Showing papers by "Thomas M. Badger published in 2002"
TL;DR: There are significant differences in the pharmacokinetics of sulfate and glucuronide conjugates of isoflavones in humans after the consumption of a drink made with soy-protein isolate, which may have important implications for the meal frequency and maintenance of target tissue bioactivity required to elicit potential health benefits.
189 citations
TL;DR: Results from several studies suggest that the effects of diets made with SPI+ differ significantly from those of diets to which purified soy is oflavones are added, and it seems that soy protein processed to contain lower levels of isoflavones also provides significant health benefits.
Abstract: Infants fed soy formula are the segment of the U. S. population that consumes the most soy. Before birth and after weaning, most Americans are not exposed to appreciable levels of soyfoods other than foods that have small amounts of processed soy components. The opposite scenario occurs in Asia, because Asians are more likely to consume relatively high levels of soyfoods throughout life, except between birth and weaning, when breastfeeding or milk-based formula are common. Soy formula is made with soy protein isolate containing isoflavones (SPI+) and supports normal growth and development in term infants. Recent data suggest that there are no long-term adverse effects of early exposure to soy formula through young adulthood. It is as yet unknown whether soy formula consumption by infants will result in health problems or benefits upon aging, but multigenerational animal studies with diets made with SPI+ have not revealed any problems. Soy isoflavones can function as estrogen agonists, antagonists or selective estrogen receptor modulators, depending on the conditions, and much research has focused on health effects of purified isoflavones. Results from several studies suggest that the effects of diets made with SPI+ differ significantly from those of diets to which purified soy isoflavones are added. Furthermore, it seems that soy protein processed to contain lower levels of isoflavones also provides significant health benefits. Further research is needed to confirm the results of the few studies that have been conducted and new studies are needed to investigate the more subtle effects that could occur during development or that could surface later in life.
122 citations
TL;DR: It is demonstrated that short-term systemic administration of IL-1 and TNF antagonists together protect rapid bone formation during DO from the deleterious effects of chronic ethanol but are ineffective in regard to intact bone homeostasis.
Abstract: Chronic ethanol exposure inhibits rapid bone formation during distraction osteogenesis (DO; fracture and limb lengthening) and decreases volumetric bone mineral density (BMD) in a model of intragastric dietary infusion [total enteral nutrition (TEN)] in the rat. The hypothesis tested herein was that overexpression of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha mediates these deleterious effects of ethanol on the rat skeleton. Two studies (study 1, female rats; study 2, male rats) were performed to test the potential protective effects of the IL-1 and TNF antagonists: IL-1 receptor antagonist (IL-1ra) and 30-kDa polyethylene glycol-conjugated soluble TNF receptor type 1 (sTNFR1). All rats were infused with a liquid diet +/- ethanol (EtOH) and underwent tibial fractures and DO. During distraction, the animals received a combination of IL-1ra (1.8-2.0 mg/kg/day) and sTNFR1 (2.0 mg/kg/2 days) or vehicle. A comparison of distracted tibial histological sections demonstrated 1) significant antagonist-related increases in bone column formation over the EtOH controls (studies 1 and 2), and 2) restoration of new bone equivalent to that of the TEN controls (study 2). In contrast, examination of intact proximal tibial metaphyses by peripheral quantitative computerized tomography revealed decreases in volumetric BMD of both EtOH control and EtOH antagonist groups (study 2). These results demonstrate that short-term systemic administration of IL-1 and TNF antagonists together protect rapid bone formation during DO from the deleterious effects of chronic ethanol but are ineffective in regard to intact bone homeostasis.
51 citations
TL;DR: In this paper, the expression of osteopontin (OPN) during distraction osteogenesis (DO) using standard immunohistochemical (IHC) staining techniques was investigated.
Abstract: Distraction osteogenesis (DO) is a limb-lengthening procedure that combines mechanical tension stress with fracture healing to provide a unique opportunity for detailed histological examination of bone formation Osteopontin (OPN) is a multifunctional matricellular protein believed to play a key role in wound healing and cellular response to mechanical stress We studied the expression of OPN during DO using standard immunohistochemical (IHC) staining techniques In addition, we compared the expression of OPN to proliferation (PCNA-positive cells) in the DO gap After 14 days of distraction in the rat, these stains revealed variations in OPN expression and its relationship to proliferation according to the cell type, tissue type, and mode of ossification examined Fibroblast-like cells within the central fibrous area exhibited intermittent low levels of OPN, but no relationship was observed between OPN and proliferation In areas of transchondral ossification, OPN expression was very high in the morphologically intermediate oval cells During intramembranous ossification, osteoblasts appeared to exhibit a bimodal expression of OPN Specifically, proliferating pre-osteoblasts expressed osteopontin, but OPN was not detected in the post-proliferative pre-osteoblasts/osteoblasts that border the new bone columns Finally, intracellular OPN was detected in virtually all of the mature osteoblasts/osteocytes within the new bone columns, while detection of OPN in the matrix of the developing bone columns may increase with the maturity of the new bone These results imply that the expression of OPN during DO may be more similar to that seen during embryogenesis than would be expected from other studies Furthermore, the biphasic expression of OPN during intramembranous ossification may exemplify the protein's multi-functional role Early expression may facilitate pre-osteoblastic proliferation and migration, while the latter downregulation may be necessary for hydroxyapatite crystal formation
51 citations
TL;DR: These data provide the first evidence for the mechanism by which ethanol regulates rat hepatic Class I ADH gene expression in vivo, which involves the C/EBP site and the enhancer binding proteins β and γ.
43 citations
TL;DR: The TEN system is a viable model to study ethanol's effects on the skeleton and that chronic ethanol delivery via TEN decreases trabecular bone density, cortical area, and mature bone strength, and the DO studies demonstrate, for the first time, that chronic alcohol inhibits rapid bone formation during limb lengthening.
Abstract: Chronic alcohol abuse decreases bone mass, inhibits osteoblast differentiation and function, increases fracture incidence, and delays fracture healing. Four studies were designed to use intragastric ethanol delivery as part of a total enteral nutrition (TEN) system to determine the negative systemic effects of chronic ethanol on 1) the rat skeleton and 2) local rapid bone formation during limb lengthening (distraction osteogenesis, DO). In study 1, three-point bending tests demonstrated that after 75 days of ethanol exposure, the tibiae had significantly lower load to failure versus control diet (p = 0.0006) or ad libitum chow-fed rats (p = 0.0029). Study 2 examined alcohol's effects on the density and cross-sectional area of the proximal tibial metaphysis using peripheral quantitative computed tomography and found that after 25 days of ethanol exposure the trabecular volumetric bone mineral density (p = 0.011) and cortical cross-sectional area (p = 0.011) were lower compared with controls. In study 3, a comparison of distracted tibial radiographs and histological sections demonstrated ethanol-related decreases in both gap mineralization (p = 0.03) and bone column formation (p = 0.01). Histological comparisons in study 4 reproduced the ethanol-related deficits in new bone formation during DO (p = 0.001). These results indicate that the TEN system is a viable model to study ethanol's effects on the skeleton and that chronic ethanol delivery via TEN decreases trabecular bone density, cortical area, and mature bone strength. Also, the DO studies demonstrate, for the first time, that chronic ethanol inhibits rapid bone formation during limb lengthening.
42 citations
TL;DR: The application of LC/MS/MS to analyze isoflavone metabolites is simple and sensitive, and appears to be an excellent method for determining the bioavailability and metabolism of food phytochemistry.
Abstract: Isoflavone phytoestrogens found in soybeans are the most widely studied phytochemicals in human diets and soy infant formulas. The health benefits of the isoflavones daidzein and genistein have been reported, and concerns about potential adverse effects have also been raised. However, the results of direct analysis of isoflavones and their metabolites in biological fluids after consumption of soy-containing diets are scarce. This study describes an LC/MS/MS method for the analysis of isoflavones and their metabolites in the urine of female rats fed diets made with soy protein isolate. Five isoflavones (daidzein, genistein, glycitein, dihydrodaidzein, and O-desmethylangolensin) were identified by comparison with authentic standards. Seventeen conjugates of isoflavones were characterized in the urine, the most unusual being genistein 5-glucuronide and four glucuronide conjugates of reductive metabolites of daidzein. The application of LC/MS/MS to analyze isoflavone metabolites is simple and sensitive, and appears to be an excellent method for determining the bioavailability and metabolism of food phytochemistry.
39 citations
TL;DR: Results show that the type of dietary protein alters the phenotype of mammary epithelia in the TEBs, and the SPI- and WPH-dependent changes in mammary differentiation may contribute to the reduced sensitivity to DMBA-induced mammary cancer in rats fed these proteins.
27 citations
TL;DR: Results suggest that 12-month-old mice have a relative deficit in endosteal bone formation compared with that in younger mice, a hypothesis that aging will result in decreased bone formation during distraction osteogenesis.
Abstract: This paper describes a study conducted to test the hypothesis that aging will result in decreased bone formation during distraction osteogenesis (DO). DO is a unique clinical method for the stimulation of new bone formation and subsequent bone lengthening. When applied to other species DO reflects the clinical situation in which older DO patients demonstrate significant delays in mineralization. Given the considerable value of mouse genetics for studying the mechanism(s) of bone formation, we have developed a murine DO model and utilized it to investigate the effect of age on bone formation. Four- and 12-month-old CB57BL/6 male mice ( n 5 10 per group) underwent DO. External fixators were placed on the left tibiae, and mid-diaphyseal tibial osteotomies were performed immediately following fixator placement. Distraction, which began 6 days after surgery at 0.075 mm twice a day (0.15 mm/day) for 14 days, resulted in a total lengthening of 2.1 mm. Following distraction, the distracted tibiae were removed for high-resolution radiography and histological evaluation. Analysis of radiographs and representative histological sections was performed by video microscopy. Radiographic analysis demonstrated a significant decrease in the mineralized area of distraction gaps of 12- (33.5 6 4.8%) versus 4-month-old (51.4 6 5.4%) mice ( p , 0.039). Histological analysis of representative specimens confirmed the decrease in bone formation observed in the radiographs ( p , 0.001). Endosteal new bone was predominantly intramembranous and appeared highly oriented toward the distraction axis. These results suggest that 12-month-old mice have a relative deficit in endosteal bone formation compared with that in younger mice. The application of this murine DO model to genetically manipulated mice may provide critical insights into the mechanisms of bone formation, repair, and regeneration in a geriatric setting.
16 citations