1,721,035 research outputs found
Il calcium sensing receptor determinante genetico dell'ipercalciuria primaria
No full textAlterations in calcium sensing receptor (CaSR) function lead to calcium metabolism disorders. The non-conservative polymorphism Arg990Gly seems to induce a gain-of-function of the receptor that could predispose to primary hypercalciuria. The aims of this study were to confirm the increased frequency of 990Gly allele of CaSR in subjects with primary hypercalciuria, to evaluate if 990Gly allele produces a gain-of-function for CaSR in transfected HEK-293 cells and to investigate the response to calcimimetic treatments (NPS-R568). The clinical study confirmed that 990Gly allele frequency was higher in hypercalciuric subjects (8.5%) than in normocalciuric ones (1.7%, chi-square=11.5; df=1, p=0.001). The calcium urinary escretion was increased in subjects bearing 990Gly allele (7.59±0.63mmol/24h vs 5.82±0.19mmol/24h, 0=0.006). The functional study demonstrated that both CaCl2 and NPS-R568 EC50 were lower in HEK-990Gly cells in comparison with HEK-990Arg cells (respectively: 2.69±0.11mM [n=19] vs 4.49±0.28mM [n=12], p=0.0001; 0.67(0.08mM [n=15] vs 1.41(0.09mM [n=16], p=0.0001). We concluded that Arg990Gly polymorphism results in a gain-of-function for CaSR and individuals bearing 990Gly allele may be predisposed to primary hypercalciuria
Calcium-sensing receptor gene polymorphisms in patients with calcium nephrolithiasis
No full textPURPOSE OF REVIEW:
The calcium-sensing receptor gene (CaSR, chr. 3q13.3-21) is a candidate to explain nephrolithiasis. This review analyzes the potential role of CaSR in lithogenesis according to findings of functional and genetic studies.
RECENT FINDINGS:
CaSR is a cation receptor located in the tubular cell plasma membrane. Its activation decreases calcium reabsorption in the ascending limb and distal convoluted tubule, but increases phosphate reabsorption in proximal tubules and decreases water and proton reabsorption in collecting ducts. Its effects in proximal tubules and collecting ducts can limit the calcium phosphate precipitation risk induced by the increase in calcium excretion. The nonconservative CaSR gene Arg990Gly polymorphism was associated with nephrolithiasis and hypercalciuria in different populations. Arg990Gly is located on exon 7 and produces a gain of the CaSR function. rs7652589 and rs1501899 were also associated with nephrolithiasis in patients with normal citrate excretion. These polymorphisms are located in the CaSR gene regulatory region and may modify CaSR gene promoter activity.
SUMMARY:
The activating Arg990Gly polymorphism may predispose to nephrolithiasis by increasing calcium excretion. Polymorphisms at the regulatory region may predispose to nephrolithiasis by changing tubular expression of the CaSR. CaSR genotype may be a marker to identify patients prone to develop calcium nephrolithiasi
La calcolosi renale di calcio : prospettive diagnostiche e preventive
No full textKidney stone disease is one of the main causes of hospitalization in Italy. Its prevalence increased in the last century and is probably still increasing. The pathogenesis of the disease is not known, although two main theories have been elaborated. The first hypothesizes that hydroxyapatite deposition in the interstitium of the renal papillae (Randall's plaque) precedes urinary calcium oxalate precipitation on the ulcered surface of the papilla to form a stone. The second presumes the tubular lumen of Bellini's duct to be the site where calcium-oxalate salts precipitate to form the nucleus for stone formation within the urinary tract. These pathogenetic processes may be favored by different dietary and genetic factors. The genes involved are not known, although many studies have been performed. Polymorphisms of genes coding for the vitamin D receptor, calcium-sensing receptor, interleukin-1 receptor antagonist, and urokinase were found to be associated with kidney stones, but these results have not been replicated. Different nutrients are suspected to predispose patients to calcium kidney stone disease. A high intake of animal proteins, sodium, vitamin C and oxalate has been implicated in stone formation, whereas calcium, alkalis and phytate may have a protective effect. The prevention of calcium stone formation is based on the recognition of risk factors like those already mentioned here. Furthermore, a family history of kidney stones may be useful in identifying subjects predisposed to become calcium stone formers. However, the expectations of the scientific community are turned to the advances in genetics and to the findings of genetic studies, which may provide diagnostic tools and criteria to define the risk profile of the single individual
Molecular and clinical aspects of the target therapy with the calcimimetic cinacalcet in the treatment of parathyroid tumors
No full textParathyroid tumors are almost invariably associated with parathormone (PTH) hypersecretion resulting in primary (PHPT) or secondary (SHPT) hyperparathyroidism. PHPT is the third most common endocrine disorder with a prevalence of 1-2% in post-menopausal women; SHPT is a major complication of chronic kidney failure, the prevalence of which is increasing. The calciumsensing receptor (CASR) is the key molecule regulating PTH synthesis and release from the parathyroid cells in response to changes in extracellular calcium concentrations. A potent calcimimetic, cinacalcet, has been developed in the last ten years and made available for medical treatment of both PHPT and SHPT. Cinacalcet has been demonstrated to be effective in inhibiting PTH secretion, though the drug fails to normalize PTH release, both in PHPT and SHPT patients with different degrees of disease severity, including patients with parathyroid carcinomas and with MEN1-related parathyroid tumors. Here we reviewed the molecular aspects of CASR target therapy and the effect of the CASR gene single nucleotide polymorphisms. Clinical data concerning the efficacy and safety of cinacalcet in controlling hyperparathyroidism are reported, focusing on the treatment of the different types of parathyroid tumors. Finally, limits of this target therapy are analyzed, pointing out the lack of efficacy in improving kidney and bone morbidities in PHPT and cardiovascular diseases in SHPT. Though cinacalcet is a target therapeutic option for parathyroid tumors, further approaches are warranted to fully control these metabolic disorders and the underlying tumors
FSM-based power modeling of wireless protocols: the case of Bluetooth
No full textThe proliferation of pervasive computing applications relying
on battery–powered devices and wireless connectivity is
posing great emphasis on the issue of power optimization.
While node–level models and approaches have been widely
discussed, a problem requiring even greater attention is that
of power associated with the communication protocols. We
propose a high–level modeling methodology based on Finite
State Machines useful to predict the energy consumption
of given communication tasks with very low computational
cost, which can be applied to any protocol. We use this
methodology to create a power model of Bluetooth that we
characterize and validate experimentally on a real implementation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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