Biomedical subjects

Kathy Keiver

Publications and source records attributed to Kathy Keiver.

6 recordsLinked to original sources

PubMed2007

Effect of chronic ethanol consumption on the response of parathyroid hormone to hypocalcemia in the pregnant rat.

BACKGROUND: Chronic alcohol (ethanol) consumption during pregnancy results in maternal/fetal hypocalcemia, which may underlie some of ethanol's adverse effects on maternal and fetal bone, and fetal/neonatal health. Ethanol appears to alter the relationship between parathyroid hormone (PTH) and blood calcium (Ca) level, and PTH does not increase in response to ethanol-induced hypocalcemia. However, it is not known whether ethanol actually prevents PTH from responding, or whether the ability to regulate blood Ca is intact, but ethanol lowers the level of Ca maintained. The objective of this study was to determine whether chronic ethanol consumption impairs the ability of the pregnant female to increase PTH in response to acute hypocalcemia. METHODS: Rats were fed isocaloric diets with ethanol (36% ethanol-derived calories, E group) or without ethanol [pair-fed (PF) and control (C) groups], before and throughout 21 days of gestation. On day 21 gestation, rats received an intraperitoneal injection of ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (300 or 500 mumol/kg body weight) or saline (saline group), or no injection (baseline group). Blood was collected from the baseline group, and at 30 or 60 minutes postinjection (saline and EGTA groups), and analyzed for ionized Ca (iCa), pH, and PTH. RESULTS: Consistent with previous studies, ethanol consumption decreased blood iCa levels at baseline, but PTH levels did not differ among groups. Administration of EGTA significantly decreased blood iCa levels by 30 minutes, but ethanol did not prevent PTH from increasing in response to the hypocalcemia. In all diet groups, PTH levels were significantly increased by 30 minutes. Ethanol did, however, appear to decrease the maximum PTH level achievable in blood. CONCLUSIONS: These data suggest that chronic ethanol consumption does not impair the ability of the pregnant rat to raise serum PTH levels in response to acute hypocalcemia, but ethanol's effect on maximal PTH secretion could impair the ability of the pregnant female to sustain high PTH levels in response to chronic hypocalcemia.

Animals↗

PubMed2005

Ethanol administration results in a prolonged decrease in blood ionized calcium levels in the rat.

Previous studies have shown that ethanol decreases the level of ionized calcium (iCa) in the blood, and appears to prevent a compensatory increase in parathyroid hormone level. We have shown, however, that the presence of ethanol interferes with the measurement of blood iCa by the most commonly used iCa analyzer. It is impossible to interpret ethanol-induced alterations in Ca-regulating hormone levels without accurate measurement of blood iCa, thus the purpose of this study was to determine if ethanol decreases blood iCa levels independent of methodological artifacts. The time course of ethanol's effect and the relationship between iCa and blood ethanol concentration (BEC) were also examined. Rats (n=22) received ethanol (1.5 or 3 g/kg body weight) or saline by intraperitoneal injection. Blood samples were obtained by tail nick at 0, 2, 6, 24, 48 h and 8 days postinjection, and analyzed for iCa, pH, and BEC. Blood iCa and pH were measured using the I-Stat Clinical Analyzer, whose performance is not affected by the presence of ethanol. Ethanol administration resulted in a decrease in blood iCa levels. The magnitude and time course of the decrease varied with dose of ethanol, being greater and more prolonged with the higher dose, and blood iCa levels were not fully recovered at 48 h postinjection. No significant relationship was found between individual iCa and BEC values. This study confirms that ethanol decreases blood iCa levels, independent of methodological artifacts. Prolonged disruptions in Ca homeostasis resulting from ethanol consumption could have implications for long-term bone health.

Alcohol Drinking↗

PubMed2004

Accuracy of DXA scanning of the thoracic spine: cadaveric studies comparing BMC, areal BMD and geometric estimates of volumetric BMD against ash weight and CT measures of bone volume.

Biomechanical studies of the thoracic spine often scan cadaveric segments by dual energy X-ray absorptiometry (DXA) to obtain measures of bone mass. Only one study has reported the accuracy of lateral scans of thoracic vertebral bodies. The accuracy of DXA scans of thoracic spine segments and of anterior-posterior (AP) thoracic scans has not been investigated. We have examined the accuracy of AP and lateral thoracic DXA scans by comparison with ash weight, the gold-standard for measuring bone mineral content (BMC). We have also compared three methods of estimating volumetric bone mineral density (vBMD) with a novel standard-ash weight (g)/bone volume (cm3) as measured by computed tomography (CT). Twelve T5-T8 spine segments were scanned with DXA (AP and lateral) and CT. The T6 vertebrae were excised, the posterior elements removed and then the vertebral bodies were ashed in a muffle furnace. We proposed a new method of estimating vBMD and compared it with two previously published methods. BMC values from lateral DXA scans displayed the strongest correlation with ash weight (r=0.99) and were on average 12.8% higher (p<0.001). As expected, BMC (AP or lateral) was more strongly correlated with ash weight than areal bone mineral density (aBMD; AP: r=0.54, or lateral: r=0.71) or estimated vBMD. Estimates of vBMD with either of the three methods were strongly and similarly correlated with volumetric BMD calculated by dividing ash weight by CT-derived volume. These data suggest that readily available DXA scanning is an appropriate surrogate measure for thoracic spine bone mineral and that the lateral scan might be the scan method of choice.

Absorptiometry, Photon↗

PubMed2004

Ethanol interferes with the measurement of extracellular ionized calcium.

BACKGROUND: Maintenance of extracellular calcium (Ca) concentration within narrow limits is critical for normal cell function and optimization of bone health. Ionized Ca (iCa), the form of Ca that is regulated, has been reported to vary inversely with blood alcohol concentration (BAC). The mechanism by which ethanol decreases blood iCa levels is unknown. However, one possible explanation is that it is, at least partially, a methodological artifact due to an effect of ethanol on the function of the ion selective electrode used to measure iCa. The purpose of this study was to determine if ethanol interferes with the measurement of iCa and if this interference can account for the typically observed in vivo effects of ethanol consumption on blood iCa levels. METHODS: Ethanol (0-5 microl/ml) was added to blood or iCa standards and the iCa concentration measured using the ICA2 iCa analyzer (Radiometer) or the I-Stat Clinical Analyzer (Abbott Laboratories). Both instruments use an ion selective electrode to measure iCa. The relationship between iCa and BAC determined from the ex vivo addition of ethanol to blood was compared with relationships obtained in vivo during chronic ethanol consumption. RESULTS: Addition of ethanol to blood or iCa standards resulted in a dose-dependent decrease in iCa concentration when iCa was measured using the ICA2 analyzer but had no effect on iCa concentration when measured with the I-Stat Clinical Analyzer. Ethanol's effect on iCa with the ICA2 analyzer did not differ between blood and standards, and ethanol had no effect on pH, suggesting that the ethanol-induced decrease in iCa was due to a methodological artifact. However, the magnitude of ethanol's effect was small and does not account entirely for the relationship between iCa and BAC observed in vivo with chronic ethanol consumption. CONCLUSION: Ethanol can interfere with the measurement of iCa using ion selective electrodes, but this interference depends on the analyzer used. This is a significant methodological issue that has largely been unrecognized in the field of alcohol research. Although this interference does not explain entirely the relationship between iCa and BAC observed in vivo in studies on chronic ethanol consumption, it complicates investigations designed to assess the effect of ethanol on Ca homeostasis.

Animals↗

PubMed2004

Effect of duration of maternal alcohol consumption on calcium metabolism and bone in the fetal rat.

BACKGROUND: Prenatal ethanol exposure can retard fetal growth and delay skeletal development. Ethanol also impairs maternal calcium (Ca) homeostasis and this impairment could mediate some of ethanol's effects on the fetal skeleton. Our previous studies suggest that the duration of maternal ethanol consumption may be an important factor for determining the severity of ethanol's effects on Ca homeostasis and fetal skeletal development. The purpose of this study was, therefore, to determine the effect of the duration of maternal ethanol consumption on fetal growth and skeletal development and to investigate the possibility that ethanol's effects may be related to perturbations in fetal/maternal Ca homeostasis. METHODS: Rats were fed ethanol (36% ethanol-derived calories) in liquid diets for 3 weeks (days 1-21 of gestation) or 6 weeks (for 3 weeks before and throughout gestation). Fetuses were collected on day 21 of gestation, and body weight and length were measured. Fetuses were stained to determine the degree of skeletal ossification, and fetal blood was analyzed for ethanol, Ca (total and ionic Ca), albumin, parathyroid hormone (PTH), and osteocalcin. RESULTS: Maternal ethanol consumption decreased fetal growth and delayed fetal skeletal development. Although there was a trend for fetal body length and serum osteocalcin levels to be more severely affected with an increased duration of maternal ethanol consumption, duration had no effect on fetal body weight or skeletal ossification. Fetal Ca homeostasis was also affected by ethanol exposure, with fetal hypocalcemia apparent after 6 weeks of maternal ethanol intake. A significant inverse relationship was found between fetal blood Ca levels and blood alcohol concentration (BAC), suggesting that the severity of the fetal hypocalcemia may have been related to differences in fetal BAC, rather than duration of maternal ethanol intake. Fetal serum PTH levels did not differ significantly among treatment groups indicating that the fetal hypocalcemia was not caused by a decrease in PTH levels. CONCLUSIONS: Prenatal ethanol exposure impaired Ca homeostasis and skeletal development in the fetal rat. The severity of ethanol's effects was only marginally dependent on the duration of maternal ethanol consumption per se and seemed to be more related to the relative exposure of the fetus to ethanol (fetal BAC). The relationship between the ethanol-induced fetal hypocalcemia and skeletal effects remains to be determined.

Alcohol Drinking↗

PubMed2003

Effect of duration of alcohol consumption on calcium and bone metabolism during pregnancy in the rat.

BACKGROUND: Little is known about the consequences of drinking during pregnancy for the long-term health of the mother. Alcohol (ethanol) has been shown to disrupt calcium (Ca) homeostasis and is known to have deleterious effects on bone. During pregnancy, bone turnover is increased to maintain Ca homeostasis; therefore, pregnancy may be a time of life when maternal bone is particularly susceptible to the effects of ethanol. This study investigated the effect of duration of ethanol consumption on Ca homeostasis and bone during pregnancy in the rat. METHODS: Rats were fed ethanol (36% ethanol-derived calories) in liquid diets for 3 (21 days gestation only) or 6 (3 weeks before and throughout 21 days gestation) weeks. Maternal blood was analyzed for Ca (total and ionized Ca [iCa]), the Ca-regulating hormones (parathyroid hormone [PTH], 1,25(OH)2D, calcitonin), and osteocalcin (a marker for bone formation). Bone was analyzed for ash (mineral) content. RESULTS: Dams consuming ethanol (E dams) had decreased blood Ca levels (total and iCa) at both 3 and 6 weeks, but iCa was lower in E dams after 6 compared with 3 weeks. Importantly, ethanol seemed to interfere with the normal compensatory response to these decreased Ca levels. In contrast to pair-fed controls, serum PTH levels actually were decreased, 1,25(OH)2D levels failed to increase, and calcitonin levels were increased in ethanol-consuming dams, regardless of duration. Moreover, ethanol decreased bone formation, as indicated by serum osteocalcin levels, after both 3 and 6 weeks consumption, and after 6 weeks, the ash content of bone also was decreased. In addition, a relationship was found between the blood alcohol concentration (BAC) and some measures of Ca and bone metabolism. Serum 1,25(OH)2D and osteocalcin levels varied inversely, whereas serum calcitonin varied directly with BAC, suggesting that time of sampling after drinking may be an important variable for interpreting ethanol's effects on Ca and bone metabolism. In all rats, serum osteocalcin levels varied directly with PTH and 1,25(OH)2D levels. CONCLUSIONS: Ethanol consumption during pregnancy impaired Ca homeostasis in the dam, regardless of duration of consumption, and resulted in decreased bone formation and ash content of bone. Significant relationships among the Ca-regulating hormones, BAC, and osteocalcin support the hypothesis that ethanol's effects on the Ca-regulating hormones may mediate some of its effects on bone.

Alcoholism↗