RESUMEN
INTRODUCTION: Reduced bone mineral and ultimate strength are regular consequences of unloading bone. The aim of this study was to determine if high dietary salt intake would reduce the bone density and strength to a greater extent in rats with unloaded bones compared to ambulatory control rats fed the same dietary calcium and phosphorus. METHODS: Mature male Sprague-Dawley rats were divided into four groups: two exposed to a spaceflight model that unloaded the hind limbs (HU) and two controls (C) with normal ambulation. Half the HU and C rats were fed normal dietary salt (0.26%, NNa) and half high dietary salt (8%, HNa). The calcium (Ca) and phosphorus (P) content of the diets was normal (Ca 0.5% and P 0.6%) in all four groups. After 4 wk of hind limb unloading, the bone mineral content (BMC) of excised femurs was measured by the ash weight and the ultimate torsional strength was determined by a torsional strength test device. RESULTS: Femoral BMC (mg) was lower in HUNNa than C rats fed normal salt diets. Femurs from HU rats fed normal salt diets showed lower (20-26%) torsional strength (Nmm), compared to all other groups. DISCUSSION: It appears that high salt diets with normal amounts of calcium and phosphorus may prevent the decrease in bone torsional strength and BMC induced by unloading the femurs in 6-mo-old rats.
Asunto(s)
Densidad Ósea/fisiología , Fémur/anatomía & histología , Fémur/fisiología , Suspensión Trasera , Sodio en la Dieta/administración & dosificación , Animales , Calcio de la Dieta/administración & dosificación , Masculino , Fósforo Dietético/administración & dosificación , Ratas , Ratas Sprague-Dawley , Torsión MecánicaRESUMEN
The human epidermal cell (HEC) assay, which uses carcinogen exposed normal skin keratinocytes to screen for cancer prevention efficacy, was used to screen possible preventive agents. The endpoints measured were inhibition of carcinogen-induced growth and induction of involucrin, an early marker of differentiation. Sixteen of twenty agents (apigenin, apomine, budesonide, N-(2-carboxyphenyl)retinamide, ellagic acid, ibuprofen, indomethacin, melatonin, (-)-2-oxo-4-thiazolidine carboxylic acid, polyphenon E, resveratrol, beta-sitosterol, sulfasalazine, vitamin E acetate, and zileuton) were positive in at least one of the two assay endpoints. Four agents (4-methoxyphenol, naringenin, palmitoylcarnitine chloride, and silymarin) were negative in the assay. Nine of the sixteen agents were positive for both endpoints. Agents that showed the greatest response included: ellagic acid > budesonide, ibuprofen > apigenin, and quinicrine dihydrochloride. Fifty-eight of sixty-five agents that have been evaluated in the HEC assay have also been evaluated in one or more rodent bioassays for cancer prevention and several are in clinical trials for cancer prevention. The assay has an overall predictive accuracy of approximately 91.4% for efficacy in rodent cancer prevention irrespective of the species used, the tissue model, or the carcinogen used. Comparison of the efficacious concentrations in vitro to plasma levels in clinical trials show that concentrations that produced efficacy in the HEC assay were achieved in clinical studies for 31 of 33 agents for which plasma levels and/or C(max) levels were available. For two agents, 9-cis-retinoic acid (RA) and dehydroepiandrosterone (DHEA), the plasma levels greatly exceeded the highest concentration (HC) found to have efficacy in vitro. Thus, the HEC assay has an excellent predictive potential for animal efficacy and is responsive at clinically achievable concentrations.
Asunto(s)
Anticarcinógenos/farmacología , Evaluación de Medicamentos , Queratinocitos , Neoplasias/prevención & control , Animales , Anticarcinógenos/farmacocinética , Células Cultivadas , Ensayos Clínicos como Asunto , Evaluación de Medicamentos/métodos , Humanos , Queratinocitos/citología , Queratinocitos/fisiologíaRESUMEN
BACKGROUND: Calcium balances, regulated by the calcium endocrine system, are negative during spaceflight but have not been reported in flight simulation models using fully mature small animals. METHODS: We conducted two calcium (Ca) balance studies in 6-mo-old male rats exposed to a model that unloads the hindlimbs (HU) for 4 wk. Control (C) and HU rats were fed diets with 0.5% Ca in the first and 0.1% Ca in the second study. Housing in metabolic cages enabled daily food and water intake measurements as well as collections of urine and fecal specimens. At necropsy, blood was obtained for measures of Ca-regulating hormones. RESULTS: Both C and HU rats adjusted to housing and diets with decreases in body weight and negative Ca balances during the first week of each experiment. Thereafter, averages of Ca balances were more negative in the unloaded rats than controls: -8.1 vs. -1.6 mg x d(-1) in rats fed 0.5% (p < 0.05). This difference was not due to urinary Ca excretion since it was lower in HU than C rats (1.27 +/- 0.51 mg x d(-1) vs. 2.35 +/- 0.82 mg x d(-1), p < 0.05). Fecal Ca in HU rats exceeded dietary Ca by 4-7%, Restricting dietary Ca to 0.1% was followed by an increase in serum 1,25-dihydroxyvitamin D (1,25-D) and greater intestinal Ca absorption than in rats fed 0.5% Ca. Ca balances in rats fed 0.1% Ca were also more negative in HU than C rats (-2.4 vs. -0.03 mg x d(-1), p < 0.05). Parathyroid hormone (PTH) was suppressed and 1,25-D increased in HU rats fed 0.5% Ca. C rats fed 0.1% Ca had increased PTH and 1,25-D was the same as in the HU group. CONCLUSION: After adaptation, Ca balances were more negative in mature male rats with unloaded hindlimbs than controls, an effect from increased secretion and loss of endogenous fecal Ca associated with increased 1,25-D in Ca-replete and Ca-restricted rats.
Asunto(s)
Calcio/metabolismo , Suspensión Trasera/fisiología , Animales , Peso Corporal , Calcio de la Dieta/administración & dosificación , Homeostasis , Absorción Intestinal , Masculino , Modelos Animales , Hormona Paratiroidea/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P < 0.05). Decreases in parathyroid hormone did not reach significance. Calcitonin showed modest decreases postflight (P < 0.02). Overall, effects of spaceflight on the calcium endocrine system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.