Effects of 1,25 (OH)2D3 treatment on lipid levels in uremic hemodialysis patients.

The aim of this study was to evaluate the effect of 1,25 (OH)2D3 treatment on lipid levels in uremic hemodialysis (HD) patients. Thirty-one HD patients who had never been treated with vitamin D nor related drugs and 12 healthy subjects with normal renal functions were studied. Uremic HD patients were randomly divided into two groups. Sixteen uremic HD patients were treated with oral calcitriol (0.5 micrograms/day) for 8 weeks. 13 uremic HD patients and 12 healthy subjects were given placebo. In all these cases before and after 8 weeks of treatments; serum total lipid, total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride levels were determined. After calcitriol treatment, triglyceride levels were significantly decreased. But total lipid, cholesterol, HDL-cholesterol and LDL-cholesterol levels did not significantly change. In the other two groups there were no significant changes. These results show that calcitriol treatment has a positive effect on triglyceride levels in uremic HD patients. This effect of mechanism of calcitriol treatment has not been known yet. But it could be due to regulation carbohydrates metabolism and normalization of parathormone (PTH) levels.     

Serum ferroxidase I and II in uremic patients under conservative treatment and maintenance hemodialysis

Serum ferroxidase I (ceruloplasmin) and ferroxidase II activities were studied in 49 uremic patients under conservative treatment, in 79 patients undergoing hemodialysis and in 56 healthy subjects, as controls. Ferroxidase I was significantly higher in both groups of patients. Ferroxidase II was significantly elevated only in patients undergoing chronic hemodialysis. The cause of this difference is not clear, but seems to be of considerable interest.     

Effects and interactions of 24R,25(OH)2D3 and 1,25(OH)2D3 on bone

The effects of various combinations of therapy with 1 alpha,25-dihydroxycholecalciferol (1,25(OH)2D3) and 24R,25-dihydroxycholecalciferol (24R,25(OH)2D3) on structural and dynamic parameters of bone were evaluated in 40 chicks raised on a vitamin D-deficient diet from time of hatching and supplemented with the dihydroxylated metabolites. The results showed that: 1) the maintenance of volumetric density of bone is dependent on the presence of 1,25(OH)2D3, 2) lack of 1,25(OH)2D3 is associated with an increase in the number of osteocytes per unit volume of bone, most probably due to decreased amounts of bone formed by each osteoblast before becoming an osteocyte, 3) adequate quantities of either 24R,25(OH)2D3 or 1,25(OH)2D3 are needed to prevent accumulation of osteoid or the production of endosteal fibrosis, and 4) maintenance of normal tetracycline label width requires both hydroxylated compounds with one of them in sufficient amounts. The data of this study demonstrate that the integrity of certain parameters of bone structure could be maintained only with 1,25(OH)2D3, others with either dihydroxylated metabolites, and still others with a combination of both. These data underscore the biological activity of 24R,25(OH)2D3 by demonstrating its effectiveness on bone.     

Bone mineral content, cortical thickness and fracture rate in osteoporotic women after withdrawal of treatment with nandrolone decanoate, 1-alpha hydroxyvitamin D3, or intermittent calcium infusions

Twenty-six post-menopausal osteoporosis patients were studied prospectively over a 2-yr period after the cessation of 2 yr of treatment with either nandrolone decanoate (anabolic steroid), 1 alpha hydroxyvitamin D3 or intermittent calcium infusions, the total observation period being 4 yr. Serial evaluations of bone mineral content in the radius, cortical thickness of the metacarpals and spinal roentgenograms were obtained. Nine patients who had been treated with 50 mg nandrolone decanoate every three weeks did not lose bone from the radius or the metacarpals during the 2 yrs following withdrawal of therapy. Eight patients who had received 1 microgram/day of oral 1 alpha hydroxyvitamin D3 retained a positive bone mineral content in the radius but lost cortical thickness from the metacarpals after withdrawal of therapy. Nine patients who had been treated with intermittent calcium infusions over 12 consecutive days annually did not lose further bone mineral content from the radius, but did lose cortical thickness at the expected rate during the 2-yr post-treatment period. The fracture rate at the end of the 4-yr observation period was 40% lower in the nandrolone decanoate group than in the 1-alpha-hydroxyvitamin D3 and calcium infusion groups. The results of this study indicate that, in contrast to oestrogen and calcium therapy, nandrolone decanoate and 1-alpha-hydroxyvitamin D3 have lasting beneficial effects, and that data obtained by photon absorptiometry do not always coincide with those obtained by radiogrammetry. These findings are highly relevant to the design of future therapeutic trials.     

Effect of vitamin E therapy on sexual functions of uremic patients in hemodialysis.

Twenty-four uremic patients on hemodialysis who had never been treated with vitamin E or related drugs and 12 control patients with normal renal function were studied. Hemodialysis patients were randomly divided into two groups; 12 were treated with oral vitamin E (300 mg/day) for eight weeks and 12 uremic patients and 12 controls were given placebo. Serum vitamin E, prolactin, FSH, LH, and free testosterone levels were measured in all patients before and after treatment. After the vitamin E treatment serum prolactin levels were significantly decreased (50.8 vs 15.4 ng/ml, p < 0.01). Vitamin E levels were significantly increased (1.11 vs 1.22 mg/dl, p < 0.05). Serum FSH, LH and free testosterone were not affected. In the other two groups there were no significant changes. These results show that vitamin E treatment lowers prolactin levels in uremic hemodialysis patients. This might be due to inhibition of central prolactin secretion. Vitamin E inhibits pituitary gland hypertrophy in vitamin E-deficient rats.     

负压创面治疗技术对大鼠慢性溃疡创面血流及缺氧诱导因子1-α表达的影响

：目的 通过观察负压创面治疗技术对大鼠慢性创面血流变化及缺氧诱导因子1-α（HIF1-α）表达的影响,探讨负压创面治疗技术对慢性创面治疗作用及机制.方法选取10～12周龄健康SD大鼠20只,进行慢性溃疡造模后随机分为实验组和对照组,均连续进行5 d创面治疗,实验组采用负压创面治疗技术治疗,对照组采用0.9%氯化钠溶液纱布换药治疗.采用激光多普勒血流检测系统对两组分别进行正常皮肤、治疗0 d创面及5 d治疗期间每天1次创面血流灌注量测量,进行两组正常对照和治疗0 d血流的组间、组内比较,比较治疗期间两组创面血流变化.每日大体观察两组创面愈合状况.5 d治疗期结束后对两组大鼠创面周围组织取材,免疫组化法测定缺氧诱导因子的表达,比较两组表达差异.结果 两组治疗0 d创面血流灌注量均比同组正常对照明显下降,差异有统计学意义（P＜0.01）,实验组治疗0 d创面血流灌注量、正常对照血流灌注量与对照组相比,差异无统计学意义（P＞0.05）.治疗期创面血流重复测量方差分析：处理效应与时间效应的交互作用有统计学意义（P＜0.01）,两组治疗期创面血流灌注均有随时间增加的趋势,但实验组增加的趋势比对照组更为明显,处理主效应有统计学意义（P＜0.01）,时间主效应有统计学意义（P＜0.01）,实验组各个治疗时点的创面血流灌注值均较对照组高,实验组HIF1-α表达明显少于对照组,差异有统计学意义（P〈0.01）.结论 负压创面治疗技术比常规换药能更迅速地改善创面血流及氧代谢,为慢性创面愈合提供良好的血流及氧代谢条件.     

Influence of estrogen on renal vitamin D hydroxylases and serum 1alpha,25-(OH)2D3 in chicks.

The influence of estrogen on the metabolism of 25-hydroxyvitamin D3 was studied in 2- to 5-wk-old chicks. Single injections of at least 500 microgram diethylstibestrol (DES) increased the conversion of 25-hydroxyvitamin D3 to 1alpha,25-dihydroxyvitamin D3 (1alpha,25-(OH)2D3) and suppressed the production of 24,25-dihydroxyvitamin D3 in chick kidney homogenates. Acute (one 5-mg) injections of testosterone or progesterone did not enhance the 25-hydroxyvitamin D3-1alpha-hydroxylase, indicating specificity. However, chronic pretreatment with DES appeared to allow the potentiation of previously unstimulatory steroids such as progesterone and testosterone. In addition, the hormonal metabolite of vitamin D3, 1alpha,25-(OH)2D3, was measured in 4- to 6-wk chick plasma after steroid treatment. Greater than 1 mg DES per day for 5 days was necessary to enhance the circulating level of 1alpha,25-(OH)2D3; testosterone alone had no effect. This elevation was rapid, occurring within 12--24 h after injection. These data suggest that estrogen (as evidenced by DES treatment) is a modulator of vitamin D metabolism along with other known regulators such as parathyroid hormone, phosphate, and 1alpha,25-(OH)2D3. The mechanism of the regulation is as yet unknown.     

Comparison of blocking effects of monoclonal antibodies anti-MO1-alpha and anti-LFA1-alpha on human neutrophil functions.

In order to analyse the role of LFA1 and MO1 on neutrophil functions, the blocking effects of two monoclonal antibodies (MAb), one (anti-MO1) recognizing an epitope of the MO1-alpha chain and the other (25.31) an epitope of the LFA1-alpha chain, were measured. Adherence of 51Cr-labelled control neutrophils was 66 + 8% (mean +/- 1 SD) on plastic nuclon plates; this figure decreased to 33 +/- 5% and 23 +/- 6% of control adherence when the neutrophils had been pretreated with anti-LFA1-alpha (anti-alpha L) and anti-MO1-alpha (anti-alpha M), respectively. On another support (plastic culture chambers), 84 +/- 6% of control neutrophils adhered and the adherence of neutrophils pretreated with anti-alpha L or anti-alpha M was 10% and 43% of the control figure, respectively. These results show that adherence of neutrophils is dependent upon the plastic used. Moreover, inhibition of adhesion by the two MAbs was also dependent upon the support used for the assay, suggesting that MO1 and LFA1 may be surface proteins with different specificities. Both antigens capped upon adhesion, while they were randomly distributed in resting neutrophils. Anti-alpha L inhibited (congruent to 50%) locomotion more than did anti-alpha M (congruent to 25%), without altering chemoattractant-induced shape changes. These results suggest that the two MAbs inhibit chemokinesis but not chemotaxis. Many other adherence-associated functions, such as ingestion of opsonized Klebsiella pneumoniae, and cytotoxicity towards K/562 cells were decreased more by anti-alpha L than by anti-alpha M. In contrast, chemiluminescence and iodination induced by opsonized zymosan were inhibited more by anti-alpha M than by anti-alpha L. Degranulation induced by zymosan or opsonized zymosan was altered by anti-alpha M only, and this alteration involved azurophilic and not specific granules. Chemiluminescence induced by phorbol myristate acetate was inhibited to a greater extent by anti-alpha M than by anti-alpha L, while degranulation induced by phorbol myristate acetate was not altered by either of the two Mabs.     

Immunomodulatory and Immunosuppressive Roles of 1α,25(OH)2D3 in Autoimmune Diseases

Autoimmune diseases are pathological conditions characterized by abnormal responses, accompanied by autoantibodies to self‐molecules. The role of vitamin D in autoimmune diseases has increased significantly in the recent past from its functions in calcium and phosphate homoeostasis, and it is now involved in the regulations and proliferations of Th1 and Th17 lymphocyte. 1α,25(OH)2D3 is very important in ameliorations of inflammatory disorders arising from autoimmune diseases, but the mechanism by which this is performed is still a bone of contentions. This review aimed to highlight the existing facts about the roles of Vitamin D in the treatment and management of autoimmune diseases. An extensive online literature search was conducted using PubMed, MEDLINE and Scopus. Accumulated bodies of research evidence are available which demonstrates that Vitamin D has a very important part to play in the regulation of immune responses in autoimmune diseases. Some of the authors suggested that Vitamin D3 carry‐out its immunosuppressive and immune modulatory action, through its actions on antigen‐presenting cells and activated T and B cells with the help of Vitamin D receptors present on the each of these cells. Vitamin D supplementation assists in autoimmune disorders by making qualitative and quantitative changes in the immune system (downregulation of Th1 and upregulations of Th2 cells). This resulted in the body to be more tolerant of self and less likely to mount autoimmune responses.     

Antiphosphaturic action of 25 (OH) vitamin D3 in experimental Fanconi syndrome.

Renal handling of phosphorus was studied in the following groups of parathyroidectomized rats with maleate-induced Fanconi syndrome: 1) 6 rats receiving intravenous parathyroid hormone, 2) 6 rats receiving intravenous dibutyryl cyclic AMP (DBcAMP), 3) 6 rats undergoing volume expansion with saline, 4) 12 rats receiving intravenous 25 (OH)vitamin D3, 5) 12 rats with acute hypercalcemia induced by intravenous CaCl2, 6) 6 rats with phosphate deprivation, and 7) 6 rats receiving intravenous calcitonin. Parathyroid hormone and calcitonin failed to increase the urinary excretion of both cAMP and phosphorus. Likewise, DBcAMP failed to increase the urinary excretion of phosphorus. Extracellular volume expansion and hypercalcemia (serum calcium 12.9 +/- 0.7 mg/100 ml) did not alter the tubular reabsorption of phosphorus. In phosphate-deprived animals, the fractional excretion 0.16 +/- 0.05 (mean +/- SE) was lower than that in the control animals (maleate-treated without phosphate depletion), 0.46 +/- 0.04 (P less than 0.001). 25 (OH)vitamin D3 decreased the fractional excretion of phosphorus from 0.39 +/- 0.03 in the control (maleate-treated not receiving 25 (OH)vitamin D3) to 0.23 +/- 0.02 (P less than 0.001) in the experimental animals. The present study demonstrated an antiphosphaturic effect of 25(OH)vitamin D3 in experimental Fanconi syndrome; the mechanism of this action is not well understood.     

浮肩损伤保守与手术治疗的Meta分析

背景：浮肩损伤在创伤疾病中较罕见,关于其治疗方法存在较多争议,至今仍无权威性的临床指导供学者达成共识。 目的：对采取保守与手术治疗浮肩损伤的疗效进行系统评价。 方法：通过计算机检索CNKI数据库,Web of Science数据库,以“floating shoulder”或“浮肩损伤”为关键词。收集所有相关对照试验,并评价纳入研究的方法学质量。采用RevMan4.2软件进行Meta分析,观察森林图显示的分析特征和结果。 结果与结论：无论保守还是手术治疗均可取得满意的治疗效果;两种治疗方法相比较,在疗效获优方面,手术治疗稍占优势;在总体疗效优良方面,保守与手术治疗两者效果相当。     

一种常用免疫分析系统对25(OH)D3和25(OH)D2回收率的评价研究

目的 以液相色谱串联质谱(LC-MS/MS)为参考方法,评价临床常用的索灵(DiaSorin)全自动免疫分析系统对25-羟基维生素D3[25(OH)D3]和25-羟基维生素D2[25(OH)D2]的回收率是否满足临床检测的要求.方法 参考实验室定值的DEQAS 5个水平质控品,用以评价索灵检测25(OH)D的准确度.索灵自带高低值质控品每日4次重复测试,连续5d检测用以评价索灵检测高低值25(OH)D的精密度.解放军总医院健康查体剩余血清样本810例,分别由索灵及LC-MS/MS检测25(OH)D.Passing-Bablok回归、组内相关系数(intraclass correlation coefficient,ICC)分析两种检验方法的相关性和一致性.所有样本根据25(OH)D3及25(OH)D2占总25(OH)D的百分含量由低到高分别分组,计算各组检测偏差,分析索灵检测偏差随25(OH)D3、25(OH)D2百分含量增加的变化趋势.结果 索灵免疫法检测25(OH)D的精密度较好(CV<10％),检测结果与LC-MS/MS相比相关性和一致性均较好,但仍然存在一定的检测偏差.810例样本平均检测偏差为-4.65ng/mL(-16.55％).索灵检测偏差与25(OH)D3或25(OH)D2百分含量不具有线性相关关系;25(OH)D3或25(OH)D2百分含量的增加不增加索灵的检测偏差.结论 索灵全自动免疫分析系统检测维生素D与LC-MS/MS一致性较好,该免疫法对25(OH)D3和25(OH)D2回收率满足临床检测的要求.     

Effects of long-term lamivudine therapy in renal-transplant patients.

BACKGROUND: Following renal transplantation (RT), chronic immunosuppression is associated in hepatitis B virus (HBV) (+) patients with a flare-up of the disease, which might be harmful in the long term. OBJECTIVES: We report on the effect of long-term lamivudine therapy given at an initial daily dose of 100mg in 18 HBV (+) RT patients. RESULTS: When lamivudine therapy was commenced, 14 patients (77%) had an increase in their aspartate (AST) and alanine (ALT) aminotransferase levels. During a mean follow-up, under treatment, of 36.5 +/- 3.5 months (up to 66 months), 10 patients (55%) had a sustained partial (HBV DNA < 4 x 10(5)copies/ml) (n = 4) or complete (HBV DNA < 400 copies/ml) (n = 6) virological response. Overall, 12 virological breakthroughs were observed. Of those who were HBe Ag(+) prior to lamivudine therapy (n = 4), one seroconverted to HBe Ab during therapy. At the last follow-up, AST and ALT levels were normal in 13 patients. When liver biopsy was repeated during treatment (n = 15), the virological responders showed a significant decrease in total Knodell score from 10 +/- 0.6 to 7 +/- 1 (P = 0.04), but no significant change in the stage of fibrosis. Conversely, in those patients with high HBV DNA titers, there were no significant changes in the total Knodell score or in the grade of fibrosis. CONCLUSION: In conclusion, lamivudine therapy is safe in HBV(+)ve renal-transplant patients. However, even if the full and partial virological response rates are still high (55%) in the long term, relapse or primary non-responses occur. The implementation of alternative efficient strategies is warranted.     

Modulation of anti-Candida activity of human alveolar macrophages by interferon-gamma or interleukin-1-alpha

The fungicidal and bactericidal activities of human alveolar macrophages (AM) and peripheral blood monocytes (PBM) from 18 healthy volunteers were evaluated. The results showed that AM were able to phagocytize and kill Candida albicans, Pseudomonas aeruginosa, and Staphylococcus aureus. However, killing of the bacteria was already complete in 2 h, whereas killing of Candida required 4 to 6 h despite an early phagocytosis of yeast cells. The fungicidal activity of freshly collected AM and PBM was also tested after effector cell exposure to interferon-gamma (IFN-gamma), interleukin-1-alpha (IL-1 alpha), endotoxin lipopolysaccharide (LPS), or interleukin 2 (IL-2). It was found that treatment with IFN-gamma, IL-1 alpha, or LPS significantly augmented macrophage and PBM candidacidal activity, whereas the addition of IL-2 was ineffective. We also evaluated killing of C. albicans by AM cultured in vitro for different times. While phagocytosis was apparently unaffected, the candidacidal activity progressively decreased over the in vitro culture period, an effect that was largely reversed by cell exposure to IFN-gamma, IL-1 alpha, or LPS. In an experimental model in which mice infected with an agerminative C. albicans strain (PCA-2) resisted lethal microbial challenge, freshly harvested AM showed increased cytotoxic activity to Aspergillus fumigatus in vitro as well as enhanced IL-1 production. In conclusion, present data confirm the crucial role of AM in the surveillance of bacterial and fungal infections and indicate that treatment of these cells with IFN-gamma or IL-1 alpha is able to enhance their antimicrobial capability.     

Abnormal cytoskeletal assembly in platelets from uremic patients.

The mechanisms involved in the hemostatic abnormality of uremic patients remain obscure. We have explored the response of normal and uremic platelets to surface activation at the ultrastructural level and analyzed changes in the composition of proteins associated with normal and uremic platelet cytoskeletons after stimulation with thrombin (0.01 and 0.1 U/ml). Cytoskeletons were obtained by extraction with Triton X-100, processed by sodium dodecylsulfate-polyacrylamide gel electrophoresis, and the presence of cytoskeletal proteins analyzed by densitometry. Under static conditions, uremic platelets spread with difficulty on formvar-coated grids. The percentage of platelets that spread fully on this polymer surface was statistically reduced compared with that of control platelets (11 +/- 1.4 vs. 21 +/- 1.6; P < 0.05). An impairment of cytoskeletal organization was observed in resting uremic platelets but abnormalities were more evident after thrombin activation. The incorporation of actin into the cytoskeletons of thrombin-stimulated uremic platelets was significantly reduced with respect to controls (6 +/- 3% vs. 29 +/- 5%; P < 0.01 after 0.01 U/ml and 28 +/- 9% vs. 59 +/- 10%; P < 0.05 after 0.1 U/ml). Decreased associations of actin-binding protein (P < 0.01), alpha-actinin (P < 0.05), and tropomyosin (P < 0.05) with the cytoskeletons of uremic platelets were also noted. No difference was observed for the incorporation of myosin into the cytoskeletons of activated uremic platelets. These results suggest functional and biochemical alterations of the platelet cytoskeleton in uremia, which may contribute to the impairment of platelet function observed in uremic patients.     

1,25(OH)2D3 regulates c-myc mRNA levels in tonsillar T lymphocytes.

The effects of 1,25(OH)2D3 on proliferation, c-myc mRNA levels and 1,25(OH)2D3 receptor expression in activated tonsillar T lymphocytes were studied. Activation of resting T cells with phytohaemagglutinin (PHA) for 72 hr led to an increase in proliferation, c-myc mRNA levels and to induction of 1,25(OH)2D3 receptor expression. However, when activation was carried out in the presence of 1,25(OH)2D3, there was inhibition of PHA-stimulated proliferation and c-myc mRNA levels. Increased cell proliferation, c-myc mRNA expression and 1,25(OH)2D3 receptor number were also observed, albeit to a lesser extent, when T cells were stimulated by phorbol myristate acetate (PMA), anti-CD3 antibody or A23187. However, in these cases 1,25(OH)2D3 was unable to prevent increased proliferation or c-myc mRNA expression. PMA and anti-CD3 used in combination produced similar or greater changes in proliferation, c-myc mRNA levels, 1,25(OH)2D3 receptor expression and responsiveness to the hormone when compared to PHA alone. Thus the inhibition of c-myc expression in activated T lymphocytes by 1,25(OH)2D3 can be related to its anti-proliferative effects. Moreover this inhibition seems to be dependent on the level of 1,25(OH)2D3 receptor expression, which in turn appears to be related to the degree of cell activation.     

Selective deficiency of hepatic triglyceride lipase in uremic patients.

To investigate the pathogenesis of hypertriglyceridemia in patients with renal disease we measured plasma lipoprotein composition as well as hepatic triglyceride lipase and lipoprotein lipase in post-heparin plasma. Three groups with renal disease were studied: conservatively treated chronic uremia; patients undergoing maintenance hemodialysis; and renal-allograft recipients. A selective decrease of hepatic triglyceride lipase with normal lipoprotein lipase was found in conservatively treated uremia and in patients undergoing hemodialysis. Elevated levels of very-low-density lipoproteins and increased triglycerides in low-density lipoproteins occurred in these patients. In contrast, hepatic triglyceride lipase and lipoprotein lipase were both normal in patients after renal transplantation who had Type II hyperlipoproteinemia as a common lipoprotein pattern with increased low-density-lipoprotein cholesterol and decreased high-density-lipoprotein cholesterol concentrations. The accumulation of a triglyceride-rich low-density lipoprotein in the majority of patients with renal disease may be the consequence of low hepatic triglyceride lipase.