Comparative study of the antioxidant and anti-inflammatory effects of the natural coumarins 1,2-benzopyrone, umbelliferone and esculetin: in silico, in vitro and in vivo analyses.

The aim of this work was to compare the anti-inflammatory and antioxidant effects of three natural coumarins: 1,2-benzopyrone, umbelliferone and esculetin. The antioxidant capacity of coumarins was evaluated using both chemical and biological in vitro assays. Chemical assays included DPPH and ABTS∙+ radical scavenging as well as ferric ion reducing ability power (FRAP) assay. Inhibition of mitochondrial ROS generation and lipid peroxidation in brain homogenates were used as biological in vitro assays. The experimental method of carrageenan-induced pleurisy in rats was used for the in vivo investigation of the anti-inflammatory activity. In silico molecular docking analysis was undertaken to predict the affinity of COX-2 to the coumarins. Considering the antioxidant capacity, esculetin was the most efficient one as revealed by all employed assays. Particularly, the mitochondrial ROS generation was totally abolished by the compound at low concentrations (IC50 = 0.57 µM). As for the anti-inflammatory effects, the COX-2 enzyme presented good affinities to the three coumarins, as revealed by the molecular docking analyses. However, considering the in vivo anti-inflammatory effects, 1,2-benzopyrone was the most efficient one in counteracting pleural inflammation and it potentiated the anti-inflammatory actions of dexamethasone. Umbelliferone and esculetin treatments failed to reduce the volume of pleural exudate. Overall, therefore, our results support the notion that this class of plant secondary metabolites displays promising effects in the prevention and/or treatment of inflammation and other diseases associated with oxidative stress, although the singularities regarding the type of the inflammatory process and pharmacokinetics must be taken into account.

Development and characterization of trans-anethole-containing solid lipid microparticles: antiinflammatory and gastroprotective effects in experimental inflammation.

The present study prepared, optimized, and characterized solid lipid microparticles that contained trans-anethole (SLMAN), evaluated their antiinflammatory activity in acute and chronic inflammation models, and investigated their effects on the gastric mucosa in arthritic rats. The microparticles were obtained by a hot homogenization process and characterized by physicochemical analyses. The acute inflammatory response was induced by an intradermal injection of 0.1 ml of carrageenan solution (200 µg) in the hind paw. The rats were treated orally with a single dose of SLMAN 1 h before induction of the inflammatory response. The chronic inflammatory response was induced by the subcutaneous application of 0.1 ml of complete Freund's adjuvant suspension (500 µg) in the hind paw. SLMAN was orally administered, starting on the day of arthritis induction, and continued for 21 days. The results showed that SLMAN was obtained with good encapsulation efficiency. Treatment with SLMAN at doses of 25 and 50 mg/kg was as effective as trans-anethole (AN) at a dose of 250 mg/kg on acute and chronic inflammatory responses. Histological analyses showed that treatment with SLMAN did not aggravate lesions in the gastric mucosa in arthritic rats. These results indicated that treatment with SLMAN at a dose that was 5-10 times lower than non-encapsulated AN exerted an inhibitory effect on acute and chronic inflammatory responses, suggesting the better bioavailability and efficacy of microencapsulated AN without aggravating lesions in the gastric mucosa in arthritic rats.

Analgesic and Anti-Inflammatory Properties of Ethanolic Extract of Piper vicosanum Leaves.

Nonclinical trials are important to validate the efficacy and safety of medicinal plants. Scientific toxicological studies with Piper vicosanum Yuncker have showed its safety; however, no studies have indicated the analgesic or antiarthritic potential of the ethanolic extract of P. vicosanum leaves (EEPV). The objective of the present work was to evaluate the antiarthritic and antinociceptive effects of EEPV in experimental mouse models. The oral administration of EEPV (100, 300, and 700 mg/kg) and dexamethasone (1 mg/kg) were performed in carrageenan-induced pleurisy, in formalin and acetic-acid-induced nociception, and in zymosan-induced articular inflammation models in Swiss mice. The EEPV (300 mg/kg) was tested in zymosan-articular inflammation, the complete Freund's adjuvant (CFA) inflammatory model, and in in situ intravitreal microscopy analysis of rolling and adhesion events of leukocytes in the mesenteric microcirculation in mice. EEPV significantly inhibited: (i) nociceptive response at phase 1 and 2, and also in the cold response in the formalin model; (ii) abdominal contortion induced by acetic acid; (iii) mechanical hyperalgesia after 4 and 6 h, knee edema after 6 h, and leukocyte migration in articular inflammation induced by zymosan. All doses of EEPV reduced the leukocyte migration to the inflamed pleural cavity and knee edema 4 h after the zymosan knee injection. The treatment with the EEPV significantly inhibited the CFA-induced edema, mechanical and cold hyperalgesia, and NAG and MPO. The EEPV also significantly inhibited carrageenan-induced leukocyte rolling and adhesion. The present study revealed, for the first time, the antiarthritic and antinociceptive effects of the EEPV.

Moderate intestinal immunopathology after acute oral infection with Toxoplasma gondii oocysts is associated with expressive levels of serotonin.

BACKGROUND: Invasion of the intestinal mucosa by T. gondii elicits a local immune response of variable intensity. These reactions can be lethal in C57BL/6 mice. The tissue damage caused by inflammation and the functional effects depend on the host immunity, strain, and developmental form of the parasite. We investigated the effects of acute oral infection with T. gondii on histoarchitecture, enteric nervous system (ENS), and inflammatory markers in the jejunum and ileum of mice. METHODS: Female C57BL/6 mice were divided into a control group and a group orally infected with 1000 sporulated T. gondii oocysts (ME-49 strain). After 5 days, jejunum and ileum were collected and processed for analyzes (e.g., histological and histopathological examinations, ENS, cytokine dosage, myeloperoxidase, nitric oxide activity). MAIN RESULTS: In infected mice, we observed a significant increase in serotonin-immunoreactive cells (5-HT IR) in the intestinal mucosa, as well as cellular infiltrates in the lamina propria, periganglionitis, and ganglionitis in the myenteric plexus. We also noted decreased neuron density in the jejunum, increased population of enteric glial cells in the ileum, histomorphometric changes in the intestinal wall, villi, and epithelial cells, remodeling of collagen fibers, and increased myeloperoxidase activity, cytokines, and nitric oxide in the intestine. CONCLUSIONS AND INFERENCES: Acute infection of female mice with T. gondii oocysts resulted in changes in ENS and a marked increase in 5-HT. These changes are consistent with its modulatory role in the development of moderate acute inflammation. The use of this experimental model may lend itself to studies aimed at understanding the pathophysiological mechanisms of intestinal inflammation in humans involving ENS.

Hepatoprotective effect of ß-myrcene pretreatment against acetaminophen-induced liver injury.

Objective: In the present study, the hepatoprotective effects of ß-myrcene (MYR) on acetaminophen-induced hepatotoxicity were investigated. Materials and Methods: A total of 40 Balb/c mice were randomly divided into five groups as follows: 1) Normal control group which received only carboxymethylcellulose (CMC), the vehicle used to dissolve acetaminophen (N-acetyl-p-aminophenol, APAP, paracetamol) and MYR; 2) APAP group which received a single dose of acetaminophen (250 mg/kg) orally on day 7; 3) Silymarin group which received 200 mg/kg/day of silymarin; and 4 and 5) pretreatment groups in which, mice were treated with 100 or 200 mg/kg/day of MYR. Liver and blood samples were collected to analyze serum aminotransferases, inflammatory response, oxidative stress markers, and histopathological insults. Results: Our results showed that MYR pretreatment attenuated liver damage and restored liver cells function and integrity as it decreased the leakage of serum aminotransferases (alanine and aspartate aminotransferases (ALT and AST, respectively)) into the blood (p<0.01). MYR treatment also reduced levels of myeloperoxidase (MPO) activity and nitric oxide (NO) (p<0.001). In addition, MYR pretreatment demonstrated significant antioxidant activity by decreasing malondialdehyde (MDA), reactive oxygen species (ROS), and reduced glutathione (GSH) levels (p<0.001). Furthermore, it restored the hepatic level of superoxide dismutase (SOD), catalase (CAT), and oxidized glutathione (GSSG) (p<0.001). Conclusion: For the first time, our results showed that MYR treatment significantly improved liver function by reducing oxidative stress and the inflammatory response induced by APAP.

Effect of Ylang-Ylang (Cananga odorata Hook. F. & Thomson) Essential Oil on Acute Inflammatory Response In Vitro and In Vivo.

The aim of this study is to evaluate the phytochemical profile, oral acute toxicity, and the effect of ylang-ylang (Cananga odorata Hook. F. & Thomson) essential oil (YEO) on acute inflammation. YEO was analyzed by gas chromatography/mass spectrometry. For in vitro tests, YEO was assessed using cytotoxicity, neutrophil chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP), and phagocytic activity tests. YEO was orally administered in zymosan-induced peritonitis, carrageenan-induced leukocyte rolling, and adhesion events in the in situ microcirculation model and in carrageenan-induced paw edema models. YEO (2000 mg/kg) was also tested using an acute toxicity test in Swiss mice. YEO showed a predominance of benzyl acetate, linalool, benzyl benzoate, and methyl benzoate. YEO did not present in vitro cytotoxicity. YEO reduced the in vitro neutrophil chemotaxis induced by fMLP and reduced the phagocytic activity. The oral treatment with YEO reduced the leukocyte recruitment and nitric oxide production in the zymosan-induced peritonitis model, reduced rolling and adherent leukocyte number induced by carrageenan in the in situ microcirculation model, and reduced carrageenan-induced edema and mechanical hyperalgesia. YEO did not present signs of toxicity in the acute toxicity test. In conclusion, YEO affected the leukocyte activation, and presented antiedematogenic, anti-hyperalgesic, and anti-inflammatory properties.

Leukocyte Behavior in Mesenteric Microcirculation upon Experimental By Leishmania Spp. in BALB/c Mice.

BACKGROUND: We aimed to determine the cellular recruitment (leukocyte rolling and adhesion) by which the Leishmania (Viannia) braziliensis, L. (Leishmania) amazonensis, and L. (Leishmania) major species in the mesenteric microcirculation of BALB/c mice. METHODS: Five experimental groups were considered: group 1 (L. braziliensis); group 2 (L. amazonensis); group 3 (L. major); group 4 (control group with PBS); group 5 (negative control group), analyzed 3, 6, 12, and 24 h after parasite inoculation. RESULTS: Infections by the different Leishmania species caused an increase in the number of rolling leukocytes: L. braziliensis a peak at 6 h; L. amazonensis and L. major a peak at 3 h. The Leishmania infections induced leukocyte adhesion: L. major and L. amazonensis showed an increase after 3 and 6 h, respectively. CONCLUSION: The kinetics of cellular recruitment in Leishmania infections, leading to infection susceptibility or resistance, indicates that distinct mechanisms regulate the initial response to Leishmania infection and determine its course.

Prostaglandin E1 prevents histopathological changes improving renal function in experimental nephropathy induced by renal microembolism.

This study investigated the effect of prostaglandin E1 (PGE-1) treatment on the biochemical and histopathological changes in a model of nephropathy that was induced using renal microembolism in rats. Wistar rats were assigned to three groups: a control group (C, normal), a renal microembolism (RM) group, and a renal microembolism treated with PGE-1 (RM + PGE-1) group. The renal microembolism was induced by an arterial injection of polymethylmethacrylate microbeads into the remaining kidney of nephrectomized rats. Intramuscular treatment with PGE-1 was initiated on the day of the induction of the renal microembolism and continued once weekly for up to 60 days. At the end of the treatment period, blood samples were taken to assess the serum creatinine and urea concentrations, and 24-h urine samples were collected to determine the total protein levels. The rats' kidneys were removed and processed for histopathological analysis using the hematoxylin and eosin, periodic acid-Schiff, Mallory-Azan, and Picro-Sirius techniques. An immunohistochemical assay with vascular endothelial growth factor receptor-2 (anti-VEGFR-2) was also performed. The results showed that the PGE-1 treatment prevented vascular, glomerular, tubular, and interstitial alterations and reduced the biochemical changes, thus improving the renal function in rats that were subjected to renal microembolism. These effects could be partially attributable to an increase in the PGE-1-induced angiogenesis, because we observed an increase in the tissue expression of VEGFR-2, a specific marker of angiogenesis.

Effect of alendronate on healing of bone defect and gingival tissue in osteopenic rats / Efecto del alendronato en la reparación de defectos óseos y tejido gingival en ratas con osteopenia

The aim was to evaluate bone repair and gingival tissue repair in osteopenic rats. Fifteen female wistar rats were included; in all of them ovariectomy was realized to induce osteopenia; after 45 days, the animals were submitted to 2 surgical techinques 1) dental extraction of the upper central incisor with no socket preservation and 2) 5 mm cranial defect in the calvarium; 5 rats were included in the control group (G1) withput alendronate application; in the group 2 (G2) was used subcutenous alendronate (0.5 mg/kg) once for three weeks and then was realizd the both surgical techniques. In group 3 (G3), after ovariectomy was realized the both dental extraction and the calvarium defect and after that was realized the alendronate protocol. In each group, after six week was realized euthanasia and descriptive histological analysis of the surgical areas involved. In bone formation of the 5 mm cranial defect was observed with good progression in the 3 experimental models and no modification in quality of bone repair was observed. For the gingival tissue in the extraction socket, no differences were observed between G1 and G3. On other hand, in G2 a thinner and reduced gingival epithelium was found. Our results showed that alendronate was not an obstacle for bone repair; deficiencies in re-epithelialization of oral mucosa show the impact of alendronate before dental extraction.

El objetivo fue evaluar la reparación ósea y gingival en ratas con osteopenia. Quince ratas wistar hembras fueron incluidas; en todas ellas se realizo ovarectomia y fue realizada la inducción de osteopenia; después de 45 días, los animales fueron sometidos a dos técnicas quirúrgicas 1) extracciones dentales del incisivo central superior sin preservación alveolar y 2) creación de un defecto craneano de 5 mm en la calota; 5 animales fueron incluidos como grupo control (G1) sin la aplicación de alendronato; en el grupo 2 (G2) se utilizó alendronato subcutáneo (0,5 mg/kg) una vez a la semana durante 3 semanas. En el grupo 3 (G3), después de la ovarectomia se realizó la exodoncia y el defecto en el cráneo y después de ello se inicio el protocolo con alendronato. En cada grupo, después de seis semanas se realizó la eutanasia con descripción histológica de los hallazgos. En el hueso formado en el defecto craneano de 5 mm se observó una adecuada progresión de reparación en los 3 modelos experimentales y no se observó cambios importantes en el modelo de reparación. Para el tejido gingival en el sitio de extracción, no se observaron diferencias entre el grupo G1 y G3. Por otra parte, el G2 presentó un tejido mas delgado con reducción del epitelio gingival; nuestros resultados demuestran que el alendronato no fue un obstáculo en la reparación ósea; deficiencias en la re epitelización de la mucosa oral muestran el impacto del alendronato después de la exodoncia.

Anti-inflammatory Effect of Low-Dose Anethole and Ibuprofen Combination Is Accompanied by Partial Prevention of Hepatic Metabolic Changes in Arthritic Rats.

Anethole (AN) is a natural compound that has attracted great scientific interest because of its numerous biological activities, including anti-inflammatory effects. However, these effects were obtained with high doses of AN, which may be one limitation of its therapeutic use. This study evaluated the effects of a low-dose AN and ibuprofen (IB) combination on inflammatory parameters in Freund's complete adjuvant-induced arthritis (AIA) and arthritis-induced hepatic metabolic changes. Holtzman rats were used and divided into groups: normal, AIA (control), arthritics treated with IB, arthritics treated with AN, and arthritics treated with AN + IB. The volume of the paws, the appearance of secondary lesions, and the number of synovial leukocytes were evaluated. Gluconeogenesis and ureagenesis from alanine were determined in the rat liver in isolated perfusion. The AN + IB (62.5 + 8.75 mg/kg) treatment exerted an inhibitory effect on inflammatory parameters and partially prevented hepatic metabolic changes that was similar to the effect of high-dose IB (35 mg/kg) and AN (250 mg/kg) treatment. This effect of the treatments on hepatic metabolism can be, partly at least, explained by the preservation of both the alanine aminotransferase (ALT) activity and the cytosolic NADH/NAD+ redox potential in the liver. Taken together, the data obtained provided evidence that the AN + IB combination at lower doses than AN and IB treatment alone had beneficial inhibitory potential for the treatment of AIA and attenuated metabolic changes in the liver. Graphical Abstract.

Mortalidade infantil por câncer no Brasil / Cancer-caused child mortality in Brazil

O objetivo deste estudo foi avaliar a mortalidade por diferentes tipos de cânceres em crianças de 0 a 4 anos, e a distribuição destes óbitos para as cinco regiões brasileiras. Os números de casos registrados e de óbitos foram provenientes do Instituto Nacional do Câncer (INCA) e Sistema de Informações sobre Mortalidade (SIM/DATASUS). As informações sobre nascidos vivos foram coletadas no SINASC. O período de análise foi de 1996 a 2017. Os tipos de neoplasias com maior número de óbitos notificados foram as leucemias e as neoplasias do Sistema Nervoso Central. O número de óbitos em crianças na faixa etária estudada por neoplasias malignas foram foi de 2.597 mortes, sendo as leucemias, as neoplasias do Sistema Nervoso Central e os neuroblastomas responsáveis por aproximadamente 70% destas mortes. A frequência de mortes em relação ao tipo de câncer indicou que as neoplasias do sistema nervoso central apresentam mortalidade de 36,27%; seguida por neuroblastomas com 32,13%; leucemias, com 29,31%; e neoplasias dos tecidos moles, 21,56%. As regiões Sudeste e Nordeste apresentaram maior número de casos. Os resultados desta pesquisa indicaram elevado número de casos de câncer e óbito de crianças de 0-4 anos, reforçando a necessidade de constantes investimentos para um melhor acesso destes pacientes ao sistema de saúde, considerando que diagnóstico e tratamento são importantes para a redução da mortalidade infantil.

Mortality by different types of cancer in 0 - 4 year-old children and its distribution for the five Brazilian regions are investigated. Method: number of registered cases and deaths were retrieved derived from the National Institute of Cancer (INCA) and from the Mortality Information System (SIM/DATASUS). Information on live births was retrieved from SINASC for the period of analysis between 1996 and 2017. Results: types of cancer with the highest number of deaths notified were leukemia and cancers of the Central Nervous System. Number of death in children within the age bracket, with malignant cancer, reached 2,597, with leukemia, cancers of the Central Nervous System and neuroblastomas causing approximately 70% of deaths. Frequency of deaths with regard to cancer type indicates that cancers of the central nervous system had a 36.27% of deaths, followed by neuroblastomas, with 32.13%, leukemias, with 29.31% and cancers of the soft tissues, with 21.65%. The southeastern and northeastern regions of Brazil had the highest indexes. Conclusions: Results reveal high incidence of cancer cases and deaths in 0 ­ 4 year-old children, requiring constant investments for better access of patients to health systems where diagnosis and treatment are essential for the decrease of child mortality.

Effect of (-)-α-Bisabolol on the Inflammatory Response in Systemic Infection Experimental Model in C57BL/6 Mice.

(-)-α-Bisabolol (BISA) is an unsaturated monocyclic sesquiterpenes compound, mainly found in the essential oil of chamomile (Matricaria chamomilla). It has been reported that this compound has several biological activities, but there are few studies evaluating the activity of this compound in the systemic inflammatory response in infectious processes. The aim of this study was to evaluate the effect of BISA on the inflammatory response and survival rate in a systemic infection model, and in vitro neutrophils phagocytic activity. BISA at concentration of 3, 10, 30, and 90 µg/ml did not presented in vitro cytotoxicity in MTT assay, and at concentrations of 1 and 3 µg/ml the BISA treatment increased in vitro phagocytic neutrophil activity. For the inflammatory response study, we verified the BISA treatment effect in a cecal ligation and puncture (CLP)-induced systemic infection model in mice; in this model, we demonstrate that BISA at dose of 100 mg/kg reduced the leukocyte recruitment in peritoneal cavity; at dose of 200 mg/kg, the NO concentration was increased in the peritoneal cavity. The bacteria CFU number was reduced in mice blood in the BISA treatment, at doses of 100 and 200 mg/kg. The BISA treatment at doses of 50 and 100 mg/kg increased the myeloperoxidase activity and reduction NO production in lung tissue of mice in CLP model. At dose of 100 mg/kg, the BISA treatment was able to reduce the mortality rate of mice submitted to CLP-induced sepsis and observed for 7 days. The results suggest an effect of BISA on inflammatory response, with activity on leukocyte chemotactic and NO production, in addition to increasing the survival rate of animals submitted to CLP model.

Nephropathy induced by renal microembolism: a characterization of biochemical and histopathological changes in rats.

The aim of this study was to investigate some biochemical parameters of renal function and the vascular, glomerular, tubular, and interstitial manifestations in the progression of nephropathy induced by renal microembolism. Renal microembolism was induced by the arterial injection of polymethacrylate microspheres in the remnant kidney of nephrectomized rats. Animals 110-120 days old were randomly divided into three groups: the control group (C; normal), the nephrectomized group (S; nephrectomized that did not undergo renal microembolism), and the model group (M, nephrectomized animals that underwent renal arterial microembolism). The animals were evaluated 30, 60, and 90 days after the induction of a renal microembolism. Blood and urine samples were collected to determine serum creatinine (Cr) and urea (Ur) concentrations and urine total protein (Pt) concentrations. The kidneys were weighed and processed for histopathological analysis using hematoxylin and eosin (HE), periodic acid-Schiff (PAS), Mallory-Azan, and Picro-Sirius staining. The samples were also subjected to immunohistochemistry with a proliferating cell nuclear antigen (PCNA) and a vascular endothelial growth factor receptor (VEGFR). The data demonstrated evidence of the occurrence of vascular, glomerular, tubular, and interstitial abnormalities in the renal tissue, and changes in the biochemical parameters of renal function (serum Cr and Ur and of 24-h urine Pt) in this experimental model of nephropathy induced by renal microembolism, which may indicate the development of chronic kidney disease (CKD). Additionally, the findings indicate that this is a good reproducibility model that may be useful for studying the pathogenesis of CKD that is caused by atheroembolism and possible treatment alternatives.

Effect of Lavender (Lavandula angustifolia) Essential Oil on Acute Inflammatory Response.

Lavandula angustifolia is a plant of Lamiaceae family, with many therapeutic properties and biological activities, such as anticonvulsant, anxiolytic, antioxidant, anti-inflammatory, and antimicrobial activities. The aim of this study was to evaluate the effect of Lavandula angustifolia Mill. essential oil (LEO) on acute inflammatory response. LEO was analyzed using gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance spectroscopy (NMR) methods and showed predominance of 1,8-cineole (39.83%), borneol (22.63%), and camphor (22.12%). LEO at concentrations of 0.5, 1, 3, and 10 µg/ml did not present in vitro cytotoxicity. Additionally, LEO did not stimulate the leukocyte chemotaxis in vitro. The LEO topical application at concentrations of 0.25, 0.5, and 1 mg/ear reduced edema formation, myeloperoxidase (MPO) activity, and nitric oxide (NO) production in croton oil-induced ear edema model. In carrageenan-induced paw edema model, LEO treatment at doses of 75, 100, and 250 mg/kg reduced edema formation, MPO activity, and NO production. In dextran-induced paw edema model, LEO at doses of 75 and 100 mg/kg reduced paw edema and MPO activity. In conclusion, LEO presented anti-inflammatory activity, and the mechanism proposed of LEO seems to be, at least in part, involving the participation of prostanoids, NO, proinflammatory cytokines, and histamine.

Behçet's Disease: Pulmonary Aneurysm Resolution with Oral Therapy and HLA B72 Allele Association.

We report the case of a woman who was diagnosed with a pulmonary artery aneurysm that was caused by Behçet's disease. The patient was initially diagnosed with community-acquired pneumonia and then pulmonary thromboembolism and aneurysm of the right pulmonary artery segmental branch was confirmed. The initial treatment consisted of anticoagulant drugs. After analysis of the family history and a positive pathergy test, the patient was diagnosed with Behçet's disease. Oral pharmacological treatment began with corticosteroids, cyclophosphamide, and anticoagulant suspension. The HLA B72 allele was identified in the patient and her two sisters, demonstrating the familial characteristic of the disease and the presence of this allele in a female patient with Behçet's disease. After 12 months of treatment, the clinical condition completely resolved.

Immunocompetent host develops mild intestinal inflammation in acute infection with Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is the causative agent of toxoplasmosis, common zoonosis among vertebrates and high incidence worldwide. During the infection, the parasite needs to transpose the intestinal barrier to spread throughout the body, which may be a trigger for an inflammatory reaction. This work evaluated the inflammatory alterations of early T. gondii infection in peripheral blood cells, in the mesenteric microcirculation, and small intestinal tissue by measurement of MPO (myeloperoxidase) activity and NO (nitric oxide) level in rats. Animals were randomly assigned into control group (CG) that received saline orally and groups infected with 5,000 oocysts for 6 (G6), 12 (G12), 24 (G24), 48 (G48) and 72 hours (G72). Blood samples were collected for total and differential leukocyte count. Intravital microscopy was performed in the mesentery to evaluate rolling and adhesion of leukocytes. After euthanasia, 0.5cm of the duodenum, jejunum and ileum were collected for the determination of MPO activity, NO level and PCR to identify the parasite DNA and also the mesentery were collected to perform immunohistochemistry on frozen sections to quantify adhesion molecules ICAM-1, PECAM-1 and P-Selectin. The parasite DNA was identified in all infected groups and there was an increase in leukocytes in the peripheral blood and in expression of ICAM-1 and PECAM-1 in G6 and G12, however, the expression of P-selectin was reduced in G12. Leukocytes are in rolling process during the first 12 hours and they are adhered at 24 hours post-infection. The activity of MPO increased in the duodenum at 12 hours, and NO increased in the jejunum in G72 and ileum in G24, G48 and G72. Our study demonstrated that T. gondii initiates the infection precociously (at 6 hours) leading to a systemic activation of innate immune response resulting in mild inflammation in a less susceptible experimental model.

Queda do mesmo nível em idosos: fatores associados ao trauma cranioencefálico e raquimedular / Caída desde altura similar en ancianos: factores asociados al trauma craneoencefálico y raquimedular / Same-level falls in older adults: factors associated with traumatic brain and spinal cord injuries

RESUMO: Objetivo: identificar fatores associados à ocorrência de trauma cranioencefálico e raquimedular entre idosos que sofreram queda do mesmo nível. Método: estudo retrospectivo, com 192 prontuários de idosos que sofreram queda do mesmo nível em 2014 e foram atendidos no Pronto Atendimento de um hospital de ensino do Paraná. Realizou-se teste Z, para comparação de proporções do grupo com (n=80) e sem (n=112) trauma cranioencefálico ou raquimedular com dados demográficos, de saúde, da queda e da avaliação/atendimento. Resultados: dos idosos identificados, 80 (41,7%) tiveram traumatismo cranioencefálico ou raquimedular. Houve associação significativa com a ocorrência de traumatismo cranioencefálico ou raquimedular: sexo masculino (p=0,0109), transporte especializado (p=0,0001), queda em via pública (p=0,0026), ausência de hipertensão arterial (p=0,0434) e presença de doença psiquiátrica (p=0,0048). Conclusão: o trauma cranioencefálico ou raquimedular é um evento frequente associado à queda do mesmo nível, o que denota a necessidade de medidas educativas e preventivas visando à redução da quedas.

RESUMEN: Objetivo: Identificar factores asociados a la ocurrencia de traumas craneoencefálicos y raquimedulares entre ancianos que sufrieron caídas desde alturas similares. Método: Estudio retrospectivo, con 192 historias clínicas de ancianos que cayeron desde alturas similares en 2014, atendidos en la Guardia de un hospital de enseñanza de Paraná. Se realizó test Z para comparación de proporciones del grupo con (n=80) y sin (n=112) trauma craneoencefálico o raquimedular con datos demográficos, de salud, de la caída y de la evaluación/atención. Resultados: Ochenta (41,7%) ancianos sufrieron traumatismo craneoencefálico o raquimedular. Existió asociación significativa con traumatismo craneoencefálico o raquimedular en: sexo masculino (p=0,0109), transporte especializado (p=0,0001), caída en vía pública (p=0,0026), ausencia de hipertensión arterial (p=0,0434) y presencia de enfermedad psiquiátrica (p=0,0048). Conclusión: El trauma craneoencefálico o raquimedular constituye un evento frecuentemente asociado a caídas desde niveles similares, expresando ello necesidad de medidas educativas y preventivas apuntando a reducir las caídas.

ABSTRACT: Objective: to identify factors associated with the occurrence of traumatic brain and spinal cord injuries among older adults who suffered a same-level fall. Method: a retrospective study, with 192 medical records of older adults that suffered a same-level fall in 2014 and were attended in the Emergency Care Unit of a teaching hospital in Paraná. The Z test was performed to compare the proportions of the groups with (n=80) and without (n=112) traumatic brain or spinal cord injuries with demographic, health, fall and evaluation/care data. Results: 80 (41.7%) of the older adults identified had traumatic brain or spinal cord injuries. There was a significant association of the occurrence of traumatic brain or spinal cord injuries with: male gender (p=0.0109), specialized transport (p=0.0001), fall on public road (p=0.0026), absence of arterial hypertension p=0.0434) and presence of psychiatric illness (p=0.0048). Conclusion: traumatic brain and spinal cord injuries are frequent events associated with same-level falls, which indicates the need for educational and preventive measures aimed at the reduction of falls.

A single administration of fish oil inhibits the acute inflammatory response in rats.

OBJECTIVE: To investigate the antiinflammatory effects of a single administration of fish oil (FO) on the acute inflammatory response. METHODS: The paw edema and pleurisy models were used to evaluate the effects of FO dissolved in olive oil (FOP) orally administered in a single dose in rats. Nitric oxide (NO) concentrations in the pleural exudate were performed according to the Griess method and the cytokine concentrations were determined by Luminex bead-based multiplex assay. RESULTS: FOP treatment (30 and 300 mg/kg) significantly reduced paw edema. FOP treatment at 18.75, 37.5, 75.0, 150.0, and 300 mg/kg decreased both the volume of pleural exudate and cellular migration into the pleural cavity and each of these doses presented the same effectiveness. Treatment with FOP (300 mg/kg) reduced NO, TNF-α, IL-1ß, and IL-6 concentrations in the pleural exudate. CONCLUSIONS: The present data provide evidence that FO has inhibitory effects on the acute inflammatory response when administered in a single dose in rats. This effect might be attributable to a direct inhibitory effect of FO on the production or release of inflammatory mediators that are involved in the pathological processes evaluated herein.

Hepatoprotective Effect of Citral on Acetaminophen-Induced Liver Toxicity in Mice.

High doses of acetaminophen (APAP) lead to acute liver damage. In this study, we evaluated the effects of citral in a murine model of hepatotoxicity induced by APAP. The liver function markers alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma-glutamyl transferase (γGT) were determined to evaluate the hepatoprotective effects of citral. The livers were used to determine myeloperoxidase (MPO) activity and nitric oxide (NO) production and in histological analysis. The effect of citral on leukocyte migration and antioxidant activity was evaluated in vitro. Citral pretreatment decreased significantly the levels of ALT, AST, ALP, and γGT, MPO activity, and NO production. The histopathological analysis showed an improvement of hepatic lesions in mice after citral pretreatment. Citral inhibited neutrophil migration and exhibited antioxidant activity. Our results suggest that citral protects the liver against liver toxicity induced by APAP.

Anethole reduces inflammation and joint damage in rats with adjuvant-induced arthritis.

AIM: This study evaluated whether anethole attenuates the inflammatory response and joint damage in a model of adjuvant-induced arthritis (AIA) in rats. METHODS: The animals were treated with 62.5-, 125-, or 250-mg/kg anethole daily for 21 days after AIA and necropsied on days 14 and 21 to evaluate the number of serum and synovial leukocytes (total and differential), serum cytokines (IL-2, IL-6, IL-12, IL-17, and TNF-α), and nitric oxide concentrations. Morphologic changes in the cartilage and bone of the femorotibial articulation in both left paw and right paw were studied in hematoxylin/eosin and Sirius Red-hematoxylin sections. RESULTS: Different doses of anethole suppressed paw swelling and the number of serum and synovial leukocytes. However, 250 mg/kg of anethole more effectively controlled local and systemic inflammation. Histological evaluation revealed significant prevention of cartilage damage and inflammatory infiltrate scores. Morphometric analysis showed pannus formation, the thickness of the articular cartilage, and bone resorption lower in the anethole-treated AIA group compared to untreated AIA group on both days 14 and 21. These significant anti-inflammatory effects in the anethole-treated AIA group were associated with downregulation of cytokines and nitric oxide levels. CONCLUSION: Therefore, anethole may be a useful intervention to treat inflammatory arthritis.