Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0205700 (ash)
 15,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test whether Cd exposure would increase Ca release from bone during pregnancy and lactation in relation to the etiological mechanism of Itai-Itai disease, virgin female mice with 45Ca prelabeled skeletons (15 microCi/mouse) were subjected to one round of pregnancy/lactation and were exposed to a Ca-deficient diet containing 0, 5, or 25 ppm Cd or 25 ppm Pb for 32 days, from conception until Lactation Day 14. A striking loss of 45Ca was found in the dam's total skeleton (-40%), right femur (-47%), and lumbar vertebrae (L1-L5) (-75%) due only to pregnancy/lactation in conjunction with Ca deficiency. At both 5 and 25 ppm, Cd administered through food induced an additional significant 45Ca loss from the total skeleton (-25% at 5 ppm Cd, -30% at 25 ppm Cd) and right femur (39% at 5 ppm Cd, -32% at 25 ppm Cd) compared to 0 ppm animals. Almost all of the 45Ca lost from the dam's skeleton appeared in the pups, with 80% transferred via the dam's milk during lactation and only 20% transferred during gestation; a very small fraction of the dam's skeletal 45Ca was excreted. Considering stable Ca values, Cd exposure nearly doubled the loss of Ca from the dam's skeleton (-78 mg Ca/mouse at 0 ppm; -146 mg Ca/mouse at 5 and 25 ppm Cd). Paralleling 45Ca losses, a Ca-deficient diet in combination with pregnancy/lactation alone caused significant decreases in weight and mineral content of the right femur and lumbar vertebrae (dry weight, ash weight, ash/dry, Ca content, Ca/dry, and Ca/ash) (-8 to -52%). Cd at both 5 and 25 ppm showed additional decreases (-15 to -32%, Cd groups compared to 0 ppm animals). Responses were specific to Cd in that no significant effect occurred due to 32 days of Pb exposure (25 ppm). This experiment supports the view that Cd exposure in conjunction with Ca deficiency and pregnancy/lactation are key etiological factors of Itai-Itai disease and that Cd at both 5 and 25 ppm in conjunction with one round of gestation/lactation and Ca deficiency can induce an extreme demineralization characteristic of Itai-Itai-like syndrome.
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PMID:Effect of cadmium on bone calcium and 45Ca in mouse dams on a calcium-deficient diet: evidence of Itai-Itai-like syndrome. 804 77

To clarify the mechanism of the effect of Cd on bone, virgin female mice with 45Ca prelabeled skeletons (15 microCi/mouse) were exposed to a Ca-deficient diet (0.002%) containing 0, 5, or 25 ppm Cd or 25 ppm Pb for 32 days. During the first 72 hr, the 0 ppm controls showed a 2.5-fold decrease in fecal 45Ca excretion (decreased bone resorption), a 12-fold decrease in total fecal stable Ca, a 5-fold decrease in endogenous fecal Ca excretion, and a significant elevation in both serum 45Ca (108%) and specific activity (92%) due to the Ca-deficient diet. In contrast, Cd immediately and significantly increased fecal 45Ca excretion (55%), total fecal stable Ca (13%), endogenous fecal Ca excretion (32%), as well as serum 45Ca (15%) and specific activity (17%) (25 ppm Cd vs 0 ppm), supporting the hypothesis of an early, direct effect of Cd on bone. Overall, during 32 days, Cd at 25 ppm induced a 60% increase in fecal 45Ca excretion compared to 0 ppm controls, providing a sensitive measure of the Cd-induced increase in bone resorption. In contrast, the effect of Cd was too small to cause a statistically significant 45Ca loss from the right femur and lumbar vertebrae, but a significant 45Ca loss (up to -13%) was seen for the remaining skeleton (25 ppm vs 0 ppm group). In addition, Cd at 25 ppm induced small but statistically significant decreases in ash weight (-12%), ash weight to dry weight (-5%), Ca/dry (-7%), and Ca/ash (-2%) in the right femur and significant decreases in ash/dry (-7%) and Ca/dry (-12%) in the lumbar vertebrae compared with the controls. Our present study supports the hypothesis that Cd at 25 ppm had a significant direct effect on bone, with no effect at 5 ppm Cd or 25 ppm Pb, and no appearance of the extreme demineralization characteristic of Itai-Itai disease, although mice were exposed to a Ca-deficient diet for 32 days. Our results from this and earlier studies support the view that chronic Cd exposure along with nutritional deficiency contributed to the pathogenesis of Itai-Itai disease among multiparous, postmenopausal women in Japan.
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PMID:Effect of cadmium on bone calcium and 45Ca in nonpregnant mice on a calcium-deficient diet: evidence of direct effect of cadmium on bone. 851 92

We investigated the effect of intratracheally instilled coal fly ash (FA) and copper smelter dust (CU) on the lung integrity and on the ex vivo release of tumor necrosis factor alpha (TNF-alpha) by alveolar phagocytes. Groups of female NMRI mice received a single intratracheal administration of different particles normalized for the arsenic content (20 micrograms/kg body weight, i.e., 600 ng arsenic/mouse) and the particle load (100 mg/kg body weight, i.e., 3 mg/mouse). Mice received tungsten carbide (WC) alone (100 mg/kg), FA alone (100 mg/kg, i.e., 20 micrograms arsenic/kg), CU mixed with WC (CU, 13.6 mg/kg, i.e., 20 micrograms arsenic/kg; WC, 86.4 mg/kg) and Ca3(AsO4)2 mixed with WC (20 micrograms arsenic/kg; WC, 100 mg/kg). Animals were sacrificed at 1, 6, or 30 d posttreatment and analyzed by bronchoalveolar lavage for total protein (TP) content, inflammatory cell number and type, and TNF-alpha production. Additional mice were studied to evaluate particle retention by measuring total arsenic retention in the lung at appropriate times. Instillation of WC induced a mild and transient (d 1) inflammatory reaction characterized by an increase of TP and an influx of polymorphonuclear leukocytes in the alveolar compartment. Compared to WC, Ca3(AsO4)2 produced a significant increase of TP content in BALF. CU particles caused a severe but transient inflammatory reaction, while a persisting alveolitis (30 d) was observed after treatment with FA. Compared to control saline, a marked inhibition of TNF-alpha release was observed in response to LPS in all groups at d 1. Cytokine production was upregulated in WC- and Ca3(AsO4)1-treated animals after 6 and 30 d, respectively. However, a 90% inhibition of TNF-alpha production was still observed at d 30 after administration of CU and FA. Although arsenic was cleared from the lung tissue 6 d after Ca3(AsO4)2 administration, a significant fraction persisted (10-15% of the arsenic administered) in the lung of CU- and FA-treated mice at d 30. We hypothetize that suppression of TNF-alpha production is dependent upon the slow elimination of the particles and their metal content from the lung.
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PMID:Reduction of the ex vivo production of tumor necrosis factor alpha by alveolar phagocytes after administration of coal fly ash and copper smelter dust. 917 58

Integrins that bind RGD (arginine-glycine-aspartic acid) containing peptides, especially the vitronectin receptor alpha(v)beta3, have been implicated in the regulation of osteoclast function. Echistatin, an RGD-containing snake venom peptide with high affinity for beta3 integrins, as well as nonpeptide RGD mimetics, were shown to inhibit osteoclastic bone resorption in vitro and in vivo. To evaluate the role of RGD-binding integrins in bone metabolism, we examined by several methods the effects of echistatin on ovariectomy (OVX)-induced bone loss in mice and rats. First, we confirmed that echistatin binds in vitro with high affinity (Kd, 0.5 nM) to alpha(v)beta3 integrin purified from human placenta and established a competitive binding assay to measure echistatin concentrations in serum. We find that echistatin infused for 2 or 4 weeks at 0.36 microg/h x g body weight (approximately 50 nmol/day x mouse) completely prevents OVX-induced cancellous bone loss in the distal femora of ovariectomized mice. Echistatin has no effect on uterine weight, body weight, and femoral length changes induced by OVX, nor does it cause any apparent changes in major organs other than bone. In OVX rats, echistatin infusion at 0.26 microg/h x g for 4 weeks effectively prevents bone loss, evaluated by dual energy x-ray absorptiometry of the femur, by femoral ash weight, and by bone histomorphometry of the proximal tibia. At effective serum concentrations of 20-30 nM, measured at the end of the infusion period, echistatin maintains histomorphometric indices of bone turnover at control levels but does not decrease osteoclast surface. In conclusion, these results provide in vivo evidence, at the level of bone histology, that RGD-binding integrins, probably alpha(v)beta3, play a rate-limiting role in osteoclastic bone resorption and suggest a therapeutic potential for integrin ligands in the suppression of bone loss.
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PMID:The integrin ligand echistatin prevents bone loss in ovariectomized mice and rats. 949 78

The castration of male mice results in osteopenia which is a suitable model for evaluating the effect of thiazides on bone. The bones of castrated mice were characterized by a decrease of ash weight, bone density and calcium and phosphate bone content. When such castrated mice were treated with high dose of hydrochlorothiazide (2 mg/day/mouse) the changes in bone density and bone mineral concentration resulting from the castration were prevented. Our data indicate a beneficial effect of long-term thiazide administration on bone mineral content in male mice, which is dose dependent.
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PMID:Hydrochlorothiazide prevents bone loss in castrated male mice. 1093 46

Airborne particulate matter (PM) is hypothesized to play a role in increases in asthma prevalence, although a causal relationship has yet to be established. To investigate the effects of real-world PM exposure on airway reactivity (AHR) and bronchoalveolar lavage (BAL) cellularity, we exposed naive mice to a single dose (0.5 mg/ mouse) of ambient PM, coal fly ash, or diesel PM. We found that ambient PM exposure induced increases in AHR and BAL cellularity, whereas diesel PM induced significant increases in BAL cellularity, but not AHR. On the other hand, coal fly ash exposure did not elicit significant changes in either of these parameters. We further examined ambient PM-induced temporal changes in AHR, BAL cells, and lung cytokine levels over a 2-wk period. Ambient PM-induced AHR was sustained over 7 d. The increase in AHR was preceded by dramatic increases in BAL eosinophils, whereas a decline in AHR was associated with increases in macrophages. A Th2 cytokine pattern (IL-5, IL-13, eotaxin) was observed early on with a shift toward a Th1 pattern (IFN-gamma). In additional studies, we found that the active component(s) of ambient PM are not water-soluble and that ambient PM-induced AHR and inflammation are dose- dependent. We conclude that ambient PM can induce asthma-like parameters in naive mice, suggesting that PM exposure may be an important factor in increases in asthma prevalence.
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PMID:Ambient urban Baltimore particulate-induced airway hyperresponsiveness and inflammation in mice. 1170 92