Sevelamer hydrochloride with or without alphacalcidol or higher dialysate calcium vs calcium carbonate in dialysis patients: an open-label, randomized study.

BACKGROUND: Sevelamer hydrochloride was recently proposed as a phosphate binder to prevent hypercalcaemia in place of calcium alkaline salts in dialysis patients. So far, it has been evaluated only in patients receiving calcitriol, without comparison with CaCO(3) alone, although the latter was found to be as effective as the combination of calcitriol and Al(OH)(3) in suppressing parathyroid hormone (PTH) without inducing hypercalcaemia and to have a better lowering effect on serum phosphate. Moreover, this bile salt binder may decrease serum 25-OH vitamin D. Therefore, we compared for 5 months two strategies for controlling moderate hyperparathyroidism: CaCO(3) alone vs sevelamer in conjunction with measures to increase calcium balance. METHODS: Forty-two patients were randomized: 21 continued their treatment with 4.8 g/day CaCO(3) and 21 were switched to sevelamer (initial dose: 2.4 g/day, increased to 4.4 g/day). Each month, when serum-corrected calcium decreased below 2.30 mmol/l, dialysate calcium was increased or alphacalcidol was given at each dialysis session, according to serum PO(4) levels. The following parameters were monitored: serum Ca, PO(4), bicarbonate and protein, weekly; and serum PTH, 25-OH vitamin D and total, LDL and HDL cholesterol monthly. RESULTS: Except for higher serum phosphate at month 1, lower serum bicarbonate at month 2 and lower LDL cholesterol at month 5 in the sevelamer group, no difference was found between the two groups. Compared with baseline levels, PTH increased and 25-OH vitamin D decreased significantly in both groups, these two parameters being inversely correlated. CONCLUSIONS: Given comparable control of plasma calcium, phosphate and 25-OH vitamin D, PTH control is comparable in both strategies. Sevelamer does not induce greater vitamin D depletion than CaCO(3). The transient decrease of serum bicarbonate after discontinuation of CaCO(3) in the sevelamer group suggests a less optimal prevention of acidosis. The sevelamer-induced decrease in LDL cholesterol gives this drug a potential advantage in cardiovascular prevention.     

局灶性脑缺血对细胞周期蛋白D1/CDK4基因表达的影响

目的观察脑缺血后细胞周期蛋白（cyclin）D1和它的酶CDK4基因表达，以及这种表达的改变是否影响神经细胞凋亡。方法成年雄性SD大鼠32只随机分为假手术组（n=4）和实验组（n=28），实验组再进一步分为7个亚组（再灌注2h，6h，12h，1d，3d，7d和14d，每组n=4）。应用线栓法建立SD大鼠大脑中动脉阻塞／再灌注模型．TUNEL法检测神经细胞凋亡。原位杂交检测cyclinD1和CDK4mRNA的表达。结果CyclinD1mRNA和CDK4mRNA的表达与凋亡细胞的区域基本相同。再灌注2h脑组织即开始出现神经细胞凋亡，并于1d分别在皮层区和纹状体区达高峰（分别为72．80±4．66和87．75±0．85）。神经细胞cyclinD1mRNA和CDK4mRNA的表达分别于再灌注2h和6h开始逐渐增强，并于12h和1d达高峰（皮质区分别为94．50±2．75和85．75±3．73，纹状体区分别为88．25±5．06和89．80±2．93）。结论CyclinD1和CDK4选择性地在形态学完整或已经有改变的缺血侧神经元和少突胶质细胞内表达。CyclinD1／CD1（4mRNA表达可能是诱导细胞凋亡的重要因素之一。     

Amplified fragment length polymorphism analysis of the VNTR locus D1S80 in central Spain

Summary The polymorphism of the D1S80 locus has been analyzed in a population sample of 203 unrelated individuals living in Madrid (central Spain) by PCR and subsequent semi-dry discontinuous polyacrylamide gel electrophoresis (Tris-chloride/Tris-glycine buffer system) followed by silver staining, The electrophoretic system described in this study offers high resolution in the separation of the different D1S80 alleles allowing the detection of microvariability around the allele T22 in the spanish population. Twenty different alleles containing 17–40 repeats of the basic 16bp unit were distinguished. The alleles T18 and T24 were found to be relatively common in Spain, as in other populations:, with frequencies of 0.224 and 0.372, respectively. No evidence of significant deviations from Hardy-Weinberg equilibrium was found in these preliminary population data.     

Effects of vitamin D3 and cyclosporin A on HgCl2-induced autoimmunity in Brown Norway rats

BACKGROUND.: Mercuric chloride (HgCl₂ induces a lymphoproliferative disorderand autoimmune glomerulonephritis in Brown Norway (BN) rats.This syndrome is the consequence of T cell-dependent polyclonalB cell activation and autoantibody production. We have previouslyshown that HgCl₂-induced autoimmune perturbations can be preventedin BN rats by the administration of cyclosporin A (CsA). Themost potent vitamin D₃ metabolite 1,25(OH)₂ D₃ (Vit D₃) sharescertain immunomodulatory properties with CsA. We therefore choseto compare the effects of Vit D₃ to those of CsA in BN ratstreated with HgCl₂ in order to establish whether Vit D₃ eitheralone or in combination with CsA can attenuate an autoimmunesyndrome in vivo. METHODS.: BN rats were treated with HgCl₂ according to a standard protocol.Subgroups of rats were also given CsA alone, Vit D₃ or syntheticanalogues of Vit D₃ alone, or combinations of both agents. Differentdoses and routes of administration were compared. The followingmarkers of disease activity were evaluated: mortality, peakproteinuria, serum IgE concentrations, and renal immunoglobulindeposition. RESULTS.: Disease activity was markedly attenuated in all rats treatedwith CsA alone. Vit D₃ and certain of its synthetic analoguesadministered alone also tempered the autoimmune process, butto a lesser extent than did CsA. The effect of CsA alone wasso potent, that no additive or synergistic effects could bedemonstrated when CsA was administered in combination with VitD₃. CONCLUSIONS.: Despite similar described immunomodulatory effects in vitro,CsA is clearly more effective than Vit D₃ in preventing HgCl₂autoimmune disease in BN rats. This suggests that there is adifference in the cellular targets of these two agents in vivo,and/or a difference in the potency with which HgCl2-triggeredimmune activation is suppressed.     

Techniques in facial identification: Computer-aided facial reconstruction using a laser scanner and video superimposition

A facial image was reconstructed from the skull, part of a complete skeleton found in woodland, of a male person who had hanged himself from a tree. In addition, video superimposition was carried out with antemortem photographs of a person suspected of being the victim, and a good match was obtained. In a further case, a cheaper video-transparency superimposition was carried out, with identity later being confirmed on the basis of dental records. The techniques and the problems encountered are discussed. According to our experience, 3D computer reconstruction and video superimposition have a useful role in the process of identification, particularly in the early stages of an investigation and when other more definitive methods may not be available.     

Fast Three Dimensional Magnetic Resonance Imaging

To reduce the scan time in three-dimensional (3D) imaging, the authors consider alternative trajectories for traversing k-space. They differ from traditional 3D trajectories, such as 3DFT, in that they employ time-varying gradients allowing longer readouts and in turn a reduced scan time. Some of these trajectories reduce by an order of magnitude the number of excitations compared with 3DFT and provide flexibility for trading off signal-to-noise ratio for scan time. Other concerns are the minimum echo time and flow/motion properties. As examples, the authors show two applications: A 3D data set of the head (field of view of 30 x 30 x 7.5 cm and resolution of 1.5 x 1.5 x 1.5 mm) acquired in 56 s using a stack of spirals in 3D k-space; and a 3D movie of the heart (20 x 20 x 20 cm field of view, 2 x 2 x 2 mm resolution, and 16 time frames per cardiac cycle) acquired in 11 min using a cones trajectory.     

Prostaglandin D2 measurement in nasal secretions is not a reliable marker for mast cell activation in atopic patients

Background Prosia gland in D2 (PGD2) is a very important mast cell product during the early-phase nasal allergic reaction. However, the quantification of PGD2 in nasal secretions has not yet been well established. Objective Quantitative determination of PGD2 in nasal secretions of atopic patients (n=17) after nasal allergen challenge (NAC) and in non-allergic healthy volunteers (n=10). Methods The nasal microsuction sampling technique was used to obtain the nasal secretions with an exactly known and minimally diluted volume. A sensitive and specific enzyme immunoassay was chosen to measure the more stable 11-methoxime derivative of PGD2. which was obtained after extraction in acelone/ethanol and conversion using methoxamine-HCl. The concentrations of PGD2 in nasal secretions obtained from 10 non-allergic healthy volunteers were used as reference values. Results There was no significant difference in the concentrations of PGD2 between men (median: 569pg/mL) and women (median: 407pg/mL), nor between the baseline concentrations from atopic patients (median: 410pg/mL) and non-allergic controls (median: 477 pg/mL). In the atopic patient group, PGD2 did not significantly increase during the entire sampling period after NAC. The absence of PGD2 response contrasted with the nasal symptoms manifested by sneezing, increased nasal airway resistance, and the significant increases of the concentrations of histamine, tryptase, and leukotriene C4 (LTC4) 5min after NAC. Conclusion This observation suggests that the measurement of PGD2 alone in the nasal secretions does not give reliable information on mast cell activation during a nasal allergic reaction.     

Effects of chemical mediators of anaphylaxis on ciliary function

We assessed the effects of selected chemical mediators of anaphylaxis on CBF in vitro. Ciliated epithelial cells were obtained from the trachea of conscious sheep with a cytology brush and suspended in a perfusion chamber containing KH. Ciliary activity was viewed microscopically and recorded on videotape for subsequent slow-motion analysis of CBF. Prostaglandin E1 (10(-8) M to 10(-6) M), prostaglandin E2 (10(-10) M to 10(-6) M), and leukotriene-C4 (10(-8) M) increased CBF between 7% and 33%. Histamine caused ciliostimulation only at the relatively high concentrations above 10(-5) M (7% increase in CBF), whereas prostaglandin F2 alpha (10(-10) M and 10(-6) M) was without effect. In no preparation was ciliary discoordination observed. These findings indicate that several chemical mediators of anaphylaxis stimulate CBF and that the previously described impairment of mucociliary transport in stable allergic asthma or antigen-induced bronchoconstriction is probably not caused by a primary alteration of ciliary function.     

Cytogenetic analysis in human breast tumors

Cytogenetic analysis using C-, G-, and Ag-nucleolus organizer region (NOR) staining techniques, performed on established cell lines as well as directly processed breast tumor effusions, revealed that: 1) chromosome No. 1 is involved in translocation; 2) based on 1q translocation chromosome, breast tumors could be classified into two groups; and 3) double minutes and homogeneously staining regions may be present in breast tumor cells in vivo as well as in vitro, and that homogeneously staining regions may exhibit some heterogeneity in staining.