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Insect blood meal studies using radiosodium 24Na and 22Na.

Rabbits were infused with 3.7 GBq (100 mCi) of [24Na]Na ion in a 100-ml sodium carbonate solution. Beta particles were detected using a Tennelec Counting System; background counts were 1.6 +/- 1 counts per minute (cpm). Counts for one nanoliter of blood ranged from 22 to 30 cpm. Blood volumes on the mouthparts of tabanids following a 15-sec interrupted feeding were estimated to be 12.5 nl for Tabanus fuscicostatus, 10.8 nl for T. nigrovittatus and 6.12 nl for Chrysops fuliginosus. Estimates of the quantity of blood adhering to 22-gauge needles and insect pins (size 2) following a percutaneous intramuscular needle-stick were 8.8 +/- 1.0 nl and 5.7 +/- 1.8 nl, respectively. Mosquitoes, Aedes aegypti females, were fed to repletion with a 22Na-artificial diet, and radioactivity was measured using a Packard Autogamma 5650. The estimated average blood meal size was 2.80 +/- 0.94 microliters.

Aedes↗

Radon update: facts concerning environmental radon: levels, mitigation strategies, dosimetry, effects and guidelines. SNM Committee on Radiobiological Effects of Ionizing Radiation.

The risk from environmental radon levels is not higher now than in the past, when residential exposures were not considered to be a significant health hazard. The majority of the radon dose is not from radon itself, but from short-lived alpha-emitting radon daughters, most notably 218Po(T1/2 3 min) and 214Po (T1/2 0.164 msec) along with beta particles from 214Bi (T1/2 19.7 min). Radon gas can penetrate homes from many sources and in various fashions. Measuring radon in homes is simple and relatively inexpensive and may be accomplished in a variety of ways. Although it is not possible to radon-proof a house, it is possible to reduce the level. In high radon areas, if the average level is higher than 4-8 pCi/liter (NCRP recommended level is 8 pCi/liter; EPA recommended level is 4 pCi/liter), appropriate action is advised. The shape of the dose response curves for miners exposed to alpha-emitting particles in the workplace is consistent with current biologic knowledge. It is linear in the low dose range and saturates in the high dose range. No detectable increase in lung cancer frequency is seen in the lowest exposed miners (those with exposures < 120 WLM, the relevant dose interval for most homes). Evidence for a health effect from radon exposure is based on data from animal studies and epidemiologic studies of mines. Extensive radiobiologic data predict a linear dose-response curve in the low dose region due to poor biological repair mechanisms for the high density of ionizing events that alpha particles create. However, no compelling evidence for increased cancer risks has yet been demonstrated from "acceptable" levels (< 4-8 pCi/liter).

Air Pollutants↗

Bone marrow transplantation in dogs after radio-ablation with a new Ho-166 amino phosphonic acid bone-seeking agent (DOTMP).

beta-emitting 166Ho (t1/2 = 26.78 hours, E(beta)max = 1.8 MeV) complexed with the phosphonic acid chelator, 1,4,7,10 tetraazacyclododecane-1,4,7,10-tetra(methylene phosphonic acid) (DOTMP) at a ligand-to-metal ratio of 1.5:1 binds to bone. This radioactive complex is a marrow-ablating radiopharmaceutical that appears useful for preparation of bone marrow (BM) transplant recipients without the morbidity usually associated with total body irradiation preparatory regimens. We have found with seven splenectomized young adult beagle dogs that a 166Ho radiopharmaceutical dosage of 370 MBq/kg body weight provides an initial skeletal radioactivity burden of at least 1.5 GBq/kg skeleton and results in complete ablation of hematopoietic marrow cell populations within 7 days. The beta particle flux distribution in BM-forming skeletal tissue is not uniform. Red marrow radiation doses varied from 30 to 115 Gy as estimated by direct radioassay and autoradiographic analyses of both bone biopsies and postmortem samples; the median value of 61 Gy agreed with our theoretical expectations. In vivo radioactivity distribution was evaluated with nuclear imaging methods. Apparently, normal hematopoiesis was restored in three dogs with autologous BM transplants performed 5 to 6 days after administration of the marrow ablative radiopharmaceutical, 166Ho-DOTMP. BM biopsies at 7 to 10 months posttransplantation indicate continued normal hematopoietic activity.

Animals↗

[Radiosynovectomy with dysprosium-165 iron hydroxide].

Treatment of chronic rheumatoid synovitis (RS) is directed to control the inflammatory process causing pain and disability. Radiation synovectomy is suggested to be an alternative to surgical treatment, but its clinical use has been restricted because of significant leakage (> 10%) associated with the use of the standard radionuclide 90-Yttrium (used as 90-Yttrium silicate colloid) and because of its long physical half-life of 64 hours prolonging the patients' stay in the hospital. 165-Dysprosium possesses promising nuclear properties for the treatment of patients suffering from RS. The maximum soft tissue penetration of its beta-particles is 5.7 mm which is the range being necessary to penetrate the inflamed synovia. Using as carrier ferric hydroxide macroaggregates (DFH) 165-Dy is expected to minimize the cumulative radiation dose to non-target organs by its very low leakage. Animal studies were performed in 13 rats and 6 rabbits to obtain the rationale and safety data for its clinical evaluation. These studies revealed that 98.2 +/- 0.6% of the injected dose remained in the joint with a nontarget organ uptake of less than 0.1%. Clinical results were obtained from 8 patients with rheumatoid arthritis. 24 hours after injection scintigraphy was performed over the treated joint and the liver region revealing no detectable leakage of the injected activity from the joint. Blood pool activity was also assessed revealing a leakage of 0.02% of the dose injected in the knee 24 hours after injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Biological effects of inhaled 144CeCl3 in beagle dogs.

The biological effects of 144Ce were studied in beagle dogs that were exposed to graded activity levels of 144CeCl3 via a single, brief inhalation exposure and observed for their life span. The long-term retained body burdens ranged from 0.06 to 13 MBq/kg with a median of 1.2 MBq/kg. After a short residence time in the lung, most of the 144Ce was translocated to liver and skeleton, where the 144Ce was retained with a half-time approaching the physical half-life of 144Ce, 284 days. Significant radiation doses were delivered to the lung, 28 Gy (median) and 2.5-370 Gy (range); liver, 68 Gy (median) and 6.1-250 Gy (range); and skeleton, 21 Gy (median) and 1.9-100 Gy (range). Lesions induced by the beta-particle radiation were noted in the lung, liver, skeleton, bone marrow, and oral and nasal mucosae closely associated with bone. Early deaths (within 2.5 years) were generally related to hematological dyscrasia, radiation pneumonitis, or hepatocellular degeneration and atrophy. Neoplasms that occurred relatively early, from 2.2-6.8 years after exposure, were noted in the liver, bone, bone marrow and oral mucosa closely associated with bone. Neoplasms that occurred later, beyond 7 years after exposure, were noted in the liver, lung and nasal mucosa closely associated with bone. Increased numbers of neoplasms were not found in two other organs that had relatively high radiation doses, namely the thyroid and kidney. Only one primary bone tumor was noted, but 11 tumors of bone-associated tissues (oral and nasal mucosae and bone marrow) were found. Radiation doses and effects in tissues adjacent to bone, especially those of epithelial or marrow origin, should be considered when determining risks from internally deposited bone-seeking radionuclides, such as 144Ce. The property of 144Ce in depositing on and remaining associated with bone surfaces for long times may be an important factor in the radiation dose to bone marrow and epithelium adjacent to bone.

Administration, Inhalation↗

Comparison of copper-67- and iodine-125-labeled anti-CEA monoclonal antibody biodistribution in patients with colorectal tumors.

UNLABELLED: Copper-67 has comparable beta-particle emissions to that of 131I, but it displays more favorable gamma emission characteristics for application in radioimmunotherapy (RIT). This study investigates the potential of 67Cu-labeled monoclonal antibody (MAb) 35 for RIT of colorectal carcinoma. METHODS: Biokinetics of simultaneously injected 67Cu- and 125I-labeled MAb35 were studied in six patients scheduled for surgery of primary colorectal cancer. RESULTS: Whole-body clearance (T 1/2) of 67Cu, estimated from sequential anterior and posterior whole-body scans and corrected for decay of 67Cu, was 41 hr. Serum clearance of 67Cu was faster (27.41 hr) than that of 125I (38.33 hr). Mean tumor uptake of the 67Cu-labeled compound (0.0133% ID/g) exceeded that of 125I (0.0095% ID/g), and tumor-to-blood ratios were higher for 67Cu than for 125I, with averages of 6.07 and 2.41, respectively. The average 67Cu/125I ratio was 1.9 for tumor uptake, 0.7 for blood and 2.6 for tumor-to-blood ratios. Nonspecific liver uptake of 67Cu as calculated from whole-body scans was high in four patients, up to 25% of residual whole-body activity at 48 hr, but did not increase with time. We also observed some nonspecific bowel activity, as well as moderate to high uptake in benign polyps. CONCLUSION: Copper-67-labeled MAb35 is more favorable than its radioiodine-labeled counterpart for RIT of colorectal carcinoma due to higher tumor-to-blood ratios, but the problem of nonspecific liver and bowel uptake must first be overcome. The absolute accumulation of activity in tumor remains low, however, so the probability of cure with this compound alone is questionable. The use of 67Cu as one component of a multimodality adjuvant treatment seems to remain the most appropriate application for RIT.

Aged↗

The role of strontium-89 systemic radiotherapy in the management of osseous metastases from prostate cancer.

Strontium-89 systemic radiotherapy can play a significant role in the palliation of symptomatic osseous metastases from prostate cancer. Given as a single injection, strontium's affinity for osteoblastic activity draws it to all sites of osseous involvement simultaneously. The metastases are bathed with beta-particles whose short range in tissues spares the surrounding normal structures. This article will review the rationale, physiology, and patient selection criteria for its use. Approximately 80% of patients will respond to treatment as documented by the authors experience and by a review of the literature.

Adult↗

Rhenium-188(Sn)HEDP for treatment of osseous metastases.

UNLABELLED: Rhenium-188 (tin) hydroxyethylidine diphosphonate [188Re(Sn)HEDP] is a new radiopharmaceutical that localizes in skeletal metastases and emits beta particles that may be therapeutically beneficial. METHODS: It was evaluated by in vitro and in vivo testing in the laboratory, in animals and in humans using 188Re from a variety of sources. It may be produced by a desk-top method developed previously for 186Re(Sn)HEDP using 188Re produced through neutron irradiation of either enriched 187Re or naturally occurring rhenium targets or the use of a 188W/188Re generator. RESULTS: So long as the mass of rhenium in the 188Re-perrhenate to be processed into 188Re(Sn)HEDP is at least 100 microg, satisfactory radiochemical yields and purity may be obtained by all methods. The 188Re(Sn)HEDP has biodistribution and radiation dosimetry characteristics that are similar to those noted previously for 186Re(Sn)HEDP and appears to result in similar benefits and toxicities in patients with skeletal metastases. External radiation exposure monitoring indicates that, only 4 hr after a therapeutic administration of 1110 MBq (30 mCi) of 188Re(Sn)HEDP, average exposure rates at 1 meter from the patient would be only 0.5 mR/hr. CONCLUSION: Same-day, on-demand, outpatient therapy of disseminated skeletal metastases appears to be feasible with 188Re(Sn)HEDP.

Aged↗

Effects of radiolysis on yttrium-90-labeled Lym-1 antibody preparations.

UNLABELLED: The physical half-life of 2.6 days and 2.2 MeV beta emissions of 90Y provide excellent properties for radioimmunotherapy applications. However, the clinically useful beta particles may be a source of radiation-induced damage of 90Y-labeled immunoconjugate radiopharmaceuticals during preparation or short-term storage. The stability of 90Y-labeled Lym-1 antibody was studied in standard radiopharmacy conditions to establish a formulation at which radiolysis is not a problem. METHODS: Lym-1-21T-BAD immunoconjugate intermediate was prepared according to our standard procedure, then labeled with 90Y at 1, 2, 4 and 9.4 mCi/mg Lym-1 using 0.5 M tetramethylammonium acetate, pH 7, labeling buffer. Each mixture was challenged in diethylenetriaminepentaacetic acid to remove nonspecifically bound 90Y. The 90Y-21T-BAD-Lym-1 products were purified by centrifuged molecular sieving column chromatography. The radiochemical purity and immunoreactivity of each preparation was monitored daily by high-performance liquid chromatography (HPLC) and solid-phase radioimmunoassay, respectively, for 3 days. The preparation at 2 mCi/mg was also formulated in 4% (wt/vol) human serum albumin (HSA) overall and at 9.4 mCi/mg in five-fold water, 4 and 10% (wt/vol) HSA overall; all were monitored as above. RESULTS: The monomeric quality and purity profile of products at 1 and 2 mCi/mg were retained (> or = 80%) as was their immunoreactivity (> or = 75%) over 3 days. The radiochemical purity and immunoreactivity of the product at 4 mCi/mg declined to 65% and 28%, respectively, by 3 days after preparation and in just 48 hr, the product at 9.4 mCi/mg had degraded to 21% in radiochemical purity with only 3% immunoreactivity. The current HPLC data and earlier published chromatographic evidence did not support a compromised radiochemical integrity of 90Y-DOTA complexes by loss of 90Y from the DOTA chelate. CONCLUSION: Radiolysis of 90Y-labeled antibody preparations did not appear to be a problem at 90Y-21T-BAD-Lym-1 products < or = 2 mCi/mg. Human serum albumin proved to be an effective radioprotectant as the initial 100% immunoreactivity of the product at 2 mCi/mg was retained for 72 hr. The results underscore the need for appropriate formulations and dilutions of clinical doses of 90Y immunopharmaceuticals immediately after manufacture.

Antibodies, Monoclonal↗

Toxicity of inhaled 91YCl3 in dogs.

This study was conducted in dogs to determine the toxicity of inhaled 91YCl3, which is of interest because 91Y is a fission-product radionuclide that is abundant in a reactor inventory after sustained operation. Yttrium-91 has a short half-life, 59 days, and decays with the emission of beta particles and low-yield gamma rays. The study was conducted in 58 beagle dogs with equal numbers of males and females. Forty-six dogs inhaled the 91YCl3 aerosol, while 12 served as controls. Four exposure levels were used. To determine the long-term retained burden (LTRB) of 91Y, each dog was periodically whole-body counted and its excreta were analyzed radiochemically. Over time, the 91Y transferred from the lung primarily to the skeleton and liver. The dogs were observed over their life spans for biological effects. Fatal hematological dyscrasia occurred from 12 to 33 days after exposure in the dogs with the highest LTRBs. Bone-associated tumors of the nasal and oral mucosae occurred in 5 dogs from 2000 to 5800 days after they inhaled the 91YCl3 aerosols. Five dogs died with malignant lung tumors and 2 dogs with malignant liver tumors. The results of this study were compared to those from similar studies in beagles that inhaled 90SrCl2 or 144CeCl3 or were injected with 137CsCl. The comparison showed that the biological effects in each study were clearly dependent on the cumulative doses to critical organs.

Administration, Inhalation↗

Intratumoral injection of rhenium-188 microspheres into an animal model of hepatoma.

UNLABELLED: Intratumoral injection of 90Y microspheres is a potential alternative in the treatment of primary liver tumor. However, complicated preparation and lack of a gamma ray for imaging are the disadvantages of 90Y. In this study, we used 188Re, a generator-produced radioisotope with 155-keV gamma ray emission, to label microspheres. After intratumoral injection of 188Re microspheres into rats with hepatoma, biodistributions and survival times were analyzed. METHODS: Twelve male rats with hepatoma were killed at 1, 24 and 48 hr (4 rats at each time point) after intratumoral injection of approximately 7.4 MBq 188Re microspheres. Samples of various organs were obtained and used to calculate the tissue concentrations. In addition, 30 male rats bearing hepatoma were divided into two groups (15 rats in each group) to evaluate survival time. Group 1 received intratumoral injection of 37 MBq 188Re microspheres, whereas Group 2 served as the control group and received an intratumoral injection of 0.1 ml normal saline only. Survival time was calculated from the day of injection to 2 mo after treatment. RESULTS: Radioactivity in the tumor was very high throughout. Biological half-time was 170.8 hr. Radioactivity in the lung was 1.78% injected dose (i.d.)/g at 1 hr but declined rapidly over time. The concentration in the urine was approximately 6.14% i.d./ml after the first hour and rapidly declined thereafter. The concentrations of radioactivity in other organs, such as normal liver, muscle, spleen, bone, testis and whole blood, were quite low throughout the study. Twelve of 15 (80%) of rats survived over 60 days after intratumoral injection of 188Re microspheres, whereas only 4 of 15 (26.7%) survived more than 60 days after injection of normal saline only. The difference between the groups was significant (p < 0.05). CONCLUSION: Rhenium-188 offers cost-effectiveness, on-site availability, short half-life, energetic beta particle, emission of gamma photons for imaging, easy preparation, easy clinical administration and apparent lack of radiation leakage from the treated tumor. Direct intratumoral injection of 188Re microspheres is extremely attractive as a clinical therapeutic alternative in hepatoma patients.

Animals↗

[Electron microscopic study of glycogen granules in the epithelial cells of human endometrial glands].

At the early secretory stage of the menstrual cycle part of glycogen granules in the human endometrial glandular cells are limited with threelayered membranes 6--9 nm thick. Transitional forms between the above mentioned granules and vesicles derived from the Golgi cisterns were found. On moving away from the Golgi apparatus the density of these granules with the membranes disappearing, thus suggesting that the Golgi apparatus of the human endometrial glandular cells may give rise to beta-particles of glycogen, whose polysaccharid nature is confirmed by amylase digestion.

Adult↗

Fractal analysis of beta-cyclodextrin-indomethacin particles compacted by ultrasound.

An association between indomethacin and beta-cyclodextrin (beta-CD) was obtained by compacting a 1:2 molar physical mixture by ultrasound. The product prepared by this technique was compared with the initial physical mixture and with materials having the same composition but prepared by a simple compaction and kneading process. The samples examined by scanning electron microscopy revealed morphological differences related to the methods of preparation. In particular the material obtained by ultrasound had a smooth surface and on milling produced particles of uniform size; moreover EDAX analysis (energy dispersion analysis by X-rays) also revealed a homogeneous distribution of the two components in each particle examined. Surface fractal dimension of the surface of these particles is very low, suggesting the presence of a regular and smooth surface whereas the sample obtained by kneading had a higher value. The reactive dimension related to dissolution was much higher than the corresponding surface dimension in all cases and had comparable values for all samples regardless of the techniques used. This behavior was attributed to the hydrophilicity of beta-CD, which levels the differences during dissolution and which could be originated by surface imperfections. Experimental results suggested that the material obtained by ultrasound had a dissolution rate comparable to that measured with the kneaded material. The use of ultrasound, however, can both reduce the production time and improve the homogeneity of the association between indomethacin and beta-CD.

Cyclodextrins↗

Messenger RNA processing and nuclear structure: isolation of nuclear ribonucleoprotein particles containing beta-globin messenger RNA precursors.

To explore the relationships between transcription, messenger RNA (mRNA) processing, and nuclear structure, ribonucleoprotein particles containing heterogeneous nuclear RNA (hnRNP) have been purified from globin-producing mouse Friend erythroleukemia cells. These nuclear hnRNP particles sediment at 50S-200S and contain, in addition to high molecular weight hnRNA, a specific set of nuclear proteins predominated by a major component of approximately 38,000 mol wt. The hnRNP particles are free of histones and ribosomal structural proteins, indicating their purification from the two other major nucleoprotein components of the nucleus: chromatin and nucleolar ribosomal precursor RNP particles. Th authenticity of the Friend cell hnRNP particles is demonstrated by the results of reconstruction experiments with deproteinized hnRNA, and by the resistance of the articles to dissociation during isopycnic banding in Cs2SO4 gradients without prior aldehyde fixation. Hybridization analysis with cloned mouse beta-globin DNA demonstrates that hnRNP particles from induced Friend cells contain newly synthesized transcripts of the beta-globin gene. Agarose gel electrophoresis of hnRNP particle-derived RNA denatured in glyoxal followed by "Northern" transfer to diazobenzyloxymethyl paper and hybridization with 32P-labeled cloned mouse beta-globin DNA reveals the presence in hnRNP of two size classes of beta-globin gene transcripts, the larger of which corresponds to the pre-spliced 15S beta-globin mRNA precursor previously identified in whole nuclear RNA, and the smaller of which corresponds to completely processed 9S beta-globin mRNA. These results establish, for the first time, that the nuclear transcripts of a specific, well-defined eukaryotic structural gene can be isolated in an RNP particle form, and that their RNP structure persists throughout mRNA splicing.

Animals↗

Nucleotide-dependent binding of the GTPase domain of the signal recognition particle receptor beta-subunit to the alpha-subunit.

The signal recognition particle (SRP) receptor (SR) is a heterodimer of two polypeptides (SRalpha and SRbeta) that each contain a GTP-binding domain. The GTP-binding domain in the peripheral membrane SRalpha subunit has a well defined role in regulating targeting of SRP-ribosome-nascent chain complexes to the translocon. The only well established function for the transmembrane SRbeta subunit is anchoring SRalpha on the endoplasmic reticulum membrane. Deletion of the amino-terminal transmembrane domain of SRbeta did not affect receptor dimerization, but revealed a cryptic translocation signal that overlaps the GTPase domain. We demonstrate that the domain of SRalpha that binds SRbeta does so by binding directly to the nucleotide-bound form of the GTPase domain of SRbeta. An SRbeta mutant containing an amino acid substitution that allows the GTPase domain to bind XTP dimerized with SRalpha most efficiently in the presence of XTP or XDP, but not ATP. Our results suggest an additional level of regulation of SRP receptor function based on regulated dissociation of the receptor subunits.

Amino Acid Sequence↗

Partial isolation of two classes of dopamine beta-hydroxylase-containing particles undergoing rapid axonal transport in rat sciatic nerve.

The rapid bidirectional transport of dopamine beta-hydroxylase (DBH) in adrenergic axons provides a means of analyzing the life cycle of adrenergic storage vesicles. We compared the physical characteristics of DBH-containing particles traveling to or returning from the terminal varicosities of ligated rat sciatic nerves. Density gradient centrifugation and Sephacryl S1000 gel-permeation chromatography were used to fractionate extracts from nerve segments proximal or distal to the ligatures. A series of experiments indicated the existence of at least two populations of rapidly transported DBH-containing particles, a "light" 85-nm particle and a larger "dense" 120-nm particle. The 85-nm particles were prevalent in unligated nerve, but accounted for only one-third of the total anterogradely transported DBH activity accumulated after 18 h. The 120-nm particles were barely detectable in the unligated nerve, but they accumulated at twice the rate of the 85-nm particles and accounted for the rest of the anterogradely transported particulate DBH activity. These two populations of particles were readily isolated from proximal nerve extracts by sucrose density gradient centrifugation. Similar-appearing dense and light peaks of particulate DBH activity were obtained from distal nerve extracts. Much of the retrogradely transported DBH of the extracts, however, was associated with large particles (greater than 300 nm) not resolved by Sephacryl S1000. Retrogradely transported exogenous NGF was found only in the dense sucrose gradient peak. We propose that the 85-nm DBH-containing particles correspond to "large dense-cored vesicles," and that the 120-nm particles are derived from the dense tubules visualized in adrenergic nerves by the chromaffin reaction.

Animals↗

Direct determination of 90Sr and 147Pm in Chernobyl hot particles collected in Kiev using beta absorption method.

59 hot particles were collected in Kiev, Ukraine, in 1987. All but one were prepared from a moss carpet of 360 cm2 area. Radionuclide composition of the hot particles was investigated by gamma-spectrometry and beta absorption method. Pure beta emitters 90Sr and 147Pm were determined in 25 hot particles measuring the beta absorption curves of the hot particles with an end-window Geiger-Müller counter and decomposing the curves in order to obtain the contributions of 90Sr and 147Pm to the total beta counting rate. All but one of the hot particles were found to be the debris of the fuel. The activity ratio 90Sr:l44Ce was 0.052 in good agreement with theoretical calculations on core inventories. This means that strontium behaved as a nonvolatile element in the process of the formation of the hot particles investigated. The activity ratio 147Pm:144Ce was 0.078 which is half of the theoretical result. Although 147Pm is considered to be a refractory nuclide, it seems that significant part of 147Pm went to the homogeneous fraction of the general fallout. The surface density of hot particles (of higher than about 50 Bq activity) was about 1,600 m(-2) and that of the activities of the nuclides 90Sr, 106Ru, 134Cs, 137Cs, 144Ce and 147Pm as components of hot particles was 12.2, 54.3, 5.9, 9.7, 234 and 18.3 kBq m(-2) (activity values counted for 26 April 1986), respectively, in downtown Kiev city in 1987.

Beta Particles↗

Localisation of osteogenic and osteoclastic cells in porous beta-tricalcium phosphate particles used for human maxillary sinus floor elevation.

We and others have shown earlier that porous beta-tricalcium phosphate (TCP) (Cerasorb) can be used in patients to augment the maxillary sinus floor prior to placement of oral dental implants. To better understand the transformation of TCP particles into bone tissue, we analyse here the appearance of cells with osteogenic or osteoclastic potential in relation to these particles. In biopsies taken at 6 months after sinus floor augmentation we observed bone growth into the TCP particles but also replacement by soft connective tissue. To identify possible osteoprogenitor cells in this tissue, histological sections were immunostained with an antibody to Runx2/Cbfa1, an essential and early transcription factor for osteoblast differentiation. The osteogenic potential of cells was further confirmed by immunostaining for bone sialoprotein (BSP) and osteopontin (OPN). Other sections were stained for Tartrate Resistant Acid Phosphatase (TRAP) activity to identify cells with osteoclastic capacity. Runx2/Cbfa1 positive connective tissue cells were found in abundance throughout and around the TCP particles, even at a distance of several millimetres from the maxillary bone surface. About 95% of the cells found within TCP particles stained positive for Runx2/Cbfa1. Fewer cells stained positive for BSP and OPN, suggesting more mature osteoblastic properties. Mono- and binucleate TRAP-positive cells, but no multinucleate TRAP-positive osteoclasts, were found in the soft tissue infiltrating the TCP and at the surface of the TCP particles. Both the Runx2/Cbfa1 positive and the TRAP-positive cells decreased apically with increasing vertical distance from the maxillary bone surface. This data suggests that the TCP particles attract osteoprogenitor cells that migrate into the interconnecting micropores of the bone substitute material by 6 months. The lack of large multinucleate TRAP positive cells suggests that resorption of the TCP material by osteoclasts plays only a minor role in its replacement by bone. Chemical dissolution, possibly favoured by a high cell metabolism in the particles, seems the predominant cause of TCP degradation. The abundance of Runx2/Cbfa1 positive cells would indicate that with a greater time of healing there will be further bone deposition into these particles.

Bone Substitutes↗