Comparison of silicate-substituted calcium phosphate (Actifuse®) with rhBMP-2 (Infuse®) in posterolateral instrumented lumbar fusion

Study Design This was a randomised controlled trial in patients with degenerative disc disease (DDD) who underwent instrumented posterolateral lumbar fusion (PLF) surgery. Objective The aim of this study was to assess the efficacy of the bone grafting substitute, silicate-substituted calcium phosphate (SiCaP) compared with bone morphogenetic protein (rhBMP-2) and to evaluate clinical outcomes over a period of two years. Methods Patients undergoing PLF surgery for DDD at a single centre were recruited and randomised to one of two groups; SiCaP (n=9) or rhBMP-2 (n=10). One patient withdrew prior to randomisation and another from the rhBMP-2 group after randomisation. The radiological and clinical outcomes were examined and compared. Fusion was assessed at 12 months with computed tomography (CT) and plain radiographs. Clinical outcomes were evaluated by recording measures of pain, quality of life, disability and neurological status from six weeks to two years postoperatively. Results In the SiCaP and rhBMP-2 groups, fusion was observed in 9/9 and 8/9 patients respectively. Pain and disability scores were reduced and quality of life increased in both groups. Leg pain, disability and satisfaction scores were similar between the groups at each postoperative time point, however, back pain was less at six weeks and quality of life was higher at six months in the SiCaP group than the rhBMP-2 group. Conclusions SiCaP and rhBMP-2 were comparable in terms of achieving successful bone growth and fusion. Both groups similarly alleviated pain and improved quality of life, neurological, satisfaction and return to work outcomes following PLF surgery.

Calcium phosphate flocs and the clarification of sugar cane juice from whole of crop harvesting

Sugar cane biomass is one of the most viable feedstocks for the production of renewable fuels and chemicals. Therefore, processing the whole of crop (WC) (i.e., stalk and trash, instead of stalk only) will increase the amount of available biomass for this purpose. However, effective clarification of juice expressed from WC for raw sugar manufacture is a major challenge because of the amounts and types of non-sucrose impurities (e.g., polysaccharides, inorganics, proteins, etc.) present. Calcium phosphate flocs are important during sugar cane juice clarification because they are responsible for the removal of impurities. Therefore, to gain a better understanding of the role of calcium phosphate flocs during the juice clarification process,the effects of impurities on the physicochemical properties of calcium phosphate flocs were examined using small-angle laser light scattering technique, attenuated total reflectance Fourier transformed infrared spectroscopy, and X-ray powder diffraction. Results on synthetic sugar juice solutions showed that the presence of SiO2 and Na+ ions affected floc size and floc structure. Starch and phosphate ions did not affect the floc structure; however, the former reduced the floc size, whereas the latter increased the floc size. The study revealed that high levels of Na+ ions would negatively affect the clarification process the most, as they would reduce the amount of suspended particles trapped by the flocs. A complementary study on prepared WC juice using cold and cold/intermediate liming techniques was conducted. The study demonstrated that, in comparison to the one-stage (i.e., conventional) clarification process, a two-stage clarification process using cold liming removed more polysaccharides (≤19%),proteins (≤82%), phosphorus (≤53%), and SiO2 (≤23%) in WC juice but increased Ca2+ (≤136%) and sulfur (≤200%)

Autosomal dominant familial calcium pyrophosphate dihydrate deposition disease is caused by mutation in the transmembrane protein ANKH

Familial autosomal dominant calcium pyrophosphate dihydrate (CPPD) chondrocalcinosis has previously been mapped to chromosome 5pl5. We have identified a mutation in the ANKH gene that segregates with the disease in a family with this condition. ANKH encodes a putative transmembrane inorganic pyrophosphate (PPi) transport channel. We postulate that loss of function of ANKH causes elevated extracellular PPi levels, predisposing to CPPD crystal deposition.

Inhibition by poly(acrylic acid) and morphological changes in calcium carbonate and calcium carbonate/calcium sulfate crystallization on silica fibers

An intrinsic exposed core optical fiber sensor (IECOFS) made from fused silica was used to monitor the crystallization of calcium carbonate (CaCO3) and CaCO3/calcium sulfate (CaSO4) composite at 100 and 120 °C in the absence and presence of low-molar-mass (Mn ≤ 2000) poly(acrylic acid) (PAA) with different end groups. The IECOFS responded only to deposition and growth processes on the fiber surface rather than changes occurring in the bulk of the solution. Hexyl isobutyrate-terminated PAA (Mn = 1400) and hexadecyl isobutyrate-terminated PAA (Mn = 1700) were the most effective species in preventing CaCO3 deposition. Phase transformation from vaterite to aragonite/calcite decreased with increasing hydrophobicity of the PAA end group. Low-molar-mass PAA at 10 ppm showed very significant inhibition of CaCO3/CaSO4 composite formation for all end groups investigated.

Novel ANKH amino terminus mutation (Pro5Ser) associated with early-onset calcium pyrophosphate disease with associated phosphaturia

This report describes a 32-year-old woman presenting since childhood with progressive calcium pyrophosphate disease (CPPD), characterized by severe arthropathy and chondrocalcinosis involving multiple peripheral joints and intervertebral disks. Because ANKH mutations have been previously described in familial CPPD, the proband's DNA was assessed at this locus by direct sequencing of promoter and coding regions and revealed 3 sequence variants in ANKH. Sequences of exon 1 revealed a novel isolated nonsynonymous mutation (c.13 C>T), altering amino acid in codon 5 from proline to serine (CCG>TCG). Sequencing of parental DNA revealed an identical mutation in the proband's father but not the mother. Subsequent clinical evaluation demonstrated extensive chondrocalcinosis and degenerative arthropathy in the proband's father. In summary, we report a novel mutation, not previously described, in ANKH exon 1, wherein serine replaces proline, in a case of early-onset severe CPPD associated with metabolic abnormalities, with similar findings in the proband's father.

Genetic studies of disorders of calcium crystal deposition

In summary, although many factors are likely to be involved in regulating calcification and ossification processes, studies of the causation of articular chondrocalcinosis and disorders of spinal ossification, such as DISH and OPLL, implicate control over inorganic pyrophosphate levels as being one of the most important factors in their aetiopathogenesis. The findings of these studies may prove relevant to other rheumatic diseases in which ectopic ossification occurs, such as AS.

Coronary calcium scoring: Calcium location needs to be integrated!

Coronary calcium scoring (CCS) has been a topic of great interest lately. In a large population-based study comprising 6,722 patients, Detrano et al. (1) have effectively shown that CCS can be a strong predictor of incident coronary heart disease among different racial groups. Henneman et al. (2) have, however, reported that CCS does not reliably exclude the presence of (significant) atherosclerosis. This topic is quite controversial as there is significant evidence from Detrano's work that higher CCS is associated with an increased risk of acute coronary events. We think that the location of calcium within the coronary arteries should also be considered. Li et al. (3,4) have shown that the position of the calcium in the plaque is a better determinant of plaque vulnerability than the total calcium load. Using a biomechanical model, predicted maximum stress was found to increase by 47.5% when calcium deposits were located in the thin fibrous cap. The presence of calcium deposits in the lipid core or remote from the fibrous cap resulted in no increase in maximum stress. It was also noted that the presence of calcification within the lipid core may even stabilize the plaque. Integration of calcium location in CCS will, therefore, enable better assessment of severity of atherosclerosis and prediction of future cardiovascular events.

Does calcium deposition play a role in the stability of atheroma? Location may be the key

Background: Rupture of vulnerable atheromatous plaque in the carotid and coronary arteries often leads to stroke and heart attack respectively. The role of calcium deposition and its contribution to plaque stability is controversial. This study uses both an idealized and a patient-specific model to evaluate the effect of a calcium deposit on the stress distribution within an atheromatous plaque. Methods: Using a finite-element method, structural analysis was performed on an idealized plaque model and the location of a calcium deposit within it was varied. In addition to the idealized model, in vivo high-resolution MR imaging was performed on 3 patients with carotid atheroma and stress distributions were generated. The individual plaques were chosen as they had calcium at varying locations with respect to the lumen and the fibrous cap. Results: The predicted maximum stress was increased by 47.5% when the calcium deposit was located in the thin fibrous cap in the model when compared with that in a model without a deposit. The result of adding a calcium deposit either to the lipid core or remote from the lumen resulted in almost no increase in maximal stress. Conclusion: Calcification at the thin fibrous cap may result in high stress concentrations, ultimately increasing the risk of plaque rupture. Assessing the location of calcification may, in the future, aid in the risk stratification of patients with carotid stenosis.

Atheroma: Is calcium important or not? A modelling study of stress within the atheromatous fibrous cap in relation to position and size of calcium deposits

Atheromatous plaque rupture h the cause of the majority of strokes and heart attacks in the developed world. The role of calcium deposits and their contribution to plaque vulnerability are controversial. Some studies have suggested that calcified plaque tends to be more stable whereas others have suggested the opposite. This study uses a finite element model to evaluate the effect of calcium deposits on the stress within the fibrous cap by varying their location and size. Plaque fibrous cap, lipid pool and calcification were modeled as hyperelastic, Isotropic, (nearly) incompressible materials with different properties for large deformation analysis by assigning time-dependent pressure loading on the lumen wall. The stress and strain contours were illustrated for each condition for comparison. Von Mises stress only increases up to 1.5% when varying the location of calcification in the lipid pool distant to the fibrous cap. Calcification in the fibrous cap leads to a 43% increase of Von Mises stress when compared with that in the lipid pool. An increase of 100% of calcification area leads to a 15% stress increase in the fibrous cap. Calcification in the lipid pool does not increase fibrous cap stress when it is distant to the fibrous cap, whilst large areas of calcification close to or in the fibrous cap may lead to a high stress concentration within the fibrous cap, which may cause plaque rupture. This study highlights the application of a computational model on a simulation of clinical problems, and it may provide insights into the mechanism of plaque rupture.

Neonatal intestinal obstruction associated with oral calcium supplementation

A case report of a 920 g infant developing a small intestinal obstruction following therapy for congestive cardiac failure is presented. Although the causation was thought to be milk curd obstruction, subsequent analysis revealed high concentration of calcium and phosphate in the stools. The possible pathogenesis is discussed in relation to the inspissated milk syndrome.

GABAAα1 and GABAAρ1 subunits are expressed in cultured human RPE cells and GABAA receptor agents modify the intracellular calcium concentration.

Purpose: Gamma-aminobutyric acid A (GABAA) receptors (GABAARs), which are ionotropic receptors involving chloride channels, have been identified in various neural (e.g., mouse retinal ganglion cells) and nonneural cells (e.g., mouse lens epithelial cells) regulating the intracellular calcium concentration ([Ca(2+)]i). GABAAR β-subunit protein has been isolated in the cultured human and rat RPE, and GABAAα1 and GABAAρ1 mRNAs and proteins are present in the chick RPE. The purpose of this study was to investigate the expression of GABAAα1 and GABAAρ1, two important subunits in forming functional GABAARs, in the cultured human RPE, and further to explore whether altering receptor activation modifies [Ca(2+)]i. Methods: Human RPE cells were separately cultured from five donor eye cups. Real-time PCR, western blots, and immunofluorescence were used to test for GABAAα1 and GABAAρ1 mRNAs and proteins. The effects of the GABAAR agonist muscimol, antagonist picrotoxin, or the specific GABAAρ antagonist 1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on [Ca(2+)]i in cultured human RPE were demonstrated using Fluo3-AM. Results: Both GABAAα1 and GABAAρ1 mRNAs and proteins were identified in cultured human RPE cells; antibody staining was mainly localized to the cell membrane and was also present in the cytoplasm but not in the nucleus. Muscimol (100 μM) caused a transient increase of the [Ca(2+)]i in RPE cells regardless of whether Ca(2+) was added to the buffer. Muscimol-induced increases in the [Ca(2+)]i were inhibited by pretreatment with picrotoxin (300 μM) or TPMPA (500 μM). Conclusions: GABAAα1 and GABAAρ1 are expressed in cultured human RPE cells, and GABAA agents can modify [Ca(2+)]i.

Mathematical models of calcium and tight junctions in normal and reconstructed epidermis

This project investigated the calcium distributions of the skin, and the growth patterns of skin substitutes grown in the laboratory, using mathematical models. The research found that the calcium distribution in the upper layer of the skin is controlled by three different mechanisms, not one as previously thought. The research also suggests that tight junctions, which are adhesions between neighbouring skin cells, cannot be solely responsible for the differences in the growth patterns of skin substitutes and normal skin.

The influence of impurities on calcium phosphate floc structure and size in sugar solutions

Settling, dewatering and filtration of flocs are important steps in industry to remove solids and improve subsequent processing. The influence of non-sucrose impurities (Ca2+, Mg2+, phosphate and aconitic acid) on calcium phosphate floc structure (scattering exponent, Sf), size and shape were examined in synthetic and authentic sugar juices using X-ray diffraction techniques. In synthetic juices, Sf decreases with increasing phosphate concentration to values where loosely bound and branched flocs are formed for effective trapping and removal of impurities. Although, Sf did not change with increasing aconitic acid concentration, the floc size significantly decreased reducing the ability of the flocs to remove impurities. In authentic juices, the flocs structures were marginally affected by increasing proportions of non-sucrose impurities. However, optical microscopy indicated the formation of well-formed macro-floc network structures in sugar cane juices containing lower proportions of non-sucrose impurities. These structures are better placed to remove suspended colloidal solids.

Electrochemical properties and intermediate-temperature fuel cell performance of dense yttrium-doped barium zirconate with calcium addition

Although BaZr 0.8Y 0.2O 3-δ(BZY) possesses large bulk proton conductivity and excellent chemical stability, its poor sinterability and grain boundaries block proton conduction. In this work, the effect of Ca as a co-dopant and as a sintering aid (as CaO), on the sinterability, proton conductivity, and fuel cell performance of BZY was investigated. The addition of 4 mol% CaO significantly improved the BZY sinterability: BZY pellets with densities of 92.7% and 97.5% with respect to the theoretical density were obtained after sintering at 1500°C and 1600°C, respectively. The improved BZY sinterability by CaO addition resulted also in a large proton conductivity; at 600°C, the total conductivity of BZY-CaO was 2.14 × 10 -3 S/cm, in wet Ar. Anode-supported fuel cells with 25 μm-thick BZY-CaO electrolyte membranes were fabricated by a dual-layer co-firing technique. The peak power density of the fuel cell with a BZY-Ni/BZY-4CaO/BZY-LSCF (La 0.6Sr 0.4Fe 0.8Co 0.2O 3-δ) configuration was 141 mW/cm 2 at 700°C, several times larger than the reported values of BZY electrolyte membrane fuel cells sintered with the addition of CuO or ZnO, demonstrating promising features for practical fuel cell applications.