Phosphate Aggregates Research Articles

Highly Stable Amorphous (Pyro)phosphate Aggregates: Pyrophosphate as a Carrier for Bioactive Ions and Drugs in Bone Repair Applications

Highly Stable Amorphous (Pyro)phosphate Aggregates: Pyrophosphate as a Carrier for Bioactive Ions and Drugs in Bone Repair Applications

Correction for Fidopiastis et al., "Vibrio fischeri Possesses Xds and Dns Nucleases That Differentially Influence Phosphate Scavenging, Aggregation, Competence, and Symbiotic Colonization of Squid".

Correction for Fidopiastis et al., "Vibrio fischeri Possesses Xds and Dns Nucleases That Differentially Influence Phosphate Scavenging, Aggregation, Competence, and Symbiotic Colonization of Squid".

Corrected and republished from: "Vibrio fischeri Possesses Xds and Dns Nucleases That Differentially Influence Phosphate Scavenging, Aggregation, Competence, and Symbiotic Colonization of Squid".

Cells of Vibrio fischeri colonize the light organ of Euprymna scolopes, providing the squid bioluminescence in exchange for nutrients and protection. The bacteria encounter DNA-rich mucus throughout their transition to a symbiotic lifestyle, leading us to hypothesize a role for nuclease activity in the colonization process. In support of this, we detected abundant extracellular nuclease activity in growing cells of V. fischeri. To discover the gene(s) responsible for this activity, we screened a V. fischeri transposon mutant library for nuclease-deficient strains. Interestingly, only one strain, whose transposon insertion mapped to nuclease gene VF_1451, showed a complete loss of nuclease activity in our screens. A database search revealed that VF_1451 is homologous to the nuclease-encoding gene xds in Vibrio cholerae. However, V. fischeri strains lacking xds eventually revealed slight nuclease activity on plates upon prolonged incubation. This led us to hypothesize that a second secreted nuclease, identified through a database search as VF_0437, a homolog of V. cholerae dns, might be responsible for the residual nuclease activity. Here, we show that Xds and/or Dns are involved in essential aspects of V. fischeri biology, including natural transformation, aggregation, and phosphate scavenging. Furthermore, strains lacking either nuclease were outcompeted by the wild type for squid colonization. Understanding the specific role of nuclease activity in the squid colonization process represents an intriguing area of future research.IMPORTANCEFrom soil and water to host-associated secretions such as mucus, environments that bacteria inhabit are awash in DNA. Extracellular DNA (eDNA) is a nutritious resource that microbes dedicate significant energy to exploit. Calcium binds eDNA to promote cell-cell aggregation and horizontal gene transfer. eDNA hydrolysis impacts the construction of and dispersal from biofilms. Strategies in which pathogens use nucleases to avoid phagocytosis or disseminate by degrading host secretions are well-documented; significantly less is known about nucleases in mutualistic associations. This study describes the role of nucleases in the mutualism between Vibrio fischeri and its squid host Euprymna scolopes. We find that nuclease activity is an important determinant of colonization in V. fischeri, broadening our understanding of how microbes establish and maintain beneficial associations.

Influence of Proteins and Building Direction on the Corrosion and Tribocorrosion of CoCrMo Fabricated by Laser Powder Bed Fusion.

Cobalt-chromium-molybdenum (CoCrMo) alloys are common wear-exposed biomedical alloys and are manufactured in multiple ways, increasingly using additive manufacturing processes such as laser powder bed fusion (LPBF). Here, we investigate the effect of proteins and the manufacturing process (wrought vs LPBF) and building orientation (LPBF-XY and XZ) on the corrosion, metal release, tribocorrosion, and surface oxide composition by means of electrochemical, mechanical, microscopic, diffractive, and spectroscopic methods. The study was conducted at pH 7.3 in 5 g/L NaCl and 5 mM 2-(N-morpholino) ethanesulfonic acid (MES) buffer, which was found to be necessary to avoid metal phosphate and metal-protein aggregate precipitation. The effect of 10 g/L bovine serum albumin (BSA) and 2.5 g/L fibrinogen (Fbn) was studied. BSA and Fbn strongly enhanced the release of Co, Cr, and Mo and slightly enhanced the corrosion (still in the passive domain) for all CoCrMo alloys and most for LPBF-XZ, followed by LPBF-XY and the wrought CoCrMo. BSA and Fbn, most pronounced when combined, significantly decreased the coefficient of friction due to lubrication, the wear track width and severity of the wear mechanism, and the tribocorrosion for all alloys, with no clear effect of the manufacturing type. The wear track area was significantly more oxidized than the area outside of the wear track. In the reference solution without proteins, a strong Mo oxidation in the wear track surface oxide was indicative of a pH decrease and cell separation of the anodic and cathodic areas. This effect was absent in the presence of the proteins.

Towards bone regeneration: Understanding the nucleating ability of proline-rich peptides in biomineralisation

Obtaining rapid mineralisation is a challenge in current bone graft materials, which has been attributed to the difficulty of guiding the biological processes towards osteogenesis. Amelogenin, a key protein in enamel formation, inspired the design of two intrinsically disordered peptides (P2 and P6) that enhance in vivo bone formation, but the process is not fully understood. In this study, we have elucidated the mechanism by which these peptides induce improved mineralisation. Our molecular dynamics analysis demonstrated that in an aqueous environment, P2 and P6 fold to interact with the surrounding Ca2+, PO43− and OH− ions, which can lead to apatite nucleation. Although P2 has a less stable backbone, it folds to a stable structure that allows for the nucleation of larger calcium phosphate aggregates than P6. These results were validated experimentally in a concentrated simulated body fluid solution, where the peptide solutions accelerated the mineralisation process compared to the control and yielded mineral structures mimicking the amorphous calcium phosphate crystals that can be found in lamella bone. A pH drop for the peptide groups suggests depletion of calcium and phosphate, a prerequisite for intrinsic osteoinduction, while S/TEM and SEM suggested that the peptide regulated the mineral nucleation into lamella flakes. Evidently, the peptides accelerate and guide mineral formation, elucidating the mechanism for how these peptides can improve the efficacy of P2 or P6 containing devices for bone regeneration. The work also demonstrates how experimental mineralisation study coupled with molecular dynamics is a valid method for understanding and predicting in vivo performance prior to animal trials.

Combined Use of Ultrasonic and Electromagnetic Fields for the Study of Bonding Mechanisms between Dexamethasone Disodium Phosphate Molecules

We have investigated the ultrasonically induced birefringence traces of aqueous solutions of dexamethasone disodium phosphate, a derivative of hydrocortisone (cortisol). The stationary birefringence and the transient built-up and decay relaxation processes were studied as a function of solution concentration, ultrasound frequency and intensity, as well as a function of temperature. The results were analyzed in view of structural peculiarities of the system in an effort to gain further insights into the molecular relaxation dynamics and the proposed self-association process occurring in the system. The detected ultrasonically induced birefringence relaxation is motivated by the rotational diffusion of dexamethasone disodium phosphate aggregates due to self-association depending on the solution concentration. The observed relaxation mechanism is directly linked to the hydrodynamic size of the acoustic field-induced self-assembly. The systematic analysis of the transient birefringence signals caused by the applied ultrasonic field allowed us to evaluate the interplay between permanent and induced dipoles with changing concentration, temperature, and ultrasound properties. The birefringence traces are adequately fitted with a stretched exponential law indicating the polydispersive nature of the self-aggregated molecular structures. The obtained results are described in the light of recent studies performed on this system.

Phosphate aggregation, diffusion, and adsorption on kaolinite in saline solutions by molecular dynamics simulation

Large amounts of phosphates are required for the survival of cells. However, undesirable algae overgrowth requires phosphorus levels to be kept under control. For large bodies of water, cost-effective and ecosystem-friendly ways to export phosphate are needed. The use of clays appears to be the most promising method in seawater. However, for a broader application, the mechanisms of phosphate adsorption on kaolinite, the conditions for effective flocculation, and the impact of salt must first be addressed. In this study, molecular dynamics simulations are used to determine the adsorption and anchoring mechanisms of two species of phosphates that predominate at neutral pH, the dihydrogen phosphate ion H2PO4− and the hydrogen phosphate ion HPO42−, in a 1:1 ratio, on each of the three kaolinite principal planes, the basal surfaces, octahedral gibbsite (001) and tetrahedral siloxane (001¯), and the edge sites (010), in aqueous NaCl at a concentration of 0.6 M to mimic seawater. Phosphate aggregation is enhanced by Na bridges, although at very high concentrations, the number of aggregates and the size of the largest cluster decrease. Calculated diffusion coefficients for both phosphate species drop sharply in hypersaline solutions, although the decay rate is higher for the HPO42− species. Diffusion results are in close agreement with experimental data. Phosphate adsorption on kaolinite occurs in clusters. The hydrophilic surface (001) adsorbs increasing amounts of each of the phosphate species as the salt concentration increases, more HPO42− than H2PO4−. The hydrophobic (001¯) surface remains non-reactive to any species. The hydrophilic (010) edge surface increases adsorption of H2PO4− and drastically decreases that of HPO42− as salt concentration increases. Bidentate adsorption of HPO42− on the much rougher edge surface, even if saturated with adsorbed Na ions, is sterically impeded. The dominant adsorption mechanism is through cationic bridges on the gibbsite surface and at the edges. The adsorption capacity of kaolinite, including all its surfaces, increases with salt concentration, reaching its highest value in synthetic seawater. The values are of the order, although lower than the experimental ones obtained with less-accessible clays with atomic substitutions. The use of clays to control phosphate content in coastal waters is expected to contribute to public health and sustainability of marine industrial activities.

Quantification of the initial levels of calciprotein particles as a screening marker of mineral homeostasis in patients with cardiovascular disease and in patients with chronic kidney disease

Aim. To evaluate the initial concentration of calciprotein particles (CPPs), which are scavengers of excessive calcium and phosphate, in patients with cardiovascular disease and in patients with chronic kidney disease as compared with the healthy volunteers.Material and methods. The study included 308 individuals as follows: 1) 88 participants of the PURE study without hemodynamically relevant carotid athero scle rosis and symptomatic coronary atherosclerosis; 2) 88 patients with cere brovascular disease (CVD) who required carotid endarterectomy; 3) 88 pa tients with coronary artery disease (CAD) who required percutaneous coronary intervention or coronary artery bypass graft surgery; 4) 63 patients with stage 5 chronic kidney disease (CKD). We measured following mineral homeostasis parameters: total and ionized calcium, phosphate, total protein, albumin, and fetuin-A. Then, we determined a baseline serum CPP concentration by flow cytometry using a fluorescent-labeled bisphosphonate OsteoSense 680EX. Results. In comparison with other patients, healthy volunteers had the highest serum CPP concentration (249 CPPs/µL), indicating the retained ability to compensate mineral homeostasis disturbances by aggregation of excessive calcium and pho sphate with acidic proteins (mineral chaperones). Reduced serum CPP concentration in patients with CVD (170 CPPs/µL), CAD (139 CPPs/µL), and stage 5 CKD (193-203 CPPs/µL) showed impaired aggregation of excessive serum calcium and phosphate, which was also reflected by an increased level of blood ionized calcium.Conclusion. Patients with CVD, CAD, and stage 5 CKD have lower serum CPP concentration than healthy individuals. In combination with elevated ionized calcium and reduced albumin, this suggests the depletion of calcium binding buffers in the serum of patients with cardiovascular and renal diseases.

Libyan Desert Glass: New evidence for an extremely high-pressure-temperature impact event from nanostructural study

Abstract The origin of Libyan Desert Glass (LDG) found in the western parts of Egypt close to the Libyan border is debated in planetary science. Two major theories of its formation are currently competing: (1) melting by airburst and (2) formation by impact-related melting. While mineralogical and textural evidence for a high-temperature event responsible for the LDG formation is abundant and convincing, minerals and textures indicating high shock pressure have been scarce. This paper provides a nanostructural study of the LDG, showing new evidence of its high-pressure and high-temperature origin. We mainly focused on the investigation of Zr-bearing and phosphate aggregates enclosed within LDG. Micro- and nanostructural evidence obtained with transmission electron microscopy (TEM) are spherical inclusions of cubic, tetragonal, and orthorhombic (Pnma or OII) zirconia after zircon, which indicate high-pressure, high-temperature decomposition of zircon and possibly, melting of ZrO2. Inclusions of amorphous silica and amorphous Al-phosphate with berlinite composition (AlPO4) within mosaic whitlockite and monazite aggregates point at decomposition and melting of phosphates, which formed an emulsion with SiO2 melt. The estimated temperature of the LDG melts was above 2750 °C, approaching the point of SiO2 boiling. The variety of textures with different degrees of quenching immediately next to each other suggests an extreme thermal gradient that existed in LDG through radiation cooling. Additionally, the presence of quenched orthorhombic OII ZrO2 provides direct evidence of high-pressure (>13.5 GPa) conditions, confirming theory 2, the hypervelocity impact origin of the LDG.

Vibrio fischeri Possesses Xds and Dns Nucleases That Differentially Influence Phosphate Scavenging, Aggregation, Competence, and Symbiotic Colonization of Squid.

Cells of Vibrio fischeri colonize the light organ of Euprymna scolopes, providing the squid bioluminescence in exchange for nutrients and protection. The bacteria encounter DNA-rich mucus throughout their transition to a symbiotic lifestyle, leading us to hypothesize a role for nuclease activity in the colonization process. In support of this, we detected abundant extracellular nuclease activity in growing cells of V. fischeri. To discover the gene(s) responsible for this activity, we screened a V. fischeri transposon mutant library for nuclease-deficient strains. Interestingly, only one strain, whose transposon insertion mapped to nuclease gene VF_1451, showed complete loss of nuclease activity in our screens. A database search revealed that VF_1451 is homologous to the nuclease-encoding gene xds in Vibrio cholerae. However, V. fischeri strains lacking xds eventually revealed slight nuclease activity on plates after 72 h. This led us to hypothesize that a second secreted nuclease, identified through a database search as VF_0437, a homolog of V. cholerae dns, might be responsible for the residual nuclease activity. Here, we show that Xds and/or Dns are involved in essential aspects of V. fischeri biology, including natural transformation, aggregation, and phosphate scavenging. Furthermore, strains lacking either nuclease were outcompeted by the wild type for squid colonization. Understanding the specific role of nuclease activity in the squid colonization process represents an intriguing area of future research. IMPORTANCE From soil and water to host-associated secretions such as mucus, environments that bacteria inhabit are awash in DNA. Extracellular DNA (eDNA) is a nutritious resource that microbes dedicate significant energy to exploit. Calcium binds eDNA to promote cell-cell aggregation and horizontal gene transfer. eDNA hydrolysis impacts construction of and dispersal from biofilms. Strategies in which pathogens use nucleases to avoid phagocytosis or disseminate by degrading host secretions are well documented; significantly less is known about nucleases in mutualistic associations. This study describes the role of nucleases in the mutualism between V. fischeri and its squid host, Euprymna scolopes. We find that nuclease activity is an important determinant of colonization in V. fischeri, broadening our understanding of how microbes establish and maintain beneficial associations.

Ex vivo serum treatment with magnesium sulfate and edta disodium salt dihydrate abrogates calcium- and phosphate-induced formation of calciprotein particles

Background and Aims : Calciprotein particles (CPPs), generated in human blood to cope with mineral stress, mediate aggregation and clearance of excessive calcium and phosphate from the circulation. However, increased serum propensity to produce CPPs has been associated with arterial hypertension, cerebrovascular disease, myocardial infarction, and cardiovascular death by causing endothelial dysfunction. As CPPs might represent a link between disturbed mineral homeostasis and cardiovascular disease, we conducted ex vivo testing of potential anti-CPP treatment modalities: albumin (Ca2+-binding protein), Mg2+ supplementation and chelation therapy.

Raloxifene HCl – quercetin co-amorphous system: preparation, characterization, and investigation of its behavior in phosphate buffer

Purpose Raloxifene HCl (RLX), a practically insoluble drug used in the treatment of osteoporosis in post-menopausal women; was modified at its molecular level to enhance its solubility using co-amorphous technology. Methods In this study, RLX was co-amorphized with Quercetin (QCT; a nutraceutical flavonoid) using solvent evaporation (SE), quench cooling (QC), and ball milling (BM) techniques. The prepared co-amorphous systems (CAMs) were characterized using XRD, DSC, and FT-IR. For the simultaneous analysis of RLX and QCT, an RP-HPLC method was developed to quantify the drugs in the prepared systems. Behavior in aqueous media was investigated by studying amorphous and equilibrium solubility, and drug release of RLX using USP phosphate buffer pH 6.8. Results Solvent evaporation (RQ(SE)) was able to produce a homogeneous system, where quench cooling showed thermal degradation of the drug, and ball milling was not able to amorphize the blend. From the DSC results, it was found that RQ(SE) was able to increase the glass transition temperature by 40 °C. It was observed that the solubility of RLX reduced, as RLX formed phosphate aggregates in the buffer media which further formed complexes with QCT; this was determined by investigating the residual particles from solubility studies. Though the solubility was reduced, drug release of RQ(SE) exhibited improvement in concentration by 2.3 times. Conclusions RQ(SE) formed a stable CAM; though the solubility of RLX in presence of QCT reduced, from the drug release study, it was apparent that the co-amorphous technique improved the concentration of RLX.

Formation and Evolution of Nanoscale Calcium Phosphate Precursors under Biomimetic Conditions

Simulated body fluids (SBFs) that mimic human blood plasma are widely used media for in vitro studies in an extensive array of research fields, from biomineralization to surface and corrosion sciences. We show that these solutions undergo dynamic nanoscopic conformational rearrangements on the timescale of minutes to hours, even though they are commonly considered stable or metastable. In particular, we find and characterize nanoscale inhomogeneities made of calcium phosphate (CaP) aggregates that emerge from homogeneous SBFs within a few hours and evolve into prenucleation species (PNS) that act as precursors in CaP crystallization processes. These ionic clusters consist of ∼2 nm large spherical building units that can aggregate into suprastructures with sizes of over 200 nm. We show that the residence times of phosphate ions in the PNS depend critically on the total PNS surface. These findings are particularly relevant for understanding nonclassical crystallization phenomena, in which PNS are assumed to act as building blocks for the final crystal structure.

SNF472: mechanism of action and results from clinical trials.

Vascular calcification (VC) is associated with increased cardiovascular event rates, particularly in patients with end-stage kidney disease (ESKD). Dysregulated mineral metabolism and inflammation have been shown to promote VC, however, treatment options targeting VC specifically are not available. This review outlines the pathophysiological mechanisms contributing to VC in ESKD and describes recent studies evaluating the effects of the first-in-class inhibitor of VC, SNF472. SNF472 directly inhibits calcium phosphate crystal formation and aggregation. SNF472 has completed early phase clinical trials with a favourable safety profile and Phase 2 clinical trial data have shown attenuation of coronary artery and aortic valve calcification in patients receiving hemodialysis. Therapeutic agents that directly target VC may prevent the multiple complications associated with dystrophic calcification in patients with ESKD.

Surface-Dependent Activation of Model α-Al2 O3 -Supported P-Doped Hydrotreating Catalysts Prepared by Spin Coating.

Requirements for improved catalytic formulations is continuously driving research in hydrotreating (HDT) catalysis for biomass upgrading and heteroatom removal for cleaner fuels. The present work proposes a surface-science approach for the understanding of the genesis of the active (sulfide) phase in model P-doped MoS2 hydrotreating catalysts supported on α-Al2 O3 single crystals. This approach allows one to obtain a surface-dependent insight by varying the crystal orientations of the support. Model phosphorus-doped catalysts are prepared via spin-coating of Mo-P precursor solutions onto four α-Al2 O3 crystal orientations, C(0001), A(11 0), M(10 0) and R(1 02) that exhibit different speciations of surface -OH. 31 P and 95 Mo liquid-state NMR are used to give a comprehensive description of the Mo and P speciation of the phospho-molybdic precursor solution. The speciation of the deposition solution is then correlated with the genesis of the active MoS2 phase. XPS quantification of the surface P/Mo ratio reveal a surface-dependent phosphate aggregation driven by the amount of free phosphates in solution. Phosphates aggregation decreases in the following order C(0001)≫M(10 0)>A(11 0), R(1 02). This evolution can be rationalized by an increasing strength of phosphate/surface interactions on the different α-Al2 O3 surface orientations from the C(0001) to the R(1 02) plane. Retardation of the sulfidation with temperature is observed for model catalysts with the highest phosphate dispersion on the surface (A(11 0), R(1 02)), suggesting that phosphorus strongly intervene in the genesis of the active phase through a close intimacy between phosphates and molybdates. The surface P/Mo ratio appears as a key descriptor to quantify this retarding effect. It is proposed that retardation of sulfidation is driven by two effects: i) a chemical inhibition through formation of hardly reducible mixed molybdo-phosphate structures and ii) a physical inhibition with phosphate clusters inhibiting the growth of MoS2 . The surface-dependent phosphorus doping on model α-Al2 O3 supports can be used as a guide for the rational design of more efficient HDT catalysts on industrial γ-Al2 O3 carrier.

Clinicopathological and imaging features of pulmonary alveolar microlithiasis in a dog \u2013 a case report

BackgroundThe aetiology of pulmonary alveolar microlithiasis (PAM) in animals is still unknown. In humans, this pulmonary disorder is a rare autosomal recessive disorder triggered by a mutation in the gene SLC34A2, which causes deposition and aggregation of calcium and phosphate in the pulmonary parenchyma with formation of microliths. Although histopathological examination is required for a definite diagnosis, in humans, imaging modalities such as computed tomography can demonstrate typical patterns of the disease. This is the first description of the computed tomographic (CT) features of a histologically confirmed PAM in dogs.Case presentationThe following report describes a case of a 7-year-old female Boxer dog evaluated for paroxysmal loss of muscle tone and consciousness with excitement. The main differential diagnoses considered were syncope, seizures, and narcolepsy-cataplexy. The results of the complete blood count, serum biochemistry panel, urinalysis, arterial blood pressure, echocardiography, abdominal ultrasound, Holter monitoring, and ECG were all within normal limits. Additional exams included thoracic radiographs, head and thorax CT, bronchoalveolar lavage (BAL), and CT-guided cytology. Thoracic radiographs revealed micronodular calcifications in the lungs, with sandstorm appearance. Computed tomography of the thorax showed the presence of numerous mineralized high-density agglomerates of multiple sizes throughout the pulmonary parenchyma, a reticular pattern with ground glass opacity and intense mineralized fibrosis of the pleural lining. Head CT was unremarkable. BAL and CT-guided cytology were inconclusive, but imaging features strongly suggest the diagnosis of PAM, which was histologically confirmed after necropsy.ConclusionsThis case report contributes to the clinicopathological and imaging characterization of pulmonary alveolar microlithiasis in dogs. In this species, the diagnosis of PAM should be considered when CT features evidence a reticular pattern with ground glass opacity and the presence of an elevated number and size of calcifications.

Localized electron microscopy analysis of steel corrosion processes in the presence of zinc phosphate flake-type particles

Abstract Zinc phosphate particles are used in coatings that protect steel from corrosion. The corrosion of coated steel was examined at the microscopic scale in proximity of zinc phosphate flakes. The coatings were prepared by dispersing the zinc phosphate flakes in epoxy-phenolic resin matrix, spray coating on the steel substrate, and curing. Such prepared coatings were then scratched, and corroded in the artificial weathering conditions by means of a condensate climate test. The ongoing corrosion process was examined using environmental scanning electron microscopy (ESEM). By applying this approach, we observed the influence of the anisotropic particles of zinc phosphate on the formation of corrosion products. Local areas at the edge of the scratch that were in direct contact with the zinc phosphate aggregates, revealed the formation of a different crystal type compared to the plain areas of the scratch. The obtained data indicates that a partial dissolution of the zinc phosphate particles took place, and suggests that the influence of zinc phosphate on the formation of corrosion products was mediated by the presence of water.

The Significance of Utilizing In Vitro Transfer Model and Media Selection to Study the Dissolution Performance of Weak Ionizable Bases: Investigation Using Saquinavir as a Model Drug.

This study investigated the dissolution behavior of BCS class II ionizable weak base Saquinavir and its mesylate salt in the multi-compartment transfer setup employing different composition of dissolution media. The dissolution behavior of Saquinavir was studied by using a two-compartment transfer model representing the transfer of drug from the stomach (donor compartment) to the upper intestine (acceptor compartment). Various buffers like phosphate, bicarbonate, FaSSIF, and FeSSIF were employed. The dissolution was also studied in the concomitant presence of the additional solute, i.e., Quercetin. Further, the dissolution profiles of Saquinavir and its mesylate salt were simulated by GastroPlusTM, and the simulated dissolution profiles were compared against the experimental ones. The formation of in situ HCl salt and water-soluble amorphous phosphate aggregates was confirmed in the donor and acceptor compartments of the transfer setup, respectively. As the consequence of the lower solubility product of HCl salt of Saquinavir, the solubility advantage of mesylate salt was vanished leading to the lower than the predicted dissolution in the acceptor compartment. However, the formation of water-soluble aggregates in the presence of the phosphate salts was observed leading to the higher than the predicted dissolution of the free base in the transfer setup. Interestingly, the formation of such water-soluble aggregates was found to be hindered in the concomitant presence of an ionic solute resulting in the lower dissolution rates. The in situ generation of salts and aggregates in the transfer model lead to the inconsistent prediction of dissolution profiles by GastroPlusTM.

Histological evaluation of pulpal response to direct pulp capping using statins with α-tricalcium phosphate and mineral trioxide aggregate in human teeth.

Background:The purpose of this study was to compare the outcome of direct pulp capping by statins with α-tricalcium phosphate (α-TCP) and mineral trioxide aggregate (MTA) on pulp tissue of human teeth through histological evaluation.Aims:The aim of the present study is to compare the pulpal response of statins (simvastatin or atorvastatin) with α-TCP to that of MTA on human teeth by light microscopic histological evaluation.Materials and Methods:Ninety intact premolar teeth scheduled for orthodontic extraction were used for the study. Class 1 cavities were prepared, and the pulp was mechanically exposed under rubber dam isolation. The samples were divided into three groups of thirty teeth each (Group I – simvastatin + α-TCP, Group II – atorvastatin + α-TCP, and Group III – MTA), and the test materials were placed accordingly. After the experimental periods of 7, 30, and 90 days, the teeth were extracted atraumatically. The samples were then evaluated for the degree of inflammation, tissue damage, and hard tissue formation under light microscope, and they were scored based on the histopathologic findings.Statistical Analysis:The results were analyzed statistically using the Chi-square test.Results:There was no statistically significant difference between Groups I, II, and III in terms of inflammation, tissue damage, and hard tissue formation for all the three observation periods (P > 0.05).Conclusions:Simvastatin and atorvastatin with α-TCP were found to be effective in inducing dentin bridge formation which was comparable to MTA.

Single Grain (U-Th)/He Ages from EET14074, an Acapulcoite Meteorite

EET14074 is a member of the acapulcoite-lodranite family of meteorites and was discovered in Antarctica in 2014 by the Korean Polar Research Institute (KOPRI). Herein, we obtained (U-Th)/He ages from 20 phosphate aggregates in EET14074 to constrain the sample’s thermal history. The ages range between 116.8 Ma ± 145.7 Ma (1σ) and 4211.5 Ma ± 1089.1 Ma, with an average of 2530 ± 260 Ma (n=20). Excluding outlier ages with large uncertainties, the 13 most concentrated ages yielded a theoretical minimum age of 3000 ± 150 Ma. This age corresponds to a fraction helium loss (f) of ~31% assuming crystallization age of ~4.55 Ga. The uranium abundances in single aliquots are in the range of 1.52 - 289.93 fmol, with an average of 58.00 fmol (n = 20), whereas the thorium abundance ranges between 2.51 and 2337.06 fmol with an average of 1149.29 fmol (n = 20). To explain the observed He loss, thermal diffusion modeling was performed with an assumption that the He loss occurred during a recent passage of the meteorite in Earth’s atmosphere. For the most likely t-T condition of compressional heating in Earth’s atmosphere of this meteorite (T = ~430 ˚C, t = ~10 sec), a fractional loss of 29.3% was calculated when the diffusion domain radius (r) of 92.8 µm was assumed. This estimation is nearly indistinguishable from the observed fractional loss of 31.3%. Additionally, diffusion modeling for another set of data with a different size (r = 40.4 µm) yielded a very similar fractional loss. Therefore, the observed (U-Th)/He age distribution is likely derived from compressional heating during the passage of EET14074 in Earth’s atmosphere.