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Role of phosphophoryn in dentin mineralization.

Mineral deposition is essential for the development of hard tissues like bone and teeth. In matrix-mediated mechanisms responsible for dentin formation, type I collagen defines the framework for mineral deposition and by itself is not sufficient to support nucleation of hydroxyapatite. However, in the presence of non-collagenous proteins, nucleation sites have been identified within the hole regions of the fibrils, and at these sites, mineral crystals can grow and propagate. Non-collagenous proteins constitute 5-10% of the total extracellular matrix proteins. They are embedded within the mineral deposits, suggesting a possible interaction with the mineral phase. During dentin formation, phosphophoryn (PP), an abundant macromolecule in the extracellular matrix, can initiate mineral deposition in localized regions by matrix-mediated mineralization mechanism. In our work, we have demonstrated that PP, due to its highly phosphorylated post-translational modification, can bind calcium ions with high affinity and at the same time aggregate collagen fibrils at the mineralization front. Molecular modeling has further demonstrated that the spacing of the carboxyl and phosphate groups present on PP might be essential for dictating the crystal orientation relative to the collagen substrate. Thus, PP may provide the interface linkage between mineral crystal and collagen fibrils.

Animals↗

The effect of mineral-derived zinc ions on in vitro glucose metabolism of Streptococcus mutans NCTC 10449.

Mouthrinses containing zinc ions inhibit plaque acidogenicity, but the effect is transient. Zinc-containing apatite or zinc phosphate precipitated within dental plaque might serve as a reservoir for zinc ions, thus providing prolonged inhibition of acid formation. Zinc-containing fluorhydroxyapatite was prepared from solutions containing CaCl2, KH2PO4, NaF and increasing amounts of ZnCl2 (0.0, 0.005, 0.02, 0.1, 0.2 or 1 mM; minerals No. 1-6, respectively) by raising the pH with ammonia. Zinc phosphate tetrahydrate (mineral No. 7) was prepared in a similar manner from a solution containing ZnCl2 and KH2PO4 only. Dense cell suspensions of Streptococcus mutans NCTC 10449 were incubated with 14C-glucose and one of the test minerals (No. 1-7). Glycolysis was allowed to proceed, with or without pH control, in a pH-stat. Samples were withdrawn at 1, 2, and 3 min, and extracellular glycolytic metabolites were identified by HPLC. Mineral No. 7 inhibited glycolysis and any pH fall almost completely. With the pH fixed at 5.5, reduction of glucose consumption and lactate formation was 83 and 93%, respectively, compared to the no-zinc control mineral (No. 1). No changes in glucose consumption or lactate formation were evident in the presence of minerals No. 2-6. All apatitic minerals had a buffering effect and, in the absence of pH control, glycolysis was increased due to the higher pH. Detectable levels of fluoride were not released by any mineral into the incubation mixture, and zinc only by minerals No. 6 and 7 in greater than trace amounts.(ABSTRACT TRUNCATED AT 250 WORDS)

Acids↗

Effects of ethnicity and age or menopause on osteoblast function, bone mineralization, and osteoid accumulation in iliac bone.

We measured histologic indices of osteoblast function, bone mineralization, and osteoid accumulation separately on the cancellous, endocortical, and intracortical subdivisions of the endosteal envelope and on the combined total surface in transiliac biopsies obtained after double tetracycline labeling in 142 healthy women, aged 20-74 years, 34 who were black (19 pre- and 15 postmenopausal) and 108 white (42 pre- and 66 postmenopausal). The data were subjected to two-way analysis of variance of the four groups defined by age/menopause and ethnicity. Also, linear regressions of selected variables on age and between functionally related but independently measured variables were examined. None of the interaction terms was significant, and none of the regression slopes on age differed between blacks and whites, indicating that, as for the previously reported structural and remodeling indices, the effects of ethnicity and of age/menopause are independent. Accordingly, the data were analyzed separately for the effects of ethnicity (pre- and postmenopausal combined) and age/menopause (blacks and whites combined). The analyses led to the following conclusions (1) Osteoid surface and volume were higher and adjusted apposition rate and osteoid mineralization rate lower in postmenopausal than in premenopausal subjects, but none of the indices of osteoid accumulation differed between blacks and whites. (2) Each index of osteoid accumulation was significantly correlated with its primary independently measured kinetic determinant (osteoid thickness with adjusted apposition rate, osteoid surface/bone surface with activation frequency, and osteoid volume/bone volume with bone formation rate/bone volume). None of the regression parameters differed significantly between blacks and whites. (3) The ratio of mineralizing surface to osteoid surface (MS/OS) was substantially lower in all demographic groups than could be accounted for by the later onset of mineralization than of matrix apposition at individual bone forming sites. (4) The low values for MS/OS can be explained by terminal mineralization being too slow to trap enough tetracycline molecules to produce detectable fluorescence, and do not require that mineralization be interrupted. (5) MS/OS was about 25% lower in blacks than in whites on all surfaces with corresponding differences in derived indices based on MS/OS, including adjusted apposition rate, mineralization lag time, and formation period. (6) The lower values for MS/OS in blacks are most likely due to slower terminal mineralization. This could not be accounted for by a lower serum level of calcidiol, but is consistent with the reported effect of reduced bone blood flow. (7) All differences in bone cell function between blacks and whites that we have observed could be the result of the ethnic, and presumably genetic, difference in bone accumulation during growth. Higher bone mass would result in less fatigue microdamage, less need for repair by directed bone remodeling, lower bone turnover, lower bone blood flow, and slower terminal mineralization. (8) If this explanation is correct, there are no fundamental differences in the biology of bone remodeling between ethnic groups.

Adult↗

Regional and hormone-dependent effects of apolipoprotein E genotype on changes in bone mineral in perimenopausal women.

We studied 479 perimenopausal Danish women aged 45-58 years to examine differences between APOE genotypes with respect to (1) baseline total body bone mineral density (BMD) and densities measured in five different regions (ultradistal forearm, proximal forearm, lumbar spine, femoral neck, and total hip region); (2) serum levels of alkaline phosphatase, bone isoenzyme alkaline phosphatase, osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D, and urine hydroxyproline/creatinine excretion ratio; and (3) changes in bone mineral during 5 years of follow-up. Baseline BMDs were identical, whereas serum levels of alkaline phosphatase and its bone isoenzyme were higher in women with APOE 2-2 and APOE 2-3 than in women with APOE 3-3 and APOE 3-4 and lower in women with APOE 4-4. Among women not receiving hormonal-replacement therapy (HRT; n = 262), those with APOE 2-2 and APOE 2-3 had 30-40% lower rates of femoral neck and total hip bone mineral loss than women with APOE 3-3 and APOE 3-4, whereas the rates of mineral loss in other skeletal regions did not differ between these APOE genotypes. Women with APOE 4-4 appeared to have lower rates of bone mineral loss in all regions. Women treated with hormones throughout the follow-up period (n = 113) gained bone mineral, and women with APOE 3-4 and APOE 4-4 gained relatively more mineral than other women. A comparison of untreated and treated women with APOE 2-3, APOE 3-3, and APOE 3-4 suggests a possible modification of the effect of APOE genotype by HRT. In conclusion, the common APOE polymorphism has a complex effect on bone metabolism in perimenopausal Danish women including possible modification by hormone use: (1) among women not receiving HRT, those with APOE*2 have lower bone mineral losses in the femoral neck and hip region than other women, and (2) among women receiving HRT, those with APOE*4 gain more bone mineral than other women.

Alkaline Phosphatase↗

Bone morphogenetic protein-2 restores mineralization in glucocorticoid-inhibited MC3T3-E1 osteoblast cultures.

UNLABELLED: The anti-glucocorticoid potential of BMP-2 in osteoblasts was tested in MC3T3-E1 cells using dexamethasone (1 microM) and rhBMP-2 (10 or 100 ng/ml). rhBMP-2 restored mineralization but not condensation or collagen accumulation. These results demonstrate the potential and limitations of BMPs in counteracting glucocorticoids. INTRODUCTION: Pharmacologic glucocorticoids (GCs) inhibit osteoblast function and induce osteoporosis. Bone morphogenetic proteins (BMPs) stimulate osteoblast differentiation and bone formation. Here we tested the anti-glucocorticoid potential of BMP-2 in cultured osteoblasts. MATERIALS AND METHODS: MC3T3-E1 cells were treated with dexamethasone (DEX; 1 microM) and/or recombinant human BMP-2 (rhBMP-2; 10 or 100 ng/ml). Culture progression was characterized by cell cycle profiling, biochemical assays for DNA, alkaline phosphatase (ALP), collagen, and calcium, and by reverse transcriptase-polymerase chain reaction (RT-PCR) of osteoblast phenotypic mRNAs. Mineralization was characterized by Alizarin red and von Kossa staining and by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). RESULTS: DEX inhibited differentiation-related cell cycle, nodule formation, collagen accumulation, osteocalcin, and BMP-2 gene expression as well as mineralization. Replenishment of GC-inhibited cultures with 10 or 100 ng/ml rhBMP-2 dramatically rescued mineral deposition. The rhBMP-2-rescued mineral was bone-like apatite nearly identical to the mineral of control cultures. The rhBMP-2 rescue was associated with increased mRNA levels for alpha1(I) collagen, osteocalcin, and Cbfa1 types I and II, as well as ALP activity. In contrast, rhBMP-2 did not rescue the GC-inhibited differentiation-related cell cycle, nodule formation, or collagen accumulation. When administered alone, rhBMP-2 also increased the mRNA levels for alpha1(I) collagen, osteocalcin, and Cbfa1 types I and II, as well as ALP activity. However, treatment with rhBMP-2 alone inhibited cell cycle progression, nodule formation, and collagen accumulation. Surprisingly, in contrast to its rescue of mineralization in DEX-treated cultures, rhBMP-2 inhibited mineralization in the absence of DEX. In parallel to its bimodal effect on mineralization, rhBMP-2 stimulated endogenous BMP-2 mRNA in the presence of DEX, but inhibited endogenous BMP-2 mRNA in the absence of DEX. CONCLUSIONS: Suppression of BMP-2 gene expression plays a pivotal role in GC inhibition of osteoblast differentiation. However, the inability of rhBMP-2 to rescue the entire osteoblast phenotype suggests BMP-2-independent inhibitory effects of CCs. BMP-2 exerts both positive and negative effects on osteoblasts, possibly depending on the differentiation stage and/or the existing BMP signaling.

Animals↗

Abnormalities in bone mineral density and bone histology in thalassemia.

UNLABELLED: This study demonstrated that there was extensive iron staining on trabecular surface and marked reduction in trabecular bone volume without significant alteration in bone formation and bone resorption rates as well as significant reduction in bone mineral density in 18 thalassemic patients. Serum IGF-I was reduced and may modulate the reduction of bone mass. INTRODUCTION: Bone histomorphometric studies in thalassemia to show alterations in bone histology and their relationship to biochemical parameters are very limited. Therefore, this study was systematically conducted to determine the alterations in thalassemia patients. METHODS: Serum biochemical parameters, trans-iliac crest bone biopsy, and determination of bone mineral density of femur and lumbar spine were done in 18 thalassemic patients (10 females and 8 males). RESULTS: Serum osteocalcin, carboxy terminal teleopeptide fragment of type I collagen, and parathyroid hormone levels were within normal limits, but serum 25(OH) vitamin D (19.3 +/- 1.6 ng/ml) and 1,25(OH)2 vitamin D (33.77 +/- 1.51 pg/ml) levels were decreased. Serum insulin-like growth factor I (IGF-I; 145.2 +/- 20 ng/ml) was suppressed, whereas serum ferritin (1366.6 +/- 253.9 ng/ml) was markedly elevated. Reduced bone mineral density was found in all studied areas. Trabecular bone volume was significantly decreased (16.65 +/- 1.12%), whereas bone formation rate, eroded surface, and other bone histomorphometric parameters were within normal limits. The trabecular bone volume varied significantly with bone mineral density of total femur (r = 0.48, p = 0.04). There was an extensive stainable iron surface on the mineral front (9-60%). Significant correlation between serum IGF-I, serum ferritin, stainable iron surface, and bone mineral density, lumbar spine, and total femur were found. Serum IGF-I correlated with trabecular bone volume (r = 0.6, p = 0.03), inversely with both serum ferritin level (r = -0.6, p < 0.01), and inversely with stainable iron surface (r = -0.53, p = 0.02). Multiple regression analysis demonstrated that IGF-I was the only independent variable that determined bone mineral density of lumbar spine and total femur. CONCLUSION: Low bone mineral density and reduced trabecular bone volume with extensive iron deposition are the predominant findings in thalassemic patients. There was no evidence of increased bone resorption or mineralization defect. A reduction in circulatory IGF-I may modulate the reduction of bone mass.

Adult↗

Tenofovir disoproxil fumarate and an optimized background regimen of antiretroviral agents as salvage therapy: impact on bone mineral density in HIV-infected children.

OBJECTIVE: Tenofovir disoproxil fumarate, a nucleotide analog HIV reverse transcriptase inhibitor with demonstrated activity against nucleoside-resistant HIV, is approved for use in adults but not children. Metabolic bone abnormalities have been seen in young animals given high-dose tenofovir and HIV-infected adults that were treated with oral tenofovir disoproxil fumarate. However, tenofovir disoproxil fumarate is being used in children despite a lack of bone safety data. We hypothesized that, given the higher rate of bone turnover that is associated with normal skeletal growth, the potential for TDF-related bone toxicity may be greater in children than in adults. METHODS: Fifteen highly antiretroviral-experienced HIV-infected children who were 8 to 16 years of age (mean +/- SD: 12 +/- 2) and required a change in therapy received tenofovir disoproxil fumarate 175 to 300 mg/m2 per day (adult dose equivalent) as part of highly active antiretroviral therapy for up to 96 weeks. Bone mineral density of the lumbar spine, femoral neck, and total hip by dual-energy x-ray absorptiometry and blood and urine markers of bone metabolism were measured at 0, 24, 48, 72, and 96 weeks. RESULTS: Median z score (SD score compared with age, gender, and ethnicity-matched control subjects) of the lumbar spine, femoral neck, and total hip were decreased from baseline at 24 weeks and 48 weeks and then stabilized. Lumbar spine bone mineral apparent density (which estimates volumetric bone mineral density independent of bone size) z scores also decreased at 24 weeks. Absolute decreases in bone mineral density were observed in 6 children; the mean age of these children was significantly younger than the bone mineral density stable group (10.2 +/- 1.1 vs 13.2 +/- 1.8 years). The change in lumbar spine bone mineral density correlated with decreases in HIV plasma RNA during treatment. Metabolic markers of bone formation and resorption were variable. Two children in whom tenofovir disoproxil fumarate was discontinued because of bone loss that exceeded protocol allowances demonstrated partial or complete recovery of bone mineral density by 96 weeks. CONCLUSIONS: Tenofovir disoproxil fumarate use in children seems to be associated with decreases in bone mineral density that, in some children, stabilize after 24 weeks. Increases in bone markers and calcium excretion suggest that tenofovir disoproxil fumarate may stimulate bone resorption. Bone turnover is higher in children than in older adolescents and adults because of skeletal growth, potentially explaining the greater effect seen in young children. Decreases in bone mineral density correlate with decreases in viral load and young age, suggesting that young responders may be at greater risk for bone toxicity.

Adenine↗

Age-related bone loss: relationship between age and regional bone mineral density.

We assessed the changes in regional bone mineral density according to age and examined the relationship between various regional bone mineral densities. The study was conducted in 985 Japanese women divided into < 50-years group (n = 435) and > or = 50 years group (n = 550). The total body bone mineral density and that of the head, arm, leg, thoracic (T)-spine, lumbar (L)-spine, ribs, and pelvis were measured using dual energy x-ray absorptiometry. There was a significant generalized reduction of bone mineral density in all regions after the age of 50 years. The most marked age-related decrease was observed in the L-spine. Bone mineral densities in all regions significantly correlated to each other in both age groups, but the degree of significance varied among regions. The relationship between bone mineral density of the L-spine and that of T-spine regions was the most significant in both groups. In the < 50-years group, the correlation between bone mineral density of the pelvis and that of L-spine and T-spine was the highest, followed by that between the pelvis and the leg. On the other hand, in the > or = 50-years group, the correlation between bone mineral density of the pelvis and that of the leg was the highest, but not the L-spine or T-spine. Since spine measurements are affected by vertebral deformity and/or aortic calcification, our findings suggest the pelvis may be a useful region for screening measurements of bone mineral density, especially in older women.

Absorptiometry, Photon↗

The effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty.

BACKGROUND: Bone mineral density around the knee is related to the mechanical properties of bone. Alendronate has been shown to be effective for the treatment of osteoporosis and for reducing the rate of osteoporotic fractures. The purpose of the present study was to investigate the effect of alendronate on bone mineral density in the distal part of the femur and proximal part of the tibia after total knee arthroplasty in women. METHODS: Ninety-six women with an average age of seventy years who were undergoing total knee arthroplasty were randomly divided into two groups. Patients in the study group received oral alendronate at a dose of 10 mg/day for six months, whereas patients in the control group did not. The bone mineral density in the distal part of the femur and proximal part of the tibia was determined preoperatively and at six and twelve months postoperatively. RESULTS: In the control group, the bone mineral density showed significant decreases of 13.8% (p < 0.001) and 7.8% (p = 0.003) in the distal part of the femur and of 6.5% (p = 0.002) and 3.6% (p = 0.141) in the proximal part of the tibia at six and twelve months, respectively. In the study group, however, the bone mineral density showed significant increases of 10.0% (p = 0.010) and 1.9% (p = 0.049) in the distal part of the femur and of 9.4% (p < 0.001) and 5.4% (p = 0.032) in the proximal part of the tibia at six and twelve months, respectively. The overall differences in bone mineral density between the study and control groups were significant (p = 0.011 for the proximal part of the tibia, and p = 0.033 for the distal part of the femur). CONCLUSIONS: We found significant postoperative decreases in bone mineral density in the distal part of the femur and proximal part of the tibia in women who had undergone total knee arthroplasty. Oral administration of alendronate for six months postoperatively significantly improved the bone mineral density. While the clinical benefits of alendronate after total knee arthroplasty remain unproven and the duration of follow-up in the present study was quite short, the improvement in bone mineral density may have a clinically important effect on prosthetic fixation and the rate of periprosthetic fractures after total knee arthroplasty.

Absorptiometry, Photon↗

Three-year changes in bone mineral density around the knee after a six-month course of oral alendronate following total knee arthroplasty. A prospective, randomized study.

BACKGROUND: Bone mineral density decreases after total knee arthroplasty and is believed to affect prosthetic fixation. Treatment with alendronate has been shown to improve short-term bone mineral density after total knee arthroplasty; however, the long-term effects of this therapy are unknown. The purpose of this study was to evaluate the long-term effects of a six-month course of alendronate on bone mineral density after total knee arthroplasty. METHODS: Sixty patients were randomly assigned to receive either oral alendronate at a dosage of 10 mg/day for six months or no alendronate. The bone mineral density in the distal aspect of the femur and the proximal aspect of the tibia was measured preoperatively and at six, twelve, and thirty-six months after total knee arthroplasty. RESULTS: Fifty-four patients (twenty-nine in the alendronate group and twenty-five in the control group) completed the study. The alendronate group showed significant increases in bone mineral density in the distal aspect of the femur compared with the controls at six months (+4.8% and -14.2%, respectively; p < 0.01) and twelve months (+1.6% and -11.5%, respectively; p < 0.01). No significant difference in bone mineral density was detected between the groups at thirty-six months (-3.9% and -12.2%, respectively; p = 0.08). Similar trends in bone mineral density changes were also observed in the proximal aspect of the tibia. CONCLUSIONS: A six-month course of alendronate initially increased bone mineral density at six and twelve months after total knee arthroplasty, but no difference was noted after thirty-six months. The effect of alendronate on bone mineral density after total knee arthroplasty may be limited after discontinuation of therapy.

Administration, Oral↗

Potential mineralization of four herbicides in a ground water--fed wetland area.

Herbicides may leach from agricultural fields into ground water feeding adjacent wetlands. However, only little is known of the fate of herbicides in wetland areas. The purpose of the study was to examine the potential of a riparian fen to mineralize herbides that could leach from an adjacent catchment area. Slurries were prepared from sediment and ground water collected from different parts of a wetland representing different redox conditions. The slurries were amended with O2, NO3-, SO4(2-), and CO2, or CO2 alone as electron acceptors to simulate the in situ conditions and their ability to mineralize the herbides mecoprop, metsulfuron-methyl, isoproturon and atrazine. In addition, the abundance of bacteria able to utilize O2, NO3-, SO4(2-) + CO2, and CO2 as electron acceptors was investigated along with the O2-reducing and methanogenic potential of the sediment. The recalcitrance to bacterial degradation depended on both the type of herbicide and the redox conditions pertaining. Mecoprop was the most readily degraded herbicide, with 36% of [ring-U-14C]mecoprop being mineralized to 14CO2 under aerobic conditions after 473 d. In comparison, approximately 29% of [phenyl-U-14C]metsulfuron-methyl and 16% of [ring-U-14C]isoproturon mineralized in aerobic slurries during the same period. Surprisingly, 8 to 13% of mecoprop also mineralized under anaerobic conditions. Neither metsulfuron-methyl nor isoproturon were mineralized under anaerobic conditions and atrazine was not mineralized under any of the redox conditions examined. The present study is the first to report mineralization of meco-prop in ground water in a wetland area, and the first to report mineralization of a phenoxyalcanoic acid herbicide under both aerobic and anaerobic conditions.

2-Methyl-4-chlorophenoxyacetic Acid↗

Low bone mineral density in hormone-naïve men with prostate carcinoma.

BACKGROUND: The objective of this study was to determine the prevalence of low bone mineral density in men with prostate carcinoma and no history of androgen-deprivation therapy. METHODS: The authors conducted a cross-sectional study in 41 hormone-naïve men with locally advanced, lymph node positive, or recurrent prostate carcinoma and no radiographic evidence of bone metastases. Bone mineral density of the total hip, posterior-anterior (PA) lumbar spine, and lateral lumbar spine was determined by dual-energy X-ray absorptiometry (DXA) using a densitometer. Trabecular bone mineral density of the lumbar spine was determined by quantitative computed tomography (QCT). Bone mineral density results were expressed in standard deviation units relative to young adult men (T score) and relative to age-matched men (Z score). RESULTS: Fourteen of 41 men (34%; 95% confidence interval [95% CI], 20-51%) had T scores < -1.0 at one or more skeletal sites by DXA, 12 of 41 men (29%; 95% CI, 16-42%) had T scores between -1.0 and -2.5, and 2 of 41 men (5%; 95% CI, 1-17%) had T scores < -2.5. Thirty-nine of 41 men (95%; 95% CI, 83-99%) had T scores < -1.0 by QCT, 13 of 41 men (31%; 95% CI 18-48%) had T scores between -1.0 and -2.5, and 26 of 41 men (63%; 95% CI, 47-78%) had T scores < -2.5. T scores for trabecular bone mineral density of the lumbar spine were significantly lower than T scores for either the total hip (P < 0.001) or the PA lumbar spine (P < 0.001). The mean Z score for trabecular bone mineral density of the lumbar spine was -0.7 +/- 0.9. Hypogonadism, hypovitaminosis D, and dietary calcium intakes below the Recommended Daily Allowance were observed in 20%, and 17%, and 59% of study participants, respectively. CONCLUSIONS: Many hormone-naïve men with prostate carcinoma have low bone mineral density. QCT is a more sensitive method than DXA for diagnosing low bone mineral density in this patient population. Trabecular bone mineral density is lower than expected for age and risk factors for osteoporosis are common.

Age Factors↗

Longitudinal study of the FEV1, cumulative exposure to dusts and silicosis in gold miners.

OBJECTIVES: The aim of this longitudinal study was to assess the rate of decline in FEV1 (deltaFEV1) in gold miners with silicosis and to relate these findings with the radiographic picture, age, smoking habits and cumulative exposure to dusts. METHODS: The study included 73 gold miners with silicosis and 73 miners exposed to dusts but without silicosis. The clinical, radiological and functional assessment was made at least twice in each miner at the beginning and at the end of an adequate interval of the investigation which was extended for a mean period of 38.9 months for the group with silicosis and 33.6 months for the group without silicosis. RESULTS: In the group of miners with silicosis deltaFEV1 was much higher (187 ml/year) as compared with the mean value found in the miners without silicosis (43.2 ml/year). No significant differences were found for deltaFEV1 according to the age criterion (in both groups) and to their smoking habits (in the group with silicosis). In silicosis, a very good correlation exists between the index of cumulative exposure to dusts and the magnitude of the decline rate of FEV1. In the miners, group without silicosis, deltaFEV1 had not any significant correlation with cumulative exposure to dusts. CONCLUSIONS: Our observations revealed that the cumulative exposure to dusts affected the decline rate of FEV1 only to the extent to which it determined silicosis and intervened less in the functional decline in miners without silicosis. Smoking habits increased AFEV1 only in miners without silicosis.

Adult↗

Cigarette smoking and federal black lung benefits in bituminous coal miners.

The records of 1000 consecutive coal miners applying for benefits under the Federal Coal Mine Health and Safety Act were examined to determine the contribution of age, dust accumulation, and cigarette smoking to the profile of the miner who satisfies the current pulmonary criteria for disability. Using the presence of pneumoconiosis on chest radiograph as the indication of significant coal dust accumulation, the miners were separated into Group A--those without pneumoconiosis (n = 316) and Group B--those with pneumoconiosis (n = 684). The federal spirometric criteria for disability identified 55/316 miners in Group A (14.5%) and 99/684 miners in Group B (17.4%) potentially eligible for an award (P = .27). The mean ages of miners in both groups did not differ significantly, nor was there difference in the mean ages of groups that did or did not meet the federal criteria. In both groups, those miners potentially eligible for a financial award smoked more cigarettes than did their counterparts (Group A, 31.0 v 18.5 pack-years, P less than .001; Group B, 31.3 v 23.6 pack-years, P less than .001). There was no difference in the smoking histories of the miners from either group who met the federal criteria. Our data indicate that, in the case of bituminous coal miners, the present federal legislation intended to identify and remunerate those who suffer lung impairment from chronic occupational exposure to coal dust is biased in favor of those who sustain additional damage to their ventilatory capacity by smoking cigarettes.

Coal↗

Relationship between grip strength and related regional bone mineral content.

This study of postmenopausal women had two objectives: (1) to determine whether there is a correlation between the strength of grip muscles and bone mineral content in the midradius where these muscles attach, and (2) to determine whether this correlation is of sufficient magnitude to predict cortical bone content by measuring grip muscle strength. Nondominant power grip and bone mineral content of the midradius were measured in 63 healthy postmenopausal Caucasian women. Significant positive correlations (p less than 0.001) were noted between regional bone mineral content and nondominant power grip, and significant negative correlations (p less than 0.001) were found between nondominant power grip and age and between regional bone mineral content and age. When bone mineral data were normalized for skeletal size, there was no significant improvement of the correlation. In addition, the correlation between grip strength and bone mineral content at the midradius was not sufficiently strong to permit the use of grip strength measurements for prediction of midradius bone mineral content for clinical decision-making or epidemiologic studies. Furthermore, the correlation between grip strength and bone mineral content at the muscle insertion site was not better than the correlation between grip strength and bone mineral content at more distal sites on the same bone.

Aged↗

Characterization of the nucleational core complex responsible for mineral induction by growth plate cartilage matrix vesicles.

The factors that drive mineralization of matrix vesicles (MV) have proven difficult to elucidate; in the present studies, various detergent, chemical, and enzyme treatments were used to reveal the nature of the nucleational core. Incubation with detergents that permeabilized the membrane enhanced calcification of treated MV incubated in synthetic cartilage lymph. While detergents removed most of the membrane lipid, they left significant amounts of the MV annexins and nearly all of the Ca2+, Pi, and Zn2+. Extraction with 1 M NaCl removed much of the Ca2+ and Pi present in MV, markedly reducing Ca2+ accumulation; these effects could be prevented by low levels of Ca2+ and Pi in the NaCl extractant. Treatment with chymotrypsin appeared to damage proteins required for MV mineralization; further treatment with detergents to bypass the membrane reactivated MV mineralization. Treatment of MV with pH 6 citrate removed Ca2+ and Pi, destroying their ability to mineralize; subsequent treatment with detergents did not reactivate these MV. Incubation of the detergent-resistant core with o-phenanthroline complexed Zn2+ and stimulated mineralization; addition of Zn2+ to synthetic cartilage lymph blocked the ability of the core to mineralize. These studies show that once the nucleational core complex is formed, the membrane-enclosed domain is no longer essential for MV calcification. Our findings indicate that the MV core contains two main components as follows: a smaller membrane-associated complex of Ca2+, Pi, phosphatidylserine, and the annexins that nucleates crystalline mineral formation, and a larger pool of Ca2+ and Pi bound to lumenal proteins. These proteins appear to bind large amounts of mineral ions, stabilize the nucleational complex, and aid its transformation to the first crystalline phase. Once nucleated, the crystalline phase appears to feed on protein-bound mineral ions until external ions enter through the MV ion channels. Zn2+ appears to regulate gating of the ion channels and conversion of the nucleational complex to the crystalline state.

Alkaline Phosphatase↗

The mineral composition and enamel ultrastructure of hypocalcified amelogenesis imperfecta.

Hypocalcified amelogenesis imperfecta is characterized clinically by a yellow-brown colored enamel that is prone to severe attrition, often leading to rapid destruction of the crown. While the enamel is thought to be poorly mineralized few studies have evaluated the mineral content, or the histological or microradiographic features of this specific AI type. The purpose of this investigation was to examine teeth affected with autosomal dominant hypocalcified AI histologically using light microscopy (LM), scanning electron microscopy (SEM), and to evaluate the degree of enamel mineralization chemically and with microradiography. Four AI teeth were obtained from an affected individual for comparison with age-matched teeth from normal healthy individuals. Thin sections approximately 100 microns were cut with a diamond disc for examination by LM and microradiography. Using SEM, fractured enamel samples were examined either untreated or after removal of organic material using NaOCl or urea. Normal and AI enamel particles were dissected from thin sections to evaluate the mineral per volume and carbonate content. The enamel was not uniformly affected in all areas of the teeth with the lingual surfaces of the mandibular central incisors appearing clinically and histologically normal. The affected enamel was porous and appeared opaque with LM. Both SEM and LM showed the enamel to be prismatic with relatively normal prism morphology. However, the enamel crystallites were rough and granular compared with those of normal enamel. Extraction to remove organic material did not change the appearance of the crystallites indicating their granular appearance was due to mineral and not residual organic material such as enamel protein. Microradiography showed the enamel was less radiodense and therefore poorly mineralized compared with normal enamel. This was confirmed by chemical determination of the mineral per volume, which showed some areas of the AI enamel had as much as 30% less mineral compared with normal enamel. The carbonate content was found to be similar in AI and normal enamel. Hypocalcified AI is associated with decreased mineralization as well as ultrastructural defects in the crystallite structure. The combined histological and biochemical features of hypocalcified AI seen in this investigation indicate that this AI type is distinctly different from the hypoplastic and hypomaturation AI types.

Amelogenesis Imperfecta↗

[Survival ability of Trichomonas vaginalis in mineral baths].

The role of mineral thermal baths and particularly of bath fittings such as benches and toilet seats in the spreading of Trichomonas vaginalis is controversial. In order to clarify the possibility of transmission by smear infection of this ubiquitous urogenital parasite the ability to survive was investigated in 11 mineral baths in Baden-Württemberg by contamination of water samples of varying mineral content. In addition, Trichomonas-contaminated water samples were placed in Petri-dishes on different benches in the bath area to determine the different milieu-factors influencing survival and thus the possibility of smear infections. The determination of viable cells was carried out by recultivation and semiquantitative extinction measurement. The survival time of Trichomonas vaginalis in the water samples of the 11 mineral baths varied considerably from 30 min up to more than 3 hours. The total mineral content played the most important role. When exposed in Petri dishes in addition the evaporation of the medium (mineral water) is of importance. Generally at high evaporation rates the cells will lose viability faster than in closed tubes. But also in open dishes in 4 mineral baths viable Trichomonads were still detectable after 3 hours. Generally the ability of Trichomonas vaginalis to survive in water of a total mineral content of 0.05-2.2% is increased to such an extent that infection is theoretically possible. Transmission in the mineral pool itself appears nevertheless highly unlikely due to the dilution effect of the enormous water volume. However transmission of infection via wet, contaminated benches and toilet seats cannot be generally ruled out.

Animals↗