Effect of chronic elevation of plasma calcium concentration by PTH or vitamin D3 on blood pressure and hypotensive activity of nifedipine in rats

The influence of a chronically elevated total plasma calcium concentration on blood pressure and heart rate was investigated in conscious normotensive rats. The plasma calcium concentration was elevated by continuous subcutaneous infusion with parathormone (PTH) after parathyreoidectomy, and by oral treatment with vitamin D₃. In both groups an elevated blood pressure was observed at the 1st day of treatment only. Blood pressure was returned to pretreatment values from the second day of treatments onaards. No significant changes in heart rate, due to hypercalcaemia, were observed. In hypercalcaemic rats, the calcium entry inhibitor nifedipine proved more potent in reducing blood pressure than in normocalcaemic control animals. Hydralazine was equipotent in reducing blood pressure in both groups. It is suggested, that the vasoconstrictor effects of a chronically elevated total plasma calcium concentration in conscious rats does not obviously result in a chronically elevated blood pressure, but rather in an enhanced sensitivity of the blood pressure towards calcium entry blockade.     

1Alpha,25-dihydroxyvitamin D3 restores thymocyte apoptosis sensitivity in non-obese diabetic (NOD) mice through dendritic cells

AIMS/HYPOTHESIS: Resistance of NOD thymocytes to apoptosis-inducing signals is restored by 1alpha,25-dihydroxyvitamin D3 (1alpha,25OH2D3), a therapy preventing diabetes in NOD mice. We studied whether modulation of thymocyte apoptosis is due to direct effects on thymic T lymphocytes or indirect effects via thymic dendritic cells, since both cell types constitute known targets for 1alpha,25OH2D3. METHODS AND RESULTS: Female NOD mice were treated with 1alpha,25OH2D3 (5microg/kg/2d) from 21 to 70 days. Vehicle-treated NOD and NOR mice served as controls. Analysis of thymic T lymphocytes from 1alpha,25OH2D3)-treated mice revealed a decrease in number of apoptosis-resistant CD4+CD8+ and CD4+CD8-HSA(high) T lymphocyte subsets, higher pro-apoptotic IL-2 and FasL, and lower anti-apoptotic Bclx-L mRNA expression levels. Thymic dendritic cells from 1alpha,25OH2D3-treated NOD mice had increased CD8alpha+FasL+ and CD80+/86+ expression compared to control NOD mice. In a syngeneic co-culture system of thymocytes and thymic dendritic cells, apoptosis levels were 20% higher only in co-cultures where both T cell- and dendritic cell-compartments originated from 1alpha,25OH2D3-treated mice. Activation-induced cell death-sensitivity in peripheral T lymphocytes was comparable to levels present in NOR mice, confirming better thymic selection in 1alpha,25OH2D3-treated mice. CONCLUSION/INTERPRETATION: We conclude that 1alpha,25OH2D3 needs both thymic T cell- and dendritic cell-compartments to exert its apoptosis-restorative effects in NOD thymocytes.     

Circadian variation of blood clotting time and circulating vitamin K in the athletic horse

In equine sport medicine, blood clotting and fibrinolysis variations are well investigated, given the practical implications of several pathophysiological conditions affecting the athlete horse such as exercise-induced pulmonary haemorrhage (EIPH) and other bleeding disorders whose etiology and pathogenesis mechanisms are not yet clearly understood. The purpose of the present investigation was to gain evidence of a daily rhythm of several blood clotting indices such as prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), plasma fibrinogen concentration and serum vitamin K concentration in the athletic horses. Blood samples from five thoroughbred mares were collected at 4-h intervals for 48 h (starting at 08:00 h on day 1 and finishing at 4:00 on day 2 via an intravenous catheter inserted into the jugular vein. Prothrombin time, activated partial thromboplastin time, thrombin time and plasma fibrinogen concentration were assessed by means of a Seac Clot 2 coagulometer (SEAC, Italy), while serum vitamin K concentration was measured by HPLC. Data analysis was conducted by one-way repeated analysis of variance (ANOVA) and by the single cosinor method. ANOVA showed a significant influence of time on all parameters investigated, in all horses, on either day. Cosinor analysis defined the periodic parameters and their acrophases (expressed in hours) during the 2 days of monitoring. PT showed a nocturnal acrophase, whereas serum vitamin K concentration acrophase occurred during the evening. The results of this study reflect the physiological peculiarities of the horse that is subjected to a number of exogenous (environmental, nutritional, physical) and endogenous stimuli capable of entraining the circadian rhythm specifically and thus producing time-dependent variations not always comparable with those observed in humans or laboratory animals.     

慢性乙型肝炎患者血清维生素E水平与肝组织病理的关系研究

目的 探讨慢性乙型肝炎(CHB)患者血清维生素E水平与肝组织病理的关系.方法 选择66例慢性乙型肝炎患者进行肝穿刺病理学检查,健康对照组10例.化学比色法检测血清维生素E表达水平,同时检测HBV DNA、HBeAg及肝功能.结果 与正常对照组相比,慢性乙型肝炎患者血清维生素E水平明显降低(P<0.01);HBeAg阳性组与HBeAg阴性组比较,血清维生素E水平无明显差别(P0.05).CHB患者血清维牛素E水平与肝脏组织炎症呈负相关关系(r=-0.451,P<0.05),而与肝脏组织纤维化程度无明显相关(r=0.02,P0.05).结论 维生素E作为体内重要的抗氧化剂,参与了慢性乙型肝炎的炎症过程.在肝脏炎症过程中,适当补充维生素E,可能有助于缓解病情.     

兔饮食所致高同型半胱氨酸血症血管内皮功能的实验研究

目的：观察高同型半胱氨酸血症对血管内皮功能的影响。 方法： 建立兔高同型半胱氨酸血症模型。将18只新西兰兔随机分为：正常对照组（control组）6只、高蛋氨酸饮食组（M组）12只；于实验第4周始，将M组再随机分为两组，M+0组6只，继续饲高蛋氨酸饮食；M+F组6只，在高蛋氨酸饮食基础上，再加以叶酸、VitB12，继续观察3周；6周时统一处死动物，取腹主动脉，制备主动脉血管环，比较M+0组与M+F组及C组主动脉血管对Ach的最大舒张反应。同时，对3组高同型半胱氨酸血症形成过程中0周、3周、6周时血清中Hcy、ET-1、Ang-II、NO2ˉ/NO3ˉ、NOS各指标及处死动物时局部血管组织中ET-1、Ang-II、NO2ˉ/NO3ˉ、NOS指标进行检测并进行比较。 结果： （1）M+0组主动脉血管对Ach的最大舒张反应性(Emax=26.73±4.51)低于M+F组（Emax=47.84±5.62, P<0.05）及control组（Emax=56.42±7.82， P＜0.05）；(2) 3周时，M+0组及M+F组血清中Hcy、ET-1、Ang-II各指标均明显高于对照组及0周时（P＜0.05）；NO2ˉ/NO3ˉ、NOS明显低于对照组及0周时（P＜0.05）；(3)6 周时，M+0组上述指标继续升高；M+F组血清中Hcy低于 M+0组（P＜0.05）;NO2-/NO3-、NOS高于M+0组（P＜0.05）;ET-1、Ang-II各指标与M+F组无明显差异（P>0.05）。 结论： 高同型半胱氨酸血症对血管内皮最大舒张功能具有明显的抑制作用；其机制可能是通过影响局部血管组织内皮细胞 ET-1、Ang-II、NO的分泌而发挥作用的；早期以叶酸、VitB12干预治疗对血管内皮功能具有一定的拮抗作用。     

Einsparung von Diclofenac durch B-Vitamine: Ergebnisse einer randomisierten Doppelblindprüfung mit reduzierten Tagesdosierungen von Diclofenac (75 mg Diclofenac versus 75 mg Diclofenac plus B-Vitamine) bei akuten Lendenwirbelsäulensyndromen

Summary Pain syndromes of the lumbar spine are one of the main problems in orthopedic practice. The therapeutic effect of NSAIDs is not subject to doubt in this connection.But considering that the application of NSAIDs is frequently associated with side effects, a reduction of dosage would be to the patient's benefit. Clinical studies have shown that concomitant treatment with vitamins B₁, B₆, B₁₂ and diclofenac leads to a more efficient pain relief than treatment using diclofenac alone and thus provides the possibility of saving NSAIDs.This clinical trial was carried out in order to determine whether these results can also be achieved when a reduced dosage of diclofenac (75 mg daily) is used.123 patients with acute pain syndromes of the lumbar spine were treated with either B-vitamins and diclofenac or diclofenac alone for a maximum of 7 days. There was the option to terminate therapy in the trial after 3–4 days in the case of total pain relief.45 patients could stop the treatment due to remission of symptoms. 30 patients belonged to the combination therapy group, the other 15 took diclofenac alone; this difference is statistically significant (p< 0.05).All parameters concerning pain relief and movement of the vertebral column showed statistically significant differences in favour of the B-vitamin-diclofenac-combination, too.The results document the positive influence of B-vitamins on painful vertebral syndromes and indicate that B-vitamins contribute to saving of NSAIDs by shortening the treatment time and reducing daily NSAID-dosage.

     

The schilling test cannot be replaced by an absorption test with unlabeled vitamin B12

Summary It was the purpose of this study to evaluate the diagnostic usefulness of an oral absorption test using nonlabeled Vit B12 suggested by a commercial distributor as an alternative for the more expensive Schilling test (ST). Plasma levels of Vit B12 were measured with a commercial kit before and 4 h after oral administration of 1 mg Vit B12 in 32 normals, in 16 patients with normal ST, and in 14 patients with abnormal ST for determination of sensitivity and specificity with the ST as golden standard. In normals, a mean of 767±404 pg/ml before and 1096±776 pg/ml after oral Vit B12 with a mean increase of 331±453 pg/ml was measured. Because of the obvious large variation, no meaningful range for normal absorption could be established. In the two patient subsets, there was no Gaussian distribution of the results, with a meridian of Vit B12 increase after absorption of 142 pg/ml, range 27–2668 pg/ml, in the group with normal ST and a meridian of 244 pg/ml ranging from 40 to 2453 pg/ml in the group with abnormal ST. Statistical nonparametric analysis did not reveal any difference between the two groups. Assuming a minimum required increase of 100 pg/ml, as suggested by the kit distributor, a sensitivity of only 27% and a specificity of 75% was obtained. The lack of any diagnostic value of this approach might be caused by the known nonintrinsic-factor mediated absorption of approximately 1% of any B12 given orally even in complete intrinsic factor deficiency and by the relatively large amount of oral Vit B12 needed for a cold absorption test. The latter can, thus, not replace the Schilling test.Abbreviations Vit B12 Vitamin B12     

Changes in Cell Characteristics Due to Culture Conditions in Cell Lines From Human Small Cell Lung Cancer

Eight cultured cell lines were established from human smallcell lung cancers. Every cell line showed the morphologicaland biochemical characteristics of small cell cancer. Changesin cell characteristics were observed in many of these celllines when culture conditions were changed: "oat cell type"changed to "intermediate cell type" and vice versa when serum-freemedium was changed to serum-supplemented medium; a deficiencyof vitamin A in the medium caused a change to squamous cellsand vice versa; and a tumor promoter (teleocidin B) enhancedthe adherence of these cells to the surface of plastic culturedishes. These findings provide evidence that many small celllung cancer cell lines can change their morphology with changesin the environment of the cells.     

The protective effect of vitamin E on cerebral ischemia

Using the "canine model of the completely ischemic brain regulated with a perfusion method," the effects on cerebral ischemia of vitamin E, which is known to act as an antioxidant, were investigated. After pretreatment with vitamin E by oral or intravenous administration, cerebral blood flow was reduced to 1/10th the normal state and, 1 hour later, allowed to return to normal. Subsequent changes in electrical activity were observed, and the effects of vitamin E were evaluated. In the control group, no recovery of electrical activity was seen. In the groups given vitamin E, the recovery time was significantly shortened in the dogs given 30 mg/kg of vitamin E intravenously. Furthermore, in the groups treated with vitamin E, distinct recovery of electroencephalographic potentials at 3 hours after recirculation was apparent. These effects were more favorable in the case of intravenous administration than in the case of oral administration. These experimental results indicate that the administration of vitamin E is effective in protecting the brain from cerebral ischemia.     

Extended treatment of primary osteoporosis by sodium fluoride combined with 25 hydroxycholecalciferol

Summary Nineteen patients suffering from primary osteoporosis, all having at least one vertebral collapse, initially received 50 mg of sodium fluoride alone per day for 6–18 months. Subsequently fluoride was associated with 25–50g of 25 OH cholecalciferol (calcifediol) per day for 6–18 months in 12 of these patients and 9 were treated for 31–58 months. As control group, 9 patients were given placebo for 6–18 months. The effect of the treatment was assessed by three methods: 1) the metacarpal index (MI) determined by radiogrammetry, 2) the calcium content of the hand bone (Ca) measured by local neutron activation, 3) the iliac bone histomorphometry. MI and (Ca) did not change significantly at any time in any group. In each group there was a significant increase in trabecular bone volume, osteoid volume, osteoid surfaces and a significant decrease in mineralization fronts. On the other hand, the changes in osteoblastic surfaces, osteoclastic surfaces, number of osteoclasts/mm2 were not significant in any group. No change was observed in the placebo group. These data suggest that the increase in the trabecular volume of fluorided bone is mainly due to the increase in osteoid which itself is due to a bone mineralization defect despite the association of calcifediol. This is probably one of the reasons why (Ca) does not change significantly.