They are usually associated with hypercalciuria, and on occasions with urinary pH values above 6.0. The study also showed the effectiveness of specific crystallization inhibitors in slowing calculi fragment growth.Ĭalcium oxalate dihydrate renal calculi constitute the most prevalent and recurrent type of renal lithiasis. This observation suggests COD calculi residual fragments in the kidneys together with hypercalciuria and high urinary pH values may be a risk factor for stone growth. The growth rate of COD calculi fragments under pH = 6.5 hypercalciuria conditions was approximately ten times that observed under the other three conditions. In contrast, 5.29 mM citrate did not inhibit fragment mass increase under pH = 6.5 hypercalciuria conditions. A study of three crystallization inhibitors demonstrated that phytate completely inhibited fragment growth (2.27 μM at pH = 5.5 and 4.55 μM at pH = 6.5, both under hypercalciuria conditions), while 69.0 μM pyrophosphate caused an 87% reduction in mass under pH = 6.5 hypercalciuria conditions. Under pH = 6.5 hypercalciuria conditions, large amounts of COD, COM, hydroxyapatite and brushite crystals formed (growth rate = 3.87 ± 0. Under pH = 5.5 hypercalciuria and under pH = 6.5 normocalciuria conditions, COM crystals and a small number of new COD crystals formed (growth rate = 0.32 ± 0.03 μg/mg Under pH = 5.5 normocalciuria conditions, only COM crystals formed (growth rate = 0.22 ± 0.04 μg/mg ResultsĬalcium oxalate monohydrate (COM) crystals formed on COD renal calculi fragments under all conditions. Fragment growth was standardized by calculating the relative mass increase. Fragment growth was evaluated by measuring increases in weight. Post-ESWL COD calculi fragments were incubated in chambers containing synthetic urine varying in pH and calcium concentration: pH = 5.5 normocalciuria (3.75 mM), pH = 5.5 hypercalciuria (6.25 mM), pH = 6.5 normocalciuria (3.75 mM) or pH = 6.5 hypercalciuria (6.25 mM). This study examined the effect of various urinary conditions and crystallization inhibitors on the regrowth of spontaneously-passed post-ESWL COD calculi fragments. However, the retention of post-ESWL fragments within the kidney remains an important health problem. To make a comment you must login or register.The use of extracorporeal shock wave lithotripsy (ESWL) to treat calcium oxalate dihydrate (COD) renal calculi gives excellent fragmentation results. How the AICD may regulate signal transduction is uncertain but the authors found a 3-hour lag between inhibition of γ-secretase and inhibition of Ca2+-signaling, which would be sufficient time to modulate transcription.-Tom Fagan Comments Furthermore, in AβPP-negative cells, Ca2+-signaling was markedly disrupted but could be rescued by transfection with whole AβPP or with just the AICD transfection with an AβPP construct devoid of the AICD failed to restore signaling.Ī role for AICD in regulation of endoplasmic reticulum (ER) calcium was suggested by the fact that PS1/PS2- or AβPP-negative fibroblasts, or those treated with γ-secretase inhibitors had lower ER calcium, an observation that agrees with previous data ( Yoo et al 2000). Calcium signaling was also blocked by γ-secretase inhibitors, which blocked signal transduction as potently as they inhibited the protease. The authors showed that mouse embryonic fibroblasts devoid of presenilin 1, the likely active component of γ-secretase, poorly mobilized intracellular calcium in response to external stimuli. The researchers report in tomorrow's Proceedings of the National Academy of Sciences that AICD plays an important role in intracellular calcium signaling. Steps toward addressing the latter shortcoming have been taken by an international collaboration lead by Frank LaFerla, University of California at Irvine, and including Michael Wolfe at Harvard Medical School and Bart DeStrooper at Flanders Interuniversity, Leuven, Belgium. However, there is currently no evidence that AICD enters the nucleus, nor have any potential downstream targets of the intracellular domain been identified. This idea is supported by yeast two-hybrid experiments, which show that the AICD can promote transcription of a reporter gene when bound to Fe65, a protein that interacts strongly with histone acetyltransferases (see related ARF news item). The similarities between the γ-secretase-mediated processing of AβPP and the Notch receptor suggest that the AβPP intracellular domain (AICD), like its Notch counterpart, could play a role in signal transduction.
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