Mechanism of action of SNF472, a novel calcification inhibitor to treat vascular calcification and calciphylaxis.

Background And Purpose: No therapy is approved for vascular calcification or calcific uraemic arteriolopathy (calciphylaxis), which increases mortality and morbidity in patients undergoing dialysis. Deposition of hydroxyapatite (HAP) crystals in arterial walls is the common pathophysiologic mechanism. The mechanism of action of SNF472 to reduce HAP deposition in arterial walls was investigated.

Characterization of SNF472 pharmacokinetics and efficacy in uremic and non-uremic rats models of cardiovascular calcification.

End-stage renal disease is strongly associated with progressive cardiovascular calcification (CVC) and there is currently no therapy targeted to treat CVC. SNF472 is an experimental formulation under development for treatment of soft tissue calcification. We have investigated the pharmacokinetics of SNF472 administration in rats and its inhibitory effects on CVC.

Direct Covalent Grafting of Phytate to Titanium Surfaces through Ti-O-P Bonding Shows Bone Stimulating Surface Properties and Decreased Bacterial Adhesion.

Myo-inositol hexaphosphate, also called phytic acid or phytate (IP6), is a natural molecule abundant in vegetable seeds and legumes. Among other functions, IP6 inhibits bone resorption. It is adsorbed on the surface of hydroxyapatite, inhibiting its dissolution and decreasing the progressive loss of bone mass.

Relationship between Urinary Level of Phytate and Valvular Calcification in an Elderly Population: A Cross-Sectional Study.

Pathological calcification generally consists of the formation of solid deposits of hydroxyapatite (calcium phosphate) in soft tissues. Supersaturation is the thermodynamic driving force for crystallization, so it is believed that higher blood levels of calcium and phosphate increase the risk of cardiovascular calcification. However several factors can promote or inhibit the natural process of pathological calcification.

Validation of an LC-MS bioanalytical method for quantification of phytate levels in rat, dog and human plasma.

Myo-inositol hexakisphosphate (phytate, IP6) is a naturally occuring compound whose determination in biological matrices is chanllenging. Several benefitial properties have been attributed to IP6 in parallel with the development of suitable analytical methodologies for its analytical determination in urine and some tissues. However, there is a lack of appropriate tools for its determination in plasma samples.

Urinary lithogenesis risk tests: comparison of a commercial kit and a laboratory prototype test.

Objective: Renal stone formation is a multifactorial process depending in part on urine composition. Other parameters relate to structural or pathological features of the kidney. To date, routine laboratory estimation of urolithiasis risk has been based on determination of urinary composition.

Evolution of post-ESWL residual lithiasis depending on the type of calculus and urine composition.

Objectives: Extracorporeal shock wave lithotripsy (ESWL) is one of the most commonly used procedures for removal of renal calculi from the upper urinary tract, but complete expulsion of the fragments generated is not always achieved. This can lead to new lithiasic episodes, and it is considered that 10-26% of fragmented calculi can undergo regrowth. This in vitro study investigated the influence of fragment and urinary composition on post-ESWL growth of fragments, with the aims of establishing the effect and importance of these parameters, and identifying effective prophylactic measures.

Phytate reduces age-related cardiovascular calcification.

The aim of this research was to evaluate the effect of dietary phytate on cardiovascular calcification in rats during aging. Male Wistar rats (10 weeks old) were randomly assigned to four diet groups. The control group was fed with a balanced diet (UAR-A04) containing phytate.

Phytate inhibits bovine pericardium calcification in vitro.

Objective: The present study examined the inhibitory effects of pyrophosphate, etidronate, and phytate on bovine pericardium calcification in vitro.

Methods: Bovine pericardium was glutaraldehyde fixed and then placed in a flow chamber in the presence of a synthetic physiological fluid alone (control) or the fluid plus various concentrations of pyrophosphate, etidronate, or phytate. Following a 96-h incubation, fragments were removed and assayed for calcification by measuring calcium and phosphorus levels.

Effect of crystallization inhibitors on vascular calcifications induced by vitamin D: a pilot study in Sprague-Dawley rats.

Background: Pathological calcification in soft tissues (ie, ectopic calcification) can have severe consequences. Hydroxyapatite is the common mineral phase present in all tissue calcifications. In general, the development of tissue calcifications requires a pre-existing injury as an inducer (heterogeneous nucleant), whereas further progression requires the presence of other promoter factors (such as hypercalcemia and/or hyperphosphatemia) and/or a deficiency in calcification repressor factors (crystallization inhibitors and cellular defense mechanisms).

Uric acid as inducer of calcium oxalate crystal development.

Objective: This paper deals with the mechanism by which uric acid affects calcium oxalate crystallization and the role of crystallization inhibitors in this process.

Material And Methods: Pure uric acid crystals and fragments of uric acid renal calculi were used to induce calcium oxalate crystal formation and development. These studies were performed in flow systems, using synthetic urine and similar conditions to those found in real renal situations.

Phytate acts as an inhibitor in formation of renal calculi.

The aim of this study was to assess the inhibitory action of phytate in formation of renal calculi. Hypertension (induced by nicotine) combined with hypercalcemia (induced by D vitamin) was used to induce calcification in renal tissue in male Wistar rats that were fed a purified phytate free diet. Phytate non-treated rats developed significant calcium deposits in kidneys and papillae, as well as in kidney tubules and vessels, whereas calcium deposits were absent in control and phytate treated rats.

Phytate (Myo-inositol hexakisphosphate) inhibits cardiovascular calcifications in rats.

Calcification is an undesirable disorder, which frequently occurs in the heart vessels. In general, the formation of calcific vascular lesions involves complex physicochemical and molecular events. Calcification (hydroxyapatite) is initiated by injury and is progressed by promoter factors and/or the deficit of inhibitory signals.

Factors affecting the regrowth of renal stones in vitro: a contribution to the understanding of renal stone development.

Objective: The exact mechanism of renal stone formation is still not totally understood. Thus, the role of crystallization inhibitors at different stages of stone development, the influence of preexisting solid particles and the effects of variations in urine composition require further clarification. The aim of this paper is to clarify some of these questions by studying the regrowth achieved by real spontaneously passed post-extracorporeal shock wave lithotripsy (post-ESWL) fragments of calcium oxalate monohydrate (COM) renal calculi.

Study of the absorption of myo-inositol hexakisphosphate (InsP6) through the skin.

Recently, some properties of myo-inositol hexakisphosphate (InsP(6)) are related to its dermatological use as discolouring agent, on preventing calcinosis cutis or due to its important role on premature aging. Some studies also seem to demonstrate a capacity of InsP(6) to inhibit skin cancer. In this paper, a first study of the absorption of InsP(6) through the skin is developed.

Role of the organic matter in calcium oxalate lithiasis.

Urine contains variable amounts of organic matter derived from cell degradation. The cellular detritus is composed by membranous and cytosolic glycoproteins, etc. The aim of this paper was to study the role of organic matter in calcium oxalate crystal development and to evaluate the action of some crystallization inhibitors on this process.

Absorption of myo-inositol hexakisphosphate (InsP6) through the skin: study of the matrix effects. mechanism of phytate topical absorption.

Myo-inositol hexakisphosphate (InsP6, phytate) is a molecule to which diverse beneficial properties have been attributed. Some of these properties are related to its dermatological use as discolouring agent, on preventing calcinosis cutis or due to its important role on premature aging. Other studies also seem to demonstrate a capacity of InsP6 to inhibit skin cancer.

The role of glycoproteins in calcium oxalate crystal development.

Objective: To assess the effects of a glycoprotein (mucine) on calcium oxalate crystal development in different conditions and situations, to clarify some of its possible effects.

Materials And Methods: Crystallization was assessed using a batch system in presence of mucine suspensions, by kinetic-turbidimetric measurements, and using a flow system in the presence of retained agglomerates of mucine, evaluating the precipitated calcium oxalate.

Results: In batch conditions low mucine concentrations (<15 mg/L) inhibited calcium oxalate nucleation and higher concentrations (<250 mg/L) inhibited calcium phosphate nucleation, whereas at high concentrations there was also promotion.