风湿性疾病中高同型半胱氨酸血症的临床研究

目的　分析多种风湿性疾病患者血浆中同型半胱氨酸(Hcy)水平及其相关因素。方法脊柱关节病(uSpA)患者和 62例正常对照的Hcy、VitB12、叶酸的水平和亚甲基四氢叶酸还原酶(MTHFR)基因 677位的多态性。结果　(1)各疾病组Hcy水平分别为:SLE组 (19 04±6 86)μmol/L,RA组(19 07±7 43)μmol/L,AS组(16 47±6 50)μmol/L,uSpA组(16 59±6 72)μmol/L,对照组(12 24±3 58)μmol/L,各疾病组Hcy水平明显较对照组高,其差异有统计学意义 (P<0 01 ); ( 2 )Hcy与VitB12、叶酸呈负相关,相关系数分别为-0 701和-0 443,P<0 01; (3)MTHFR基因 677位C→T的突变使Hcy水平升高, CC型 ( 13 41±5 78 )μmol/L,CT型 ( 16 81±4 22 )μmol/L,TT型(20 88±6 60)μmol/L,P<0 01;TT基因型是高Hcy血症的易感基因 (OR=84 46,P<0 05);TT基因型还是SLE的易感基因(OR=7 56,P<0 05)。结论　(1)SLE、RA、AS、uSpA4种疾病患者普遍存在高Hcy血症。(2)导致高Hcy血症的原因可能有叶酸、VitB12的水平降低和MTHFR基因的突变。(3)TT型基因是Hcy异常升高的易感基因,也是SLE的易感基因。     

Physical training decreases total plasma homocysteine and cysteine in middle-aged subjects

AIMS: The aim of this study was to evaluate whether endurance exercise in middle-aged men induces changes in plasma total homocysteine (tHcy) and total cysteine (tCys), and whether these changes depend on the diet especially on vitamin B(6), folic acid and vitamin B(12) intakes. METHODS: Twelve trained subjects (52.33 +/- 2.4 years) and twelve untrained subjects (56.23 +/- 0.9 years) volunteered for the present study. tHcy and tCys were measured with high-pressure liquid chromatography at rest in both groups and during an incremental exercise performed on a cycle ergometer until exhaustion in the trained subjects. RESULTS: At baseline homocysteinemia and cysteinemia were lower in trained subjects (7.48 +/- 0.4 and 183.45 +/- 13.6 micromol/l) compared with untrained subjects (9.79 +/- 0.4 micromol/l, p < 0.001; 229.01 +/-14.7 micromol/l, p < 0.05, respectively). Incremental exercise also induced a decrease in tHcy and tCys concentrations. Moreover, tHcy concentration was negatively related to the folic acid and B(12) intakes in untrained (r = -0.589, p < 0.05; r = -0.580, p < 0.05, respectively) as well as in trained groups (r = -0.709, p < 0.01; r = -0.731, p < 0.01, respectively) whereas no correlation between tCys and vitamin in the diet was observed. CONCLUSION: This study demonstrates that the combined effects of a chronic physical exercise and a high folate and vitamin B(12) intake could be responsible for the reduction of plasma tHcy and tCys concentrations that might be a key for the prevention of many diseases.     

Homocysteine levels and C677T polymorphism of methylenetetrahydrofolate reductase in women with polycystic ovary syndrome

The aim of this study was to investigate the homocysteine (Hcy) levels and the C677T polymorphism of 5,10-methylenetetrahydrofolate reductase (MTHFR), a crucial factor of the Hcy metabolism in young women with polycystic ovary syndrome (PCOS). Seventy young women with PCOS and another 70 healthy women with low folate intake were enrolled. Cases and controls were matched for age, body mass index, and allele frequency. Hcy, vitamin B(12), and folate levels were measured, and a genetic analysis of 5,10-MTHFR at nucleotide 677 was performed in all subjects. No difference in mean Hcy levels was observed between PCOS women in comparison to the control group. Considering the different MTHFR polymorphism, no significant difference was found in serum Hcy levels between subjects with PCOS and controls showing CC (10.4 +/- 3.1 vs. 9.7 +/- 2.9 micromol/liter +/- SD) and CT genotypes (10.9 +/- 3.8 vs. 11.0 +/- 3.2 micromol/liter +/- SD). In subjects with a TT homozygous state, a significant (P < 0.05) difference was observed between PCOS and control women (11.5 +/- 3.9 vs. 22.0 +/- 7.8 micromol/liter +/- SD). In conclusion, our data show that in PCOS women, the serum Hcy levels are normal, and the C677T polymorphism of MTHFR does not influence the Hcy levels like in controls.     

Prevalence and mechanisms of hyperhomocysteinemia in chronic alcoholics

BACKGROUND: Homocysteine (Hcy) is formed as an intermediary in methionine metabolism. Impairment of Hcy remethylation or transulfuration leads to hyperhomocysteinemia, which is considered as a risk factor for atherosclerotic vascular disease and stroke in chronic alcoholics. The aim of the study was to investigate the prevalence of hyperhomocysteinemia in chronic alcoholics and the influence of alcohol consumption, vitamin deficiencies and liver damage on the plasma levels of Hcy. METHODS: 228 chronic alcoholic patients consecutively admitted for detoxication, classified according to clinical and biochemical data in normal liver (n = 117), and in mild to moderate liver disease (n = 111), and 49 healthy controls were studied. Blood levels of Hcy, vitamin B6, vitamin B12 and folate were measured. RESULTS: Plasma Hcy was significantly higher in chronic alcoholics than in controls (9.66 +/- 8.1 vs. 6.93 +/- 2.33 mumol/liter, p < 0.025). Furthermore, plasma Hcy levels were significantly higher in chronic alcoholics with liver injury (12.17 +/- 10.14 mumol/liter) than in those with normal liver and in controls (p < 0.001). The prevalence of hyperhomocysteinemia was also significantly higher in alcoholics with liver damage than in those with normal liver and in controls (29.7%, 5.1%, and 2%, respectively, p < 0.001). Serum folate values were lower in chronic alcoholics than in controls (4.7 +/- 2.6 vs. 7.6 +/- 2.4 nmol/liter, p < 0.001). The lowest values of folate were found in alcoholics with liver disease, especially in those with hyperhomocysteinemia, with a negative correlation between the two parameters. CONCLUSIONS: Moderate hyperhomocysteinemia is common in chronic alcoholics, mainly in those with liver damage, suggesting that, although folate deficiencies may have a contributory role, liver impairment, through changes in methionine metabolism, is the most important mechanism for the elevated plasma Hcy found in these patients.     

Plasma folate, vitamin B(12), and total homocysteine and homozygosity for the C677T mutation of the 5,10-methylene tetrahydrofolate reductase gene in patients with Alzheimer's dementia. A case-control study.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels are considered a risk factor for cerebrovascular disease and may also play an important role in the pathogenesis of Alzheimer's disease (AD). High values of plasma tHcy and low levels of vitamin B(12) and folate are frequently present in AD patients. Moreover, the homozygous mutation (C677T) of the methylene tetrahydrofolate reductase (MTHFR) gene, related to a thermolabile type of the encoded enzyme, causes hyperhomocysteinemia by reducing the 5-methyltetrahydrofolate availability. OBJECTIVE: The aim of the study was to investigate plasma levels of folate, vitamin B(12) and tHcy in patients with AD. These values were also related to the severity and the duration of the disease and to the possible role of the MTHFR genotype (C677T). METHOD: Plasma tHcy levels, homozygosity for the C677T mutation of the MTHFR gene, and folate and vitamin B(12) plasma levels were evaluated in 74 patients with AD (45 men, 29 women, mean age 68 years) and in 74 healthy matched controls (42 men, 32 women, mean age 68 years). RESULTS: AD patients had higher mean (+/- SD) plasma levels of tHcy (20.9 +/- 15 micromol/l compared to 11.8 +/- 5 micromol/l, p < 0.001) and lower mean plasma folate (5.7 +/- 2.1 ng/ml compared to 8.5 +/- 3.2 ng/ml, p < 0.001) and vitamin B(12) (491 +/- 144 pmol/l compared to 780 +/- 211 pmol/l, p < 0.001) concentrations. Homozygosity for the C677T mutation of the MTHFR gene had a similar prevalence among controls (18%) and AD patients (20%). Homozygous AD patients (n = 15) had higher plasma tHcy values than nonhomozygotes, in spite of similar mean plasma folate and vitamin B(12) levels. This difference in plasma tHcy levels was not observed in controls. Patients with levels of plasma tHcy above and of plasma folate below the normal limits were more frequent in the homozygous AD group. The duration of the disease correlated with plasma levels of tHcy (r = +0.832, p < 0.001), plasma folate (r = -0.580, p < 0.05), and vitamin B(12) (r = -0.460, p < 0.05). However, when all the data were corrected for age, serum creatinine levels, and duration of the disease, mean plasma tHcy, folate, and vitamin B(12) levels were not statistically different between controls and AD patients. CONCLUSIONS: Our data suggest that rather than a risk factor for AD, hyperhomocysteinemia is related to its progression and increasing severity. This might be particularly relevant in homozygotes for the C677T mutation of the MTHFR gene and supports the possible need for continuous supplements in this setting.     

Effects of different levels of exercise volume on endothelium-dependent vasodilation: roles of nitric oxide synthase and heme oxygenase

The objective of this study was to examine the effects of moderate and high levels of exercise volume on endothelium-dependent vasodilation and associated changes in vascular endothelial/inducible nitric oxide synthase (eNOS and iNOS) and heme oxygenase (HO). Male Sprague-Dawley rats were assigned to sedentary control, acute (2 weeks), or chronic (6 weeks) treadmill running at moderate intensity (50% maximal aerobic velocity) with different durations of exercise episodes: 2 h/d (endurance training, moderate volume) and 3 h/d (intense training, high volume). Endothelium-dependent vascular function was examined in isolated thoracic aorta. Co-localization and contents of aortic eNOS/iNOS and HO-1/HO-2 were determined with immunofluorescence and Western blotting. Compared with sedentary controls, rats subjected to acute and chronic endurance training showed enhanced endothelium-dependent relaxation (p<0.01). Whereas acetylcholine-induced dilation was inhibited completely by NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) in sedentary controls, the dilation in the training groups was only partly blocked by L-NAME (inhibition was 98+/-3%, 79+/-6%, and 77+/-5% in sedentary control, acute, and chronic training groups, respectively, p<0.01). The remnant dilation in the training groups was further inhibited by HO inhibitor protoporphyrin IX zinc, with concomitant elevation in aortic eNOS as well as HO-1 and HO-2. In contrast to endurance exercise, high-volume intense training resulted in mild hypertension with significant impairment in endothelium-dependent vasodilation and profuse increases in aortic iNOS and eNOS (p<0.01). In conclusion, endothelium-dependent vasodilation is improved by endurance exercise but impaired by chronic intense training. Elevations of vascular eNOS and HO-1/HO-2 may contribute to enhanced vasodilation, which can be offset by intense training and elevation in vascular iNOS.     

Plasma homocysteine levels in patients with early coronary artery stenosis and high risk factors

The aim of this study was to study the relationship between plasma homocysteine (Hcy), folic acid, vitamin B12 and early coronary artery disease (early-CAD) and high coronary risk factors. The plasma Hcy levels of 58 cases with early-CAD and 31 subjects without CAD were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. Plasma folic acid and Vitamin B12 levels were measured with radioassay method. The plasma Hcy level was significantly higher in the early-CAD patients than in the controls [(13.7 +/- 5.1) micromol/L vs (10.3 +/- 5.7) micromol/L]. The plasma folic acid and Vitamin B12 levels were significantly lower in the early-CAD patients than in the controls. The plasma Hcy level was higher in patients with more than 3 risk factors of CAD than in patients with 1 or 2 risk factors and in the controls [(17.3 +/- 5.1) micromol/ L vs (12.9 +/- 4.8) micromol/L, (7.8 +/- 2.5) micromol/L]. Other than gender, all classical coronary risk factors were related to the elevated Hcy level. Hcy levels were elevated in patients with early-CAD and with high risk factors. Hyperhomocysteinemia plays an important role in the pathogenesis of CAD.     

Hyperhomocysteinemia in winter elite athletes: a longitudinal study

Hyperhomocysteinemia is a well-established risk factor for cardiovascular diseases. The aims of this study were to longitudinally investigate, in a group of elite athletes, plasma homocysteine levels and to search for relationships with the muscular workload and the vitamin status. One hundred and three athletes (59 males and 44 females, respectively) were evaluated in different periods: namely the recovery period, the training period, and the competition period; 84 subjects (37 males and 47 females), served as controls. The evaluation sessions consisted in blood sampling and medical examination. The percentages of athletes with normal and elevated homocysteine levels, defined by levels below or above the limit of 15 mumol/l, were 68.0% and 32.0%, respectively, in the recovery period, and these percentages remained unchanged during the following periods. In the control group, relevant percentages were 92.9% and 7.1%, respectively. The comparison between plasma homocysteine of male and female, evaluated in the recovery period, showed significantly higher levels in the former group (18.8+/-18.0 micromol/l vs 10.7+/-5.9 micromol/l, p<0.001 respectively), as well as a higher proportion of individuals with hyperhomocysteinemia (24/59 vs 9/44, p<0.05). The correlation analyses showed a weak but significant negative correlation between homocysteine and folate in the three periods considered, while no significant relationship was observed between homocysteine and creatine-kinase. We found excess prevalence of hyperhomocysteinemia in elite athletes of winter sports. A strategy to understand which mechanisms in these athletes subserve hyperhomocysteinemia is essential in order to reduce the potential risk for future cardio-vascular morbidity and mortality.     

Angiotensin-converting enzyme genotype predicts cardiac and autonomic responses to prolonged exercise.

OBJECTIVES: The purpose of this study was to investigate the phenomenon of left ventricular (LV) dysfunction after ultraendurance exercise. BACKGROUND: Subclinical LV dysfunction in response to endurance exercise up to 24 h duration has been described, but its mechanism remains elusive. METHODS: We tested 86 athletes before and after the Adrenalin Rush Adventure Race using echocardiography, impedance cardiography, and plasma immunoassay. RESULTS: At baseline, athletes demonstrated physiology characteristic of extreme endurance training. After 90 to 120 h of almost-continuous exercise, LV systolic and diastolic function declined (fractional shortening before the race, 39.6 +/- 0.65%; after, 32.2 +/- 0.84%, p < 0.001; mitral inflow E-wave deceleration time before the race, 133 +/- 5 ms; after, 160 +/- 5 ms, n = 48, p < 0.001) without change in loading conditions as defined by LV end-diastolic dimension and total peripheral resistance estimated by thoracic impedance. There was a compensatory increase in heart rate (before, 55 +/- 1.3 beats/min; after, 59 +/- 1.5 beats/min, p = 0.05), which left cardiac output unchanged, as well as significant-but-subclinical increases in brain natriuretic peptide and troponin I. In addition, we found that athletes who were homozygous for the intron-16 insertion polymorphism of the angiotensin-converting enzyme (ACE) gene exhibited a significantly greater decrease in fractional shortening than athletes who were homozygous for the deletion allele. Heterozygotes showed an intermediate phenotype. In addition, the deletion group manifest an enhanced sympathovagal balance after the race, as evidenced by greater power in the low-frequency component of blood pressure variability. CONCLUSIONS: The ACE genotype predicts the extent of reversible subclinical LV dysfunction after prolonged exercise and is associated with a differential postactivity augmentation of sympathetic nervous system function that may explain it.     

Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes

BACKGROUND: Whereas a high prevalence of bronchial abnormalities has been reported in endurance athletes, its underlying mechanisms and consequences during exercise are still unclear. STUDY OBJECTIVES: The purpose of this study was to assess the following: (1) bronchial responsiveness to methacholine and to exercise; (2) airway inflammation; and (3) airflow limitation during intense exercise in endurance athletes with respiratory symptoms. DESIGN: Cross-sectional observational study. SETTING: Lung function and exercise laboratory at a university hospital. PATIENTS AND MEASUREMENTS: Thirty-nine endurance athletes and 13 sedentary control subjects were explored for the following: (1) self-reported respiratory symptoms; (2) bronchial hyperresponsiveness (BHR) to methacholine and exercise; (3) airflow limitation during intense exercise; and (4) bronchial inflammation using induced sputum and nitric oxide (NO) exhalation. RESULTS: Fifteen athletes (38%) showed BHR to methacholine and/or exercise in association with bronchial eosinophilia (mean [+/- SD] eosinophil count, 4.1 +/- 8.5% vs 0.3 +/- 0.9% vs 0%, respectively), higher NO concentrations (19 +/- 10 vs 14 +/- 4 vs 13 +/- 4 parts per billion, respectively), a higher prevalence of atopy, and more exercise-induced symptoms compared with non-hyperresponsive athletes and control subjects (p < 0.05). Furthermore, airflow limitation during intense exercise was observed in eight athletes, among whom five had BHR. Athletes with airflow limitation reported more symptoms and had FEV1, FEV1/FVC ratio, and forced expiratory flow at midexpiratory phase values of 14%, 9%, and 29%, respectively, lower compared with those of nonlimited athletes (p < 0.05). CONCLUSION: BHR in endurance athletes was associated with the criteria of eosinophilic airway inflammation and atopy, whereas airflow limitation during exercise was primarily a consequence of decreased resting spirometric values. Both BHR and bronchial obstruction at rest with subsequent expiratory flow limitation during exercise may promote respiratory symptoms during exercise in athletes.     

Homocysteine, hypothyroidism, and effect of thyroid hormone replacement.

Elevation of total plasma concentration of homocysteine (t-Hcy) is an important and independent risk factor for cardiovascular disease. Hypothyroidism is possibly also associated with an increased risk for coronary artery disease, which may be related to atherogenic changes in lipid profile. Because hypothyroidism decreases hepatic levels of enzymes involved in the remethylation pathway of homocysteine, we prospectively evaluated fasting and postload t-Hcy in patients before and after recovery of euthyroidism. Fasting and postload t-Hcy levels were higher in 40 patients with peripheral hypothyroidism (14 with autoimmune thyroiditis and 26 treated for thyroid cancer) in comparison with those of 26 controls (13.0 +/- 7.5 vs. 8.5 +/- 2.6 micromol/L, p < .01, respectively, and 49.9 +/- 37.3 vs. 29.6 +/- 8.4 micromol/L p < .001, respectively). On univariate analysis, fasting Hcy was positively related to thyrotropin (TSH) and inversely related to folates. Multivariate analysis confirmed TSH as the strongest predictor of t-Hcy independent of age, folate, vitamin B12, and creatinine. Thyroid hormone replacement significantly decreased fasting but not postload t-Hcy. We conclude that t-Hcy is elevated in hypothyroidism. The association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state. Thyroid hormone failed to completely normalize t-Hcy. Potential benefit of treatment with folic acid in combination with thyroid hormone replacement has to be tested given that hypothyroid patients were found to have lower levels of folate.     

Usefulness of plasma vitamin B(6), B(12), folate, homocysteine, and creatinine in predicting outcomes in heart transplant recipients

Atherothrombotic complications are frequently seen in patients undergoing heart transplantation. These patients have high plasma total homocysteine concentrations associated with lower folate and vitamin B(6) levels. The relation between these metabolic abnormalities and the development of vascular complications, however, remains unclear. Fasting plasma total homocysteine, folate, vitamin B(12), vitamin B(6), and creatinine were measured in 160 cardiac transplant recipients who were followed for a mean duration of 28 +/- 9 months after blood draw (mean 59 +/- 28 months after transplant). Cardiovascular events and causes of mortality were determined and Cox proportional-hazards regression analysis was used to identify the independent predictors for cardiovascular events and mortality. Twenty-five patients developed cardiovascular events and 17 died (11 cardiovascular deaths). Mean +/- SD total homocysteine value was 18.4 +/- 8.5 (range 4.3 to 63.5 micromol/L). Hyperhomocysteinemia (> or =15 micromol/L) was seen in 99 patients (62%). Levels were no different in patients with or without cardiovascular complications/death (16.8 +/- 6.2 vs 18.9 +/- 9 micromol/L, p = 0.4). However, vitamin B(6) deficiency was seen in 21% of recipients with and in 9% without cardiovascular complications/death (p = 0.05). The relative risk for cardiovascular events, including cardiovascular death, increased 2.7 times (confidence interval 1.2 to 5.9) for B(6) levels < or =20 nmol/L compared with those with normal B(6) levels (p = 0.02). Thus, hyperhomocysteinemia is common in transplant recipients but may have no causal role in the atherothrombotic vascular complications of transplantation. Deficiency of vitamin B(6), however, may predict adverse outcomes, suggesting a possible role for supplementation with this vitamin.     

Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus

OBJECTIVES: Metformin is widely used in patients with type 2 diabetes but may decrease vitamin B(12) levels and increase levels of homocysteine (Hcy), a cardiovascular risk factor. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, may reduce markers of inflammation. We investigated whether 6 weeks' treatment with metformin or rosiglitazone affects serum concentrations of Hcy, folate, or vitamin B(12) in subjects with newly diagnosed type 2 diabetes compared with controls. METHODS: We examined 165 patients with type 2 diabetes. Fasting blood samples, a physical examination, and a complete medical history were performed at the beginning and at the end of the treatment. All blood samples were obtained after a 12-h fast. RESULTS: After treatment, metformin use was associated with an increase in levels of Hcy by 2.36 micromol/l and decreases in folate and vitamin B(12) concentrations by -1.04 ng/ml and -20.17 pg/ml. During rosiglitazone treatment, Hcy levels decreased by -0.92 micromol/l; folate and vitamin B(12) levels remained unchanged. Metformin and rosiglitazone significantly decreased levels of triglyceride (TG), low-density lipoprotein (LDL), total cholesterol (total-C), HbA1c, insulin, and homeostasis model assessment (HOMA). Metformin also significantly decreased body weight. In controls, there was no change in Hcy, folic acid, vitamin B(12), TG, LDL, total-C, HbA1c, insulin, or HOMA levels. Homocysteine change did not correlate with insulin, folate, or vitamin B(12) changes in the metformin and rosiglitazone groups. CONCLUSIONS: In patients with type 2 diabetes, metformin reduces levels of folate and vitamin B(12) and increases Hcy. Conversely, rosiglitazone decreases Hcy levels in this time period. The clinical significance of these findings remains to be investigated.     

Evidence of local exercise-induced systemic oxidative stress in chronic obstructive pulmonary disease patients.

Chronic inactivity may not be the sole factor involved in the myopathy of chronic obstructive pulmonary disease (COPD) patients. One hypothesis is that exercise-induced oxidative stress that leads to muscle alterations may also be involved. This study investigated whether exercise localised to a peripheral muscle group would induce oxidative stress in COPD patients. Eleven COPD patients (FEV1 1.15+/-0.4 L (mean+/-SD)) and 12 healthy age-matched subjects with a similar low quantity of physical activity performed endurance exercise localised to a peripheral muscle group, the quadriceps of the dominant leg. The authors measured plasma levels of thiobarbituric reactive substances (TBARs) as an index of oxidative stress, the release in superoxide anion (O2*-) by stimulated phagocytes as an oxidant, and blood vitamin E as one antioxidant. Quadriceps endurance was significantly lower in the COPD patients compared with healthy subjects (136+/-16 s versus 385+/-69 s (mean+/-SEM), respectively). A significant increase in TBARs 6 h after quadriceps exercise was only found in the COPD patients. In addition, significantly higher O2*- release and lower blood vitamin E levels were found in COPD patients than in controls at rest. This blood vitamin E level was significantly correlated with the resting level of plasma TBARs in the COPD patients. This study mainly showed that quadriceps exercise induced systemic oxidative stress in chronic obstructive pulmonary disease patients and that vitamin E levels were decreased in these patients at rest. The exact relevance of these findings to chronic obstructive pulmonary disease myopathy needs to be elucidated.     

Hyperhomocysteinemia and related factors in 600 hospitalized elderly subjects

Hyperhomocysteinemia (HHcy) is a metabolic disorder frequently occurring in the elderly population. Recently several reports have suggested abnormalities in homocysteine (tHcy) metabolism implicating HHcy as a metabolic link in the multifactorial processes characterizing many geriatric illnesses-with special emphasis on atherosclerotic vascular diseases and cognitive impairment. The present study was undertaken in a large sample of elderly hospitalized subjects to determine (1) the prevalence of HHcy, (2) the association of HHcy with vascular and cognitive disorders, and (3) the factors independently predicting Hhcy. Six hundred elderly subjects (264 men and 336 women; mean age, 79 +/- 9 years) were randomly chosen from those admitted as inpatients over a period of 3 years. In all patients, body mass index (BMI), mid-upper arm muscle area (MUAMA), plasma cholesterol, triglycerides, total proteins, albumin, lymphocyte count, creatinine, homocysteine (fasting and 4 hours after methionine oral load), serum vitamin B(6), vitamin B(12), and folate concentrations were measured. The presence of disease or use of medications known to affect homocysteine plasma levels were also recorded. The mean fasting tHcy level was 16.8 +/- 12 micromol/L in the whole sample, 18.18 +/- 13.25 micromol/L in men, and 15.86 +/- 12.14 micromol/L in women (P =.005 men v women). The mean Hcy level 4 hours after methionine load was 37.95 +/- 20.9 in the whole sample. Prevalence of hyperhomocysteinemia (fasting Hcy > or = 15 micromol/L or 4 hours after methionine load > or = 35 micromol/L) was 61% (365/600) (67% in men and 56% in women, P <.05). HHcy was rarely (8%) an isolated disorder; in addition to diabetes (20%), renal failure (48.2%), and malnutrition (20.2%), it was often associated with heart failure (30%), malignancies (20.5%), and the use of diuretics (56%) and anticonvulsant drugs (13%). Plasma homocysteine progressively increases across subjects from those with no diabetes, malnutrition, renal failure, obesity, inflammatory bowel disease, heart failure to those with 1, 2, or more concurrent diseases. Multiple stepwise regression analysis showed that 72% of plasma total fasting tHcy variability was explained by age, serum folate, plasma albumin, use of diuretics, and renal function (measured as plasma creatinine clearance). In conclusion, the present study documents that hyperhomocysteinemia, in elderly hospitalized patients is (1) a common finding, (2) frequently associated with vascular and cognitive disorders, and (3) probably a secondary phenomenon in most cases. The major predictor of high plasma homocysteine levels were age, serum folate, plasma albumin, plasma creatinine clearance, and use of diuretic drugs. These variables explain a large proportion of plasma Hcy variability.     

Effect of chronic alcohol consumption on total plasma homocysteine level in rats

BACKGROUND: Chronic alcoholism in humans is associated with the development of hyperhomocysteinemia, the mechanism of which remains unclear. Among the causes of hyperhomocysteinemia is depletion of folate, vitamin B12, or vitamin B6. Population-based studies indicate that folate is the strongest vitamin determinant of hyperhomocysteinemia and, in most settings, folate supplementation effectively lowers elevated homocysteine levels. However, it is not clear whether folate deficiency is the cause of alcohol-related hyperhomocysteinemia. METHODS: In the present study, 10 male Sprague Dawley rats were fed ethanol-containing Lieber-DeCarli diets with 13 mg of folic acid per kilogram of diet. This represents a folate intake more than 20 times the basal requirement. Ethanol represented 36% of total energy, which yielded a concentration of 6.2% (vol/vol). The same number of rats were pair-fed with isocaloric control diets that contained an identical level of folate in which ethanol was entirely replaced by maltodextrin. RESULTS: At the end of 4 weeks, alcohol-fed rats did not show any significant reduction in plasma or hepatic folate concentrations, plasma pyridoxal-5'-phosphate concentration, or plasma vitamin B12 concentration. On the other hand, alcohol-fed rats were significantly hyperhomocysteinemic (17.24 +/- 4.63 micromol/liter,p < 0.01) compared to the nonalcohol group (10.73 +/- 2.76 micromol/liter). Alcohol-fed rats also had a significantly lower hepatic S-adenosylmethionine and higher hepatic S-adenosylhomocysteine levels. CONCLUSIONS: Chronic alcohol consumption produces hyperhomocysteinemia by a mechanism that is related to interference with one-carbon metabolism, and not through vitamin depletion.     

非酒精性脂肪肝患者血浆同型半胱氨酸水平测定及临床意义

目的 探讨非酒精性脂肪性肝病(NAFLD)患者空腹血清同型半胱氨酸(Hcy) 浓度变化的临床意义,同时探讨在NAFLD中Hcy浓度与叶酸及维生素B12浓度变化的相关性.方法 对352例健康体检人群行B超检查,其中NAFLD组159例,正常对照组193例,分别检测血浆Hcy、丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移...     

Effects of physical deconditioning after intense endurance training on left ventricular dimensions and stroke volume

To determine the role of preload in maintaining the enhanced stroke volume of upright exercise-trained endurance athletes after deconditioning, six highly trained subjects undergoing upright and supine bicycle ergometry were characterized before and after 3, 8 and 12 weeks of inactivity that reduced oxygen uptake by 20%. During exercise, oxygen uptake, cardiac output by carbon dioxide rebreathing, cardiac dimensions by M-mode echocardiography, indirect arterial blood pressure and heart rate were studied simultaneously. Two months of inactivity resulted in a reduction in stroke volume, calculated as cardiac output/heart rate, during upright exercise (p less than 0.005) without a significant change during supine exercise. A concomitant decrease in the left ventricular end-diastolic dimension from the trained to the deconditioned state was observed in the upright posture (5.1 +/- 0.3 versus 4.6 +/- 0.3 cm; p = 0.02) but not with recumbency (5.4 +/- 0.2 versus 5.1 +/- 0.3 cm; p = NS). There was a strong correlation between left ventricular end-diastolic dimension and stroke volume (r greater than 0.80) in all subjects. No significant changes in percent fractional shortening or left ventricular end-systolic dimension occurred in either position after cessation of training. Estimated left ventricular mass was 20% lower after 3 and 8 weeks of inactivity than when the subjects were conditioned (p less than 0.05 for both). Thus, the endurance-trained state for upright exercise is associated with a greater stroke volume during upright exercise because of augmented preload. Despite many years of intense training, inactivity for only a few weeks results in loss of this adaptation in conjunction with regression of left ventricular hypertrophy.     

Free and conjugated plasma catecholamines, lactate behavior and oxygen uptake at rest and in staged physical exertion as well as alpha receptor density in intact thrombocytes in trained athletes

The influence of chronic static training on free and conjugated plasma catecholamines was investigated in 8 statically trained athletes (21 +/- 2 years of age) at rest and during incremental ergometric cycling. Plasma catecholamines are seen as biochemical indicators of the over-all sympathetic activity. Alpha-2-adrenoreceptors were additionally determined as one parameter of the organism's sensitivity to catecholamines. During modest and heavy exercise, free plasma noradrenaline and adrenaline are comparably low in statically and endurance trained athletes. They are lower than in untrained subjects. During exhaustion, however, free adrenaline responses of the statically trained athletes only amount to 30-50% of the concentrations observed in endurance trained athletes and untrained subjects. Free plasma dopamine and conjugated plasma catecholamines do not show any significant changes during ergometric exercise. Free and conjugated catecholamines correlate positively. Positive correlations are also observed between blood pressure and plasma catecholamines. These correlations however are clearer between conjugated catecholamines and blood pressure. This is also recognizable for the negative correlation between alpha-2-receptor density on intact platelets (1078 +/- 323 binding sites per cell) and conjugated catecholamines. In conclusion, statically trained athletes also show an alteration of sympathetic tone (catecholamines) comparable to that observed in endurance trained athletes. Maximal adrenaline responses however are lower in statically trained athletes than in endurance trained or untrained subjects. The alpha-adrenoreceptor density on intact thrombocytes seems to be increased in statically trained athletes.     

Life-style habits and homocysteine levels in an elderly population

BACKGROUND AND AIMS: Increased plasma total homocysteine (Hcy) is a known cardiovascular disease (CVD) risk factor, related to several components of the established CVD risk profile. Observational studies support the role of modifying life-style related risk factors such as diet, physical activity and alcohol consumption in CVD prevention. Regular physical activity protects against coronary artery disease, possibly through its role in controlling risk factors such as hypertension, diabetes mellitus and obesity, but also independently. The aim of our study was to test the hypothesis that there is an association between physical activity, life-style habits and plasma Hcy levels in an elderly population. METHODS: In this cross-sectional study, 423 males and females aged 69.0 +/- 6.7 years completed an interview and laboratory examinations. Our main outcome measure was plasma levels of Hcy. RESULTS: Mean Hcy values were 10.5 +/- 5.5 micromol/L (11.4 +/- 6.1 for males and 9.3 +/- 4.5 for females; p < 0.001). Smoking and BMI were not found to be associated with Hcy levels. Physically active subjects, as well as B vitamin supplement users, had significantly lower Hcy levels (p = 0.002 and p = 0.004, respectively). In a multiple linear regression model, the Hcy level was 10% higher amongst participants with a sedentary life-style, 17% higher amongst males, 1% higher for each one-year increment in age, and 10% higher amongst participants who used no B vitamin supplements. CONCLUSIONS: Any level of physical activity was found to be an independent life-style habit associated with a lower Hcy level in an elderly population. This study supports existing recommendations for elderly persons to maintain a physically active life-style.