Chlorophyll treatment combined with photostimulation increases glycolysis and decreases oxidative stress in the liver of type 1 diabetic rats

Photodynamic therapy (PDT) promotes cell death, and it has been successfully employed as a treatment resource for neuropathic complications of diabetes mellitus (T1DM) and hepatocellular carcinoma. The liver is the major organ involved in the regulation of energy homeostasis, and in pathological conditions such as T1DM, changes in liver metabolic pathways result in hyperglycemia, which is associated with multiple organic dysfunctions. In this context, it has been suggested that chlorophyll-a and its derivatives have anti-diabetic actions, such as reducing hyperglycemia, hyperinsulinemia, and hypertriglyceridemia, but these effects have not yet been proven. Thus, the biological action of PDT with chlorophyll-a on hepatic parameters related to energy metabolism and oxidative stress in T1DM Wistar rats was investigated. Evaluation of the acute effects of this pigment was performed by incubation of isolated hepatocytes with chlorophyll-a and the chronic effects were evaluated by oral treatment with chlorophyll-based extract, with post-analysis of the intact liver by in situ perfusion. In both experimental protocols, chlorophyll-a decreased hepatic glucose release and glycogenolysis rate and stimulated the glycolytic pathway in DM/PDT. In addition, there was a reduction in hepatic oxidative stress, noticeable by decreased lipoperoxidation, reactive oxygen species, and carbonylated proteins in livers of chlorophyll-treated T1DM rats. These are indicators of the potential capacity of chlorophyll-a in improving the status of the diabetic liver.

Differences between genders in anaerobic capacity during a supramaximal effort

Aim: The present study aimed to verify if there is a difference between genders in anaerobic capacity estimated by energetic equivalents of glycolytic and phosphagen pathways (AC[La-]+EPOCfast). Methods: In this way, 8 men and 8 women (physical education students) were subjected to the following sequence of tests: session 1) graded exercise test to measure the maximal oxygen consumption (VÖ½ O2max) and intensity associated with VÖ½ O2max (iVÖ½ O2max); sessions 2 to 3) familiarization with supramaximal effort at 115% of iVÖ½ O2max; session 4) supramaximal effort at 115% of iVÖ½ O2max to measure AC[La-]+EPOCfast. Results: The AC[La-]+EPOCfast was lower in women compared to men when expressed in absolute and relative values (-38.11%; p=0.01 and -25.71%; p=0.03, respectively). A non-significant difference was observed in performance in the supramaximal effort (-12.08%; p=0.15), besides which, a likely negative inference was observed when comparing women to men. In addition, energetic equivalents of the glycolytic pathway (e[La- ]) were also lower in women when expressed in relative and absolute values (-47.01%; p=0.001 and -36.71%; p=0.001, respectively), however no statistical difference was found for energetic equivalents of the phosphagen pathway (ePCr) (p>0.05). Conclusion: The AC[La-]+EPOCfast is lower in women compared to men, mainly due to differences in the glycolytic pathway.(AU)

Total Lesion Glycolysis Using 18F-FDG PET/CT as a Prognostic Factor for Locally Advanced Esophageal Cancer

Standardized uptake value (SUV), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) have been considered prognostic factors for survival in many cancers. However, their prognostic value for radiotherapy-treated squamous esophageal cancer has not been evaluated. In this study, SUV, MTV, and TLG were measured to predict their prognostic role in overall survival (OS) in 38 esophageal cancer patients who had undergone 18F-FDG PET/CT before radiotherapy. TLG demonstrated higher sensitivity and specificity for predicting OS than MTV and SUV; and a better OS was observed in patients with low TLG compared to those with high TLG in locally advanced disease (OS, 46.9 months; 95% confidence interval [CI], 33.50-60.26 vs. 25.3 months; 95% CI, 8.37-42.28; P=0.003). Multivariate analyses in these patients determined that TLG and the use of combination chemotherapy were the independent prognostic factors for OS (hazard ratio [HR], 7.12; 95% CI, 2.038-24.857; P=0.002 and HR, 6.76; 95% CI, 2.149-21.248; P=0.001, respectively). These results suggest that TLG is an independent prognostic factor for OS and a better predictor of survival than MTV and SUV in patients with locally advanced esophageal cancer treated with radiotherapy.

Obesity Preserves Myocardial Function During Blockade of the Glycolytic Pathway / A Obesidade Preserva a Função do Miocárdio Durante o Bloqueio da Via Glicolítica

Background: Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished. Objective: Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity. Methods: 30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV). Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway. Results: Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C. Conclusion: The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle. .

Fundamento: A obesidade é definida por um acúmulo excessivo do tecido adiposo em relação a massa magra tecidual. Estudos realizados nos últimos anos sugerem que a função cardíaca em animais obesos pode se encontrar preservada, aumentada ou reduzida. Objetivo: Estudar o balanço energético do miocárdio com a hipótese de que o aumento na oxidação de ácidos graxos e redução de glicose levam à disfunção cardíaca na obesidade. Métodos: Ratos Wistar machos com 30 dias de idade foram alimentados com uma dieta padrão ou hipercalórica durante 30 semanas. A função e morfologia cardíacas foram analisadas. Neste trabalho foram estudadas as características gerais e comorbidades associadas com a obesidade. A estrutura cardíaca foi determinada pelo peso do coração e do ventrículo esquerdo (VE). A função do miocárdio foi avaliada pela análise de músculos papilares isolados do VE, na condição basal e depois de manobras inotrópicas e lusitrópicas: rigidez do miocárdio, contração pós-pausa, aumento da concentração extracelular de Ca2+, mudança na frequência de estímulos e inibição da via glicolítica. Resultados: Os ratos obesos tiveram um aumento de tecido adiposo e comorbidades associadas à obesidade em relação aos ratos do grupo controle. A análise funcional após o bloqueio pelo iodoacetato não mostrou diferença na regressão linear da tensão desenvolvida (TD), entretanto, a tensão de repouso (TR) apresentou uma diferença estatística significativa entre o grupo controle e o grupo obeso, mais notadamente na inclinação da curva no grupo C. Conclusão: O desequilíbrio energético na obesidade não promoveu ...

Red neural por defecto y enfermedad de Alzheimer / Default mode network and Alzheimer's disease

Brainfunctioning is mainly intrinsic, notprimarily reflexive. This is supported by the high energy requirements ofthe resting brain (20% ofall the energy consumed) which only marginally increases with changes in brain activity. Modern neuroimaging and neurophysiological techniques have led to the discovery of the so called brain default mode network (DMN), a constellation of brain regions which support brain activity at rest and whose discharges decrease during task-induced activities. Another characteristic ofthe DMN are the elevated levéis of aerobic glycolysis (Warburg effect), that is, metabolism ofglucose to lactic acid in thepresence ofsufficient levéis ofoxygen. In Alzheimer's disease there is amyloid deposition and metabolic disruption at the DMN regions. Changes in connectivity among the different nodes ofthe DMN and its connections with the hippocampus have been reported. The characteristics ofthe DMN and its relation to Alzheimer's disease are discussed. This issue is ofinterest in the pathogenesis and possibly for its usefulness as a biomarker ofthe disease.

Metabolism and brain cancer

Cellular energy metabolism is one of the main processes affected during the transition from normal to cancer cells, and it is a crucial determinant of cell proliferation or cell death. As a support for rapid proliferation, cancer cells choose to use glycolysis even in the presence of oxygen (Warburg effect) to fuel macromolecules for the synthesis of nucleotides, fatty acids, and amino acids for the accelerated mitosis, rather than fuel the tricarboxylic acid cycle and oxidative phosphorylation. Mitochondria biogenesis is also reprogrammed in cancer cells, and the destiny of those cells is determined by the balance between energy and macromolecule supplies, and the efficiency of buffering of the cumulative radical oxygen species. In glioblastoma, the most frequent and malignant adult brain tumor, a metabolic shift toward aerobic glycolysis is observed, with regulation by well known genes as integrants of oncogenic pathways such as phosphoinositide 3-kinase/protein kinase, MYC, and hypoxia regulated gene as hypoxia induced factor 1. The expression profile of a set of genes coding for glycolysis and the tricarboxylic acid cycle in glioblastoma cases confirms this metabolic switch. An understanding of how the main metabolic pathways are modified by cancer cells and the interactions between oncogenes and tumor suppressor genes with these pathways may enlighten new strategies in cancer therapy. In the present review, the main metabolic pathways are compared in normal and cancer cells, and key regulations by the main oncogenes and tumor suppressor genes are discussed. Potential therapeutic targets of the cancer energetic metabolism are enumerated, highlighting the astrocytomas, the most common brain cancer.

Efeito da desnutrição protéica pré e pós-natal sobre a morfologia, a diferenciação e o metabolismo do tecido muscular estriado esquelético em ratos / The effects of prenatal and postnatal malnutrition on the morphology, differentiation, and metabolism of skeletal striated muscle tissue in rats

OBJETIVO: Estudar características morfológicas, metabolismo e habilidades contráteis do músculo submetido a desnutrição protéica pré e pós-natal. MÉTODOS: Distribuição dos animais em dois grupos: controle, dieta normoprotéica (GC; n = 15; 5/5/5) e desnutrido, dieta hipoprotéica (GD; n = 15; 5/5/5), observados respectivamente no sétimo, 14º e 28º dia do período experimental. Foram avaliados massa corporal total, peso, habilidades contráteis e a morfologia do músculo tibial anterior. Amostras de tecidos com 8 m de espessura de ratos com idades de 7, 14 e 28 dias, corados por hematoxilina e eosina, e outros submetidos aos métodos histoquímicos nicotinamida adenina tetrazólio redutase (NADH-TR) e miofibrilar (m-ATPase) (pH = 4,4). RESULTADOS: Os pesos corporal e muscular apresentaram-se menores nos grupos desnutridos. Aos 7 dias de desnutrição, o músculo apresentou fibras com menor diâmetro, maior polimorfismo e maior teor de tecido conjuntivo endomisial. Nas histoquímicas, tipos de fibras sem delimitação segura. Aos 14 dias de desnutrição, fibras menores, mais polimórficas, muitas com núcleos centrais e moderado teor de tecido conjuntivo endomisial. Quanto à contração, a reação m-ATPase evidenciou fibras lentas e rápidas. A reação NADH-TR revelou os tipos de fibras slow oxidative, fast oxidative glycolytic e fast glycolytic. Aos 28 dias de desnutrição, fibras menores, agrupadas com contornos variáveis. Quanto ao tipo de contração e metabolismo, os três tipos de fibras apresentaram limites de reconhecimento indistinto. CONCLUSÃO: Os resultados experimentais sugerem que, além da redução no número de fibras, a desnutrição promove um retardamento na diferenciação das características morfológicas, metabólicas e contráteis dos tipos de fibras musculares esqueléticas em ratos na fase de crescimento.

OBJECTIVE: To study the contractile properties, metabolism and morphological characteristics of muscles submitted to prenatal and postnatal protein malnutrition. METHODS: Animals were distributed into two groups: Control, normoprotein diet (CG; n = 15; 5/5/5), and Malnourished, hypoprotein diet (MG; n = 15; 5/5/5), and examined on the 7th, 14th, and 28th days of the experiment. Total body mass, weight, and the contractile properties and morphology of the anterior tibial muscle were assessed. Several 8 µm-thick tissue samples were taken from 7, 14, and 28 day old rats and stained with HE or subjected to NADH-TR or m-ATPase (pH = 4.4) techniques. RESULTS: Body and muscle weight were lower in the malnourished group. On the 7th day of malnutrition, muscle samples exhibited fibers with smaller diameter, higher polymorphism and higher endomysial conjunctive tissue content. Histochemical methods were unable to precisely determine the types of fiber present. On the 14th day, there were smaller muscle fibers, more polymorphism, many of them with central nuclei and moderate endomysial conjunctive tissue content. With reference to contractile properties, the m-ATPase reaction identified both slow and fast fibers. The NADH-TR reaction revealed the following types of fiber: slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (FG). On the 28th day smaller, bunched muscle fibers varying shapes. All three types of fiber exhibited unclear recognition limits with respect to contraction and metabolism. CONCLUSION: Our experimental results suggest that, in addition to the reduction in numbers of fibers, malnutrition retards the differentiation of the morphological, metabolic, and contractile characteristics of skeletal muscle fibers in growing rats.

Relation between increased anaerobic glycolysis and visual acuity in long-standing type 2 diabetes mellitus without retinopathy.

In long-standing diabetes mellitus, blood flow to essential organs including the retina is reduced owing to macrovascular and/or microvascular changes. Poor glycolytic pathway of glucose metabolism owing to tissue hypoxia caused by ischemia at capillary bed of essential organs produces excessive lactic acid and less of adenosine triphosphate, which lead to poor cellular function. The purpose of the study was to evaluate the relationship between increased anaerobic glycolysis and visual acuity in type 2 diabetes mellitus without retinopathy. Fifty patients of type 2 diabetes mellitus of 10-12 years duration, without retinopathy, constituted the study group. The controls were 50 age-matched healthy persons without diabetes mellitus. Blood lactate level and best-corrected visual acuity (BCVA) were measured in both the groups. The mean blood lactate level was 1.05 mM/l in the control group and 2.32 mM/l in the study group. BCVA of 20/20 (log MAR 0) was seen in 48 (96%) patients of the control group and in 27 (54%) patients of the study group. BCVA of 20/30 (log MAR 0.2) was seen in 23 (46%) patients in the study group and 2 (4%) in the control group. Association of higher blood lactate level with decreased BCVA in the study group was statistically significant (P< 0.001).

Evaluation of the influence of cetylamine fluoride and sodium fluoride on acid production by S. mutans

The acidogenic character of Streptococcus mutans has been pointed out as one of the most important physiological aspects associated with dental caries establishment. Fluoride is a key component of oral health promotion. Amine fluorides (AmF) have been used in products such as mouth rinses, toothpastes, gels and other topical fluoride agents for over 30 years in several European countries. In Brazil, the use of such substances was limited to toothpaste until August 2000, when a new resolution was published to approve the use of three AmFs in mouth rinses and other formulations for odontological purposes. In this report the influence of cetylamine fluoride (CAmF) and sodium fluoride (NaF) on acid production...

Influence of exercise on the activity and the distribution between free and bound forms of glycolytic and associated enzymes in tissues of horse mackerel

The effects of short-term burst (5 min at 1.8 m/s) swimming and long-term cruiser (60 min at 1.2 m/s) swimming on maximal enzyme activities and enzyme distribution between free and bound states were assessed for nine glycolytic and associated enzymes in tissues of horse mackerel, Trachurus mediterraneus ponticus. The effects of exercise were greatest in white muscle. The activities of phosphofructokinase (PFK), pyruvate kinase (PK), fructose-1,6-bisphosphatase (FBPase), and phosphoglucomutase (PGM) all decreased to 47, 37, 37 and 67 percent, respectively, during 60-min exercise and all enzymes except phosphoglucoisomerase (PGI) and PGM showed a change in the extent of binding to subcellular particulate fractions during exercise. In red muscle, exercise affected the activities of PGI, FBPase, PFK, and lactate dehydrogenase (LDH) and altered percent binding of only PK and LDH. In liver, exercise increased the PK activity 2.3-fold and reduced PGI 1.7-fold only after 5 min of exercise but altered the percent binding of seven enzymes. Fewer effects were seen in brain, with changes in the activities of aldolase and PGM and in percent binding of hexokinase, PFK and PK. Changes in enzyme activities and in binding interactions with subcellular particulate matter appear to support the altered demands of tissue energy metabolism during exercise

Intermediary metabolism of fast-growth tumor cells

Tumor cells show several modifications in their metabolism in comparison with normal cells. In particular, tumor cells show an accelerated glycolysis and a low O2 dependence, which are matabolic modifications involved in the resistance of many tumor cell lines to radiation. Thus, a strategy to enhace the radiosensitivity could be the transformation of the glycolytic metabolism of tumor cells into an oxidative type of metabolism, i.e., to induce the ATP supply to dependend solely on oxidative phosphorylation. Therefore, this review emphasizes the relevance of oxidative phosphorylation on tumor cells regarding (a) its contributions to ATP supply for cell duplication during the proliferative phase, and (b) the possible therapeutic implications of having oxidative rather than glycolytic tumor cells

Effect of protein malnutrition on the glycolytic and glutaminolytic enzyme activity of rat thymus and mesenteric lymph nodes

The activity of important glycolytic enzymes (hexokinase, phosphofructokinase, aldolase, phosphohexoseisomerase, pyruvate kinase and lactate dehydrogenase) and glutaminolytic enzymes (phosphate-dependent glutaminase) was determined in the thymus and mesenteric lymph nodes of wistar rats submited to protein malnutrition (6 percent protein in the diet rather than 20 percent) from conception to 12 weeks after birth. The wet weight (g) of the thymus and mesenteric lymph nodes decreased due to protein malnutrition by 87 percent (from 0.30 + 0.05 to 0.04 + 0.01) and 75 percent (0.40 + 0.04 to 0.10 + 0.02), respectively. The protein content was reduced only in the thymus from 102.3 + 4.4 (control rats) to 72.6 + 6.6 (malnourished rats). The glycolytic enzymes were not affected by protein malnutrition, but the glutaminase activity of the thymus and lymph nodes was reduced by halfing in protein-malnourished rats as compared to controls. This fact may lead to a decrease in the cellularity of the organ and thus in its size, weight and protein content.

Enzymes of glycolytic and pentose phosphate pathways in cytosolic and leucoplastic fractions of developing seeds of Brassica campestris.

Distribution of the enzymes of glycolytic and pentose phosphate pathways were studied in cytosolic and leucoplastic fractions of the developing seeds of Brassica. Leucoplasts were isolated using a discontinuous percoll gradient. Intactness of leucoplasts was checked by ADP-glucose pyrophosphorylase assay in presence and absence of triton X-100. No contamination by microbodies, mitochondria and cytosol was observed as assessed by measuring the activities of marker enzymes. The recovery, latency and specific activity of each enzyme in different fractions were compared. The leucoplastic fraction contained complete set of the enzymes of glycolytic and pentose phosphate pathways, indicating that the two subcellular compartments metabolize carbon independently by these pathways. However, the enzymes showed higher activities in cytosolic fraction as compared to those in the leucoplasts, suggesting the need for exchange of metabolites in the two compartments through various translocators, for acting in cooperation to produce energy, reducing power and carbon skeletons for different biosynthetic activities in the non-photosynthetic plastids. Based on these compartmentation studies, a model for carbon flow for fatty acid synthesis in leucoplasts of developing Brassica seeds has been proposed.

6-fosfofructo-1-quinasa (PFK-1) / 6-phosphofructo-1-kinase

El objetivo de la presente revisión es describir los efectos que tienen algunos moduladores descritos recientemente en la literatura, sobre la actividad de la 6-fosfofructo-1-quinasa. Esta enzima es clave del proceso glicolitico y su control se realiza mediante fosforilación/defosforilación, en los distintos tejidos estudiados