Nutritional assessment by subjective methods versus computed tomography to predict survival in oncology patients.

OBJECTIVES: The aim of this study was to analyze the association between survival and two validated methods of nutritional assessment: body composition through computed tomography (CT) scans and Patient-Generated Subjective Global Assessment (PG-SGA). METHODS: Cancer-bearing patients (n = 103) hospitalized in the Oncology Ward of Clínica Alemana in Santiago, Chile, for palliative or curative treatment were assessed by both methods. Images from abdominal CT scans at the L3 level were analyzed by SliceOmatic (version 5.0), to measure muscle and fat areas and densities. Skeletal muscle mass index (MMI) was calculated using total abdominal mass area (psoas + rest of muscles)/ height2. These were compared with those obtained for assessment of trauma of 130 healthy young adults (18-40 y of age), as reference control values. Sarcopenia was established as MMI<1 SD compared with control participants. RESULTS: Patients with cancer had less muscle and higher abdominal fat areas compared with controls (P < 0.05). According to the PG-SGA, ~50% were classified as malnourished. Patients were followed for 38 mo, when 53% had died. Survival time was significantly and negatively correlated with PG-SGA score, cancer stage, and sarcopenia, independent of age and sex. Multivariate analysis included both cancer stage and nutritional assessment variables. CONCLUSIONS: Together with cancer stage, both CT measurements and subjective assessment of nutritional status through PG-SGA can adequately identify cancer patients with a higher mortality risk, independent of age and sex. However, the latter is less costly and simple to use; it should be included as a valuable tool during management of patients with cancer.

Effects of Two Training Modalities on Body Fat and Insulin Resistance in Postmenopausal Women.

Henríquez, S, Monsalves-Alvarez, M, Jimenez, T, Barrera, G, Hirsch, S, de la Maza, MP, Leiva, L, Rodriguez, JM, Silva, C, and Bunout, D. Effects of two training modalities on body fat and insulin resistance in postmenopausal women. J Strength Cond Res 31(11): 2955-2964, 2017-Our objective was to compare the effects of a low-load circuit resistance training protocol and usual aerobic training in postmenopausal women. Postmenopausal women with at least 1 feature of the metabolic syndrome were randomly allocated to a low-load circuit resistance training protocol or traditional aerobic training in a braked cycle ergometer. The intervention consisted in supervised sessions lasting 40 minutes, 3 times per week, during 6 months. At baseline and at the end of the intervention, fasting serum lipid levels, serum interleukin 6, C-reactive protein, 8 isoprostanes, and insulin resistance (assessed through QUICKI and HOMA-IR) were measured. Body fat was measured by double-beam X-ray absorptiometry and by computed tomography densitometric quantification at lumbar 3 vertebral level. Twenty-one women aged 58 (54-59) years were allocated to aerobic training and 21 women aged 55 (52-61) years were allocated to the low-load circuit resistance training protocol. Eighteen and 16 women in each group completed the 6 months training period. Women in both groups experienced significant reductions in blood pressure, total body, subcutaneous, and intraabdominal body fat. Reductions in total cholesterol and triacylglycerol levels were also observed. No changes in insulin resistance indexes, 8 isoprostanes, C-reactive protein, or interleukin 6 were observed in either group. No significant differences between treatment groups were observed in any of the measured parameters. We conclude that low-load circuit resistance training and aerobic training resulted in the same reductions in body fat and serum lipid levels.

Irisin is weakly associated with usual physical activity in young overweight women

PURPOSE: To determine if irisin plasma levels are associated with regular physical activity, body composition and metabolic parameters in women subjected to calorie restriction. SUBJECTS AND METHODS: We studied 42 women aged 34 ± 13 years with a body mass index of 27.7 ± 1.8 kg/m2, who were subjected to a calorie restriction for three months. At baseline and at the end of the study, weight, waist and hip circumference, laboratory parameters, body composition by DEXA, resting and activity energy expenditure by indirect calorimetry and 72 hours actigraphy were measured. Fasting serum irisin was quantified using an ELISA kit. RESULTS: After the intervention period, participants lost 1.5 (0.4-3.4) kg and irisin levels did not change. Irisin baseline levels were positively but weakly correlated with the level of physical activity. This association was lost at the end of the intervention. No association was found between irisin levels and body composition or insulin sensitivity or their changes after calorie restriction. No association between serum irisin levels and PGC-1αexpression in peripheral blood mononuclear cells and serum irisin was observed. CONCLUSIONS: Fasting serum irisin was weakly associated with usual physical activity and did not change after calorie restriction.

Folates Induce Colorectal Carcinoma HT29 Cell Line Proliferation Through Notch1 Signaling.

Folic acid (FA) consumption at high levels has been associated with colon cancer risk. Several mechanisms have been proposed to explain this association. The Notch signal pathway has been implicated in the regulation of cellular proliferation. Our aim was to demonstrate that high concentrations of FA or its reduced form, 5-methyltetrahydrofolic acid (5-MTHF), increase colorectal carcinoma HT29 cell proliferation through an increase of Notch1 activation and to prove if the inhibition of Notch1 activation by gamma secretase inhibitor, reduce the effect of folic acid. HT29 cells were cultured in high (400 nM), low (20 nM), or 0 nM FA or 5-MTHF concentrations during 96 h with or without DAPT (gamma secretase inhibitor). Cell proliferation was determined by the methylthiazole tetrazolium method, and Notch1-intracellular domain (NICD) was analyzed by flow cytometry. HT29 cells exposed to 400 nM FA or 5-MTHF showed higher proliferation rate than those exposed to 20 nM of FA or 5-MTHF (P < 0.01) during 96 h. NICD expression increased at higher FA or 5-MTHF concentrations compared with lower concentrations (P < 0.01). This effect on proliferation was partially reversible when we blocked Notch1 activation with the inhibitor of γ-secretase (P < 0.05).These data suggest that high concentration of FA and 5-MTHF induce HT29 cell proliferation activating Notch1 pathway.

Relación entre estado nutricional y evolución postoperatoria, en cirugía oncológica digestiva / Nutritional status and postoperative complications in patients with digestive cancer

Background: Risk of malnutrition is elevated among oncologic patients, and this increases postoperative morbidity and mortality. Aim: To study the association between nutritional status and postoperative outcomes in a group of patients with gastrointestinal cancers. Patients and Methods: We studied 129 patients with diagnosis of digestive cancer, previous to potentially curative surgery. Nutritional status was evaluated through anthropometric measures, Subjective Global Assessment (SGA), dietary intake recalls and routine biochemical parameters. Functional performance was assessed by the Karnofsky index (KI). Cancer stage was classified according to TNM4. During the postoperative period, complications, length of stay at the critical care ward and duration of hospitalization were registered. Thirty days after discharge, patients were contacted, and the appearance of new complications was listed. Results: According to SGA 14.7% of patients were classified as well nourished (A), 57.3% as moderately undernourished or at risk of malnutrition (B) and 27.9% as severely malnourished (C). The incidence of total complications was 25.5%. Nutritional status was not associated with cancer stage. The frequency of complications among patients classified as A, B and C were 5.5, 25.3 and 37.1% respectively (p = 0.03). Conclusions: We detected a high frequency of malnutrition in this group of patients. Overall the frequency of postoperative complications was low, however malnourished patients exhibited a higher rate of surgical complications.

[Nutritional status and postoperative complications in patients with digestive cancer]. / Relación entre estado nutricional y evolución postoperatoria, en cirugía oncológica digestiva.

BACKGROUND: Risk of malnutrition is elevated among oncologic patients, and this increases postoperative morbidity and mortality. AIM: To study the association between nutritional status and postoperative outcomes in a group of patients with gastrointestinal cancers. PATIENTS AND METHODS: We studied 129 patients with diagnosis of digestive cancer, previous to potentially curative surgery. Nutritional status was evaluated through anthropometric measures, Subjective Global Assessment (SGA), dietary intake recalls and routine biochemical parameters. Functional performance was assessed by the Karnofsky index (KI). Cancer stage was classified according to TNM4. During the postoperative period, complications, length of stay at the critical care ward and duration of hospitalization were registered. Thirty days after discharge, patients were contacted, and the appearance of new complications was listed. RESULTS: According to SGA 14.7% of patients were classified as well nourished (A), 57.3% as moderately undernourished or at risk of malnutrition (B) and 27.9% as severely malnourished (C). The incidence of total complications was 25.5%. Nutritional status was not associated with cancer stage. The frequency of complications among patients classified as A, B and C were 5.5, 25.3 and 37.1% respectively (p = 0.03). CONCLUSIONS: We detected a high frequency of malnutrition in this group of patients. Overall the frequency of postoperative complications was low, however malnourished patients exhibited a higher rate of surgical complications.

Bariatric surgery decreases carotid intima-media thickness in obese subjects.

BACKGROUND: Obesity has long been associated with an increased risk of cardiovascular disease (CVD). The aim of this study was to evaluate the impact of substantial weight loss induced by bariatric surgery on carotid intima media thickness (C-IMT) (surrogate marker of early atherosclerosis) and classic factors of cardiovascular risk (CVRFs). METHODS: thirty-one obesity patients were evaluated for bariatric surgery. Twenty-seven were undergone surgery, 14 Roux-en-Y gastric bypass surgery (GBS) and 13 sleeve gastrectomy. The four obese patients who did not undergo surgery, were performed the same evaluations. MEASUREMENTS: Body weight, BMI, blood pressure, total cholesterol, TC levels, LDL-C, HDL-C, TG, fasting plasma glucose and insulin, HOMA IR, and US B-mode C-IMT was measured. RESULTS: After 354 ± 92 days follow up, 27 patients that underwent bariatric surgery evidenced a mean body mass index decrease from 38 to 27 k/m² (p < 0.001), simultaneously was observed improvement in CVRFs, 10 years Framingham risk and a significant reduction of therapeutic requirements. C-IMT diminished from a mean of 0.58 ± 0.14 mm to 0.49 ± 0.09 mm (p = 0.0001). Four patients that did not undergo surgery increased C-IMT from 0.52 ± 0.12 to 0.58 ± 0.13 mm (p = 0.03) with no significant changes in CVRFs. CONCLUSION: Weight loss, one year after bariatric surgery, GBS and sleeve gastrectomy, decreases C-IMT; improve CVRFs and 10 years Framingham risk.

Introducción: La obesidad se ha asociado a un aumento del riesgo cardiovascular. El objetivo de este estudio fue evaluar el impacto de la baja de peso a través de la cirugía bariátrica en el grosor íntima media carotídea (GIMc, marcador subrogado de aterosclerosis subclínica) y los factores de riesgo cardiovascular clásicos. Métodos: Un total de 31 pacientes obesos fueron evaluados para cirugía bariátrica, 27 fueron intervenidos quirúrgicamente, 14 sometidos a un bypass gástrico en Y de Roux y 13 a gastrectomía en manga. En los 4 pacientes que no fueron sometidos a cirugía bariátrica se realizó las mismas evaluaciones. Parámetros: peso, índice de masa corporal (IMC), presión arterial, colesterol total, LDL, HDL, triglicéridos, glicemia e insulina de ayunas, HOMA IR y medición del GIMc mediante ultrasonido. Resultados: Luego de 354 + 92 días de seguimiento, en los 27 pacientes intervenidos se evidenció una disminución del IMC promedio de 38 a 27 k/m2 (p < 0,001), al mismo tiempo se observó una reducción en los marcadores de riesgo cardiovascular, en el riesgo de Framingham a 10 años, y una significativa reducción de la terapia farmacológica. El promedio del GIMc se redujo de 0,58 ± 0,14 mm a 0,49 ± 0,09 mm (p = 0,0001). Los cuatro pacientes que no fueron intervenidos presentaron un aumento del GIMc 0,52 ± 0,12 a 0,58 ± 0,13 mm (p = 0,03) sin cambios significativos en los marcadores de riesgo cardiovascular durante el período observado. Conclusión: La pérdida de peso inducida por la cirugía bariátrica, tanto bypass gástrico como gastrectomía en manga, a un año de seguimiento disminuye el GIMc, mejora los factores de riesgo cardiovascular y el riesgo de Framingham a 10 años.

Natural killer cell cytotoxicity is not regulated by folic acid in vitro.

OBJECTIVES: Folate supplementation may be associated with an increased risk of developing several types of cancer and a derangement of immune function. Among the latter, Natural killer (NK) cells are involved in non-MHC-restricted natural immunity against malignant target cells. Abnormalities in NK cell number or function have been associated with a higher cancer risk. The aim of this study was to study in vitro the possible effect of different concentrations of 5-methyltetrahydrofolic acid (5-MTHF) or folic acid on NK cell cytotoxic function, and expression of the stimulatory and inhibitory receptors KIRDL4, KIRDL3, and NKG2D. METHODS: Volunteer-derived peripheral mononuclear cells (PBMC) and highly enriched NK cells (95% CD56+ CD16+) were grown in folic acid free-RPMI 1640, supplemented either with folic acid or 5-MTHF (15-100 nM) during 72 h to 96 h. RESULTS: No differences in the cytolytic activity of PBMC and enriched NK cells were observed. After 96 h of in vitro culture without folate or supplemented with FA or 5-MTHF (30 or 100 nM), there were no changes in the percentage of HPNK receptor-positive cells. CONCLUSIONS: Our data indicate that a high dose of 5-MTHF or folic acid does not influence NK cell function in vitro.

Estudio piloto sobre entrenamiento físico durante hemodiálisis / A pilot study on physical training of patients in hemodialysis

Background: Exercise training during the dialytical procedure may have positive cardiovascular effects and prevent or revert muscle wasting in patients undergoing chronic hemodialysis. Aim: To evaluate the effects of an exercise training program in patients undergoing chronic hemodialysis. Material and Methods: Fifteen patients on chronic hemodialysis aged 21 to 69 years (three females) were included in the study. Nine of these were included in an exercise training program. During 16 weeks, exercise sessions were carried out during each dialytical procedure that included a warm-up period, aerobic exercises done using standing cycles, and resistance exercises, performed using Thera-Band® elastic bands and loops. Borg scale was used to control the intensity of training. At baseline and at the end of the study, a blood sample prior and after the dialytical procedure was obtained to measure C reactive protein, tumor necrosis factor α and interleukin 6. Quadriceps muscle strength, six minutes´ walk and quality of life using the SF-36 questionnaire, were also measured. Results: Four experimental subjects did not complete the study period, two that withdrew before starting, one due to problems with the venous access and one that decided to withdraw after 1 month of training. Among the five patients that finished the training period, significant improvements in the six minutes´ walk and quadriceps strength were observed in the experimental group. No significant changes were observed among controls. No changes were observed in either group in C reactive protein, tumor necrosis factor and interleukin 6 levels or quality of life. Conclusions: Among patients undergoing chronic hemodialysis exercise training improves endurance and muscle strength.

[A pilot study on physical training of patients in hemodialysis]. / Estudio piloto sobre entrenamiento físico durante hemodiálisis.

BACKGROUND: Exercise training during the dialytical procedure may have positive cardiovascular effects and prevent or revert muscle wasting in patients undergoing chronic hemodialysis. AIM: To evaluate the effects of an exercise training program in patients undergoing chronic hemodialysis. MATERIAL AND METHODS: Fifteen patients on chronic hemodialysis aged 21 to 69 years (three females) were included in the study. Nine of these were included in an exercise training program. During 16 weeks, exercise sessions were carried out during each dialytical procedure that included a warm-up period, aerobic exercises done using standing cycles, and resistance exercises, performed using Thera-Band(®) elastic bands and loops. Borg scale was used to control the intensity of training. At baseline and at the end of the study, a blood sample prior and after the dialytical procedure was obtained to measure C reactive protein, tumor necrosis factor α and interleukin 6. Quadriceps muscle strength, six minutes' walk and quality of life using the SF-36 questionnaire, were also measured. RESULTS: Four experimental subjects did not complete the study period, two that withdrew before starting, one due to problems with the venous access and one that decided to withdraw after 1 month of training. Among the five patients that finished the training period, significant improvements in the six minutes' walk and quadriceps strength were observed in the experimental group. No significant changes were observed among controls. No changes were observed in either group in C reactive protein, tumor necrosis factor and interleukin 6 levels or quality of life. CONCLUSIONS: Among patients undergoing chronic hemodialysis exercise training improves endurance and muscle strength.

Diagnóstico, evaluación y tratamiento no farmacológico del paciente con sobrepeso u obesidad / Statement about diagnosis assessment ano non pharmacological treatment of obesity

The risk of complications of obesity is proportional to body mass index and is higher in severe or morbid obesities and when abdominal or visceral fat is predominant. In Chile the prevalence of obesity is increasing. According to the World Health Organization, obese subjects must reduce at least a 5 percent of their weight to reduce the risk of complications. Although this amount of reduction is seldom achieved with non pharmacological treatments, better results are obtained with multidisciplinary/ approaches that include a medical, psychosocial and laboratory assessment, to determine obesity level and different factors involved and the associated complications. In a second stage, goals of treatment are set and a personalized treatment is designed including dietary changes and physical activity. The aim is to obtain perdurable lifestyles modifications.

Tratamiento farmacológico o quirúrgico del paciente con sobrepeso u obesidad / Statement about the medical and surgical treatment of overweight and obesity

This is an updated review of the available treatments for obesity, which can be used when lifestyles modifications fail. Using the available information and the experience of the members of this advisory group, a recommendation is given about the most useful treatments, according to the severity of obesity and its complications. With regards to pharmacological treatments, only sibutramine and orlistat are approved on a worldwide basis for the treatment of obesity. These medications achieve a 10 percent higher weight reduction than lifestyles modification. A third medication, rimonobant, is also more effective than lifestyles modifications, but it was withdrawn due to psychological safety issues. The indications for surgical treatment and a brief description of the available techniques, success rates and complications are outlined. Finally, the need to have followed up protocols for patients and the formation of multidisciplinary treatment teams is underscored.

Colon cancer in Chile before and after the start of the flour fortification program with folic acid.

BACKGROUND: Folate depletion is associated with an increased risk of colorectal carcinogenesis. A temporal association between folic acid fortification of enriched cereal grains and an increase in the incidence of colorectal cancer in the USA and Canada has, however, been recently reported. AIM: To compare the rates of hospital discharges owing to colon cancer in Chile before and after the start of the mandatory flour fortification program with 220 microg of synthetic folic acid/100 g of wheat flour. METHODS: Cancer and cardiovascular hospital discharge rates were compared using rate ratios between two study periods, 1992-1996, before folic acid fortification and 2001-2004, after the flour fortification with folic acid was established in the country. Standard errors of the log rate ratio to derive confidence intervals, and to test the null hypothesis of no difference, were calculated. RESULTS: The highest rate ratio between the two periods was for colon cancer in the group aged 45-64 years (rate ratio: 2.6, confidence interval: 99% 2.93-2.58) and in the 65-79 years (rate ratio: 2.9, confidence interval: 99% 3.25-2.86). CONCLUSION: Our data provide new evidence that a folate fortification program could be associated with an additional risk of colon cancer.

Relationship between protein and mitochondrial DNA oxidative injury and telomere length and muscle loss in healthy elderly subjects.

A blood sample and muscle biopsies were obtained from 54 elderly subjects. Twenty-seven subjects aged 77+/-3 years, had experienced a change in fat free mass (FFM) of +194+/-282g/year (lean body mass maintainers) and 27 subjects aged 78+/-3 years, had a change in FFM of -487+/-209g/year (lean body mass losers). Muscle biopsies were also obtained from 10 healthy subjects aged 34+/-4 years. In muscle, the ratio of mitochondrial DNA (mtDNA) to nuclear DNA (nDNA) and telomere length were assessed and deposition of 4-hydroxy-2-nonenal adducts (4HNE) was visualized by electron microscopy. In FFM maintainers, losers and young controls, the ratio of mtDNA to nDNA was 2.1 (95% confidence intervals (CI), 0.1-31.7), 1.5 (95% CI, 0.2-15.7) and 18.6 (95% CI, 2.8-46.2), respectively. 4HNE deposition was 5.9 (95% CI, 1.5-28), 4.9 (95% CI, 0.9-13) and 3.4 (95% CI, 1.1-4.6) gold particles/microm(2), respectively. Telomere length, expressed as T/S ratio, was 0.06 (95% CI, 0.01-0.16), 0.06 (95% CI, 0.03-0.27) and 0.34 (95% CI, 0.1-1.34), respectively (p<0.02 or less for all comparisons between elderly and young subjects).

Weight increase is associated with skeletal muscle immunostaining for advanced glycation end products, receptor for advanced glycation end products, and oxidation injury.

BACKGROUND: Tissue accumulation of advanced glycation end products (AGEs) is associated with ageing, both in diabetics and nondiabetic subjects. AIM: The purpose of this study was to assess immunostaining for AGEs, specifically carboxymethyl-lysine (CML) and receptor for AGEs (RAGE), in muscle tissue of healthy male subjects differing in age and weight stability. METHODOLOGY: Muscle tissue was obtained during hernia surgery in middle-aged men reporting weight maintenance (WM, n = 10) or weight gain (WG, n = 7), and also in 4 elderly men. Tissue inmunostaining for CML and RAGE was performed. RESULTS: Intensity of CML and RAGE staining were highly correlated (r = 0.84) and also significantly associated with weight change and age. Muscle AGEs accretion was statistically associated with muscle expression of oxidative injury (8-hydroxy-deoxyguanosine and 4-hydroxy-2-nonenal) and inflammatory markers (tumor necrosis factor-alpha). DISCUSSION: The increase of skeletal muscle AGEs/RAGE and markers of inflammation and oxidative injury in association with weight gain and old age suggest a pathogenic role of AGEs in weight gain and in sarcopenia of aging.

Lack of effect of diet-induced hypomethylation on endothelium-dependent relaxation in rats.

BACKGROUND: Endothelial dysfunction is a key process in atherosclerosis. Hypomethylation is one of the postulated mechanisms involved in atherogenesis and is mainly secondary to a decrease in essential factors such as, folate and vitamin B12 for the biosynthesis of S-adenosylmethionine (SAM), the main methyl-group donor for methylation reactions. AIM: To investigate in an animal model, whether hypomethylation, secondary to folate or vitamin B12 deficiency, affects endothelium-dependent relaxation (EDR) induced by acetylcholine (ACh). METHODS: Adult male Wistar rats were divided into 4 groups of 12 rats each: folate and B12 deficiency (FB12D 0mg folate/kg, 0 microg/kg B12), folate deficiency (FD 0mg folate/kg and 50 microg/kg B12), B12 deficiency (B12D: 8 mg/kg folate and 0 microg/kg B12 and control diet (CD)). After eight weeks the animals were killed and thoracic aorta and liver removed. Serum concentration of homocysteine, folate and vitamin B12 were determined. Hepatic levels of SAM and S-adenosylhomocysteine (SAH) were measured, as indicator of hypomethylation. ACh-induced EDR and sodium nitroprusside (SNP)-induced endothelium-independent relaxation (EIR), in isolated aorta rings were evaluated. RESULTS: Hcy concentrations were significantly increased in the folate and B12 deficient groups. SAM and the SAM/SAH ratio were lower in the FD and FB12D than in the control and B12D group. Folate, B12 deficiency, serum Hcy levels and hepatic SAM/SAH ratio did not affect EDR neither EIR. CONCLUSIONS: In adult Wistar rats, chronic folate or folate plus vitamin B12 deficiency generates hypomethylation which is not related to an alteration of endothelial function.

Efecto del probiótico Saccharomyces boulardii en la prevención de la diarrea asociada con antibióticos en adultos ambulatorios en tratamiento con amoxicilina / Effect of probiotic Saccharomyces boulardii on prevention of antibiotic-associated diarrhea in adult outpatients with amoxicillin treatment

Background: Antibiotic-associated diarrhea is one of the most common adverse effects of antimicrobials. Any antimicrobial can potentially produce diarrhea but beta-lactamics have a higher risk. Among these, amoxicillin is widely indicated in ambulatory practice. One ofthe alternatives suggested to prevent antibiotic-associated diarrhea, is the use of the probiotic Saccharomyces boulardii. Aim: To evalúate whether the concomitant use of Saccharomyces boulardii and amoxicillin can prevent antibiotic associated diarrhea in ambulatory adults with acute infections diseases, without provoking other adverse effects. Material and Methods: Eighty six adults (aged 15 to 81 years) with acute infectious diseases, excluding those arising in the gastrointestinal tract, that received a prescription of oral amoxicillin for 5 to 10 days, were included. In a controlled randomized, double blind trial, 41 patients were assigned to receive lyophilized Saccharomyces boulardii (500 mg/day) duríng 12 days, and 45 patients were assigned to placebo for the same period. Results: Ten percent of patients (9/86) reported acute diarrhea, 9,8 percent (4/41) in the experimental group and 11.196 (5/45) in the control group (p = 100). No adverse effects were associated to the use of the probiotic. Conclusions: Saccharomyces boulardii (500 mg/day) did not prevent diarrhea related to amoxicillin.

Methylation status in healthy subjects with normal and high serum folate concentration.

OBJECTIVE: We assessed the impact of high serum folate concentration on erythrocyte S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) concentrations, SAM/SAH ratio, CpG methylation levels across the promoter region of the extracellular superoxide dismutase (ec-SOD) gene, and ec-SOD activity in healthy men. METHODS: Serum folate levels were measured in 111 subjects who were categorized in quintiles according to their folate status. Subjects located at the lowest, middle, and upper quintiles were selected for assessment of SAM and SAH by high-performance liquid chromatography, C677T genotype of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, ec-SOD methylation of CpG sites in lymphocytes genomic DNA by bisulfate treatment, and ec-SOD activity by a chemical assay. RESULTS: Sixteen subjects were in the lowest serum folate quintile (<23.6 nmol/L), 17 in the middle (>34-<42 nmol/L), and 14 in the highest (>45nmol/L). SAM concentration was higher in the upper than in the middle and lowest quintiles (5.57 +/- 1.58, 2.52 +/- 0.97, 2.29 +/- 1.2 micromol/L; P < 0.0001). SAH concentration was higher in the upper compared with the lowest quintile (0.76 +/- 0.24 versus 0.52 +/- 0.23 micromol/L, P < 0.001). There were no differences in the SAM/SAH ratio, ec-SOD activity, methylation status of CpG sites of the ec-SOD gene, and TMTHFR C677T genotype between groups. CONCLUSION: Serum folate concentrations in the highest quintile among healthy humans are associated with increased erythrocyte SAM and SAH concentrations, but not with SAM/SAH ratio or with methylation levels of CpG sites across the promoter region of the ec-SOD gene. Further research is required to determine if these findings are beneficial or harmful.

Weight increase and overweight are associated with DNA oxidative damage in skeletal muscle.

BACKGROUND AND AIMS: Weight maintenance within normal standards is recommended for prevention of conditions associated with oxidative injury. To compare oxidative damage in a post mitotic tissue, between adults differing in long-term energy balance. METHODS: During hernia surgery, a sample of skeletal muscle was obtained in 17 non-obese adults. Subjects were divided into two groups according to their self-reported weight change: weight maintainers (WM) reported <4kg increase, and weight gainers (WG) reported >5kg increment. Muscle immunohistochemistry for 8-hydroxy-deoxyguanosine (8OHdG), 4-Hydroxy-2-nonenal (4HNE), and TNF-alpha, as markers of oxidative injury and inflammation, were performed. As known positive controls for oxidative injury, we included 10 elderly subjects (66-101yr). Anthropometric measures and blood samples for clinical laboratory and serum cytokines (TNF-alpha and IL-6) were obtained. RESULTS: 8OHdG was higher in WG compared with WM (149.1+/-16.2 versus 117.8+/-29.5, P=0.03), and was associated with anthropometric indicators of fat accumulation. 4HNE was similar in WG compared with WM (10.9+/-7.6 versus 9.8+/-6.3) but noticeably higher in elderly subjects (21.5+/-15.3, P=0.059). TNF-alpha protein in WG was higher compared with WM (114.0+/-41.7 versus 70.1+/-23.3, P=0.025), and was associated with weight increase. CONCLUSIONS: Moderate self-reported weight increase, and body fat accumulation, suggesting long-term positive energy balance is associated with muscle DNA oxidative injury and inflammation.

Soy isoflavones affect platelet thromboxane A2 receptor density but not plasma lipids in menopausal women.

OBJECTIVES: It has been suggested that isoflavones protect the cardiovascular system, in part by improving lipid profile. The purpose of the present research was to examine the effect of a 12-week soy isoflavone supplementation on lipoprotein status and platelet thromboxane A2 receptor density. METHODS: Twenty-nine healthy postmenopausal women were invited to take part in a randomised study to receive either 100 mg/day isoflavone supplement (n=15) or identical placebo capsules (n=14). Blood samples obtained at baseline and after 12 weeks were analysed for isoflavones, total cholesterol, high density lipoprotein cholesterol, triglycerides, glucose, insulin, estradiol, testosterone, gonadotrophins, sex hormone-binding globulin (SHBG) and platelet thromboxane A2 receptor density. Blood pressure measurements, body mass index, subcutaneous fat at entrance and at the end of treatment were also registered. Changes in variables between groups were compared by ANOVA for repeated measures. RESULTS: Blood pressure, body mass index, subcutaneous fat, insulin, serum lipoprotein, sex hormones and SHBG did not differ among groups. However, platelet thromboxane A2 receptor density declined significantly (from 181.9+/-30.9 to 115.2+/-16.2 fmol/10(8) platelets) in the experimental group, remaining mostly unchanged in the placebo group (176.3+/-27.3 to 170.4+/-28.2 fmol/10(8) platelets). The dissociation constant (Kd) values were unchanged. The change in platelet thromboxane A2 receptors correlated negatively with isoflavones serum concentration (r=-0.59, p<0.001). CONCLUSIONS: In this study we demonstrated that the beneficial effects of isoflavones in menopausal women could be more related to platelet function than to improving classical cardiovascular risk factors.