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1.
Public Health ; 229: 24-32, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38382178

RESUMO

OBJECTIVES: The aim of this study was to estimate smoking-attributable mortality (SAM) in the population aged 35 years and over in Brazil's 27 federal units by sex, in 2019. STUDY DESIGN: This is an attributable mortality analysis. METHODS: We applied a method dependent on the prevalence of smoking, based on the population attributable fractions. Data on mortality due to causes causally related to smoking were derived from Brazil's Death Registry, data on prevalence of smoking from a survey conducted in Brazil in 2019, and data on relative risks from five US cohorts. Crude and age-adjusted SAM rates were calculated by sex. Estimates of SAM were calculated by specific causes of death and major mortality groups for each federal unit by sex. RESULTS: In 2019, smoking caused 480 deaths per day in Brazil. Although the SAM varied among the federal units, the pattern is not clear, with the greatest difference being between Rio Grande do Sul (crude rate: 248.8/100,000 inhabitants) and Amazonas (106.0/100,000). When the rates were adjusted by age, the greatest differences were observed between Acre (271.1/100,000) and Distrito Federal (131.1/100,000). SAM was higher in males; however, while the main specific cause of SAM in men was ischemic heart disease, in women it was chronic obstructive pulmonary disease. The major mortality group having the greatest impact on SAM across all federal units was the cardiometabolic diseases. CONCLUSIONS: The variability in the burden of SAM in the different regions of Brazil reaffirms the need for SAM data disaggregated at the geographic level.


Assuntos
Isquemia Miocárdica , Doença Pulmonar Obstrutiva Crônica , Masculino , Humanos , Feminino , Brasil/epidemiologia , Fumar/epidemiologia , Prevalência , Mortalidade
2.
J Dairy Sci ; 106(10): 6951-6960, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37500437

RESUMO

Studies evaluating the crude protein (CP) supplementation strategies across the year for grazing cattle and its association with the enzymes involved in the urea cycle and muscle and mammary gland developments are scarce. Thus, we aimed to evaluate the effect of supplementation with different levels of CP on the expression of genes involved in the urea cycle and muscle and mammary gland development of Holstein × Gyr crossbreed heifers grazing intensively managed Brachiaria decumbens throughout the year. Thirty-eight heifers with average initial BW of 172.5 ± 11.15 kg (mean ± SE) and 8.2 ± 0.54 mo of age were randomly assigned to 1 of 4 treatments: 3 protein supplements (SUP) fed at 5g/kg of body weight, plus a control group (CON, non-supplemented animals). The supplement CP levels evaluated were: 12, 24, and 36%. The study was divided into 4 seasons: rainy, dry, rainy-dry transition (RDT), and dry-rainy transition (DRT). On the penultimate day of each season, ultrasound images of the carcass and mammary gland were taken. Five animals from each treatment were randomly chosen on the last day of each season, and liver and muscle tissue biopsies were performed. The target genes were the mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) in the muscle samples. Carbamoyl phosphate synthetase (CPS), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS), arginosuccinate lyase (ASL), and arginase (ARG) were evaluated in the liver samples. Data were analyzed using PROC GLIMMIX of the SAS with repeated measures. We observed a greater rib eye area (cm2) and fat thickness (mm) in SUP animals than in non-supplemented animals. However, we did not observe differences among SUP levels for both variables. No effects of supplementation were detected on mammary gland development. Nevertheless, seasonal effects were observed, where the RDT and dry season had the most and least accumulated fat in the mammary gland. In muscle, we observed greater expression of AMPK in non-supplemented animals than SUP animals. On the other hand, no differences were observed in gene expression between SUP and non-supplemented animals and among SUP animals for mTOR. Season affected both AMPK and mTOR; heifers had a greater AMPK gene expression on rainy than RDT. For mTOR, we observed greater gene expression in RDT and DRT than in rainy. No differences were observed among RDT, dry, and DRT, and between dry and rainy seasons for mTOR. We observed greater CPS, ASL, and ARG gene expression in SUP animals than in non-supplemented animals. Among SUP animals, supplement CP linearly affected CPS. In conclusion, the supplementation strategy did not affect mammary gland development and mTOR expression in muscle tissue. However, we observed a seasonal effect on mammary gland development and AMPK and mTOR expression. The CP supplementation increased the rib eye area and fat thickness, directly affecting AMPK expression in the muscle. Moreover, the CP supplementation increased urea cycle enzyme expression, indicating greater urea production in the liver.


Assuntos
Proteínas Quinases Ativadas por AMP , Suplementos Nutricionais , Bovinos , Animais , Feminino , Músculos , Ureia , Serina-Treonina Quinases TOR , Ração Animal/análise , Dieta/veterinária , Mamíferos
4.
Animal ; 16(9): 100613, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35964480

RESUMO

Holstein × Gyr and Holstein are the primary dairy breeds used in tropical systems, but when rearing under pasture, feed intake, behavior, and performance might differ between them. This study aimed to evaluate the voluntary intake, nutrient digestibility, performance, and ingestive behavior of Holstein and Holstein × Gyr (½ Holstein × ½ Gyr) heifers managed in a rotational system of Guinea grass (Panicum maximum Jacq. cv. Mombaça). The experiment was conducted during the summer season throughout four periods of 21 d. Two 8-heifers (four Holstein and four Holstein × Gyr) groups, averaging 258.6 ±â€¯24.79 kg and 157.1 ±â€¯24.99 kg BW, were used. Each group grazed a separate set of 16 paddocks, and all heifers received a concentrate supplement daily. Heifers were weighed at the beginning and end of the experiment. Fecal, forage and concentrate samples were evaluated for their DM, CP, crude fat, ash, NDF, and indigestible NDF. Feeding behavior was evaluated through 24 h of live observation for 48 h of each experimental period. Grazing, ruminating, resting, and intake of concentrate times were recorded, and rumination criteria, bout criteria, mealtime, meal frequency, and meal duration were calculated. There was no difference in total dry matter intake (DMI), but forage DMI of Holstein × Gyr was 11.70 % greater than the Holstein heifers. The Holstein × Gyr heifers had greater NDF intake and feed efficiency tended to show greater CP and NDF digestibilities, consequently, they had greater average daily gain (ADG). Holstein grazed less than Holstein × Gyr heifers in the afternoon. Ruminating time was 18.43 % lower for Holstein than Holstein × Gyr heifers, and rumination criteria (i.e. longest non-feeding interval within a rumination event) were greater for Holstein heifers. Holstein heifers presented more prolonged rumination bouts and resting time than Holstein × Gyr heifers. Holstein × Gyr can ingest and ruminate greater amounts of fibrous material, and Holstein heifers needed to spend more time ruminating the cud. Overall, even though the behavior was not markedly different between breeds, rearing young Holstein heifers in tropical pasture conditions is less suitable than Holstein-Gyr because of their lower ADG. Therefore, this management condition seems appropriate for Holstein × Gyr but inappropriate for Holstein dairy heifers.


Assuntos
Ração Animal , Poaceae , Ração Animal/análise , Animais , Bovinos , Dieta/veterinária , Digestão , Comportamento Alimentar , Feminino , Melhoramento Vegetal , Estações do Ano
5.
Nat Clim Chang ; 11(6): 492-500, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34221128

RESUMO

Climate change affects human health; however, there have been no large-scale, systematic efforts to quantify the heat-related human health impacts that have already occurred due to climate change. Here, we use empirical data from 732 locations in 43 countries to estimate the mortality burdens associated with the additional heat exposure that has resulted from recent human-induced warming, during the period 1991-2018. Across all study countries, we find that 37.0% (range 20.5-76.3%) of warm-season heat-related deaths can be attributed to anthropogenic climate change and that increased mortality is evident on every continent. Burdens varied geographically but were of the order of dozens to hundreds of deaths per year in many locations. Our findings support the urgent need for more ambitious mitigation and adaptation strategies to minimize the public health impacts of climate change.

6.
Rev. chil. nutr ; 46(5): 606-613, oct. 2019. tab
Artigo em Inglês | LILACS | ID: biblio-1042701

RESUMO

Countless strategies have been proposed to change dietary patterns to promote weight loss. Many of these strategies are controversial, with questions of effectiveness and possible negative consequences to health, even if weight loss effects are achieved. Ketogenic diets, with or without calorie restrictions, are framed in this context. In the present systematic review, evidence on ketogenic diets for weight loss was investigated. Studies on ketogenic diet with or without calorie restriction related to weight loss published between 2012 and 2017 were selected from MEDLINE, Scielo and Web of Science databases. Results show there is a lack of knowledge on specific physiological mechanisms involved in the ketogenic diet. Much of the evidence published, despite showing specific effects on weight loss, BMI and fat percentage reduction, did not precisely assess its effects on specific physiological and biochemical parameters, mainly on the hepatic, cardiac and renal tissues. We conclude that strategies to control overweight and obesity do not necessarily need to impose restrictions on certain nutrients, especially carbohydrates, or increase the intake of food groups whose excessive consumption has been associated with different pathologies.


Innumerables estrategias se han propuesto para cambiar el patrón de la dieta y así promover la pérdida de peso. Muchas de estas estrategias aún son controversiales con respecto a la efectividad y las consecuencias negativas para la salud. Las dietas cetogénicas, con o sin restricciones calóricas, se enmarcan en este contexto. En la presente revisión sistemática, se investigaron las evidencias sobre las dietas cetogénicas para la pérdida de peso. Para esto, se seleccionaron los estudios de dieta cetogénica con o sin restricción calórica relacionada con la pérdida de peso publicados entre 2012 y 2017 a través de las bases de datos MEDLINE, Scielo y Web of Science. Los resultados muestran falta de conocimiento sobre mecanismos fisiológicos específicos implicados en la dieta cetogénica. Gran parte de la evidencia publicada, a pesar de mostrar efectos específicos sobre la pérdida de peso, IMC y reducción del porcentaje de grasa, no evaluó con precisión sus efectos sobre parámetros fisiológicos y bioquímicos, principalmente en los tejidos hepático, cardíaco y renal. Concluimos que las estrategias para controlar el sobrepeso y la obesidad no necesariamente tienen que imponer restricciones sobre nutrientes, especialmente los carbohidratos, o aumentar la ingesta de grupos de alimentos cuyo consumo excesivo se ha asociado con diferentes patologías.


Assuntos
Humanos , Redução de Peso/fisiologia , Dieta Cetogênica , Composição Corporal
7.
Malays J Pathol ; 40(2): 199-202, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30173239

RESUMO

A 43-year-old man presented with two-month history of fatigue, weakness, paleness, rectal bleeding, sweating, and weight loss of 10 kg in the past one month. A complete blood count revealed anaemia. The patient underwent a right hemicolectomy. The microscopic examination revealed an adenosquamous carcinoma associated with a mucinous adenocarcinoma in a patient with microsatellite instability due to loss of MLH1 and PMS2 expression and retention of MSH2 and MSH6 expression in both the squamous and glandular components. We also observed an atypical immunohistochemical phenotype in the adenocarcinoma component showing CK7 expression and reduced CK20 and CDX2 expression.


Assuntos
Adenocarcinoma Mucinoso/patologia , Carcinoma Adenoescamoso/patologia , Neoplasias do Colo/patologia , Instabilidade de Microssatélites , Neoplasias Primárias Múltiplas/patologia , Adenocarcinoma Mucinoso/genética , Adulto , Carcinoma Adenoescamoso/genética , Neoplasias do Colo/genética , Humanos , Masculino , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Proteína 1 Homóloga a MutL/genética , Neoplasias Primárias Múltiplas/genética
8.
Braz. j. biol ; 77(3): 622-631, July-Sept. 2017. tab, graf
Artigo em Inglês | LILACS | ID: biblio-888791

RESUMO

Abstract The large estuaries can present long narrow branches called subestuaries or tidal creeks. These types of subsystems are distributed along the Uruguayan coast of the Río de la Plata estuary and are very important as nursery and refuge areas for fish. For the first time, the seasonal composition and abundance of the fish community of the Solís Chico subestuary was studied by using beach and gill nets. Fourteen species, mainly euryhaline (86%) presented a significant representation of juvenile stages. The fish community was dominated by Odontesthes argentinensis, Platanichthys platana, Mugil liza, Brevoortia aurea, Micropogonias furnieri and Paralichthys orbignyanus, similar to adjacent subestuaries. While Micropogonias furnieri and B. aurea were the most abundant species, some other species were rarely caught. A seasonal variation of the fish assemblage abundance was detected, with higher values in autumn showing a positive correlation with temperature. Species that complete their life cycle in the Río de la Plata estuary, some of which are relevant to fisheries (64% of the analyzed species) were captured in the Solís Chico subestuary. The importance of this environment as a transitional system for some estuarine fish species is advised.


Resumo Os grandes estuários podem apresentar longos ramos estreitos chamados subestuários e riachos de maré. Estes subsistemas estão distribuídos ao longo da costa uruguaia no estuário do Río de la Plata e são muito importantes como áreas de reprodução e refúgio para os peixes. Pela primeira vez, a composição sazonal e abundância da comunidade de peixes do subestuário Solís Chico foi estudada usando redes de arrasto de praia e rede de emalhar. Quatorze espécies com predominância das eurialinas foram capturadas, havendo uma representação significativa das fases juvenis e espécies alvo para a pesca. A comunidade de peixes foi dominada por Odontesthes argentinensis, Platanichthys platana, Mugil liza, Brevoortia aurea, Micropogonias furnieri e Paralichthys orbignyanus, semelhante aos subestuários adjacentes. Enquanto, M. furnieri e B. aurea foram as espécies com maior número de individuos. Solís Chico apresentou espécies exclusivas com baixa abundância e ocorrência. Foi verificada uma variação sazonal da abundância de peixes, com valores maiores no outono, mostrando uma correlação positiva com a temperatura. Algumas espécies relevantes para a pesca que completam seu ciclo de vida no estuário do Río de la Plata foram capturadas (64% das espécies estudadas) no subestuário Solís Chico, indicando a importância deste ambiente como um sistema transitório para algumas espécies estuarinas de peixes.


Assuntos
Animais , Biomassa , Biodiversidade , Peixes/fisiologia , Estações do Ano , Uruguai , Densidade Demográfica , Estuários , Pesqueiros
9.
Braz J Med Biol Res ; 50(4): e5892, 2017 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-28355353

RESUMO

Few studies have examined the influence of a low level of schooling on age-related cognitive decline in countries with wide social and economic inequalities by using the Cambridge Automated Neuropsychological Test Battery (CANTAB). The aim of the present study was to assess the influence of schooling on age-related cognitive decline using unbiased cognitive tests. CANTAB allows cognitive assessment across cultures and education levels with reduced interference of the examiner during data acquisition. Using two-way ANOVA, we assessed the influences of age and education on test scores of old adults (61-84 years of age). CANTAB tests included: Visual Sustained Attention, Reaction Time, Spatial Working Memory, Learning and Episodic Memory. All subjects had a minimum visual acuity of 20/30 (Snellen Test), no previous or current history of traumatic brain/head trauma, stroke, language impairment, chronic alcoholism, neurological diseases, memory problems or depressive symptoms, and normal scores on the Mini Mental State Examination (MMSE). Subjects were grouped according to education level (1 to 7 and ≥8 years of schooling) and age (60-69 and ≥70 years). Low schooling level was associated with significantly lower performance on visual sustained attention, learning and episodic memory, reaction time, and spatial working memory. Although reaction time was influenced by age, no significant results on post hoc analysis were detected. Our findings showed a significantly worse cognitive performance in volunteers with lower levels of schooling and suggested that formal education in early life must be included in the preventive public health agenda. In addition, we suggest that CANTAB may be useful to detect subtle cognitive changes in healthy aging.


Assuntos
Cognição/fisiologia , Envelhecimento Cognitivo/fisiologia , Envelhecimento Cognitivo/psicologia , Escolaridade , Memória Episódica , Memória de Curto Prazo/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Atenção/fisiologia , Estudos Transversais , Feminino , Avaliação Geriátrica/métodos , Humanos , Aprendizagem/fisiologia , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Tempo de Reação/fisiologia , Análise e Desempenho de Tarefas , Fatores de Tempo
10.
Braz J Biol ; 77(3): 622-631, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27783761

RESUMO

The large estuaries can present long narrow branches called subestuaries or tidal creeks. These types of subsystems are distributed along the Uruguayan coast of the Río de la Plata estuary and are very important as nursery and refuge areas for fish. For the first time, the seasonal composition and abundance of the fish community of the Solís Chico subestuary was studied by using beach and gill nets. Fourteen species, mainly euryhaline (86%) presented a significant representation of juvenile stages. The fish community was dominated by Odontesthes argentinensis, Platanichthys platana, Mugil liza, Brevoortia aurea, Micropogonias furnieri and Paralichthys orbignyanus, similar to adjacent subestuaries. While Micropogonias furnieri and B. aurea were the most abundant species, some other species were rarely caught. A seasonal variation of the fish assemblage abundance was detected, with higher values in autumn showing a positive correlation with temperature. Species that complete their life cycle in the Río de la Plata estuary, some of which are relevant to fisheries (64% of the analyzed species) were captured in the Solís Chico subestuary. The importance of this environment as a transitional system for some estuarine fish species is advised.


Assuntos
Biodiversidade , Biomassa , Peixes/fisiologia , Animais , Estuários , Pesqueiros , Densidade Demográfica , Estações do Ano , Uruguai
11.
Hypertens Pregnancy ; 35(3): 280-94, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27315325

RESUMO

Hypertensive disorders are a major cause of maternal death. Preeclampsia (PE) affects about 5% of pregnancies and is associated to high cardiovascular death risk. Understanding of its origin and cause is difficult and many etiologies have been proposed. So far, little can be done for real prevention and the only treatment is pregnancy interruption, increasing the child's risk for prematurity complications. Early markers of disease are a promising path for understanding the pathogenesis and developing new strategies for prediction and eventually disease prevention.


Assuntos
Pré-Eclâmpsia/etiologia , Pré-Eclâmpsia/prevenção & controle , Feminino , Humanos , Pré-Eclâmpsia/fisiopatologia , Gravidez , Primeiro Trimestre da Gravidez , Fatores de Risco
12.
Oncogene ; 35(48): 6262-6269, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27157617

RESUMO

Helicobacter pylori (H. pylori) is the strongest identified risk factor for gastric cancer, the third most common cause of cancer-related death worldwide. An H. pylori constituent that augments cancer risk is the strain-specific cag pathogenicity island, which encodes a type IV secretion system (T4SS) that translocates a pro-inflammatory and oncogenic protein, CagA, into epithelial cells. However, the majority of persons colonized with CagA+ H. pylori strains do not develop cancer, suggesting that other microbial effectors also have a role in carcinogenesis. Toll-like receptor 9 (TLR9) is an endosome bound, innate immune receptor that detects and responds to hypo-methylated CpG DNA motifs that are most commonly found in microbial genomes. High-expression tlr9 polymorphisms have been linked to the development of premalignant lesions in the stomach. We now demonstrate that levels of H. pylori-mediated TLR9 activation and expression are directly related to gastric cancer risk in human populations. Mechanistically, we show for the first time that the H. pylori cancer-associated cag T4SS is required for TLR9 activation and that H. pylori DNA is actively translocated by the cag T4SS to engage this host receptor. Activation of TLR9 occurs through a contact-dependent mechanism between pathogen and host, and involves transfer of microbial DNA that is both protected as well as exposed during transport. These results indicate that TLR9 activation via the cag island may modify the risk for malignancy within the context of H. pylori infection and provide an important framework for future studies investigating the microbial-epithelial interface in gastric carcinogenesis.


Assuntos
Proteínas de Bactérias/metabolismo , Infecções por Helicobacter/metabolismo , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Receptor Toll-Like 9/metabolismo , Sistemas de Secreção Tipo IV , Proteínas de Bactérias/genética , Transporte Biológico , Carcinogênese , DNA Bacteriano/genética , DNA Bacteriano/metabolismo , Infecções por Helicobacter/complicações , Humanos , Mutação , Neoplasias Gástricas/etiologia
13.
Oncogene ; 35(42): 5480-5488, 2016 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-27041578

RESUMO

Chronic inflammation contributes to the development of various forms of cancer. The polyamine catabolic enzyme spermine oxidase (SMOX) is induced in chronic inflammatory conditions, including Helicobacter pylori-associated gastritis, where its production of hydrogen peroxide contributes to DNA damage and subsequent tumorigenesis. MicroRNA expression levels are also altered in inflammatory conditions; specifically, the tumor suppressor miR-124 becomes silenced by DNA methylation. We sought to determine if this repression of miR-124 is associated with elevated SMOX activity and concluded that miR-124 is indeed a negative regulator of SMOX. In gastric adenocarcinoma cells harboring highly methylated and silenced mir-124 gene loci, 5-azacytidine treatment allowed miR-124 re-expression and decreased SMOX expression. Overexpression of an exogenous miR-124-3p mimic repressed SMOX mRNA and protein expression as well as H2O2 production by >50% within 24 h. Reporter assays indicated that direct interaction of miR-124 with the 3'-untranslated region of SMOX mRNA contributes to this negative regulation. Importantly, overexpression of miR-124 before infection with H. pylori prevented the induction of SMOX believed to contribute to inflammation-associated tumorigenesis. Compelling human in vivo data from H. pylori-positive gastritis tissues indicated that the mir-124 gene loci are more heavily methylated in a Colombian population characterized by elevated SMOX expression and a high risk for gastric cancer. Furthermore, the degree of mir-124 methylation significantly correlated with SMOX expression throughout the population. These results indicate a protective role for miR-124 through the inhibition of SMOX-mediated DNA damage in the etiology of H. pylori-associated gastric cancer.


Assuntos
Epigênese Genética , Regulação da Expressão Gênica , Inativação Gênica , MicroRNAs/genética , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Regiões 3' não Traduzidas , Biópsia , Metilação de DNA , Regulação para Baixo , Gastrite/etiologia , Gastrite/patologia , Infecções por Helicobacter/complicações , Helicobacter pylori , Humanos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/patologia , Poliamina Oxidase
14.
Oncogene ; 34(14): 1865-71, 2015 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-24837365

RESUMO

Helicobacter pylori is the strongest risk factor for the development of gastric cancer. Although the specific mechanisms by which this pathogen induces carcinogenesis have not been fully elucidated, high-expression interleukin (IL)-1ß alleles are associated with increased gastric cancer risk among H. pylori-infected persons. In addition, loss of matrix metalloproteinase 7 (MMP7) increases mucosal inflammation in mouse models of epithelial injury, and we have shown that gastric inflammation is increased in H. pylori-infected MMP7(-/-) C57BL/6 mice. In this report, we define mechanisms that underpin such responses and extend these results into a genetic model of MMP7 deficiency and gastric cancer. Wild-type (WT) or MMP7(-/-) C57BL/6 mice were challenged with broth alone as an uninfected control or the H. pylori strain PMSS1. All H. pylori-challenged mice were successfully colonized. As expected, H. pylori-infected MMP7(-/-) C57BL/6 mice exhibited a significant increase in gastric inflammation compared with uninfected or infected WT C57BL/6 animals. Loss of MMP7 resulted in M1 macrophage polarization within H. pylori-infected stomachs, as assessed by Luminex technology and immunohistochemistry, and macrophages isolated from infected MMP7-deficient mice expressed significantly higher levels of the M1 macrophage marker IL-1ß compared with macrophages isolated from WT mice. To extend these findings into a model of gastric cancer, hypergastrinemic WT INS-GAS or MMP7(-/-) INS-GAS mice were challenged with H. pylori strain PMSS1. Consistent with findings in the C57BL/6 model, H. pylori-infected MMP7-deficient INS-GAS mice exhibited a significant increase in gastric inflammation compared with either uninfected or infected WT INS-GAS mice. In addition, the incidence of gastric hyperplasia and dysplasia was significantly increased in H. pylori-infected MMP7(-/-) INS-GAS mice compared with infected WT INS-GAS mice, and loss of MMP7 promoted M1 macrophage polarization. These results suggest that MMP7 exerts a restrictive role on H. pylori-induced gastric injury and the development of premalignant lesions by suppressing M1 macrophage polarization.


Assuntos
Gastrite/microbiologia , Infecções por Helicobacter/patologia , Macrófagos/imunologia , Metaloproteinase 7 da Matriz/genética , Estômago , Animais , Modelos Animais de Doenças , Mucosa Gástrica/citologia , Mucosa Gástrica/imunologia , Mucosa Gástrica/microbiologia , Gastrite/imunologia , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Helicobacter pylori/patogenicidade , Hiperplasia/genética , Inflamação/imunologia , Inflamação/microbiologia , Macrófagos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/microbiologia , Estômago/imunologia , Estômago/microbiologia , Estômago/patologia , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/microbiologia
15.
Oncogene ; 34(26): 3429-40, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25174398

RESUMO

Helicobacter pylori infection causes gastric cancer, the third leading cause of cancer death worldwide. More than half of the world's population is infected, making universal eradication impractical. Clinical trials suggest that antibiotic treatment only reduces gastric cancer risk in patients with non-atrophic gastritis (NAG), and is ineffective once preneoplastic lesions of multifocal atrophic gastritis (MAG) and intestinal metaplasia (IM) have occurred. Therefore, additional strategies for risk stratification and chemoprevention of gastric cancer are needed. We have implicated polyamines, generated by the rate-limiting enzyme ornithine decarboxylase (ODC), in gastric carcinogenesis. During H. pylori infection, the enzyme spermine oxidase (SMOX) is induced, which generates hydrogen peroxide from the catabolism of the polyamine spermine. Herein, we assessed the role of SMOX in the increased gastric cancer risk in Colombia associated with the Andean mountain region when compared with the low-risk region on the Pacific coast. When cocultured with gastric epithelial cells, clinical strains of H. pylori from the high-risk region induced more SMOX expression and oxidative DNA damage, and less apoptosis than low-risk strains. These findings were not attributable to differences in the cytotoxin-associated gene A oncoprotein. Gastric tissues from subjects from the high-risk region exhibited greater levels of SMOX and oxidative DNA damage by immunohistochemistry and flow cytometry, and this occurred in NAG, MAG and IM. In Mongolian gerbils, a prototype colonizing strain from the high-risk region induced more SMOX, DNA damage, dysplasia and adenocarcinoma than a colonizing strain from the low-risk region. Treatment of gerbils with either α-difluoromethylornithine, an inhibitor of ODC, or MDL 72527 (N(1),N(4)-Di(buta-2,3-dien-1-yl)butane-1,4-diamine dihydrochloride), an inhibitor of SMOX, reduced gastric dysplasia and carcinoma, as well as apoptosis-resistant cells with DNA damage. These data indicate that aberrant activation of polyamine-driven oxidative stress is a marker of gastric cancer risk and a target for chemoprevention.


Assuntos
Adenocarcinoma , Infecções por Helicobacter/complicações , Helicobacter pylori/fisiologia , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/fisiologia , Neoplasias Gástricas , Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Adenocarcinoma/microbiologia , Adulto , Animais , Células Cultivadas , Colômbia/epidemiologia , Dano ao DNA/genética , Indução Enzimática , Gerbillinae , Infecções por Helicobacter/genética , Humanos , Peróxido de Hidrogênio/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Fatores de Risco , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/microbiologia , Poliamina Oxidase
16.
J Anim Sci ; 92(5): 2214-24, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24663200

RESUMO

Nitrate can be a source of NPN for microbial growth at the same time that it reduces ruminal methane production. The objective of this study was to evaluate the effects of 2 encapsulated nitrate products used as urea replacers on blood and rumen constituents, methane emission, and growth performance of lambs. Eighteen Santa Inês male lambs (27 ± 4.9 kg) were individually allotted to indoor pens and assigned to a randomized complete block design with 6 blocks and 3 dietary treatments: control (CTL) = 1.5% urea, ENP = 4.51% encapsulated nitrate product (60.83% NO3(-) in the product DM), and ENP+CNSL = 4.51% ENP containing cashew nut shell liquid (60.83% NO3(-) and 2.96% cashew nut shell liquid [CNSL] in the product DM). Diets were isonitrogenous with 60:40 concentrate:forage (Tifton 85 hay) ratio. The experiment lasted for 92 d and consisted of 28 d for adaptation (a weekly 33% stepwise replacement of CTL concentrate by nitrate-containing concentrates) and 64 d for data collection. The ENP and ENP+CNSL showed greater (P < 0.05) red blood cell counts than CTL. Blood methemoglobin (MetHb) did not differ (P > 0.05) among treatments, with mean values within normal range and remaining below 1.1% of total hemoglobin. There was an increase (P < 0.05) in total short-chain fatty acids concentration at 3 h postfeeding for ENP, with an additional increase (P < 0.05) observed for ENP+CNSL. No treatment effects (P > 0.05) were observed on acetate to propionate ratio. Methane production (L/kg DMI) was reduced (P < 0.05) with nitrate inclusion, recording 28.6, 19.1, and 19.5 L/kg DMI for CTL, ENP, and ENP+CNSL, respectively. Addition of CNSL did not result (P > 0.05) in further reduction of methane production when compared with ENP. Final BW, DMI, ADG, and feed efficiency were similar (P > 0.05) among treatments. Values for DMI were 1.11, 1.03, and 1.04 kg/d and for ADG were 174, 154, and 158 g for CTL, ENP, and ENP+CNSL, respectively. In conclusion, encapsulated nitrate products showed no risks of toxicity based on MetHb formation. The products persistently reduced methane production without affecting performance. Inclusion of cashew nut shell liquid in the product formulation had no additional benefits on methane mitigation.


Assuntos
Anacardium , Metano/metabolismo , Nitratos/farmacologia , Extratos Vegetais/farmacologia , Rúmen/química , Ovinos/crescimento & desenvolvimento , Ração Animal/análise , Animais , Dieta/veterinária , Masculino , Nitratos/química , Extratos Vegetais/química , Ovinos/sangue , Ovinos/metabolismo
17.
Scott Med J ; 59(1): 50-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24424462

RESUMO

BACKGROUND AND AIMS: Phase III trials have shown that the addition of a taxane to cisplatin/5FU-based induction chemotherapy (TPF) improves response rates and overall survival in unresectable stage III/IV head and neck cancer. We sought to assess the tolerability, compliance and clinical outcomes of this treatment regime. METHODS: A retrospective study of patients treated within a single centre between September 2007 and November 2010. Toxicities were graded according to CTCAE version 3.0. Survival, distant metastasis and local control rates are expressed as percentages at two years using the Kaplan-Meier method. RESULTS: A total of 100 patients were identified (11% stage III, 86% stage IV) and 32% of patients were admitted as an emergency after TPF. The rate of neutropenic fever was 31%, this number fell to 9% when prophylactic G-CSF was used. In addition, 89% of patients underwent radical chemoradiation. Of these, 96% completed the full radiotherapy course. However, only 64% of patients received a minimum of two cycles of concurrent platinum chemotherapy. The two-year overall survival, metastasis free survival and local control rates were 62.6%, 88.5% and 73.3%, respectively. CONCLUSIONS: TPF chemotherapy can be delivered safely in a non-trial cohort of patients. There is, however, a significant reduction in concurrent chemotherapy dose intensity. The long-term impact of this remains unclear.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Neoplasias de Cabeça e Pescoço/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/administração & dosagem , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Metástase Neoplásica , Estudos Retrospectivos , Taxoides/administração & dosagem
18.
Rev. pediatr. electrón ; 10(1)abr. 2013. ilus
Artigo em Espanhol | LILACS | ID: lil-718964

RESUMO

En el presente estudio se presentan los resultados de una investigación cualitativa cuyo objetivo fue reconstruir las Representaciones Sociales del abuso sexual intrafamiliar de mujeres adultas habitantes de dos comunas de la Región Metropolitana, Chile. Fueron entrevistadas 52 mujeres adultas: madres con hijos abusados sexualmente por un familiar o conocido cercano, mujeres sin hijos y mujeres con hijos sin ser abusados. Las entrevistas fueron transcritas textualmente y analizadas según los procedimientos metodológicos formulados por Glaser y Strauss en la Teoría Fundada Empíricamente. La sección resultados incluye un Análisis Descriptivo de la información recolectada, de la cual se desprenden cuatro categorías: antecedentes contextuales, antecedentes de género, experiencias de su historia sexual y reacción a la develación de abuso sufrida por un menor; Análisis Relacional entre los antecedentes y reacción; y finalmente un Modelo Hipotético Interpretativo donde se explican los factores asociados al abuso intrafamiliar en las mujeres adultas.


This study presents the results of a qualitative research whose objective was to reconstruct the social representations of intrafamilial sexual abuse of adult women living in two municipalities of the Metropolitan Region, Chile. We interviewed 52 adult women: mothers with children sexually abused by a family member or close acquaintance, childless women and women with children without being abused. The interviews were transcribed verbatim and analyzed according to the methodological procedures formulated by Glaser and Strauss in empirically grounded theory. The results section includes a descriptive analysis of the data collected, from which emerge four categories: contextual history, gender history, experiences of sexual history and reaction to the unveiling of abuse suffered by a minor; Relational Analysis between the background and reaction, and finally an Interpretive hypothetical model which explains the factors associated with domestic abuse in adult women.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Abuso Sexual na Infância/psicologia , Mães/psicologia , Percepção Social , Autoimagem , Chile , Entrevistas como Assunto , Estado Civil , Identidade de Gênero , Pesquisa Qualitativa , Sociologia
19.
Gastroenterol. latinoam ; 24(supl.1): S64-S67, 2013. tab
Artigo em Espanhol | LILACS | ID: lil-763724

RESUMO

Budd-Chiari syndrome and porto-spleno-mesenteric thrombosis are less prevalent patologies, but related to high morbimortality, that present in context of chronic hepatopathies, myeloproliferative neoplasms and other prothrombotic conditions. Review of local experience and of current available literature of endovascular management of last five years was made. In relation to Budd-Chiari syndrome, early anticoagulation with low molecular weight heparines and transition to oral anticoagulation with K vitamin antagonists was recomended, also managing subyacent pathology, identifying and treating portal hypertension signs and endovascular therapy with angioplasty or Transjugular Intrahepatic Portosystemic Shunt (TIPS), depending on the thrombus extension. For portal vein thrombosis the same scheme was recommended, with emphasis in treating portal hypertension signs in chronic cases. Endovascular approach includes localized thrombolisis, thrombectomy and TIPS in previous non-effective therapy. We propose a management algorithm of these diseases.


El síndrome de Budd-Chiari y la trombosis venosa porto-espleno-mesentérica son patologías de baja prevalencia, pero de gran morbimortalidad asociada, que se presentan en contexto de hepatopatías crónicas, neoplasias mieloproliferativas y otras condiciones protrombóticas. Se revisó casuística local y literatura disponible del abordaje endovascular de estas patologías en los últimos cinco años. En relación al síndrome de Budd-Chiari, se recomienda la anticoagulación precoz con heparinas de bajo peso molecular y traslape con antagonistas de vitamina K, tratar la patología subyacente, identificar y tratar signos de hipertensión portal y realizar terapia endovascular con angioplastia o instalación de Shunt portosistémico transyugular (TIPS) según la extensión del compromiso. Se recomienda un esquema similar para la trombosis porto-espleno-mesentérica, con énfasis en manejo de hipertensión portal en los casos crónicos. El abordaje endovascular incluye la trombolisis localizada, trombectomía y TIPS en caso de fracaso del tratamiento previo. Se propone un algoritmo de manejo de dichas patologías.


Assuntos
Humanos , Procedimentos Endovasculares , Hepatopatias/complicações , Síndrome de Budd-Chiari/terapia , Trombose Venosa/terapia , Veias Mesentéricas , Veia Porta , Derivação Portossistêmica Transjugular Intra-Hepática , Fatores de Risco
20.
Pathog Glob Health ; 106(2): 107-12, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22943546

RESUMO

We report here for the first time the in vitro effects of (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2·2·1]heptan-2-yl-3',4',5'-trimethoxy benzoate (1) and (1S,2R,4S)-1,7,7-trimethyl-bicyclo[2·2·1]heptan-2-yl benzoate (2) on the growth and ultrastructure of Trypanosoma cruzi. These two synthetic compounds exerted an antiproliferative effect on the epimastigote forms of the parasite. The ICs(50/72h) of two synthetic L-bornyl benzoates, 1 and 2, was 10·1 and 12·8 µg/ml, respectively. Both compounds were more selective against epimastigotes than HEp-2 cells. Ultrastructural analysis revealed intense cytoplasmic vacuolization and the appearance of cytoplasmic materials surrounded by membranes. The treatment of peritoneal macrophages with compounds 1 and 2 caused a significant decrease in the number of T. cruzi-infected cells. L-Bornyl benzoate derivatives may serve as a potential source for the development of more effective and safer chemotherapeutic agents against T. cruzi infections.


Assuntos
Antiprotozoários/farmacologia , Benzoatos/farmacologia , Canfanos/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/síntese química , Antiprotozoários/toxicidade , Benzoatos/síntese química , Benzoatos/toxicidade , Canfanos/síntese química , Canfanos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Citoplasma/ultraestrutura , Células Hep G2 , Humanos , Concentração Inibidora 50 , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/parasitologia , Camundongos , Camundongos Endogâmicos BALB C , Trypanosoma cruzi/crescimento & desenvolvimento , Trypanosoma cruzi/ultraestrutura
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