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PubMed2003

Surface reactivity of calcium phosphate based ceramics in a cell culture system.

Surface reactivity of Calcium Phosphate materials--Hydroxyapatite (HA), Tricalcium Phosphate (beta-TCP), Hydroxyapatite-Tricalcium Phosphate (HA-TCP) were elucidated in a cell culture system. MG-63 osteoblast-like cells were seeded onto the ceramic discs to evaluate changes in the cell morphology and functionality with respect to the different substrates. The dissolution and re-precipitation of calcium phosphate phases on the surface of the discs in the culture medium was found to be prominent on beta-TCP when compared with HA. Low calcium (Ca), magnesium (Mg) and alkaline phosphatase (ALP) levels and high phosphorous (P) levels in the medium of beta-TCP were observed. This indicated that P must have leached out into the medium from beta-TCP and Ca in turn deposited from the medium onto beta-TCP resulting in the apatite phase transformation. The low ALP activity in beta-TCP medium is however an indication of low osteoblastic activity. Under the phase contrast microscope, the osteoblast cells around HA material were found to be confluent and viable, while in the vicinity of beta-TCP only cellular debris was observed. In the case of HA-TCP, only a few viable cells surrounded the material amidst the debris. Scanning electron microscopy revealed numerous cells on the surface of HA showing different cell behaviour like anchorage, attachment, adhesion and spreading in the early time period as the surface was only slightly disturbed with re-crystallisation. But with time the entire surface of HA had changed due to precipitation and re-crystallization which did not support cell behaviour while the cells surrounding the material showed normal growth. On the contrary, cells were scarcely observed on the entirely changed surface of beta-TCP and HA-TCP even from the earlier days of the culture and the morphology of cells surrounding the material too started changing. These results establish that HA promoted the activity of osteoblast cells. HA surface remained unaltered for some time, while the surface of beta-TCP underwent dissolution of surface ions and resulted in the re-crystallization of apatite over the surface. The resulting changes in the surrounding milieu of beta-TCP with high phosphate and low Ca levels probably was responsible for the death of the cells.

Calcium Phosphates↗
PubMed1982

[Cardiovascular effects of (+)- and (-)-tranylcypromine compared to other monoamine oxidase inhibitors in animal studies (author's transl)].

The effect of (+)- and (-)-tranylcypromine (TCP), (-)-deprenyl and pargyline was tested and the interaction of these MAO inhibitors with tyramine and noradrenaline was compared on the circulation of the cat and on the isolated guinea-pig atria. 1. Anesthetised cats: An i.v. injection of 1 mg/kg of (+)- as well as (-)-TCP leads to an increase in the blood pressure and dp/dtmax. This effect is getting weaker on repeated doses. (-)-Deprenyl and pargyline decrease blood pressure and dp/dtmax. After a preadministration of (+)-TCP or pargyline the effect of tyramine on the blood pressure and contractility is prolonged. (-)-TCP prolongs slightly the cardiac effect of tyramine and is less effective than (+)-TCP. (-)-Deprenyl does not influence the effect of tyramine. The noradrenaline effect is not affected by the MAO-inhibitors. 2. Conscious cats: An i.v. injection of (+)- as well as (-)-TCP increases the blood pressure and decreases the heart rate. Desipramine (DMI) blocks this effect. Preadministration of (+)- as well as (-)-TCP and pargyline, but not (-)-deprenyl, potentiates the effect of tyramine on the blood pressure. According to this activity one can arrange these MAO-inhibitors as follows: (+)-TCP greater than (-)-TCP greater than pargyline. 3. Atrial preparations of guinea pigs: (+)- and (-)-TCP have a positive inotropic effect at concentrations from 10(-6) to 10(-5) mol/l, which is blocked by bupranolol and DMI. A pretreatment with reserpine prevents the effect of (-)- and weakens that of (+)-TCP. (+)-TCP, pargyline and (-)-deprenyl potentiate the effect of tyramine, while that of noradrenaline is potentiated by (+)- as well as (-)-TCP and (-)-deprenyl.

Animals↗
PubMed1988

Role of apical tubules in endocytosis in nonciliated cells of the ductuli efferentes of the rat: a kinetic analysis.

The apical region of nonciliated cells of the ductuli efferentes of the rat contains tubular coated pits (TCP) connected to the apical plasma membrane, apical tubules (AT) which occasionally show a partial coat, and endosomes which are often continuous with one or more apical tubules. To investigate the formation and fate of TCP and AT, a quantitative analysis was performed on the labeling indices of these structures at various time intervals (0.5-120 min) after a single injection of a tracer, cationic ferritin (CF), into the lumen of the rete testis. The labeling indices of both TCP and AT exhibited similar cyclical patterns, first reaching a peak at 25 min, then dropping to a minimum at 35 min, then rising to a second peak at 60 min. Since TCP were well labeled at 30 sec while AT were not, the tracer must rapidly enter TCP and thence AT. However, since tracer was virtually absent from the lumen by 30 min, it was not possible to reconcile the second peak of labeling index of TCP and AT by this mechanism. In another experiment, rats were injected once as before, injected again at 30 min, and then sacrificed at 30 min following the second injection. The results from this experiment showed that the labeling index of TCP and AT did not drop but was similar to that of the 60-min peak after a single injection. The interpretation is that there was recycling of tracer, which had already migrated from TCP to AT to endosomes, back to the apical plasma membrane via apical tubules. Moreover, when rats were injected once, injected again at 30 min, and sacrificed 3 min following the second injection, the labeling index for TCP and AT was significantly higher (P less than .05) than at the 30-min time interval after a single injection, indicating that recycled apical tubules were functionally capable of binding further CF. Morphological observations on images of transition between TCP and AT and the fact that AT were often found connected to endosomes suggest that TCP detach from the cell surface to give rise to AT, which in turn fuse to form endosomes. The kinetic analysis demonstrates in quantitative terms that a portion of the AT, which fuses to form endosomes, recycles back to the apical plasma membrane and contributes to the formation of new TCP.

Animals↗
PubMed2006

Impact of long-term partial aeration on the removal of 2,4,6-trichlorophenol in an initially methanogenic fluidized bed bioreactor.

A fluidized bed bioreactor (FBBR) was operated for more than 1000 days under two regimes, Methanogenic (M) and Methanogenic-Aerobic (M-A), to remove 2,4,6-trichlorophenol (TCP) and phenol (Phe) from a synthetic wastewater, containing different amounts of TCP and Phe, using different aeration flow-rates (0, 2.13, and 1.06 NL O(2)/L.day). M conditions (80:20 mg/L of TCP:Phe, 0 NL O(2)/L.day) showed similar TCP and Phe removal (>95%). Nevertheless accumulation of 4-chlorophenol (4CP) up to 16 mg/L and Phe up to 4 mg/L was observed, while in M-A conditions (80:20 mg/L of TCP:Phe, 2.13 NL O(2)/L.day) TCP and Phe removal achieved 99.9(+)% and after 70 days no accumulation of intermediates were detected. The increase of TCP and Phe in the influent under M-A conditions from 80:20 to 120:30 mg/L of TCP:Phe did not negatively affect the removal of TCP, intermediates and Phe; in fact, they were similar to those in previous M-A conditions. The decrease in the oxygen flow rate from 2.13 to 1.06 NL O(2)/L.day had no negative effect on pollutant removals, which were as high as in previous two M-A conditions. The specific methanogenic activity of bioparticles of the fluidized bed decreased with long-term partial aeration, starting from 1.097 mmol CH(4)/h.g(TKN) in the M regime (day 60) to <0.02 mmolCH(4)/h.g(TKN) at day 1050, suggesting aerobic regime in the bioreactor rather than an M-A regime. In conclusion, complete removal of TCP and less chlorinated intermediates could be achieved in an initially methanogenic FBBR under conditions of partial aeration, although long-term operation seemed to negatively affect the methanogenic activity of biomass. It is also likely that after extended aeration the microbial community was finally enriched with strains with the ability to attack 2,4,6-TCP under aerobic conditions. This report represents the first evidence of a long exposure to oxygen of an anaerobic microbial consortium that efficiently remove TCP.

Air↗
PubMed2004

Bone formation and bioresorption after implantation of injectable beta-tricalcium phosphate granules-hyaluronate complex in rabbit bone defects.

The objective of this study was to evaluate the effects of a complex of beta-tricalcium phosphate (beta-TCP) granules and 3.5% hyaluronate (beta-TCP granules-HY complex) compared with a beta-TCP block, in terms of osteoconductivity and biodegradability, to determine whether this complex would be a good candidate for bone void filler. Both materials were implanted into cavities drilled in rabbit femoral condyles. New bone formation and mineral apposition rate were evaluated to analyze osteoconductivity, whereas residual beta-TCP within the defects and tartrate-resistant acid phosphatase (TRAP) cellular activity were studied for beta-TCP resorption. The results show that both the beta-TCP block and the beta-TCP granules-HY complex support bone ingrowth; however, bioresorption was rapid for beta-TCP granules-HY but weak for beta-TCP block. This biodegradation mechanism was considered to be a cell-mediated disintegration by numerous TRAP-positive giant cells. The time lag between the peak value of TRAP-positive giant cell population and that of new bone formation rate suggests that a coupling-like phenomenon could be occurring in the beta-TCP-filled bone defects. In addition, beta-TCP granules-HY complex, which is an injectable, pastelike material, has similar osteoconductive properties to beta-TCP block. Thus, this complex may be useful as a bone filler in clinical application.

Absorbable Implants↗
PubMed1995

Expression of the axolotl homologue of mouse chaperonin t-complex protein-1 during early development.

Molecular chaperones assist in the folding of proteins, but their role during development is not well understood. Here we report the temporal and spatial expression pattern of the axolotl homologue of mouse chaperonin TCP-1 during normal amphibian embryogenesis and in several models of abnormal embryogenesis. A partial axolotl TCP-1 cDNA (646 bp; 519 coding bp) isolated by 3' RACE PCR shows considerable homology to mouse TCP-1. Developmental Northerns and RT-PCR analyses of whole axolot1 embryos revealed a low level of maternal TCP-1 transcripts in fertilized eggs. The maternal transcripts were down-regulated to a non-detectable level in early gastrulae. Zygotic TCP-1 transcripts first appeared during gastrulation. They were mainly expressed in mid-neurula and later stage embryos. Whole-mount in situ hybridization studies showed abundant TCP-1 transcripts in the blastopore at the mid-gastrula stage and in the brain and spinal cord beginning at the neurula stage, and in the somites (myotomes) at the tailbud stage. RT-PCR analysis of TCP-1 expression in axolotl embryos treated with either high salt (causing exogastrulation) or ultraviolet (UV) irradiation (causing ventralization) substantiated the correlation between TCP-1 expression and neural and somitic development. In high salt-induced exogastrulated embryos TCP-1 mRNA was detectable in the ectoderm part (with neural tissues) but not in its exogastrulated endoderm part. Lower levels of TCP-1 expression were detected in UV-irradiated, ventralized embryos with smaller head and reduced neural and somitic tissues. Normal levels of TCP-1 expression were detected in embryos with double axes/heads. These studies provide strong evidence that at the transcript level axolotl chaperonin TCP-1 is regulated both temporally and spatially during embryogenesis, especially in neural and somitic development.

Ambystoma↗
PubMed2005

Ectopic osteoinduction and early degradation of recombinant human bone morphogenetic protein-2-loaded porous beta-tricalcium phosphate in mice.

The present study investigated the ectopic osteoinduction and early degradation of recombinant human bone morphogenetic protein-2 (rhBMP-2)-loaded porous beta-tricalcium phosphate (beta-TCP) in mice. The porous beta-TCP with 50 microg of rhBMP-2 (n = 25) and porous beta-TCP (control group, n = 25) were implanted into muscle pouches in the right and left thigh of 28-day-old mice (n = 25), respectively. At every time point (3, 7, 14, 21 and 28 days after implantation), five mice were euthanized and the histological examinations of implantation sites were performed. In addition, the alkaline phosphatase (ALP) activity was also quantitatively analyzed. For the rhBMP-2-loaded group, blood vessel formation and immature cartilage was observed within the porous beta-TCP 3 days after implantation. Mature cartilage was observed 7 days after implantation of rhBMP-2-loaded porous beta-TCP. Newly formed woven bone, lamellar bone as well as marrow were observed 14 and 21 days after implantation of the rhBMP-2-loaded porous beta-TCP. Lamellar bone and marrow were observed 28 days after implantation of the rhBMP-2-loaded porous beta-TCP. For the control group, no bone or cartilage was observed at all time points. However, multinucleated giant cells and fibrous tissues were observed in the control group at 7 and 28 days after implantation, respectively. At 21 and 28 days after implantation, porous beta-TCP was observed to fragment indicating early degradation of the porous beta-TCP in both groups. In addition, ALP was observed to be significantly higher in the rhBMP-2-loaded beta-TCP as compared to the control beta-TCP. It was concluded from this study that the rhBMP-2-loaded porous beta-TCP induced blood vessel and ectopic bone formation.

Absorbable Implants↗
PubMed2001

The required number of treatment imaging days for an effective off-line correction of systematic errors in conformal radiotherapy of prostate cancer--a radiobiological analysis.

BACKGROUND AND PURPOSE: To use radiobiological modelling to estimate the number of initial days of treatment imaging required to gain most of the benefit from off-line correction of systematic errors in the conformal radiation therapy of prostate cancer. MATERIALS AND METHODS: Treatment plans based on the anatomical information of a representative patient were generated assuming that the patient is treated with a multi leaf collimator (MLC) four-field technique and a total isocentre dose of 72 Gy delivered in 36 daily fractions. Target position variations between fractions were simulated from standard deviations of measured data found in the literature. Off-line correction of systematic errors was assumed to be performed only once based on the measured errors during the initial days of treatment. The tumour control probability (TCP) was calculated using the Webb and Nahum model. RESULTS: Simulation of daily variations in the target position predicted a marked reduction in TCP if the planning target volume (PTV) margin was smaller than 4 mm (TCP decreased by 3.4% for 2 mm margin). The systematic components of target position variations had greater effect on the TCP than the random components. Off-line correction of estimated systematic errors reduced the decrease in TCP due to target daily displacements, nevertheless, the resulting TCP levels for small margins were still less than the TCP level obtained with the use of an adequate PTV margin of approximately 10 mm. The magnitude of gain in TCP expected from the correction depended on the number of treatment imaging days used for the correction and the PTV margin applied. Gains of 2.5% in TCP were estimated from correction of systematic errors performed after 6 initial days of treatment imaging for a 2 mm PTV margin. The effect of various possible magnitudes of systematic and random components on the gain in TCP expected from correction and on the number of imaging days required was also investigated. CONCLUSIONS: Daily variations of target position markedly reduced the TCP if small margins were used. Off-line correction of systematic errors can only partly compensate for these TCP reductions. The adequate number of treatment imaging days required for systematic error correction depends on the magnitude of the random component compared with the systematic component, and on the size of PTV margin used. For random components equal to or smaller than the systematic component, 3 consecutive treatment imaging days are estimated to be sufficient to gain most of the benefit from correction for current clinically used margins (6-10 mm); otherwise more days are required.

Humans↗
PubMed1991

[Preventive effect of post-ischemic reperfusion injury by terminal Nicorandil-Mg cardioplegia].

In this study, we evaluated the postischemic myocardial tissue blood flow, specific enzymes, and functional recovery infused with a Nicorandil vasodilator-magnesium solution (Nico.: 8 mg/L, Mg: 20 mEq/L) given just prior to reperfusion (Terminal Cardioplegia, TCP). 27 patients undergoing valve replacement were divided into two groups; the hearts of group non-TCP (nTCP) (n = 15) were reperfused after ischemia without TCP, and in the other hearts of group TCP (n = 12), TCP was given for 2 min prior to reperfusion. During the reperfusion period, myocardial tissue blood flow (TBF) on the anterior wall of left ventricle were monitored by a laser blood flow-meter. Thereafter, serum CK-MB levels, MM3/MM1 values by CK-MM subbands (MM1, MM2, MM3) levels and LVSWI were measured until 24 hours after surgery. At 5 and 10 min of reperfusion, Group TCP had a significantly greater TBF than Group nTCP (5 min; G-TCP: 69.9 +/- 19.0 ml/100 g.min, G-nTCP: 47.5 +/- 20.9, p less than 0.05, 10 min; G-TCP: 74.9 +/- 22.8, G-nTCP: 56.1 +/- 23.4, p less than 0.05). At 3 hrs after surgery, an increase of MM3/MM1 values was significantly suppressed in Group TCP compared to Group nTCP (G-TCP: 2.6 +/- 0.6, G-nTCP: 3.4 +/- 1.0, p less than 0.05). Also, Group TCP had better recovery of LVSWI. These results indicate that the TCP might reduce the postischemic reperfusion injury by the improvement of myocardial TBF and metabolism.

Heart Arrest, Induced↗
PubMed2005

Effect of acidic pretreatment combined with a silane coupling agent on bonding durability to silicon oxide ceramic.

This study examined the effect of different acidic treatments and the role of a phosphate monomer in a silane coupling agent on the durability of the dual-cure resin cement/silicon oxide bond. Ceramic blocks (Vita Celay Blanks) were cut into multiple 3 mm-thick slices and polished using 600 grit SiC paper. Two pairs were left untreated [controls (CTRL)], two pairs were treated with 40% phosphoric acid and rinsed with water for 30 s (PA), and another two pairs treated with 20% hydrofluoric acid followed by 30 s water rinsing (HF). Half the specimens were silanated with Tokuso Ceramics Primer (TCP) (Tokuyama) and the other half with TCP formulated without phosphate monomer (TCP-NoPM). All the pairs were bonded with Bistite II dual-cure resin cement (Tokuyama) and light cured. After 24 h water storage at 37 degrees C, 0.7 mm-thick slabs were serially sectioned. Immediately, after 6 months and after 1 year of water storage, two slabs were randomly selected from each subgroup, and sliced into beams (6 x 0.7 x 0.7 mm) for the microtensile bond strength (muTBS) test. The muTBS data were statistically analyzed using multiple Wilcoxon Signed Rank tests (p < 0.05). Failure modes were determined using a confocal laser-scanning microscope. Ceramic surface morphology after the different acidic treatments was examined using an SEM. After 1 day, in the case of silane treatment with TCP, there were no significant differences in muTBS between the control and acid-treated groups (p > 0.05), whereas with TCP-NoPM, the muTBS of the control was significantly lower than the acid-treated groups (p < 0.05). All the TCP and acid-treated TCP-NoPM groups exhibited significant reductions in muTBS after 6 months (p < 0.05). After 1 year, the muTBS of the acid-treated TCP groups were not significantly different from the control TCP group (p > 0.05). There was also no significant difference between the HF-treated TCP and TCP-NoPM groups (p > 0.05) after 1 year, all exhibiting greater than 10 MPa tensile bond strength. It is suggested that acidic pretreatment of the ceramic surface does not improve the durability of the dual-cure resin cement/silicon oxide ceramic bond when an acidic phosphate monomer is present as an activator in a ceramic primer.

Acid Etching, Dental↗
PubMed2007

Histological and histomorphometrical comparative study of the degradation and osteoconductive characteristics of alpha- and beta-tricalcium phosphate in block grafts.

The purpose of the present study was to compare alpha- and beta-tricalcium phosphate (TCP) as bone graft material for augmenting highly resorbed alveolar ridges. The cranial bones of 15 rabbits were used. Three titanium chambers filled with porous blocks of alpha-TCP, beta-TCP, or blood clots were placed in each slit. The two TCP blocks had similar inner/outer structures and purities. Animals were sacrificed after 2, 4, and 8 weeks. Specimens were embedded in polyester resin as nondecalcified specimens, and evaluated both histologically and histomorphometrically. In both TCP groups, blocks had hardly degraded at 2 weeks while in the alpha-TCP group, the block had notably started degrading after 4 weeks. In the beta-TCP group, degradation began at 4 weeks and this degradation had increased just slightly after 8 weeks. The alpha-TCP block degraded significantly more than the beta-TCP block. Residual alpha-TCP particles surrounded by newly formed bone decreased over time, and both particles and newly formed bone were simultaneously absorbed by osteoclast-like cells. These observations suggest that residual alpha-TCP particles surrounded by newly formed bone may disappear progressively from bone and could be incorporated into the bone remodeling cycle in combination with newly formed bone.

Absorbable Implants↗
PubMed1987

Examination of the reproductive effects of tricresyl phosphate administered to Long-Evans rats.

Tricresyl phosphate (TCP) is used commercially as a plasticizer and a flame retardant. The reproductive effects of TCP (less than 9.0% TOCP) were examined. Male Long-Evans rats received 0, 100, or 200 mg/kg and females received 0, 200, or 400 mg/gk TCP in corn oil by gavage. The 100 mg/kg TCP males were mated with 200 mg/kg TCP females, and 200 mg/kg TCP males were bred with 400 mg/kg TCP females. Males were dosed for 56 days and females for 14 days prior to breeding and throughout the 10-day breeding period. Following breeding, the males were necropsied and evaluated for sperm parameters and reproductive tract histopathology. Females were dosed throughout gestation and lactation. Pups and adult females were necropsied on postnatal day 21. Sperm concentration, motility, and progressive movement were decreased for 200 mg/kg dose group males. A dose-dependent increase in abnormal sperm morphology was observed for males in both TCP dose groups. The percent of sperm-positive females per group was unchanged, but the number of females delivering live young was severely decreased by TCP exposure. Litter size and pup viability were decreased in the 400 mg/kg dose group. Pup body weight and developmental landmarks were unaffected by TCP exposure. Histopathologic changes were observed in the testes and epididymides of male rats and in the ovaries of female rats exposed to TCP.

Animals↗
PubMed2004

Dose-volume conundrum for response of prostate cancer to brachytherapy: summary dosimetric measures and their relationship to tumor control probability.

PURPOSE: Although it is known that brachytherapy dose distributions are highly heterogeneous, the effect of particular dose distribution patterns on tumor control probability (TCP) is unknown. It is unlikely that clinical results will throw light on the question in the near future, given the long follow-up and detailed dosimetry required for each patient. We used detailed dose distribution data from 50 patients combined with radiobiologic parameters consistent with what is known about TCP curves for prostate cancer to study the changes in TCP that accompany gross dosimetric measures and particular dosing irregularities (e.g., moderate underdosing of large volumes vs. extreme underdosing of small volumes). METHODS AND MATERIALS: For each of the 50 patients with organ-confined prostate cancer who had undergone 125I prostate implants alone at our clinic, postimplant CT scans were obtained approximately 1 month after implantation. Dose distribution information was obtained from postimplant dosimetry. The percentage of the prostate volume receiving a specified dose was recorded from the respective differential dose-volume histograms in 10-Gy bins. In addition, the percentage of prostate volume underdosed at varying fractions of the prescription dose were determined, as was the minimal prostate dose. The log-normal distributions of the radiobiologic parameters [ln(initial clonogen number), alpha, and alpha/beta] were adjusted so that the predicted population parameters (steepness and location) of the dose-response curves for external beam radiotherapy agreed with the published estimates. The variability in the dose-volume details was increased by scaling the dose distributions by factors ranging from 0.7 to 1.5, thereby simulating, for each of the patients, nine new patients with different total doses but identical relative distributions of the dose over the voxels. Radiobiologic variability between the selected dose distributions was then removed by averaging >50 randomly chosen sets of radiobiologic parameters from the log-normal distributions to estimate the TCP for each of the dose distributions, giving some insight into the TCP variations with conventional dosimetric indexes and different patterns of underdosing. RESULTS: Using the 450 dose distributions created by expanding the 50-patient data set, the volume of the prostate that was extremely underdosed (between 50% and 70% of the prescription dose) was related to the volume that was moderately underdosed (between 80% and 100% of the prescription dose). We found that the individual TCP is greatly dependent on the inhomogeneous dose distribution and the dosimetric indexes, such as the volume of prostate receiving 100% of the prescribed dose (V100) and the maximal dose received by 90% of the prostate volume (D90), which, by themselves, are not always accurate predictors of control probabilities. In a multivariate analysis of the dependence of TCP on these parameters (V100, D90, minimal dose, and moderately and severely underdosed volumes), only D90 and the minimal dose were statistically significant. Generally speaking, however, a lower minimal dose means a lower TCP. CONCLUSION: The work described here was an hypothesis-generating study. Our results showed that even if the V100 and D90 are nearly identical for 2 patients, there can be (and frequently are) significant differences in the dose distributions in the subvolumes of the prostate. Under simulated dose-response conditions (i.e., with variations in the dose distribution), the D90 and minimal dose significantly affected the TCP but the V100 and the volumes moderately or severely underdosed did not. In general, one must consider the totality of the dose distribution to evaluate the dosimetric quality of a low-dose-rate prostate implant. TCP is not a monotonic function of extreme or moderate underdosing. In some instances, extreme underdosing of relatively small volumes may result in a greater TCP than moderate underdosing of relatively large volumes and vice versa.

Brachytherapy↗
PubMed1997

Beta-cell function and insulin sensitivity in tropical calcific pancreatitis from north India.

Tropical calcific pancreatitis (TCP) is a variant of chronic pancreatitis, occurring only in developing countries. It frequently leads to diabetes at a young age. To determine the pathogenesis of glucose intolerance, beta-cell function and insulin sensitivity were measured in 11 TCP patients with normal glucose tolerance (TCP-NGT), six TCP patients with mild hyperglycemia [TCP-DM] median fasting plasma glucose, 6.1 mmol/L), and 16 healthy control subjects. The technique of continuous infusion of glucose with model assessment (CIGMA) was used to calculate beta-cell function (%B) and insulin sensitivity (%S), based on plasma glucose and insulin levels achieved after an intravenous infusion of glucose. %S was similar in both groups of TCP patients and controls. In contrast, %B was significantly lower in TCP-DM patients (median, 53; interquartile range, 41 to 62) compared with controls (90; 65 to 143; P < .01) and with TCP-NGT patients (119; 91 to 159; P < .01). TCP-NGT and control subjects had similar beta-cell function. Among patients with TCP, %B negatively correlated with the duration of pancreatitis (r = -.63, P < .05). Our results suggest that patients with TCP develop diabetes due to a diminution in beta-cell function, and that insulin resistance does not play a significant role in its pathogenesis.

Blood Glucose↗
PubMed2003

Structure and composition of silicon-stabilized tricalcium phosphate.

Silicon stabilized tricalcium phosphate [Si-TCP] is formed within the calcium hydroxyapatite (HA)-tricalcium phosphate (TCP) system when a stoichiometric precipitate of hydroxyapatite is fired at 1,000 degrees in the presence of SiO(2). This paper proposes a composition range and crystallographic structure for Si-TCP. Reitveld XRD powder diffraction, transmission electron microscopy, infrared and proton nuclear magnetic resonance measurements show that crystalline Si-TCP is associated with the displacement of OH from an initial hydroxyapatite structure. The resulting calcium phosphate is modified by the incorporation of silicon into its structure with excess silica contributing to an amorphous component. Si-TCP has a monoclinic structure with a space group P2(1)/a akin to alpha-TCP with estimated lattice constants of a=12.863+/-0.004 A, b=9.119 +/-0.003 A, c=15.232+/-0.004 A, beta=126.3+/-0.1 degrees. It is proposed that Si(4+) substitutes for P(5+)in the TCP lattice with the average chemical composition of Si-TCP set primarily by the mechanisms available for charge compensation. While the formation of OH vacancies in HA initiates the transformation to Si-TCP, two mechanisms of charge compensation in the Si-TCP structure are plausible. If O(2-) vacancies provide charge compensation, the composition of Si-TCP is Ca(3)(P(0.9)Si(0.1)O(3.95))(2) derived for the addition of 0.33 mol SiO(2):mol HA. If excess Ca(2+) compensates, the composition is Ca(3.08)(P(0.92)Si(0.08)O(4))(2) derived for the addition of 0.25 mol SiO(2):mol HA. The reaction occurs most effectively when SiO(2) is added as a colloidal suspension rather than by the in-situ thermal decomposition of a silicon metallorganic compound. The material is a bioceramic of major biological interest because of its osteoconductivity and unique influence on skeletal tissue repair and remodeling.

Absorption↗
PubMed1997

Reduced tissue oxygenation and its reversibility by glycemic control in diabetic patients.

Relationship of transcutaneous oxygen pressure (TcP(O2)) to glycemic control and diabetic complications was investigated in patients with non-insulin dependent diabetes mellitus. TcP(O2) was measured in 103 patients with non-insulin dependent diabetes mellitus. Correlation of TcP(O2) to HbA1c, fasting blood sugar (FBS), age, duration of diabetes, serum lipids, hypertension, and diabetic complications were examined. We divided the patients into three groups according to their glycemic control: good control group (HbA1c < 7.0%), fair control group (HbA1c, 7.0-8.9%) and poor control group (HbA1c > or = 9.0). We compared TcP(O2) of these three groups with 19 non-diabetic controls. In 103 patients, TcP(O2) at baseline correlated with HbA1c, FBS and age (P < 0.001, P < 0.01 and P < 0.05, respectively), but did not correlate with duration of diabetes mellitus, neuropathy, nephropathy or retinopathy. TcP(O2) of good and fair control group was not reduced comparing to the non-diabetic control (63 +/- 11, 59 +/- 10 and 64 +/- 12 mmHg, respectively). The poor control group had significantly reduced TcP(O2) (55 +/- 10 mmHg) comparing to non-diabetic control (P < 0.005) and good control group (P < 0.005). Furthermore, in an independent study, TcP(O2), arterial oxygen pressure (Pa(O2)), oxygen pressure of dorsal pedal vein (PV(O2)) and erythrocyte 2,3-diphosphoglycerate (2,3-DPG) in eight patients with poor glycemic control were followed prospectively. Six patients with improvement of glycemic control showed a significant increase of TcP(O2) and Pa(O2) (P < 0.001 and P < 0.005, respectively). However, two patients without improvement of hyperglycemia had no change in TcP(O2) and Pa(O2). PV(O2) and 2,3-DPG levels of erythrocytes were not changed in six patients. These findings suggest that tissue oxygenation in diabetic patients was deteriorated in relation to hyperglycemia and was reversed with glycemic control. Improvement of Pa(O2) might contribute partly to the increase of TcP(O2).

2,3-Diphosphoglycerate↗
PubMed1999

Initial anchoring and proliferation of fibroblast L-929 cells on unstable surface of calcium phosphate ceramics.

Calcium phosphate ceramics constructed from beta-tricalcium phosphate (TCP) and hydroxyapatite (HAP) have been successfully used as implant materials. However, there is a possibility that these materials are responsible for an unwanted inflammatory response during wound healing. Since TCP is soluble in the body, the instability of this material may contribute to this inflammatory response. Using composite ceramics of TCP and HAP that possessed Ca/P molar ratios of 1.50, 1.55, 1.60, 1.64, and 1.67, the effect of surface instability on fibroblast L-929 cells was investigated. The time-dependent variation of the initial anchoring ratio, cell density, and cell viability were measured. In general, the cells were severely damaged and ruptured on the highly soluble thin surface layer of the TCP-HAP ceramics. The initial anchoring ratio for TCP-HAP ceramics was as high as that for the polystyrene dish (Lux, control). However, viability at 6 h decreased to less than 50% of the initial cell density on ceramics with a Ca/P molar ratio of 1.64 (20% TCP-80% HAP), while 85% of the cells were viable on Lux. The viability on 100% TCP, whose surface is the most highly soluble among the TCP-HAP ceramics used in this study, was reduced to 20%. Morphological observation showed that the anchored cells were ruptured when grown in culture medium on the 100% TCP. Although the high solubility of the thin surface layer on the TCP-HAP ceramics of the carrier was found to be the dominant factor in the decreasing cell viability, the initial viability was enhanced by the stabilization of the surface of the TCP-HAP ceramics by pre-incubating the scaffolds in a culture medium containing 10% fetal bovine serum for 3 d.

Journal Article↗
PubMed2003

Idiopathic tumefactive chronic pancreatitis: clinical profile, histology, and natural history after resection.

BACKGROUND & AIMS: Little is known about subjects with idiopathic tumefactive chronic pancreatitis (TCP), that is, chronic pancreatitis whose clinical presentation, usually with a mass or obstructive jaundice, suggests cancer. METHODS: We independently reviewed clinical data and histology of 45 TCP (27 idiopathic, 18 alcohol induced) resected at Mayo Clinic (January 1985-March 2001). Follow-up data were obtained from medical records and mailed questionnaires. RESULTS: Compared with alcoholic subjects, idiopathic TCP patients were older (58 +/- 2 vs. 48 +/- 3 yr, P < 0.001), had shorter symptom duration (median 3 vs. 24 wk, P < 0.001), were more likely to have no or mild abdominal pain (70% vs. 17%, P = 0.001), and were more often jaundiced (67% vs. 33%, P = 0.02). Three distinct histologic patterns were identified in TCP. Typical CP (n = 19) showed lobular atrophy, fat necrosis, and ductal changes (dilatation, protein plugs, and stones). Lymphoplasmacytic sclerosing pancreatitis (LPSP) (n = 14) was characterized by periductal lymphoplasmacytic infiltration, obliterative phlebitis, and cholangitis with edema. Idiopathic duct-centric CP (IDCP) (n = 12) had neutrophil-predominant lobular inflammation, without phlebitis. On correlation of clinical and histologic diagnosis, 17 of 18 (94%) patients with alcohol-induced TCP had typical CP, and 25 of 27 (93%) with idiopathic TCP had LPSP or IDCP. LPSP and IDCP were indistinguishable clinically except for higher incidence of jaundice in LPSP (93% vs. 42%, P = 0.005). In idiopathic TCP no recurrence of symptoms was observed after resection (median follow-up 49 mo). CONCLUSIONS: Idiopathic TCP is clinically and histologically distinct from alcohol-induced TCP. It is unclear whether LPSP and IDCP, 2 unique patterns of histologic injury observed in idiopathic TCP, are part of the spectrum of the same disease or represent 2 or more different entities. Resection of mass prevents recurrence of symptoms in idiopathic TCP.

Bile Ducts↗