Cysteine Regulates Oxidative Stress and Glutathione-Related Antioxidative Capacity before and after Colorectal Tumor Resection.

Cysteine might scavenge free radicals and is a limiting substrate for the cellular synthesis of glutathione (GSH). We investigated the association of cysteine with oxidative stress and GSH-related antioxidant capacity in colorectal cancer (CRC) patients. Plasma samples were drawn from 66 patients 1 day before (pre-resection) and 4 weeks after resection (post-resection). Tumor and adjacent normal tissues were collected. We measured levels of plasma and tissue cysteine, homocysteine, oxidative stress indicators (malondialdehyde, MDA; advanced oxidation protein products, AOPP), GSH, and antioxidant enzyme activities. After tumor resection, patients had significantly higher levels of plasma cysteine, homocysteine, MDA, AOPP, and GSH-related antioxidant enzyme activities when compared with pre-resection. Levels of cysteine, homocysteine, AOPP and all antioxidant capacity indicators in tumor tissue were significantly higher than those levels in the adjacent normal tissue. Plasma cysteine levels measured at pre-resection were positively associated with MDA levels in the tumor and in the adjacent normal tissues. Cysteine levels in tumor and adjacent normal tissues were significantly associated with tissue levels of homocysteine, almost as indicators of oxidative stress and antioxidant capacities. Cysteine in the circulation was likely utilized to mediate GSH-related antioxidant capacity and further cope with increased oxidative stress in tumor and adjacent normal tissues.

Role of vitamin B6 status on antioxidant defenses, glutathione, and related enzyme activities in mice with homocysteine-induced oxidative stress.

BACKGROUND: Vitamin B6 may directly or indirectly play a role in oxidative stress and the antioxidant defense system. OBJECTIVE: The purpose of this study was to examine the associations of vitamin B6 status with cysteine, glutathione, and its related enzyme activities in mice with homocysteine-induced oxidative stress. DESIGN: Four-week-old male BALB/c mice were weighed and divided into one of four dietary treatment groups fed either a normal diet (as a control group and a homocysteine group), a vitamin B6-deficient diet (as a B6-deficient group), or a B6-supplemented diet (a pyridoxine-HCl-free diet supplemented with 14 mg/kg of pyridoxine-HCl, as a B6 supplement group) for 28 days. Homocysteine thiolactone was then added to drinking water in three groups for 21 days to induce oxidative stress. At the end of the study, mice were sacrificed by decapitation and blood and liver samples were obtained. RESULTS: Mice with vitamin B6-deficient diet had the highest homocysteine concentration in plasma and liver among groups. Significantly increased hepatic malondialdehyde levels were observed in the vitamin B6-deficient group. Among homocysteine-treated groups, mice with vitamin B6-deficient diet had the highest plasma glutathione concentration and relatively lower hepatic glutathione concentration. The glutathione peroxidase activities remained relatively stable in plasma and liver whether vitamin B6 was adequate, deficient, or supplemented. CONCLUSIONS: Mice with deficient vitamin B6 intakes had an aggravate effect under homocysteine-induced oxidative stress. The vitamin B6-deficient status seems to mediate the oxidative stress in connection with the redistribution of glutathione from liver to plasma, but not further affect glutathione-related enzyme activities in mice with homocysteine-induced oxidative stress.

Higher plasma pyridoxal phosphate is associated with increased antioxidant enzyme activities in critically ill surgical patients.

Critically ill patients experience severe stress, inflammation and clinical conditions which may increase the utilization and metabolic turnover of vitamin B-6 and may further increase their oxidative stress and compromise their antioxidant capacity. This study was conducted to examine the relationship between vitamin B-6 status (plasma and erythrocyte PLP) oxidative stress, and antioxidant capacities in critically ill surgical patients. Thirty-seven patients in surgical intensive care unit of Taichung Veterans General Hospital, Taiwan, were enrolled. The levels of plasma and erythrocyte PLP, serum malondialdehyde, total antioxidant capacity, and antioxidant enzyme activities (i.e., superoxide dismutase (SOD), glutathione S-transferase, and glutathione peroxidase) were determined on the 1st and 7th days of admission. Plasma PLP was positively associated with the mean SOD activity level on day 1 (r = 0.42, P < 0.05), day 7 (r = 0.37, P < 0.05), and on changes (Δ (day 7 - day 1)) (r = 0.56, P < 0.01) after adjusting for age, gender, and plasma C-reactive protein concentration. Higher plasma PLP could be an important contributing factor in the elevation of antioxidant enzyme activity in critically ill surgical patients.

Higher plasma homocysteine is associated with lower vitamin B6 status in critically ill surgical patients.

BACKGROUND: Hyperhomocysteinemia might be at least partially due to compromised B vitamin status in critically ill patients and has been linked with critical illness. This study was conducted to examine the association between plasma homocysteine with B vitamins and clinical outcomes in critically ill surgical patients. METHODS: Thirty-two patients in the surgical intensive care unit (SICU) were enrolled. Disease severity (Acute Physiology and Chronic Health Evaluation II score), hematological values, serum and erythrocyte folate, serum vitamin B12, plasma, and erythrocyte pyridoxal 5'-phosphate (PLP) were determined within 24 hours of admission and again after 7 days. RESULTS: The prevalence of hyperhomocysteinemia in the patients was either 46.9% (plasma homocysteine ≥12 µmol/L) or 31.3% (plasma homocysteine ≥15 µmol/L) on day 1 in the SICU and increased to 62.5% (plasma homocysteine ≥12 µmol/L) and 37.5% (plasma homocysteine ≥15 µmol/L) on day 7 after admission to the SICU. Plasma homocysteine, serum folate, and vitamin B12 significantly increased by day 7, whereas plasma and erythrocyte PLP remained constant throughout the study. Plasma homocysteine was not correlated with serum folate and vitamin B12. However, plasma and erythrocyte PLP on day 1 were adversely associated with day 1 levels of plasma homocysteine after adjusting for potential confounders. Plasma homocysteine on day 1 or changes (Δ day 7-day 1) did not show any association with clinical outcomes. CONCLUSIONS: Lower plasma PLP might be a significant factor for increased plasma homocysteine in critically ill surgical patients. The association between plasma homocysteine and clinical outcomes was not found.

Chair-sitting exercise intervention does not improve respiratory muscle function in mechanically ventilated intensive care unit patients.

BACKGROUND: Chair-sitting may allow for more readily activated scalene, sternocleidomastoid, and parasternal intercostal muscles, and may raise and enlarge the upper thoracic cage, thereby allowing the thoracic cage to be more easily compressed. OBJECTIVE: To evaluate the effect of chair-sitting during exercise training on respiratory muscle function in mechanically ventilated patients. METHODS: We randomized 16 patients to a control group and 18 patients to a chair-sitting group. The patients in the chair-sitting group were transferred by 2 intensive care unit nurses from bed to armchair and rested for at least 30 min, based on the individual patient's tolerance. We measured heart rate, blood pressure, S(pO(2)), and respiratory rate. In the treatment group, before transferring the patient from bed to armchair, and 30 min after the completion of chair-sitting we measured respiratory muscle function variables, including the ratio of respiratory rate (f) to tidal volume (V(T)), S(pO(2)), maximum inspiratory pressure (P(Imax)) and maximum expiratory pressure (P(Emax)). In the control patients we took those same measurements while the patient was in semirecumbent position, before and after treatments, for at least 6 days or until the patient was discharged from the intensive care unit or died. RESULTS: The 2 groups did not significantly differ in age, sex, or clinical outcomes. Respiratory rate, V(T), f/V(T), S(pO(2)), P(Imax), and P(Emax) were not significantly better in the chair-sitting group. The study period significantly improved respiratory rate, V(T), P(Imax), and P(Emax) (all P < .001), but not f/V(T). CONCLUSIONS: Six days of chair-sitting exercise training did not significantly improve respiratory muscle function in mechanically ventilated patients.

Higher plasma pyridoxal 5'-phosphate is associated with better blood glucose responses in critically ill surgical patients with inadequate vitamin B-6 status.

BACKGROUND & AIMS: Stress, inflammation, and clinical conditions may increase the utilization and metabolic turnover of vitamin B-6 and lower the body pool of vitamin B-6. There is the possibility that hyperglycemia in critically ill patients might be at least partially due to compromised vitamin B-6 status. The purpose of this study was to compare blood glucose responses between critically ill surgical patients with adequate and deficient vitamin B-6 status. METHODS: The study was designed as a cross-sectional observational study. Thirty-four patients in the surgical intensive care unit (SICU) were enrolled. The severity of illness (APACHE II score), the length of ventilation dependency, and the lengths of SICU and hospital stay were recorded. The levels of serum hemoglobin, hematocrit, albumin, prealbumin, C-reactive protein, glucose, insulin, glycated hemoglobin, C-peptide and creatinine were determined. Vitamin B-6 intake was recorded for 7 days. Vitamin B-6 status was assessed by direct measures [plasma and erythrocyte pyridoxal 5'-phosphate (PLP), pyridoxal (PL) and 4-pyridoxic acid (4-PA), and urinary 4-PA] and indirect measures [erythrocyte alanine and aspartate aminotransaminase activity coefficient]. RESULTS: Fourteen patients were classified into the deficient vitamin B-6 group (plasma PLP < 20 nmol/L), while there were 20 patients in the adequate vitamin B-6 group. The mean serum glucose concentration of both groups indicated patients was in the hyperglycemic state (serum glucose > 126 mg/dL). However, mean serum glucose concentration significantly decreased by day 7 in the adequate vitamin B-6 group, whereas patients still remained in the hyperglycemic state (serum glucose > 126 mg/dL) in the deficient vitamin B-6 group. There were significantly correlations of relatively higher plasma PLP at admission (day 1) with the reduction of blood glucose concentration (r(s) = 0.72, p = 0.029) on day 7 in the deficient vitamin B-6 group. However, erythrocyte PLP concentration was positively associated with blood glucose level (r(s) = 0.88, p = 0.002) at admission in the deficient vitamin B-6 group after adjusting for age, gender, APACHE II score, diabetic history and insulin therapy. CONCLUSIONS: Surgically ill patients with adequate plasma PLP concentration at admission showed improved blood glucose response at day 7. Higher plasma PLP at admission was a major contributing factor in the reduction of glucose concentration in critically ill surgical patients with deficient vitamin B-6 status.

Waist-to-hip ratio is a better anthropometric index than body mass index for predicting the risk of type 2 diabetes in Taiwanese population.

Body mass index (BMI) has been reported to be related to the risk of type 2 diabetes and hypertension. However, waist circumference or waist-to-hip ratio (WHR) can better reflect the accumulation of intra-abdominal fat and might be a better predictor than BMI of the risk of type 2 diabetes and hypertension. We hypothesized that other anthropometric indices rather than BMI could more accurately predict the risk of type 2 diabetes and hypertension. The purpose of this study was to determine which anthropometric index can be a better predictor for forecasting the risk of type 2 diabetes and hypertension in the Taiwanese population. We conducted a cross-sectional study and reviewed data derived from the Nutrition and Health Survey in Taiwan, 1993-1996. The subjects were 2545 men and 2562 women, aged 18 to 96 years. Receiver operating characteristic curve analysis was used to measure the predictive diabetic and hypertensive performance of each anthropometric measurement based on the area under the curve (AUC). Among 5 anthropometric indices, WHR had a significantly adjusted odds ratio (OR) and the highest AUC (0.72 for men and 0.80 for women) to predict the risk of type 2 diabetes. Although BMI had a significantly adjusted OR, the AUC was not the highest among the 5 anthropometric indices used to predict the risk of hypertension. Our findings suggested that WHR is a better anthropometric index for predicting the risk of type 2 diabetes, and the optimal cutoff values of WHR are considered as 0.89 for men and 0.82 for women in the Taiwanese population.

Vitamin B-12 status is not associated with plasma homocysteine in parents and their preschool children: lacto-ovo, lacto, and ovo vegetarians and omnivores.

OBJECTIVE: Vegetarians may be at risk of certain nutrient deficiencies, particularly vitamin B-12. Vitamin B-12 deficiency may increase plasma homocysteine concentration and thus may potentially increase the risk of cardiovascular disease in vegetarians. The purpose of this study was to assess and compare plasma homocysteine and vitamin B-12 status in vegetarian and omnivorous preschool children and their parents. In addition, the association between parents' and children's homocysteine and vitamin B-12 concentration was also examined. METHODS: Fifty-six omnivores (28 preschool children and one of their parents), 34 lacto-ovo vegetarians (16 parents and 18 children), 5 ovo vegetarians (2 parents and 3 children), 1 lacto vegetarian parent, and 2 vegan parents were enrolled in this study. The mean age of preschool children was 5.1 +/- 1.3 years and that of their parent was 35.4 +/- 4.2 years. Nutrient intakes were recorded using 3-day dietary records. Fasting venous blood samples were obtained to measure serum creatinine, high-sensitivity C-reactive protein, hematological parameters, plasma homocysteine, serum folate, and vitamin B-12 concentrations. RESULTS: There was no significant difference in dietary folate intake between vegetarian and omnivores within parent and child groups. The mean plasma homocysteine level of vegetarian parents and their children was in the physiological range, and they had slightly but not significantly higher plasma homocysteine levels than omnivores. Omnivorous parents and their children had significantly higher vitamin B-12 intake than vegetarian participants but similar serum vitamin B-12 concentrations. Plasma homocysteine concentration was significantly and negatively associated with only serum folate levels (beta = -0.15) and dietary vitamin B-12 intake (beta = -0.05) in the omnivorous parents after adjusting for age, gender, body mass index, and serum creatinine. CONCLUSION: Vegetarian parents and their preschool children had a lower vitamin B-12 intake than omnivorous parents and their preschool children but similar plasma vitamin B-12 and homocysteine concentrations. Plasma homocysteine was not associated with serum vitamin B-12 levels in the parent, child, or pooled group.

Serum folate is a reliable indicator of hyperhomocysteinemia and borderline hyperhomocysteinemia in young adults.

Serum folate has been shown to correlate well with fasting plasma homocysteine; however, erythrocyte folate concentration is a better index of tissue folate stores and probably could be a more reliable indicator for reflecting long-term supply of the vitamin and homocysteine status. The present study was undertaken to test the hypothesis that serum folate and erythrocyte folate levels had a different degree of correlation to fasting plasma homocysteine in young Taiwanese adults. This study had a cross-sectional design. Healthy young adults were divided into either a hyperhomocysteinemia (HHcy; > or =14.9 micromol/L; n = 13), borderline HHcy (BHcy; fasting homocysteine, 14.9-10.2 micromol/L; n = 52), or normohomocysteinemia (fasting homocysteine, <10.2 micromol/L; n = 65) groups based on fasting homocysteine levels. The concentrations of plasma fasting homocysteine, serum folate, erythrocyte folate, vitamin B(12), and plasma pyridoxal 5'-phosphate were measured. Fasting homocysteine was only significantly and inversely affected by serum folate (beta = -0.21, P < .05) concentration after adjusting for potential confounders. Only serum folate concentration remained to decrease the risk of fasting HHcy (odds ratio, 0.73; confidence interval, 0.56-0.95) after the other B vitamins were additionally adjusted. Serum folate also had the highest area under the receiver operating characteristic (AUC) curve to predict the risk of HHcy (AUC, 0.81) and BHcy (AUC, 0.77). Serum folate is a reliable indicator of fasting hyperhyperhomocysteinemia and BHcy in young adults.

Dietary intake and nutritional status of vegetarian and omnivorous preschool children and their parents in Taiwan.

The aim of this study was to assess and compare dietary intake and nutritional status of vegetarian and omnivorous preschool children and their parents. Fifty-six omnivores (28 children and 28 parents) and 42 vegetarians (21 preschool children with 18 lacto-ovo-vegetarians and 3 ovo-vegetarians; 21 parents with 16 lacto-ovo-vegetarians, 2 ovo-vegetarians, 1 lacto-vegetarian, and 2 vegans) were recruited. Anthropometric measurements were taken; body mass index and weight-for-height index (WHI) were calculated. Nutrient intake was recorded using 3-day dietary records. Fasting venous blood samples were obtained to estimate hematologic and vitamin status parameters. Height, weight, body mass index, WHI, and triceps skinfold thickness value differences between omnivores and vegetarians in both parent and child groups were not found. Both omnivorous parents and their children had significantly higher fat and lower fiber intakes than vegetarian parents and children. Omnivorous children had significantly higher protein and lower vitamin C intakes than vegetarian children, whereas omnivorous parents had significantly lower vitamin A and iron intakes than vegetarian parents. Vegetarians and omnivores in both parent and child groups had mean calcium consumption less than 75% of the Taiwan dietary intakes. All mean hematologic and biochemical nutrient status indices were within the reference range in any groups. However, both vegetarian parents and children had significantly lower mean total cholesterol and serum ferritin concentrations than those of omnivorous parents and children. Our vegetarian and omnivorous preschool children had normal growth and adequate nutritional status. However, both parents and children had inadequate calcium intakes, which may potentially affect bone health, especially for preschool children in the growing stage.

Low plasma pyridoxal 5'-phosphate concentration and MTHFR 677C-->T genotypes are associated with increased risk of hypertension.

Few studies have linked homocysteine, B vitamins and/or genetic defects to the risk of hypertension. The purpose of this study was to investigate homocysteine, B-vitamins, and genetic mutation in relation to the risk of hypertension. Subjects were assigned to the hypertension (HTN) group (n = 50) or non-hypertension (non-HTN) group (n = 123). All subjects' blood pressure (systolic blood pressure, SBP; diastolic blood pressure, DBP), biochemical values, plasma homocysteine, pyridoxal 5'-phosphate (PLP), serum folate, vitamin B12 concentrations, and methylenetetrafolate reductase (MTHFR) 677C-->T gene polymorphism were measured. Results showed that subjects with T-allele were positively associated with DBP (beta = 4.22, p = 0.04) but the significance became weaker (p = 0.06) after homocysteine and B vitamins were additionally adjusted. A significant association of plasma PLP with SBP remained (beta = -0.06, p = 0.01) even after homocysteine and T-allele genotypes were additionally adjusted (beta = -0.07, p = 0.02). The combined presence of low PLP (< 30 nmol/L) and carried T-allele enhanced the risk of hypertension and the risk magnitude was substantially greater (OR, 16.44, p < 0.001). Taken together, the results show that low plasma PLP levels and MTHFR 677C-->T genotypes might be significant risk factors for hypertension.

Low pyridoxal 5'-phosphate is associated with increased risk of coronary artery disease.

OBJECTIVE: The purpose of this study was to investigate the association between plasma pyridoxal 5'-phosphate (PLP) status and lipid profiles and to estimate the relation to the risk of coronary artery disease (CAD). METHODS: Patients who were identified by cardiac catheterization as having > or =70% stenosis of one major coronary artery were assigned to the case group (n = 184). The control group (n = 516) was comprised of healthy individuals with normal blood biochemical values. Plasma PLP, homocysteine, high-sensitivity C-reactive protein, lipid profiles (total cholesterol, low-density lipoprotein, high-density lipoprotein, very low-density lipoprotein, and triacylglycerol) were determined. RESULTS: Subjects with a plasma PLP level <30 nmol/L exhibited a significantly increased risk of CAD compared with subjects with a plasma PLP level > or =30 nmol/L (odds ratio, 1.85; 95% confidence interval, 1.16-2.95) after adjusting for homocysteine and high-sensitivity C-reactive protein. The association between PLP and the risk of CAD remained significant after each lipid profile was additionally adjusted. In addition, the combined presence of low PLP level and an abnormal lipid level increased the risk of CAD to an even greater degree. CONCLUSIONS: A borderline vitamin B6 deficiency (plasma PLP concentration <30 nmol/L) is strongly associated with the risk of CAD. The combined presence of low PLP and abnormal lipid levels increased the risk of CAD even further.

Estimation of energy requirements for mechanically ventilated, critically ill patients using nutritional status.

BACKGROUND: There is very little information on what is considered an adequate energy intake for mechanically ventilated, critically ill patients. The purpose of the present study was to determine this energy requirement by making use of patients' nutritional status. METHODS: The study was conducted in a multidisciplinary intensive care unit of Taichung Veterans General Hospital, Taiwan. Patients were hemodynamically stable and not comatose, and were requiring at least 7 days of mechanical ventilation. Fifty-four patients successfully completed this study. The resting energy expenditure was measured using indirect calorimetry. The total energy requirement was considered 120% of the measured energy expenditure. The daily nutrient intake was recorded. Nutritional status was assessed using single and multiple parameters, nitrogen balance, and medical records, and was performed within 24 hours of admission and after 7 days in the intensive care unit. RESULTS: Fifteen patients were being underfed (<90% of total energy requirement), 20 patients were in the appropriate feeding (AF) group (within +/- 10% of total energy requirement), and 19 patients received overfeeding (>110% of total energy requirement). Patients in the underfeeding group received only 68.3% of their energy requirement, while the overfeeding group patients received up to 136.5% of their required calories. Only patients in the AF group had a positive nitrogen balance (0.04 +/- 5.1) on day 7. AF group patients had a significantly higher Nutritional Risk Index value at day 7 than at day 1. CONCLUSION: AF patients had more improvement in nutritional status than patients in the other feeding groups. To provide at least 120% of the resting energy expenditure seemed adequate to meet the caloric energy needs of hemodynamically stable, mechanically ventilated, critically ill patients.

The status of plasma homocysteine and related B-vitamins in healthy young vegetarians and nonvegetarians.

BACKGROUND: Exclusion of animal products and having only plant protein in vegetarian diets may affect the status of certain B-vitamins, and further cause the elevation of plasma homocysteine concentration. AIM: The purpose of this study was to assess the status of homocysteine and related B-vitamins in vegetarians and nonvegetarians. The effects of biochemical parameters of B-vitamins and dietary protein on plasma homocysteine were also examined. METHODS: The study was performed at the Chung Shan Medical University, Taichung, in the central part of Taiwan. Thirty-seven vegetarians (28.9 +/- 5.5 y) and 32 nonvegetarians (22.9 +/- 1.6 y) were recruited. Nutrient intake was recorded using 3-day dietary records. Fasting venous blood samples were obtained. Plasma homocysteine, folate and vitamin B-12 were measured. Vitamin B-6 status was assessed by direct measures [plasma pyridoxal 5'-phosphate (PLP) and urinary 4-pyridoxic acid (4-PA)] and indirect measures [erythrocyte alanine (EALT-AC) and aspartate (EAST-AC) aminotransaminase activity coefficient]. RESULTS: There was no significant difference in vitamin B-6 intake between the two groups, although the vegetarian group had a significantly lower vitamin B-12 intake than the nonvegetarian group. Vegetarian subjects had significantly lower mean plasma PLP and vitamin B-12 concentrations than did nonvegetarian subjects (p < 0.05); however, a significantly higher mean plasma folate concentration was found in the vegetarian group. Vegetarian subjects had a significantly higher mean plasma homocysteine concentration than nonvegetarian subjects (13.2 +/- 7.9 vs. 9.8 +/- 2.2 micromol/L). Negative correlations were seen between plasma homocysteine and vitamin B-12 concentrations in the vegetarian (p = 0.004), nonvegetarian (p = 0.026), and pooled (p < 0.001) groups. From best subsets regression analyses, the plasma homocysteine concentration could be significantly predicted by total protein intake (p = 0.027) and plasma vitamin B-12 concentration (p = 0.005) in the pooled group. When the intake of protein is not considered, vitamin B-12 concentration is still a strong predictor of plasma homocysteine concentration (p = 0.012). CONCLUSIONS: Vitamin B-12 intake and mean plasma vitamin B-12 concentration were lower for vegetarian subjects than for nonvegetarian subjects, leading to an increase in plasma homocysteine concentration. Vitamin B-6 and folate had little effect on plasma homocysteine concentration when individuals had adequate vitamin B-6 and folate status.