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As modificações sociais se intensificaram após a revolução industrial, desde a modernização no meio tecnológico e econômico, baseado na transformação da matéria-prima em diversos bens de consumo, como riscos para a saúde humana, inclusive o risco físico denominado ruído ocupacional. O presente estudo tem como objetivo avaliar as perdas auditivas induzidas por ruído, assim como a incidência de efeitos extra-auditivos baseando-se na apreciação dos exames e anamneses realizadas no período de junho de 2011 a junho de 2021, em trabalhadores com audição normal na admissão, com pelo menos cinco anos de atividade laboral, sendo homens e mulheres de duas madeireiras do Oeste de Santa Catarina. Os resultados de avaliação dos prontuários dos trabalhadores indicam positivamente para ambas as empresas desencadeamentos e agravamentos de Perda Auditiva Induzida por Ruído Ocupacional (PAIRO) desde a admissão com associação diversas patologias extra-auditivas incluindo primordialmente casos de hipertensão e diabetes, assim como com sintomas dos mais diferentes aspectos auditivos e extra-auditivos (dores de cabeça, insônia, zumbido, vertigem e disacusia). Relacionando com outros hábitos de vida observa-se que a maioria dos trabalhadores com alterações possuem mais de 35 anos de idade, mais de nove anos de atividade laboral exposta a ruídos, uso de medicamento contínuo para patologias diversas, tabagismo, exposição a ruídos não ocupacionais (competição de som automotivo, atividades de lazer entre outros). No que se refere a observação dos Programas de Conservação Auditiva estes não foram implantados em nenhuma das empresas, apenas segue-se a rotina de exames ocupacionais conforme previsto na NR- 7, além de pequenos treinamentos e visitas técnicas por parte de técnicos de segurança do trabalho em âmbito laboral. Com isso, verifica-se a necessidade de transformação deste estudo em artigo científico para que a cada dia a visão tecnicista na saúde do trabalhador migre para uma ótica integral do indivíduo que trabalha em ambiente ruidoso, e para que possamos trabalhar diretamente na área de prevenção de perdas auditivas junto ao setor madeireiro estudado.

The gastric healing and gastric ulcer recurrence preventive effect of Lupeol Stearate (LS) was measured in this study. To evaluate the gastric healing effect, rats were submitted to the 80% acetic acid-induced ulcer model and treated with vehicle (1 ml/kg, p.o.), LS (1 mg/kg, p.o.) or omeprazole (20 mg/kg, p.o.) twice a day for seven days. The gastric injury was evaluated macroscopically, histologically and histochemical; and biochemical parameters were also quantified. To evaluate the effects of LS on gastric ulcer recurrence, mice were ulcerated by gastric instillation of 10% acetic acid and treated with vehicle (1 ml/kg, p.o.), LS (1 mg/kg, p.o.) or ranitidine (20 mg/kg, p.o.) twice a day for ten days. Then, the ulcer recurrence in these animals was induced by IL- 1β (1 µg/kg i.p) at five day after the end of the treatment period. The area of the lesion recurred were measured, as well as the activity of myeloperoxidase and TNF levels. Oral treatment with LS accelerated gastric healing by 63% compared to the group treated with vehicle, which was also evidenced by histological improvement and increased production of mucin in the gastric epithelium. LS elevated the activity of the glutathione S-transferase and reduced the activity of myeloperoxidase, but did not change the levels of reduced glutathione or the activity of superoxide dismutase and catalase at the ulcer site in rats. Regarding the recurrence, the LS treatment reduced the recurred lesions, reducing MPO activity but not TNF levels at ulcer site. It can be concluded that LS promotes the healing of gastric lesions by favoring the mucus production and reducing the migration of neutrophils and that it can reduce the severity of the ulcer recurrence.

A infecção pelo Papilomavirus Humano (HPV) é um problema de saúde pública associado ao câncer de colo do útero, principalmente em países em desenvolvimento. Diante da complexidade de fatores que podem estar associados à progressão da doença, objetivou-se realizar uma revisão integrativa que sintetize os principais fatores de risco. A análise dos artigos selecionados mostra que os principais fatores de risco para a infecção pelo HPV são o uso prolongado de método contraceptivo hormonal, início precoce da atividade sexual, múltiplos parceiros ao longo da vida e a associação destes fatores ao tabagismo. Além disso, uma dieta pobre em antioxidantes e com alto grau glicêmico, tabagismo e doença intestinal inflamatória, são determinantes na evolução de pacientes HPV positivas para lesões de colo do útero, incluindo o câncer.

Este é um estudo descritivo, retrospectivo, transversal e quantitativo, realizado em 2019 através da análise dos prontuários das pessoas privadas de liberdade no município de Caçador–SC, com objetivo de analisar as condições de saúde da população carcerária. Coletaram-se dados sociodemográficos, histórico de hábitos e vícios, doenças, uso de medicamentos, realização de teste rápido e consultas médicas. A análise se deu por estatística descritiva e ocorreu através do teste de Qui-quadrado. Considerou-se prontuários de 266 detentos (com superlotação), sendo: maioria do sexo masculino (96,24%); 20 a 39 anos (72,26%); pardos (48,04%) e brancos (44,53%); desempregados (45,7%); solteiros (61,57%), baixa escolaridade (52,94% até fundamental); uso de benzodiazepínicos (28,38%), uso de antidepressivos (18,02%) e de antipsicóticos (14,44%); consumo de tabaco (58,2%), seguido da maconha (44,53%); 95,31% dos homens e todas mulheres realizaram testes rápidos para hepatite B, sífilis e HIV no momento da admissão, e em dias subsequentes à entrada, tanto homens quanto mulheres, duas consultas médicas. O consumo de álcool, maconha e crack mostrou correlação com depressão. O contexto apresentado, mostra a necessidade de investimentos em políticas públicas para melhoria na prevenção de doenças e promoção da saúde de pessoas com privação de liberdade.

Glyphosate is one of the most widely used herbicides in Brazil and worldwide for controlling weeds in various agricultural crops, which raises concern on possible environmental impacts and human health. The present study aimed at assessing the induction of mutagenic changes and oxidative stress in different tissues of animals exposed to glyphosate and Trop®. Male Swiss mice were submitted to gavage treatment with glyphosate and Trop® at the concentrations of 50 and 200 mg/kg for 5 days. After the treatments the animals were euthanized and their bone marrow, liver, lung, and kidney were collected. The bone marrow was used for micronucleus. The liver, lung and kidney were submitted to biochemical analyzes of thiobarbituric acid reactive substances (TBARS), catalase enzyme, total antioxidant, in addition to evaluating the expression of Bax, Bcl2 and p53 proteins, as well as the expression of p53 gene transcription. The animals were weighed before and after the treatments. The results showed a significant weight reduction in the animals treated for 5 days. The occurrence of micronuclei was significant in the bone marrow. A significant increase in lipid peroxidation, besides changes in both, the catalase enzyme and total antioxidant levels were seen in all tissues. There was a decrease in p53 gene and Bax protein expression, and an increase of the Bcl2 protein expression. These results might suggest that the exposure to glyphosate and the consumption of antioxidant defenses can cause oxidative stress. In addition, changes in cellular biomarkers regarding glyphosate and Trop® were similar.

Introdução: A pandemia da COVID-19 afetou todo o sistema de saúde, uma das áreas que foi afetada foi a assistência ao pré-natal. Objetivo: o presente estudo buscou avaliar a influência da COVID-19 sobre a incidência de sífilis gestacional e a sua relação com o Índice de Desenvolvimento Humano (IDH) da Atenção Básica no estado de Santa Catarina. Método: foi analisado os casos de sífilis gestacional que foram notificados nas macrorregiões, microrregiões de saúde, além de alguns municípios polo de Santa Catarina. Foram analisados os dados disponíveis no Sistema de Informação de Agravos de Notificação (SINAN) disponibilizados pela Diretoria de Vigilância Epidemiológica de Santa Catarina (DIVE). Utilizaram-se as seguintes variáveis: ano de diagnóstico, macrorregião, microrregião e cidade. Também foi realizado um levantamento de dados referente ao IDH da atenção básica das cidades utilizadas para o estudo no Sistema de Indicadores de Desenvolvimento Municipal Sustentável. Resultados: A macrorregião da Grande Florianópolis apresentou a maior redução em 2020, 34,4% em comparação ao ano anterior. Das microrregiões, Xanxerê apresentou a maior redução (-42,5%). A região do Vale Itapoacu teve um aumento de 80%. O município polo de Florianópolis teve a maior redução (77%), Jaraguá do Sul apresentou o maior aumento 187%. Conclusão: houve uma diminuição no número de diagnósticos durante a pandemia. Em relação ao IDH da Atenção Básica, em alguns municípios, essa relação ficou evidente, em outros nem tanto. Também, levantou-se a hipótese de a cultura de algumas regiões podem ter impactado o segmento do pré-natal durante a pandemia.

The antimicrobial potential of cranberry hydro alcoholic extracts (CrE) was evaluated against Escherichia coli isolated from women with urinary tract infection (UTI). CrE was diluted based on the percentage of proanthocyanidins (PACs) in extract powder for final concentrations: 1.26%; 2.52%; 3.35%, 5.03% and 10.06%. CrE antimicrobial potential was evaluated by disk and well diffusion assays, and by in vitro direct action against E. coli. Antibacterial action was observed for all performed tests: minimal inhibitory concentration (MIC) was 1.26% PACs per disk diffusion assay and 2.52% of PACs by well diffusion assay. The in vitro antimicrobial direct action against E. coli resulted 3.8 Log10 cycles reduction for a concentration of 5.03% of PACs. One of the isolates showed multi resistance to antibiotics. But it was also inhibited more than any of the antibiotic tested in well diffusion assay. Only for concentrations 1.26%, 2.52% and 3.45% the inhibition of Escherichia coli by cranberry extract was dose-dependent, i.e directly proportional to the concentration of PACs. The results indicate a inhibitory action high potential of CrE. However, more in vitro and in vivo analysis can be performed to fix which the best concentration of CrE capable of causing a real beneficial effect on UTI´s.

O glifosato e um herbicida utilizado em varios tipos de culturas e e considerado de baixa toxicidade, no entanto, os mecanismos de toxicidade das formulacoes ainda nao estao bem esclarecidos. O objetivo do estudo foi avaliar os efeitos do Trop® e do glifosato sobre os parâmetros oxidativos, potencial genotoxico, funcao renal e hepatica, em animais submetidos ou nao ao tratamento com vitamina E. Utilizou-se camundongos Swiss machos albinos, divididos em nove grupos (n=8): Controle (salina); glifosato (50 e 500 mg/kg); Trop ® (50 e 500 mg/kg); Glifosato e vitamina E (20 e 200 mg/kg); Trop ® e vitamina E (20 e 200 mg/kg). O tratamento foi realizado em dose unica via oral. Apos 48 horas, os animais foram sacrificados o sangue e o figado coletados. O potencial genotoxico foi avaliado pela tecnica de micronucleos, a peroxidacao lipidica atraves das especies reativas ao acido tiobarbiturico (TBARS); a capacidade antioxidante pela concentracao de glutationa reduzida (GSH) e catalase (CAT); a funcao renal atraves das dosagens de ureia e creatinina e a funcao hepatica atraves das dosagens da Alanina-amino-transferase (ALT) e Aspartato-amino-transferase (AST). Os resultados mostram que nao houve um aumento no numero de micronucleos nos eritrocitos demonstrando assim que nao houve danos no DNA. Os niveis de TBARS e atividade da CAT teve aumento significativo em comparacao aos animais controle e reducao da GSH. Os valores de ureia e creatinina tiveram um aumento significativo quando os animais foram tratados com as doses de 500mg/Kg, no entanto, estes efeitos foram revertidos quando os animais foram tratados com combinacao de vitamina E 200 mg/Kg. As dosagens de AST e ALT nao evidenciaram alteracoes entre os grupos tratados. Os resultados mostram que uma exposicao unica ao glifosato pode causar dano oxidativo hepatico e alteracao na funcao renal que pode ser revertido pela administracao de anti-oxidantes em particular a vitamina E. Palavras-chave : Glifosato. Dano Oxidativo. Potencial Genotoxico. TROLOX OF PROTECTIVE ACTION FRONT OXIDATIVE DAMAGE INDUCED BY GLYPHOSATE AND TROP ® IN ANIMAL MODEL ABSTRACT: Glyphosate is an herbicide used in various types of cultures, considered to have low toxicity, however, the mechanisms of toxicity of the formulations are not wellunderstood. Theaim of the study was to evaluate the effects of Glyphosate on Trop ® and oxidative parameters, potential genotoxic an drenal function in animals submitted or not to treatment with vitamin E. Male albino Swiss mice were used divided into nine groups (n=8). The control group (saline); Glyphosate (50 and 500mg/kg); Trop ® (50 and 500mg/kg); Glyphosate + Vitamin E (20 and 200 mg/kg); Trop® + Vitamin E (20 and 200 mg/kg). Treatment was performed in a single oral dose, 48 hours after treatment the animals were sacrificed the blood and liver were collected. The genotoxic potential was assessed by micronucleus technique. The evaluation of lipid peroxidation was accomplished by determination of thiobarbituric acid reactive species (TBARS). The antioxidant status was evaluated by concentration of reduced glutathione (GSH) and the catalase (CAT) activity. The renal function was evaluated through the urea and creatinine dosages. The results show that there was not increase in the number of micronuclei in erythrocytes of the peripheral blood of animals treated with Glyphosate or Trop ® thus demonstrating that DNA damage has not occurred when animals were treated with the herbicide. However, the oxidative parameters were altered, the levels of TBARS and CAT activity had a significant increase compared to control animals and significantly reduced GSH. The values of urea and creatinine were significantly higher when animals were treated with doses of 500mg/Kg, however, these effects were reversed when the animals were treated with combination of vitamin E 200mg/Kg. The results show that even a single exposure to Glyphosate may cause hepatic oxidative and renal damage which can be reversed by the administration of antioxidants in particular vitamin E. Keywords: Glyphosate. Oxidative damage. Genotoxic potential.

© The Author(s)., [Background]: Trastuzumab-based therapies are the therapeutic option for HER2 positive (HER2+) breast cancer. HER2 amplification is the only biomarker validated for trastuzumab-based therapies. However, a proportion of tumors become refractory during treatment course. For this reason, the finding of new biomarkers beyond HER2 overexpression to identify patients who would benefit most from trastuzumab regimens is of outstanding importance., [Methods]: Models of trastuzumab-resistant or hypersensitive cells were generated by exposure to trastuzumab. Cell surface, total HER2, and analyses of proteins involved in cell cycle or apoptosis were analyzed by western blotting. Cell proliferation was analyzed by cell counting, cell cycle and apoptosis was evaluated by FACS. Transcriptomic characterization of the cellular models was performed using bioinformatic online tools, and clinico-genomic analyses were performed using the PAMELA clinical trial data., [Results]: Besides differing in sensitivities to trastuzumab, the different cellular models also showed distinct response to other anti-HER2 drugs (lapatinib, neratinib, pertuzumab and T-DM1) used in the clinic. That differential effect was not due to changes in cell surface, total or activated HER2. Trastuzumab caused important induction of cell death in hypersensitive cells but not in parental or resistant cells. Transcriptomic analyses of these cellular models together with querying of online databases allowed the identification of individual genes and gene signatures that predicted prognosis and trastuzumab response in HER2+ breast cancer patients., [Conclusion]: The identification of trastuzumab response biomarkers may be used to select patients particularly sensitive to facilitate the use of trastuzumab-based therapies and refine follow-up guidelines in patients with HER2+ tumors., A Pandiella: Ministry of Economy and Competitiveness of Spain (BFU2015–71371-R), the Junta de Castilla y León (CSI146P20), the Instituto de Salud Carlos III through CIBERONC, the Scientific Foundation of the Spanish Association Against Cancer (AECC), ALMOM, ACMUMA and the CRIS Cancer Foundation. LDG is recipient of a predoctoral contract of the Consejería de Educación of the Castilla y León Autonomous Government. Work carried out in our laboratory receives support from the European Community through the Regional Development Funding Program (FEDER). FBM: Fundación Científica Asociación Española Contra el Cáncer AECC_Postdoctoral17–1062

Trata-se de uma revisão sistemática que objetivou identificar quais instrumentos são utilizados para avaliar a qualidade de vida (QV) de portadores da Doença de Alzheimer (DA). A DA é uma doença crônica, progressiva e neurodegenerativa comum em pessoas idosas e sua prevalência está aumentando devido aumento da expectativa de vida. Os processos patológicos decorrentes da progressão da patologia podem gerar profundas inabilidades e fragilidades afetando dimensões afetivas, psíquicas e funcionais que intensificam o comprometimento da QV, pois comprometem a adaptação psicossocial e a interação do idoso com o ambiente. A avaliação da QV de idosos comprometidos cognitivamente apresenta uma série de desafios, até porque questões sobre a capacidade destas pessoas com declínio cognitivo fazerem julgamentos subjetivos e sobre a partir de qual ponto elas se tornam incapazes de fazê-los, podem também ser levantadas, já que as variações nos déficits de memória, atenção, julgamento e comunicação influenciam a habilidade destes indivíduos compreenderem questões ou comunicarem seus estados subjetivos. Concluiu-se que o atualmente o instrumento mais fidedigno e inclusive mais utilizado para avaliar a qualidade de vida de portadores da Doença de Alzheimer é o QdV-DA.

Theorical framework: Hepatocellular carcinoma is a unique cancer that typically arises in the setting of chronic liver disease at a rate dependent upon the complex interplay between the host, disease, and environmental factors. Unfortunately, with contemporary management, patients with advanced hepatocellular carcinoma have few treatment options, and the prognosis is poor. Objective: Evaluate the role of antioxidants in the treatment of hepatocellular carcinoma. Methodology: It is an integrative review, with a qualitative approach. Based on research on ScienceDirect and PubMed databases, 12 articles were selected that were consistent with the theme and the inclusion and exclusion criteria, through the association of descriptors and keywords. Results: Studies in vivo demonstrated a positive correlation of antioxidants in the treatment of hepatocellular carcinoma. The antioxidants were able to promote inhibition of development tumor through promotes decrease of proinflammatory cytokines IL-1 and IL-6 and changes the ratios of Bax/Bcl2 that supports apoptosis. In oxidative stress, may be able to direct free radical scavenging activity. Among the main antioxidants with advanced preclinical evidence in the treatment of hepatocellular carcinoma is curcumin with tests in humans, and gallic acid, quercetin and resveratrol with several tests in vitro and in vivo. Conclusion: This study highlights that antioxidants can be a promising therapy in the treatment of hepatocellular carcinoma. Marco teórico: el carcinoma hepatocelular es un cáncer singular que suele surgir en el context de una enfermedad hepatica crónica dependiente de la interacción entre el huésped, los factores ambientales y la capacidad de desarrolar la enfermedad. Desafortunadamente, con el tratamiento actual, los pacientes con carcinoma hepatocelular Avanzado tienen pocas opciones de tratamiento y el pronóstico es malo. Objetivo: evaluar el papel de los antioxidantes en el tratamiento del carcinoma hepatocelular. Metodología: se trata de una revision integradora, con enfoque cualitativo. A partir de búsquedas en las bases de datos ScienceDirect y PubMed, se seleccionaron 12 artículos que fueron consistentes con la temática y los criterios de inclusion y exclusion, mediante la asociación de descriptors y palabras clave. Resultados: Los estudios realizados in vivo han demonstrado una correlación positiva en el uso de antioxidantes en el tratamiento del carcinoma hepatocelular. Los antioxidantes fueron capaces de promover la inhibición del desarrollo tumoral al disminuir las citocinas proinflamatorias IL-1 e IL-6 y alterar la relación entre Bax/Bcl2 que apoyan la apoptosis, además de dirigir la eliminación de especies reactivas. Entre los principals antioxidantes con evidencia preclínica avanzada en el tratamiento del carcinoma hepatocelular se encuentra la curcumina con pruebas en humanos, ácido gálico, quercetina y resveratrol con varias pruebas in vitro e in vivo. Conclusión: Este studio destaca que los antioxidantes pueden ser una terapia prometedora en el tratamiento del carcinoma hepatocelular. Marco teórico: o carcinoma hepatocelular é um câncer único que geralmente surge no contexto de doença hepática crônica dependente da interação entre hospedeiro, fatores ambientais e a capacidade de desenvolvimento da doença. Infelizmente, com o manejo contemporâneo, os pacientes com carcinoma hepatocelular avançado tem poucas opções de tratamento, e o prognóstico é ruim. Objetivo: avaliar o papel dos antioxidants no tratamento do carcinoma hepatocelular. Metodologia: trata-se de uma revisão integrativa, com abordagem qualitativa. Com base em pesquisas nas bases de dados ScienceDirect e PubMed, foram selecionados 12 artigos que foram consistentes com o tema e os critérios de inclusão e exclusão, por meio da associação de descritores e palavras-chave. Resultados: Estudos realizados in vivo demonstraram uma correlação positiva no uso de antioxidantes no tratamento do carcinoma hepatocelular. Os antioxidantes foram capazes de promover a inibição do desenvolvimento tumoral diminuíndo as citocinas pró-inflamatórias IL-1 e IL-6 e alterando a relação entre Bax/Bcl2 que suportam a apoptose, além de direcionar a eliminação de espécies reativas. Entre os principais antioxidantes com evidências pré-clínicas avançadas no tratamento do carcinoma hepatocelular está a curcumina com testes em humanos, o ácido gálico, quercetina e resveratrol com vários testes in vitro e in vivo. Conclusão: Este estudo destaca que os antioxidantes podem ser uma terapia promissora no tratamento do carcinoma hepatocelular.

Acne vulgaris (AV), a severe chronic inflammatory dermatosis, commonly treated with systemic or topical antibiotics that exacerbate bacterial resistance and pose adverse side effects, new approaches for suppressing or reducing Propionibacterium acnes-induced inflammatory responses and thereby treating AV remain necessary. In response, the goal of our study was to investigate the therapeutic potential of phenolic compounds in the in vivo inflammatory process induced by P. acnes. Mice were intradermally challenged with a suspension containing 1.0 × 107 CFU/mL of P. acnes per ear, after which groups of mice were variously treated with 20 μg of resveratrol, quercetin, gallic acid, or benzoyl peroxide. Mice ears were measured (mm) before each inducement and treatment. At the end of the experiment, activity catalase and superoxide dismutase, levels of myeloperoxidase (MPO), interleukin-1 beta (IL-1β), tumor necrosis factor alpha, thiobarbituric acid reactive substances (TBARS), and glutathione were evaluated. Mice treated with resveratrol, quercetin, or gallic acid produced a 40%, 40%, and 30% reduction of the edema, respectively, while mice treated with resveratrol or gallic acid produced a 50 and 45% reduction in IL-1β, also respectively, and a 35% reduction in MPO. Compared to mice in the control group (210 ± 21 μmol/mg protein) and ones treated with benzoyl peroxide (339.7 ± 21.3 μmol/mg protein), mice treated with resveratrol, quercetin, or gallic acid showed low levels of TBARS (71 ± 12 μmol/mg, 62 ± 10 μmol/mg, and 104 ± 15 μmol/mg protein, respectively). Such results suggest that phenolic compounds are a good alternative for the development of cosmetics that can be used to treat AV.

Metastasis is the main cause of cancer-related death and requires the development of effective treatments with reduced toxicity and effective anticancer activity. Gallic acid derivatives have shown significant biological properties including antitumoral activity as shown in a previous study with octyl gallate (G8) in vitro. Thus, the aim of this work was to evaluate the antimetastatic effect of free and solid lipid nanoparticle-loaded G8 in mice in a lung metastasis model. Animals inoculated with melanoma cells presented metastasis in lungs, which was significantly inhibited by treatment with G8 and solid lipid nanoparticle-loaded G8, named G8-NVM. However, G8-treated mice showed an increase in several toxicological parameters, which were almost completely circumvented by G8-NVM treatment. This study supports the need for pharmacological studies on new potential medicinal plants to treat cancer and can provide new perspectives on using nanotechnology to improve biological activities while decreasing the chemotherapy toxicological effects of anticancer drugs.

Gallic acid (3,4,5-trihydroxybenzoic acid, GA), a natural phenolic acid has been reported as a strong antioxidant. Therefore the present study was designed to evaluate the effects of GA and dodecyl gallate (DGA) against acute and chronic carbon tetrachloride (CCl4)-induced hepatotoxicity. For acute model, rats were orally treated with GA and DGA for 7 d prior to CCl4 by intraperitoneally (i.p.) injection. For the chronic model, rats were orally treated with GA or DGA and CCl4 i.p. twice a week for four weeks. In both acute and chronic models, the CCl4-treated groups showed significantly increase in serum hepatic enzyme activities and histopathologic alterations, as well as a disruption in antioxidative status. In contrast, the treatment with GA and DGA restored serum hepatic enzymes activities, improved histopathologic alterations, increased glutathione (GSH) and decreased lipid peroxidation levels. The activities of liver antioxidant enzymes were increased by GA and DGA only in acute model. The expression of p53 gene increased about 3.5 times after GA and DGA treatments, which could result in cell death of damaged hepatocytes preventing of a lifelong liver failure. Thus, these results suggest that GA and DGA has the potential to prevent liver damages as the case of fibrosis condition.

Titanium dioxide nanoparticles (TiO2 NP) are present in several daily use products, and the risks associated with their bioaccumulation must be stablished. Thus, an evaluation of several toxicological-related effects was conducted after intraperitoneal injection of TiO2 NPs in mice. Mice were divided into two groups, which received 2 mg kg−1 day−1 of TiO2 NPs or vehicle saline. Assessments of body and organ weight as well as biochemical, hematological, and histopathological analyses were performed in order to evaluate adverse effects. The results showed that treatment resulted in an increased visceral and abdominal fat deposition, as well as a mononuclear inflammatory infiltrates in the abdominal fat tissue. The TiO2 NPs induced significant decrease in the weight gain and splenomegaly. Additionally, TiO2 NP-treated mice showed altered hematological parameters and significant liver injuries, which were characterized by histopathological and biochemical changes. Our results also indicated that TiO2 NPs were absorbed and significantly accumulated in the spleen, liver, and kidney. These results showed the ability of TiO2 NPs to infiltrate different organs and to induce inflammation and liver and spleen damage with visceral fat accumulation. The data obtained are useful for the governmental authorities to legislate and implement regulations concerning the use and the production of this kind of material that might be hazardous to the living beings, as well as to the environment.

Superparamagnetic iron oxide nanoparticles (SPIONS) were synthesized by thermal decomposition of an organometallic precursor at high temperature and coated with a bi-layer composed of oleic acid and methoxy-polyethylene glycol-phospholipid. The formulations were named SPION-PEG350 and SPION-PEG2000. Transmission electron microscopy, X-ray diffraction and magnetic measurements show that the SPIONs are near-spherical, well-crystalline, and have high saturation magnetization and susceptibility. FTIR spectroscopy identifies the presence of oleic acid and of the conjugates mPEG for each sample. In vitro biocompatibility of SPIONS was investigated using three cell lines; up to 100μg/ml SPION-PEG350 showed non-toxicity, while SPION-PEG2000 showed no signal of toxicity even up to 200μg/ml. The uptake of SPIONS was detected using magnetization measurement, confocal and atomic force microscopy. SPION-PEG2000 presented the highest internalization capacity, which should be correlated with the mPEG chain size. The in vivo results suggested that SPION-PEG2000 administration in mice triggered liver and kidney injury. From the Clinical Editor The potential use of superparamagnetic iron oxide nanoparticles (SPIONS) in the clinical setting have been studied by many researchers. The authors synthesized two types of SPIONS here and investigated the physical properties and biological compatibility. The findings should provide more data on the design of SPIONS for clinical application in the future.

In this work in vivo experiments were conducted in order to characterize the biocompatibility of polyurethane nanoparticles (PU-NPs) after intraperitoneal (i.p.) and oral administration. Additionally, ex vivo assays were performed to assess human blood compatibility as well as in vitro assays to assess protein binding. Our results indicated that administration of three different concentrations of PU-NPs induced a significant increase in visceral fat accumulation after oral dosing. In addition, fat tissue of mice intraperitoneally treated with the highest concentration of nanoparticles showed diffuse mononuclear inflammatory infiltrate in the fat tissue. Histopathological assessment showed inflammatory infiltrate and hepatocyte vacuolization in the liver, inflammatory infiltration and vascular congestion in the lung and glomerular necrosis in the kidney. Hepatic enzymes related with liver function were significantly increased in both groups of mice treated with PU-NPs. The PU-NPs did not affect the human blood cells number as well as coagulation time but showed a susceptibility to bind in proteins commonly found in the blood stream. In addition, increased amounts of pro inflammatory cytokines in vivo, as well as ex vivo in human cells were observed. Further studies to establish the consequences of long-term exposure to PU-NPs are warranted.

Acne vulgaris (AV), a severe chronic inflammatory dermatosis, commonly treated with systemic or topical antibiotics that exacerbate bacterial resistance and pose adverse side effects, new approaches for suppressing or reducing Propionibacterium acnes-induced inflammatory responses and thereby treating AV remain necessary. In response, the goal of our study was to investigate the therapeutic potential of phenolic compounds in the in vivo inflammatory process induced by P. acnes. Mice were intradermally challenged with a suspension containing 1.0 × 10

Ilex paraguariensis A. St.- Hil., Aquifoliaceae, is a native species of subtropical and temperate regions of South America, whose leaves and steams are used to make tea and traditional infusions, such as chimarrão and tereré. These beverages are considered beneficial to health because of their physiological effects on the treatment of rheumatism, obesity, fatigue, fluid retention, hypertension and liver disorders. This study examined the effects of aqueous extract of I. paraguariensis leaves on the oxidative stress of rats fed a cafeteria diet. A total of 40 male Wistar rats were equally divided into four groups and fed distinct diets for 15 days: group C (rat chow and water), group E (rat chow and aqueous extract of I. paraguariensis), group CD (cafeteria diet and water) and group ED (cafeteria diet and aqueous extract of I. paraguariensis). Lipid peroxidation (TBARS), reduced glutathione (GSH) and catalase activity (CAT) were subsequently assessed. Brain and liver histological analyses were also carried out. The results showed that aqueous extract of I. paraguariensis was able to reverse the oxidative stress caused by the cafeteria diet on serum, as well as significantly reduce lipid peroxidation in liver and brain tissues. A significant increase in GSH levels in the brain of animals fed the cafeteria diet was observed. However, this effect was only observed in the liver of animals fed with rat chow. Therefore, the aqueous extract of I. paraguariensis has important effects on the modulation of antioxidant defenses and oxidative stress, possibly being beneficial to health after eating the cafeteria diet.

Solid lipid nanoparticles (SLNs) are an alternative drug delivery system compared to emulsions, liposomes and polymeric nanoparticles. Due to their unique sizes and properties, SLNs offer possibility to develop new therapeutic approaches. The ability to incorporate drugs into nanocarriers offers a new prototype in drug delivery that could be used for drug targeting. However, toxicity of these new formulations has not been investigated thus far. In this study, we carried out an in vivo toxicity study. For that mice were divided into three groups and treated intraperitoneally with triestearin-based SLNs (TN), natural wax-based SLNs (VN) or vehicle for 10 days. After that, necropsies, histopathological and hematological analysis, as well as hepatic and renal functions were performed. Our results indicated that both TN and VN were absorbed post-exposure and induced an inflammatory response in adipose tissue. However, histopathological analysis demonstrated the absence of toxicity in both treated groups. In addition, the body weights were similar among the groups and low toxicity was also indicated by the unchanged serum biochemical parameters. This study provides a preliminary data for toxicological studies of two different SLNs in long-term in vivo exposure. However, further studies should be conducted in order to investigate the inflammatory response in order to establish the safety of these SLNs.

The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been identified as a promising material for biomedical applications. These include as contrast agents for medical imaging, drug delivery and/or cancer cell treatment. The nanotoxicological profile of SPIONs has been investigated in different studies and the distribution of SPIONs in the human body has not been fully characterized. The aim of this study was to develop a physiologically-based pharmacokinetic (PBPK) model to predict the pharmacokinetics of SPIONs. The distribution and accumulation of SPIONs in organs were simulated taking into consideration their penetration through capillary walls and their active uptake by specialized macrophages in the liver, spleen and lungs. To estimate the kinetics of SPION uptake, a novel experimental approach using primary macrophages was developed. The murine PBPK model was validated against in vivo pharmacokinetic data, and accurately described accumulation in liver, spleen and lungs. After validation of the murine model, a similar PBPK approach was developed to simulate the distribution of SPIONs in humans. These data demonstrate the utility of PBPK modeling for estimating biodistribution of inorganic nanoparticles and represents an initial platform to provide computational prediction of nanoparticle pharmacokinetics. Fil: Henrique Silva, Adny. Universidade Federal de Santa Catarina; Brasil Fil: Lima, Enio Junior. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Vasquez Mansilla, Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Zysler, Roberto Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Mojica Pisciotti, Mary Luz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Comisión Nacional de Energía Atómica. Centro Atómico Bariloche; Argentina Fil: Locatelli, Claudriana. Universidade do Alto Vale do Rio do Peixe; Brasil. Universidade do Oeste de Santa Catarina; Brasil Fil: Kumar Reddy Rajoli, Rajith. University of Liverpool; Reino Unido Fil: Owen, Andrew. University of Liverpool; Reino Unido Fil: Creczynski Pasa, Tânia Beatriz. Universidade Federal de Santa Catarina; Brasil Fil: Siccardi, Marco. University of Liverpool; Reino Unido

Lipid nanoparticles have received considerable attention in the field of drug delivery, due their ability to incorporate lipophilic drugs and to allow controlled drug release. Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and nanoemulsion (NE) are three different lipid nanostructured systems presenting intrinsically physical properties, which have been widely studied in recent years. Despite the extensive applicability of lipid nanoparticles, the toxicity of these systems has not been sufficiently investigated thus far. It is generally believed that lipids are biocompatible. However, it is known that materials structured in nanoscale might have their intrinsic physicochemical properties modified. Thus, the aim of this study was to evaluate the cytotoxicity of these three nanoparticle systems. To this end, in vitro and in vivo toxicity studies were carried out. Our results indicate that nanoparticles containing the solid lipid GMS (SLN and NLC) induced an important cytotoxicity in vitro, but showed minimal toxicity in vivo--evidenced by the body weight analysis. The NE did not induce in vitro toxicity and did not induce body weight alteration. On the contrary, the SLN and NLC possibly induce an inflammatory process in vivo. All nanoparticle systems induced lipid peroxidation in the animals' livers, but only SLN and NLC induced a decrease of antioxidant defences indicating that the main mechanism of toxicity is the induction of oxidative stress in liver. The higher toxicity induced by SLN and NLC indicates that the solid lipid GMS could be the responsible for this effect. Nevertheless, this study provides important insights for toxicological studies of different lipid nanoparticles systems.

We evaluated the toxicity of hepatic, hematological, and oxidative effects of glyphosate-Roundup® on male and female albino Swiss mice. The animals were treated orally with either 50 or 500 mg/kg body weight of the herbicide, on a daily basis for a period of 15 days. Distilled water was used as control treatment. Samples of blood and hepatic tissue were collected at the end of the treatment. Hepatotoxicity was monitored by quantitative analysis of the serum enzymes ALT, AST, and γ-GT and renal toxicity by urea and creatinine. We also investigated liver tissues histopathologically. Alterations of hematological parameters were monitored by RBC, WBC, hemoglobin, hematocrit, MCV, MCH, and MCHC. TBARS (thiobarbituric acid reactive substances) and NPSH (non-protein thiols) were analyzed in the liver to assess oxidative damage. Significant increases in the levels of hepatic enzymes (ALT, AST, and γ-GT) were observed for both herbicide treatments, but no considerable differences were found by histological analysis. The hematological parameters showed significant alterations (500 mg/kg body weight) with reductions of RBC, hematocrit, and hemoglobin, together with a significant increase of MCV, in both sexes of mice. In males, there was an important increase in lipid peroxidation at both dosage levels, together with an NPSH decrease in the hepatic tissue, whereas in females significant changes in these parameters were observed only at the higher dose rate. The results of this study indicate that glyphosate-Roundup® can promote hematological and hepatic alterations, even at subacute exposure, which could be related to the induction of reactive oxygen species.

Malignant melanoma is a lethal disease, and the incidence and mortality associated with it are increasing worldwide. It has a significant tendency to develop both metastasis and resistance to chemotherapy. The tumor cells show abnormal redox regulation, and although the molecular mechanisms involved are not well characterized, they seem to be related to oxidative stress. In a previous study, we showed the antitumoral properties of gallic acid ester derivatives in leukemia cells. Here, we show the effect of octyl, decyl, dodecyl and tetradecyl gallates on B16F10 cells, a melanoma cell line. All compounds induced cytotoxic effects, and the IC(50) values obtained were between 7microM and 17microM after 48h of incubation. Cell death occurred through apoptosis, as demonstrated by the genomic DNA fragmentation pattern. The gallates were able to induce significant production of free radicals, deplete both glutathione and ATP, activate NF-kappaB and promote the inhibition of cell adhesion under the experimental conditions. The glutathione depletion induced by these compounds was related to the inhibition of gamma-glutamylcysteine synthase activity. These results suggest that gallates induce tumoral cell death through apoptosis as a consequence of oxidative stress, though they use different mechanisms to do so. These findings are important since melanoma cells are resistant to death because of their high level of antioxidant defense, adhesion capability and propensity to metastasize.

Gallic acid and gallates with the same number of hydroxyl groups and varying the length of the side carbon chain, with respective lipophilicity being defined through the ClogP values, were examined for their ability to induce apoptosis (through the DNA ladder fragmentation pattern), mitochondrial and cytoplasmic GSH depletion and NF-kappaB activation in murine lymphoblastic L1210 leukemia cells. A relationship between cytotoxic effect and a limited degree of lipophilicity was observed.

Several obstacles are encountered in conventional chemotherapy, such as drug toxicity and poor stability. Nanotechnology is envisioned as a strategy to overcome these effects and to improve anticancer therapy. Nanoemulsions comprise submicron emulsions composed of biocompatible lipids, and present a large surface area revealing interesting physical properties. Chalcones are flavonoid precursors, and have been studied as cytotoxic drugs for leukemia cells that induce cell death by different apoptosis pathways. In this study, we encapsulated chalcones in a nanoemulsion and compared their effect with the respective free compounds in leukemia and in non-tumoral cell lines, as well as in an in vivo model. Free and loaded-nanoemulsion chalcones induced a similar anti-leukemic effect. Free chalcones induced higher toxicity in VERO cells than chalcones-loaded nanoemulsions. Similar results were observed in vivo. Free chalcones induced a reduction in weight gain and liver injuries, evidenced by oxidative stress, as well as an inflammatory response. Considering the high toxicity and the side effects induced generally by all cancer chemotherapies, nanotechnology provides some options for improving patients’ life quality and/or increasing survival rates.

The current review presents the antitumoral properties of gallic acid and its ester derivatives. Numerous studies have indicated that the alkyl esters are more effective against tumor cell lines than gallic acid, and that this activity is related to their hydrophobic moiety. All related studies have shown that the antitumor activity is interconnected to the induction of apoptosis by different mechanisms and it depends on the cell type. The results presented in this review may help to emphasize that these compounds could be promising as a new alternative for the treatment of cancer, either alone or in combination with other antitumor drugs to potentiate their effects.

Malignant melanoma is a tumor that originates from the melanocytes and manifests mainly on the skin. Melanomas are usually strongly pigmented, however amelanotic forms have been observed. Relative to the tumor mass, melanomas have an early tendency to metastasize; the prognosis is therefore poor. Malignant melanoma is responsible for about 90% of skin cancer related mortality [1]. Several risk factors for the development of melanoma have been identi‐ fied. Ethnic origin is particularly important with a disease that mostly affects people of European origin. Epidemiological studies have shown that exposure to the sun, especially in childhood, is a major environmental cause of melanoma, and that up to 65% of the cases of melanoma are frequently related to sunburn [2,3].

Gallates with eight or more carbon atoms in the lateral chain show potent anticancer activity against various cell lines. However, studies regarding the in vivo antimelanoma activity of tetradecyl gallate (C(14)) have not yet been reported. In this study an evaluation of the ability of C(14) to inhibit metastasis, using lung metastases as a model, was carried out. The experimental mouse melanoma model was established by intravenous injection of metastatic B16F10 melanoma cells. The systemic toxicity of C(14) was evaluated in vivo by monitoring the weight, survival, biochemical and hematological parameters, and through histological analysis. It was observed that C(14) decreased lung metastasis in vivo by 80% and increased the survival rate of the animals without toxic effects. Additionally, C(14) induced cytotoxic effects on B16F10 cells, inhibited the inter-cellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expression, and significantly decreased cell adhesion. These results reveal that C(14) has potent antimetastatic ability and is a good candidate for further study as a potential therapeutic agent for tumor metastases.

Background: Many fruits have been used as nutraceuticals because the presence of bioactive molecules that play biological activities. Objective: The present study was designed to compare the anti-inflammatory and antioxidant effects of methanolic extracts of Lycium barbarum (GOJI), Vaccinium macrocarpon (CRAN) and Vaccinium myrtillus (BLUE). Materials and Methods: Mices were treated with extracts (50 and 200 mg/kg, p.o.), twice a day through 10 days. Phytochemical analysis was performed by high-performance liquid chromatography. Antioxidant activity was determine by 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, reducing power, lipid peroxidation thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and catalase (CAT) activity. Anti-inflammatory activity was evaluated by paw edema followed by determination of myeloperoxidase (MPO) and TBARS. Results: High amount of phenolic compounds, including rutin, were identified in all berries extracts. However, quercetin was observed only in BLUE and CRAN. GOJI presents higher scavenging activity of DPPH radical and reducing power than BLUE and CRAN. The extracts improved antioxidant status in liver; BLUE showed the largest reduction (75.3%) in TBARS when compared to CRAN (70.7%) and GOJI (65.3%). Nonetheless, CAT activity was lower in BLUE group. However, hepatic concentrations of GSH were higher in animals treated with GOJI rather than CRAN and BLUE. Despite all fruits caused a remarkable reduction in paw edema and TBARS, only BLUE and CRAN were able to reduce MPO. Conclusion: These results suggest that quercetin, rutin, or other phenolic compound found in these berry fruits extracts could produce an anti-inflammatory response based on modulation of oxidative stress in paw edema model. SUMMARY Within fruits broadly consumed because of its nutraceuticals properties include, Lycium barbarum (Goji berry), Vaccinium myrtillus (Blueberry or Bilberry) and Vaccinium macrocarpon (Cranberry)The objectives of this study were the investigation and comparison of chemical composition, antioxidant activity “in vitro” and “in vivo” and anti inflammatory property of berry fruits bought dry form.In summary, two main findings can be addressed with this study: (1) Berry fruits presented antioxidant and anti inflammatory activities “in vitro” and “in vivo”; (2) the extracts of GOJI, CRAN, and BLUE modulate the inflammatory process by different mechanisms.

The lipid lowering activity of chitosan associated with Aloe vera L. or hydrosoluble chitosan with Brassica olearaceae L. has been studied in rats. In this study, rats were submitted to different treatments with hydrosoluble chitosan alone (4% diet), hydrosoluble chitosan associated with Aloe vera L. or hydrosoluble chitosan with Brassica olearaceae L. (1:4, 4% diet) for 35 days, to identify the formula with the highest hypolipaemic potential. The results showed that all treatments reduced blood lipid levels but that hydrosoluble chitosan associated with Brassica olearaceae L. proved most efficient, because it decreased the levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglycerides in blood serum. The overall results suggest that the hydrosoluble chitosan/Brassica olearaceae L. association is a therapeutic alternative for hyperlipidaemia, and in this way may contribute to the prevention of atherogenic processes. Copyright © 2006 John Wiley & Sons, Ltd.

Albendazole (ABZ) and mebendazole (MBZ) are two benzimidazole-derived drugs that show remarkable antihelmintic activity and are widely used in the treatment and control of helminths. Some antihelmintic drugs seem to act through the deleterious generation of reactive oxygen and nitrogen species (ROS and RNS, respectively) to which helminths have no, or relatively low, antioxidant defences (AD), when compared to aerobic organisms. The main objective of the present study consisted of the evaluation of the effect of both drugs on the AD and on some oxidative stress indicators in the host liver. Adult, male, Wistar rats were treated with ABZ or MBZ at doses of 40 mg/kg for different periods of time (2, 4, 8 and 10 days). After treatment, the activities of superoxide dismutase, catalase, glutathione reductase, and glutathione S-transferase, as well as the concentrations of TBARS, reduced glutathione, oxidized glutathione and total glutathione, were evaluated in rat hepatocytes. The serum nitrogen monoxide, usually known as nitric oxide (NO) levels, was also measured. The results showed that both drugs provoked an oxidative stress condition, demonstrated through the elevation of TBARS contents and through the decrease of some AD. Moreover, ABZ showed to be a strong ROS and RNS generator while MBZ showed a low and transient effect on ROS generation. It is suggested that MBZ could be the first-choice drug in the treatment of helminthiasis because it shares a similar therapeutic indication with ABZ, and because it causes only a mild oxidative stress to the host.

This work investigates the activities of nisin and gallic acid, used either alone or in combination, against Listeria monocytogenes Scott A CmrEmr. The antimicrobial activity was determined using agar diffusion tests. The growth profile was evaluated by measurements of optical density and the numbers of viable cells. Lipid peroxidation was measured by the thiobarbituric acid-reactive substances (TBARS) technique, and the levels of reduced glutathione (GSH) were determined by the 5,5-dithio-bis-2-nitrobenzoic acid (DTNB) method. Growth of the pathogen was inhibited by the combined use of nisin and gallic acid, with an inhibition zone of approximately 11 mm at concentrations of 8 mg/ml and 100 IU/ml, respectively. No significant reduction in the number of viable pathogen cells was observed after 18 hours of exposure to nisin and gallic acid. There was a significant increase in the GSH concentration, and a decrease in lipid peroxidation, when the pathogen was exposed to increasing concentrations of nisin and gallic acid, used either alone or in combination, for a period of 18 hours. It was concluded that the Listeria monocytogenes cell line studied was able to resist the action of oxidizing agents by increasing the synthesis of GSH.