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.     

强迫谱系障碍与第Ⅱ组代谢型谷氨酸受体相关候选基因位点的连锁分析

目的 了解代谢型谷氨酸受体mGlu2受体（mGluR2）基因、mGlu3受体（mGluR3）基因等与强迫谱系障碍（OCSDs）的连锁关系。方法 选取一个连续三代发病的强迫谱系障碍家系，采集到该家系中12个正常个体，8个受累个体的血样，选取mGluR2、mGluR3基因附近7对微卫星标记引物，采用两点和多点非参数分析的方法对该家系进行连锁分析。结果 7对微卫星标记位点的两点和多点非参数分析LOD值（NPL值），位于mGluR3基因附近的标记D7S644两点非参数分析NPL值为1．719（P=0．078），多点非参数分析NPL值为1．712（P=0．078），达到验证性连锁的阈值（NPL=1．2），但未达到提示性连锁的阕值（NPL=2．2），D7S2481两点非参数分析NPL值为0．628（P=0．179），多点非参数分析NPL值为0．852（P=0．141），接近验证性连锁的阈值，其余5对微卫星标记位点非参数分析NPL值均未达到验证性连锁的阈值。结论 提示mGluR3基因与OCSDs可能存在连锁关系，不能排除mGluR2基因与OCSDs的相关性。     

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 相似文献   

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.     

Leber’s hereditary optic neuropathy and vitamin B12 deficiency

Background Leber’s hereditary optic neuropathy (LHON) is a maternally inherited optic neuropathy caused by mutations in mitochondrial DNA (mtDNA). It is also believed that several epigenetic factors have an influence on the development of LHON.Methods A case series was observed.Results Three patients who developed bilateral optic neuropathy are presented. All patients had a primary LHON mutation in their mtDNA, but also a subnormal vitamin B12 serum level at the time of presentation.Conclusions The clinical picture of optic neuropathy associated with vitamin B12 deficiency shows similarity to that of LHON. Both involve the nerve fibres of the papillomacular bundle. The present case reports suggest that optic neuropathy in patients carrying a primary LHON mtDNA mutation may be precipitated by vitamin B12 deficiency. Therefore, known carriers should take care to have an adequate dietary intake of vitamin B12 and malabsorption syndromes like those occurring in familial pernicious anaemia or after gastric surgery should be excluded.     

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.     

Morphine exposure prevents up-regulation of MR and GR binding sites in the brain of adult male and female rats due to prenatal stress

Our previous work demonstrated that the hormone response to stress and the negative feedback inhibition to these hormones are sex-dependently altered by prenatal morphine exposure in adult rats. An alteration in the glucocorticoid negative feedback inhibition is mediated by glucocorticoid receptors (GR) that are distributed throughout the brain, and mineralocorticoid receptors (MR) localized mainly in the hippocampus and involved in a tonic influence of brain functions. Therefore, the present study examined the binding characteristics of MR and GR in young adult male and female rats exposed prenatally (E11-E18) to morphine (10 mg/kg/2 x /day), saline or no treatment at all (controls). At 60-90 days of age, animals were adrenalectomized (ADX) 24 h prior to decapitation. The hippocampus and hypothalamus were dissected for saturation binding assays. The data demonstrate that prenatal stress due to maternal saline injections up-regulates MR and GR binding in the hippocampus of adult male rats and this effect is prevented by prenatal morphine exposure. There is no effect of prenatal morphine exposure on GR binding in the hypothalamus of males. In female rats, prenatal morphine exposure does not affect the binding of MR and GR in the hippocampus or GR in the hypothalamus relative to controls; however, they are affected by ovarian hormone fluctuation. Moreover, prenatal stress decreases MR binding in the hippocampus of diestrous females and GR binding in the hypothalamus of estrous females. Both decreases are prevented by prenatal morphine exposure. Thus, the present study demonstrates that: (1) prenatal stress due to maternal saline injections alters MR and GR binding of adult male and female rats and is prevented by prenatal morphine exposure; (2) the MR and GR binding in adult female rats are affected by ovarian hormone fluctuations.     

多巴胺受体与其他血压调节系统的交互作用在高血压研究中的地位

肾脏是人体负责钠排泄的重要器官,多巴胺由于其强大的抑制肾脏钠重吸收作用而在原发性高血压的发生、发展中发挥重要作用。多巴胺受体的5个亚型均直接或间接通过与其他血压调节系统的交互作用,参与肾脏钠通道或血压的调节。现就多巴胺受体在调节机体血压和肾脏利钠、利尿作用中所发挥的重要作用作一综述。     

Androgen receptors in colorectal adenomas

Summary To evaluate the potential effect of androgens on the development and growth of human colorectal adenomas, the prevalence and concentration of cytosolic androgen receptors (AR) were analysed in 26 adenomas and 19 samples of normal colonic mucosa by a hybrid ligand receptor-binding assay. AR were detected in 7 of the adenomas (26.9%), and in 6 of the normal mucosa samples (31.6%). In the adenomas, AR levels demonstrated were low, ranging from 6 to 31 fmol/mg cytosol protein, and dissociation constants (Kds) ranged from 0.17–2.7x10^-9 M. Of 13 adenomas excised from men, 6 (46%) had positive receptor activity, whereas only 1 of 13 (7.7%) from women was positive (P=0.03, Fisher's exact test). There was no correlation between AR titre and patient age, or between adenoma size and histological type or degree of dysplasia. In normal mucosa, AR levels ranged from 7 to 33 fmol/mg and Kds ranges from 0.24–3.1x10^-9 M. There was no significant difference between either AR prevalence or levels in the adenomas and normal mucosa. The sex difference was exclusive to the adenoma. Endogenous androgen may play a role in adenoma development early in the promotional process.