Different fatty acid metabolism effects of (−)-epigallocatechin-3-gallate and C75 in adenocarcinoma lung cancer

Background Fatty acid synthase (FASN) is overexpressed and hyperactivated in several human carcinomas, including lung cancer. We characterize and compare the anti-cancer effects of the FASN inhibitors C75 and (−)-epigallocatechin-3-gallate (EGCG) in a lung cancer model. Methods We evaluated in vitro the effects of C75 and EGCG on fatty acid metabolism (FASN and CPT enzymes), cellular proliferation, apoptosis and cell signaling (EGFR, ERK1/2, AKT and mTOR) in human A549 lung carcinoma cells. In vivo, we evaluated their anti-tumour activity and their effect on body weight in a mice model of human adenocarcinoma xenograft. Results C75 and EGCG had comparable effects in blocking FASN activity (96,9% and 89,3% of inhibition, respectively). In contrast, EGCG had either no significant effect in CPT activity, the rate-limiting enzyme of fatty acid β-oxidation, while C75 stimulated CPT up to 130%. Treating lung cancer cells with EGCG or C75 induced apoptosis and affected EGFR-signaling. While EGCG abolished p-EGFR, p-AKT, p-ERK1/2 and p-mTOR, C75 was less active in decreasing the levels of EGFR and p-AKT. In vivo, EGCG and C75 blocked the growth of lung cancer xenografts but C75 treatment, not EGCG, caused a marked animal weight loss. Conclusions In lung cancer, inhibition of FASN using EGCG can be achieved without parallel stimulation of fatty acid oxidation and this effect is related mainly to EGFR signaling pathway. EGCG reduce the growth of adenocarcinoma human lung cancer xenografts without inducing body weight loss. Taken together, EGCG may be a candidate for future pre-clinical development.

Trabecular Bone Score (TBS)--A Novel Method to Evaluate Bone Microarchitectural Texture in Patients With Primary Hyperparathyroidism.

Context: In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture. Objective: The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT. Design and Setting: This was a cross-sectional study conducted in a referral center. Patients: Participants were 22 postmenopausal women with PHPT. Main Outcome Measures: Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia. Results: TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight. Conclusion: TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT.

Effect of growth regulators on 'Brookfield' apple gas diffusion and metabolism under controlled atmosphere storage

The objective of this work was to evaluate the effect of growth regulators on gas diffusion and on metabolism of 'Brookfield' apple, and to determine their correlation with quality characteristics of fruit stored in controlled atmosphere. A completely randomized design was used with four replicates. After eight months of storage, the effects of water (control), aminoethoxyvinylglycine (AVG), AVG + ethephon, AVG + naphthaleneacetic acid (NAA), ethephon + NAA, sole NAA, 1-MCP, ethylene absorption by potassium permanganate (ABS), AVG + ABS, and of AVG + 1-MCP - applied at different rates and periods - were evaluated on: gas diffusion rate, ethylene production, respiratory rate, internal ethylene concentration, internal CO2 content, mealiness, and intercellular space. Fruit from the control and sole NAA treatments had the highest mealiness occurrence. Growth regulators significantly changed the gaseous diffusion through the pulp of 'Brookfield' apple, mainly in the treatment AVG + ABS, which kept the highest gas diffusion rate. NAA spraying in the field, with or without another growth regulator, increased ripening metabolism by rising ethylene production and respiration rate, and reduced gas diffusion during shelf life. AVG spraying cannot avoid the ethephon effect during the ripening process, and reduces both the internal space and mealiness incidence, but it is not able to induce ethylene production or to increase respiration rates.

Metabolism of oral glucose in children born small for gestational age : evidence for an impaired whole body glucose oxidation

Résumé Les études épidémiologiques indiquent que la restriction intra-utérine confère un risque accru de développement de diabète de type 2 au cours de la vie. Certaines études ont documenté la présence d'une résistance à l'insuline chez les jeunes adultes ou les adolescents nés petits pour l'âge gestationnel. Comme la plupart des études ont impliqués des individus post-pubères et comme la puberté influence de manière marquée le métabolisme énergétique, nous avons évalué le devenir du glucose administré oralement dans un groupe incluant essentiellement des enfants pré-pubères ou en début de puberté avec restriction intra-utérine, et chez des enfants matchés pour l'âge et pour le poids. Tous les enfants ont eu une évaluation de leur composition corporelle par mesure des plis cutanés. Ils ont ensuite été étudiés dans des conditions standardisées et ont reçu 4 charges consécutives orales de glucose à raison de 180 mg/kg de poids corporel jusqu'à atteindre un état d'équilibre relatif. La dépense énergétique et l'oxydation des substrats ont été évaluées durant la quatrième heure par calorimétrie indirecte. Comparativement avec les enfants matchés pour l'âge et le poids, les enfants nés petits pour l'âge gestationnel avaient une plus petite stature. Leur dépense énergétique n'était pas significativement abaissée, mais leur oxydation du glucose était plus basse. Ces résultats indiquent que des altérations métaboliques sont présentes précocement chez les enfants nés petits pour l'âge gestationnel, et qu'elles sont possiblement reliées à des altérations de la composition corporelle. Abstract: Epidemiological studies indicate that intrauterine growth restriction confers an increased risk of developing type 2 diabetes mellitus in subsequent life. Several studies have further documented the presence of insulin resistance in young adults or adolescent children born small for gestational age. Since most studies addressed postpubertal individuals, and since puberty markedly affects energy metabolism, we evaluated the disposal of oral glucose in a group including mainly prepubertal and early pubertal children with intrauterine growth restriction and in healthy age- and weight-matched control children. All children had an evaluation of their body composition by skinfold thickness measurements. They were then studied in standardized conditions and received 4 consecutive hourly loads of 180 mg glucose/kg body weight to reach a near steady state. Energy expenditure and substrate oxidation were evaluated during the fourth hour by indirect calorimetry. Compared to both age- and weight-matched children, children born small for gestational age had lower stature. Their energy expenditure was not significantly decreased, but they had lower glucose oxidation rates. These results indicate that metabolic alterations are present early in children born small for gestational age, and are possibly related to alterations of body composition.

Growth and energy metabolism of Nile tilapia juveniles fed glycerol

The objective of this work was to evaluate the effect of inclusion of dietary glycerol in replacement to starch on the growth and energy metabolism of Nile tilapia juveniles. The experiment was carried out in a completely randomized design with four treatments (0, 5, 10, and 15% purified glycerol) and six replicates. Pelleted, isonitrogenous, and isocaloric diets were provided for 60 days. Growth performance parameters and muscle glucose and protein concentrations were not affected by dietary glycerol levels. The treatment with 15% glycerol presented higher levels of muscle and liver triglycerides. A quadratic effect of treatments on muscle and liver triglyceride concentrations was observed. The treatment with 0% glycerol presented higher hepatic glucose levels than the one with 15%. Treatments did not differ for concentrations of liver protein, as well as of plasma glucose, triglycerides, and protein. Treatments with 10 and 15% glycerol showed higher activity of the glucose-6-phosphate-dehydrogenase enzyme than the treatment with 5%; however, there were no significant differences in the hepatic activities of the malic and glycerol kinase enzymes. A linear positive effect of treatments was observed on the activity of the glycerol kinase enzyme in liver. Levels of glycerol inclusion above 10% in the diet of Nile tilapia juveniles characterize it as a lipogenic nutrient.

Dimethylarginines, homocysteine metabolism, and cerebrospinal fluid markers for Alzheimer's disease.

Dimethylarginine and homocysteine metabolism are closely linked and alterations of both were observed in plasma and cerebrospinal fluid (CSF) of patients with Alzheimer's disease (AD). CSF parameters of homocysteine metabolism have recently been found to be associated with the CSF level of the AD biomarker phosphorylated tau (ptau) in AD patients. To investigate possible relationships between homocysteine and dimethylarginine metabolism and the AD CSF biomarkers ptau181 and amyloid-β 1-42 (Aβ42), we assessed parameters of homocysteine metabolism (CSF homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), 5-methyltetrahydrofolate (5-MTHF)) and dimethylarginine metabolism (plasma and CSF asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, L-arginine) as well as CSF Aβ42 and ptau181 in 98 controls and 51 AD patients. Multivariate linear regression analyses were performed to assess associations between the considered parameters. SAH concentrations show significant associations to CSF ADMA levels, and CSF ADMA and L-arginine to ptau181, but not to Aβ42 concentrations in AD patients. When including concentrations of homocysteine, 5-MTHF, SAM, and SAH into the analysis, CSF ADMA concentrations independently predicted ptau181 levels in AD patients but homocysteine-related metabolites were associated with ptau181 only when ADMA was removed from the analysis model. These results suggest that CSF ADMA may interact with CNS homocysteine metabolism and may contribute to neurodegeneration and accumulation of phosphorylated tau in AD. Functional and interventional studies are needed to further proof this hypothesis.

Dry matter accumulation and mineral nutrition of arracacha in response to nitrogen fertilization

Abstract:The objective of this work was to evaluate the effect of nitrogen fertilization on the growth and yield of arracacha (Arracacia xanthorrhiza), as well as on the plant's nutrient uptake, distribution, and removal. The experiment was carried out in a typical Oxisol, with sandy texture. A randomized complete block design was used, with four replicates. The treatments consisted of five N rates: 0, 50, 100, 200, and 400 kg ha-1. The plots were composed of three 8-m-length rows, spaced at 0.60 m between rows and 0.40 m between plants. The plants were harvested after an 8-month cycle. Nitrogen fertilization significantly increased the proportion of N and S accumulated in stems, and of Ca, Mg, Fe, and Mn in leaves. N supply increased Zn distribution to stems and leaves, whereas high N rates increased Cu allocation to stems more than to the rootstock. High N rates increase plant dry matter (DM) production and nutrient uptake and removal, but do not result in the greatest yield due to the greater development of leaves and stems, and to the lower allocation of DM in storage roots.

Qualitative structure-metabolism relationships in the hydrolysis of carbamates.

The aims of this review were 1) to compile a large number of reliable literature data on the metabolic hydrolysis of medicinal carbamates and 2) to extract from such data a qualitative relation between molecular structure and lability to metabolic hydrolysis. The compounds were classified according to the nature of their substituents (R³OCONR&supl;R²), and a metabolic lability score was calculated for each class. A trend emerged, such that the metabolic lability of carbamates decreased (i.e., their metabolic stability increased), in the following series: Aryl-OCO-NHAlkyl >> Alkyl-OCO-NHAlkyl ~ Alkyl-OCO-N(Alkyl)? ? Alkyl-OCO-N(endocyclic) ? Aryl-OCO-N(Alkyl)? ~ Aryl-OCO-N(endocyclic) ? Alkyl-OCO-NHAryl ~ Alkyl-OCO-NHAcyl?>> Alkyl-OCO-NH? > Cyclic carbamates. This trend should prove useful in the design of carbamates as drugs or prodrugs.

CRESCIMENTO DE MUDAS DE CAJUEIRO-ANÃO-PRECOCE 'CCP¾ 76' SUBMETIDAS À ADUBAÇÃO ORGÂNICA E MINERAL

A adição de doses de matéria orgânica e fertilizante mineral ao substrato, para a produção de mudas em recipientes é uma técnica bastante utilizada nos sistemas modernos de produção de mudas. Contudo, para a cultura do cajueiro são poucas as informações que definam passíveis doses de matéria orgânica e fertilizantes minerais capazes de produzirem mudas vigorosas a curtos intervalos de tempo. Durante a fase de produção de mudas de cajueiro-anão-precoce 'CCP 76', conduziu-se um ensaio na área experimental do Departamento de Irrigação e Drenagem da Universidade Federal do Ceará em Fortaleza, Ceará, no período de abril a junho de 1995. Utilizou-se como substrato à camada arável (0-30cm) de um Podzólico Vermelho-Amarelo Distrófico, textura média. Para o plantio, utilizaram-se sementes oriundas de um único genótipo de cajueiro- anão-precoce progênie 'CCP 76'. Os tratamentos constaram da aplicação de quatro doses de matéria orgânica (0; 100; 200 e 300 cm³/2,5 Kg solo) e quatro doses da mistura mineral (0; 1,92; 3,34 e 6,18 g) contendo uréia, superfosfato triplo, cloreto de potássio, gesso, calcário e fritas tipo MIB-3. O delineamento experimental utilizado foi o inteiramente casualizado, com 16 tratamentos, em 4 repetições, seguindo o modelo fatorial 4². Foram realizadas as seguintes determinações: altura de planta (cm), diâmetro do caule (mm), número de folha/planta, comprimento da raiz principal (cm), peso da matéria seca da parte aérea e do sistema radicular (g/planta). Os resultados enfatizam que a aplicação de doses combinadas de matéria orgânica e fertilizante mineral promoveu acréscimos significativos sobre a altura da planta, peso da matéria seca da parte aérea e número de folhas.

CIANAMIDA HIDROGENADA, THIDIAZURON E ÓLEO MINERAL NA QUEBRA DA DORMÊNCIA E NA PRODUÇÃO DO PESSEGUEIRO cv. CHIRIPÁ

Este trabalho foi realizado no ano de 1999, na Estação Experimental Agronômica da Universidade Federal do Rio Grande do Sul, localizada no município de Eldorado do Sul, Estado do Rio Grande do Sul, latitude 30°05'52" S, longitude 51°39'08" W e altitude de 46 metros. Foram testados os efeitos da Cianamida Hidrogenada (C.H.) e Óleo Mineral (O.M.) em mistura, Óleo Mineral (O.M.) e Thidiazuron (TDZ) com Óleo Mineral (O.M.), sobre brotação, frutificação, produção e antecipação de colheita. Os tratamentos foram aplicados quando as plantas estavam no estádio fenológico A. Foram testados os seguintes tratamentos: C.H. 0,5%, 1,0% e 1,5% + O.M 1,0%, O.M. 1,0% e 2,0%, TDZ 200 e 400 ppm + O.M. 2,0% e testemunha (sem pulverização). Os tratamentos não anteciparam a brotação das gemas vegetativas. O tratamento C.H. 1,5% com O.M. 1,0% proporcionou produção suficiente para viabilizar o cultivo do "Chiripá" em condições de inverno ameno, mas não houve diferenças significativas no peso médio dos frutos. O TDZ, nas dosagens testadas, não se mostrou eficiente na quebra de dormência desta cultivar. Não houve efeito na antecipação da colheita.

Glucose metabolism, gray matter structure, and memory decline in subjective memory impairment.

OBJECTIVE: To identify biological evidence for Alzheimer disease (AD) in individuals with subjective memory impairment (SMI) and unimpaired cognitive performance and to investigate the longitudinal cognitive course in these subjects. METHOD: [¹⁸F]fluoro-2-deoxyglucose PET (FDG-PET) and structural MRI were acquired in 31 subjects with SMI and 56 controls. Cognitive follow-up testing was performed (average follow-up time: 35 months). Differences in baseline brain imaging data and in memory decline were assessed between both groups. Associations of memory decline with brain imaging data were tested. RESULTS: The SMI group showed hypometabolism in the right precuneus and hypermetabolism in the right medial temporal lobe. Gray matter volume was reduced in the right hippocampus in the SMI group. At follow-up, subjects with SMI showed a poorer performance than controls on measures of episodic memory. Longitudinal memory decline in the SMI group was associated with reduced glucose metabolism in the right precuneus at baseline. CONCLUSION: The cross-sectional difference in 2 independent neuroimaging modalities indicates early AD pathology in SMI. The poorer memory performance at follow-up and the association of reduced longitudinal memory performance with hypometabolism in the precuneus at baseline support the concept of SMI as the earliest manifestation of AD.

The Lin28/let-7 axis regulates glucose metabolism.

The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promote an insulin-sensitized state that resists high-fat-diet induced diabetes. Conversely, muscle-specific loss of Lin28a or overexpression of let-7 results in insulin resistance and impaired glucose tolerance. These phenomena occur, in part, through the let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. In addition, the mTOR inhibitor, rapamycin, abrogates Lin28a-mediated insulin sensitivity and enhanced glucose uptake. Moreover, let-7 targets are enriched for genes containing SNPs associated with type 2 diabetes and control of fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism.

Moderate hypercapnia exerts beneficial effects on splanchnic energy metabolism during endotoxemia.

PURPOSE: Low tidal volume ventilation and permissive hypercapnia are required in patients with sepsis complicated by ARDS. The effects of hypercapnia on tissue oxidative metabolism in this setting are unknown. We therefore determined the effects of moderate hypercapnia on markers of systemic and splanchnic oxidative metabolism in an animal model of endotoxemia. METHODS: Anesthetized rats maintained at a PaCO(2) of 30, 40 or 60 mmHg were challenged with endotoxin. A control group (PaCO(2) 40 mmHg) received isotonic saline. Hemodynamic variables, arterial lactate, pyruvate, and ketone bodies were measured at baseline and after 4 h. Tissue adenosine triphosphate (ATP) and lactate were measured in the small intestine and the liver after 4 h. RESULTS: Endotoxin resulted in low cardiac output, increased lactate/pyruvate ratio and decreased ketone body ratio. These changes were not influenced by hypercapnia, but were more severe with hypocapnia. In the liver, ATP decreased and lactate increased independently from PaCO(2) after endotoxin. In contrast, the drop of ATP and the rise in lactate triggered by endotoxin in the intestine were prevented by hypercapnia. CONCLUSIONS: During endotoxemia in rats, moderate hypercapnia prevents the deterioration of tissue energetics in the intestine.

Composição mineral da folha em abacaxizeiro: efeito da parte da folha analisada

A padronização da amostragem para a análise foliar em abacaxizeiros é importante para a obtenção de resultados confiáveis. Neste aspecto, este trabalho visa a esclarecer a variação da composição mineral da folha de abacaxi, em plantas desenvolvidas em solo arenoso, sem irrigação. As folhas foram coletadas, limpas e divididas em 4 porções: aclorofilada, basal, mediana e apical. Após a secagem, as amostras foram pesadas, submetidas à digestão e analisadas pela metodologia adequada a cada nutriente. Uma grande variação no teor dos nutrientes foi encontrada ao longo da folha de abacaxi. Uma comparação confiável pode ser estabelecida entre as análises feitas com a folha inteira e a porção clorofilada da folha; o mesmo já não pode ser dito para a porção aclorofilada. Assim, este trabalho vem confirmar a necessidade da padronização da amostragem.

Efeito da aplicação de cianamida hidrogenada e óleo mineral na quebra de dormência e producão do pessegueiro-'Flamecrest'

Com o objetivo de aumentar a produção e qualidade de frutos do pessegueiro- 'Flamecrest', de alta exigência em frio, realizou-se um experimento no Município de Farroupilha-RS, no ano de 2000, com o uso de cianamida hidrogenada e óleo mineral. Estudou-se o efeito de duas diferentes épocas de aplicação dos tratamentos (15-7 e 2-8) sobre a brotação, floração, frutificação, produção e antecipação de colheita. Foram testados os efeitos dos seguintes tratamentos: cianamida hidrogenada (C.H.) 1,22; 2,45; 3,675 e 4,90 g de i.a.L-1 com óleo mineral (O.M.) 10 g de i.a.L-1; O.M. 10 g de i.a.L-1 isolado e testemunha (sem pulverização). Os tratamentos não anteciparam a brotação das gemas floríferas, porém C.H. 2,45 e 4,90 g de i.a.L-1 com O.M. a 10 g de i.a.L-1 proporcionaram plantas com maior brotação das gemas vegetativas. Não houve efeito marcante dos tratamentos sobre a floração e a porcentagem de frutos vingados nas duas épocas. O número de frutos raleados por planta foi superior para os tratamentos com C.H. 2,45 e 4,90 g de i.a.L-1 com O.M. 10 g de i.a.L-1 quando aplicados na segunda época. Já, para o número e massa total dos frutos colhidos, destacaram-se, na primeira época (15-7), os tratamentos com C.H. 1,22 e 3,675 g de i.a.L-1 + O.M. 10 g de i.a.L-1 e, na segunda época (2-8), os tratamentos com C.H. 2,45 e 4,90 g de i.a.L-1 + O.M. 10 g de i.a.L-1. Os tratamentos da segunda época resultaram em produções médias superiores à primeira. A massa média dos frutos não foi alterada de forma clara pelos tratamentos, assim como o teor de sólidos solúveis totais e a resistência de polpa.