Interference in Macrophage Balance (M1/M2): The Mechanism of Action Responsible for the Anti-Inflammatory Effect of a Fluorophenyl-Substituted Imidazole.

Traditionally, the treatment of inflammatory conditions has focused on the inhibition of inflammatory mediator production; however, many conditions are refractory to this classical approach. Recently, an alternative has been presented by researchers to solve this problem: The immunomodulation of cells closely related to inflammation. Hence, macrophages, a critical key in both innate and acquired immunity, have been presented as an alternative target for the development of new medicines. In this work, we tested the fluorophenyl-imidazole for its anti-inflammatory activity and possible immunomodulatory effect on RAW 264.7 macrophages. We also evaluated the anti-inflammatory effect of the compound, and the macrophage repolarization to M2 was confirmed by the ability of the compound to reduce the M1 markers TNF-α, IL-6, MCP-1, IL-12p70, IFN-γ, and TLR4, the high levels of p65 phosphorylated, iNOS and COX-2 mRNA expression, and the fact that the compound was not able to induce the production of M1 markers when used in macrophages without lipopolysaccharide (LPS) stimulation. Moreover, fluorophenyl-imidazole had the ability to increase the M2 markers IL-4, IL-13, CD206, apoptosis and phagocytosis levels, arginase-1, and FIZZ-1 mRNA expression before LPS stimulation. Similarly, it was also able to induce the production of these same M2 markers in macrophages without being induced with LPS. These results reinforce the affirmation that the fluorophenyl-imidazole has an important anti-inflammatory effect and demonstrates that this effect is due to immunomodulatory activity, having the ability to trigger a repolarization of macrophages from M1 to M2a. These facts suggest that this molecule could be used as an alternative scaffold for the development of a new medicine to treat inflammatory conditions, where the anti-inflammatory and proregenerative properties of M2a macrophages are desired.

Amazonia Phytotherapy Reduces Ischemia and Reperfusion Injury in the Kidneys.

Acute kidney injury (AKI) is defined as a sudden decrease in kidney function. Phytomedicines have shown positive effects in the treatment of AKI worldwide. The aim of this study was to evaluate the effect of Abuta grandifolia on the renal function of rats submitted to AKI. A phytochemical study of the plant was performed through liquid chromatography coupled with mass spectrometry (CL-EM) and DPPH and ABTS antioxidant tests. Renal function tests were performed in 20 male adult Wistar rats weighing from 250 to 300 g distributed in the following groups: SHAM (submitted to laparotomy with simulation of renal ischemia); ABUTA (animals that received 400 mg/kg of AG, orally-VO, once a day, for 5 days, with simulation of renal ischemia); I/N (animals submitted to laparotomy for clamping of bilateral renal pedicles for 30 min, followed by reperfusion); ABUTA + I/R (animals that received AG-400 mg/kg, 1× per day, VO, for 5 days, submitted to renal ischemia after treatment with herbal medicine). The results suggest that the consumption of Abuta grandifolia promoted renoprotection, preventing the reduction of renal function induced by ischemia, oxidizing activity, and deleterious effects on the renal tissue, confirmed by the decrease of oxidative metabolites and increase of antioxidants in the animals' organisms.

Seagrass deformation affects fluid instability and tracer exchange in canopy flow.

Monami is the synchronous waving of a submerged seagrass bed in response to unidirectional fluid flow. Here we develop a multiphase model for the dynamical instabilities and flow-driven collective motions of buoyant, deformable seagrass. We show that the impedance to flow due to the seagrass results in an unstable velocity shear layer at the canopy interface, leading to a periodic array of vortices that propagate downstream. Our simplified model, configured for unidirectional flow in a channel, provides a better understanding of the interaction between these vortices and the seagrass bed. Each passing vortex locally weakens the along-stream velocity at the canopy top, reducing the drag and allowing the deformed grass to straighten up just beneath it. This causes the grass to oscillate periodically even in the absence of water waves. Crucially, the maximal grass deflection is out of phase with the vortices. A phase diagram for the onset of instability shows its dependence on the fluid Reynolds number and an effective buoyancy parameter. Less buoyant grass is more easily deformed by the flow and forms a weaker shear layer, with smaller vortices and less material exchange across the canopy top. While higher Reynolds number leads to stronger vortices and larger waving amplitudes of the seagrass, waving amplitude is maximized at intermediate grass buoyancy. All together, our theory and computations develop an updated schematic of the instability mechanism consistent with experimental observations.

Leiomiossarcoma paratesticular: relato de caso e revisão de literatura / Paratesticular leiomysarcoma: a case of report and review of the literature

Introdução: O leiomiossarcoma é um tumor maligno de células mesenquimais. Este estudo tem como objetivo apresentar um caso clínico de sarcoma paratesticular subtipo leiomiossarcoma, tendo em vista sua escassez na literatura. Relato de caso: Paciente, 40 anos, sexo masculino, negro, hígido, iniciou quadro de dor em região de bolsa escrotal. Foi submetido à ultrassonografia que evidenciou tumor testicular à esquerda. Foi realizada abordagem cirúrgica. Considerações finais: O leiomiossarcoma é um tumor maligno com envolvimento de músculo liso. Devido à raridade do leiomiossarcoma paratesticular, não existe protocolo estabelecido na literatura. A importância da equipe multidisciplinar e especializada com acompanhamento longitudinal tem o intuito de instituir a terapia padrão-ouro e evitar recorrência.

Introduction: Leiomyosarcoma is a malignant tumor of mesenchymal cells. This study aims to present a clinical case of paratesticular sarcoma subtype leiomyosarcoma given its scarcity in the literature. Case report: The patient, 40 years old, male, black, healthy, started with pain in the scrotal region. He was submitted to ultrasonography which showed a testicular tumor on the left. A surgical approach was performed. Final consideration: Leiomyosarcoma is a malignant tumor with smooth muscle involvement. Due to the rarity of paratesticular leiomyosarcoma, there is no established protocol in the literature. The importance of a multidisciplinary and specialized team with longitudinal follow-up to establish the gold standard therapy and avoid recurrence.

The anti-inflammatory activity of 2-iminothiazolidines: evidence for macrophage repolarization.

Nowadays, macrophages are recognized as key cells involved in chronic inflammatory conditions, and play central roles in all inflammatory diseases and cancer. Due to their extensive involvement in the pathogenesis of inflammatory diseases, they are now considered a relevant therapeutic target in the development of new therapeutic strategies. 2-Iminothiazolidines are associated with important anti-inflammatory activity and represent a rich source for the development of new drugs and treatments. Our research focuses on evaluating the anti-inflammatory capacity of these compounds and their relationship with M1/M2 macrophage polarization. The results demonstrate that 2-iminothiazolidines have the capacity to decrease the levels of anti-inflammatory biomarkers, such as cytokines (IL-1ß, TNF-α, and IL-6), nitric oxide synthase (with impact on NOx production), and COX-2, following a significant decline in NF-kB activation. We also observed an increase in levels of anti-inflammatory cytokines (IL-4 and IL-13) in the in vitro model of RAW 264.7 macrophages induced by LPS. Moreover, this is the first report, suggesting that the anti-inflammatory activity of 2-iminothiazolidines is associated with the ability to enhance phagocytosis, increase Arginase-1 and CD206 expression, and increase the secretion of IL-10. Furthermore, an in vivo study using the acute lung injury model induced by LPS proved the anti-inflammatory activity of a selected 2-iminothiazolidine, named methyl 2-(benzoylimino)-3-methyl-4-(4-nitrobenzyl)-1,3-thiazolidine-4-carboxylate. All these results, taken together, lead us to hypothesize that the mechanism of anti-inflammatory effect observed with this compound is closely related to the ability of this compound to produce macrophage repolarization, from the M1 to the M2 phenotype.

Parasitism of Nelore (Bos indicus) calf from northern Brazil by Ctenocephalides felis.

Ctenocephalides felis is the most common hematophagous ectoparasite of domestic cats and dogs worldwide, causing allergic dermatitis, anemia, itching, discomfort, and it is responsible for the transmission of many pathogens. In cattle, parasitism is not common but occurs due to the high adaptability of this flea species. This study aimed to report infestation of a Nellore (Bos indicus) calf from Northern Brazil by C. felis and its clinical findings. A 45 kg male calf presented diarrhea, progressive emaciation after 50 days of birth, and flea infestation. Anemia was observed (4.11 × 106/µL of erythrocytes; 20.48% of hematocrit). Coproparasitological examination and molecularly detection of Anaplasma spp. and Babesia spp. indicated negatively. Fleas were collected and taxonomically identified as C. felis. Clinical manifestations of this ectoparasite in cattle were unspecific; however, they can develop severe conditions, such as restlessness and weakness, accompanied by alopecia, emaciation, anemia, and edema of the lower limbs with intense itching and self-excoriation.

Inflammatory biomarkers on an LPS-induced RAW 264.7 cell model: a systematic review and meta-analysis.

INTRODUCTION: Several experimental models have been designed to promote the development of new anti-inflammatory drugs. The in vitro model using RAW 264.7 cells has been widely used. However, there is still no consensus on which inflammatory mediators should initially be measured to screen for possible anti-inflammatory effects. To determine the rationality of measuring inflammatory mediators together with NO, such as the levels of tumor necrosis factor (TNF)-α, and interleukins (IL) 1ß and 6, we carried out this systematic review (SR) and meta-analysis (MA). METHODOLOGY: We conducted this SR and MA in accordance with the Preferred Reporting of Systematic Reviews and Meta-Analysis and the Cochrane Handbook for Systematic Reviews of Intervention. This review was registered in the Open Science Framework ( https://doi.org/10.17605/OSF.IO/8C3HT ). RESULTS: LPS-induced cells produced high NO levels compared to non-LPS induced, and this production was not related to cell density. TNF-α, IL-1ß, and IL-6, also showed high levels after cells had been stimulated with LPS. Though with some restrictions, all studies were reliable, as the risk of bias was detected in the test compounds and systems. CONCLUSION: Measurement of NO levels may be sufficient to screen for possible anti-inflammatory action in the context of LPS-induced RAW 264.7 cells.

Carcass and meat traits of bubaline finished on sugarcane-based diets supplemented with spineless cactus as a replacement for wheat bran.

OBJECTIVE: An experiment was conducted to evaluate the effects of increasing levels of spineless cactus (0%, 33%, 66%, and 100%) used as a substitute for wheat bran in buffalo diets on quantitative and qualitative traits of the meat and carcass. METHODS: Twenty Murrah buffaloes at 18 months of age, with a mean initial weight of 292.9±57.3 kg, were randomly allocated to four treatments with five replicates. The animals were slaughtered after 90 days in the feedlot. The effects of spineless cactus as a replacement for wheat bran in the diet of the buffaloes on the carcass and meat traits, slaughter weight, carcass yield and carcass measurements were studied. RESULTS: Increased spineless cactus levels led to linear reduction in average daily gain, slaughter weight, hot and cold carcass weight, compactness index and in the amount of muscle in the carcass, and there is no difference between the control treatment and the 33% replacing level for these parameters. The quality of the meat was not influenced by the treatments. CONCLUSION: Spineless cactus can replace wheat bran by up to 33% in sugarcane-based diets for buffaloes, without influencing quantitative and qualitative traits of the meat and carcass.

Assessing the technical efficiency of Brazil's teaching hospitals using data envelopment analysis. / Avaliação da eficiência técnica dos hospitais de ensino do Brasil utilizando a análise envoltória de dados.

The general objective of this study was to assess the technical efficiency of Brazil's teaching hospitals using data envelopment analysis (DEA). To this end, a quantitative exploratory study was conducted with secondary data from the national health information system (DATASUS) using an output-oriented DEA model. The study population consisted of 29 large-sized teaching hospitals located in the country's Center-West, South, Southeast, and North regions. Twelve hospitals were shown to be on the efficient frontier (technically efficient) and 17 were off the frontier. Absolute efficiency values were calculated for the hospitals that were off the frontier, using benchmarks with weighting for benchmarking. Private for-profit hospitals were shown to be the most efficient, followed by private not-for-profit and public facilities. The findings of this study suggest that DEA has potential for assessing technical efficiency in hospital settings in relation to operational capacity.

O objetivo geral deste estudo foi avaliar a eficiência técnica dos hospitais de ensino do Brasil por meio da análise envoltória de dados. Para tanto, foi realizada uma pesquisa exploratória de natureza quantitativa utilizando dados secundários do Ministério da Saúde. Foi utilizado o método da análise envoltória de dados (DEA - Data Envelopment Analysis), orientada a output. A população deste estudo constituiu em 29 hospitais de ensino de grande porte nas regiões Centro-Oeste, Sul, Sudeste e Norte do Brasil. Identificou-se que 12 hospitais ficaram localizados na fronteira de eficiência, ou seja, foram relacionados como eficientes na maximização dos outputs (produtos), e 17 ficaram abaixo. Foi estabelecido o valor absoluto para a eficiência daqueles que não atingiram a fronteira por meio de benchmarks com pesos para o espelhamento. Identificou-se, quanto à natureza jurídica, que a personalidade "entidades empresariais" foi mais eficiente, seguida das "entidades sem fins lucrativos" e, por último, da "administração pública". Os resultados desta pesquisa sugerem que a DEA tem potencial para avaliação de eficiência técnica no âmbito hospitalar quando avaliada a capacidade de produção do estabelecimento.

New intragastric sleeve technique reduces adipose tissue in pig experimental model: tomographic study.

In order to implement a new bariatric surgery technique, we verify the efficacy of intragastric sleeve to reduce weight gain and subcutaneous adipose tissue (SAT). Animals were divided into two groups: G1 (single-port intragastric sleeve) and G2 (sham group). The stomach was surgically reduced by single-port intragastric sutures to fo a gastric sleeve. Animals were submitted to computer tomography (CT) before the surgical procedure and after 18 weeks. Images were analyzed and measurements of the thickness of SAT, depth and width of the longissimus dorsi muscle and the rib eye area were made. Body weight and CT measurements were analyzed using the GLM PROC. The correlation coefficients were calculated among weight, moments and measures. There was a significant difference in weight gain, in which G1 had an average of 42.803 ± 3.206 kg, lower than G2 (45.966 ± 4.767 kg). The mean values for SAT and muscle measurements differed significantly between groups, in which G1 achieved the lowest values. All variables had significant correlations and high magnitude. Intragastric sleeve surgery induced a significant decrease of SAT. The new intragastric sleeve technique is feasible, safe and effective, mainly in reducing fat deposition, making it an important alternative in bariatric surgical treatment.

Investigation of phenolic compounds, antioxidant and anti-inflammatory activities in stingless bee honey (Meliponinae).

The objective of this study was to investigate and quantify the composition phenolic, reducing capacity, the free radical scavenging activity, as well as, the anti-inflammatory effect evaluated against lipopolysaccharides-stimulated RAW264.7 macrophages through modulation of inflammatory mediators, in eight stingless bee honey types (Meliponinae) from southern Brazil. Stingless bee honey did not show to be cytotoxic at the tested concentrations (1-100 µM) and also reduced nitric oxide and the secretion of the pro-inflammatory cytokine in the inflamed macrophages. Two honey samples showed the ability to increase the secretion of anti-inflammatory cytokine (interleukin-10), suggesting a significant anti-inflammatory effect. All these findings indicate that stingless bee honey could be an important source of natural compounds presenting anti-inflammatory and antioxidant effect, which could would provide health benefits when included in the diet.

Evidence That the Anti-Inflammatory Effect of Rubiadin-1-methyl Ether Has an Immunomodulatory Context.

BACKGROUND: In spite of the latest therapeutic developments, no effective treatments for handling critical conditions such as acute lung injuries have yet been found. Such conditions, which may result from lung infections, sepsis, multiple trauma, or shock, represent a significant challenge in intensive care medicine. Seeking ways to better deal with this challenge, the scientific community has recently devoted much attention to small molecules derived from natural products with anti-inflammatory and immunomodulatory effects. AIMS: In this context, we investigated the anti-inflammatory effect of Rubiadin-1-methyl ether isolated from Pentas schimperi, using an in vitro model of RAW 264.7 macrophages induced by LPS and an in vivo model of acute lung injury (ALI) induced by LPS. METHODS: The macrophages were pretreated with the compound and induced by LPS (1 µg/mL). After 24 h, using the supernatant, we evaluated the cytotoxicity, NOx, and IL-6, IL-1ß, and TNF-α levels, as well as the effect of the compound on macrophage apoptosis. Next, the compound was administered in mice with acute lung injury (ALI) induced by LPS (5 mg/kg), and the pro- and anti-inflammatory parameters were analyzed after 12 h using the bronchoalveolar lavage fluid (BALF). RESULTS: Rubiadin-1-methyl ether was able to inhibit the pro-inflammatory parameters studied in the in vitro assays (NOx, IL-6, and IL-1ß) and, at the same time, increased the macrophage apoptosis rate. In the in vivo experiments, this compound was capable of decreasing leukocyte infiltration; fluid leakage; NOx; IL-6, IL-12p70, IFN-γ, TNF-α, and MCP-1 levels; and MPO activity. In addition, Rubiadin-1-methyl ether increased the IL-10 levels in the bronchoalveolar lavage fluid (BALF). CONCLUSIONS: These findings support the evidence that Rubiadin-1-methyl ether has important anti-inflammatory activity, with evidence of an immunomodulatory effect.

Effect of physical exercise on the cardiorespiratory fitness of men-A systematic review and meta-analysis.

This systematic review and meta-analysis analyzes the effect of physical exercise on the cardiorespiratory fitness of men according to type, intensity and duration of intervention, using data from randomized clinical trials; it also seeks to verify the dose-response relationship between duration and intensity of exercise and level of fitness. Databases were searched for reports of relevant studies. A methodological evaluation was carried out. In the statistical analysis, mean, standard deviation and sample size of each group were used. The mean age of the participants was 48.2 ±â€¯17.1 years. The effect on men's VO2 (a measure of cardiovascular fitness) of five to 120 weeks of exercise of moderate to vigorous intensity was found to be a change of 10.190 L/min-1. A meta-regression analysis did not reveal significant results. A positive effect on VO2 of men of different age groups was observed after aerobic and resistance exercise interventions, indicating the beneficial effects of exercise on cardiorespiratory fitness.

Concurrent training protocol for men with androgen deficiency in the aging male: a randomized clinical trial.

BACKGROUND: The androgen deficiency in the aging male (ADAM) affects physical, sexual, and psychological aspects with characteristics symptoms of middle-aged men. The practice of regular physical activity and physical exercise can attenuate these symptoms. The aim of this randomized clinical trial is to propose a physical exercise protocol based on concurrent training for middle-aged men with ADAM. METHOD: Randomized clinical trial with a 6-month intervention will randomly divided into two groups: experimental group (EG) and control group (CG). Four evaluations will be carried out, (1) pre-intervention; (2) in the first month of intervention; (3) in the third month of intervention; (4) post-intervention, evaluating: physical, psychological, sexual, and hormonal aspects. The intervention protocol with concurrent training will have duration of 6 months; frequency of 3 times weekly, with 60 min per session. The two-way ANOVA test will be used for the inter-group and intra-group comparisons with repeated measurements, and also Sydak's comparison test. CONCLUSION: This protocol was developed with the intent of easing the symptoms of ADAM. In addition, it is believed that the concurrent training protocol could be capable to recover hormonal, physical, psychological, and sexual aspect of middle-aged men with ADAM.

Phenolic Compounds Present Schinus terebinthifolius Raddi Influence the Lowering of Blood Pressure in Rats.

This study identified two phenolic compounds in Schinus terebinthifolius Raddi fruits: naringenin (first report in this species) and gallic acid. Their structures were elucidated by nuclear magnetic resonance (NMR) data (¹H-, 13C-NMR) and a high-performance liquid chromatography (HPLC) technique. A high content of phenolics (659.21 mg of gallic acid equivalents/g of sample-Folin-Ciocalteau method) and total flavonoids (140.69 mg of rutin equivalents/g of sample-aluminum chloride method) were quantified in S. terebinthifolius, as well as high antioxidant activity (77.47%-2,2-diphenyl-1-picrylhydrazyl, DPPH method). The antihypertensive activity related to its phenolic content was investigated. After intravenous infusion in Wistar rats, these phenolics significantly reduced (p < 0.05) the systolic, median, and diastolic arterial pressures of individuals. The rotarod test was performed to determine the mechanism of action of the sample vasorelaxant effect. It was found that its action exceeded that of the positive control used (diazepam). This confirmed the vasodilatory activity exerted by S. terebinthifolius fruits is related to the phenolic compounds present in the plant, which are potent antioxidants and inhibit oxidative stress, mainly in the central nervous system.

Predictors of mortality in patients submitted to nephrectomy for non-metastatic renal cell carcinoma at a referral center in Northeastern Brazil. / Preditores de mortalidade em pacientes submetidos à nefrectomia por carcinoma de células renais não metastático em um centro de referência no Nordeste Brasileiro.

OBJECTIVE:: to identify predictors of mortality in patients submitted to nephrectomy for non-metastatic renal cancer. METHODS:: we conducted a retrospective cohort study based on the records of patients with renal cancer submitted to radical or partial nephrectomy at the Ceará Cancer Institute. RESULTS:: we studied 117 patients, with mean and median age of 59.14 and 59 years, respectively. The male gender was slightly predominant. The right kidney was most frequently affected (64%). The most common histopathological diagnosis was clear-cell carcinoma (77%). Stage pT1 and Fuhrman grade II were predominant. The only predictive variables of overall survival were pathological stage (pT) and lymph node involvement. CONCLUSION:: pathological stage (pT) and lymph node involvement are important prognostic factors in patients undergoing nephrectomy for non-metastatic renal cancer.

Preditores de mortalidade em pacientes submetidos à nefrectomia por carcinoma de células renais não metastático em um centro de referência no Nordeste Brasileiro / Predictors of mortality in patients submitted to nephrectomy for non-metastatic renal cell carcinoma at a referral center in Northeastern Brazil

RESUMO Objetivo: identificar fatores prognósticos envolvidos no carcinoma de células renais não metastático. Métodos: estudo tipo coorte retrospectivo, utilizando dados obtidos em revisão de prontuários de pacientes portadores de carcinoma de células renais, submetidos à nefrectomia radical ou parcial, no Instituto do Câncer do Ceará. Resultados: foram estudados 117 pacientes com média de idade de 59,14 anos e mediana de 59 anos. Não houve predominância de sexo, o rim direito foi o mais acometido (64%) e o tipo histopatológico mais comum foi o carcinoma de células claras (77%). Predominou o estádio pT1 e o grau GII. Das variáveis analisadas, apenas o estadiamento patológico (pT) e o acometimento linfonodal revelaram-se preditoras de sobrevida global. Conclusão: o estadiamento patológico (pT) e o acometimento de linfonodos regionais são fatores prognósticos importantes em pacientes portadores de carcinoma de células renais não metastáticos submetidos a nefrectomia.

ABSTRACT Objective: to identify predictors of mortality in patients submitted to nephrectomy for non-metastatic renal cancer. Methods: we conducted a retrospective cohort study based on the records of patients with renal cancer submitted to radical or partial nephrectomy at the Ceará Cancer Institute. Results: we studied 117 patients, with mean and median age of 59.14 and 59 years, respectively. The male gender was slightly predominant. The right kidney was most frequently affected (64%). The most common histopathological diagnosis was clear-cell carcinoma (77%). Stage pT1 and Fuhrman grade II were predominant. The only predictive variables of overall survival were pathological stage (pT) and lymph node involvement. Conclusion: pathological stage (pT) and lymph node involvement are important prognostic factors in patients undergoing nephrectomy for non-metastatic renal cancer.