Synergistic renal protection by combining alkaline-diuresis with lipid peroxidation inhibitors in rhabdomyolysis: possible interaction between oxidant and non-oxidant mechanisms

BACKGROUND AND PURPOSE.: Heme-proteins, besides causing renal tubular obstruction, maycontribute to rhabdomyolysis-induced renal injury through aheme-iron-mediated lipid peroxidation process. In the presentstudy, we compared the combined therapy of a lipid peroxidationinhibitor, 21-aminosteroid (21-AS) and fluid-alkaline-mannitol(FAM) diuresis with either of them alone to determine the efficacyof the combination therapy and to delineate the roles of lipidperoxidation and cast formation. METHODS AND RESULTS.: Employing Raman spectroscopy, we confirmed in vitro the abilityof 21-AS to inhibit iron-induced fatty acid peroxidation. 21-ASwas then administered to rats developing renal failure fromglycerol-induced rhabdomyolysis. Although 21-AS inhibited rhabdomyolysis-inducedplasma and renal lipid peroxidation, renal protection was incomplete.Administration of FAM to inhibit cast formation afforded a betterrenal protection. However, when these therapies were combinedto inhibit both lipid peroxidation and cast formation, therewas a synergistic renal functional protection. This was accompaniedby a maximum inhibition of renal and plasma lipid peroxidation,as well as, renal tubular necrosis and cast formation. Comparedto combination therapy, FAM therapy alone, despite identicalvolume, was accompanied by a higher tubular necrosis and castformation. CONCLUSIONS.: That combining a lipid peroxidation inhibitor with fluid-alkalinediuresis in rhabdomyolysis further lowers renal lipid peroxidation,tubular necrosis and cast formation and synergistically limitsrenal dysfunction (i) supports a role for lipid peroxidationin the pathophysiology of rhabdomyolysis ARF, (ii) underscoresthe role of intratubular heme retention, a cause for tubularobstruction as well a source for prodigious amount of iron,likely involved in the lipid peroxidation, and (iii) raisesthe possibility of interactions between non-oxidant and oxidantmechanisms.     

The role of Na+/K+ ATPase activity during low flow ischemia in preventing myocardial injury: A 31P, 23Na and 87Rb NMR spectroscopic study

An increase in intracellular Na⁺ during ischaemia has been associated with myocardial injury. In this study, we determined whether inhibition of Na⁺/K⁺ ATPase activity contributes to this increase and whether Na⁺/K⁺ ATPase activity can be maintained by provision of glucose to perfused rat hearts during low flow, 0.5 ml/min, ischemia. We used ³¹P NMR spectroscopy to determine changes in myocardial energetics and intracellular and extracellular volumes. ²³Na NMR spectroscopy, with DyTTHA^3- present as a shift reagent, was used to measure changes in intracellular Na⁺ and ⁸⁷Rb NMR spectroscopy was used to estimate Na⁺/K⁺ ATPase activity from Rb⁺ influx rates, Rb⁺ being an NMR-sensitive congener of K⁺. In hearts provided with 11 mM glucose throughout ischemia, glycolysis continued and ATP was twofold higher than in hearts without glucose. In the glucose-hearts, Rb⁺ influx rate was threefold higher, intracellular Na⁺ was fivefold lower at the end of ischemia and functional recovery during reperfusion was twofold higher. We propose that continuation of glycolysis throughout low flow ischemia allowed maintenance of sufficient Na⁺/K⁺ ATPase activity to prevent the increase in intracellular Na⁺ that would otherwise have led to myocardial injury.     

频闪喉镜对声带病理情况观察的研究

对1997年以来423例病态喉的频闪喉镜表现进行分析,结果显示声带有病理改变者其粘膜波、振幅、闭合相、运动周期性、对称性均有不同程度的变化,这种变化能直接反映声带病变的深度及范围,对喉部疾病的诊断、鉴别诊断、治疗指导及预后评价具有重要意义.     

Fragmentation process of current laser lithotriptors

Background and Objective: Flashlamp pumped dye (FPDL), Q-switched Nd:YAG, and alexandrite lasers are the most clinically used laser lithotriptors. Although calculi are fragmented by laser induced mechanical stresses for all lithotriptors, different fragment sizes and fragmentation efficiencies have been reported. In this work the effect of the pulse duration and pulse shape on the fragmentation processes is studied. Material and Methods: Fragmentation processes are characterized on model stones and on sensing target fibers. Stone fragmentation and cavitation bubble generation are observed by video flash photography. Shock wave occurrence and strength are monitored with an hydrophone. Results: For the FPDL, stone fragmentation is induced by the collapse of the large cavitation bubble formed. For the Q-switched Nd:YAG, fragmentation is already observed during the laser pulse, at the plasma onset, although further fragmentation can occur at the bubble collapse. For pulse durations corresponding to the alexandrite, an intermediate fragmentation regime is observed. Conclusion: For the first time the physical basis of the observed differences in the fragmentation efficiencies of current laser lithotriptors is described. For nanosecond durations the fragmentation processes are governed by plasma induced shock waves. On the contrary, for microsecond durations fragmentation is governed by cavitation. The high fragmentation efficiency of microsecond lasers is due to a high laser energy transfer into cavitation. © 1995 Wiley-Liss, Inc.     

The relation between conduction velocity and axonal length

Motor evoked potentials (MEPs) obtained by electrical root stimulation and F waves were used to examine the proximal nerve conduction velocity (CV) to tibialis anterior (TA), extensor digitorum brevis (EDB), flexor carpi radialis (FCR), and abductor pollicis brevis (APB) muscles in 40 humans. By subtracting motor latencies obtained by stimulating the peripheral nerve at the same point from the F-wave and MEP latencies, we could measure the CV over identical proximal segments. It was found that proximal CV to TA and FCR was significantly higher than to EDB and APB, respectively. Combining the data of the proximal CV to all four muscles in relation with axonal length resulted in a highly significant inverse relationship (r² = 0.77). Thus the axonal length explained to a large extent the higher CV of the arm nerves and also the inverse relation between body height and CV. The distal CV was always lower than proximal CV; however, there was no support for an additional effect of this gradient in explaining the relationship between CV and height since it was constant for all body heights. © John Wiley & Sons, Inc.     

The distribution of lead in human hemopoietic tissue and spongy bone after lead poisoning and Ca-EDTA chelation therapy

Two iliac crest needle biopsies were taken from a 43-year-old lead-poisoned woman during and after completion of a Ca-EDTA treatment. By atomic absorption spectroscopy the first and second biopsy were found to contain 56, respectively 41.6 g lead/g wet tissue. In both biopsies 36% of the lead was extractable in 0.1 N HCl. Electron microbeam X-ray analysis proved to have too low sensitivity for quantitation of the lead in these biopsies. Laser microbeam mass analysis (LAMMA), performed only on the second biopsy, revealed a high and fairly constant residual lead concentration in all bone marrow cell nuclei (approximately 55 g/g) and a low lead concentration in the cytoplasm of the same cells (4–12 (g/g). The extracellular bone matrix lead was greatly concentrated in the superficial 3–6 m osteoid zone of the bony trabeculae and totally absent from deeper parts of the mineralized matrix. The LAMMA results are in good agreement with those of subcellular fractionation experiments and atomic absorption spectroscopy, provided that the relative volume fraction of nucleus and cytoplasm is accounted for. The high residual osteoid lead after completed chelation therapy indicates that lead has a stronger affinity for the organic than the mineral components of bone matrix.     

不同剂量体外冲击波治疗肱骨外上髁炎的疗效对比

目的 比较不同能流密度的体外冲击波(extracorporeal shock wave, ESW)治疗肱骨外上髁炎(lateral epicondylitis, LE)的短期临床疗效,探索ESW的最佳治疗剂量。方法 将120例LE患者分为A、B、C和D 4组,均使用ESW治疗4周,各组的能流密度分别为0.06、0.08、0.10、0.12 mJ/mm²。分别在治疗前及治疗后4、24及48周,比较4组患者疼痛视觉模拟量表(visual analogue scale, VAS)评分、肱骨外上髁炎功能评估(patient-rated tennis elbow evaluation, PRTEE)评分及末次随访患者满意度和复发率。结果 按时间点比较,各组VAS评分治疗前最高,治疗后48周降至最低(P<0.05),4组患者满意度及复发率比较差异无统计学意义(P>0.05),但C组患者满意度(96.67%)明显高于A组(80%),差异具有统计学意义(P=0.04)。按组间比较观察,治疗前各组患肘VAS评分差异无统计学意义(P>0.05);治疗后4、24和48...     

Human slow-wave sleep and the cerebral cortex

SUMMARY  Recent hypotheses about the roles of human slow-wave sleep (hSWS—delta EEG activity) are appraised. The possible linkage between hSWS and the functions of the prefrontal cortex (PFC) are explored with respect to normal subjects and to disorders involving PFC deficits.     

Identification of GRASP-1 as a novel 97 kDa autoantigen localized to endosomes

We have identified an autoantigen that is recognized by antibodies from an 18-year-old female with a history of recurrent infections who later in her clinical course developed Raynaud's phenomenon and telangiectasias. By indirect immunofluorescence (IIF), the index serum produced a unique cytoplasmic discrete speckled (CDS) staining pattern that partially colocalized with early endosome antigen 1 (EEA1) but not Golgi complex or other cytoplasmic organelles in HEp-2 cells. When HEp-2 cells were treated with 0.1 N HCl, the cytoplasmic speckled staining of the index serum was markedly decreased, suggesting that the reactive antigen was soluble. Western blot analysis showed a reactive approximately 97 kDa protein in a saline soluble protein preparation from HeLa cells. Mass spectrometric analysis of the excised 97 kDa band that was immunoprecipitated from HeLa cell extracts identified GRASP-1 as a possible target. The index serum and anti-GRASP-1 antibodies colocalized to structures in the cytoplasm of HEp-2 cells. Synthetic peptides representing the full-length GRASP-1 protein were used to identify reactive epitopes. Like many other cytoplasmic autoantigens, GRASP-1 has numerous coiled-coil domains throughout the protein with the exception of short segments at the amino and carboxyl terminus.     

Quantitative Characterization of Epicardial Wave Fronts During Regional Ischemia and Elevated Extracellular Potassium Ion Concentration

This study applied zero-delay wave number spectral estimation as a means of quantifying the changes in activation and recovery sequences of propagating plane waves on the epicardial surface of in situ porcine hearts during regional hyperkalemia and ischemia. Unipolar electrograms (104) were recorded from the left ventricular surface of nine hearts using a plaque electrode array with 1 mm spatial sampling intervals. The objectives were (1) to define a set of parameters capable of quantifying the spatial and temporal changes in measured extracellular potentials associated with localized ischemia prior to the onset of conduction block; (2) to elevate regional levels of extracellular potassium ion concentration and quantify potential changes due to this known physiologic manipulation; and (3) to use quantitative parameters to make statistical comparisons in order to distinguish wave fronts during normal, ischemic and hyperkalemic conditions. Results showed that the parameters of wave number and average temporal frequency and the associated power, as determined from the wave number spectrum, provided statistically significant (p < 0.05) quantification of changes in wave front features during normal and ischemic or hyperkalemic conditions. The results were consistent with results obtained from conventional time–space domain methods like isochronal mapping and electrograms, with the advantage of a quantitative result enabling simple comparisons and trend analysis for large numbers of heart beats. © 1998 Biomedical Engineering Society. PAC98: 8759Wc, 8722Fy, 8780+s