.004 , respectively). However, only PLR showed a significant positive correlation with hs-CRP (p = 0.015). The best cutoff point for NLR to detect inflammation was 1.98, with 76.19% sensitivity and 48.44% specificity. For PLR, it was 116.07, with 85.71% sensitivity and 51.56% specificity. There was no significant difference between the area under the NLR and PLR curve (0.71 vs. 0.64; p = 0.186) for this population. Conclusions. This study showed that PLR was positively correlated with hs-CRP in nondialysis CKD patients and can be used to identify inflammation in this population. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) are cell-extruded DNA strands coated with neutrophils' nuclear proteins and enzymes from cytotoxic granules, produced by NETosis, a cell death pathway. They perform an important defensive role in innate immunity, but their increased production and/or inefficient degradation expose new antigens, such as DNA or citrullinated histone peptides, triggering autoimmunity. This study aimed to access possible associations between serum NETs levels with epidemiological, clinical, and serological data from a well-characterized SLE Brazilian patients' cohort. NET levels were evaluated in one hundred seventy serum samples of patients with Systemic Lupus Erythematosus (SLE) using an Immunoassay. Univariate and multivariate binary logistic regression used clinical patients' data as independent variables. Parametric and non-parametric tests compared log10 base serum NET levels transformed between patients' groups. SLE patients were also dichotomized into "High serum NET levels" and "Low serum NET levels" groups. All analyses were performed in R language 4.1.2, and p < 0.05 were considered significant. Increased susceptibility for high serum NET levels was observed in SLE patients with Raynaud's phenomenon (OR = 2.30, 95 % CI = 1.06–5.21 and p = 0.039), independently of any other risk factor. Also, SLE patients with Raynaud's phenomenon presented higher mean NET serum levels (mean = −0.13 vs. −0.51, p = 0.01). In addition, higher mean NET serum levels were associated with glomerulonephritis (mean = -0.45 vs. −0.12, p = 0.03). Ultimately, the SLEDAI index scored higher in the high NETs serum levels group (median = 2.0 vs. 0.0, p = 6 × 10−3). The formation of NETs might be implicated in Raynaud's phenomenon, glomerulonephritis, and disease index score in SLE patients. Our results highlight the importance of serum NET levels as a possible therapeutical target to modulate the clinical course of SLE. [ABSTRACT FROM AUTHOR]

Background Our goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. Methods Genotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4 498 586 imputed single-nucleotide variants (SNVs). A genome-wide association study (GWAS) using linear mixed models took account of genetic diversity/ethnicity/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL) and chromatin interaction mapping was performed in Functional Mapping and Annotation (FUMA). Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay. Results Positional mapping identified 32 genomic loci associated with CL, none achieving genome-wide significance (P < 5 × 10−8). Lead SNVs at 23 loci occurred at protein coding or noncoding RNA genes, 15 with eQTLs for functionally relevant cells/tissues and/or showing differential expression in lesions. Of these, the 6 most plausible genetic risk loci were SERPINB10 (P imputed_1000G = 2.67 × 10−6), CRLF3 (P imputed_1000G = 5.12 × 10−6), STX7 (P imputed_1000G = 6.06 × 10−6), KRT80 (P imputed_1000G = 6.58 × 10−6), LAMP3 (P imputed_1000G = 6.54 × 10−6), and IFNG-AS1 (P imputed_1000G = 1.32 × 10−5). LAMP3 (P adjusted = 9.25 × 10−12; +6-fold), STX7 (P adjusted = 7.62 × 10−3; +1.3-fold), and CRLF3 (P adjusted = 9.19 × 10−9; +1.97-fold) were expressed more highly in CL biopsies compared to normal skin; KRT80 (P adjusted = 3.07 × 10−8; −3-fold) was lower. Multiple cis-eQTLs across SERPINB10 mapped to chromatin interaction regions of transcriptional/enhancer activity in neutrophils, monocytes, B cells, and hematopoietic stem cells. Those at IFNG-AS1 mapped to transcriptional/enhancer regions in T, natural killer, and B cells. The percentage of peripheral blood CD3+ T cells making antigen-specific interferon-γ differed significantly by IFNG-AS1 genotype. Conclusions This first GWAS for CL identified multiple genetic risk loci including a novel lead to understanding CL pathogenesis through regulation of interferon-γ by IFNG antisense RNA 1. [ABSTRACT FROM AUTHOR]

• Laboratory results from 178 887 Brazilian COVID-19 patients and controls were evaluated. • Distinct disease profiles influenced by age and sex were detected. • Such profiles may underly the occurrence of severe disease. The progression and severity of COVID-19 vary significantly in the population. While the hallmarks of SARS-CoV-2 and severe COVID-19 within routine laboratory parameters are emerging, the impact of sex and age on these profiles is still unknown. A multidimensional analysis was performed involving millions of records of laboratory parameters and diagnostic tests for 178 887 individuals from Brazil, of whom 33 266 tested positive for SARS-CoV-2. Analyzed data included those relating to complete blood cell count, electrolytes, metabolites, arterial blood gases, enzymes, hormones, cancer biomarkers, and others. COVID-19 induced similar alterations in laboratory parameters in males and females. CRP and ferritin were increased, especially in older men with COVID-19, whereas abnormal liver function tests were common across several age groups, except for young women. Low peripheral blood basophils and eosinophils were more common in the elderly with COVID-19. Both male and female COVID-19 patients admitted to intensive care units displayed alterations in the coagulation system, and higher values for neutrophils, CRP, and lactate dehydrogenase. Our study uncovered the laboratory profiles of a large cohort of COVID-19 patients, which formed the basis of discrepancies influenced by aging and biological sex. These profiles directly linked COVID-19 disease presentation to an intricate interplay between sex, age, and immune activation. [ABSTRACT FROM AUTHOR]

Background: Summer Pasture Associated Obstructive Pulmonary Disease (SPAOPD), or Equine Pasture Asthma (EPA), has been described as an environmentally-induced respiratory disease that occurs during the warmer and more humid months, leading to reversible airway obstruction, persistent and non-specific airway hyper-responsiveness, and chronic neutrophilic airway inflammation. Exacerbation of clinical signs vary according to warm seasons and range from mild to severe episodes of wheezing, coughing, and laboured breathing, being highly debilitating to the equine. This report described two cases of Equine Pasture Asthma that showed clinical and environmental similarities with Summer Pasture Associated Obstructive Pulmonary Disease. Cases: The patients were crossbreed geldings that have never been stabled and were used for cattle management in a farm in southeastern Brazil. They presented poor performance and a persistent cough for over 3 years. Initially, the respiratory signs were only observed after exercise but, over the years, it gradually progressed to being observed when the horses were at rest. Both animals had a history of regular deworming and were previously treated by other veterinarians with antibiotics, clenbuterol, and mucokinetics. Little improvement was noticed by the owner and the signs returned over time as treatment was often discontinued. Clinical findings were compatible with the grade 3 mucus classification as well as with score 2 for Severe Asthma. BALF cytology was done according to routine procedure. Animal 1 presented slides with free yeast, macrophages, and mucus with Curschmann's spiral and counting of 29.7% of neutrophils (NE), 43.7% of lymphocytes (LP), 25.3% of macrophages (MC) and 1.3% of eosinophils (EO). Animal 2 presented slides with phagocytized yeast, mucus and counting of 27% of NE, 38.5% of LP, 33% of MC and 1.5% of EO. Discussion: Diagnostic findings were compatible with the clinical score 2 for Severe Asthma, where the animals presented frequent cough with periods of no coughing, nostrils flares in inspiration and exhalation, obvious abdominal flattening and "heave line", pulmonary auscultation with crackles, and scarce mucous nasal discharge. Our cytological findings also fall within the Severe Asthma classification, when the specific counting of 300 cells is equivalent to = 20% of neutrophils on BALF analysis and the animal present increase in respiratory rate/effort at rest. Similar counts were found by other authors counting 200 cells, 300 cells, and 5 fields (of at least 100 cells) on a cytocentrifuge smear. The present report took place in a region of the Rio de Janeiro State, southeastern Brazil, which shows predisposing climatic characteristics similar to those described in previous SPAOPD reports. Yet, this very climate remains somewhat constant throughout the year, as seasonality in the Rio de Janeiro State is not as marked as in the Northern Hemisphere. Given this contrasting aspect, we believe that the term Equine Pasture Asthma, instead of SPAOPD, is more appropriate to describe the cases presented here. Also, to the best of the authors' knowledge, this is the first documented description in Brazil of Equine Pasture Asthma in animals that were never stabled or fed with hay. This documented evidence of a chronic respiratory condition consistent with Equine Pasture Asthma but little related to seasonal changes presents as a warning to other possible cases that might go unnoticed in equine herds in Brazil and in similar climates. [ABSTRACT FROM AUTHOR]

Ehrlichia and Anaplasma species are the most common tick‐borne disease (TBD) pathogens in dogs worldwide. Ehrlichia canis, the aetiological agent of the Canine Monocytic Ehrlichiosis (CME), is known to replicate within the cytoplasm of mononuclear cells into clusters of organisms called morulae. However, detection of morulae in neutrophils is commonly observed in dogs infected by Ehrlichia ewingii or Anaplasma phagocytophilum. We report uncommon clinical cases of canine ehrlichiosis presenting morulae compatible with E. ewingii and A. phagocytophilum in dogs from two distinct regions of Brazil. Eight dogs were admitted to two veterinary teaching hospitals from Brazil, showing clinical or haematological signs suggestive of TBD. Blood or peritoneal fluid was withdrawn for haematological and cytologic analysis. All samples were evaluated by PCR assays for Ehrlichia and Anaplasma using genus‐specific primers for dsb, 16S rRNA and groEL genes, followed by sequencing. Samples were also evaluated by nested PCR assays for the 16S rRNA gene of E. ewingii and groEL gene of A. phagocytophilum and Anaplasma platys. Seven dogs revealed thrombocytopenia, six dogs had monocytosis and five presented lymphopenia and anaemia. All dogs showed morulae structures compatible with Ehrlichia spp. in neutrophils and were PCR‐positive for the dsb and 16S rRNA gene fragments of Ehrlichia, with sequences showing 100% identity with multiple E. canis sequences deposited in the GenBank™. Sequencing of 16S rRNA and groEL gene fragments from one PCR‐positive dog showed 100% identity with A. platys. Overall, our data suggest that in endemic regions for E. canis, that is Brazil, the presence of morulae in neutrophils may indicate infection by this bacterium. Herein, morulae were also found in neutrophils present in the peritoneal fluid of a dog. Also, this is the first report of E. canis and Hepatozoon canis co‐infection in neutrophils from naturally infected dogs confirmed by DNA sequencing. [ABSTRACT FROM AUTHOR]

We analyzed the toxic effects of the organophosphate insecticide chlorpyrifos (Klorpan® 480 EC formulation) on the blood leukocyte profiles of Odontophrynus carvalhoi tadpoles, a neotropical species endemic to Brazil, exposed to four different concentrations of that insecticide (10, 100, 200, and 400 μg L−1) for 192 h. The tadpoles were anesthetized and their blood was collected by cardiac puncture, with subsequent cell smears and staining with May–Grunwald–Giemsa and Wright. The numbers and types of leukocytes were determined after different periods of exposure (24 h, 48 h, 96 h, and 192 h) by analyzing 100 leukocytes from each tadpole (under 1000× magnification). The tadpoles exposed to different concentrations of chlorpyrifos exhibited reductions in their numbers of lymphocytes, monocytes, and basophils, but increases in the numbers of neutrophils and eosinophils. As such, exposure to chlorpyrifos altered cell type proportions, which could alter the capacity of those tadpoles to respond to environmental stresses, make them more susceptible to infection by diverse pathogens, and thus compromise their chances of survival. That scenario would be even more serious for species having restricted distributions, as population declines would be more severe and impacting. Therefore, the use of chlorpyrifos constitutes a serious risk for anuran amphibians that occur in or near agricultural fields by contributing to immunosuppression and threatening their survival. [ABSTRACT FROM AUTHOR]

Introduction: Leukemoid reaction (leukocyte count >50 cells ×109 L) is a rare but extremely relevant finding. Since little has been published on this condition's clinical relevance and prognosis, we investigated leukemoid reaction in patients with a white blood cell count of >50 × 109 L, including etiology and outcomes. Methods: This retrospective cohort study included all patients at a Brazilian tertiary hospital between January 2016 and July 2018 > 18 years with a total leukocyte count >50 cells×109 L. Demographics, complete blood count, clinical features, and the exams used to diagnose and determine leukemoid reaction etiology were analyzed. A Kaplan‐Meyer survival analysis was performed, and a binary logistic regression model identified variables associated with death. Results: Of the 267 cases with white blood cell count of >50 × 109, 162/267 (60%) were secondary to hematopoietic neoplasm and 105/267 (40%) presenting as a true leukemoid reaction. The primary causes of the true leukemoid reaction cases were infection (59), nonhematopoietic neoplasm (17), or other causes (29). Patient deaths (66) differed significantly between groups (P <.001, log‐rank [Mantel‐Cox] Test). Lower hemoglobin, older age, and increased segmented neutrophil count were associated with increased risk of death. Conclusions: This was a modern cohort analysis of leukemoid reactions, inclusive of all etiologies. The most common cause was infection, which involved several microorganisms. Paraneoplastic leukemoid reaction was also common. Both conditions have a poor prognosis with high mortality, being a major medical challenge. [ABSTRACT FROM AUTHOR]

The species Tynanthus micranthus Corr. Méllo, is popularly known as "Cipó Cravo" or "Craveiro", and is usually used as a stimulant and aphrodisiac, and found in the north of the State of Paraná - Brazil. The isolate the alkane dotriacontane from T. micranthus and to verify its action on the activation of human neutrophils to produce superoxide anions by the nitroblue tetrazolium reduction method (NBT), in comparison with the activation obtained by commercial dotriacontane. The ethanolic extract dried leaves was prepared by modified Soxhlet apparatus. Then the ethanolic extract was fractionated with n-hexane to obtain the hexane fraction which was submitted to the chromatographic column to obtain the compound dotriacontane. The substance was identified by ¹H and 13 C NMR spectroscopy. Isolated and commercial dotriacontane were evaluated by the NBT assay for verification of the activation of human neutrophils. The isolated and commercial dotriacontane activated neutrophils (10.0 µg/mL) when compared to phorbol myristate acetate (PMA) (10.0 µg/mL). In the quantitative test commercial dotriacontane induced significant activation when compared to PMA (10.0 µg/mL). The substance dotriacontane, first time identified in the genus Tynanthus. The dotriacontane was shown to be important to confirm the activation of human neutrophils to produce superoxide anions. [ABSTRACT FROM AUTHOR]

Background: Physiological values reflect the health condition and responses of individuals to handling in captivity. The aim of this study was to establish hematological and serum biochemistry parameters of clinically healthy animals of the Alouatta guariba clamitans subspecies. Methods: We collected blood samples from adult males and females kept at the Center for Biological Research of Indaial after chemical containment with 3.9 mg/kg of tiletamine hydrochloride and zolazepam. Results: Significant differences between males and females were found in the levels of erythrocytes, hemoglobin, hematocrit, lymphocytes, neutrophils, platelets, mean corpuscular hemoglobin concentration (MCHC), and gamma‐glutamyltranspeptidase (GGT). Conclusions: Our results suggest the existence of sexual dimorphism in some physiological parameters of A guariba clamitans. The parameters reported herein can be used as reference values for other populations kept under similar conditions. [ABSTRACT FROM AUTHOR]

Background: Safety data on the yellow fever vaccine 17DD in People Living with HIV (PLWH) are limited. This study explored the occurrence of post-vaccination 17DD viremia and the kinetics of hematological and liver laboratorial parameters in PLWH and HIV-uninfected participants [HIV(-) controls]., Methods: We conducted a secondary analysis of a longitudinal interventional trial (NCT03132311) study that enrolled PLWH and HIV(-) controls to receive a single 17DD dose and were followed at 5, 30 and 365 days after vaccination in Rio de Janeiro, Brazil. 17DD viremia (obtained throughreal-time PCR and plaque forming units' assays), hematological (neutrophils, lymphocytes and platelets counts) and liver enzymes (ALT and AST) results were assessed at baseline and Days 5 and 30 post-vaccination. Logistic regression models explored factors associated with the odds of having positive 17DD viremia. Linear regression models explored variables associated with hematological and liver enzymes results at Day 5., Results: A total of 202 PLWH with CD4 ≥ 200 cells/µL and 68 HIV(-) controls were included in the analyses. 17DD viremia was found in 20.0 % of the participants and was twice more frequent in PLWH than in HIV(-) controls (22.8% vs. 11.8 %, p-value < 0.001). Neutrophils, lymphocytes and platelets counts dropped at Day 5 and returned to baseline values at Day 30. 17DD viremia was associated with lower nadir of lymphocytes and platelets at Day 5. ALT levels did not increase post-vaccination and were not associated with 17DD viremia., Conclusions: 17DD was safe and well-tolerated in PLWH with CD4 ≥ 200 cells/µL. Post-vaccination viremia was more frequent in PLWH than in controls. Transient and self-limited decreases in lymphocytes and neutrophils occurred early after vaccination. 17DD viremia was associated with lower lymphocytes and platelets nadir after vaccination. We did not observe elevations in ALT after 17DD vaccination., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Infectologia. Published by Elsevier España, S.L.U. All rights reserved.)

The neutrophil to lymphocyte ratio (NLR) at admission is a prognostic marker for acute coronary syndrome (ACS). However, no study was performed exclusively with older people. The present study evaluated the NLR in older people with ACS as a predictor of death, combined major in-hospital outcomes (death, stroke, reinfarction), hospital stay, ventricular ejection fraction, use of vasoactive drugs, and extent of coronary artery disease. We conducted a retrospective cohort study with in-hospital follow-up using data from a single center in Recife, Brazil. Patients aged 60 and older admitted with ACS were selected. The patients were followed until discharge or death. A total of 272 individuals were evaluated; 55.8% were men and the mean age was 73 years. The NLR was not a predictor of in-hospital death. A higher NLR upon admission was associated with a longer hospital stay (β = 0.131; 95% confidence interval [CI]: 0.017-0.246; P = .024) and an ejection fraction <50% (relative risk = 2.1; 95% CI: 1.19-3.57; P = .001). The other outcomes did not reach significance. The NLR was associated with a longer hospital stay and a left ventricular ejection fraction <50% in older people with ACS. [ABSTRACT FROM AUTHOR]

Leishmania (L.) amazonensis is one of the etiological agents of cutaneous leishmaniasis (CL) in Brazil. Currently, there is no vaccine approved for human use against leishmaniasis, although several vaccine preparations are in experimental stages. One of them is Leishvacin, or LaAg, a first-generation vaccine composed of total L. amazonensis antigens that has consistently shown an increase of mouse resistance against CL when administered intranasally (i.n.). Since Toll-like receptor 9 (TLR9) is highly expressed in the nasal mucosa and LaAg is composed of TLR9-binding DNA CpG motifs, in this study we proposed to investigate the role of TLR9 in both L. amazonensis infection and in LaAg vaccine efficacy in C57BL/6 (WT) mice and TLR9-/- mice. First, we evaluated, the infection of macrophages by L. amazonensis in vitro, showing no significant difference between macrophages from WT and TLR9-/- mice in terms of both infection percentage and total number of intracellular amastigotes, as well as NO production. In addition, neutrophils from WT and TLR9-/- mice had similar capacity to produce neutrophil extracellular traps (NETs) in response to L. amazonesis. L. amazonensis was did not activate dendritic cells from WT and TLR9-/- mice, analysed by MHCII and CD86 expression. However, in vivo, TLR9-/- mice were slightly more susceptible to L. amazonensis infection than WT mice, presenting a larger lesion and an increased parasite load at the peak of infection and in the chronic phase. The increased TLR9-/- mice susceptibility was accompanied by an increased IgG and IgG1 production; a decrease of IFN-γ in infected tissue, but not IL-4 and IL-10; and a decreased number of IFN-γ producing CD8+ T cells, but not CD4+ T cells in the lesion-draining lymph nodes. Also, TLR9-/- mice could not control parasite growth following i.n. LaAg vaccination unlike the WT mice. This protection failure was associated with a reduction of the hypersensitivity response induced by immunization. The TLR9-/- vaccinated mice failed to respond to antigen stimulation and to produce IFN-γ by lymph node cells. Together, these results suggest that TLR9 contributes to C57BL/6 mouse resistance against L. amazonensis, and that the TLR9-binding LaAg comprising CpG motifs may be important for intranasal vaccine efficacy against CL. [ABSTRACT FROM AUTHOR]

Copyright of Revista Odonto Ciencia is the property of EDIPUCRS - Editora Universitaria da PUCRS and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: To analyze the association between four biomarkers and overall survival in patients with breast cancer (BC).Methodology: This cohort study had a sample of 2374 women over the age of 18, diagnosed and treated in a single reference center for BC in Brazil, during the year 2008-2009. The following pretreatment indices were analyzed: neutrophil-lymphocyte ratio (NLR), a derived neutrophil-lymphocyte ratio (dNLR), absolute neutrophil count (ANC) and platelet-lymphocyte ratio (PLR). A descriptive analysis was performed using median (range) and absolute and relative frequency as categorical variables. Exploratory survival evaluation was performed using the Kaplan-Meier method and the log-rank test for comparison between survival curves, with a statistical significance level of 5%. The variables with p<0.20 were selected for inclusion in a multivariate Cox regression model, considering as statistically significant p<0.05.Results: After adjusting for clinical variables, the biomarkers associated with worse overall survival were NLR >5 (HR=1.66 95%CI 1.08-2.55; p=0.021) and PLR >300 (HR=1.82 95%CI 1.10-2.99; p=0.019). When stratified by molecular subtype, the independent markers related to death were PLR >300 for triple negative (HR 3.27 95%CI 1.38-7.76; p=0.007); NLR >5 (HR 2.47 95%CI 1.16-5.28; p=0.019), ANC >7500 (HR 1.84 95%CI 1.17-2.90; p=0.008) and dNLR >3 (HR 2.45 95%CI 1.29-4.66; p=0.006) for luminal.Conclusion: NLR and PLR are independent markers of prognosis in BC. Further studies are needed in patients with overexpression of HER 2. [ABSTRACT FROM AUTHOR]

Ethnopharmacological importance The hemiparasitic species Psittacanthus plagiophyllus Eichl. (Loranthaceae), also known as erva de passarinho , is used in folk medicine in the Santarém region in the state of Pará, Brazil, to treat gastritis and a variety of inflammatory disorders. In view of the lack of pharmacological studies on this species in the literature and the fact that it is used constantly by the local population, this study sought to standardize the extract of the leaves of P. plagiophyllus (AEPp) and to assess its anti-inflammatory potential in in vivo tests. Material and methods Quality control and standardization of AEPp were performed following the 5th edition of the Brazilian Pharmacopeia. To assess the in vivo anti-inflammatory activity of AEPp, the carrageenan-induced and dextran-induced rat paw edema models were initially used. To investigate the effect of AEPp on carrageenan-induced leukocyte recruitment and exudate production, the air pouch inflammation model was used. In addition, the antioxidant activity of AEPp was assessed in vitro by the DPPH radical scavenging method. Results The chromatographic profile of AEPp indicated the presence of flavonoids, coumarins and hydrolyzable and condensed tannins. Measurement of phenolics revealed the following percentages in the extract: 12.62±0.18% total phenolics, 5.39±0.01% total tannins, 12.54±0.24% hydrolyzable tannins, 8.37±0.32% condensed tannins and 1.23±0.02% total flavonoids. In 500 and 1000 mg/kg doses (p.o.) AEPp had significant edema-inhibiting activity ( p <0.01) in both the models used, suggesting that the extract may act in vascular and cell events in the inflammatory response and exert an inhibitory effect on mediators responsible for edema. In all the doses tested [250, 500 and 1000 mg/kg (p.o.)], AEPp inhibited total leukocyte and neutrophil migration and reduced the amount of exudate in the air pouch in a dose-dependent manner. Both effects were statistically significant ( p <0.01). The extract also reduced the DPPH radical (maximum reduction 93.13±1.71% at a concentration of 75 µg/mL), indicating that it has antioxidant activity. AEPp, therefore, exhibited considerable in vivo anti-inflammatory activity and in vitro antioxidant activity. This may be due to its high phenolics content. Conclusion These findings provide evidence to support the use of P. plagiophyllus in folk medicine to treat inflammatory disorders. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Mandevilla longiflora, popularly known as “velame" in central Brazil, is a subshrub widely distributed in South America. Its xylopodium is used in the form of a decoction or infusion to treat inflammation and other ailments. Aim of the Study This study aimed to evaluate the anti-inflammatory potential of M. longiflora in an in vivo model of ovalbumin-induced immediate hypersensitivity, identifying its effects on leukocyte infiltration, IgE and LTB 4 levels, and Th2 cytokine production. In addition, HPLC fingerprint of the extract was performed. Material and methods The hydroethanolic extract 70% of M. longiflora (HEMI) was obtained by maceration of the plant xylopodium. Swiss mice were sensitized by i.p. injection OVA-aluminium hydroxide on days 1 and 10. Nine days after the last sensitisation animals were challenged for 6 consecutive days with OVA solution for 20 min daily in a closed chamber under continuous flow of aerosol. The animals were treated with HEMl (20, 50 and 200 mg/kg p.o.), 2 times per day, and euthanized 24 h later. Animals treated with vehicle (2% Tween-20) or dexamethasone were used as negative and positive controls, respectively. The recruitment of inflammatory cells into the pulmonary cavity was evaluated by counting cells present in broncho-alveolar lavage fluid (BALF). Lung tissue was also collected for histopathology and infiltration analysis. Quantification of IL-4, IL-5 and IL-13 from the BALF, and IgE, and LTB 4 from plasma, were conducted by immunoassay. Results and conclusions The HEMl attenuated leukocyte migration into the airways, which was evidenced by a decrease in eosinophils, neutrophils and mononuclear cells, both in BALF quantification and by histopathological analysis, as well as decreasing the concentrations of IL-4, IL-5, IL-13, IgE and LTB 4 . All of these events are typical of air-mucosa inflammatory disease. These findings scientifically evidence for the first time the ethnopharmacological use of M. longiflora to treat chronic inflammatory events, such as asthma, and suggest a potential therapeutic use or complementary therapy for this plant extract. [ABSTRACT FROM AUTHOR]

Objectives. Diagnostic markers of infection have had little innovation over the last few decades. CD64, a marker expressed on the surface of neutrophils, may have utility for this purpose. Methods. This study was conducted in an adult intensive care unit (ICU) in São Paulo, Brazil, with 89 patients. We evaluated CD64 in patients with documented or clinically diagnosed infection (infection group) and controls (patients without any evidence of infection) by two different methodologies: method #1, an in house assay, and method #2, the commercial kit Leuko64 (Trillium Diagnostics). Results. CD64 displayed good discriminating power with a 91.2% sensitivity (95% CI 90.7–91.6%) for detecting infection. The commercial kit (Leuko64) demonstrated higher specificity (87.3%) compared with method #1 as well as better accuracy (88.8%). Conclusions. CD64 seems to be a promising marker of infection in the intensive care setting, with Leuko64 showing a slight advantage. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ethnopharmacological studies are important tools as records and documentation of the empirical uses of medicinal plants in traditional communities with the purpose of generating useful knowledge to lead to the development of new medicines, biodiversity conservation and enhancement of knowledge and local culture. Poikilacanthus glandulosus is widely used by the population of City of Santiago, in Brazil, nevertheless, it does not have any validation regarding its use and its medicinal effects. Aim The objective of this study was to perform one ethnopharmacological survey about P. glandulosus in the City of Santiago and determine the anti-inflammatory activity in order to prove its uses in popular medicine. Methods Personal and ethnopharmacological data were collected through a prepared questionnaire. The phytochemical analysis was performed observing the individual methodology for each reaction and by HPLC-UV. The antiedematogenic and anti-inflammatory (cell infiltration and histological procedure) activities of the P. glandulosus (0.01–1000 μg/ear) were evaluated in the ear edema model induced by topical application of croton oil. Results P. glandulosus is known in City of Santiago as “Gaiana” and its macerated leaves and branches are prepared with alcohol or sugarcane liquor especially for insect bites, cicatrization and inflammation. HPLC analysis revealed the presence of maslinic acid (2.024±0.10 mg/g), uvaol (0.124±0.02 mg/g) and sitosterol (0.502±0.05 mg/g). The topical application of crude extract of P. glandulosus reduced in a dose-dependent manner the croton oil-induced ear edema and myeloperoxidase activity (neutrophils infiltration marker) with maximum inhibition of 87±2% and 64±12%, respectively at 1000 µg/ear. Dexamethasone (100 µg/ear), used as a positive control, inhibited croton oil-induced ear edema in 89±3% and decreased myeloperoxidase activity in 50±3%. Both P. glandulosus as dexamethasone reduced cell infiltration when evaluated by histological procedure Conclusion This work allowed us to understand the specie P. glandulosus through ethnopharmacological study and it showed that the crude extract presented antiedematogenic and anti-inflammatory actions, proving their traditional use as anti-inflammatory. [ABSTRACT FROM AUTHOR]

Stryphnodendron species, popularly named “barbatimão,” are traditionally used in Brazil as anti-inflammatory agents. This study aimed to investigate the effect of barbatimão and 11 other species on the production of tumor necrosis factor-alpha (TNF-α) in lipopolysaccharide- (LPS-) stimulated THP-1 cells, as well as their anti-arthritis activity. The extracts of Stryphnodendron adstringens, Stryphnodendron obovatum, Campomanesia lineatifolia, and Terminalia glabrescens promoted a concentration-dependent inhibition of TNF-α. Mice injected with LPS in the knee joint were treated per os with fractions from the selected extracts. Both the organic (SAO) and the aqueous (SAA) fractions of S. adstringens promoted a dose-dependent reduction of leukocyte migration and neutrophil accumulation into the joint, but none of them reduced CXCL1 concentration in the periarticular tissue. In contrast, treatment with C. lineatifolia and T. glabrescens fractions did not ameliorate the inflammatory parameters. Analyses of SAO by Ultra Performance Liquid Chromatography (UPLC) coupled to electrospray ionization mass spectrometry (ESI-MS) led to the identification of gallic acid along with 11 prodelphinidins, characterized as monomers and dimers of the B-type. Our findings contribute to some extent to corroborating the traditional use of S. adstringens as an anti-inflammatory agent. This activity is probably related to a decrease of leukocyte migration into the inflammatory site. Polyphenols like gallic acid and prodelphinidins, identified in the active fraction, may contribute to the observed activity. [ABSTRACT FROM AUTHOR]

Purpose: Idiopathic pulmonary fibrosis (IPF) is a chronic fibrosing interstitial pneumonia, which involves aberrant serotonin (5-hydroxytryptamine [5-HT]) and Akt signaling. As protective effects of chronic aerobic training (AT) have been demonstrated in the context of lung injury, this study investigated whether AT attenuates bleomycin-induced lung fibrosis partly via a reduction of 5-HT and AKT signaling. Methods: Seventy-two C57BL/6 male mice were distributed in Control (Co), Exercise (Ex), Fibrosis (Fi), and Fibrosis + Exercise (Fi + Ex) groups. Bleomycin (1.5 UI⋅kg-1) was administered on day 1 and treadmill AT began on day 15 and continued for 60 min⋅d-1, 5 d⋅wk-1 for 4 wk. We evaluated total and differential cell counts in bronchoalveolar lavage (BAL), interleukin (IL)-1β, IL-6, CXCL1/KC, IL-10, tumor necrosis factor α, and transforming growth factor β levels in BAL, collagen content in lung parenchyma, 5-HT levels in BAL fluid and in serum, the expression of 5-HT2B receptor, and Akt phosphorylation in lung tissue. Results: AT reduced bleomycin-increased number of total cells (P < 0.001), neutrophils (P < 0.01), macrophages (P < 0.01), and lymphocytes (P < 0.05) in BAL. It also reduced the levels of IL-1β (P < 0.01), IL-6 (P < 0.05), CXCL1/KC (P < 0.001), tumor necrosis factor α (P <0.001), and transforming growth factor Β(P < 0.001). It increased expression of ant-inflammatory cytokine IL-10 (P < 0.001). It reduced bleomycin-increased 5-HT levels in BAL (P < 0.001) and in serum (P < 0.05). Reductions in collagen fiber deposition (P < 0.01), 5-HT2B receptor expression (P < 0.01), and Akt phosphorylation in lung tissue were observed. Conclusions: AT accelerates the resolution of lung inflammation and fibrosis in a model of bleomycin-induced lung fibrosis partly via attenuation of 5-HT/ Akt signaling. [ABSTRACT FROM AUTHOR]

Background: Ocular toxoplasmosis is a prominent and severe condition of high incidence in Brazil. The current study provides new insights into the immunological events that can be associated with retinochoroiditis in the setting of congenital toxoplasmosis in human infants.Methods: Flow cytometry of intracytoplasmic cytokines in leukocyte subsets following in vitro short-term antigenic recall in infants with congenital T. gondii infection.Results: Our data demonstrates that whereas neutrophils and monocytes from T. gondii-infected infants display a combination of proinflammatory and regulatory cytokine profiles, natural killer cells showed a predominantly proinflammatory profile upon in vitro T. gondii stimulation. The proinflammatory response of CD4(+) and CD8(+) T cells, characterized by the production of interferon γ (IFN-γ) and interleukin 17 in patients with an active retinochoroidal lesion, revealed the presence of IFN-γ and tumor necrosis factor α during early and late immunological events. This specific proinflammatory pattern is associated with early events and active retinochoroidal lesion, whereas a robust monocyte-derived interleukin 10-mediated profile is observed in children with cicatricial ocular lesions.Conclusions: These findings support the existence of a progressive immunological environment concomitant with the initial, apical, and cicatricial phases in the process of retinochoroidal lesion formation in infants with congenital toxoplasmosis that may be relevant in the establishment of stage-specific clinical management. [ABSTRACT FROM AUTHOR]

Brazilian native fruits are unmatched in their variety, but a poorly explored resource for the development of food and pharmaceutical products. The aim of this study was to evaluate the phenolic composition as well as the antioxidant and anti-inflammatory activities of the extracts of leaves, seeds, and pulp of four Brazilian native fruits (Eugenia leitonii, Eugenia involucrata, Eugenia brasiliensis, and Eugenia myrcianthes). GC—MS analyses of the ethanolic extracts showed the presence of epicatechin and gallic acid as the major compounds in these fruits. Antioxidant activity was measured using synthetic DPPH free-radical scavenging, β-carotene bleaching assay, and reactive oxygen species (ROO·, O2·−, and HOCl). The fruit extracts also exhibited antioxidant effect against biologically relevant radicals such as peroxyl, superoxide, and hypochlorous acid. In general, the pulps were the fruit fractions that exhibited the lowest antioxidant activities, whereas the leaves showed the highest ones. The anti-inflammatory activity was assessed in an in vivo model using the carrageenan-induced neutrophil migration assay, which evaluates the inflammatory response in the acute phase. The pulp, seeds, and leaves of these fruits reduced the neutrophil influx by 40% to 64%. Based on these results, we suggest that the anti-inflammatory activity of these native fruits is related to the modulation of neutrophil migration, through the inhibition of cytokines, chemokines, and adhesion molecules, as well as to the antioxidant action of their ethanolic extracts in scavenging the free-radicals released by neutrophils. Therefore, these native fruits can be useful to produce food additives and functional foods. [ABSTRACT FROM AUTHOR]

Purpose: Our study aimed to evaluate whether obesity induced by cafeteria diet changes the neutrophil effector/inflammatory function and whether treatment with green tea extract (GT) can improve neutrophil function. Methods: Male Wistar rats were treated with GT by gavage (12 weeks/5 days/week; 500 mg/kg of body weight), and obesity was induced by cafeteria diet (8 weeks). Neutrophils were obtained from the peritoneal cavity (injection of oyster glycogen). The following analyses were performed: phagocytic capacity, chemotaxis, myeloperoxidase activity (MPO), hypochlorous acid (HOCl), superoxide anion (O), hydrogen peroxide (HO), IL-1β, IL-6 and TNFα, mRNA levels of inflammatory genes, calcium mobilisation, activities of antioxidant enzymes, hexokinase and G6PDH. Results: Neutrophils from obese rats showed a significant decrease in migration capacity, HO and HOCl production, MPO activity and O production. Phagocytosis and CD11b mRNA levels were increased, while inflammatory cytokines release remained unmodified. mRNA levels of TLR4 and IκK were enhanced. Treatment of obese rats with GT increased neutrophil migration, MPO activity, HO, HOCl and O production, whereas TNF-α and IL-6 were decreased (versus obese). Similar reductions in TLR4, IκK and CD11b mRNA were observed. Catalase and hexokinase were increased by obesity, while SOD and G6PDH were decreased. Treatment with GT reduced catalase and increased the GSH/GSSG ratio. Conclusion: In response to a cafeteria diet, we found a decreased chemotaxis, HO release, MPO activity and HOCl production. We also showed a significant immunomodulatory effect of GT on the obese condition recovering some of these factors such HO and HOCl production, also reducing the levels of inflammatory cytokines. [ABSTRACT FROM AUTHOR]

Lippia sidoides Cham (Verbenaceae) is largely distributed in the northeastern region of Brazil. It is popularly known as 'Alecrim-pimenta'. Recent studies have shown that some species of Lippia have interesting pharmacological activities. This study aimed to evaluate the effect of a nanostructured thymol gel (TG) 1.2 mg/g on acute phase of ligature-induced periodontitis model [acute periodontal disease (APD)] in rats. APD was induced in 24 Wistar rats subjected to ligature placement on left molars in maxillae. Animals were treated with TG, immediately after APD induction. Saline-based gel was utilized as negative control and diethylammonium diclofenac gel 10 mg/g was used as positive control. Animals were randomly assigned into the groups. The periodontium and the surrounding gingiva were examined at histopathology, as well as the neutrophil influx into the gingiva was assayed using myeloperoxidase activity levels by ELISA method. TG treatment reduced tissue lesion at histopathology coupled to decreased myeloperoxidase activity production in gingival tissue when compared with the saline gel control group (p < 0.05). The TG gel was able to provide a significant myeloperoxidase decreasing in gingiva tissue confirming to be effective in reducing gingival inflammation in this model. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Schinus terebinthifolius is a species of plant from the Anacardiaceae family, which can be found in different regions of Brazil. Schinus is popularly known as aroeirinha, aroeira-vermelha, or Brazilian pepper. In folk medicine, S. terebinthifolius is used for several disorders, including inflammatory conditions, skin wounds, mucosal membrane ulcers, respiratory problems, gout, tumors, diarrhea and arthritis. According to chemical analyses, gallic acid, methyl gallate and pentagalloylglucose are the main components of hydroalcoholic extracts from S. terebinthifolius leaves. In the present study, we demonstrated the ability of a hydroalcoholic extract to inhibit cell migration in arthritis and investigated the mechanisms underlying this phenomenon. Materials and methods The anti-inflammatory effect of S. terebinthifolius hydroalcoholic leaf extract (ST-70) was investigated in a zymosan-induced experimental model of inflammation. Male Swiss and C57Bl/6 mice received zymosan (100 µg/cavity) via intra-thoracic (i.t.) or intra-articular (i.a.) injection after oral pre-treatment with ST-70. The direct action of ST-70 on neutrophils was evaluated via chemotaxis. Results ST-70 exhibited a dose-dependent effect in the pleurisy model. The median effective dose (ED 50 ) was 100 mg/kg, which inhibited 70% of neutrophil accumulation when compared with the control group. ST-70 reduced joint diameter and neutrophil influx for synovial tissues at 6 h and 24 h in zymosan-induced arthritis. Additionally, ST-70 inhibited synovial interleukin (IL)-6, IL-1β, keratinocyte-derived chemokine (CXCL1/KC) and Tumor Necrosis Factor (TNF)-α production at 6 h and CXCL1/KC and IL-1β production at 24 h. The direct activity of ST-70 on neutrophils was observed via the impairment of CXCL1/KC-induced chemotaxis in neutrophils. Oral administration of ST-70 did not induce gastric damage. Daily administration for twenty days did not kill any animals. In contrast, similar administrations of diclofenac induced gastric damage and killed all animals by the fifth day. Conclusions Our results demonstrated significant anti-inflammatory effects of ST-70, suggesting a putative use of this herb for the development of phytomedicines to treat inflammatory diseases, such as joint inflammation. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Garcinia brasiliensis , a plant native to the Brazilian Amazon Rainforest, is used in traditional medicine to treat inflammation of the urinary tract, peptic ulcers, arthritis and other conditions. Aim of the study The purposes of this study were to analyze the chemical constituents of G. brasiliensis branches and leaves and to evaluate the potential of isolated compounds to act as inhibitors of both the oxidative burst of stimulated neutrophils and oxidative damage in human erythrocyte membranes to verify the antioxidant and anti-inflammatory effects of this plant. Materials and methods Neutrophils were isolated from the blood of healthy donors by Ficoll–Paque density gradient centrifugation. Superoxide anion and total reactive oxygen species (ROS) produced by stimulated neutrophils were measured by WST-1 reduction and luminol-enhanced chemiluminescence assays, respectively. Radical-induced lipoperoxidation and hemolysis were performed using erythrocytes from the blood of healthy donors. Compounds were isolated from G. brasiliensis branches and leaves by HPLC microfractionation, and structure elucidation of the isolated compounds was performed based on NMR and HR-MS analyses. Results The biflavonoids procyanidin, fukugetin, amentoflavone and podocarpusflavone isolated from G. brasiliensis showed potent inhibitory effects on the oxidative burst of human neutrophils, inhibiting ROS production by 50% at 1 μmol L −1 . These biflavonoids also proved to be potent inhibitors of hemolysis (with 88±7% inhibition at 50 µmol L −1 for procyanidin) and lipid peroxidation in human erythrocytes, with a malondialdehyde level (a biomarker of oxidative stress) of 8.5±0.3 nmol/mg Hb at 50 µmol L −1 for procyanidin. Conclusions These findings indicate that the biflavonoids extracted from G. brasiliensis branches and leaves modulate oxidative stress via inhibition of NADPH oxidase and ROS production by stimulated human neutrophils. Furthermore, the biflavonoids exhibited potent inhibition of oxidant hemolysis and lipid peroxidation induced by AAPH in human erythrocytes. Therefore, these studies suggest the use of G. brasiliensis extract as an antioxidant and anti-inflammatory agent. [ABSTRACT FROM AUTHOR]

Copyright of ConScientiae Saúde is the property of Nove de Julho University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective Infiltration of neutrophils into the joints plays an important role in bone erosion and articular destruction in rheumatoid arthritis (RA). Neutrophil trafficking during inflammation is a process that involves activation of chemotactic receptors. Recent findings suggest that changes in chemotactic receptor patterns could occur in neutrophils under certain inflammatory conditions. The aim of this study was to evaluate the gain of responsiveness of neutrophils to CCL2 in RA patients and to assess the role of CCL2 in driving neutrophil infiltration into the joints. Methods Neutrophils were purified from the peripheral blood of patients with RA or from mice with antigen-induced arthritis (AIA). Expression of CCR2 was evaluated using polymerase chain reaction, flow cytometry, and immunofluorescence analyses. In vitro chemotaxis to CCL2 was assayed to evaluate the functional significance of de novo CCR2 expression. The murine AIA model was used to evaluate the in vivo role of CCR2 in neutrophil infiltration into the joints. Results High CCR2 expression and responsiveness to CCL2 were observed in neutrophils from the blood of patients with early RA and in neutrophils from the blood and bone marrow of mice with AIA. Genetic deficiency or pharmacologic inhibition of CCR2 protected against the infiltration of neutrophils into the joints. This protection was not associated with an impairment of the neutrophil chemotactic ability or CXC chemokine production in the joints. Moreover, adoptive transfer of wild-type mouse neutrophils to CCR2-deficient mice restored neutrophil infiltration and the articular mechanical hyperalgesia associated with joint inflammation. Conclusion These findings suggest that CCR2 is directly involved in the detrimental infiltration of neutrophils into the joints in patients with RA, showing a new inflammatory role of CCR2 during RA flares or active disease. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Senecio brasiliensis (Spreng) Less ( S. brasiliensis ), known as “Flor-das-almas”, “Margaridinha” or “Maria mole”, is used in folk medicine as an anti-inflammatory and to treat gastric ulcers and stomach pain. While the Senecio genus has been widely studied for its pharmacological activities to support its use in traditional medicine, few studies focus on the anti-inflammatory activities of the species. Aim of the study To investigate the anti-inflammatory activities of S. brasiliensis , a specie native to Brazil, using a murine model of pleurisy induced by carrageenan. Material and methods The flowers of S. brasiliensis were air-dried for 3 days and subjected to ethanol (96%) extraction for 7 days to obtain the crude extract (CE). The CE was subjected to acid–base extraction to obtain the alkaloid fraction (AF). The hexane (HEX), dichloromethane (DCM) and ethyl acetate (EtOAc) fractions were obtained by extracting from CE with different solvents. The alkaloids senecionine (Sen), integerrimine (Int) and senecionine N-oxide were obtained from AF by chromatographic fractionation and a mixture of 1,4-, 3,4-, 3,5- and 4,5-dicaffeoylquinic acids (DCQs) were obtained from the EtOAc fraction. The isolated alkaloids were identified through spectroscopic analysis of IR, NMR and LC–MS coupled with electrospray ionization mass spectrometry (ESI-MS), and the dicaffeoylquinic acids through the hierarchical key method. Swiss mice were used in the in vivo experiments. We evaluated the effect of the CE, its derived fractions (AF, HEX, DCM and EtOAc), and the isolated compounds (Sen, Int, N-oxide senecionine, and DCQs) on: leukocyte migration, exudate concentrations, myeloperoxidase (MPO) and adenosine-deaminase (ADA) activities, and tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 17A levels in the fluid leakage from the pleural cavity using a mouse model of pleurisy induced by carrageenan. The effects of the isolated compounds, Sen, Int, N-oxide senecionine and DCQs, were also analyzed for their ability to inhibit p65 phosphorylation (p-p65) in the nuclear factor-kappa B (NF-κB) pathway in the lung tissue. MPO and ADA were analyzed by colorimetric assays, and the cytokines and protein p65 levels were determined using an enzyme immunoassay (EIA). Results The CE, its EtOAc and AF fractions, and its isolated compounds (Sen, Int and DCQs), significantly reduced leukocyte migration ( P< 0.05), MPO and ADA activities ( P< 0.01), and TNF-α ( P< 0.05), and IL-17A levels ( P< 0.01). The CE, the EtOAc and AF fractions, and the DCQs also decreased IL-1β levels ( P< 0.01). The isolated compounds, Sen, Int and the DCQs, inhibited p65 phosphorylation (NF-κB) ( P< 0.05). Conclusion This study demonstrated that S. brasiliensis has important anti-inflammatory properties that are capable of inhibiting activated leukocytes by decreasing neutrophil migration. This effect may be attributed to the inhibition of pro-inflammatory cytokines and the reduction of the NF-κB pathway. The compounds Sen, Int, and DCQs may be responsible for the anti-inflammatory actions of S. brasiliensis . [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Helicteres sacarolha A. St.- Hil. et al. popularly known in Brazil as ‘semente-de-macaco’, is widely employed in the popular medicine in many of parts of Brazil in the alleviation of symptoms of ailments such as peptic ulcer and inflammation. Up to the present, there is no study addressing the gastroprotective activity of the hydroethanolic extract of H. sacarolha and its possible mechanism of actions. Materials and methods The hydroethanolic (70%) extract of H. sacarolha (HEHs) was obtained by maceration. The gastroprotective activity was assessed using gastric ulcer models induced by acidified ethanol, piroxicam, and water restraint stress in mice and rats at doses of 20, 50 and 250 mg/kg p.o. Mechanistic studies involved the antisecretory assay evaluated with pylorus ligation in rats and pre-treatments with appropriate antagonists/inhibitors such as yohimbine, glibenclamide, indomethacin and l -NAME, effect on catalase and myeloperoxidase activities and gastric mucus determination using acidified ethanol- induced ulcer in mice. Results HEHs at all doses tested demonstrated potent gastroprotective activities in the acute ulcer models. The gastroprotective activity of HEHs was attenuated by pre-treatments with yohimbine, glibenclamide, indomethacin and l -NAME. HEHs effectively reduced basal gastric juice production without any effect on the free and total acidity. The gastroprotective action of HEHs involved increasing the antioxidant enzyme catalase and mucus secretion and inhibition of neutrophyl infiltration as reflected by the reduction in the myeloperoxidase activity. Conclusion The results of this study gave a scientific support for the popular use of the leaves of H. sacarolha in the treatment of gastric ulcers and that it has a multi-targeted action. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Arrabidaea chica (Bignoniacea) has been used in popular medicine in Brazil to treat inflammation, skin diseases and leukemia. This work aimed to investigate the anti-inflammatory and antitumoral activities of the A. chica aqueous (AE) and ethanol (EE) extracts. Materials and methods The murine sponge model was used to evaluate the anti-inflammatory and antiangiogenic activities of AE and EE. Accumulation of neutrophil and macrophage in the implants were determined by assaying myeloperoxidase and N-acetyl-glucosaminidase activities and the neovascularization evaluated by the amount of hemoglobin present in the implant using the Drabkin method. The antitumoral activity was evaluated using the MTT colorimetric method against Jurkat, HL60 and MCF-7 cells. Semi-purified fractions F1-F4 from the EE extract were obtained by a liquid–liquid solvent extraction method and their in vitro anti-proliferative effects were also investigated. Results Ethanol and aqueous extracts of A. chica decreased neutrophil accumulation and hemoglobin content in the sponge implants without altering the level of cytokines (IL-2, IL- 4, IL-5, IFN-γ, TNF-α and VEGF) and the albumin/globulin ratio in the serum of treated animals. There was no sign of toxicity (clinical, laboratory or histopathology). The ethanol extract presented antiproliferative activity (IC 50 21.5–36.3 µg/mL) against HL60 and Jurkat cell lineages and proapoptotic activity at 50 µg/mL in HL60 cells. The fraction F1 also demonstrated significant antiproliferative activity (IC 50 38.5 µg/mL) and proapoptotic activity against HL60 cells in a dose dependent manner. Conclusions Aqueous and ethanol extracts of A. chica attenuate the inflammatory and angiogenic components of the subcutaneous fibrovascular tissue induced by the synthetic matrix in mice. In addition, the ethanol extract from Arrabidaea chica and its fraction F1 presented in vitro antiproliferative activity and could be useful for developing potential chemopreventive substances. [ABSTRACT FROM AUTHOR]

Introduction: Engraftment is a critical milestone of the hematopoietic stem cell transplantation (HSCT) process. The immature platelet fraction (IPF) and immature reticulocyte fraction (IRF) are considered early indicators of bone marrow recovery. The objective of this study was to assess these parameters as predictors of HSCT engraftment. Methods: Neutrophil and platelet engraftment were defined as the first of three consecutive days with an absolute neutrophil count >0.5 × 109/L or platelet count >20 × 109/L, respectively. The IRF cutoff was 12%. Two IPF cutoffs were used: >6.2% and >10%. Results: The study sample comprised 44 patients, of whom 24 had undergone autologous HSCT and 20 had undergone allogeneic HSCT. Absolute neutrophil counts >0.5 × 109/L were preceded by IRF >12% in 86% of patients (38 of 44). Platelet counts >20 × 109/L were preceded by an IPF >6.2% in 90% of patients (37 of 41) and by an IPF >10% in 63% of patients (26 of 41). Conclusion: The results show that IRF and IPF are engraftment predictors. Peak in IPF was observed before rise in platelet count, while IRF rises before absolute neutrophil count (ANC) and persists increased. This indicates that IRF and IPF can be considered as new tools for hematopoietic assessment after HSCT. [ABSTRACT FROM AUTHOR]

Objective: To relate preevacuation platelet count and leukogram findings, especially neutrophil/lymphocyte ratios (NLR) and platelet/lymphocyte ratios with the occurrence of gestational trophoblastic neoplasia (GTN) after complete hydatidiform mole (CHM) among Brazilian women., Methods: Retrospective cohort study of patients with CHM followed at Rio de Janeiro Federal University, from January/2015-December/2020. Before molar evacuation, all patients underwent a medical evaluation, complete blood count and hCG measurement, in addition to other routine preoperative tests. The primary outcome was the occurrence of postmolar GTN., Results: From 827 cases of CHM treated initially at the Reference Center, 696 (84.15%) had spontaneous remission and 131 (15.85%) developed postmolar GTN. Using optimal cut-offs from receiver operating characteristic curves and multivariable logistic regression adjusted for the possible confounding variables of age and preevacuation hCG level (already known to be associated with the development of GTN) we found that ≥2 medical complications at presentation (aOR: 1.96, CI 95%: 1.29-2.98, p<0.001) and preevacuation hCG ≥100,000 IU/L (aOR: 2.16, CI 95%: 1.32-3.52, p<0.001) were significantly associated with postmolar GTN after CHM. However, no blood count profile findings were able to predict progression from CHM to GTN., Conclusion: Although blood count is a widely available test, being a low-cost test and mandatory before molar evacuation, and prognostic for outcome in other neoplasms, its findings were not able to predict the occurrence of GTN after CHM. In contrast, the occurrence of medical complications at presentation and higher preevacuation hCG levels were significantly associated with postmolar GTN and may be useful to guide individualized clinical decisions in post-molar follow-up and treatment of these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Braga et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Neutrophils provide the first line of defense of the innate immune system by phagocytosing, killing and digesting bacteria and fungi. During this process, neutrophils produce reactive oxygen species (ROS), which in excess, can damage the cells themselves and surrounding tissues. The carotenoid fucoxanthin (Fc) has been studied concerning its antioxidant and anti-inflammatory actions. Vitamin c (Vc) also demonstrates potent antioxidant action. This study aimed to evaluate the effect of Fc (2 μM) in association with Vc (100 μM) on functional parameters of human neutrophils in vitro. Materials and methods: We evaluated the migration and phagocytic capacity, intracellular calcium mobilization, ROS production (O, HO, HOCl), myeloperoxidase activity, profile of antioxidant enzymes, phosphorylation of p38 MAPK and p65 NFκB subunit, GSH/GSSG ratio and release of pro-inflammatory cytokines (TNF-α and IL-6) in neutrophils under different stimuli. Results: We verified an increase in phagocytic capacity for all treatments, together with an increase in intracellular calcium only in cells treated with Fc and Fc + Vc. ROS production was reduced by all treatments, although Vc was a better antioxidant than Fc. Phosphorylation of the p-65 subunit of NFκB was reduced in cells treated with Fc + Vc and release of TNF-α and IL-6 was reduced by all treatments. These findings indicate that the regulation of inflammatory cytokines by neutrophils is not exclusively under the control of the NFκB pathway. Fc reduced the activity of some antioxidant enzymes, whereas Vc increased GR activity and the GSH/GSSG ratio. Conclusion: In conclusion, the results presented in this study clearly show an immunomodulatory effect of the carotenoid fc alone or in combination with Vc on the function of human neutrophils. [ABSTRACT FROM AUTHOR]

Background: The neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte ratio (PLR), and red blood cell distribution width (RDW) have been previously studied as predictors of survival in different malignancies., Objective: The aim of this study was to evaluate the predictive value of these hematologic inflammatory biomarkers for patients with brain metastases (BM)., Methods: We reviewed a consecutive cohort of patients at Instituto do Cancer do Estado de São Paulo (ICESP-FMUSP) from 2011 to 2016 with ≥ 1 BM treated primarily by surgical resection. The primary outcome was 1-year survival. We optimized the NLR, MLR, PLR, and RDW cutoff values, preserving robustness and avoiding overestimation of effect size., Results: A total of 200 patients (mean age 56.1 years; 55.0% female) met inclusion criteria. Gross-total resection was achieved in 89.0%. The median (quartiles) preoperative and postoperative KPS scores were 60 (50-80) and 80 (60-90), respectively. Preoperative NLR was significantly associated with survival (HR 2.66, 95% CI: 1.17-6.01, p  = 0.019). A NLR cutoff value of 3.83 displayed the most significant survival curve split., Conclusions: Preoperative NLR is an independent predictor of survival in newly diagnosed BM. We propose a cutoff value of 3.83 for preoperative NLR testing may be clinically useful as predictor of poor survival in this population. The wide accessibility of the NLR favors its inclusion in clinical decision-making processes for BM management., Competing Interests: The authors have no conflict of interest to declare., (Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Schinopsis brasiliensis Engl. is an endemic tree of the Brazilian semi-arid regions belonging to the Anacardiaceae family. It is the main representative of the genus Schinopsis , mostly native to Brazil and popularly known as "braúna" or "baraúna". Different parts of this plant are employed in Brazilian folk medicines to treat inflammation in general, sexual impotence, cough, and influenza. This work describes the antinociceptive (acetic acid-induced writhing and formalin-induced nociception) and anti-inflammatory (paw edema and neutrophil migration) activities of the extract of the root of S. brasiliensis. Besides, the evaluation of total phenolic compounds and antioxidant, antimicrobial (including MRSA bacteria), and acetylcholinesterase inhibition activities were also determined. The pure compounds were isolated by different chromatographic techniques and their chemical structures have been unambiguously elucidated based on extensive spectroscopic methods, including 1D (1H, 13C, DEPT, and NOEdiff) and 2D (HSQC, HMBC, and NOESY) NMR experiments, MS data, and comparison with the literature data of similar compounds. The antinociceptive and anti-inflammatory activities were evaluated by acid acetic writhing test, formalin paw edema, and by the investigation of neutrophil migration to the peritoneal cavities of mice. For antimicrobial evaluation were determined MIC and MBC, antioxidant activities were obtained by TPC and DPPH tests, and AChE inhibition by Elmann's methodology. The extracts showed antinociceptive and anti-inflammatory activities and two unusual new compounds, a cyclobutanyl chalcone trimer (schinopsone A) and a cyclohexene-containing chalcone dimer (schinopsone B), with six known compounds were isolated from the active extracts. Additionally, the acetylcholinesterase inhibitory activity for isolated compounds was reported for the first time in this study. Molecular docking studies indicated that the isolated compounds are responsible for the interaction with anti-inflammatory targets (COX 1 and 2 and LOX) with variable binding affinities, indicating a possible mechanism of action of these compounds. These findings indicate for the first time the correlation between the anti-inflammatory activity different enriched polyphenol-organic soluble fractions of S. brasiliensis , and it contributes to the understanding of the anti-inflammatory potential of S. brasiliensis. [Display omitted] • Chalcone Dimer and trimers were isolated from Schinopsis brasiliensis roots. • A new chalcone trimer fused in a cyclobutane ring is occurring in the first time in Anacardiaceae. • Extracts show antinociceptive/anti-inflammatory activities of traditional medicine. • The isolated compounds show acetylcholinesterase inhibitory activities. • Docking indicated binding of pro-inflammatory COX1/COX2 and LOX and the isolates. [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: The great potential of phytotherapic drugs for treating and preventing inflammatory diseases mediated by increased neutrophil reactive oxygen species (ROS) generation has guided the search for new natural products with antioxidant and immunomodulatory properties. Baccharis dracunculifolia D.C. (Asteraceae), the main botanical source of Brazilian green propolis, is a native plant from Brazil widely used in folk medicine as anti-inflammatory. This study aims: (a) to determine the influence of seasonality on the chemical profile and biological activity of Baccharis dracunculifolia (Asteraceae) leaf extracts (BdE); (b) to analyze the correlation between the major compounds and the ability of BdE to modulate the superoxide anion and total ROS generation by human neutrophils. Materials and methods: The extracts were obtained from leaf samples collected monthly during one year. The superoxide anion and total ROS generation were assessed by the lucigenin (CL-luc)- and luminol (CL-lum)-enhanced chemiluminescence assays. Results: Seasonality influenced more the quantitative than the qualitative chemical profile of B. dracunculifolia, and affected its biological activity. The major compounds identified were caffeic acid, p-coumaric acid, aromadendrin-4′-methyl ether (AME), isosakuranetin and artepillin C. The IC50 values obtained for CL-lum and CL-luc inhibition by BdE ranged from 8.1–15.8 and 5.8–13.3µgmL−1, respectively, and correlated positively with caffeic acid concentration. CL-luc inhibition correlated negatively with the concentration of artepillin C, AME, isosakuranetin and total flavonoids. The BdE sample from May/07 inhibited CL-lum and CL-luc the most strongly (IC50=8.1±1.6 and 5.8±1.0µgmL−1, respectively), and contained the highest ratio of caffeic acid to the other isolated compounds; so, this ratio could be employed as chemical marker for this biological activity of B. dracunculifolia. Conclusion: The ability of B. dracunculifolia to inhibit the neutrophil ROS generation depends more on the type and ratio of phenolic compounds and flavonoids than on their high absolute concentrations. Together, our results help select the most appropriate plant material for the production of phytotherapic drugs to be used in the treatment of inflammatory diseases mediated by increased neutrophil activation. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms. Aim of the study: In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect. Materials and methods: ONP fraction (25 and 50mg/kg/day) was orally administered 48, 24 and 1h prior to the induction of colitis and 24h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays. Results: TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50mg/kg) treatment significantly reduced the macroscopic inflammation scores (p<0.05 and p<0.01, respectively) and morphological alterations associated with an increase in the mucus secretion. Similarly, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Moreover, COX-2 expression was up regulated in TNBS-treated rats. In contrast, ONP fraction (50mg/kg) administration reduced COX-2 overexpression. Conclusions: We have shown that the ONP fraction obtained from Arctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases. [Copyright &y& Elsevier]