Vitamin D,Cardiovascular System,and Longevity of Hemodialysis Patients

Abstract: The risk of cardiovascular death is high in hemodialysis (HD) patients, and thickening, stiffening and calcification of the arterial wall have been shown as its predictive factors. Activated vitamin D preparations are used for the treatment of secondary hyperparathyroidism in HD patients, but as they increase serum phosphate and calcium concentrations, there is a concern that they promote vascular calcification and, consequently, exacerbate the outcomes. In this article, the effects of vitamin D therapy on survival, cardiac function, arteriosclerosis, immunity, and inflammation are evaluated by reviewing the literature. In HD patients, the risk of death (particularly cardiovascular death) is significantly lower in those treated than in those not treated with vitamin D. Moreover, activated vitamin D improves cardiac function and alleviates cardiac hypertrophy in HD patients. Experimental data in cultured macrophages, vascular smooth muscle cells, and vascular endothelial cells suggest that it has antiatherosclerotic effects. In vivo, the administration of vitamin D improves immune functions and normalizes inflammatory reactions. In HD patients, vascular calcification is related to the dose of calcium carbonate, but its relationship with the administration of vitamin D is not significant. These observations suggest that, contrary to the general concerns, activated vitamin D exerts favorable effects on the cardiovascular system in HD patients as long as it is used in appropriate clinical doses.     

Continuously moving table 3D MRI with lateral frequency-encoding direction.

A method is presented for 3D MRI in an extended field of view (FOV) based on continuous motion of the patient table and an efficient acquisition scheme. A gradient-echo MR pulse sequence is applied with lateral (left-right (L/R)) frequency-encoding direction and slab selection along the direction of motion. Compensation for the table motion is achieved by a combination of slab tracking and data alignment in hybrid space. The method allows fast k-space coverage to be achieved, especially when a short sampling FOV is chosen along the direction of table motion, as is desirable for good image quality. The method can be incorporated into different acquisitions schemes, including segmented k-space scanning, which allows for contrast variation with the use of magnetization preparation. Head-to-toe images of volunteers were obtained with good quality using 3D spoiled gradient-echo sequences. As an example of magnetization-prepared imaging, fat/water separated images were acquired using chemical shift selective (CHESS) presaturation pulses.     

中国优秀马拉松运动员ACE基因I/D多态性频率分布特征

通过分析中国马拉松运动员ACE基因I/D多态频率分布特征,探讨其作为杰出耐力基因标记的可行性。选择我国马拉松健将、国际健将级运动员26名作为马拉松运动员组,汉族学生216名作为对照组。对两组受试者进行ACE基因I/D多态性测定。结果显示:我国马拉松运动员组的等位基因频率和基因型频率与对照组比较无显著差异,其中15名国际健将中无一DD型纯合子,提示我国优秀马拉松运动员的纯合子DD型频率低下是其ACE基因多态频率分布的主要特征。     

Renal function and 25-hydroxyvitamin D concentrations predict parathyroid hormone levels in renal transplant patients.

BACKGROUND: Recent guidelines suggest supplementation with ergocalciferol (vitamin D(2)) in chronic kidney disease stages 3 and 4 patients with elevated parathyroid hormone (PTH) levels and 25-hydroxyvitamin D (25OHD) levels <75 nmol/l. These guidelines are also applied to renal transplant patients. However, the prevalence rates of 25OHD deficiency and its association with PTH levels in renal transplant populations have not been extensively examined. We aimed to document the prevalence rates of 25OHD deficiency [defined by serum levels <40 nmol/l (<16 ng/ml)] and insufficiency [<75 nmol/l (<30 ng/ml)] in a single renal transplant centre, and examine its relationship with PTH levels. METHODS: Serum 25OHD and PTH concentrations were measured in 419 transplant patients attending a single renal transplant clinic over a 4-month period. Demographic and biochemical data were also collected, including serum creatinine, calcium, phosphate and albumin. Simple and multiple linear regression analysis were performed. RESULTS: In 27.3% of the patients, 25OHD deficiency was present, and 75.5% had insufficiency. On univariate analysis, 25OHD, serum albumin and estimated glomerular filtration rate (eGFR) were significantly associated with PTH levels (P < 0.0001, P = 0.004 and P < 0.0001, respectively). Multiple linear regression demonstrated that only 25OHD, eGFR and serum phosphate were significantly predictive of PTH levels (R(2) = 0.19, P < 0.0001). In this model, a 75 nmol/l increase in 25OHD will only result in a maximal reduction in PTH of 2.0 pmol/l. CONCLUSIONS: We conclude that 25OHD deficiency and insufficiency are common in renal transplant patients and may exacerbate secondary hyperparathyroidism. However, 25OHD, eGFR and phosphate only account for 19% of the variability in PTH levels. In addition, even a large increase in serum 25OHD levels is likely to result in only a small reduction in PTH. Therefore, alternative approaches to managing hyperparathyroidism in renal transplant recipients rather than supplementation with ergocalciferol are warranted.     

Prevalence of vitamin D depletion among morbidly obese patients seeking gastric bypass surgery

BACKGROUND: Abnormalities in calcium and vitamin D metabolism have been reported after bariatric surgery. The purpose of this study was to evaluate vitamin D nutritional status among morbidly obese patients before gastric bypass surgery. METHODS: We prospectively studied 279 morbidly obese patients seeking gastric bypass surgery for vitamin D nutritional status as assessed by serum 25-hydroxyvitamin D level. In addition, serum samples were analyzed for calcium, alkaline phosphatase (AP), intact parathyroid hormone (PTH), and 1,25-dihydroxyvitamin D. RESULTS: Mean patient age was 43 +/- 9 years; 87% of the study patients were women, and 72% were white. Serum calcium and AP levels were normal in 88% and 89% of the patients, respectively. Vitamin D depletion, defined as serum 25-hydroxyvitamin D level vitamin D level and both body mass index (r = .15; P = .012) and serum PTH level (r = .45; P < .001). Vitamin D depletion was significantly more prevalent in the African-American patients than in the white patients (91% vs 48%; P < .001). CONCLUSIONS: Before gastric bypass surgery, a majority of morbidly obese patients have vitamin D depletion and secondary hyperparathyroidism. Studies evaluating the effects of gastric bypass on vitamin D metabolism must consider preoperative vitamin D nutritional status.     

Vitamin D receptor genotype and risk of osteoporotic hip fracture in elderly women of Utah: an effect modified by parity

Introduction The associations between vitamin D receptor (VDR) Bsm I and Fok I genotypes, parity, and risk of osteoporotic hip fracture were evaluated in a statewide population-based case-control study in Utah.Methods Women age 50–89 years with hip fracture (n=882) were ascertained via surveillance of 18 Utah hospitals from 1997 to 2001. Age-matched controls were randomly selected (n=897). Participants were interviewed in their homes, and blood samples were collected for genotyping.Results In logistic regression analyses that controlled for multiple confounders, Bsm I VDR genotype but not Fok I genotype was associated with risk of osteoporotic hip fracture (OR bb vs. BB genotype: 0.68; 95% CI: 0.50, 0.95). In similar analyses, no overall association was observed between parity status and risk of osteoporotic hip fracture. However, the effect of VDR genotype was modified by parity status. Among nulliparous women (n=140), Bsm I genotype was not associated with risk of hip fracture (OR bb vs. BB: 0.82; 95% CI: 0.28, 2.4); among primiparous women (n=133), bb genotype was associated with increased risk of hip fracture (OR bb vs. BB: 3.30; 95% CI: 0.96, 11.29); among multiparous women (n=1,400), bb genotype was associated with decreased risk of hip fracture (OR bb vs. BB: 0.59; 95% CI: 0.42, 0.84).Conclusion VDR Bsm I genotype was associated with risk of hip fracture in Utah women, and this effect was modified by parity status. Hormonal or lifestyle factors related to parity may underlie this interaction.     

Serum 25-hydroxyvitamin D concentrations of New Zealanders aged 15 years and older

Introduction Vitamin D plays an important role in bone health. Our purpose was to measure serum 25-hydroxyvitamin D concentrations and their determinants in a national sample (n=2,946) of New Zealanders aged 15 years and over.Findings Mean (99% CI) serum 25-hydroxyvitamin D concentrations were 47 (45–50) nmol/l in women and 52 (49–55) nmol/l in men. Mean concentrations in New Zealand European and Others (NZEO, n=2,440), Mori (n=370), and Pacific (n=136) were 51 (49–53), 42 (38–46) and 37 (33–42) nmol/l, respectively. Three percent of New Zealanders had serum 25-hydroxyvitamin D concentrations indicative of deficiency (≤17.5 nmol/l); 48% and 84% were insufficient based on cutoffs of ≤50 and ≤80 nmol/l. Determinants of serum 25-hydroxyvitamin D concentrations in women were age, ethnicity, obesity, latitude and season; determinants in men were ethnicity and season. Serum 25-hydroxyvitamin D in women declined with age; mean concentration was 13 (8–18) nmol/l lower in women 65 years or older and 9 (5–13) nmol/l lower in women 45–64 years compared with women 15–18 years. Spring to summer differences in serum 25-hydroxyvitamin D were 31 (28–34) and 28 (25–31) nmol/l in women and men, respectively. Obese women had lower vitamin status than normal-weight women by 6 (3–10). Women living in the South Island had a mean serum 25-hydroxyvitamin D that was 6 (3–9) nmol/l lower than women living in the North Island. Ethnicity and season are the major determinants of serum 25-hydroxyvitamin D in New Zealanders.Conclusion The high prevalence of vitamin D insufficiency in New Zealanders, particularly in older women, may warrant strategies to improve vitamin D status.     

Subtype determination of soma-dendritic α2-autoreceptors in slices of rat locus coeruleus

The aim of the study was to subclassify the soma-dendritic α₂-autoreceptors in the locus coeruleus (LC) of the rat by means of antagonists. To this end, the frequency of spontaneous action potentials was recorded extracellularly from single LC neurones in brain slices. The neurones fired spontaneously at an average rate of 1 Hz. The selective α₂-adrenoceptor agonist 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK 14,304) and noradrenaline decreased the action potential discharge with IC₅₀ values of 5 and 510 nM, respectively. The concentration-inhibition curves of UK 14,304 and noradrenaline were shifted to the right by phentolamine (0.15 μM) and rauwolscine (0.15 μM) but not by prazosin (1 μM). Apparent K _d values of phentolamine were 17 nM (against UK 14,304) and 20 nM (against noradrenaline). Apparent K _d values of rauwolscine were 47 nM (against UK 14,304) and 70 nM (against noradrenaline). (+)-Oxaprotiline (1 μM) suppressed the firing of the neurones within 10 to 33 min. In the continued presence of oxaprotiline, phentolamine and rauwolscine restored firing with EC₅₀ values of 120 and 250 nM, respectively. Prazosin (1 μM) again was ineffective. All three antagonist affinity estimates – against UK 14,304, exogenous noradrenaline and endogenous noradrenaline (that accumulates in the extracellular space in the presence of oxaprotiline) – yield an affinity order phentolamine > rauwolscine >> prazosin, prazosin being ineffective even at a concentration of 1 μM. These findings identify the soma-dendritic α₂-autoreceptors of the LC as the rat variant of the α_2A/D-adrenoceptor, i.e. α_2D. Not only presynaptic but also soma-dendritic α₂-autoreceptors may at least predominantly be α_2A/D throughout the nervous system. Received: 3 March 1997 / Accepted: 21 April 1997     

1 alpha(OH)D3 (ETALPHA) treatment and receptor studies in 16 patients with chronic and myeloproliferative disorders

10 patients with CLL and 2 with CML were treated with gradually increasing doses of 1 alpha(OH)D3, up to 4 micrograms daily during 6 wk. 3 patients with preleukemia and 1 with myelofibrosis were treated with 2 micrograms daily of 1 alpha(OH)D3 for a prolonged period up to 17 wk. The treatment with 1 alpha (OH)D3 did not result in changes of disease parameters in any of the patients under study. Receptor studies for 1,25(OH)2D3 were performed in 8 CLL patients and revealed only 1 patient with increased specific receptor binding capacity. The maximum tolerable dose of 1 alpha(OH)D3 varied individually, but was in the range of 2-4 micrograms daily.