Asociación de obesidad general y abdominal con hipertensión, dislipemia y presencia de prediabetes en el estudio PREDAPS / Association of general and abdominal obesity with hypertension, dyslipidemia and prediabetes in the PREDAPS study

Introducción y objetivos: Algunas medidas antropométricas muestran mayor capacidad que otras para discriminar la presencia de factores de riesgo cardiovascular. Este trabajo estima la magnitud de la asociación de diversos indicadores antropométricos de obesidad con hipertensión, dislipemia y prediabetes (glucemia basal o glucohemoglobina alteradas). Métodos: Análisis transversal de la información recogida en 2.022 sujetos del estudio PREDAPS (etapa basal). Se definió obesidad general como índice de masa corporal ≥ 30 kg/m2 y obesidad abdominal con 2 criterios: a) perímetro de cintura (PC) ≥ 102 cm en varones/PC ≥ 88 cm en mujeres, y b) índice cintura/estatura (ICE) ≥ 0,55. La magnitud de la asociación se estimó mediante regresión logística. Resultados: La hipertensión arterial mostró la asociación más alta con la obesidad general en mujeres (OR = 3,01; IC95%, 2,24-4,04) y con la obesidad abdominal según el criterio del ICE en varones (OR = 3,65; IC95%, 2,66-5,01). La hipertrigliceridemia y los valores bajos de colesterol unido a lipoproteínas de alta densidad mostraron la asociación más alta con obesidad abdominal según el criterio del ICE en mujeres (OR = 2,49; IC95%, 1,68-3,67 y OR = 2,70; IC95%, 1,89-3,86) y la obesidad general en varones (OR = 2,06; IC95%, 1,56-2,73 y OR = 1,68; IC95%, 1,21-2,33). La prediabetes mostró la asociación más alta con obesidad abdominal según el criterio del ICE en mujeres (OR = 2,48; IC95%, 1,85-3,33) y con obesidad abdominal según el criterio del PC en varones (OR = 2,33; IC95%, 1,75-3,08). Conclusiones: Los indicadores de obesidad abdominal mostraron la mayor asociación con la presencia de prediabetes. La relación de los indicadores antropométricos con hipertensión y con dislipemia mostró resultados heterogéneos (AU)

Introduction and objectives: Some anthropometric measurements show a greater capacity than others to identify the presence of cardiovascular risk factors. This study estimated the magnitude of the association of different anthropometric indicators of obesity with hypertension, dyslipidemia, and prediabetes (altered fasting plasma glucose and/or glycosylated hemoglobin). Methods: Cross-sectional analysis of information collected from 2022 participants in the PREDAPS study (baseline phase). General obesity was defined as body mass index ≥ 30 kg/m2 and abdominal obesity was defined with 2 criteria: a) waist circumference (WC) ≥ 102 cm in men/WC ≥ 88 cm in women, and b) waist-height ratio (WHtR) ≥ 0.55. The magnitude of the association was estimated by logistic regression. Results: Hypertension showed the strongest association with general obesity in women (OR, 3.01; 95%CI, 2.24-4.04) and with abdominal obesity based on the WHtR criterion in men (OR, 3.65; 95%CI, 2.66-5.01). Hypertriglyceridemia and low levels of high-density lipoprotein cholesterol showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.49; 95%CI, 1.68-3.67 and OR, 2.70; 95%CI, 1.89-3.86) and with general obesity in men (OR, 2.06; 95%CI, 1.56-2.73 and OR, 1.68; 95%CI, 1.21-2.33). Prediabetes showed the strongest association with abdominal obesity based on the WHtR criterion in women (OR, 2.48; 95%CI, 1.85-3.33) and with abdominal obesity based on the WC criterion in men (OR, 2.33; 95%CI, 1.75-3.08). Conclusions: Abdominal obesity indicators showed the strongest association with the presence of prediabetes. The association of anthropometric indicators with hypertension and dyslipidemia showed heterogeneous results (AU)

A Computational Approach to Studying Protein Folding Problems Considering the Crucial Role of the Intracellular Environment.

Intracellular protein folding (PF) is performed in a highly inhomogeneous, crowded, and correlated environment. Due to this inherent complexity, the study and understanding of PF phenomena is a fundamental issue in the field of computational systems biology. In particular, it is important to use a modeled medium that accurately reflects PF in natural systems. In the current study, we present a simulation wherein PF is carried out within an inhomogeneous modeled medium. Simulation resources included a two-dimensional hydrophobic-polar (HP) model, evolutionary algorithms, and the dual site-bond model. The dual site-bond model was used to develop an environment where HP beads could be folded. Our modeled medium included correlation lengths and fractal-like behavior, which were selected according to HP sequence lengths to induce folding in a crowded environment. Analysis of three benchmark HP sequences showed that the modeled inhomogeneous space played an important role in deeper energy folding and obtained better performance and convergence compared with homogeneous environments. Our computational approach also demonstrated that our correlated network provided a better space for PF. Thus, our approach represents a major advancement in PF simulations, not only for folding but also for understanding functional chemical structure and physicochemical properties of proteins in crowded molecular systems, which normally occur in nature.

Modeling Intercellular Communication as a Survival Strategy of Cancer Cells: An In Silico Approach on a Flexible Bioinformatics Framework.

Intercellular communication is very important for cell development and allows a group of cells to survive as a population. Cancer cells have a similar behavior, presenting the same mechanisms and characteristics of tissue formation. In this article, we model and simulate the formation of different communication channels that allow an interaction between two cells. This is a first step in order to simulate in the future processes that occur in healthy tissue when normal cells surround a cancer cell and to interrupt the communication, thus preventing the spread of malignancy into these cells. The purpose of this study is to propose key molecules, which can be targeted to allow us to break the communication between cancer cells and surrounding normal cells. The simulation is carried out using a flexible bioinformatics platform that we developed, which is itself based on the metaphor chemistry-based model.

The hemicellulose preparation, Natramune (PDS-2865), increases macrophage phagocytosis and nitric oxide production and increases circulating human lymphocytes levels.

BACKGROUND: Hemicellulose containing nutritional supplements demonstrate benefits to the immune system in vitro and in vivo. Here we show that Natramune (PDS-2865) stimulates phagocytosis, nitric oxide production and boosts viability in J774A.1 murine machrophages. We also show that dietary supplementation with Natramune (PDS-2865) significantly increases the levels of circulating lymphocytes in human subjects. MATERIAL/METHODS: In order to measure the beneficial effects of Natramune (PDS-2865) on cells of the immune system, phagocytosis was measured by J774A.1 uptake of fluorescently labeled E. Coli bioparticles, nitric oxide production was measured by the formation of nitrite, and cell proliferation and viability was measured by NADH reduction of WST-8. The effect of Natramune (PDS-2865) on human circulating leukocyte levels was measured in 18 volunteers after an 8 week regimen of two 250 mg doses daily after which blood was collected and blood cell number and types were counted. RESULTS: Natramune (PDS-2865) stimulated phagocytosis, nitric oxide production and promoted proliferation/viability in J774A.1 cells by 65%, 517%, and 155% respectively. Further, Natramune (PDS-2865) did boost human circulating total lymphocyte levels (18%) in a statistically significant manner and while all lymphocyte subtype levels also increased, the individual subtype increases were not statistically significant. CONCLUSIONS: Dietary supplementation with Natramune (PDS-2865) enhances immune system function and vitality.

Natramune and PureWay-C reduce xenobiotic-induced human T-cell alpha5beta1 integrin-mediated adhesion to fibronectin.

BACKGROUND: In vitro and in vivo studies demonstrate that nutritional supplementation reduces inflammation and inflammatory markers associated with T-cell adhesion mechanisms. Here, we investigate the effects of the nutritional supplements, Natramune (PDS-2865) and PureWay-C, on xenobiotic-induced alpha5beta1 integrin-mediated T-cell adhesion to fibronectin. MATERIAL/METHODS: The human CD4+ lymphoblastoid cell line CEM SS was treated with combinations of bifenthrin, blocking antibodies to human beta1 and alpha5 integrin, and nutrient supplements. After 30 minutes unattached cells were aspirated and the percent of attached cells was determined. RESULTS: Bifenthrin stimulated T-cell adhesion to fibronectin at concentrations between 1.0 and 100 microM with a maximal stimulation of 8.3-fold at 10 microM. At 500 microg/ml, Natramune reduced 100 microM bifenthrin-induced adhesion by nearly 90%. PureWay-C reduced by 1.5-fold the level of T-cell adhesion stimulated by bifenthrin concentrations of both 10 microM and 100 microM. The combination of Natramune and PureWay-C resulted in a 6.3 and 7.5-fold inhibition at 10 microM and 100 microM bifenthrin respectively. Antibody blocking studies demonstrated that bifenthrin induced CEM SS adhesion to fibronectin is mediated through alpha5beta1 integrin. Inhibition of T-cell adhesion achieved by anti-integrin antibodies was further reduced with 50 and 500 microg/ml Natramune treatment. Pretreatment of fibronectin with Natramune did not alter induced T-cell adhesion to fibronectin. CONCLUSIONS: These data demonstrate that xenobiotic-induced alpha5beta1 integrin mediated T-cell adhesion to fibronectin is reduced by nutritional supplementation with Natramune (PDS-2865) and PureWay-C. These data suggest the possibility that inflammatory responses associated with exposure to pollutants can be mitigated by nutritional supplementation.

Absorption rates and free radical scavenging values of vitamin C-lipid metabolites in human lymphoblastic cells.

BACKGROUND: In this study we investigated the cellular absorption rates, antioxidant and free radical scavenging activity of vitamin C-lipid metabolites. The absorption was measured in a human lymphoblastic cell line using a spectrophotometric technique. MATERIAL/METHODS: Cellular vitamin C levels in the human lymphoblastic H9 cell line were measured using the 2,4-dinitrophenylhydrazine spectrophotometric technique. Free radical scavenging activity of vitamin C-lipid metabolites was measured by the reduction of 1,1-diphenyl-2-picryl hydrazyl (DPPH) to 1,1-diphenyl-2-picryl hydrazine. Vitamin C-lipid metabolite scavenging of peroxyl radical oxygen reactive species (ORAC) was determined by fluorescence spectrophotometry. RESULTS: Compared to ascorbic acid (AA), calcium ascorbate (CaA), and calcium ascorbate-calcium threonate-dehydroascorbate (Ester-C), vitamin C-lipid metabolites (PureWay-C) were more rapidly absorbed by the H9 human T-lymphocytes. The vitamin C-lipid metabolites (PureWay-C) also reduced pesticide-induced T-lymphocyte aggregation by 84%, while calcium ascorbate-calcium threonate-dehydroascorbate (Ester-C) reduced aggregation by only 34%. The vitamin C-lipid metabolites (PureWay-C) demonstrated free radical scavenging activity of nearly 100% reduction of DPPH at 20 microg/ml and oxygen radical scavenging of over 1200 micro Trolox equivalents per gram. CONCLUSIONS: These data demonstrate that the vitamin C-lipid metabolites (PureWay-C) are more rapidly taken-up and absorbed by cells than other forms of vitamin C, including Ester-C. This increased rate of absorption correlates with an increased protection of the T-lymphocytes from pesticide toxicities. Further, vitamin C-lipid metabolites (PureWay-C) are a potent antioxidant and have significant free radical scavenging capabilities.

A novel vitamin C preparation enhances neurite formation and fibroblast adhesion and reduces xenobiotic-induced T-cell hyperactivation.

BACKGROUND: Vitamin C (ascorbic acid, ascorbate) has been shown to enhance neurite outgrowth, promote fibroblast adhesion during wound healing, and reduce xenobiotic-induced leukocyte hyperactivity and inflammatory damage. In this study, a comparison was made between Ester-C and PureWay-C on these various cellular activities. MATERIAL/METHODS: PC12 cells were stimulated to form neurites with nerve growth factor, NIH 3T3 fibroblasts were seeded on fibronectin and H9 T-cells were stimulated to aggregate with the pyrethroid pesticide bifenthrin. The rate of neurite formation, fibroblast adhesion and T-cell homotypic aggregation was then measured in the absence and presence of various formulations of vitamin C including Ester-C and PureWay-CTM. RESULTS: With PureWay-C treatment, 12% of PC12 cells extended neurites within one hour of treatment and 45% of the cells extended neurites by hour nine. With Ester-C, 0% and 15% extended neurites at one and nine hours, respectively. NIH-3T3 fibroblast adhesion to fibronectin was enhanced by 4.7-fold with a 30 minute PureWay-CTM treatment while Ester-C increased fibroblast adhesion by only 1.5 fold. Further, PureWay-CTM reduced pesticide-mediated T-cell homotypic aggregation by 83% within 30 minutes of treatment while the reduction seen with Ester-C was only 33%. CONCLUSIONS: These data confirm the previous observations that vitamin C supplementation can promote neurite outgrowth, increase fibroblast adhesion and reduce xenobiotic induce immunocytes aggregation. More importantly, these data show that PureWay-C has a faster and greater beneficial effect on these parameters when compared to other vitamin C formulations.

PolicosanolPlus and Neuroprevin ameliorate pesticide-mediated inhibition of neurite outgrowth and neurite degeneration.

BACKGROUND: Pesticide exposure is a recognized risk factor for neurodegenerative diseases. Recently, bifenthrin, a pyrethroid pesticide, was shown to inhibit the formation of neurites and cause neurite retraction, raising concern that these newer and less toxic pesticides may also contribute to neurodegenerative diseases. PolicosanolPlus and Neuroprevin are nutraceutical supplements which promote the survival of neurites in neuronal cell cultures. Here we determine if PolicosanolPlus and Neuroprevin can ameliorate the neurodegenerative effects of bifenthrin. MATERIAL/METHODS: PC12 cells were treated with NGF, bifenthrin, PolicosanolPlus and Neuroprevin in various combinations and the formation of neurites was assessed microscopically at times ranging from 12 to 72 hours post treatment. Bifenthrin was also withheld at the time of NGF, PolicosanolPlus and Neuroprevin treatment and added after neurite formed to assess neurite retraction. RESULTS: Bifenthrin (1 x 10(-6) M) inhibits neurite outgrowth, in the absence of cell death, by more than 50% at 12 hours and by more than 80% at 72 hours. With addition of PolicosanolPlus and/or Neuroprevin at the time of cell seeding, bifenthrin does not inhibit neurite outgrowth. Addition of bifenthrin to differentiated cells results in a retraction of 90% of neurites, while those with PolicosanolPlus and Neuroprevin show no significant retraction of neurites. CONCLUSIONS: The pesticide, bifenthrin, inhibits neurite formation and causes neurite retraction. PolicosanolPlus and Neuroprevin are nutraceutical supplements which ameliorate the effects of bifenthrin on neurite outgrowth and retraction. Dietary supplementation with PolicosanolPlus and Neuroprevin may protect against developmental and long-term neurodegenerative events that result from exposure to pesticides.