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Animal models of pathologic calcification.

Recent progress in genetics and mouse genomics enables researchers to unveil the molecular basis for mouse phenotypes that express pathologic calcification in soft tissue and/or articular tissues. A newly identified multipass transmembrane protein, ANK, appears to function as an inorganic pyrophosphate (PPi) transporter or regulator of PPi transport. Abnormal extracellular PPi (ePPi) metabolism has been implicated in abnormal calcification, decreased concentrations predisposing to basic calcium phosphate (BCP) deposition, and increased concentrations promoting calcium pyrophosphate dihydrate (CPPD) crystal deposition in articular tissues. The chromosomal location of human ANK overlaps the locus identified in several kindreds affected with familial chondrocalcinosis. Deficient generation of ePPi by the ectoenzyme nucleoside triphosphate pyrophosphohydrolase also results in excessive ossification and ectopic deposition of BCP crystals in tiptoe-walking mice and PC-1 null mice. Recent studies reinforce the important regulatory role of ePPi in pathologic and physiologic calcification.

Animals↗

Vitamin-D-dependent calcium-binding-protein and parvalbumin occur in bones and teeth.

Vit-D-Dependent calcium binding protein and parvalbumin have both been detected in ameloblasts and calcified cartilage by immunohistochemical techniques. These two Ca2+ binding proteins may play a crucial role in the local accumulation of Ca2+ ions during the process of mineralization. The mechanisms underlying the deposition of inorganic substances in bone and teeth during physiologic calcification are still the object of intense debate [1, 2]. The hypotheses concerning the factors controlling the initiation of mineralization can be subdivided into three large categories: enzymatic (or non-enzymatic) local elevation of phosphate and calcium [3,4,5,6,7], enzymatic removal of inhibitors of calcification [8] and direct nucleation of CaPO4 crystals on collagen fibrils [9]. In support of the first line of thought we report here the simultaneous occurrence of two different very high affinity Ca2+ binding proteins [vitamin-D-dependent CaBP = VD CaBP and parvalbumin = PV] in bones and teeth. During the studied age period and with immunohistochemical methods, we detected the proteins only in calcified cartilage of bones and in ameloblasts of teeth. We propose that VDCaBP and PV help increase the Ca2+ concentration at the calcification front in some regions involved in mineral deposition.

Animals↗

The effects of proteoglycans from different cartilage types on in vitro hydroxyapatite proliferation.

Proteoglycans extracted from nasal and articular cartilages have previously been shown to inhibit hydroxyapatite proliferation in vitro. This study now demonstrates that proteoglycans isolated (dissociatively extracted and reaggregated in vitro) from bovine fetal growth plate and bovine occipital condyle, as well as those from bovine nasal cartilage, all retard hydroxyapatite seeded-growth in vitro. On a weight basis (1 mg/ml), the growth plate proteoglycan preparation had a significantly greater inhibitory effect. The greater inhibitory effect of the growth plate proteoglycans as compared to the other cartilage proteoglycan preparations may be related to the unique properties of the proteoglycans in the growth plate, a tissue that undergoes physiological calcification.

Animals↗

Dietary instead of pharmacological management to counter the adverse effects of physiological adaptations to space flight.

The development of pharmacological counter-measures to the adverse effects of physiological adaptation to microgravity has received relatively more attention than alternatives such as dietary management. The manipulation of dietary cation-anion balance, and its subsequent effects on acid-base metabolism, have been routinely used for some time in managing domestic animal health. More recently, dietary intake by humans of alkalinizing potassium salts has been demonstrated to exert profound beneficial effects on calcium balance, bone mineralization, predisposition to calcium oxalate nephrolithiasis, and overall nitrogen balance. Dietary sodium restriction has also been shown to improve calcium balance, bone mineralization, and the effectiveness of neurohumoral defenses against orthostatic hypotension. It is proposed that these simple alterations in the astronauts' diets may be easily implemented to lessen the adverse effects of physiological adaptations to space flight, and to enhance or even replace prescribed pharmacological counter-measures.

Acid-Base Equilibrium↗

Long-term sealing ability of a calcium hydroxide sealer.

A calcium hydroxide sealer (Sealapex) was compared with a zinc oxide and eugenol sealer (Tubli-Seal) over a 32-wk interval to examine solubility in an in vitro simulation. After obturation with gutta-percha and the appropriate sealer, specimens were immediately immersed in a saline solution to challenge the sealers' solubility. The solutions were changed weekly to allow for a continued dissolution of the sealers and to prevent establishment of an equilibrium between the solution and the sealers. The 2- and 32-wk specimens were removed from the solutions, immersed in India ink for 3 days, and then made transparent by a clearing process. Microscopic examination was used to determine the linear penetration of the ink for each tooth. Results revealed that Sealapex statistically had no greater dissolution (based upon linear penetration) than Tubli-Seal at both 2 and 32 wk. It is suggested that Sealapex has a sealing ability comparable to Tubli-Seal and can withstand long-term exposure to tissue fluids without significant leakage. This may allow time for the biochemical action of the calcium hydroxide to stimulate physiological calcification of the apical foramen.

Calcium Hydroxide↗

[A histological and ultrastructural study of the tidemark in human condylar cartilage].

OBJECTIVE: To study the histology and ultrastructure of the tidemark in the adult condylar cartilage and their significance. METHODS: After embedded in paraffin, 50 adult condyles were stained with HE, partly with Van-Gieson and histochemical methods, then observed by light microscope. 3 cases of the tidemark region were observed by transmission electron microscope, another 5 cases were studied by scanning electron microscope. RESULTS: In the tidemark region, there had shown the presence of the AKP and calcium, absence of the proteoglycan, abundance of the membrane-bound matrix vesicles, crystals of hydroxyapatite and lipid nodule-like substances, which were often observed in the load-bearing areas. The collagen fibrils of the noncalcified cartilage crossed the tidemark gradiently and were continuous with those of the calcified cartilage; a band of horizontal fibrils surrounded the whole tidemark region, which was wider in the load-bearing areas than that in the nonload-bearing areas and which interweaved with the gradient fibrils so as to form a net. Digested with papain, the surface of the tidemark was highly undulating, and a lot of chondrocyte lacunae were seen on the surface, which were surrounded by calcified tissues. CONCLUSIONS: In the region of the tidemark, physiological calcification takes place and is more active in the load-bearing areas; gradient and horizontal fibrils interweave with each other, which is correlated with the force on the articulation.

Adult↗

Of ghost bodies and calcified globules: a common finding in the perineurium of adult human peripheral nerve.

Ghost bodies and calcified globules were found in the perineurium of three peripheral nerve samples. This is believed to be a rather common change, loosely age-dependent, and unrelated to the presence or absence of nerve pathology. Calcified globules are considered to be none other than so-called ghost bodies, which have evolved and become secondarily permeated with calcium salts. Ghost bodies of the perineurium are considered similar to or the same as the matrix vesicles of physiologic calcification and the analogous profiles of a variety of pathologic conditions.

Adult↗

[Axial computer tomography of the brain].

Computertized tomography of the brain, developed by Hounsfield - has decisively altered neuroradiologic procedures. Without the need of contrast media, cerebral structures (ventricles cisternes, sulci and physiological calcifications) and pathologic lesions (infarctions, hemorrhage, edema, tumors and malformations) may be visualized. Tumors can be diagnosed in 95 to 99% by this method. Tumors of the midline structures and of the posterior fossa are more easily detected than by conventional methods. In head injuries epidural and subdural hematoma, contusional edema and hemorrhage may be differentiated. Hydrocephalus externus and internus can be shown by computertized tomography. Probably computertized tomography will become the most frequently applied neuroradiological method in the future.

Brain↗

Physiological regulation of carbon fixation in the photosynthesis and calcification of coccolithophorids.

Emiliania huxleyi and Gephyrocapsa oceanica are the predominant coccolithophorid species that produce blooms in the ocean and affect the global environment. These species are capable of carbon fixation by both photosynthesis for organic matter production and by intracellular calcification for coccolith production. Both processes were strongly affected by the nutrient status in a laboratory culture. The coccolith production was stimulated by the addition of a high concentration of sodium bicarbonate and by the depletion of phosphate. Interestingly, when the calcification was stimulated, the increase in cell number during algal growth was greatly suppressed and then the cell volume increased. When the growth rate was increased under nutrient-sufficient conditions, the cells became very small in size and most of them bore few or no coccoliths. The data from laboratory experiments show that the cell growth and calcification proceeded apparently independently at different phases. We, therefore, assume that the coccolithophorid blooms in the ocean might be separated into two phases; firstly, the increase in cell population might be triggered by an adequate supply of nutrients to enhance algal growth and then the calcification might subsequently be stimulated when the nutrients become depleted by substantial algal growth.

Calcification, Physiologic↗