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The State of Parana has a diversity of plants that are used in the traditional medicine and among them are some of the representatives of the Piperaceae family. Piper is the one of the most important genera of this family and its species show similar morphology and different biological activities. The literature shows that approximately 54 species of Piper have been described in the State of Parana. The purpose of this study is to gather key information by means of electronic databases, about the morphoanatomy and biological activities of species of Piper found in the State of Parana. The results with regard to the morphoanatomy show that, on the whole, the species that have been described possess hypostomatic leaves, non-glandular and glandular trichomes, and calcium oxalate crystals in the leaves and stems. Several biological activities have been reported, including antimicrobial, anti-inflammatory, antifungal, digestive, diuretic, insecticidal, leishmanicidal, pesticide and trypanocide.

Rheumatic fever (RF) and chronic rheumatic heart disease (RHD) are complications of oropharyngeal infection caused by Streptococcus pyogenes. Despite the importance of the complement system against infections and autoimmunity diseases, studies on the role of the lectin pathway in RF and RHD are scarce. Thus, our aim was to evaluate the association of ficolin-3 serum levels, FCN3 polymorphisms and haplotypes with the susceptibility to RF and RHD. We investigated 179 patients with a history of RF (126 RHD and 53 RF only) and 170 healthy blood donors as control group. Ficolin-3 serum concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Three FCN3 single nucleotide polymorphisms (SNPs rs532781899, rs28362807 and rs4494157) were genotyped through the sequence-specific PCR method. Lower ficolin-3 serum levels were observed in RF patients when compared to controls (12.81 μg/mL vs. 18.14 μg/mL respectively, p 0.0001, OR 1.22 [1.12-1.34]), and in RHD in comparison to RF only (RFo) (12.72 μg/mL vs. 14.29 μg/mL respectively, p = 0.016, OR 1.38 [1.06-1.80]). Low ficolin-3 levels (10.7 μg/mL) were more common in patients (39.5 %, 30/76) than controls (20.6 %, 13/63, p = 0.018, OR = 2.51 [1.14-5.31]), and in RHD (44.4 %, 28/63) than RFo (15.4 %, 2/13, p = 0.007, OR = 3.08 [1.43-6.79]). On the other hand, FCN3 polymorphism/haplotypes were not associated with ficolin-3 serum levels or the disease. Low ficolin-3 levels might be associated with RF, being a potential marker of disease progression.

Diabetes patients present a complex healing process due to several factors directly linked to their pathology. The use of medicinal plants that aid in tissue repair can bring great benefits to such individuals. This case report describes how the topical application of the aqueous extract produced from the leaves of Piper amalago L. was used to aid the healing of a lacerated wound in the left thumb of a patient with type 2 diabetes mellitus. The aqueous extract of the leaves of Piper amalago L. was prepared in boiling water. During the boiling process the dried leaves were submerged in the boiling water and left for five min. The injured thumb was submerged in the solution and the leaves were placed on the injury. The action of the aqueous extract obtained from the leaves of P. amalago was shown to be promising in the healing of a wound in a patient with type 2 diabetes mellitus. The topical application of the aqueous extract produced from the leaves of P. amalago assisted in the healing of a lacerated wound in the left thumb of a patient with type 2 diabetes mellitus over a period of 15 days.

The role of intestinal microbioma and subclinical bowel inflammation in the etiology of sponsyloarthritis (SpA) has gained a lot of attention recently. Almost 65% of SpA patients will have asymptomatic bowel inflammation if assessed by ileocolonoscopy. The connection between intestinal inflammation and SpA originated the gut-joint axis hypothesis in which monocytes and T cells found in the joint would have origin in the gut.

Arctium lappa is a perennial species of the Asteraceae family originally from Europe and Asia. Considered a weed species in the southern region of Brazil, it is popularly used as a natural anti-inflammatory. The complement system is an important component of the innate immune response. However, its exacerbated activation can lead to harmful conditions like autoimmune and inflammatory disorders. Plants that inhibit the activation of complement can be a promising tool in the treatment of inflammatory diseases. Here, we evaluated the effect of A. lappa leaves extracts on the activation of the classical and alternative pathways of complement system. Two extracts were obtained under supercritical conditions using scCO2 with ethanol as cosolvent, at 313.15K, 15 MPa (E1) and 25 MPa (E2). Classical and alternative activation were evaluated using complement fixation test. Different concentrations of A. lappa extracts E1 and E2 showed an inhibitory effect on both complement pathways, and heparin was used as control. The IC50 of E1, E2, and heparin were 28.26, 20.12 and 92.54 µg/mL for classical and 26.12, 27.70, 27.78 µg/mL for the alternative pathway. Results demonstrate that A. lappa is a promising complementary treatment for diseases associated with complement activation.

Intending to highlight new fruits with nutraceutical potential, the present work reports the nutritional and antioxidant content of Syzygium cumini (L.) Skeels (S. cumini) and Syzygium malaccense (L.) Merr. & LM Perry (S. malaccense), and evaluates the anticancer potential against CP-H460 (lung carcinoma line) and its functionality over HEK-293 (healthy embryonic kidney line), two human cells. For this, the physical-chemical characterization of the lyophilized fruits was carried out, and the content of total phenolic compounds (Folin-Ciocalteau) and the antioxidant potential (DPPH, FRAP, and ORAC) was determined. For anticancer activity, aqueous extracts were prepared and evaluated using the MTT (3-[4,5-dimethyl-triazol-2-yl]-2,5-diphenyltetrazolium) assay for periods of 20 hours. These two species are rich in dietary fibers, mainly insoluble fibers, and are sources of natural compounds and antioxidants, which possibly explain the protective potential against cancer cells. Thus, it is expected, as two source fruits, results obtained (p

Aims To investigate whether FCN3 polymorphisms and circulating ficolin-3 levels were associated with clinical forms of chronic Chagas disease (CD) and to assess their potential use as biomarkers for the disease or its severity. Methods and results FCN3 polymorphisms (g.1637delC (rs532781899) in exon 5; g.3524_3532insTATTTGGCC (rs28362807) in intron 5 and g.4473C > A) (rs4494157) in intron 7) were determined in 178 chronic CD patients (65 asymptomatic, 68 cardiac, 21 digestive and 24 cardiodigestive), and 285 healthy controls by sequence-specific PCR. Ficolin-3 serum levels, measured by ELISA in 80 patients and 80 controls, did not differ between groups. On the other hand, ficolin-3 levels were positively correlated with left ventricular ejection fraction (P = .002; r = .5), with lower levels associated with increased risk of cardiac insufficiency (P = .033; OR 7.21, 95%IC 1.17-44.4). Ficolin-3 levels were positively correlated with ficolin-2 (P = .021; r = .63), and negatively with MBL (P = .002; r = -.36) and pentraxin-3 (P = .04; r = -.32) levels. No significant results were observed for the investigated FCN3 polymorphisms and CD. The g.1637del/1637C heterozygotes presented lower ficolin-3 levels than g.1637C/1637C homozygotes in the control group (P = .023). Conclusion Low ficolin-3 levels may play a role in the pathophysiology of cardiac insufficiency associated with CD.

Aims This study evaluated the effect of euphol isolated from Euphorbia umbellata (Pax) Bruyns latex on the activation of complement pathways (classical (CP), alternative (AP) and lectin (LP)), neutrophil chemotaxis, cytotoxic activity, cell morphology and death in HRT-18 and 3T3 cells lines. Main methods CP and AP were assessed using hemolytic assays and ELISA for LP; neutrophil chemotaxis was performed using Boyden's chamber; cytotoxicity was evaluated by neutral red methodology and characteristics of cell death were assessed by cell morphology with hematological staining. Key findings Although euphol increased CP activation (38% at a concentration of 976.1 μM), an inhibitory effect on AP, LP (31% and 32% reduction in the concentration of 976.1 μM) and neutrophil chemotaxis (inhibit 84% of neutrophil migration at a concentration 292.9 μM) was observed. In addiction euphol was able to induce significant cell death in a time-dependent manner, presenting an IC50 of 70.8 μM and 39.2 μM for HRT-18 and 3T3 cell lines respectively and it was also observed apoptotic characteristics as cellular rounding, chromatin condensation and blebs formation for both cell lines. Significance Euphol has a potential use for the treatment of complement-related inflammatory diseases due to its ability to downregulate inflammation. On the other hand, the controlled activation of CP can contribute to complement-dependent cytotoxicity in the context of monoclonal antibody-based cancer treatment.

The complement receptor of the immunoglobulin superfamily (CRIg, encoded by the VSIG4 gene) is a macrophage receptor involved in the clearance of immune complexes and autologous cells. Our results suggest that the VSIG4 rs1044165T allele is a risk factor for severe functional status of rheumatoid arthritis in women, possibly by affecting VSIG4 gene expression.

Visceral Leishmaniasis is an infectious disease that affects mainly humans and dogs, with the latter being important reservoirs of the parasite. Conversely, cats are naturally resistant. The immune system can offer important explanation to this problematic as there is no evidence on the role that the complement system plays in cats. In this context, effect of the complement system from human, dog and cat sera on Leishmania infantum was evaluated. Activation of the classical, alternative and lectin pathways was assessed through hemolytic and ELISA assays. Lytic activity of the complement on the parasite's viability was investigated by Transmission Electron Microscopy and Flow Cytometry. Complement proteins were more consumed in dog serum on the classical and alternative pathways, leading to less hemolytic activity, and only in cat serum they were consumed on the lectin pathway when incubated with L. infantum. Lytic activity on the parasite's surface was more accentuated in human serum, and varied throughout the parasite's developmental stages.

Rheumatoid arthritis (RA) is an autoimmune disease, which compromises the synovial membrane resulting in chronic inflammation. Ficolins are key proteins of the lectin pathway of complement able to recognize pathogen-associated molecular patterns, apoptotic cells, and cellular debris mediating the clearance by phagocytes. High ficolin-1 and ficolin-3 levels have been observed in RA patients, however, the influence of polymorphisms in the

Leishmania (Viannia) braziliensis is the main agent of mucocutaneous Leishmaniasis, a neglected tropical disease that affects thousands of people in Brazil. It has been shown that complement plays a critical role at early stages of Leishmania infection and that is involved in the invasion of macrophages by the promastigotes. Ficolins and collectins are soluble pattern recognition and triggering molecules of the lectin complement pathway. We investigated here whether lectin pathway activators ficolin-1, ficolin-2, ficolin-3 and CL-11 bind to live L. braziliensis promastigotes in vitro. Promastigote forms in the stationary growth phase were incubated with normal human serum (NHS) or recombinant ficolins 1, 2 and 3, MBL and CL-11, and protein binding was evaluated by confocal microscopy and flow cytometry. Ficolins 1, 2 and 3, MBL and CL-11 were able to bind to the surface of live promastigotes after incubation with either NHS or recombinant proteins. A partial inhibition by N-acetyl-d-glucosamine characterizing the participation of acetylated groups in the deposition of ficolins and CL-11 to glycoconjugates on the surface of L. braziliensis was observed. These evidences highlight a role for the lectin pathway in the innate response to L. braziliensis.

Chagas disease (CD), caused by infection with the parasite Trypanosoma cruzi, leads to severe cardiomyopathy in 20-30% of patients, whereas the remainder may stay asymptomatic and never develop cardiomyopathy or other clinical manifestations. The underlying cause for this variable outcome is not fully characterized, although previous studies have found high levels of circulating mannose-binding lectin (MBL) to be associated with cardiac failure echocardiographic changes. We report three indeterminate (asymptomatic) chronic Chagas patients who were followed up for 10 years. Two of these patients developed chronic chagasic cardiomyopathy (CCC) during this follow-up period and, when genotyped, were found to be carriers of the high MBL producer HYPA/HYPA genotype, suggesting that genetically determined high MBL serum might be associated with the risk of CCC development. These results suggest the use of MBL quantification and MBL2 genotyping as tools for clinical assessment in patients with chronic CD.

Capsaicin (trans-8-methyl-n-vanillyl-6-nonenamide) is the main pungent component found in hot peppers.In this study, we investigated the effect of capsaicin treatment on tumor growth and the metabolic indicators of cachexia in Walker 256 tumor-bearing rats.Male Wistar rats were inoculated subcutaneously in the right flank with 1 ml of a sterile suspension of 3 × 10The tumor weight on Day 14 in the non-treated group was 18 g. The rats also had a body weight loss, hypoglycemia, hyperlactacidemia, hypertriacylglycerolemia, and a depletion in glycogen storage. Treatment with capsaicin decreased tumor growth by 49% and a reversal of triacylglycerol serum. We also found a 32% reduction in tumor cell proliferation ex vivo. Lactate serum concentrations and body weight were lower but did not reach control levels.The treatment with capsaicin reduces tumor growth and cellular proliferation along with increased apoptosis and partial cachexia reversal.

Ethnopharmacological relevance The species Euphorbia umbellata (leitosinha) has been traditionally used for the treatment of inflammatory diseases and cancer. Aim of the study: Evaluation the effect of E. umbellata latex extracts obtained with hexane, chloroform, ethyl acetate and methanol on the activation of the complement pathways and neutrophil chemotaxis. Materials and methods The latex was partitioned using Soxhlet apparatus and hexane, chloroform, ethyl acetate and methanol as solvents. The classical and alternative pathway activity were performed by hemolytic assays with sensitized sheep or rabbit erythrocytes, respectively; the lectin pathway activity was quantified by ELISA, through the measurement of C4 molecules and the chemotaxis of human neutrophils was performed using 1% casein as the chemotactic inducer and Boyden's chamber. GC-Q-ToF and NMR analyses were applied to evaluate the chemical composition of E. umbellata latex extracts. Results All E. umbellata latex extracts exhibited an inhibitory effect on the activation of the alternative pathway. Methanol and ethyl acetate extracts inhibited the classical pathway while chloroform extract activated this pathway. Ethyl acetate and hexane extracts inhibited lectin activation. All E. umbellata extracts inhibited casein-induced neutrophil chemotaxis. Terpenes and phenolic compounds have been suggested to be present in the E. umbellta latex extracts. Conclusion The E. umbellata latex was able to modulate the functions of the immune system. Thus, it is possible to infer that the terpenes and phenolic compounds of the phytocomplex of E. umbellata latex can contribute for the activity on the complement pathways.

Background: Mannose binding lectin (MBL) appears to be involved in susceptibility to rheumatoid arthritis (RA), in the inflammatory process and in the genesis of atherosclerotic disease. Objective: To study the association of MBL serum levels and its genotypic variation with carotid arteries intimal thickness (IMT) in RA patients from Southern Brazil. Methods: MBL serum levels, MBL2 genotyping and IMT were investigated in 90 RA patients along with their demographic, clinical and laboratory profile. MBL levels and MBL2 genotyping were evaluated in 90 healthy controls. Results: A significant lower MBL serum concentration was observed in patients with RA in relation to controls (528 ng/mL vs 937.5 ng/mL, p = 0.05, respectively). The median IMT in RA patients was 0.59 mm (0.51 to 0.85 mm). There was no correlation between levels of MBL with disease activity, erythrocyte sedimentation rate, autoantibodies presence or IMT (p = NS). A weak and negative correlation was found between MBL and CRP levels (Rho = −0.24; p = 0.02;). The MBL2 variant at codon 54 (variant B) and HYPA haplotype were the most frequently observed in the RA sample (67.5% and 31.7%). MBL2 wild type (A/A) were associated with lower IMT when compared with heterozygotes (A/O; p = 0.04) and low producers (O/O; p = 0.05). In addition, high producers genotypes had lower levels of CRP when compared with medium (p = 0.04) or with low producers (p = 0.05). Conclusion: RA patients had lower MBL levels than controls. MBL were negatively associated with CRP serum levels; low MBL genotypes producers increased thickness of the IMT than high producers. Keywords: Mannose binding lectin, Rheumatoid arthritis, Atherosclerosis

Background Medicinal plants are an important source to identify new active pharmaceutical compounds. Traditionally, the sap of Euphorbia umbellata is widely used to treat cancer and inflammatory conditions. These effects have been attributed to the presence of terpenes and phenolic compounds in the extracts of this plant. Euphol, a tetracyclic triterpene alcohol, is one of the major compounds present in Euphorbia species, and some biological activities have been attributed to this compound. Purpose This study aimed to evaluate the in vitro cytotoxicity of euphol against Jurkat, HL-60, K-562, B16F10, and HRT-18 cells lines, as well as the biological stability, distribution, metabolism properties in vitro, and the determination of the concentration of euphol in the plasma and liver of rats. Methods The MTT reduction assay was used to evaluate the cytotoxicity of euphol against cancer cell lines, and the selectivity index, the morphology and cell cycle assays to evaluate the death mechanisms in K-562 and B16F10 lineages. UHPLC-MS was applied for the in vivo evaluation of the concentration of euphol in plasma and liver, and in vitro metabolic stability in human liver microsomes and S9 fraction, plasma protein binding, and stability in simulated gastric and intestinal fluids assays. Conclusions This study demonstrated that euphol exhibited cytotoxic effects against a variety of cancer cells lines, selectivity against leukemia and possibly, the mechanism involved is apoptosis. The evaluation of stability, distribution, and metabolism properties showed that euphol was unstable in gastric and intestinal fluids, presenting moderate plasma protein binding with two hours elimination half-life and possible phase II liver metabolism. All the results suggested that further studies could be developed to prove the viability of euphol as an anticancer agent.

Several studies have examined the complement system in schizophrenia, suggesting an involvement of the lectin pathway. We analyzed 49 patients with schizophrenia and explored the association between psychopathology of schizophrenia and complement component 3 (C3) serum levels, C-reactive protein (CRP) serum levels, ficolin activation, and mannose-binding lectin (MBL) activation. In the multiple regression analysis, a negative association was observed between the Positive and Negative Syndrome Scale (PANSS) total score and ficolin activation. Body mass index (BMI) was positively associated with the serum levels of C3 and CRP. MBL activation was not associated with any independent variables. Our findings facilitate a better understanding of the complement system in schizophrenia. Additional studies with a large sample population are needed to confirm our results.

Visceral leishmaniasis (VL) is a neglected and highly lethal disease. VL is endemic in South American countries, with Brazil being responsible for 96% of the cases. In this continent, VL is caused by the protozoan Leishmania (Leishmania) infantum (L. infantum), transmitted by the bite of infected female phlebotomine sandflies. Immediately after the inoculation of L. infantum promastigotes into the vertebrate host, the complement, as part of the first line of innate response, becomes activated. L. infantum promastigotes glycocalyx is rich in carbohydrates that can activate the lectin pathway of complement system. In this study, we evaluated whether the lectin pathway collectins [manose binding lectin (MBL) and collectin-11 (CL-11)] and ficolins (-1, -2 and -3) interact with L. infantum promastigotes, using confocal microscopy and flow cytometry. The binding of MBL, CL-11 and ficolins -1 and -3, but not ficolin-2, was observed on the surface of live metacyclic promastigotes after incubation with normal human serum (NHS) or recombinant proteins. C3 and C4 deposition as well as complement mediated lyses was also demonstrated after interaction with NHS. These results highlight a role for collectins and ficolins in the initial immune response to L. infantum.

Ankylosing spondylitis (AS) patients may have higher prevalence of mannose-binding lectin (MBL) deficiency than normal individuals. MBL deficiency may influence susceptibility to infections. The aim of the study was to verify if MBL deficiency in patients with AS predisposes to infections. We studied 60 patients with AS diagnosed according to the Assessment of SpondyloArthritis international Society (ASAS) criteria. These patients had their MBL serum levels determinated. Twenty-five individuals were identified as MBL deficient (serum values 100 ng/mL). These patients were paired with 35 "sufficient" MBL producers (median serum level = 700 ng/mL; range 150-4100 ng/mL) for gender, age, use of medications, and tobacco exposure. Medical records of all patients were retrospectively investigated for the period of 5 years and the rate of infection occurrence was compared in the two groups. AS patients with MBL deficiency had higher number of urinary tract infections (p = 0.03; IRR = 2.33; 95% CI = 0.95-6.04) and tuberculosis (p = 0.008; IRR = 9.8; 95% CI = 1.2-441.6) than controls. Regarding tuberculosis infection, one patient (2.8%) in the MBL-sufficient group and six (24.0%) from the deficient group had this infection. The MBL-sufficient patient and five from the deficient group have had latent infections, detected in the screening tests done previous to anti-TNF drug use. The other, in the deficient group, had lung infection while not on anti-TNF treatment. Another patient, from the deficient group, has had tuberculosis skeletal infection in the past. We found a significant association between MBL deficiency and higher risk of tuberculosis and urinary tract infection in patients with AS. More studies with higher number of patients are needed to confirm this finding.

This paper reports the assessment of bioactivity of inflorescences extracts of Musa paradisiaca L. obtained using supercritical CO2 (scCO2) and compressed propane as solvents. The effects of extraction conditions over the antioxidant and antibacterial activity were evaluated. The highest antioxidant activity (3576.86 ± 18.36 mg of ɑ-tocopherol/g extract) was found for extracts obtained using scCO2 as solvent at 353.15 K and 25.0 MPa. The extracts did not showed inhibition for the bacteria tested. The immunomodulatory effects of the extracts obtained by the extraction with 308.15 K and 3.0 MPa showed a significant inhibitory effect on the alternative pathway (AP) in all concentrations tested (333–5.2 μg mL−1), with at least 70% reduction in the AP-induced haemolysis when compared with the 100% haemolysis control without the use of the extract.

The complement system participates in host defense by eliminating microorganisms and triggering inflammation. However, insufficient control or exacerbated complement activation contributes to inflammatory diseases. Since promising antioxidant and anti-inflammatory activities have been identified in Arctium lappa L. extracts, this study aims to explore the effect of A. lappa extracts on the lectin pathway (LP) of complement activation. Four extracts were obtained by supercritical extraction using scCO2 with or without ethanol as co-solvent, at different temperatures and pressures (E1: 2.2 mg/mL, E2: 2.6 mg/mL and E3: 2.0 mg/mL, E4: 1.5 mg/mL). To evaluate the effect of A. lappa extracts on the LP activation, an ELISA assay using mannose binding lectin pathway of complement was carried out with C4 detection. All extracts showed a concentration-dependent inhibitory effect on the activation of complement by the LP. The following IC50 were observed for E1, E2, E3 and E4: 179.4 μg/mL, 74.69 μg/mL, 119.1 μg/mL and 72.19 μg/mL, respectively. Our results suggest that A. lappa extracts are potential candidates for the treatment of inflammatory disorders that are complement-related.

Objective: To evaluate serum concentrations of mannose-binding lectin (MBL) in women presenting with different human papillomavirus (HPV)-associated cervical lesions. Subjects and Methods: A total of 364 women, who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital (HEG), Curitiba, Brazil, were enrolled in the study. Based on the latest cervical colposcopy-guided biopsy results, the women were divided into 4 groups: cervical intraepithelial neoplasia CIN-I (n = 54), CIN-II (n = 72), CIN-III (n = 145), and invasive cancer (n = 93). A time-resolved immunofluorometric assay was used to measure the MBL concentrations in serum. The statistical analysis was done using GraphPad Prism 6.0. Comparisons were performed by Kruskal-Wallis and Mann-Whitney tests and analyzed by χ2 test; continuous variables are presented as medians and categorical variables as frequencies. Results: The median MBL concentrations in decreasing order were as follows: invasive cancer: 1,452 ng/mL, CIN-I: 1,324 ng/mL, CIN-II: 1,104 ng/mL, and CIN-III 1,098 ng/mL. However, no statistical significance was found among the 4 groups with HPV-associated lesions (p = 0.11). Equally, the MBL levels did not show a significant association between the age of the patients and the severity of the cervical lesions (p = 0.68). No statistical significance was found in the median values of MBL or in the status of MBL deficient (1,000 ng/mL) among the women in each group (p = 0.77). Conclusion: In this study, there was no statistically significant difference in MBL serum levels among the groups with CIN. Hence MBL serum concentration appeared not to have influenced the progression of HPV-related preinvasive cervical lesions into invasive cancer.

Infections are usually involved in the pathogenesis of spondyloarthritis (SpA). Mannose-binding lectin (MBL) is a component of the innate immune system with an important role in microbial defense.To study the prevalence of MBL deficiency in SpA patients as well as its influence in the clinical profile of these diseases.We studied 89 SpA patients and 89 healthy individuals, paired for age and gender. MBL serum levels were measured by ELISA test. Individuals with levels ≤100 ng/mL were considered deficient. SpA patients had determination of Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP, Bath Ankylosing Spondylitis Functional Index (BASFI), C reactive protein (CRP), erythrocyte sedimentation rate (ESR), and review of their clinical profile.SpA patients had MBL levels ranging from 100 to 4100 ng/mL (median = 375 ng/mL); controls levels ranged from 100 to 4703 ng/mL (median = 1204 ng/mL; p0.0001). The prevalence of MBL deficiency was 27/89 (30.3%) in SpA patients and 12/89 (13.5%) in controls, with p = 0.01; OR = 2.5 (95% IC = 1.2-5.3). No association/correlation was found between MBL levels with BASDAI, BASFI, age at disease onset, ASDAS-CRP, ESR, CRP, presence of uveitis, HLAB27, peripheral arthritis, or SpA subtype (all p = NS).MBL levels may be linked with the occurrence of SpA but do not influence its phenotype.

Background Chronic inflammatory diseases lead to glycation of protein, lipids and nuclear acids. One product generated in this context is pentosidine. Aim To study pentosidine levels in Systemic Lupus Erythematosus (SLE) and its possible association with disease activity and cumulative damage. Methods Pentosidine serum levels were measured in the serum by ELISA commercial kits in 79 patients with SLE. Disease activity index and cumulative damage were studied by SELENA-SLEDAI (Safety of Estrogen in Lupus National Assessment Systemic Lupus Erythematosus Disease Activity Index) and cumulative damage by SLICC/ACR DI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index for Systemic Lupus Erythematosus) respectively and simultaneously with determination of pentosidine levels. Epidemiological and clinical and serological profile were collected from the charts. Results In the 79 studied patients, the SLEDAI ranged from 0 to 12 (median of 0) and the SLICC/ACR-DI from 0 to 4 (median of 0). Serum pentosidine levels did not correlate with SLEDAI neither with SLICC. Patients with discoid skin lesions and photosensitivity had lower levels than those without them, with p ​= ​0.04 in both. Conclusion In SLE, serum pentosidine levels did not reflect activity and cumulative damage. Patients with skin manifestations had lower levels of this biomarker.

Background Antinuclear antibodies (ANA) have been found in several types of cancer although the meaning of its presence is not completely known. Aim To study the prevalence of ANA in patients with cervical intraepithelial lesion and invasive cervical cancer. Methods A total of 205 women who underwent screening for cervical cancer or treatment at the Erasto Gaertner Cancer Hospital in Curitiba - Brazil, were enrolled in the study. Based on their latest cervical colposcopy-guided biopsy results, they were divided into four groups: CIN-I: 19.4%; CIN-II: 24.0%; CIN-III: 24.0%; and invasive cancer: 32.4%. As control were studied 68 healthy controls. ANA was searched by immunofluorescence in Hep-2 cells evaluating the pattern and titer. Results Controls had 4/68 (5.8%) of ANA positivity and patients with CIN and invasive cancer had 15.1% (p = 0.001). Patients with CIN-I and CIN-II had the same prevalence of ANA as controls (p = 1.0 and p = 0.11 respectively), but not those with CIN-III (p = 0.03) and invasive cancer (p = 0.05). The most common ANA immunofluorescence pattern was fine speckled pattern (38.7%) and fine dense speckled pattern (38.7%); the mean titer was 1:160. Conclusion ANA is more common in invasive cervical lesions than in controls or non invasive lesions. To understand the meaning of this finding more studies are needed.

Gut inflammation is closely related to spondyloarthritis (SpA) pathophysiology. Fecal calprotectin has been used to measure the degree of gut inflammation. The phenotype of SpA may change according to studied population.To study the fecal calprotectin levels in a sample of SpA in Brazilian patients and its relationship with epidemiological, clinical and treatment variables as well as with the macro and microscopic degree of gut inflammation.Eighty five SpA patients were studied for epidemiological and clinical features, functional and inflammatory indexes and fecal calprotectin levels measured using a ELISA kit. Colonoscopy with intestinal biopsies were performed in 39 of them. At time of colonoscopy a second calprotectin level was done after suspension of at least 3 weeks of used anti-inflammatory nonsteroidal drugs (NSAIDs).Fecal calprotectin levels were higher in Ankylosing Spondylitis (AS) patients (p 0.0001) and in those with axial involvement (p = 0.002). No relationship was found with SpA inflammatory and functional parameters (all p = ns). After suspension of NSAIDs, a drop in fecal calprotectin levels was observed (from median levels of 215.0-76.0 μg/g; p = 0.01). In the colonoscopy, 33.3% had macroscopic signs of inflammation and these patients had higher calprotectin (p = 0.009) than others. Microscopic examination showed that all patients had lymphoplasmacytic infiltrate and eosinophilic infiltrate; epithelial erosion was present in 27.2%.Patients with ankylosing spondylitis and axial forms of diseases have higher fecal calprotectin levels. Patients with all types of SpA have microscopic inflammatory changes in the gut.

The complement system is a key component of the innate immune system, participating in the surveillance against infectious agents. Once activated by one of the three different pathways, complement mediates cell lysis, opsonization, signalizes pathogens for phagocytosis and induces the adaptive immune response. The lectin pathway is constituted by several soluble and membrane bound proteins, called pattern recognition molecules (PRM), including mannose binding lectin (MBL), Ficolins-1, -2, and -3, and Collectin 11. These PRMs act on complement activation as recognition molecules of pathogen-associated molecular patterns (PAMPs) such as N-acetylated, found in glycoproteins of viral envelopes. In this study, Ficolin-1 and Ficolin-3 plasma levels were evaluated in 178 HIV patients (93 HIV; 85 HIV/HCV) and 85 controls from southern Brazil. Demographic and clinical-laboratory findings were obtained during medical interview and from medical records. All parameters were assessed by logistic regression, adjusted for age, ancestry, and sex. Significantly lower levels of Ficolin-1 were observed in HIV/HCV coinfected when compared to HIV patients (p = 0.005, median = 516 vs. 667 ng/ul, respectively) and to controls (p < 0.0001, 1186 ng/ul). Ficolin-1 levels were lower in males than in females among HIV patients (p = 0.03) and controls (p = 0.0003), but no association of Ficolin-1 levels with AIDS was observed. On the other hand, Ficolin-3 levels were significantly lower in controls when compared to HIV (p < 0.0001, medians 18,240 vs. 44,030 ng/ml, respectively) and HIV/HCV coinfected (p < 0.0001, 40,351 ng/ml) patients. There was no correlation between Ficolin-1 and Ficolin-3 levels and age, HIV viral load or opportunistic infections. However, Ficolin-3 showed a positive correlation with T CD4 cell counts in HIV monoinfected patients (p = 0.007). We provide here the first assessment of Ficolin-1 and-3 levels in HIV and HIV/HCV coinfected patients, which indicates a distinct role for these pattern recognition molecules in both viral infections.

Mannose-binding lectin (MBL) is a pattern recognition receptor of the lectin pathway of complement system. MBL binds to carbohydrates on microorganism's surfaces leading to complement activation, opsonization and phagocytosis. Polymorphisms in the MBL gene (MBL2) are associated with variations on MBL serum levels and with the susceptibility to various infectious and autoimmune diseases. The involvement of the lectin pathway in rheumatoid arthritis (RA) has been demonstrated by several studies and although MBL has been considered to have a dual role in the pathogenesis of the disease, the association between MBL and RA remains inconclusive. In an attempt to clarify this relationship, we developed this short review summarizing accumulated evidences in regard to MBL and RA and a meta-analysis to evaluate the influence of MBL2 polymorphisms on the susceptibility to RA. Among a total of 217 articles that were identified following a predefined search strategy on PubMed, Scopus, Scielo, EMBASE and Cochrane databases, only 13 met all inclusion criteria and were included in the meta-analysis. Data assessment was conducted by three independent investigators and presented in odds ratio (OR) and 95% confidence intervals (CIs) using forest plot charts. Both heterogeneity and publication bias were analyzed. The results of the meta-analysis evidenced that MBL2 low producing OO and XX genotypes do not confer higher risk to RA, even when data were analyzed according to cohort's ethnicity. Further studies are needed in order to clarify the importance of other genes of the lectin pathway in the pathogenesis of RA.

Summary The aim of the study was to investigate the allotypic variability of complement factor B (BF) in patients and relatives with rheumatoid arthritis (RA) and its association with serological biomarkers and clinical features of the disease. BF allotypes were determined by high-voltage agarose gel electrophoresis in serum samples of 180 patients with RA, 198 relatives and 98 controls from Southern Brazil. Anticyclic citrullinated peptide (anti-CCP), antimutated citrullinated vimentin (anti-MCV) and IgA-rheumatoid factor (RF) were determined by ELISA and IgM-RF by latex agglutination in all samples. No significant differences were found in the allotypic variants of BF between patients with RA, relatives and controls, nor associations with gender and age of RA onset. BF*S07 allotype was significantly associated with extra-articular manifestations (EAMs; Secondary Sjogren Syndrome, pneumonitis, rheumatoid nodules) in patients with RA (P = 0.02; OR = 6.62). Patients with phenotype BF F had lower positivity for anti-MCV biomarker (P = 0.02; OR = 0.22) and those with allotype BF*S had higher prevalence of this autoantibody (P = 0.02; OR = 3.77). An increased frequency of RF-IgA was detected in relatives of patients with RA with BF FS07 phenotype (P = 0.02; OR = 7.78). Complement BF variability did not influence the development of RA in the studied patients, but BF variants may act as markers of disease prognosis, such as development of EAMs, corroborating with the role of the alternative pathway in the pathogenesis of RA.

Background Leprosy patients may present several osteoarticular complaints, which require further evaluation of inflammatory diseases, such as rheumatoid arthritis (RA). Therefore, an adequate clinical assessment in addition to testing for rheumatoid factors (RF) and anticyclic citrullinated peptide antibodies (anti-CCP), can be useful in order to establish the correct diagnosis. Method In this study, the relation of RF and anti-CCP with rheumatological manifestations was evaluated in 97 leprosy patients from Southern Brazil. The results were compared to RA patients and healthy controls from the same geographical area and ethnic background. Results Neuropathy was observed in 71.1% and arthritis in 35.1% of the leprosy patients. A high frequency of RF positivity was observed among the leprosy patients (41.2%, 40/97), with RF immunoglobulin A (IgA) significantly associated with arthritis (OR = 7.9, 95% CI = 1.5–40.6 P = 0.008). Anti-CCP was observed in 9.3% (9/97) of the patients, with anti-CCP2 being the most frequent subtype. Only 4.1% (4/97) of the patients were RF and anti-CCP concomitantly positive. RF IgM showed a significant association with leprosy when compared to healthy controls (P

Piper amalago L., Piperaceae, popularly known as jaborandi-manso, is a shrub that spans a height of 2–7 m. It can be found in the regions of Southern America downward up to the south of Brazil. Traditionally it is used to treat digestive problems, heart problems, and burns. This study aims to conduct an anatomical investigation and analysis of the leaves and stems of P. amalago through electron scanning and optical micro techniques. The analysis showed that P. amalago has a hypostomatic leaf, with a subepidermal layer on its surface. There are grandular trichomes that resemble sacs, conic non-glandular trichomes, dorsiventral mesophyll, and a plano-convex midrib having a single vascular bundle in the center. The petiole is short with irregularly shaped and adaxially grooved. The stem is circular in shape and contains two circles of vascular bundles and a sclerenchymatic sheath in the perimedular region. These anatomical features of the Piper amalago's leaves and stems make it easy to pick it out among other species of the Piper genus. This is helpful when conducting quality control process. Keywords: Anatomy, Quality control, Jaborandi-manso, Piper amalago, Piperaceae

We aimed to investigate the association between plasma levels of complement Factor H (FH) with cardiac involvement, inflammatory and cardiometabolic parameters in patients with chronic Chagas' disease (CD). FH plasmatic levels were determined in 80 chronic CD patients. Glycaemic index, lipidogram (high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C, triglycerides and total cholesterol) and Ultrasensitive C-Reactive Protein (uCRP) values were obtained from medical records. Height, weight, body mass index (BMI) blood pressure and left ventricular ejection fraction (LVEF) were obtained from echocardiography examinations. Comparisons between chronic CD clinical forms were performed using Mann-Whitney test and correlation Spearman's test. FH levels were correlated positively with triglycerides (P = .001, r = .39), LDL-C (P = .009, r = .3), cholesterol (P = .02, r = .28), uCRP (P = .029, r = .31) and BMI (P = .008, r = .34); and negatively with HDL-C (P = .03, r = -.25) levels. Dyslipidemic patients showed higher FH levels compared to normolipidemic, although no difference for FH levels was observed between chronic CD clinical forms. Alternative pathway of complement may be a link between immune response and metabolic disorders, with important immunoregulatory role in chronic CD.

Background/Aims: Arthropathy is the most common extraintestinal manifestation observed in patients with Crohn's disease (CD). The present study aimed to screen rheumatoid arthritis (RA) using anti-CCP antibodies and rheumatoid factor (RF) in CD patients from Southern Brazil. Additionally, the presence of arthralgia and spondyloarthritis (SpA) was evaluated. CD patients, previously diagnosed using clinical data, imaging tests, endoscopic and histological findings, were included consecutively. Methods: A total of 100 patients participated in the study, of which 60% were female, with a mean age of 41.9 ± 12.04 (16-83 years). As controls, sera from 100 healthy individuals from the same geographic area were analyzed. Results: Arthralgias were present in 55% of the patients, being more frequent in women (65.5%; 36/55), than in males (34.5%). No association was found between arthralgia and the treatment method used. Six patients (6/100) had SpA previously diagnosed. In the CD group, anti-CCP was positive only in one patient, while RF was positive in 7 patients (7%; 7/100). The anti-CCP positive patient (woman, 38 years old, RF positive), fulfilled the ACR criteria and was diagnosed as RA. In the control group, anti-CCP antibodies were detected in 1% (1/100) and RF was positive in 6 of the samples (6%). Conclusion: Our data showed low frequency of anti-CCP antibodies and RF in Brazilian patients with CD. Additionally, we found a high prevalence of arthralgia in these patients, with 6% of them diagnosed with SpA.

To investigate the association between mannose-binding lectin (MBL) serum level and MBL2 polymorphisms, and the frequency of spontaneous miscarriages in rheumatoid arthritis (RA) patients.One hundred seventy seven women (mean age 50 years) with RA from Southern Brazil were studied and 4.5% had a history of abortion (8/177). The MBL levels were determined by ELISA. MBL2 polymorphisms in the promoter (-550H/L, -221X/Y), 5' untranslated region (4 P/Q) and exon 1 (p.Gly54Asp: B allele, p.Arg52Cys: D allele and p.Gly57Glu: C allele; collectively labelled O) were genotyped by sequencing.Mannose-binding lectin levels of RA patients ranged from ≤100 ng/mL to 6640 ng/mL (median 541.5 ng/mL). There was a significant difference in MBL median levels (100 ng/mL vs. 625 ng/mL, respectively, p = .001) and frequency of MBL deficiency (75.0% vs. 24.1%, p = .007, OR = 10.3, 95%CI = 1.9-55.4), in patients with a history of miscarriage vs those without it. Patients with RA and miscarriage had more frequently haplotypes related with low MBL levels (p = .007, OR = 10.5, 95%CI = 1.3-84) than high producers. Moreover, LYPB haplotype and O allele were significantly associated with the occurrence of miscarriage (p = .001, OR = 9.7, 95%CI = 2.4-39.1 and p = .009, OR = 5.9, 95%CI = 1.4-23.4, respectively).The results suggest that MBL deficiency and the presence of MBL2 gene polymorphisms that lead to MBL deficiency are risk factors for the occurrence of miscarriage in patients with RA.

Mannan-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) are components of the lectin pathway, which activate the complement system after binding to the HCV structural proteins E1 and E2. We haplotyped 11 MASP2 polymorphisms in 103 HCV patients and 205 controls and measured MASP-2 levels in 67 HCV patients and 77 controls to better understand the role of MASP-2 in hepatitis C susceptibility and disease severity according to viral genotype and fibrosis levels. The haplotype block MASP2*ARDP was associated with protection against HCV infection (OR = 0.49, p = .044) and lower MASP-2 levels in controls (p = .021), while haplotype block AGTDVRC was significantly increased in patients (OR = 7.58, p = .003). MASP-2 levels were lower in patients than in controls (p

Trypanosoma cruzi is a protozoan parasite known to cause Chagas disease (CD), a neglected sickness that affects around 6–8 million people worldwide. Originally, CD was mainly found in Latin America but more recently, it has been spread to countries in North America, Asia, and Europe due the international migration from endemic areas. Thus, at present CD represents an important concern of global public health. Most of individuals that are infected by T. cruzi may remain in asymptomatic form all lifelong, but up to 40% of them will develop cardiomyopathy, digestive mega syndromes, or both. The interaction between the T. cruzi infective forms and host-related immune factors represents a key point for a better understanding of the physiopathology of CD. In this context, the complement, as one of the first line of host defense against infection was shown to play an important role in recognizing T. cruzi metacyclic trypomastigotes and in controlling parasite invasion. The complement consists of at least 35 or more plasma proteins and cell surface receptors/regulators, which can be activated by three pathways: classical (CP), lectin (LP), and alternative (AP). The CP and LP are mainly initiated by immune complexes or pathogen-associated molecular patterns (PAMPs), respectively, whereas AP is spontaneously activated by hydrolysis of C3. Once activated, several relevant complement functions are generated which include opsonization and phagocytosis of particles or microorganisms and cell lysis. An important step during T. cruzi infection is when intracellular trypomastigotes are release to bloodstream where they may be target by complement. Nevertheless, the parasite uses a sequence of events in order to escape from complement-mediated lysis. In fact, several T. cruzi molecules are known to interfere in the initiation of all three pathways and in the assembly of C3 convertase, a key step in the activation of complement. Moreover, T. cruzi promotes secretion of plasma membrane-derived vesicles from host cells, which prevent the activity of C3 convertase C4b2a and thereby may hinder complement. In this review, we aim to present an overview on the strategies used by T. cruzi in order to circumvent the activation of complement and, consequently, its biological effects.

Leprosy is a chronic inflammatory disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nervous system, leading to a high disability rate and social stigma. Previous studies have shown a contribution of genes encoding products of the lectin pathway of complement in the modulation of the susceptibility to leprosy; however, the ficolin-3/FCN3 gene impact on leprosy is currently unknown. The aim of the present study was to investigate if FCN3 polymorphisms (rs532781899: g.1637delC, rs28362807: g.3524_3532insTATTTGGCC and rs4494157: g.4473C>A) and ficolin-3 serum levels play a role in the susceptibility to leprosy. We genotyped up to 190 leprosy patients (being 114 (60%) lepromatous), and up to 245 controls with sequence-specific PCR. We also measured protein levels using ELISA in 61 leprosy and 73 controls. FCN3 polymorphisms were not associated with disease, but ficolin-3 levels were higher in patients with FCN3 *2B1 (CinsA) haplotype (p = 0.032). Median concentration of ficolin-3 was higher in leprosy per se (26034 ng/mL, p = 0.005) and lepromatous patients (28295 ng/mL, p = 0.016) than controls (18231 ng/mL). In addition, high ficolin-3 levels (>33362 ng/mL) were more common in leprosy per se (34.4%) and in lepromatous patients (35.5%) than controls (19.2%; p = 0.045 and p = 0.047, respectively). Our results lead us to suggest that polymorphisms in the FCN3 gene cooperate to increase ficolin-3 concentration and that it might contribute to leprosy susceptibility by favoring M. leprae infection., Author summary Leprosy is considered a neglected disease and still a public health problem in many countries where it was not yet eliminated, leading to a high disability rate and social stigma. The molecular mechanisms of M. leprae infection and immune evasion are still poorly known, raising the need for studies that may contribute to a better understanding of leprosy etiology, as well as improvement in diagnosis and treatment. Ficolin-3 is a soluble molecule of the innate immune system that recognizes a wide range of pathogen-associated molecular patterns leading to complement activation and phagocytosis. We observed high concentration of ficolin-3 in leprosy patients, likely caused by polymorphisms present in intronic regions of FCN3 gene, which may contribute to leprosy susceptibility by favoring M. leprae infection. This is the first study addressing FCN3 polymorphisms and ficolin-3 levels in leprosy, indicating it as a good candidate biomarker associated with the host response against M. leprae.

The aim of the present study was to detect natural infection by Leishmania (Leishmania) infantum in Lutzomyia longipalpis captured in Barcarena, state of Pará, Brazil, through the use of three primer sets. With this approach, it is unnecessary to previously dissect the sandfly specimens. DNA of 280 Lu. longipalpis female specimens were extracted from the whole insects. PCR primers for kinetoplast minicircle DNA (kDNA), the mini-exon gene and the small subunit ribosomal RNA (SSU-rRNA) gene of Leishmania were used, generating fragments of 400 bp, 780 bp and 603 bp, respectively. Infection by the parasite was found with the kDNA primer in 8.6% of the cases, with the mini-exon gene primer in 7.1% of the cases and with the SSU-rRNA gene primer in 5.3% of the cases. These data show the importance of polymerase chain reaction as a tool for investigating the molecular epidemiology of visceral leishmaniasis by estimating the risk of disease transmission in endemic areas, with the kDNA primer representing the most reliable marker for the parasite.

Introduction Mannose binding lectin (MBL) has been linked to predisposition to systemic lupus erythematosus (SLE) and to disease activity. Some studies found deposits of MBL in glomerular tissue of patients with lupus nephritis. There is no research about the deposition of MBL in skin. Materials and methods Skin biopsies from lesional and non lesional skin of 4 discoid lupus erythematosus (DLE) and 10 SLE patients were submitted to immunofluorescence staining for IgG, IgA, IgM, C3, C4, C1q, C5b-9 and MBL. Charts were reviewed for demographic, clinical and serological data. Patients with SLE had disease activity measured by SLEDAI. Results MBL was found only in SLE lesional skin and its presence showed an association trend towards higher disease activity. Deposition of C5b-9 occurred in vessels only in patients with SLE (70%) and in the two patients with kidney involvement. Conclusions MBL deposition was found in the lesional skin of SLE patients but not in SLE non lesional skin nor in DLE patients, and it seems to be less frequent and less strong than observed in the kidneys biopsies, suggesting that the complement participation in the pathophysiology of SLE process may not be the same in these two clinical manifestations.

Objective: The aim of this study was to investigate the frequency of the LCT*-13910C>T polymorphism associated with a high expression of lactase in the small intestine during adulthood, and to infer the lactase persistence and adult-type hypolactasia phenotypes among Euro-Brazilians and Mennonites from South Brazil. Materials and Meth ods: A sequence-specific PCR method to genotype the LCT*-13910C>T polymorphism in 292 Euro-Brazilians and 151 Mennonites (a group with European ancestry and a long history of endogamy) was developed. Using an exact test of population differentiation, the genotype and allele frequency between these and other Brazilian populations were compared. Results: The frequency of -13910*T was significantly higher among the Mennonites when compared to the Euro-Brazilian cohort (0.63 vs. 0.33, p < 0.000001). Accordingly, Mennonites had a higher prevalence of the lactase persistence genotype (88.1 vs. 55.5%, p < 0.000001). The distribution of -13910*T differed between Mennonites and all other Brazilian groups (p < 0.0001). The Euro-Brazilians from Curitiba displayed differences when compared to all other Brazilian groups (p < 0.0001), even to Euro-Brazilians from a different geographic region (p = 0.0003), but were similar to those from Porto Alegre (p = 0.2). Conclusion: Differences in the -13910*T-associated lactase persistence distribution among Euro-Brazilian groups reflect the ancestry and admixture of each particular group and should be considered for adult-type hypolactasia screening.