Diruthenium(II-III)-ibuprofen-loaded chitosan-based microparticles and nanoparticles systems: encapsulation, characterisation, anticancer activity of the nanoformulations against U87MG human glioma cells.

The aim of this work was to investigate novel formulations containing diruthenium(II-III)-ibuprofen (RuIbp) metallodrug encapsulated into the chitosan (CT) biopolymer. Microparticles (RuIbp/CT MPs, ∼ 1 µm) were prepared by spray-drying, and RuIbp/CT-crosslinked nanoparticles (NPs) by ionic gelation (RuIbp/CT-TPP, TPP = tripolyphosphate (1), RuIbp/CT-TPP-PEG, PEG = poly(ethyleneglycol (2)) or pre-gel/polyelectrolyte complex method (RuIbp/CT-ALG, ALG = alginate (3)). Ru analysis was conducted by energy dispersive x-ray fluorescence or inductively coupled plasma atomic emission spectroscopy, and physicochemical characterisation by powder x-ray diffraction, electronic absorption and FTIR spectroscopies, electrospray ionisation mass spectrometry, thermal analysis, scanning electron, transition electron and atomic force microscopies, and dynamic light scattering. The RuIbp-loaded nanosystems exhibited encapsulation efficiency ∼ 20-37%, drug loading∼ 10-20% (w/w), hydrodynamic diameter (nm): 103.2 ± 7.9 (1), 91.7 ± 12.6 (2), 270.2 ± 58.4 (3), zeta potential (mV): +(47.7 ± 2.8) (1), +(49.2 ± 3.6) (2), -(28.2 ± 2.0) (3). Nanoformulation (1) showed the highest cytotoxicity with increased efficacy in relation to the RuIbp free metallodrug against U87MG human glioma cells.

A novel µ-oxo-diruthenium(III,III)-ibuprofen-(4-aminopyridine) chloride derived from the diruthenium(II,III)-ibuprofen paddlewheel metallodrug shows anticancer properties.

Diruthenium(II,III) metal-metal multiply bonded paddlewheel complexes bearing non-steroidal anti-inflammatory drugs are promising anticancer metallodrugs. The [Ru2(Ibp)4Cl] (Ibp, ibuprofenate anion from HIbp ibuprofen drug), free or encapsulated, shows anticancer activity against glioblastoma (in vitro, in vivo), and against human breast and prostate cancer cells. Herein we report the interaction of [Ru2(Ibp)4Cl] and of [Ru2(Ac)4(H2O)2]PF6 (Ac, acetate) with the 4-aminopyridine (4Apy) drug. The N-ligand was capable of cleaving the paddlewheel unit with oxidation of Ru2(II,III) to Ru2(III,III)O µ-oxo core in the ibuprofen complex while the acetate complex underwent axial substitution of water by 4Apy. Carefully designed synthetic and chromatographic methods succeeded in giving the novel [Ru2O(Ibp)2(4Apy)6]Cl2 metallodrug, the first diruthenium(III,III) µ-oxo having chloride as counterion. Characterization was performed by elemental analysis, mass spectrometry, thermogravimetric analysis, electronic absorption and vibrational spectroscopies, molar conductivity and cyclic voltammetry. Kinetic studies for the µ-oxo complex (in 50:50 v/v ethanol:water) suggested an aquation/complexation equilibrium in consecutive step reactions with the exchange of the two 4Apy trans to the µ-oxo bridge by water (aquation) and the back coordination of 4Apy in excess of the N-ligand (complexation). Trypan blue assays for the novel compound showed time- and dose- dependent antiproliferative effects (at 5-50 µmol L-1) and cytotoxicity (> 20 µmol L-1), and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assays gave IC50 value of 7.6 ± 1.5 µmol L-1 (at 48 h, 1-20 µmol L-1) against U87MG human glioblastoma cells (aggressive brain glioma cancer) pointing the metallodrug as potential candidate for novel therapies in gliomas.

Aligning tumor mutational burden (TMB) quantification across diagnostic platforms: phase II of the Friends of Cancer Research TMB Harmonization Project.

BACKGROUND: Tumor mutational burden (TMB) measurements aid in identifying patients who are likely to benefit from immunotherapy; however, there is empirical variability across panel assays and factors contributing to this variability have not been comprehensively investigated. Identifying sources of variability can help facilitate comparability across different panel assays, which may aid in broader adoption of panel assays and development of clinical applications. MATERIALS AND METHODS: Twenty-nine tumor samples and 10 human-derived cell lines were processed and distributed to 16 laboratories; each used their own bioinformatics pipelines to calculate TMB and compare to whole exome results. Additionally, theoretical positive percent agreement (PPA) and negative percent agreement (NPA) of TMB were estimated. The impact of filtering pathogenic and germline variants on TMB estimates was assessed. Calibration curves specific to each panel assay were developed to facilitate translation of panel TMB values to whole exome sequencing (WES) TMB values. RESULTS: Panel sizes >667 Kb are necessary to maintain adequate PPA and NPA for calling TMB high versus TMB low across the range of cut-offs used in practice. Failure to filter out pathogenic variants when estimating panel TMB resulted in overestimating TMB relative to WES for all assays. Filtering out potential germline variants at >0% population minor allele frequency resulted in the strongest correlation to WES TMB. Application of a calibration approach derived from The Cancer Genome Atlas data, tailored to each panel assay, reduced the spread of panel TMB values around the WES TMB as reflected in lower root mean squared error (RMSE) for 26/29 (90%) of the clinical samples. CONCLUSIONS: Estimation of TMB varies across different panels, with panel size, gene content, and bioinformatics pipelines contributing to empirical variability. Statistical calibration can achieve more consistent results across panels and allows for comparison of TMB values across various panel assays. To promote reproducibility and comparability across assays, a software tool was developed and made publicly available.

Medical Interns and COVID-19: results of national research

SUMMARY OBJECTIVE Assess the impact of COVID-19 on medical students' internships in public and private institutions in Brasil, in addition to estimating the quality of the measures taken by their respective Universities in the face of the problem and the availability of personal protective equipment (PPE). METHODS A descriptive cross-sectional quantitative analysis study carried out with 317 students undergoing medical internship from March 31, 2020, to April 12, 2020. The survey was conducted through an online questionnaire using the SurveyMonkey tool with 20 questions. Interns from the fourth to the sixth year of medical schools in the country were randomly included in the study through a survey sent by Whatsapp application. Statistical analysis was performed using the Chi-Square, considering p <0.05 as significant. RESULTS Four main topics were identified in the research: student demographic data; how classes and courses are being taught; the use and ease of access to personal protective equipment and the students' fears and perspectives for the future. CONCLUSION The study clarified that although half of the students still have some degree of content and, in their majority, they are satisfied, there is still a lot of difficulty in obtaining personal protective equipment, which prevents students from returning safely to their internships.

RESUMO OBJETIVO Avaliar o impacto da Covid-19 durante o internato dos alunos de medicina em escolas públicas e particulares no Brasil, além de estimar a qualidade das medidas tomadas pelas respectivas universidades diante do agravo e da disponibilização de equipamento de proteção individual. MÉTODO Um estudo de análise quantitativa transversal, com caráter descritivo, foi realizado com 317 alunos cursando o internato médico durante o período de 31 de março de 2020 a 12 de abril de 2020. A pesquisa foi realizada por meio de um questionário on-line com 20 perguntas pela ferramenta SurveyMonkey. Os internos do 4o ao 6o ano das faculdades de medicina do País foram incluídos no estudo de forma randômica ao receberem a pesquisa pelo aplicativo WhatsApp. A análise estatística foi realizada por meio do Qui-quadrado, considerando p<0,05 como significante. RESULTADOS Quatro temas principais foram identificados na pesquisa: dados demográficos dos alunos; como as aulas e estágios do curso estão sendo ministrados; a utilização e facilidade de aquisição do equipamento de proteção individual e medos e perspectivas futuras dos estudantes. CONCLUSÕES O estudo mostrou que apesar de metade dos alunos continuarem tendo algum grau de conteúdo e, na maioria, estarem satisfeitos, ainda há muita dificuldade em se obter equipamento de proteção individual, o que impede que os alunos retornem com segurança aos seus campos de estágio, além de causar medo de contaminação e de continuar atendendo os pacientes.

The Potential for Plant-Based Diets to Promote Health Among Blacks Living in the United States.

Plant-based diets are associated with reduced risks of various chronic diseases in the general population. However, it is unclear how these benefits translate to Blacks living in the United States, who are disproportionately burdened with heart disease, cancer, diabetes, obesity, and chronic kidney disease. The objectives of this study were to: (1) review the general evidence of plant-based diets and health outcomes; (2) discuss how this evidence translates to Blacks following a plant-based diet; and (3) provide recommendations and considerations for future studies in this area. Interestingly, although the evidence supporting plant-based diets in the general population is robust, little research has been done on Blacks specifically. However, the available data suggests that following a plant-based diet may reduce the risk of heart disease and possibly cancer in this population. More research is needed on cardiovascular disease risk factors, cancer subtypes, and other chronic diseases. Further, attention must be given to the unique individual, familial, communal, and environmental needs that Blacks who follow plant-based diets may have. Interventions must be culturally appropriate in order to achieve long-term success, and providing low-cost, flavorful, and nutritious options will be important.

Neoplasmas cutâneos em cães: 656 casos (2007-2014) em Cuiabá, MT / Cutaneous neoplasms in dogs: 656 cases (2007-2014) from Cuiabá, MT

Os neoplasmas cutâneos em cães apresentam elevada e relevante prevalência em todo o Brasil. Sendo assim, objetivou-se determinar a frequência e algumas características epidemiológicas dos neoplasmas cutâneos em cães diagnosticados no Laboratório de Patologia da Universidade Federal de Mato Grosso (LPV-UFMT), Cuiabá, entre os anos de 2007 a 2014. Foram revisados os protocolos de necropsias e biopsias do LPV-UFMT, de cães com neoplasmas cutâneos. Dados referentes à idade, sexo, raça dos cães afetados, localização anatômica, tamanho, diagnóstico histomorfológico e comportamento biológico foram coletados e analisados através de uma análise estatística descritiva. Adicionalmente o teste χ2, foi utilizado para associações entre comportamento biológico e tamanho da massa. Dos 3566 exames realizados, 656 (18,4%) foram diagnosticados como tumores cutâneos sendo cães adultos e idosos das raças Pit Bull, Boxer e Poodle os mais acometidos. Dentre os 11 padrões morfológicos mais diagnosticados o mastocitoma, carcinoma de células escamosas (CCE) e os tumores de origem vascular foram os mais frequentemente relatados. Em relação ao sítio anatômico, a cabeça foi a mais acometida. A maioria dos tumores benignos apresentaram menos de 1cm de diâmetro e os malignos de 3 a 5cm. O aumento de neoplasmas em adultos e idosos pode estar relacionado ao somatório de danos causados por agentes carcinogênicos e o comprometimento imunológico.(AU)

Canine cutaneous neoplasms present high and relevant prevalence throughout Brazil. Here we determine the frequency and epidemiological characteristics of canine cutaneous neoplasms in dogs diagnosed at the Laboratory of Veterinary Pathology of the Federal University of Mato Grosso (LPV-UFMT), Cuiabá, from 2007 to 2014. The necropsy and biopsy protocols from canine cutaneous neoplasms diagnosed at the LPV-UFMT were reviewed. Data regarding age, sex, breed of affected dogs, anatomical location, size, histomorphological diagnosis and biological behavior of the tumors were evaluated through a descriptive statistical analysis. In addition, the χ2 test was used for associations between biological behavior and mass size. Of the 3566 examinations performed, 656 (18.4%) were diagnosed as cutaneous tumors being adult and old dogs of Pit Bull, Boxer and Poodle races most affected. Among the diagnoses, 11 morphological patterns were the most prevalent, being mastocytoma, squamous cell carcinoma (SCC) and tumors of vascular origin most frequently reported. In relation to the anatomical site, the head was the most affected. Most of the benign tumors were less than 1cm in diameter and the malignant were 3 to 5cm. The increase of neoplasms in adults and old age dogs may be associated to the sum of damage caused by carcinogenic agents and the immunological impairment.(AU)

Diruthenium(ii,iii) metallodrugs of ibuprofen and naproxen encapsulated in intravenously injectable polymer-lipid nanoparticles exhibit enhanced activity against breast and prostate cancer cells.

A unique class of diruthenium(ii,iii) metallodrugs containing non-steroidal anti-inflammatory drug (NSAID), Ru2(NSAID), have been reported to show anticancer activity in glioma models in vitro and in vivo. This work reports the encapsulation of the lead metallodrug of ibuprofen (HIbp), [Ru2(Ibp)4Cl] or RuIbp, and also of the new analogue of naproxen (HNpx), [Ru2(Npx)4Cl] or RuNpx, in novel intravenously (i.v.) injectable solid polymer-lipid nanoparticles (SPLNs). A rationally selected composition of lipids/polymers rendered nearly spherical Ru2(NSAID)-SPLNs with a mean size of 120 nm and zeta potential of about -20 mV. The Ru2(NSAID)-SPLNs are characterized by spectroscopic techniques and the composition in terms of ruthenium-drug species is analyzed by mass spectrometry. The metallodrug-loaded nanoparticles showed high drug loading (17-18%) with ∼100% drug loading efficiency, and good colloidal stability in serum at body temperature. Fluorescence-labeled SPLNs were taken up by the cancer cells in a time- and energy-dependent manner as analyzed by confocal microscopy and fluorescence spectrometry. The Ru2(NSAID)-SPLNs showed enhanced cytotoxicity (IC50 at 60-100 µmol L-1 ) in relation to the corresponding Ru2(NSAID) metallodrugs in breast (EMT6 and MDA-MB-231) and prostate (DU145) cancer cells in vitro. The cell viability of both metallodrug nanoformulations is also compared with those of the parent NSAIDs, HIbp and HNpx, and their corresponding NSAID-SPLNs. In vivo and ex vivo fluorescence imaging revealed good biodistribution and high tumor accumulation of fluorescence-labeled SPLNs following i.v. injection in an orthotopic breast tumor model. The enhanced anticancer activity of the metallodrug-loaded SPLNs in these cell lines can be associated with the advantages of the nanoformulations, assigned mainly to the stability of the colloidal nanoparticles suitable for i.v. injection and enhanced cellular uptake. The findings of this work encourage future in vivo efficacy studies to further exploit the potential of the novel Ru2(NSAID)-SPLN nanoformulations for clinical application.

Doenças de bovinos em Mato Grosso diagnosticadas no Laboratório de Patologia Veterinária da UFMT (2005-2014) / Cattle diseases in Mato Grosso diagnosed in the Veterinary Pathology Laboratory of UFMT (2005-2014)

Foi realizado um levantamento nos arquivos do Laboratório de Patologia Veterinária (LPV) da Universidade Federal de Mato Grosso (UFMT) das doenças de bovinos registradas entre os anos 2005 a 2014. Foram revisados 1124 casos. Destes, 27,6% foram amostras obtidas de necropsias realizadas por técnicos do LPV-UFMT e 72,3% foram amostras encaminhadas ao LPV-UFMT por veterinários de campo. Em 49,38% dos casos (555/1124) o diagnóstico da doença foi feito através da análise morfológica de lesões e/ou através de exames complementares. Raiva foi a principal causa de morte de bovinos neste estudo (7,82%). As doenças inflamatórias e parasitárias foram as mais prevalentes sendo diagnosticadas em 27,49% dos casos, seguida das doenças tóxicas e toxiinfecções com 9,78%. As demais categorias foram distribuídas em ordem decrescente em: neoplasmas e lesões tumoriformes (4%), doenças degenerativas (3,02%), distúrbios causados por agentes físicos (2,84%), distúrbios metabólicos e nutricionais (1,42%) e outras categorias (0,71%).(AU)

A survey was conducted on files of the Veterinary Pathology Laboratory (LPV), Federal University of Mato Grosso (UFMT), about cattle disease recorded during the years 2005 to 2014. From a total of 1124 reviewed cases, 27.6% were samples obtained from autopsies performed by technicians of the LPV-UFMT, and 72.3% were samples sent to LPV-UFMT by field veterinarians. In 49.38% of cases (555/1124) the diagnosis of the disease was made by morphological analysis of lesions and/or through additional tests. Rabies was the major cause of death in cattle in this study (7.82%). Inflammatory and parasitic disease was the most prevalent category diagnosed with 27.49% of cases, followed by toxicoses and toxinfections (9.78%). The other categories were distributed in descending order, as neoplasms and tumor-like lesions (4%), degenerative diseases (3.02%), disorders caused by physical agents (2.84%), metabolic and nutritional disorders (1.42%), and other categories (0.71%).(AU)

Avaliação dos métodos de otoscopia e exame do swab parasitológico no diagnóstico da otocariose canina: uma abordagem bayesiana / Evaluation of methods of the otoscopy and parasitological swab in diagnosis of canine otocariose: a bayes analysis

Ácaros do gênero Otodectes são parasitos encontrados frequentemente no ouvido de cães e gatos, sendo reconhecidos como os principais causadores de otite externa nesses animais. Trezentos e vinte cães, oriundos do município de Cuiabá, Mato Grosso, foram examinados através da otoscopia e do exame do swab parasitológico, com o objetivo de avaliar, através da análise bayesiana para a estimativa da prevalência, sensibilidade e especificidade destes métodos no diagnóstico da infestação causada pelo ácaro utilizando-se de dados a priori informativos e não informativos. Cada animal foi considerado uma unidade experimental. Do total de cães examinados, 142 (44,37%) apresentaram-se positivos para otocariose. Em 100 animais (31,25%) a infestação foi diagnosticada pelos dois métodos, em 31 (9,69%) apenas pelo exame do swab parasitológico, em 11 (3,44%) apenas pela otoscopia e em 178 (55,62%) animais o resultado foi negativo por ambos os métodos. A sensibilidade da otoscopia, quando comparada ao exame do swab parasitológico, foi considerada menor, a especificidade dos testes, porém, não difere estatisticamente. O modelo, a priori informativo, demonstrou ser o mais plausível e reduziu consideravelmente o intervalo de credibilidade das estimativas dos parâmetros. Conclui-se que a análise bayesiana é efetiva na estimativa da prevalência e características dos testes diagnósticos...

Mites of the genus Otodectes are parasites found frequently in the ear of dogs and cats, being recognized as the main causers of external otitis in these animals. Three hundred and twenty dogs, deriving of the city of Cuiabá, Mato Grosso, had been examined through the otoscopy and of the examination of parasitological swab, with the objective to evaluate through the bayes'analysis for the estimate of the prevalence, sensitivity and especificity of these methods in the diagnosis of the infestation caused for the mite, using dates informative and not informative a priori. Each animal was considered an experimental unit. Of the total of examined dogs, 142 (44.37%) had been presented positive for otocariosis. In 100 animals (31.25%) the infestation was diagnosed by the two methods, in 31 (9.69%) only for the examination of parasitological swab, in 11 (3.44%) only for the otoscopy and in 178 (55.62%) animal the result was negative for both the methods. The sensitivity of the otoscopy, when compared with the examination of parasitological swab, was considered lesser, however the especificity of tests they do not differ. The informative model with priori it demonstrated to be most reasonable and considerably reduced the interval of credibility of the estimates of the parameters. It can be concluded that Bayes'analysis is effective in the estimation of prevalence and characteristics of the diagnostic tests...

Vitamin A supplementation leads to increases in regulatory CD4+Foxp3+LAP+ T cells in mice.

Dietary compounds, including micronutrients such as vitamin A and its metabolite retinoic acid, directly influence the development and function of the immune system. In this study, we show that either dietary deficiency of or supplementation with vitamin A had immunologic effects in mice that were fed these diets during their development (for 8 wk during the postweaning period). Deficient mice presented higher levels of interferon-γ, interleukin (IL)-6, transforming growth factor-ß, IL-17, and IL-10 in the gut-associated lymphoid tissues and draining lymph nodes, indicating a proinflammatory shift in the gut mucosa. Serum immunoglobulin G levels also were elevated in these mice. Conversely, supplemented mice showed higher frequencies of CD4+Foxp3+LAP+ regulatory T cells in gut lymphoid tissues and spleen, suggesting that vitamin A supplementation in the diet may be beneficial in pathologic situations such as inflammatory bowel diseases.

Polysaccharide fraction isolated from Passiflora edulis inhibits the inflammatory response and the oxidative stress in mice.

OBJECTIVES: The aim of the study was to investigate the anti-inflammatory, antioxidant and antinociceptive actions of PFPe, a polysaccharide fraction isolated from the dried fruit of the Passiflora edulis. METHODS: Animals were pretreated with PFPe (0.3, 1 or 3 mg/kg, i.p.) 1 h before induction of paw oedema by carrageenan, histamine, serotonin, compound 48/80 or prostaglandin E2 (PGE2). Neutrophil migration and vascular permeability were measured after carrageenan injection into the peritoneum, and the action of the PFPe on the tumour necrosis factor-alpha, interleukin-1 beta (IL-1ß), myeloperoxidase (MPO), glutathione (GSH) and malondialdehyde (MDA) levels was also evaluated. To assay nociception, we examined acetic acid-induced writhing, formalin-induced paw licking and response latency in the hot plate test. KEY FINDINGS: Pretreatment with PFPe significantly inhibited carrageenan-induced paw oedema. PFPe also reduced paw oedema induced by compound 48/80, histamine, serotonin, and PGE2 and compound 48/80-induced vascular permeability. In addition, PFPe significantly reduced the MPO activity, MDA and GSH concentrations, and IL-1ß level. In the nociception tests, PFPe reduced acetic acid-induced writhing and formalin-induced paw licking and did not increase the response latency time. CONCLUSIONS: Our results suggest that PFPe administration reduces the inflammatory response by modulation of the liberation or synthesis of histamine and serotonin, by reduction of neutrophil migration, IL-1ß levels, and oxidative stress and nociception.

Riparin A, a compound from Aniba riparia, attenuate the inflammatory response by modulation of neutrophil migration.

Inflammation is a local tissue response to attacks characterized by vascular and cellular events, including intense oxidative stress. Riparin A, a compound obtained from Aniba riparia, has been shown to have antioxidant activity and cytotoxicity in vitro. This study was aimed at evaluating the anti-inflammatory effect of riparin A against acute inflammation. The results of our evaluations in various experimental models indicated that riparin A reduced paw edema induced by carrageenan, compound 48/80, histamine, and serotonin. Furthermore, it decreased leukocyte and neutrophil counts, myeloperoxidase activity, thiobarbituric acid reactive substance (TBARS) levels, and cytokine (tumor necrosis factor-α and interleukin-1ß) levels increased by carrageenan-induced peritonitis, and reversed glutathione levels. Riparin A also reduced carrageenan-induced adhesion and rolling of leukocytes on epithelial cells and did not produce gastric-damage as compared with indomethacin. In conclusion, the data show that riparin A reduces inflammatory response by inhibiting vascular and cellular events, modulating neutrophil migration, inhibiting proinflammatory cytokine production, and reducing oxidative stress.

Preparation and cytotoxicity of N,N,N-trimethyl chitosan/alginate beads containing gold nanoparticles.

Polyelectrolyte complex beads based on N,N,N-trimethyl chitosan (TMC) and sodium alginate (ALG) were obtained. This biomaterial was characterised by FTIR, TGA/DTG, DSC and SEM analysis. The good properties of polyelectrolyte complex hydrogel beads were associated, for the first time, with gold nanoparticles (AuNPs). Through a straightforward methodology, AuNPs were encapsulated into the beads. The in vitro cytotoxicity assays on the Caco-2 colon cancer cells and healthy VERO cells showed that the beads presented good biocompatibility on both cell lines, whereas the beads loaded with gold nanoparticles (beads/AuNPs) was slightly cytotoxic on the Caco-2 and VERO cells.

Perfil sanguíneo e peso de órgãos internos de bezerros leiteiros criados em diferentes sistemas de aleitamento / Blood profile and weight of internal organs of dairy calves in different nursing systems

Objetivou-se avaliar o perfil sanguíneo e o tamanho absoluto e relativo dos órgãos internos de bezerros em sistema de aleitamento convencional ou fracionado. Foram utilizadas 10 fêmeas, com peso corporal inicial médio de 37,53 kg (±2,36) e 12 machos com peso corporal médio de 81,6 kg (±8,6), ambos da raça Holandesa. O aleitamento convencional constituiu-se de quatro litros de leite fornecidos diariamente durante 54 dias de avaliação e o fracionado, de seis litros do 6º ao 25º dias de idade, quatro litros do 26º ao 45º dias de idade e dois litros do 46º ao 59º dias de idade, além de concentrado, feno de Cynodon sp., água e suplemento mineral fornecidos ad libitum. O delineamento experimental foi inteiramente ao acaso, com cinco repetições para os parâmetros sanguíneos e seis repetições para o desenvolvimento dos órgãos internos. As coletas de sangue foram realizadas nas fêmeas nos dias sete, 21, 28, 42, 49 e 56 de idade. Para a avaliação dos órgãos internos os machos foram abatidos aos dois meses de idade, após jejum de 16 horas. Não foram observadas diferenças para os valores de proteínas totais, albumina, globulina, creatinina, ureia, colesterol e β-hidroxibutirato nas idades avaliadas (p>0,05). Entretanto, para a concentração de glicose houve interação entre os sistemas de aleitamento e os períodos avaliados, podendo ser observado que com 21 dias de idade a concentração foi maior nas bezerras mantidas em sistema fracionado, quando comparadas aos animais do grupo convencional. O sistema de aleitamento não alterou o peso corporal final, peso corporal final vazio e o peso dos órgãos internos, exceto para o coração, demonstrando que o sistema de aleitamento fracionado não altera as avaliações dos órgãos internos...

The objective was to evaluate the blood profile together with the relative and absolute size of the internal organs of calves in conventional or fractionated feeding system. Ten females were used, with an average initial body weight of 37.53 kg (±2.36), and 12 males with a mean body weight of 81.6 kg (±8.6), both Holstein breed. The conventional feeding consisted of four liter milk supplied daily for 54 days of evaluation, and fractioned six liter milk was given from 6 to 25 days of age, four liter from 26 to 45 days of ager, and two liter from 46 to 59 days of age. Cynodon sp. hay, water and mineral supplement was provided ad libitum. The experimental design was completely randomized with five replicates for blood parameters and six replicates for the development of internal organs. Blood collections were performed in females on days seven, 21, 28, 42, 49 and 56 of age. For the evaluation of internal organs males were slaughtered at two months of age, after 16 hours of fasting. No differences occurred in the values of total protein, albumin, globulin, creatinine, urea, cholesterol and β-hydroxybutyrate in ages evaluated (p>0.05). However, for the concentration of glucose no interaction was found between lactation systems and periods evaluated. It can be noted that at 21 days of age the concentration was higher in calves kept in the fractionated system, when compared with animals of the conventional group. The feeding system did not affect the final body weight, the empty body weight or the weight of the internal organs, except for the heart, demonstrating that the fractional feeding system does not alter the assessment of the internal organs...

Phytol, a diterpene alcohol, inhibits the inflammatory response by reducing cytokine production and oxidative stress.

Studies have shown that diterpenes have anti-inflammatory and redox-protective pharmacological activities. The present study aimed to investigate the anti-inflammatory properties of phytol, a diterpene alcohol, in a mouse model of acute inflammation, and phytol effect on leukocyte recruitment, cytokines levels, and oxidative stress. The anti-inflammatory activities of phytol were assessed by measuring paw edema induced by different inflammatory agents (e.g., λ-carrageenan, compound 48/80, histamine, serotonin, bradykinin, and prostaglandin E2 [PGE2 ]), myeloperoxidase (MPO) activity, peritonitis model and cytokine levels. Further, oxidative stress was evaluated by determining glutathione (GSH) levels and malondialdehyde (MDA) concentration. The results showed that phytol (7.5, 25, 50, and 75 mg/kg) significantly reduced carrageenan-induced paw edema, in a dose-dependent manner. In addition, phytol (75 mg/kg) inhibited compound 48/80-, histamine-, serotonin-, bradykinin- and PGE2 -induced paw edema. It also inhibited the recruitment of total leukocytes and neutrophils; decreased MPO activity, tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels, and MDA concentration; and increased GSH levels during carrageenan-induced acute inflammation. These results suggest that phytol attenuates the inflammatory response by inhibiting neutrophil migration that is partly caused by reduction in IL-1ß and TNF-α levels and oxidative stress.

Anti-inflammatory and antinociceptive activity of epiisopiloturine, an imidazole alkaloid isolated from Pilocarpus microphyllus.

The aim of this study was to investigate the antinociceptive and anti-inflammatory activities of epiisopiloturine (1), an imidazole alkaloid found in the leaves of Pilocarpus microphyllus. The anti-inflammatory activity of 1 was evaluated using several agents that induce paw edema and peritonitis in Swiss mice. Paw tissue and peritoneal fluid samples were obtained to determine myeloperoxidase (MPO) activity or tumor necrosis factor (TNF)-α and interleukin (IL)-1ß levels. The antinociceptive activity was evaluated by acetic acid-induced writhing, the hot plate test, and pain induction using formalin. Compared to vehicle treatment, pretreatment with 1 (0.1, 0.3, and 1 mg/kg, ip) of mice significantly reduced carrageenan-induced paw edema (p < 0.05). Furthermore, compound 1 at a dose of 1 mg/kg effectively inhibited edema induced by dextran sulfate, serotonin, and bradykinin, but had no effect on histamine-induced edema. The administration of 1 (1 mg/kg) following carrageenan-induced peritonitis reduced total and differential peritoneal leukocyte counts and also carrageenan-induced paw MPO activity and TNF-α and IL-1ß levels in the peritoneal cavity. Pretreatment with 1 also reduced acetic acid-induced writhing and inhibited the first and second phases of the formalin test, but did not alter response latency in the hot plate test. Pretreatment with naloxone reversed the antinociceptive effect of 1.

Role of the NO/K ATP pathway in the protective effect of a sulfated-polysaccharide fraction from the algae Hypnea musciformis against ethanol-induced gastric damage in mice

Seaweeds are the most abundant source of polysaccharides such as alginates and agar, as well as carrageenans. This study aimed to investigate the gastroprotective activity and the mechanism underlying this activity of a sulfated-polysaccharide fraction extracted from the algae Hypnea musciformis (Wulfen) J.V. Lamour. (Gigartinales-Rhodophyta). Mice were treated with sulfated-polysaccharide fraction (3, 10, 30, and 90 mg/kg, p.o.) and, after 30 min, they were administered 50% ethanol (0.5 mL/25 g, p.o.). After 1 h, gastric damage was measured using a planimeter. In addition, samples of the stomach tissue were obtained for histopathological examination and for assays to determine the glutathione and malondialdehyde levels. Other groups of mice were pretreated with N G-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.), aminoguanidine (100 mg/kg, i.p.), or glibenclamide (10 mg/kg, i.p.). After 30 min to the aminoguanidine group and 1 h to the other groups, sulfated-polysaccharide fraction (30 mg/kg, p.o.) was administered and gastric damage was induced as described above. Sulfated-polysaccharide fraction prevented ethanol-induced gastric injury in a dose-dependent manner. However, treatment with L-NAME or glibenclamide reversed this gastroprotective effect. Administration of aminoguanidine did not influence the effect of sulfated-polysaccharide fraction. Our results suggest that sulfated-polysaccharide fraction exerts a protective effect against ethanol-induced gastric damage via activation of the NO/K ATP pathway.

Synthesis, characterization, and cytotoxicity of TMC-graft-poly(vinyl alcohol) copolymers.

N-trimethyl chitosan-graft-poly(vinyl alcohol) (TMC-g-PVA) copolymers were prepared. The grafting reactions were conducted in water changing the feed ratios of poly(vinyl alcohol)/6-O-succinate-N-trimethyl chitosan (PVA/STMC). The structure of TMC-g-PVA copolymers was characterized through (1)H NMR spectroscopy, thermogravimetric analysis (TGA/DTG), wide-angle X-ray scattering (WAXS) and scanning electron microscopy (SEM). The quaternization degree (DQ) and substitution degree (DS) of N-trimethyl chitosan (TMC) and 6-O-succinate-N-trimethyl chitosan (STMC) were determined by (1)H NMR, being the spectroscopy 14.0 and 5.5mol-% found, respectively. The viability of HCT-116 cancerous cells was investigated at different concentrations. The effect of PVA/STMC ratios on the cytotoxicity of the TMC-g-PVA copolymers was examined and the CC50 values determined for every case.