Sex dimorphism of weight and length at birth: evidence based on disorders of sex development.

BACKGROUND: Males have higher weight and length at birth than females. AIM: To verify the influence of the Y chromosome and the action of intrauterine androgens on weight and length at birth of children with Disorders of Sex Development (DSD). SUBJECTS AND METHODS: A cross-sectional and retrospective study. Patients with Turner syndrome (TS), complete (XX and XY), mixed (45,X/46,XY) and partial (XY) gonadal dysgenesis (GD), complete (CAIS) and partial (PAIS) androgen insensitivity syndromes and XX and XY congenital adrenal hyperplasia (CAH) were included. Weight and length at birth were evaluated. RESULTS: Weight and length at birth were lower in TS and mixed GD when compared to XY and XX DSD cases. In turn, patients with increased androgen action (117 cases) had higher weight and length at birth when compared to those with absent (108 cases) and decreased (68 cases) production/action. In birthweight, there was a negative influence of the 45,X/46,XY karyotype and a positive influence of increased androgen and gestational age. In birth length, there was a negative influence of the 45,X and 45,X/46,XY karyotypes and also a positive influence of increased androgen and gestational age. CONCLUSIONS: The sex dimorphism of weight and length at birth could possibly be influenced by intrauterine androgenic action.

Living in endemic area for infectious diseases accelerates epigenetic age.

Inflammaging is a low-grade inflammatory state generated by the aging process that can contribute to frailty and age-related diseases in the elderly. However, it can have distinct effects in the elderly living in endemic areas for infectious diseases. An increased inflammatory response may confer protection against infectious agents in these areas, although this advantage can cause accelerating epigenetic aging. In this study, we evaluated the inflammatory profile and the epigenetic age of infected and noninfected individuals from an endemic area in Brazil. The profile of cytokines, chemokines and growth factors analyzed in the sera of the two groups of individuals showed similarities, although infected individuals had a higher concentration of these mediators. A significant increase in IL-1ra, CXCL8, CCL2, CCL3 and CCL4 production was associated with leprosy infection. Notably, elderly individuals displayed distinct immune responses associated with their infection status when compared to adults suggesting an adaptive remodelling of their immune responses. Epigenetic analysis also showed that there was no difference in epigenetic age between the two groups of individuals. However, individuals from the endemic area had a significant accelerated aging when compared to individuals from São Paulo, a non-endemic area in Brazil. Moreover, the latter cohort was also epigenetically aged in relation to an Italian cohort. Our data shows that living in endemic areas for chronic infectious diseases results in remodelling of inflammaging and acceleration of epigenetic aging in individuals regardless of their infectious status. It also highlights that geographical, genetic and environmental factors influence aging and immunosenescence in their pace and profile.

The gut microbiota profile in psoriasis: a Brazilian case-control study.

The pathogenesis of psoriasis, an immune-mediated chronic inflammatory skin disease, remains unclear. Studies have shown an association between psoriasis and intestinal inflammation; in this context, the influence of the gut microbiota on the immune response of psoriasis has become a focus of recent research. The present research evaluated the composition and diversity of the gut microbiota of 21 participants with psoriasis from a Brazilian referral dermatology service compared to 24 healthy controls. A stool sample was collected from each participant at the time of inclusion in the study, and the samples were analysed by sequencing the 16S rRNA gene. The recruitment of research participants involved matching between groups by sex, age, body mass index, comorbidities and smoking and the exclusion of several criteria that could potentially influence the gut microbiota and the interpretation of the data. There was an increase in the Dialister genus and Prevotella copri species in patients with psoriasis compared to the control group. A reduction in the Ruminococcus, Lachnospira and Blautia genera, as well as in the Akkermansia muciniphila species, was also verified in the psoriasis group compared to the control group. Furthermore, patients with psoriasis exhibited less gut microbiota diversity than controls.

Tetanus vaccination in pregnant women: a systematic review and meta-analysis of the global literature.

OBJECTIVES: This study aimed to determine the effect of several factors on the uptake of tetanus vaccination in pregnant women. STUDY DESIGN: This is a systematic review and meta-analysis of the global literature. METHODS: The search strategy was carried out in the EMBASE and MEDLINE (Pubmed) databases, without language restrictions. The databases were searched from the beginning until May 2020. Fixed and random effect models were applied according to the methodological heterogeneity between the included studies. The I2 test was performed to assess the magnitude of the heterogeneity. The results were presented as a grouped odds ratio (OR) with a 95% confidence interval (CI) and a significance level of 0.05. RESULTS: The initial search strategy generated 14,349 original articles. In total, 31 studies met all inclusion criteria and 20 articles were included in the meta-analysis. The grouped and subgroup analyses showed a significant association between tetanus vaccination and the following factors: higher number of prenatal visits (OR: 2.00; 95% CI: 1.17-3.42), higher maternal age (OR: 1.24, 95% CI: 1.02-1.50), being single (OR: 1.41; 95% CI: 1.20-1.65), professional vaccine guidance (OR: 9.00; 95% CI: 1.81-44.75) and uptake of influenza vaccine (OR: 5.87; 95% CI: 1.39-24.73). CONCLUSIONS: The uptake of tetanus vaccine in pregnant women is associated with various factors. The identification of these factors is an important step towards the implementation of public health strategies aimed at improving immunisation against tetanus in pregnant women.

Sodium palatability in male spontaneously hypertensive rats.

Spontaneously hypertensive rats (SHRs) ingest more NaCl than normotensive strains. Here we investigated NaCl intake and taste reactivity in adult male SHRs and normotensive Holtzman rats treated or not with AT1 receptor antagonist centrally in euhydrated condition and after fluid depletion. Taste reactivity was measured by the number of orofacial expressions to intra-oral infusions of 0.3 M NaCl. In euhydrated condition, intra-oral infusions of 0.3 M NaCl produced greater number of hedonic responses in SHRs than in normotensive rats, without differences in the number of aversive responses. Compared to euhydrated condition, the treatment with the diuretic furosemide + low dose of captopril (angiotensin converting enzyme blocker) increased the number of hedonic and reduced the number of aversive responses to intra-oral NaCl in normotensive rats, without changing the number of hedonic or aversive responses in SHRs. Losartan (AT1 receptor antagonist, 100 ng/1 µl) injected intracerebroventricularly in SHRs abolished 0.3 M NaCl intake induced by water deprivation + partial rehydration, whereas only transiently (first 30 min of the 60 min test) reduced hedonic responses, without changes in aversive responses to intra-oral NaCl. Losartan intracerebroventricularly also only transiently (first 30 min) reduced the number of hedonic responses to intra-oral NaCl in euhydrated SHRs. The results suggest that NaCl palatability is increased and independent from body fluid balance in SHRs. The results also suggest that central AT1 receptors are part of the mechanisms activated to increase NaCl intake and palatability in SHRs. A partial dissociation between NaCl intake and palatability in SHRs is also suggested.

Linfoma difuso de grandes células em um buldogue inglês de dois anos: relato de caso / Diffuse large-cell lymphoma in a two-year-old english bulldog: case report

O linfoma é a neoplasia hematopoiética mais frequentemente diagnosticada na clínica de pequenos animais, sendo caracterizado por uma proliferação descontrolada de linfócitos, acometendo principalmente animais idosos. Dentre os achados clínicos mais comuns da doença, a linfadenopatia periférica recebe destaque. Manifestações clínicas como perda de peso, anorexia, edema subcutâneo, êmese, massas cutâneas, disfagia, ascite e dispnéia são também frequentemente encontradas. O diagnóstico dos linfomas é de extrema importância, sendo primordial para estabelecimento do prognóstico do animal, podendo ser feito através da análise citomorfológica de amostras obtidas por punção aspirativa e avaliação histopatológica. A poliquimioterapia é realizada como protocolo terapêutico de eleição para animais com linfoma. Foi atendido no Serviço de Clínica e Cirurgia Oncológica do Hospital Veterinário da Universidade Federal de Uberlândia (HV-UFU), um Buldogue Inglês, de dois anos de idade, apresentando linfonodonomegalia generalizada e diagnosticado com linfoma difuso de grandes células. O diagnóstico foi obtido por exame histopatológico e o imunohistoquímico revelou imunofenotipagem B. O paciente foi submetido a quimioterapia, sendo escolhido o protocolo Winscosin (CHOP) de 19 semanas com remissão completa ao término do protocolo. O objetivo deste trabalho é relatar um caso de linfoma difuso de grandes células em um Buldogue Inglês de dois anos de idade com remissão completa após a realização de quimioterapia.

Lymphoma is the hematopoietic neoplasm most frequently diagnosed in the clinic of small animals, being characterized by an uncontrolled proliferation of lymphocytes, affecting mainly elderly animals. Among the most common clinical findings of the disease, peripheral lymphadenopathy is highlighted. Clinical manifestations such as weight loss, anorexia, subcutaneous edema, emesis, skin masses, dysphagia, ascites and dyspnea are also frequently encountered. The diagnosis of lymphomas is extremely important, being essential for establishing the animal's prognosis and can be done through cytomorphological analysis of samples obtained by aspiration puncture and histopathological evaluation. Polychemotherapy is performed as the therapeutic protocol of choice for animals with lymphoma. It was treated at Serviço de Clínica e Cirurgia Oncológica do Hospital Veterinário da Universidade Federal de Uberlândia (HV-UFU), a two-year-old English Bulldog, with generalized lymph node enlargement and diagnosed with diffuse large cell lymphoma. The diagnosis was obtained by histopathological and immunohistochemical examination and revealed immunophenotyping B. The patient underwent chemotherapy, and the 19- week Winscosin (CHOP) protocol was chosen with complete remission at the end of the protocol. The aim of this work is to report a case of diffuse large cell lymphoma in a two-year-old English Bulldog with complete remission after chemotherapy.

LINFOMA DIFUSO DE GRANDES CÉLULAS EM UM BULDOGUE INGLÊS DE DOIS ANOS: RELATO DE CASO

O linfoma é a neoplasia hematopoiética mais frequentemente diagnosticada na clínica de pequenos animais, sendo caracterizado por uma proliferação descontrolada de linfócitos, acometendo principalmente animais idosos. Dentre os achados clínicos mais comuns da doença, a linfadenopatia periférica recebe destaque. Manifestações clínicas como perda de peso, anorexia, edema subcutâneo, êmese, massas cutâneas, disfagia, ascite e dispnéia são também frequentemente encontradas. O diagnóstico dos linfomas é de extrema importância, sendo primordial para estabelecimento do prognóstico do animal, podendo ser feito através da análise citomorfológica de amostras obtidas por punção aspirativa e avaliação histopatológica. A poliquimioterapia é realizada como protocolo terapêutico de eleição para animais com linfoma. Foi atendido no Serviço de Clínica e Cirurgia Oncológica do Hospital Veterinário da Universidade Federal de Uberlândia (HV-UFU), um Buldogue Inglês, de dois anos de idade, apresentando linfonodonomegalia generalizada e diagnosticado com linfoma difuso de grandes células. O diagnóstico foi obtido por exame histopatológico e o imunohistoquímico revelou imunofenotipagem B. O paciente foi submetido a quimioterapia, sendo escolhido o protocolo Winscosin (CHOP) de 19 semanas com remissão completa ao término do protocolo. O objetivo deste trabalho é relatar um caso de linfoma difuso de gra

Linfoma difuso de grandes células em um buldogue inglês de dois anos: relato de caso / Diffuse large-cell lymphoma in a two-year-old english bulldog: case report

O linfoma é a neoplasia hematopoiética mais frequentemente diagnosticada na clínica de pequenos animais, sendo caracterizado por uma proliferação descontrolada de linfócitos, acometendo principalmente animais idosos. Dentre os achados clínicos mais comuns da doença, a linfadenopatia periférica recebe destaque. Manifestações clínicas como perda de peso, anorexia, edema subcutâneo, êmese, massas cutâneas, disfagia, ascite e dispnéia são também frequentemente encontradas. O diagnóstico dos linfomas é de extrema importância, sendo primordial para estabelecimento do prognóstico do animal, podendo ser feito através da análise citomorfológica de amostras obtidas por punção aspirativa e avaliação histopatológica. A poliquimioterapia é realizada como protocolo terapêutico de eleição para animais com linfoma. Foi atendido no Serviço de Clínica e Cirurgia Oncológica do Hospital Veterinário da Universidade Federal de Uberlândia (HV-UFU), um Buldogue Inglês, de dois anos de idade, apresentando linfonodonomegalia generalizada e diagnosticado com linfoma difuso de grandes células. O diagnóstico foi obtido por exame histopatológico e o imunohistoquímico revelou imunofenotipagem B. O paciente foi submetido a quimioterapia, sendo escolhido o protocolo Winscosin (CHOP) de 19 semanas com remissão completa ao término do protocolo. O objetivo deste trabalho é relatar um caso de linfoma difuso de grandes células em um Buldogue Inglês de dois anos de idade com remissão completa após a realização de quimioterapia.(AU)

Lymphoma is the hematopoietic neoplasm most frequently diagnosed in the clinic of small animals, being characterized by an uncontrolled proliferation of lymphocytes, affecting mainly elderly animals. Among the most common clinical findings of the disease, peripheral lymphadenopathy is highlighted. Clinical manifestations such as weight loss, anorexia, subcutaneous edema, emesis, skin masses, dysphagia, ascites and dyspnea are also frequently encountered. The diagnosis of lymphomas is extremely important, being essential for establishing the animal's prognosis and can be done through cytomorphological analysis of samples obtained by aspiration puncture and histopathological evaluation. Polychemotherapy is performed as the therapeutic protocol of choice for animals with lymphoma. It was treated at Serviço de Clínica e Cirurgia Oncológica do Hospital Veterinário da Universidade Federal de Uberlândia (HV-UFU), a two-year-old English Bulldog, with generalized lymph node enlargement and diagnosed with diffuse large cell lymphoma. The diagnosis was obtained by histopathological and immunohistochemical examination and revealed immunophenotyping B. The patient underwent chemotherapy, and the 19- week Winscosin (CHOP) protocol was chosen with complete remission at the end of the protocol. The aim of this work is to report a case of diffuse large cell lymphoma in a two-year-old English Bulldog with complete remission after chemotherapy.(AU)

Zinc, manganese, and copper amino acid complexes improve performance and bone characteristics of layer-type chicks under thermoneutral and cold stress conditions.

Two experiments were designed to evaluate the effect of mineral-amino acid complexes (AACM) as a partial replacement of inorganic mineral (IM) in layer-type chicks' diets. Both studies had the same dietary treatments, where in experiment 1 (Exp. 1) was conducted under thermoneutral conditions from 0 to 35 D and chicks in experiment 2 (Exp. 2) were exposed to cold stress conditions at nighttime during the first 15 D and to thermoneutral condition from 16 to 35 D. For each trial, 1,200 one-day-old Lohmann Brown chicks were used, with 20 cage replicates with 30 chicks per cage. Treatments consisted of the control diet (IM; with 70, 70, and 8 mg/kg of zinc [Zn], manganese [Mn], and copper [Cu], respectively) and the treatment diet (AACM, with 40, 40, and 2.75 mg/kg of Zn, Mn, and Cu, respectively, from IM sources, along with 30, 30, and 5.25 mg/kg of Zn, Mn, and Cu, respectively). Data were submitted to analysis of variance, and means were compared using the t-test (P < 0.05). In Exp. 1, there were no significant differences between treatments on chick performance. However, AACM-fed chicks had higher thymus (P = 0.03) and cecum weight (P < 0.01), superior micromineral deposition in the tibias (P < 0.01), and reduced phosphorus excretion (P = 0.03). In Exp. 2, chicks fed with AACM had higher body weight gain (P = 0.04), better average daily feed intake (P = 0.03), lower phosphorus excretion (P = 0.02), and higher liver and pancreas weight (P < 0.01) in the last week of the study. In conclusion, chicks fed with AACM under thermoneutral conditions had higher bone mineralization and reduced excretion of phosphorus, and in adverse conditions, AACM improves performance and liver and pancreas weight, also reducing phosphorus excretion.

Effect of Saccharomyces cerevisiae UFMG A-905 in a murine model of food allergy.

Food allergy is triggered when there is an abnormal activation of the immune system by food allergens. Currently, there is no curative therapy for this pathological condition. Due to the immunomodulatory properties of probiotics they are potential candidates as therapeutic tools for food allergy. Therefore, the aim of this study was to evaluate the probiotic effect of Saccharomyces cerevisiae UFMG A-905 (905) in an in vivo model of food allergy. Probiotic effect was assessed by clinical, histological, immunological and microbiological parameters analysis. Furthermore, we also evaluated if 905 after inactivation has an effect, as well as if such an effect is dose dependent. Our results showed that oral administration of only viable 905 promotes a significant attenuation of tissue injury and myeloperoxidase (MPO) activity levels. Moreover, the treatment reduced interleukin 17 levels, and administration of the supernatant from the yeast culture also promoted a significant decrease in MPO levels. However, considering the systemic parameters, immunoglobulin (Ig)E and IgG anti-ovalbumin, which are essentials for triggering the allergic process, there was no effect, suggesting that the yeast promotes a local but not a systemic effect in the model evaluated. In addition, we found that only high doses of viable 905 were able to attenuate the signs of inflammation. In conclusion, oral administration of 905 led to a local effect that depends on the viability of the yeast.

Antisepsys and profilatic antimicrobial therapy in prevention of surgical site infection of horses / [Antissepsia e terapia antimicrobiana profilática no controle infeccioso do foco cirúrgico em equinos

The efficacy of an antisepsis protocol comprising chlorhexidine gluconate and ethyl alcohol in combination with prophylactic antimicrobial therapy in controlling surgical site infection in horses was studied. To that purpose, seven mixed breed horses received potassium penicillin and gentamicin at least 30 minutes prior to surgery. The surgical site was scrubbed with chlorhexidine gluconate and rinsed with ethyl alcohol. Samples were collected at four time points: (A) - before and (B) - immediately following shaving of the hair coat, (C) - at the end of antisepsis procedures, and (D) - at the end of the surgical procedure. Duration of surgery was recorded. Samples were cultured in three different culture mediums: Mitis Salivarus (Streptococcus sp.), Staphylococcus 110 (Staphylococcus sp.), and Mac Conkey (Enterobacteria). A high level of bacterial growth was observed in all culture mediums at (A) and (B), with no bacterial growth in (C). Staphylococcus sp. growth was observed in (D) in a single patient whose surgical procedure lasted for 120 minutes. Shaving of the hair coat reduced microbial flora on the surface of the skin. Antisepsis in combination with prophylactic antimicrobial therapy was effective in controlling surgical site infection in elective procedures with an average duration of 90 minutes.(AU)

Objetivou-se averiguar a eficácia do protocolo de antissepsia com clorexidina degermante e álcool etílico hidratado 70%, em associação com terapia antimicrobiana profilática, no controle microbiano do foco cirúrgico de equinos submetidos a procedimentos cirúrgicos. Foram utilizados 07 cavalos adultos de raças variadas, onde ambos receberam o mesmo tratamento (terapia antimicrobiana profilática e antissepsia com clorexidina degermante 2% e álcool etílico hidratado 70%), coletando-se amostras em quatro tempos distintos [(A - antes da tricotomia), (B - imediatamente após tricotomia), (C - ao término da antissepsia), (D - ao término do procedimento cirúrgico)]. O tempo de cada procedimento cirúrgico foi contabilizado. Foram utilizados três meios de cultura diferentes, cada um com especificidade para um tipo de crescimento bacteriano. Constatou-se alta incidência de crescimento bacteriano nos três meios utilizados nos tempos de coleta A e B. Para o tempo C, não foi observado crescimento bacteriano. No tempo D averiguou-se crescimento bacteriano do tipo Staphylococcus sp. em um único paciente, cujo tempo cirúrgico foi de 120 minutos de duração. Desta forma, a tricotomia reduziu a carga microbiana na superfície da pele. A antissepsia associada à terapia antimicrobiana profilática mostrou-se eficaz no controle microbiano do foco cirúrgico em procedimentos eletivos, com duração média de 90 minutos.(AU)

Antisepsys and profilatic antimicrobial therapy in prevention of surgical site infection of horses / Antissepsia e terapia antimicrobiana profilática no controle infeccioso do foco cirúrgico em equinos

The efficacy of an antisepsis protocol comprising chlorhexidine gluconate and ethyl alcohol in combination with prophylactic antimicrobial therapy in controlling surgical site infection in horses was studied. To that purpose, seven mixed breed horses received potassium penicillin and gentamicin at least 30 minutes prior to surgery. The surgical site was scrubbed with chlorhexidine gluconate and rinsed with ethyl alcohol. Samples were collected at four time points: (A) - before and (B) - immediately following shaving of the hair coat, (C) - at the end of antisepsis procedures, and (D) - at the end of the surgical procedure. Duration of surgery was recorded. Samples were cultured in three different culture mediums: Mitis Salivarus (Streptococcus sp.), Staphylococcus 110 (Staphylococcus sp.), and Mac Conkey (Enterobacteria). A high level of bacterial growth was observed in all culture mediums at (A) and (B), with no bacterial growth in (C). Staphylococcus sp. growth was observed in (D) in a single patient whose surgical procedure lasted for 120 minutes. Shaving of the hair coat reduced microbial flora on the surface of the skin. Antisepsis in combination with prophylactic antimicrobial therapy was effective in controlling surgical site infection in elective procedures with an average duration of 90 minutes.(AU)

Objetivou-se averiguar a eficácia do protocolo de antissepsia com clorexidina degermante e álcool etílico hidratado 70%, em associação com terapia antimicrobiana profilática, no controle microbiano do foco cirúrgico de equinos submetidos a procedimentos cirúrgicos. Foram utilizados 07 cavalos adultos de raças variadas, onde ambos receberam o mesmo tratamento (terapia antimicrobiana profilática e antissepsia com clorexidina degermante 2% e álcool etílico hidratado 70%), coletando-se amostras em quatro tempos distintos [(A - antes da tricotomia), (B - imediatamente após tricotomia), (C - ao término da antissepsia), (D - ao término do procedimento cirúrgico)]. O tempo de cada procedimento cirúrgico foi contabilizado. Foram utilizados três meios de cultura diferentes, cada um com especificidade para um tipo de crescimento bacteriano. Constatou-se alta incidência de crescimento bacteriano nos três meios utilizados nos tempos de coleta A e B. Para o tempo C, não foi observado crescimento bacteriano. No tempo D averiguou-se crescimento bacteriano do tipo Staphylococcus sp. em um único paciente, cujo tempo cirúrgico foi de 120 minutos de duração. Desta forma, a tricotomia reduziu a carga microbiana na superfície da pele. A antissepsia associada à terapia antimicrobiana profilática mostrou-se eficaz no controle microbiano do foco cirúrgico em procedimentos eletivos, com duração média de 90 minutos.(AU)

Chemiluminescent ELISA with multi-epitope proteins to improve the diagnosis of canine visceral leishmaniasis.

Diagnosing canine visceral leishmaniasis (CVL) is difficult because clinical signs of the disease are non-specific and a many infected animals in endemic areas, as in Brazil, are asymptomatic. Serological tests are the most common diagnostic methods employed, but most have limitations. For this reason, the implementation of a rapid, sensitive, and specific diagnostic test for CVL has become increasingly important. In this study, we adapted a chemiluminescent enzyme-linked immunosorbent assay (CL ELISA), using two multi-epitope recombinant proteins (PQ10 and PQ20) and a crude Leishmania antigen produced using promastigotes of L. infantum, as antigens to detect CVL infection in animals from Belo Horizonte. To investigate cross-reactions, samples from dogs with other infections (babesiosis, ehrlichiosis and Trypanosoma cruzi) were tested. Assay performance validations were conducted to analyse parameters such as variability, reproducibility, and stability. CL ELISA sensitivity/specificity with PQ10 antigen was 93.1%/80.0%; with the PQ20 protein 93.1%/96.6%; and with the crude antigen 75%/73.3%. Inter-assay variability and inter-operator coefficient of variation were <7% and <15%, with PQ10 and PQ20, respectively. The accuracy of the CL ELISA was classified as excellent for PQ10 (AUC = 0.95) and PQ20 (AUC = 0.98) and moderate for the crude antigen (AUC = 0.77). The kappa score for qualitative agreement between two plate lots was excellent for PQ10 (0.89) and good for PQ20 (0.65). PQ20 remained more stable than PQ10. The CL ELISA with recombinant proteins is a promising tool to diagnose CVL.

CLA-supplemented diet accelerates experimental colorectal cancer by inducing TGF-ß-producing macrophages and T cells.

Conjugated linoleic acid (CLA) has been shown to activate the nuclear receptor PPAR-γ and modulate metabolic and immune functions. Despite the worldwide use of CLA dietary supplementation, strong scientific evidence for its proposed beneficial actions are missing. We found that CLA-supplemented diet reduced mucosal damage and inflammatory infiltrate in the dextran sodium sulfate (DSS)-induced colitis model. Conditional deletion of PPAR-γ in macrophages from mice supplemented with CLA diet resulted in loss of this protective effect of CLA, suggesting a PPAR-γ-dependent mechanism mediated by macrophages. However, CLA supplementation significantly worsened colorectal tumor formation induced by azoxymethane and DSS by inducing macrophage and T-cell-producing TGF-ß via PPAR-γ activation. Accordingly, either macrophage-specific deletion of PPAR-γ or in vivo neutralization of latency-associated peptide (LAP, a membrane-bound TGF-ß)-expressing cells abrogated the protumorigenic effect of CLA. Thus, the anti-inflammatory properties of CLA are associated with prevention of colitis but also with development of colorectal cancer.

8-Hydroxy-2-(1H-1,2,3-triazol-1-yl)-1,4-naphtoquinone derivatives inhibited P2X7 Receptor-Induced dye uptake into murine Macrophages.

Extracellular adenosine 5'-triphosphate (ATP) triggers the P2X7 receptor (P2X7R) ionic channel to stimulate the release of the interleukin-IL-1ß cytokine into macrophages. The current study explored the reaction of six structurally diverse triazole derivatives on P2X7-mediated dye uptake into murine peritoneal macrophages. P2X7R activity determined by ATP-evoked fluorescent dye uptake. Triazole derivatives toxicity measured using dextran rhodamine exclusion based colorimetric assay. A740004 and BBG, both P2X7R antagonist, inhibited ATP-induced dye uptake. In contrast, the derivatives 5a, 5b, 5e, and 5f did not diminish P2X7R activity in concentrations until 100 µM. 5c and 5d analogs caused a potent inhibitory activity on P2X7-induced dye uptake. Dextran Rhodamine exclusion measurements after 24 h of continuous treatment with triazole derivatives indicated a moderated toxicity for all molecules. In conclusion, this study showed that a series of new hybrid 1,2,3-triazolic naphthoquinones reduces P2X7R-induced dye uptake into murine macrophages. In silico analysis indicates a good pharmacokinetic profile and molecular docking results of these analogs indicate the potential to bind into an allosteric site located into the P2X7R pore and juxtaposed with the ATP binding pocket. In this manner, the compounds 5c and 5d may be used as a scaffold for new P2X7R inhibitors with reduced toxicity, and good anti-inflammatory activity.

Fcγ-RI, Fcγ-RII and IL-10 as predictive biomarkers for post-therapeutic cicatrization time in monocytes from cutaneous leishmaniasis patients.

Cutaneous leishmaniasis (CL) treatment is based on therapy with Glucantime® , yet, there are few laboratory methods to monitor its success. In this study, ex vivo and in vitro evaluations of peripheral blood monocytes were performed in a longitudinal study to characterize the impact of Glucantime® on overall phenotypic/functional features of these cells from CL patients to identify predictive biomarkers for post-therapeutic monitoring by flow cytometry. The ex vivo evaluation from CL patients demonstrated a modulatory profile before treatment, with a decrease in TLR-2, FcγRII, HLA-DR, CD86, IFN-γR, TNF, IL-12, NO, and an increase in FcγRIII and IL-10R. Conversely, treatment changes some of these biomarker expressions by decreasing FcγRIII and IL-10R and increasing IFN-γR, IL-12 and NO. Moreover, an in vitro analysis of these patients showed a reduced phagocytic capacity of Leishmania braziliensis and higher levels of IL-10 and TGF-ß modulating functional profile. Regardless of the compromised L. braziliensis phagocytic capacity, treatment re-established the production of IL-12, IL-10, TGF-ß and NO at the basal level. Notably, monocytes from patients with early cicatrization showed enhanced FcγRI and FcγRII expressions and reduced IL-10, which was further corroborated by a baseline fold change analysis. Finally, the logistic regression model emphasized the performance of FcγRI, FcγRII and IL-10 as robust predictive biomarkers for post-therapeutic cicatrization during cutaneous leishmaniasis.

The increase of current atmospheric CO2 and temperature can benefit leaf gas exchanges, carbohydrate content and growth in C4 grass invaders of the Cerrado biome.

Leaf gas exchanges, carbohydrate metabolism and growth of three Brazilian Cerrado invasive African grasses were evaluated after growing for 75 days under doubled CO2 concentration and temperature elevated by 3 °C. Results showed that although the species presented photosynthetic C4 metabolism, they all had some kind of positive response to increased CO2. Urochloa brizantha and Megathyrsus maximus showed increased height for all induced environmental conditions. Urochloa decumbens showed only improvement in water use efficiency (WUE), while U. brizantha showed increased CO2 assimilation and M. maximus presented higher biomass accumulation under doubled CO2 concentration. The most significant improvement of increased CO2 in all three species appears to be the increase in WUE. This improvement probably explains the positive increase of photosynthesis and biomass accumulation presented by U. brizantha and M. maximus, respectively. The increase in temperature affected leaf carbohydrate content of M. maximus by reducing sucrose, glucose and fructose content. These reductions were not related to thermal stress since photosynthesis and growth were not harmed. Cellulose content was not affected in any of the three species, just the lignin content in U. decumbens and M. maximus. All treatments promoted lignin content reduction in U. brizantha, suggesting a delay in leaf maturation of this species. Together, the results indicate that climate change may differentially promote changes in leaf gas exchanges, carbohydrate content and growth in C4 plant species studied and all of them could benefit in some way from these changes, constituting a threat to the native Cerrado biodiversity.

Oral administration of Simbioflora® (synbiotic) attenuates intestinal damage in a mouse model of 5-fluorouracil-induced mucositis.

The use of probiotics to prevent or treat mucosal inflammation has been studied; however, the combined effect of probiotics and prebiotics is unclear. The aim of this study was to test whether oral administration of a synbiotic (Simbioflora®) preparation containing Lactobacillus paracasei, Lactobacillus rhamnosus, Lactobacillus acidophilus and Bifidobacterium lactis plus fructooligosaccharide could help control mucosal inflammation in experimental mucositis induced by 5-fluorouracil (5-FU). Male BALB/c mice were randomly divided into six groups: control (CTL), control + prebiotic (CTL+P), control + synbiotic (CTL+S), mucositis (MUC), mucositis + prebiotic (MUC+P), and mucositis + synbiotic (MUC+S). Mice from the CTL+S, MUC+S, CTL+P, and MUC+P groups received synbiotic or prebiotic daily by oral gavage for 13 days. Mice in the CTL and MUC groups received the same volume of saline. On day 11, mice in the MUC, MUC+P, and MUC+S groups received an intraperitoneal injection of 300 mg/kg 5-FU to induce mucositis. After 72 h, all mice were euthanised. Intestinal permeability, intestinal histology, and biochemical parameters were analysed. Group MUC showed a greater weight loss and increased intestinal permeability (0.020 counts per min [cpm]/g) compared to the CTL group (0.01 cpm/g) P<0.05. Both treatments attenuated weight loss compared to the MUC group. Nonetheless, the synbiotic caused a greater reduction in intestinal permeability (0.012 cpm/g) compared to the MUC (0.020 cpm/g) and MUC+P (0.016 cpm/g) groups P<0.05. Mice in groups MUC+P and MUC+S displayed significant recovery of lesions and maintenance of the mucus layer. There were no differences in the short-chain fatty acid concentrations in the faeces between the MUC and CTL groups (P>0.05). Increased acetate and propionate concentrations were evidenced in the faeces of the MUC+P and MUC+S groups. Only the synbiotic treatment increased the butyrate concentration (P<0.05). The results indicate that administration of synbiotic can decrease mucosal damage caused by mucositis.

The cytosolic sensor STING is required for intestinal homeostasis and control of inflammation.

STING (stimulator of interferon genes) is a cytosolic sensor for cyclic dinucleotides and also an adaptor molecule for intracellular DNA receptors. Although STING has important functions in the host defense against pathogens and in autoimmune diseases, its physiological relevance in intestinal homeostasis is largely unknown. In this study, we show that STING-/- mice presented defective protective mechanisms of intestinal mucosa, including decreased number of goblet cells, diminished mucus production, and lower levels of secretory IgA, when compared with wild-type (WT) mice. Fecal content and microbiota DNA could activate STING, indicating a role of this molecule in gut. Microbiota composition was altered in STING-/- mice toward a more inflammatory profile, evidencing a reduction in the Allobacolum and Bifidobacterium groups along with increase in Disulfovibrio bacteria. Absence of STING lead to decrease in induced intraepithelial lymphocytes (IEL) and to increase in group 1 innate lymphoid cell (ILC1) as well as ILC3 frequencies and decrease in ILC2 in the colon. Development and function of Foxp3+ and LAP+ regulatory T cells were also compromised in STING-/- mice. Moreover, these mice were highly susceptible to dextran sodium sulfate-induced colitis, T-cell-induced colitis, and enteric Salmonella typhimurium infection when compared with WT animals. Therefore, our results identify an important role of STING in maintaining gut homeostasis and also a protective effect in controlling gut inflammation.

Lifelong Maintenance of Oral Tolerance and Immunity Profiles in Mice Depends on Early Exposure to Antigen.

Oral tolerance is defined as a state of systemic hyporesponsiveness to an antigen that has been previously administered by the oral route. Many factors affect oral tolerance induction; some of them related to antigen, and some related to the animal. The age of the animal is one of the most important factors that affect oral tolerance as ageing brings many alterations in immune responses. Herein, we demonstrated that both the oral tolerance and pattern of immune reactivity triggered in early life were kept up to 15 months regarding the magnitude of antibody production, cell proliferation and cytokine profile when compared to immune responses induced in old mice. Therefore, our results corroborate with a promising proposal for prevaccination during childhood and young age, and a booster in older age, to make sure that the primary immunization in early life is not lost in aged individuals.