Biomedical subjects

John F Aloia

Publications and source records attributed to John F Aloia.

11 recordsLinked to original sources

PubMed2006

Optimal vitamin D status and serum parathyroid hormone concentrations in African American women.

BACKGROUND: Optimal vitamin D status for the prevention of osteoporosis has been inferred from examinations of the serum 25-hydroxyvitamin D [25(OH)D] concentration below which there is an increase in serum parathyroid hormone (PTH). OBJECTIVE: The objectives of the study were to ascertain whether a threshold for serum 25(OH)D exists below which serum PTH increases and whether persons with 25(OH)D above this threshold have lower rates of bone loss than do persons with 25(OH)D below the threshold. DESIGN: The relation of serum 25(OH)D to serum PTH was analyzed in 208 African American women studied longitudinally for 3 y. These healthy women in midlife were randomly assigned to receive placebo or 800 IU vitamin D3/d; after 2 y, the vitamin D3 supplementation was increased to 2000 IU/d. Both groups received calcium supplements to ensure an adequate calcium intake. A systematic literature review found a wide range of threshold values in part due to varied calcium intake. RESULTS: A Loess plot suggested a breakpoint between 40 and 50 nmol/L for serum 25(OH)D. A line-line model was fitted to the data, and it showed a spline knot at 44 nmol/L. A heuristic approach verified that PTH does not decline as rapidly when the serum concentration of 25(OH)D is >40 nmol/L as when it is <40 nmol/L. We found no significant difference in rates of bone loss between persons with 25(OH)D concentrations above and below 40 nmol/L. CONCLUSION: Although a threshold for 25(OH)D can be identified, we suggest that it should not be used to recommend optimal vitamin D status.

Black or African American↗

PubMed2006

A possible role for melanocortin peptides in longitudinal growth.

Clinical and in vitro data suggest a link between the elevation of the melanocortin peptide, ACTH, and longitudinal growth. Overproduction of ACTH in familial glucocorticoid deficiency (FGD) is associated with increased growth and ACTH increases the differentiation of chondrocytes along the endochondral pathway in vitro. Using the leptin-deficient obese (ob/ob) mouse along with lean control littermates (n = 9-10), we investigated the effects of adrenalectomy (ADX)-induced elevated ACTH with and without peripheral administration of the MC3-R-specific agonist, gamma2-melanocyte stimulating hormone (gamma2-MSH), on longitudinal growth. Naso-anal and tibial growth were measured together with growth plate parameters; both total and zonal heights together with the proliferative index. Data were analyzed using two-way ANOVA with post hoc comparisons made using the Bonferroni correction. ADX significantly increased naso-anal length in lean mice and ADX plus gamma2-MSH administration significantly increased naso-anal length above ADX alone in ob/ob mice. gamma2-MSH administration to ADX lean and ob/ob mice significantly increased tibial length. In ob/ob mice, these changes occurred in the context of reduced food intake. Analysis of total and zonal growth plate heights suggest an increase in hypertrophic differentiation and an overall increase in growth plate turnover in ADX lean and ob/ob mice. These in vivo data show that ADX enhances linear growth and the results of gamma2-MSH treatment suggest that the melanocortin system plays a role in linear growth.

Adrenalectomy↗

PubMed2005

A randomized controlled trial of vitamin D3 supplementation in African American women.

BACKGROUND: We conducted a randomized, placebo-controlled, double-blind trial to test the hypothesis that vitamin D(3) supplementation would prevent bone loss in calcium-replete, African American postmenopausal women. METHODS: Two hundred eight healthy black postmenopausal women, 50 to 75 years of age, were assigned to receive either placebo or 20 microg/d (800 IU) of vitamin D(3). Calcium supplements were provided to ensure a total calcium intake of 1200 to 1500 mg/d. After 2 years, the vitamin D(3) dose was increased to 50 microg/d (2000 IU) in the active group, and the study continued for an additional year. Bone mineral density (BMD) was measured every 6 months. Markers of bone turnover, vitamin D metabolites, and parathyroid hormone (PTH) levels were measured in serum. RESULTS: There were no significant differences in BMD between the active and control groups throughout the study. There was also no relationship between serum 25-hydroxyvitamin D levels attained and rates of bone loss. There was an increase in BMD of the total body, hip, and radius at 1 year in both groups. Over the 3 years, BMD declined at these sites by 0.26% to 0.55% per year. The BMD of the lumbar spine increased slightly in the placebo and active groups. There were no persistent changes in serum PTH levels or the markers of bone turnover, although there was a transient decline in PTH in both groups at 3 months. No significant adverse events were attributed to vitamin D supplementation. CONCLUSIONS: There was no observed effect of vitamin D(3) supplementation on bone loss or bone turnover markers in calcium-replete, postmenopausal African American women. Further studies are needed to determine if these findings are applicable to women of other ethnic groups.

Black or African American↗

PubMed2005

Adrenocorticotropin evokes transient elevations in intracellular free calcium ([Ca2+]i) and increases basal [Ca2+]i in resting chondrocytes through a phospholipase C-dependent mechanism.

Both clinical and in vitro evidence points to the involvement of the melanocortin peptide, ACTH, in the terminal differentiation of chondrocytes. Terminal differentiation along the endochondral pathway is responsible for linear growth, but also plays a role in osteoarthritic cartilage degeneration. Chondrocyte terminal differentiation is associated with an incremental increase in chondrocyte basal intracellular free calcium ([Ca(2+)](i)), and ACTH agonism of melanocortin receptors is known to mobilize [Ca(2+)](i.) Using differentiated resting chondrocytes highly expressing type II collagen and aggrecan, we examined the influence of both ACTH and dexamethasone treatment on matrix gene transcription and [Ca(2+)](i). Resting chondrocytes treated concurrently with dexamethasone and ACTH expressed matrix gene transcripts in a pattern consistent with that of rapid terminal differentiation. Using the fluorescent Ca(2+) indicator, fura-2, we determined that ACTH evokes transient increases in [Ca(2+)](i) and elevates basal Ca(2+) levels in resting chondrocytes. The transient increases were initiated intracellularly, were abrogated by the phospholipase C-specific inhibitor, U73122, and were partly attenuated by myo-inositol 1,4,5-triphosphate receptor inhibition via 10 mm caffeine. The initial intracellular release also resulted in store-operated calcium entry, presumably through store-operated channels. Dexamethasone priming increased both the initial ACTH-evoked [Ca(2+)](i) release and the subsequent store-operated calcium entry. These data demonstrate roles for ACTH and glucocorticoid in the regulation of chondrocyte terminal differentiation. Because the actions of ACTH are mediated through known G protein-coupled receptors, the melanocortin receptors, these data may provide a new therapeutic target in the treatment of growth deficiencies and cartilage degeneration.

Adrenocorticotropic Hormone↗

PubMed2004

Three-compartment model: critical evaluation based on neutron activation analysis.

There is renewed interest in Siri's classic three-compartment (3C) body composition model, requiring body volume (BV) and total body water (TBW) estimates, because dual-energy X-ray absorptiometry (DEXA) and in vivo neutron activation (IVNA) systems cannot accommodate subjects with severe obesity. However, the 3C model assumption of a constant ratio (alpha) of mineral (M) to total body protein (TBPro) and related residual mass density (D(RES)) based on cadaver analyses might not be valid across groups differing in sex, race, age, and weight. The aim of this study was to derive new 3C model coefficients in vivo and to compare these estimates to those derived by Siri. Healthy adults (n = 323) were evaluated with IVNA and DEXA and the measured components used to derive alpha and D(RES). For all subjects combined, values of alpha and D(RES) (means +/- SD, 0.351 +/- 0.043; 1.565 +/- 0.023 kg/l) were similar to Siri's proposed values of 0.35 and 1.565 kg/l, respectively. However, alpha and D(RES) varied significantly as a function of sex, race, weight, and age. Expected errors in percent body fat arising by application of Siri's model were illustrated in a second group of 264 adults, including some whose size exceeded DEXA limits but whose BV and TBW had been measured by hydrodensitometry and (2)H(2)O dilution, respectively. Extrapolation of predictions by newly developed models to very high weights allows percent fat error estimation when Siri's model is applied in morbidly obese subjects. The present study results provide a critical evaluation of potential errors in the classic 3C model and present new formulas for use in selected populations.

Absorptiometry, Photon↗

PubMed2004

ACTH enhances chondrogenesis in multipotential progenitor cells and matrix production in chondrocytes.

The association of melanocortin peptide overproduction with enhanced linear growth prompted the current investigation of adrenocorticotropin hormone (ACTH) effects on multipotential chondroprogenitor populations and committed chondrocytes in culture. Two multipotential progenitor populations, rat bone marrow stromal cells (BMSC) and the clonal multipotential cell line RCJ3.1, and two committed chondrocyte populations, resting chondrocytes (RC) isolated from the rib of young rats and the chondrocyte restricted cell line RCJ3.1C5.18 (C5.18), were cultured in differentiation medium plus or minus ACTH. Alcian blue stain was used to quantitate proteoglycan matrix production in all populations treated with a range of ACTH concentrations. Changes in proliferation due to ACTH treatment of all cell types were measured using 3H-thymidine incorporation. Differences in matrix production of ACTH-treated and -untreated RC and C5.18 cells were determined using 3H-proline incorporation. Relative transcript expression of the chondrocyte matrix proteins collagen type II (COLL II) and aggrecan (AGR) in treated and untreated cells was analyzed by Northern blot. Collagen type X (COLL X), a marker of hypertrophic differentiation, was measured in committed chondrocytic populations. Western analysis was used to detect the melanocortin-3 receptor (MC3-R), which was a suspected mediator of the ACTH signal. Matrix deposition was dose-dependently increased by ACTH in all cell populations as measured by alcian blue stain. ACTH treatment increased proliferation in multipotential progenitor populations (BMSC and RCJ3.1) while proliferation was decreased in committed chondrocyte populations (RC and C5.18). Total protein and total cell-associated collagen production were significantly increased by ACTH treatment in committed populations. Relative COLL II and AGR transcript expressions were significantly increased in both the RC- and C5.18-committed population and very significantly increased in the progenitor populations. Additionally, collagen type X expression was detected earlier and in greater abundance in ACTH-treated committed chondrocyte populations. Finally, the melanocortin-3 receptor was detected in all examined cell types by Western blot. These data show that ACTH promotes the development of the chondrocyte phenotype from multipotential mesenchymal progenitor populations and increases matrix production and differentiation of committed chondrocytes. These findings, together with the detection of the MC3-R in all of these cell types, indicate a role for the melanocortin system in chondrogenesis.

Adrenocorticotropic Hormone↗

PubMed2003

Total body protein: a new cellular level mass and distribution prediction model.

BACKGROUND: Protein is an important body component, and the presently accepted criterion method for estimating total body protein (TBPro) mass--in vivo neutron activation (IVNA) analysis--is unavailable to most investigators and is associated with moderate radiation exposure. OBJECTIVE: The objective was to derive a theoretical cellular level TBPro mass and distribution model formulated on measured total body potassium, total body water, and bone mineral and to evaluate the new model with the IVNA method as the criterion. DESIGN: The new model was developed on the basis of a combination of theoretical equations and empirically derived coefficients. TBPro mass estimates with the new model were evaluated in healthy women (n = 183) and men (n = 24) and in men with AIDS (n = 84). Total body nitrogen was measured by IVNA, total body potassium by whole-body (40)K counting, total body water by tritium dilution, and bone mineral by dual-energy X-ray absorptiometry. RESULTS: The group mean (+/- SD) TBPro mass estimates in healthy women and men and men with AIDS (8.2 +/- 0.9, 11.0 +/- 1.8, and 10.5 +/- 1.1 kg, respectively) with the new model were similar to IVNA criterion estimates (8.9 +/- 0.9, 11.1 +/- 1.6, and 10.9 +/- 1.2 kg, respectively). TBPro mass estimates with the new model correlated highly with the IVNA estimates in all subjects combined (r = 0.92, P < 0.001). The new model suggests that the composite TBPro mass within each group consists mainly of cellular protein (75-79%) and, to a lesser extent, protein in extracellular solids (19-23%) and extracellular fluid (approximately 2%). CONCLUSION: The new model provides a non-IVNA approach for estimating protein mass and distribution in vivo.

Absorptiometry, Photon↗

PubMed2003

Body fat content and 25-hydroxyvitamin D levels in healthy women.

Obesity is associated with alterations in the vitamin D endocrine system. Lower levels of serum 25-hydroxyvitamin D (25-OHD) in morbidly obese individuals may be secondary to an alteration in tissue distribution resulting from an increase in adipose mass. Therefore, morbidly obese individuals are expected to need higher doses of vitamin D supplementation than the general population. However, it is still unknown whether adiposity (or percentage body fat) should be taken into consideration while assessing vitamin D requirements in the general population. To study the relationship between 25-OHD levels and percentage body fat content in healthy women, we studied 410 healthy women between 20 and 80 yr of age with body mass index ranging from 17 to 30 kg/m2. We analyzed the correlation between serum 25-OHD level and percentage body fat measured by dual energy x-ray absorptiometry. We also analyzed the influence of season, dietary vitamin D intake, age, and race on this relationship. The levels of serum 25-OHD inversely correlated with percentage body fat. The correlation was -0.13 (P = 0.013) after adjusting for race, age, season, and dietary vitamin D intake. In a multiple stepwise regression, race and season were found to have a major influence on serum 25-OHD (cumulative R2 = 0.34), and percentage body fat, although modest (additional R2 = 0.02), also had an independent statistically significant influence on serum 25-OHD levels. We conclude, percentage body fat content is inversely related to the serum 25-OHD levels in healthy women.

Adipose Tissue↗

PubMed2002

Influence of growth hormone on bone marrow adipogenesis in hypophysectomized rats.

The hypophysectomized rat has been used as a model to study the effects of growth hormone deficiency on bone. Here, we have investigated the influence of growth hormone administration to hypophysectomized rats (HX) for 6 wk on accumulation of triglycerides in bone marrow and on the differentiation of primary marrow stromal cells into adipocytes under in vitro conditions. We found that hypophysectomy significantly increased triglyceride concentration in bone marrow, which was attenuated by growth hormone administration. Primary bone marrow stromal cells derived from HX rats also had more adipocytes at confluence compared with growth hormone-treated hypophysectomized (GH) rats. When stimulated with 3-isobutyl-1-methylxanthine plus dexamethasone (IBMX-Dex), preadipocyte colony counts increased more significantly in GH rats. Markers of adipocyte differentiation were higher in HX than in control or GH rats at confluence. However, after stimulation with IBMX-Dex, increased expression of markers was seen in GH compared with HX rats. In conclusion, growth hormone administration to hypophysectomized rats attenuated triglyceride accumulation in bone marrow and inhibited the differentiation of stromal cells into adipocytes in vitro.

Adipocytes↗

PubMed2002

Total body phosphorus in healthy women and ethnic variations.

Total body phosphorus (TBP) levels were measured in 90 black and 143 white healthy women to determine ethnic differences. The measurements were performed by in vivo delayed gamma neutron activation (DGNA) analysis at Brookhaven National Laboratory (BNL). Mean value of TBP in whites was 10.4% lower as compared with the black women (mean TBP in white women 401.4 +/- 57.5 g v. 447.7 +/- 57.7 g in black women). Both subgroups have a decrease in TBP with age with a rapid phase after the onset of menopause, which corresponds to bone loss. The decrease in TBP is similar in both ethnic groups with black women losing -1.59 g/yr (-0.33%/yr) and white women losing -2.08 g/yr (-0.45%/yr).

Adult↗

PubMedDate not supplied

Reference range for serum parathyroid hormone.

OBJECTIVE: To determine whether the reference range for parathyroid hormone (PTH) should be lowered (from 65 pg/mL to a proposed value of 46 pg/mL) with use of the Allegro radioimmunometric assay. METHODS: We examined the reference range for PTH, adjusted for serum 25-hydroxyvitamin D (25-OHD), in 503 healthy African American and white women, who were 20 to 80 years old. We also analyzed other factors that are thought to influence PTH levels. RESULTS: Univariate predictors of PTH were identified, and a multivariate model was developed with use of the variables and PTH. Serum PTH was significantly higher in black study subjects than in white study subjects (P<0.02). Increasing PTH was also significantly correlated with increasing body mass index, age, and serum creatinine and with decreasing dietary calcium intake and serum 25-OHD levels. A stepwise multiple linear regression analysis yielded the following predictors of PTH: body mass index (R2=9.4%), age (R2=1.0%), and serum 25-OHD (R2=0.8%). In our study population, many PTH values were above the proposed new upper limit of 46 pg/mL. CONCLUSION: The upper limit of the reference range for serum PTH should not be changed. Factors to be considered in analysis of serum PTH values in the upper reference range in patients with normocalcemia include obesity, race, 25-OHD levels, advanced age, serum creatinine, and dietary calcium intake.

Adult↗