Is bone alkaline phosphatase an adequate marker of bone metabolism during acute corticosteroid treatment?
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Alkaline Phosphatase↗
Biomedical subjects
A Peretz
Publications and source records attributed to A Peretz.
Quantitative ultrasound bone measurements: normal values and comparison with bone mineral density by dual X-ray absorptiometry.
Normative data for qualitative ultrasound (QUS) measurements: speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were established in 118 healthy women aged 20-86 years and in 42 healthy men aged 22-76 years. The relations between age, weight, height, and QUS were studied. QUS measurements were negatively correlated with age in both sexes. In women, age was accepted as first factor (R2 = 0.39 for SOS, 0.35 for BUA, and 0.45 for stiffness, P < 0.001); weight was accepted as second factor for BUA (R2 = 0.44, P < 0.001). In men, age was the only significant parameter (R2 = 0.41 for SOS, 0.39 for BUA, 0.43 for stiffness, P < 0.001). QUS measurements of the right and left feet were highly correlated unless unilateral foot pathology such as algodystrophy was present. Significant correlations were found between QUS of the calcaneus and dual X-ray absorptiometry (DXA) of the lumbar spine (R = 0.67, P < 0.01 for SOS; R = 0.57, P < 0.02 for BUA; R = 0.65, P < 0.01 for stiffness).
Absorptiometry, Photon↗
Precision and accuracy of in vivo bone mineral measurement in rats using dual-energy X-ray absorptiometry.
The aim of this study was to evaluate the precision and accuracy of dual-energy X-ray absorptiometry (DXA) for measuring bone mineral content at different sites of the skeleton in rats. In vitro the reproducibility error was very small (< 1%), but in vivo the intra-observer variability ranged from 0.9% to 6.0%. Several factors have been shown to affect in vivo reproducibility: the reproducibility was better when the results were expressed as bone mineral density (BMD) rather than bone mineral content (BMC), intra-observer variability was better than the inter-observer variability, and a higher error was observed for the tibia compared with that for vertebrae and femur. The accuracy of measurement at the femur and tibia was assessed by comparing the values with ash weight and with biochemically determined calcium content. The correlation coefficients (R) between the in vitro BMC and the dry weight or the calcium content were higher than 0.99 for both the femur and the tibia. SEE ranged between 0.0 g (ash weight) and 2.0 mg (Ca content). Using in vitro BMC, ash weight could be estimated with an accuracy error close to 0 and calcium content with an error ranging between 0.82% and 6.80%. The R values obtained between the in vivo and in vitro BMC were 0.98 and 0.97 respectively for femur and tibia, with SEE of 0.04 and 0.02 g respectively. In conclusion, the in vivo precision of the technique was found to be too low. To be of practical use it is important in the design of experimentation to try to reduce the measurement error.(ABSTRACT TRUNCATED AT 250 WORDS)
Absorptiometry, Photon↗
Clinical significance of heterogeneity of vertebral mineral density.
Important variations in Z-score per vertebra, which is a common expression of bone mineral density (BMD), are sometimes observed. The present study evaluates the clinical significance of this heterogeneity. Normal and osteoporotic subjects were defined by using strict criteria. For every scan, the minimal Z-score (the vertebra with the lowest Z-score) and the delta Z (highest Z-score--lowest Z-score) was calculated. Of the investigated subjects, 30% presented a delta Z > or = 1. No significant correlation could be found between delta Z and age, BMD, height and weight. There was no difference in delta Z between scans of good, average or poor quality. Osteoporotic subjects had significantly lowered BMD values, whether evaluated through Z-scores for the L2-L4 site (P < 0.001; t = 3.71) or by minimal Z-score (P < 0.001; t = 3.97). Reproducibility calculated for the L2-L4 site on phantoms as well as on patients was excellent (C.V. < 1%). When reproducibility was calculated on each vertebra in vitro or in vivo, an increase in variability was observed. These data show that marked heterogeneity in BMD per vertebra is not infrequent. In some subjects low BMD may be measured at certain vertebrae but not at the total site. Our data suggest that in those cases the lowest BMD should be considered. In follow-up studies however, the BMD should be calculated on the L2-L4 segment, since a loss of precision is observed when only one vertebra is measured.
Absorptiometry, Photon↗
SPECT diagnosis of Creutzfeld-Jacob disease.
SPECT with 99mTc-HMPAO was performed on a 65-yr-old patient with Creutzfeld-Jacob disease. Cerebral blood flow was heterogeneously decreased throughout the brain, differing from the pattern observed in other common types of dementia. These results suggest that HMPAO-SPECT may provide useful information in the differential diagnosis of dementia, specifically when Creutzfeld-Jacob disease is suspected.
Aged↗
TRP, a protein essential for inositide-mediated Ca2+ influx is localized adjacent to the calcium stores in Drosophila photoreceptors.
The Drosophila transient receptor potential (trp) gene product (TRP) shows some structural similarity to vertebrate voltage-gated Ca2+ channels. It appears to function as a novel Ca2+ channel responsible for light stimulated, inositol trisphosphate (InsP3)-mediated Ca2+ entry in the fly retina. The subcellular localization of TRP protein was determined in this study using immunohistochemical staining with anti-TRP antibody (MAb83F6). TRP was localized to the base of the microvilli in a region adjacent to the presumed InsP3-sensitive Ca2+ stores. This specific localization was supported by measuring the magnitude of a TRP-dependent inward current that results from spontaneous activation of the light-sensitive channels during whole-cell recordings (the rundown current, RDC). We found that reduction of the microvilli area through genetic dissection with the opsin null mutant, ninaEora, was correlated with a pronounced enhancement of the TRP-dependent inward current relative to wild type, suggesting that the TRP-dependent current was not produced along the length of the microvilli. We suggest that the functional localization of the TRP protein is on the plasma membrane loop found along the base of the rhabdomeric microvillus. Thus, the TRP channel may function in concert with the InsP3-sensitive Ca2+ stores.
Animals↗
The light response of Drosophila photoreceptors is accompanied by an increase in cellular calcium: effects of specific mutations.
Photoreceptors of dissociated Drosophila retinae were loaded with the fluorescent Ca2+ indicators, fluo-3 and Calcium Green-5N. In fluo-3-loaded, wild-type photoreceptors, a rapid increase in fluorescence (Ca2+ signal) accompanied the light-evoked inward current. Removal of extracellular Ca2+ greatly reduced the Ca2+ signal, indicating Ca2+ influx as its major cause. In Calcium Green-5N-loaded trp mutants, which lack a large fraction of the Ca2+ permeability underlying the light-evoked inward current, the Ca2+ signal was smaller relative to wild-type photoreceptors. Fluo-3-loaded norpA mutant photoreceptors, which lack a light-activated phospholipase C, generated no light-evoked inward current and no Ca2+ signal. The phosphoinositide pathway therefore appears necessary for both excitation and changes in cytosolic free Ca2+ concentration.
Aniline Compounds↗
Genetic dissection of light-induced Ca2+ influx into Drosophila photoreceptors.
Invertebrate photoreceptors use the inositol-lipid signaling cascade for phototransduction. A useful approach to dissect this pathway and its regulation has been provided by the isolation of Drosophila visual mutants. We measured extracellular changes of Ca2+ [delta Ca2+]o in Drosophila retina using Ca(2+)-selective microelectrodes in both the transient receptor potential (trp) mutant, in which the calcium permeability of the light-sensitive channels is greatly diminished and in the inactivation-but-no-afterpotential C (inaC) mutant which lacks photoreceptor-specific protein kinase C (PKC). Illumination induced a decrease in extracellular [Ca2+] with kinetics and magnitude that changed with light intensity. Compared to wild-type, the light-induced decrease in [Ca2+]o (the Ca2+ signal) was diminished in trp but significantly enhanced in inaC. The enhanced Ca2+ signal was diminished in the double mutant inaC;trp indicating that the effect of the trp mutation overrides the enhancement observed in the absence of eye-PKC. We suggest that the decrease in [Ca2+]o reflects light-induced Ca2+ influx into the photoreceptors and that the trp mutation blocks a large fraction of this Ca2+ influx, while the absence of eye specific PKC leads to enhancement of light-induced Ca2+ influx. This suggestion was supported by Ca2+ measurements in isolated ommatidia loaded with the fluorescent Ca2+ indicator, Ca Green-5N, which indicated an approximately threefold larger light-induced increase in cellular Ca2+ in inaC relative to WT. Our observations are consistent with the hypothesis that TRP is a light activated Ca2+ channel and that the increased Ca2+ influx observed in the absence of PKC is mediated mainly via the TRP channel.
Animals↗
Effects of zinc supplementation on the phagocytic functions of polymorphonuclears in patients with inflammatory rheumatic diseases.
The phagocytosis of blood polymorphonuclear cells (PMNs) was measured by cytofluorometry in 22 patients with inflammatory rheumatic diseases before and after a 60-day treatment with 45 mg zinc daily or a placebo, and the values were compared with those obtained in a group of healthy subjects. Plasma zinc was lower than controls before supplementation and phagocytosis assessed by the percentage of PMNs exhibiting phagocytic activity was significantly impaired. Zinc supplementation increased the percentage of phagocytic PMNs and the mean phagocytic activity, particularly in subjects with initial low phagocytosis. The impairment of PMN phagocytosis could therefore be corrected by zinc supplementation, but the clinical consequence of this stimulant effect remains unknown.
Administration, Oral↗
Ca2+ limits the development of the light response in Drosophila photoreceptors.
The development of the light response was followed in Drosophila photoreceptors at 25 degrees C. In whole-cell recordings from dissociated ommatidia, responses to light were first detected at 82 h post-puparium formation; over the next 8 h sensitivity to light increased exponentially by 5 or 6 orders of magnitude. The end of this phase coincided with the maturation of the rhabdomere as measured by whole-cell capacitance. There was a modest 5-10fold further increase in sensitivity over the final 10 h of pupal development (90-100 h). During a narrow developmental time window (82-87 h) no responses could be detected using non-invasive recording techniques (electroretinogram or suction electrode), and responses to light could only be elicited in whole-cell recordings when micromolar concentrations of Ca2+ are included in the pipette. It seems unlikely that cytosolic Ca2+ per se is the limiting factor, and we suggest instead that the failure to respond to light is due to the lack of Ca2+ in the InsP3-sensitive intracellular stores and that the presence of Ca2+ in these stores is an absolute requirement for phototransduction in Drosophila.
Animals↗
Protein kinase C is required for light adaptation in Drosophila photoreceptors.
Protein kinase C (PKC) is a key enzyme for many cellular processes but its physiological roles are poorly understood. An excellent opportunity to investigate the function of PKC has been provided by the identification of an eye-specific PKC in Drosophila and a null PKC mutant, inaCP209 (refs 5,6). Bright conditioning lights delivered to inaC photoreceptors lead to an abnormal loss of sensitivity in whole cell recordings from dissociated ommatidia; this has been interpreted as 'hyper-adaptation' and PKC's role has been suggested to be distinct from light adaptation. A presumably related finding is that during intense light, the response of inaC declines to baseline. Invertebrate photoreceptors use the phosphoinositide signalling cascade, responding to single photons with so-called quantum bumps which sum to form the macroscopic response to light. Light adaptation allows photoreceptors to adjust their sensitivity over the enormous range of ambient intensities. Although the molecular mechanism of light adaptation remains obscure, it is a negative-feedback process mediated by a rise in cytosolic calcium and a decrease in bump size. We now show that under physiological conditions light adaptation is severely reduced in inaC, suggesting that eye-specific PKC, itself activated by a rise in cytosolic calcium and diacylglycerol, is required for adaptation. Furthermore, we show that in the absence of PKC individual bumps fail to terminate normally, an effect that can account for the pleiotropic manifestations of the inaC phenotype.
Adaptation, Ocular↗
Decrease of bone mineral density during estrogen substitution therapy.
A decrease in bone mineral density (BMD) in patients treated with hormone replacement therapy (HRT) is sometimes observed in clinical practice. In order to assess the frequency and the characteristics of these cases, we reviewed the data of 102 women treated with HRT for more than 2 years, and who had undergone at least 3 lumbar BMD measurements during that period. For each patient, a linear function was fitted to the BMD data in relation to time. The slope was calculated. There was an overall gain in BMD during treatment, mean (+/- S.E.M.) values of slope 0.007 g/cm2/year (+/- 0.002). Fifty-three patients had a slope higher than 0.005, 28 a slope close to 0 (between 0.005 and -0.005) and 21 a slope lower than -0.005. By dividing the patients in tertiles of slopes (tertile I: slope < 0; tertile II: 0 < slope < 0.011; tertile III: slope > 0.011), significant differences were observed between the three groups of slope for the initial BMD (P < 0.001), hydroxyproline/creatinine ratio (P < 0.01), weight, DHEAS and alkaline phosphatase (P < 0.05). Only 1 of the 15 patients with a low bone mass (lower than mean +/- 1 S.D.) had a negative slope, while 9 of the 16 with a high-bone mass (higher than mean +/- 1 S.D.), had a negative slope. Under HRT, about 21% of postmenopausal women have a slight decrease in BMD as assessed by DPA. Because of the DPA coefficient of variation, however, the exact number of bone losers cannot be determined.(ABSTRACT TRUNCATED AT 250 WORDS)
Alkaline Phosphatase↗
Zinc distribution in blood components, inflammatory status, and clinical indexes of disease activity during zinc supplementation in inflammatory rheumatic diseases.
The effects of zinc supplementation on zinc status and on clinical and biological indicators of inflammation were investigated in 18 patients with chronic inflammatory rheumatic diseases and in 9 healthy control subjects. Patients with mild and recent onset disease were assigned to a 60-d trial to receive either 45 mg Zn (as gluconate)/d or a placebo, while control subjects received the zinc supplement. Baseline mean plasma zinc of the patients was low whereas mononuclear cell zinc content was elevated, suggesting a redistribution of the element related to the inflammatory process rather than to a zinc-deficient state. Zinc supplementation increased plasma zinc to a similar extent in patients and in control subjects, which suggested no impairment of zinc intestinal absorption as a result of the inflammatory process. On the contrary, erythrocyte and leukocyte zinc concentrations were not modified in the two groups examined. No beneficial effect of zinc treatment could be demonstrated on either clinical or inflammation indexes.
Adult↗
Bone mineral density measured by dual photon and dual energy X-ray absorptiometry: a problem of accuracy.
Dual photon absorptiometers (DPA) are currently being replaced by dual energy X-ray absorptiometers (DXA) for measurements of bone mineral density (BMD). In order to evaluate how to use the previously obtained BMD results by DPA (BMDo) in the follow-up of patients, the following study was performed. Ninety-five women who had had BMDo during the last 12 months were selected. L2-L4 BMD was measured twice on the same day using both DPA (BMDp) and by DXA (BMDx). BMDp was highly correlated to BMDx (R = 0.95; P < 0.001) but a wide variation of the ratio BMDp:BMDx was observed which ranged between 0.65 and 1.09 (mean 0.90, S.D. 0.05). There was no significant relationship between the ratio BDMp:BMDx and age or height but there was a significant relationship between this ratio and the weight of the patient (R = 0.31; P < 0.001). The results also indicated that the correlation between DXA and DPA was lower than that observed between the two DPA measurements (R = 0.98; P < 0.001) which, moreover, were not performed on the same day. These observations contrast with the relatively high precision of both instruments and have to be attributed to relative inaccuracy of one or probably both techniques.
Absorptiometry, Photon↗
[Osteocalcin, marker of bone metabolism].
The recent development of biochemical markers gives the opportunity to assess bone metabolism. Osteocalcin is a non collagenous protein of the bone matrix specifically synthesized by osteoblasts. The concentration of osteocalcin in serum reflects osteoblastic function and bone turnover. It has emerged as a more specific index of bone metabolism than serum alkaline phosphatase activity. Great care must be taken in blood sampling, processing and storage to avoid protein degradation. Inasmuch, we have shown in human clinical settings, the interest of this marker in patients with bone metabolic disorders characterized by increased bone turnover such as primary and secondary hyperparathyroidism or postmenopausal osteoporosis. Conversely, exogenous or endogenous high levels of corticosteroids rapidly induced a reversible decrease in osteocalcin levels.
Adrenal Cortex Hormones↗
Optimized steps in fluorometric determination of thiobarbituric acid-reactive substances in serum: importance of extraction pH and influence of sample preservation and storage.
A simple, reliable, and reproducible fluorometric method for measuring thiobarbituric acid-reactive substances (TBARS) in serum is proposed, based on the reaction between malondialdehyde (MDA) and thiobarbituric acid. Formation of TBARS was complete at pH 2.4-2.6, but extraction with n-butanol proved complete only at lower pH, i.e., 1.6-1.7. Analytical recoveries of MDA added to serum were 94%-101%; within- and between-run CVs were 2.4-3.6% and 4.6-5.5%; and the detection limit for TBARS in serum was 0.10 mumol/L. Optimized conditions included: (a) collection of either serum or heparinized plasma, (b) preservation from in vitro autoxidation by glutathione and EDTA, and (c) storage at -20 degrees C up to 35 days. The mean (+/- SD) TBARS concentration in 47 healthy adults was 1.01 (0.21) mumol/L; no sex-related difference was observed. Higher concentrations were measured in patients with renal insufficiency undergoing hemodialysis and in patients with insulin-dependent diabetes, chronic pancreatitis, or liver cirrhosis.
1-Butanol↗
Calcium channel blockers inhibit retinal degeneration in the retinal-degeneration-B mutant of Drosophila.
Light accelerates degeneration of photoreceptor cells of the retinal degeneration B (rdgB) mutant of Drosophila. During early stages of degeneration, light stimuli evoke spikes from photoreceptors of the mutant fly; no spikes can be recorded from photoreceptors of the wild-type fly. Production of spike potentials from mutant photoreceptors was blocked by diltiazem, verapamil hydrochloride, and cadmium. Little, if any, effect of the (-)-cis isomer or (+)-cis isomer of diltiazem on the light response was seen. Further, the (+)-cis isomer was approximately 50 times more effective than the (-)-cis isomer in blocking the Ca2+ spikes, indicating that diltiazem action on the rdgB eye is mediated by means of blocking voltage-sensitive Ca2+ channels, rather than by blocking the light-sensitive channels. Application of the Ca(2+)-channel blockers (+)-cis-diltiazem and verapamil hydrochloride to the eyes of rdgB flies over a 7-day period largely inhibited light-dependent degeneration of the photoreceptor cells. Pulse labeling with [32P]phosphate showed much greater incorporation into eye proteins of [32P]phosphate in rdgB flies than in wild-type flies. Retarding the light-induced photoreceptor degeneration in the mutant by Ca(2+)-channel blockers, thus, suggests that toxic increase in intracellular Ca2+ by means of voltage-gated Ca2+ channels, possibly secondary to excessive phosphorylation, leads to photoreceptor degeneration in the rdgB mutant.
Action Potentials↗
Risk of osteoporosis in men with chronic bronchitis.
Theoretically, patients with chronic bronchitis are at risk for osteoporosis. Bone metabolism was assessed in 44 male chronic bronchitics treated with oral prednisolone (C+; n = 19) or with bronchodilatory drugs alone (C-; n = 25). In both groups, serum osteocalcin was lower (p less than 0.001) than in age- and sex-matched controls (mean (ng/ml) C+ 1.0, C- 1.9, controls 4.2), while testosterone was at the lower limit of the reference range. Low trabecular bone mineral density (BMD) was noted in the C- group (median Z score -1.0), but both cortical and trabecular BMD were depressed in the C+ group (-1.0 and -1.4, respectively). In conclusion, chronic bronchitics treated with corticosteroids, even at low doses, are at risk for osteoporosis. In both groups, additional factors such as hypogonadism might be responsible for low BMD and low osteocalcin levels. A decrease in bone formation is a possible mechanism of action.
Adrenal Cortex Hormones↗