中国健康成人额叶白质,海马代谢物比值及其影响因素的氢质子波谱分析研究

目的:本研究利用氢质子磁共振波谱(1H-MRS)技术,探讨健康中国成人双侧额叶白质、双侧海马脑代谢物含量的正常值范围和影响代谢物浓度的因素。方法:对102例健康志愿者双侧额叶、双侧海马的代谢物天门冬氨酸(NAA)、胆碱(Cho)、肌酸(Cr)、肌醇(mI)进行测量,以肌酸(Cr)为内参照物计算NAA、Cho、mI相对含量(NAA/Cr、Cho/Cr、mI/Cr)。采用偏相关分析、独立样本t检验、单样本t检验进行统计处理。结果:双侧额叶白质NAA的相对含量(NAA/Cr)均随年龄的增长而下降(左侧r=-0·460,P<0·001;右侧r=-0·375,P<0·001)。左侧额叶白质NAA的相对含量在男性中(1·8808±0·29950)明显高于女性(1·7453±·19512)(P<0·05)。海马NAA的相对含量单侧化指数与1·0比较,差异有统计学意义。结论:年龄是影响额叶白质区域NAA含量的重要因素,随着年龄的增长,NAA含量会逐渐下降;性别对额叶白质代谢物相对浓度也有影响;半球偏侧化对健康成人双侧海马脑代谢物相对含量有影响。     

Circulating Vitamin D Metabolites and Subclinical Atherosclerosis in Type 1 Diabetes

OBJECTIVE

People with type 1 diabetes are at high risk of premature atherosclerosis. Existing evidence suggests that impaired vitamin D metabolism may contribute to the development of atherosclerosis. We tested associations of circulating vitamin D metabolite concentrations with subclinical atherosclerosis among 1,193 participants with type 1 diabetes in the DCCT/EDIC study.

RESEARCH DESIGN AND METHODS

We measured plasma concentrations of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and 24,25-dihydroxyvitamin D by mass spectrometry at the end of the DCCT. In a staggered cross-sectional design, we tested associations with coronary artery calcium (CAC), measured by computed tomography a median of 10 years later, and with common and internal carotid intima-media thickness (IMT), measured by B-mode ultrasonography on two occasions a median of 4 years later and a median of 10 years later. We hypothesized that lower concentrations of each vitamin D metabolite would be associated with increased risk of CAC and greater carotid IMT.

RESULTS

At the time metabolites were measured, mean age was 32.4 years and mean duration of diabetes was 7.5 years. The prevalence and severity of CAC tended to be lower—not higher—with lower concentrations of each vitamin D metabolite. For instance, in a fully adjusted multinomial logistic model, a 25 nmol/L lower 25-hydroxyvitamin D was associated with a 0.8-fold decrease in the odds of having higher CAC (95% CI 0.68–0.96, P = 0.01). No vitamin D metabolite was associated with either common or internal mean IMT.

CONCLUSIONS

We did not find evidence linking impaired vitamin D metabolism with increased subclinical atherosclerosis in type 1 diabetes.Premature atherosclerosis is a cause of substantial morbidity and mortality in type 1 diabetes (1). Treatment to control glycemia, plasma lipids, and blood pressure can reduce the risk of developing cardiovascular disease (2–4). However, identification of additional therapeutic targets is desirable to further reduce risk.Existing evidence suggests that impaired vitamin D metabolism may promote atherosclerosis (5). In animal experimental models, insufficient 1,25-dihydroxyvitamin D [1,25(OH)₂D, the active vitamin D hormone] stimulates the renin-angiotensin system, which promotes vascular damage through hemodynamic and metabolic effects and unfavorably modulates immune cell function in the arterial wall (5–8). Human studies suggest that these actions may be clinically relevant. Low circulating concentrations of 25-hydroxyvitamin D [25(OH)D, reflecting total vitamin D intake from cutaneous synthesis and oral consumption] have been associated with increased risks of coronary artery calcium (CAC), cardiovascular disease events, and death in populations with and without diabetes (9–16). Also, one study showed that low circulating levels of 1,25(OH)₂D are associated with increased risk of CAC (17). In addition, genetic variation in CYP24A1, the main enzyme responsible for catabolism of 25(OH)D to 24,25-dihydroxyvitamin D₃ [24,25(OH)₂D₃] and of 1,25(OH)₂D to 1,24,25-trihydroxyvitamin D, has been associated with risk of CAC (18).We measured serum concentrations of 25(OH)D, 1,25(OH)₂D, and 24,25(OH)₂D₃ among 1,193 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study. We hypothesized that low concentrations of each of these metabolites, reflecting decreased vitamin D intake, activity, and turnover, respectively, would be associated with increased risk of subclinical cardiovascular disease, manifest as a greater prevalence and severity of CAC and greater carotid intima-media thickness (IMT).     

Intestinal Calcium Absorption and Serum Vitamin D Metabolites in Normal Subjects and Osteoporotic Patients: EFFECT OF AGE AND DIETARY CALCIUM

Intestinal calcium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = -0.22, P < 0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P < 0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH)(2)D were positively correlated (r = 0.50, P < 0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = -0.39, P < 0.01) and with serum 1,25(OH)(2)D (r = -0.50, P < 0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH)(2)D was significantly decreased in both osteoporotic patients and elderly normals (P < 0.001). In osteoporotic patients, calcium absorption increased significantly (P < 0.001) after 7 d administration of a small dose (0.4 mug/d) of synthetic 1,25(OH)(2)D(3). In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH(2)-terminal assay) relative to age-matched controls, and mean serum phosphate was increased.The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH)(2)D contributes significantly to decreased calcium absorption and adaptation in both osteoporotics and elderly normal subjects. In patients with osteoporosis this abnormality could result from a decrease in factors that normally stimulate 1,25(OH)(2)D production, such as the decreased parathyroid hormone secretion and increased serum phosphate demonstrated in this group. In elderly subjects a primary abnormality in metabolism of 25-OH-D to 1,25(OH)(2)D, analagous to that seen in aging rats, cannot be excluded.     

Detection of Vitamin D Metabolites in Breast Milk: Perspectives and challenges for measurement by Liquid Chromatography Tandem-Mass Spectrometry

Breast milk is an emerging matrix for vitamin D assessment of breastfed infants and their mothers. It is considered a more reliable indicator of infant intake than the assessment of maternal circulating vitamin D. With the improved sensitivity of mass spectrometry-based technologies, this method principle has been the recent mainstay for the quantitation of various vitamin D metabolites in breast milk for population-based clinical trials. There are still several areas across the total testing process (pre-analytical, analytical and post-analytical) to be defined and harmonised to translate breast milk vitamin D measurement by liquid chromatography-tandem mass spectrometry (LC-MS/MS) from population-based research to routine clinical use and public health applications. Pre-analytically, the determination of the best form of vitamin D to measure in breast milk requires more evidence. Analytically, standardisation of the methods to allow for comparability of results is required. Post analytically, breast milk vitamin D decision limits are needed to turn the individual numerical outputs into clinically meaningful results. This review aims to synthesise the current evidence and utility of measurement of breast milk vitamin D by LC-MS/MS and to lead a future discussion on best practices to allow for its clinical utility beyond its current research-based use.     

Inhibition of Free Fatty Acid Oxidation by Acetoacetate in Normal Dogs

Abstract The rate of turnover and oxidation of plasma free fatty acids (FITA) was measured in 7 normal anaesthetized dogs infused at a constant rate with l-¹⁴C-palmitate for 5 h. After a control period, sustained hyperketonaemia was induced by infusing sodium aceto-acetate (AA). This produced a fall in plasma FFA (33%) and in blood sugar (24%), without changes in immuno-reactive insulin (IRI) concentrations. During the control period, the turnover rate of carbon of FFA averaged 131 μat./kg/min, 32% of which were oxidized, thus supplying 17.7% of the total CO₂ production. At the end of the AA infusion, the mean turnover rate of FFA was reduced to 75μat.C/kg/min; since only 13.9 % of these were oxidized, the contribution of FFA to total CO₂ production was reduced to 4.3%. In the light of previous work showing that ketone infusions also reduce the rate of turnover and oxidation of glucose in dogs, we conclude that, under appropriate experimental conditions, ketones may strongly reduce the role of FFA and glucose as sources of energy.     

Role of 1,25-Dihydroxyvitamin D3 on Intestinal Phosphate Absorption in Rats with a Normal Vitamin D Supply

In vitamin D-deficient rats, impaired intestinal phosphorus (P) absorption can be corrected by 1,25-dihydroxyvitamin D₃[1,25-(OH)₂D₃]. In the present study, it was investigated whether changes in 1,25-(OH)₂D₃ production can influence intestinal P transport also in animals with a normal supply of vitamin D. The intestinal P absorption was evaluated in rats using both the in situ duodenal loop technique and the determination of the overall gastrointestinal absorption under three conditions known to influence the production of 1,25-(OH)₂D₃: (a) variation in dietary P, (b) thyroparathyroidectomy (TPTX) with or without administration of parathyroid hormone (PTH), and (c) treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP). In all circumstances changes in duodenal absorption paralleled the changes in the overall fractional absorption. (a) Lowering dietary P stimulated P absorption. (b) TPTX decreased P absorption. This effect was corrected either by the administration of PTH or by the administration of 1,25-(OH)₂D₃. (c) EHDP, when given at a dose known to inhibit 1,25-(OH)₂D₃ formation, decreased the duodenal P absorption in both intact and TPTX animals. This effect was corrected by 1,25-(OH)₂D₃. In the TPTX-EHDP-treated animals, the administration of PTH did not rectify the low duodenal P absorption. These results support the thesis that, in rats with normal vitamin D supply, variations in the endogenous production of 1,25-(OH)₂D₃ change the rate of P absorption. However, these changes are in such magnitude that they are of relatively small importance when compared to the effect of variation in the dietary intake of P. These results also strongly suggest that the action of PTH on duodenal P transport is mediated by its effect on 1,25-(OH)₂D₃ production, inasmuch as the effect of the hormone is abolished after blocking the renal 1-hydroxylation with EHDP.     

Renal Extraction of Gentamicin in Anesthetized Dogs

The tubular handling of gentamicin (G) and its intrarenal distribution were determined to elucidate the mechanism of G accumulation in the kidney. At a serum level of 11.1 ± 0.5 μg/ml (10 animals), as maintained by constant infusion for 5 h, serum Na⁺ and K⁺, arterial pressure, effective renal plasma flow and glomerular filtration rate remained undisturbed. The clearance values in milliliters per minute for G, inulin, and p-aminohippuric acid were 40.3 ± 1.8, 49.9 ± 2.8, and 132 ± 14, respectively. The ratio of clearance of G to clearance of inulin was 0.82 ± 0.04 (P < 0.005), suggesting net reabsorption of G by the renal tubules. The renal cortex/serum ratio for G was 11.9 ± 2.1, and the medulla/serum ratio was 2.7 ± 0.4, indicating greater uptake of G by the cortex. The extraction ratio of p-aminohippuric acid was 0.74 ± 0.03. In contrast, the extraction ratio of G was 0.20 ± 0.03, which was significantly lower than that of inulin (0.30 ± 0.04). It is concluded that the accumulation of G in the cortex was due to tubular reabsorption. Probably some of the reabsorbed G became trapped in the epithelial cells after crossing the luminal membrane, whereas some returned to the circulation.     

成人正常阑尾的超声检查及临床意义研究

目的 探讨成人正常阑尾的显示率、超声表现、血流特点及临床意义.方法 对194例既往无右下腹痛病史的成人正常阑尾进行超声检查,并与106例经超声检查且得到手术及病理证实的成人急性阑尾炎进行比较.结果 成人正常阑尾显示率97.9%,横断面呈圆形或椭圆形,平均直径(5.5±1.1)mm,腔内可无内容物,也可见气体、液体及粪渣等.加压可致阑尾滑动、形态改变及腔内容物流动.正常组与对照组阑尾直径、壁厚度、壁彩色血流显示率、壁动脉收缩期最大峰速(PSV)及阻力指数(RI)比较差异具有非常显著性意义(P<0.01).结论 成人正常阑尾超声可以显示,急腹症中可将阑尾作为一个常规部位进行检查,探及正常阑尾声像即可排除急性阑尾炎.     

呼吸对正常犬血流动力学影响的超声心动图研究

目的研究正常自主呼吸胸压变化对血流动力学的影响,进一步探讨呼吸影响心功能的机制.方法 11条心功能正常杂种犬,使用Acuson Sequoia 512彩色电脑声像仪,同步记录心电图、呼吸曲线和心内各瓣口血流速度,观察瓣口血流速度随呼吸变化的规律.结果三尖瓣和肺动脉瓣口血流速度随呼吸周期呈现规律性变化,但二尖瓣和主动脉瓣口的血流在部分呼吸周期中的变化并无明显规律,峰值血流速度出现与呼吸时相间有不确定性.结论自主呼吸所引起的胸压变化使室间隔左右摆动,但由于肺组织本身弹性的差异,胸内压和肺毛细血管内压间存在的压差使全胸内系统血液重新分布.这种血液重新分布取决于肺组织的弹性,从而导致二尖瓣和主动脉瓣口血流速度变化与呼吸时相间具有不确定性.     

聚合酶链反应限制性片段长度多态性检测维生素D受体基因型

目的建立一种简便、实用、准确的人维生素Ｄ受体（ＶＤＲ）基因型的检测方法，以利于ＶＤＲ基因变异在骨质疏松研究中的应用。方法采用聚合酶链反应（ＰＣＲ）特异性扩增ＶＤＲ基因序列，扩增产物用限制性内切酶ＢｓｍⅠ酶切，琼脂糖凝胶电泳后，观察酶切位点的限制性片段长度多态性（ＲＦＬＰ）图谱。结果应用ＰＣＲＲＦＬＰ法检测了１１０名健康汉族人ＶＤＲ基因型，ｂｂ、Ｂｂ、ＢＢ基因型分布频率分别是９４％（１０３例）、６％（７例）、０。结论该方法简便、准确、重复性好，适用于一般实验室及流行病学调查。     

Electrophysiological Effects of Monophasic and Biphasic Stimuli in Normal and Infarcted Dogs

Though some biphasic waveforms significantly decrease the energy required for defibrillation, little is known about the effect of biphasic stimulation on the determination of other electrophysiological parameters in normal and infarcted hearts. To evaluate this, nine normal dogs and 12 dogs with myocardial infarction had activation threshold (AT), effective refractory period (ERP), strength-interval curves, and ventricular fibrillation threshold (VFT) determined with constant current stimulation to a pair of right ventricular plunge electrodes, and upper limit of vulnerability (ULV) and defibrillation threshold (DFT) determined with truncated exponential shocks delivered to a pair of wire electrodes coiled to contour the right and left ventricular epicardium. Each electrophysiological parameter was determined with a 5.5 msec monophasic and 5.5-msec biphasic (3.5 msec first phase) waveform. Though AT and VFT were not significantly different for the two waveforms, the ERP was significantly longer, the strength-interval curve shifted rightward, and the threshold for repetitive responses higher for biphasic stimuli. Compared to the monophasic waveform, the ULV and DFT were significantly decreased in a parallel fashion for the biphasic waveform. Neither the presence nor size of myocardial infarction significantly affected any of the measured electrophysiological parameters. In six additional dogs, sigmoid defibrillation probability curves were constructed from biphasic shocks of four energies including that of the DFT and ULV. The ULV energy predicted an effective dose that defibrillated 97% of the time (range 90%-100%). In conclusion, the increased defibrillation efficacy of the biphasic waveform is independent of its ability to activate fully repolarized myocardium and cannot be explained by a greater ability of biphasic waveforms to activate partially depolarized tissue. The parallel decrease in the ULV and DFT for biphasic stimulation and the finding that the ULV energy defibrillates with a high probability of success suggest similar underlying mechanisms for the ULV and defibrillation.     

正常成人声带区解剖结构的超声成像

目的评价超声显示正常成人声带区结构的能力。方法对104例健康成人行声带区超声检查,以甲状软骨为声窗,采取前侧横切面,从前至后显示声带区结构,实时观察声带区结构的运动情况。总结声带区解剖结构声像图特点,分析超声成像水平在不同性别及年龄中的差异。结果超声对声带区各解剖结构的显示率分别为:甲状软骨100%,假声带、真声带及杓状软骨93.97%,声门裂84.62%,杓肌、后侧环状软骨板及环杓后肌73.08%。超声成像水平在不同性别和年龄方面比较差异有统计学意义(P0.01)。结论超声对正常成人声带区解剖结构具有较好的显示能力,可满足超声评价声带麻痹研究的需要。     

Studies of Vitamin D Deficiency in Man

Highly sensitive assays have been developed that enable 25-hydroxycholecalciferol(25-hydroxyvitamin D₃) and 25-hydroxyergocalciferol (25-hydroxyvitaminD₂) to be measured in the same serum sample. With these assaysit has been shown that endogenously produced cholecalciferol(vitamin D₃) is important in man; the findings further emphasizethe role of vitamin D metabolites as hormones rather than vitaminsin the traditional sense. Dietary sources of vitamin D appear to be inadequate and vitaminD deficiency has been shown to be the cause of rickets and osteomalaciain Asian immigrants to Britain. This condition may be readilytreated with small doses of vitamin D. In addition, sub-clinicaldeficiency was found in the Asian community. In the elderly, also, vitamin D deficiency was established asan important cause of osteomalacia and again evidence for theexistence of a sub-clinical deficiency state was found. It istherefore suggested that the present prophylactic practicesshould be reviewed. Secondary hyperparathyroidism (reflected by elevated concentrationsof circulating immunoassayable parathyroid hormone) was shownto be the rule rather than the exception in vitamin D deficiency.Some patients, however, had failed to respond to a hypocalcaemicstimulus. In others, there were high concentrations of parathyroidhormone despite normal serum calcium concentrations. Thus therelationship between parathyroid hormone and metabolites ofvitamin D may not be mediated through changes in serum calciumalone, and it is postulated that metabolites of vitamin D maydirectly affect the secretion of parathyroid hormone.     

Maternal Vitamin D Supplementation to Improve the Vitamin D Status of Breast-fed Infants: A Randomized Controlled Trial

ObjectiveTo determine whether a single monthly supplement is as effective as a daily maternal supplement in increasing breast milk vitamin D to achieve vitamin D sufficiency in their infants.Patients and MethodsForty mothers with exclusively breast-fed infants were randomized to receive oral cholecalciferol (vitamin D₃) 5000 IU/d for 28 days or 150,000 IU once. Maternal serum, breast milk, and urine were collected on days 0, 1, 3, 7, 14, and 28; infant serum was obtained on days 0 and 28. Enrollment occurred between January 7, 2011, and July 29, 2011.ResultsIn mothers given daily cholecalciferol, concentrations of serum and breast milk cholecalciferol attained steady levels of 18 and 8 ng/mL, respectively, from day 3 through 28. In mothers given the single dose, serum and breast milk cholecalciferol peaked at 160 and 40 ng/mL, respectively, at day 1 before rapidly declining. Maternal milk and serum cholecalciferol concentrations were related (r=0.87). Infant mean serum 25-hydroxyvitamin D concentration increased from 17±13 to 39±6 ng/mL in the single-dose group and from 16±12 to 39±12 ng/mL in the daily-dose group (P=.88). All infants achieved serum 25-hydroxyvitamin D concentrations of more than 20 ng/mL.ConclusionEither single-dose or daily-dose cholecalciferol supplementation of mothers provided breast milk concentrations that result in vitamin D sufficiency in breast-fed infants.Clinical Trial Registrationclinicaltrials.gov NCT01240265     

正常成人主肺动脉的超声测量及其意义

目的　探讨通过正常成人主肺动脉的超声测量诊断肺动脉高压与否的可能性。方法　连续测量14 9例正常成人主肺动脉直径 (内径 )并测量膈处降主动脉直径 (内径 )的比值 ,另外采用相同方法测量 17例 6 0～ 78岁一组经彩色 Doppler证实的慢性肺阻塞疾病 (chronic obstructive pulmonary disease,COPD)患者主肺动脉直径及与降主动脉直径的比值并与正常组比较。结果　正常成人不同年龄主肺动脉直径不同并有随年龄增长而增大的趋势 (P<0 .0 5 ) ,其比值与年龄有关 (P<0 .0 5 ) ,且其比值与 COPD患者的比值比较存在显著差异 (P<0 .0 1)。结论　正常成人不同年龄组主肺动脉与降主动脉的比值可作为判断肺动脉高压与否的简单、敏感的指标。