Blood Ca Research Articles

The effect of an HMG-CoA reductase inhibitor on arteriosclerotic nanoplaque formation and size in a biosensor model

Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution, thereby representing a receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques. Low-density lipoprotein (LDL) was found to deposit strongly at the proteoheparan sulfate-coated surface, particularly in the presence of Ca 2+, apparently through complex formation ‘proteoglycan–LDL–calcium’. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. HDL bound to heparan sulfate proteoglycan protected against LDL deposition and completely suppressed calcification of the proteoglycan–lipoprotein complex. In addition, HDL was able to decelerate the ternary complex deposition and to disrupt newly formed nanoplaques. Therefore, HDL attached to its proteoglycan receptor sites is thought to raise a multidomain barrier, selection and control motif for transmembrane and paracellular lipoprotein uptake into the arterial wall. The molecular arteriosclerosis model was tested on its reliability in a biosensor application in order to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. The very low-density lipoprotein (VLDL)/intermediate-density lipoprotein (IDL)/LDL and VLDL/IDL/LDL/HDL plasma fractions from a high-risk patient with dyslipoproteinemia and type 2 diabetes mellitus showed beginning arteriosclerotic nanoplaque formation already at a normal blood Ca 2+ concentration, with a strong increase at higher Ca 2+ concentrations. Nanoplaque formation and size of the HDL-containing lipid fraction remained well below that of the LDL-containing lipid fraction. Fluvastatin, whether applied acutely to the patient (one single 80 mg slow release matrix tablet) or in a 2-months medication regimen, markedly slowed down this process of ternary aggregational nanoplaque build-up and substantially inhibited nanoplaque size development at all Ca 2+ concentrations used. The acute action resulted without any significant change in lipid concentrations of the patient. Furthermore, after nanoplaque generation, fluvastatin, similar to HDL, was able to reduce nanoplaque formation and size. These immediate effects of fluvastatin have to be taken into consideration while interpreting the clinical outcome of long-term studies.

Effect of anionic salts on some blood and urine minerals, acid-base balance and udder oedema of dry pregnant cows

The objective of this study was to determine the effect of an anionic diet on mineral metabolism, acid-base status and udder oedema of dairy cows fed grass silage based diets during the dry period. Eighteen pregnant, non-lactating Friesian cows were divided randomly into two groups according to their expected calving date. Dietary cation-anion balance (DCAB), calculated as mill equivalents [(Na + + K + ) - (Cl - + S 2- )], for high DCAB (control) and low DCAB treatments were +254 and -41 mEq kg -1 dry matter (DM), respectively. Anionic salts were ammonium chloride (NH 4 Cl), magnesium chloride (MgCl 2 ) and magnesium sulphate (MgSO 4 ). Cows received grass silage (5.2 kg DM), hay (0.9 kg DM) and a concentrate mixture (2.7 kg DM) until calving. Blood and urine samples were collected 4, 3, 2 and 1 week before the expected calving date, at calving, 1 day and 1 week after calving. Udder oedema was evaluated by a quantitative and a subjective method. Acidification resulted in a marked decrease in urinary pH, increased urinary Ca excretion and a change in blood acidbase balance. Blood Ca 2+ and plasma Ca tot concentrations were more stable at parturition for the anionic group, although such differences were not statistically significant. Anionic salts (DCAB -41 mEq kg -1 DM) did not cause udder oedema in experimental cows.;

Which Parameter Is More Influential on the Development of Arteriosclerosis in Hemodialysis Patients?

Arteriosclerosis is characterized by stiffening of arteries. The incremental elastic modulus (Einc) measurement is a good marker of arterial wall stiffness. Metabolic, inflammatory and hemodynamic alterations cause structural changes and vascular complications in end stage renal disease. The aim of the present study was to evaluate the factors that may affect the development of arteriosclerosis by measurement of Einc in hemodialysis (HD) patients. Thirty-two patients (16 men; 16 female) on chronic HD with a mean age of 42.2 ± 19.3 (range: 15–80) were included in the study. The carotid Einc was measured to determine arteriosclerosis by high-resolution echo-tracking system (Acuson Aspen, Acuson Corp., Mountain View, California, USA). Einc measurement was calculated from transcutaneous measurements of common carotid arterial (CCA) internal diameter and wall thickness and carotid pulse pressure. Common carotid compliance and distensibility were determined from changes in carotid artery diameter during systole and simultaneously measured carotid pulse pressure. Common carotid artery stuffiness (Einc) was influenced by age, systolic blood pressure (SBP), pulse pressure (PP), calcium (Ca) and alkaline phosphatase (ALP). The distensibility of CCA was correlated with age, SBP, diastolic blood pressure (DBP), PP, Ca, ALP, and parathormone (PTH). The inflammatory parameter, hs-CRP, was increased with Einc. The mean Einc measurement was found significantly increased in patient receiving vitamin D. In conclusion, the stiffening of carotid artery in HD patients is related not only to hemodynamic changes (increased SBP, PP) but also to metabolic (increased Ca) and to inflammation (increased hs-CRP). Carotid Einc is accepted independent risk factor for cardiovascular mortality. Because of the positive correlation between Einc and serum Ca, vitamin D and Ca containing phosphorus (P) binders should be used carefully.

The acute effect of fluvastatin on lipoprotein deposition in a model substrate for ellipsometry studies at an endothelial membrane equivalent

Proteoheparan sulfate can be adsorbed to a methylated silica surface in a monomolecular layer via its transmembrane hydrophobic protein core domain. Due to electrostatic repulsion, its anionic glycosaminoglycan side chains are stretched out into the blood substitute solution representing one receptor site for specific lipoprotein binding through basic amino acid-rich residues within their apolipoproteins. The binding process was studied by ellipsometric techniques. LDL was found to deposit strongly at the proteoheparan sulfate, particularly in the presence of Ca 2+ thus creating the complex formation proteoglycan — low-density lipoprotein — calcium. This ternary complex build-up may be interpreted as arteriosclerotic nanoplaque formation on the molecular level responsible for the arteriosclerotic primary lesion. Although much remains unclear regarding the mechanism of lipoprotein depositions at proteoglycan-coated surfaces, it seems clear that the use of such systems offers possibilities for investigating lipoprotein deposition at a nanoscopic level under close to physiological conditions. Therefore, we tested the system on its reliability in a biosensor application in order to unveil possible acute pleiotropic effects of the lipid lowering drug fluvastatin. Already with a normal blood Ca 2+ concentration, the VLDL/IDL/LDL plasma fraction from a high-risk patient with dyslipoproteinemia and type 2 diabetes mellitus showed beginning arteriosclerotic nanoplaque formation that massively increased at higher Ca 2+ concentrations. Fluvastatin, whether applied to the patient (one single 80 mg slow release matrix tablet) or acutely in the experiment (2.2 μmol/l), markedly slowed down this process of ternary aggregational nanoplaque complexation at all Ca 2+ concentrations used. This action resulted without any change in lipid concentrations of the patient. Furthermore, after ternary complex build-up, fluvastatin was able to reduce nanoplaque adsorption and size. These immediate effects of fluvastatin have to be taken into consideration while interpreting the results of long-term studies. Altogether, the proteoglycan coated hydrophobic silica surface used in these experiments, mimics the endothelial cell membrane in quite a perfect manner with respect to lipoprotein interactions at the blood-endothelium-matrix interface.

Direct raises in blood Ca levels by infusing a high-Ca solution into the blood stream accelerate the secretion of calcitonin from the ultimobranchial gland in eels.

In eels, a CaCl(2) solution was infused into the pneumatic duct vein. Plasma Ca levels were significantly increased during 3 hr and were followed by significant raises in plasma calcitonin levels. These results strongly suggest that, in eels, direct raises in blood Ca levels by infusion of a high-Ca solution via blood vessels can accelerate the secretion of calcitonin from the ultimobranchial gland.

The calcimimetic agents: Perspectives for treatment

Recognition of the role of the extracellular calcium sensing receptor (CaR) in mineral metabolism has greatly improved our understanding of calcium homeostasis. The biology of the low affinity, G-protein-coupled CaR and the effects of its activation in various tissues are reviewed. Physiological roles include regulation of parathyroid hormone (PTH) secretion by small changes in ionized calcium (Ca++), and control of urinary calcium excretion with small changes in blood Ca++. The CaR also affects the renal handling of sodium, magnesium, and water. Mutations affecting the CaR that make it either less or more sensitive to Ca++ cause various clinical disorders. Disorders, such as primary and secondary hyperparathyroidism, may exhibit acquired abnormalities of the CaR. Calcimimetic drugs, which amplify the sensitivity of the CaR to Ca++, can suppress PTH levels with a resultant fall in blood Ca++. Experiences with R-568 in patients with secondary and primary hyperparathyroidism and parathyroid carcinoma are summarized. In humans with hyperparathyroidism, these agents produce a dose-dependent fall in PTH and blood Ca++, with larger doses causing more sustained effects. The second generation calcimimetic, AMG 073, with a better pharmacokinetic profile appears to be an effective and safe treatment for secondary hyperparathyroidism, producing suppression of PTH levels with a simultaneous reduction in serum phosphorus levels and the calcium X phosphorus product. The advantage of controlling PTH secretion without the complications related to hypercalcemia, hyperphosphatemia, and increased calcium X phosphorus product is very promising. Treatment trials have been relatively short-term except for one patient treated with R-568 for more than 600 days for parathyroid carcinoma; nonetheless the drug had no major side effects and appeared to be safe. Further long-term controlled studies are underway to further confirm the effectiveness and safety of these compounds.

Effects of ECL cell extracts and granule/vesicle-enriched fractions from rat oxyntic mucosa on cAMP and IP(3) in rat osteoblast-like cells.

The existence of an osteotropic hormone (referred to as gastrocalcin) in the ECL cells of the gastric mucosa has been suggested. Both gastrin and an extract of the oxyntic mucosa lower blood Ca(2+) and stimulate Ca(2+) uptake into bone. The ECL cells are known to operate under gastrin control and, conceivably, gastrin lowers blood Ca(2+) indirectly by releasing the hypothetical ECL cell hormone. We have shown earlier that extracts of isolated ECL cells or of the granule/vesicle fraction of the oxyntic mucosa evoke a typical Ca(2+)-mediated second messenger response in osteoblastic cells. In the present study, we characterize this response further. An increase in intracellular inositol 1,4,5-trisphosphate (IP(3)) concentration was observed after treatment of UMR-106.01 osteoblast-like cells with extracts of ECL cells or granule/vesicle-enriched fractions from oxyntic mucosa. Intracellular cyclic adenosine monophosphate (cAMP) concentrations were not affected. Inhibition of phospholipase C (PLC) by U-73122 abolished the increase in [Ca(2+)](i). Preincubation of UMR-106.01 cells with pertussis toxin, which blocks many G-proteins, did not prevent the increases in IP(3) and [Ca(2+)](i). It was also found that the novel peptide hormone ghrelin, produced in the A-like cells of the oxyntic mucosa, did not evoke any Ca(2+) signal in osteoblastic cells. The results indicate that the extracts mediate their effects through a pertussis toxin-insensitive mechanism, and that binding to a receptor leads to activation of PLC and production of IP(3) resulting in increased [Ca(2+)](i). The putative osteotropic hormone is distinct from ghrelin.

Gastrectomized Rats Respond with Exaggerated Hypercalcemia to Oral and Intravenous Calcium Loads because of Impaired Ability of Bone to Take Up Ca 2+

Background: Gastrectomy (GX) causes osteopenia. The hypothesis tested in the present study is that GX affects Ca homeostasis and that an impaired ability to handle Ca contributes to the GX-evoked osteopenia. Methods: SHAM-operated and GX rats were compared with respect to changes in blood Ca 2+ after oral or intravenous loads of CaCl 2 1-2 weeks or 2-4 months after the operations. Results: Different doses of oral CaCl 2 raised blood Ca 2+ more in GX than in SHAM rats, more so after 2-4 months than after 1-2 weeks. The rise was greater in fasted (48 h) rats than in fed rats regardless of whether they were SHAM or GX. While SHAM rats tolerated high doses of CaCl 2 well, GX rats died when exposed to quite modest doses, particularly 2-4 months after GX. Intravenous infusion of CaCl 2 (2500 w mol/kg/h) induced a greater and steeper rise in blood Ca 2+ in GX rats than in SHAM rats. Kinetic analysis of the blood Ca 2+ data showed GX rats to display: 1) a decreased Ca 2+ elimination clearance from the central distribution compartment (blood), 2) a reduced size of the peripheral distribution compartment (the so-called bone fluid compartment), and 3) a spectacular decrease in the intercompartmental clearance (transfer of Ca 2+ from blood to bone). These effects were notably apparent after 2-4 months. At sacrifice, the GX-evoked osteopenia was confirmed by planimetric analysis of the calvariae, revealing 40% reduction of bone tissue after 2-4 months. Conclusions: Based on the present data we argue that GX rats respond with exaggerated hypercalcemia to oral and intravenous CaCl 2 loads because of a greatly impaired transfer of Ca 2+ from blood to bone. We suggest that with time this impairment results in osteopenia.

Effects of Calcium Deficiency and Calcium Supplementation on Gastrectomy-induced Osteopenia in the Young Male Rat

Background: Surgical removal of the stomach (gastrectomy, Gx) induces osteopenia. In this study we compared the osteopenic effect of Gx with that induced by calcium (Ca) deficiency. Methods: Young male rats were subjected to Gx and/or low Ca diet (-Ca). A group of Gx rats received standard diet + oral Ca supplementation (+Ca). The rats were killed at various times after the operation/start of treatment (longest time 12 weeks). After 8 weeks on low Ca diet, the blood Ca 2+ concentration was lowered slightly in both Sham-operated and Gx rats. The calvariae were subjected to transillumination analysis and quantitative histomorphometry. Also the tibiae were subjected to histomorphometry. Results: Transillumination of the calvariae revealed extensive bone loss in the rats that had been subjected to Gx and/or low Ca diet. Gx + Ca induced the same bone loss as Gx alone. These observations were later confirmed in quantitative terms by histomorphometry (Sham-Ca 56%, Gx 35%, Gx + Ca 32%, Gx - Ca 58% less bone area than in Sham). The osteopenia induced by Gx+ low Ca diet seemed more rapid in onset than that induced by Gx or low Ca diet alone. Tibiae from Gx rats and rats given a low Ca diet displayed a reduced trabecular bone volume (Sham-Ca 27% remaining, Gx 36%, Gx + Ca 44%, Gx - Ca 17%) and reduced trabecular number (Sham-Ca 44% remaining, Gx 41%, Gx + Ca 56%, Gx - Ca 33%). The trabecular thickness was reduced in the Gx rats and Gx - Ca rats (Gx 78% remaining, Gx-Ca 63%) but not in Sham-operated rats receiving a low Ca-diet (95% remaining). Conclusion: Although the pattern of osteopenia was qualitatively quite similar in Gx rats and Cadeficient rats, in quantitative terms the low Ca diet was more detrimental to bone than Gx. Ca deficiency induced a similar degree of osteopenia in both Sham and Gx rats. Ca supplementation failed to prevent the Gx-induced osteopenia.

Effects of supplemental vitamin D3 on feed intake, carcass characteristics, tenderness, and muscle properties of beef steers.

Research was conducted to determine the effects of supplemental dietary vitamin D3 on DMI, carcass traits, Warner Bratzler shear (WBS) force, calpastatin activity, plasma minerals, pH (0, 3, 12, and 24 h after slaughter), water-holding capacity (WHC), and sensory characteristics of three muscles. Pre-slaughter vitamin D3 treatments included no supplemental vitamin D3, 6 x 106 IU (MIU) of vitamin D3 for 4 d, or 6 MIU of vitamin D3 for 6 d. Cattle were slaughtered and carcasses were chilled for 48 h before removal of steaks from the longissimus, gluteus medius, and biceps femoris muscles. Steaks were aged at 2 degrees C for 7, 14, or 21 d before cooking to a final internal temperature of 70 degrees C for WBS and sensory panel analysis. Dry matter intake was lower for steers supplemented with vitamin D3 for 4 or 6 d. Live and carcass weights were lower (P < 0.05) in steers supplemented with vitamin D3. Supplementing 6 MIU/6 d of vitamin D3 decreased (P < 0.05) WBS values of gluteus steaks (pooled over aging times). Longissimus steaks from steers supplemented with vitamin D3 for 6 d had lower (P < 0.05) WBS force values than these steaks from control steers or steers fed vitamin D3 for 4 d at 7 d postmortem. Biceps femoris steaks from steers receiving vitamin D3 for 4 d had higher WBS values than steaks from control steers at 14 and 21 d postmortem. Feeding vitamin D3 at 6 MIU for 6 d decreased (P < 0.05) the percentage of steaks that had WBS values > or = 3.86 kg for all steaks. Feeding vitamin D3 had no effect on palatability traits evaluated by trained panelists. Blood Ca concentrations were greater (P < 0.05) when vitamin D3 was fed and with increased vitamin D3 feeding time. Feeding vitamin D3 for 6 d (vs 4 d) delayed pH decline for all muscle types after 0, 3, and 12 h postmortem. Water-holding capacity was increased (P > 0.02) after 0 h, 24 h, and 21 d postmortem when vitamin D3 was fed and was greater at 0 and 24 h if vitamin D3 was fed for 6 d rather than 4 d. These data suggest that supplementing 6 MIU of vitamin D3 will decrease DMI and improve beef tenderness through increased blood plasma Ca concentrations and WHC.

Evaluation of a transportable [Ca++] and pH analyser and of the impact of different anticoagulants and sampling sites in cattle.

A mobile, hand-held ionized calcium and pH analyser, the IRMA (Immediate Response Mobile Analyser) SL (Diametrics Medical Inc. St. Paul, MN, USA), was evaluated and results interpreted with help from data derived on biological variation in five dry cows. The maximum allowable analytical imprecision (CMAX) was estimated as 1.33% for [Ca++] and 0.12% for pH; the maximal allowable analytical inaccuracy (BMAX) was estimated to be 1.82% ([Ca++]) and 0.09% (pH), and the maximum allowable difference between two methods (MAXDIFF) was calculated as 0.89% ([Ca++]) and 0.08% (pH). These values were compared with the coefficient of variation obtained by calculation from analysis results in blood samples obtained from 51 cows, heifers and calves. The between-cow coefficient of variation (CV), within-cow CV, critical difference (two-sided) and index of individuality were estimated as 4.77, 2.66 and 14.29%, and 1.08 for [Ca++] analysis. For pH measurements, values of 0.12, 0.24 and 0.96% and 2.95 were estimated. The number of samples required to determine the true value of either [Ca++] or pH in an individual cow was 5 and 1, respectively. Further, it was observed that, in investigations of blood Ca++ and blood pH in cattle, neither the use of electrolyte-balanced syringes interchangeable with sodium-heparin vacutainer nor the use of different blood sampling sites was to be recommended. IRMA SL did not correlate significantly with the chosen reference analyser (Stat Profile 5 Analyser; Nova Biomedical, Waltham, MA) with regard to plasma [Ca++] analyses (correlation coefficient r = -0.24, P = 0.22). However, a significant correlation coefficient (r = 0.63, P < 0.01) was found between analyses of pH performed on IRMA SL and Stat Profile 5 Analyser. Analysis on IRMA SL was very easy to perform. It could be a very useful aid in veterinary clinical practice, when determination of plasma pH in cattle is needed. The analyser should not yet be applied uncritically with respect to [Ca++] analyses in cattle.

Physiological blocking of the mechanisms of cold death: theoretical and experimental considerations

The cold inhibited functions of skin thermoreceptors, of the thermoregulation centre, and the respiration centre during deep hypothermia can be restored without rewarming the body. The methods used were developed to test the hypothesis that during deep hypothermia calcium ion concentration [Ca 2+] i in the cytoplasm increases. This causes a perturbation of cell metabolism, the impairment of cell membrane function that cause the inhibition of cell functioning, resulting in cell death. Such an increase in [Ca 2+] i most likely would result from an energy deficit in a deeply cooled cell, which would compromise the processes that maintain the [Ca 2+] i at about 10 −7 M. These processes require large amounts of energy since they occur against a large concentration gradient. With the use of EDTA the extracellular concentration of Ca 2+ has been lowered by 15–27%, so reducing the concentration gradient for Ca 2+ between the cell and the medium and in consequence facilitated the process the extrusion of cell Ca 2+. During a period of cooling, sufficient to impair normal functioning, the experimental lowering of blood Ca 2+ allowed the restoration of normal function without the need to rewarm. In such cases the animals survived after cooling the body to temperatures at which they would normally have succumbed. The data presented support the stated hypothesis that the impairment of cellular function in mammals by low temperatures is the result of an uncorrected rise in [Ca 2+] i .

Mucoadhesive DL-Lactide/Glycolide Copolymer Nanospheres Coated with Chitosan to Improve Oral Delivery of Elcatonin

The purpose of this work was to develop a novel mucoadhesive DL-lactide/glycolide copolymer (PLGA) nanosphere system to improve peptide absorption and prolong the physiological activity following oral administration. The desired PLGA nanospheres with elcatonin were prepared by the emulsion solvent diffusion method to coat the surface of the resultant nanospheres with a mucoadhesive polymer such as chitosan, poly(acrylic acid), and sodium alginate. Their mucoadhesive properties were evaluated by measuring the nanospheres adsorbed to a rat everted intestinal sac (in vitro). The chitosan-coated nanospheres showed higher mucoadhesion to the everted intestinal tract in saline than the other polymer-coated nanospheres. There was no mucoadhesion site-specificity of the chitosan-coated nanospheres between duodenal, jejunal, and ileal sacs. The payload of drug in the chitosan-coated nanospheres was successfully increased by using the solvent diffusion method in oil. The pattern of drug release of the resultant nanospheres did not differ markedly from that of uncoated nanospheres. The chitosan-coated nanospheres with elcatonin were administered intragastrically to fasted Wistar rats. The chitosan-coated nanosphere reduced significantly the blood calcium level compared with elcatonin solution and uncoated nanospheres, and the reduced calcium level was sustained for a period of 48 hr. Even under nonfasting conditions, the mucoadhesion of chitosan-coated nanospheres was unaltered and the reduction in blood Ca levels was maintained satisfactorily.

Hormonal Control of Ca Homeostasis in Lower Vertebrates: Considering the Evolution

Abstract Early vertebrates may have had genes that would later produce hormones concerning Ca homeostasis in advanced vertebrates. These genes may possibly have expressed the respective product for the local control of Ca in some tissues, which must be a paracrine control. When vertebrates acquired the jaw, however, delicate but systemic Ca control system may have been needed to cope with fluctuations in blood Ca levels resulting from the digestion of food. Furthermore, when vertebrates were transferred from freshwater to seawater or to land, new control systems must have been required. Therefore, such vertebrates might have coped with two ways in their evolution. One is the increase of the number of local production sites of hormones, for the delicate control of Ca in various tissues, which must be the paracrine control. The other is the creation of new glands for the systemic control of Ca homeostasis by making paracrine cells independent from tissues. This style must be an endocrine control. Therefore,...

Long-Term Systemic Administration of Human Recombinant Interleukin-1β Induces a Dose-Dependent Fall in Circulating Parathyroid Hormone in Rats

The synergism/antagonism between interleukin (IL)-1β and parathyroid hormone (PTH) has been the subject of in vitro and in vivo work, but a possible direct action of the cytokine on PTH release has not been reported. We have investigated the effect of a continuous infusion of human recombinant IL-1β (rIL-1β) on circulating PTH during a 14-day period in 7-week-old female rats. This time interval was chosen in order to exclude initial hypercalcemia and to enable data collection under steady-state conditions. Five groups of 20 animals each had miniosmotic pumps (Alzet 2002, 200 µl) implanted subcutaneously and primed to release either distilled water (controls) or 100, 500, 1,000 and 2,000 ng/24 h of rIL-1β. Blood was drawn on days 1 and 14 for PTH, corticosterone and Ca²⁺ determinations. Adequate biological activity of the infused rIL-1β was supported by elevated rectal temperature records and significant elevations of plasma corticosterone on day 14. The 100-ng dose had no effect but 500–2,000 ng rIL-1β/24 h significantly reduced plasma PTH in a dose-dependent manner down to 54% of basal value (20.4 ± 1.1 vs. 15.3 ± 1.4 pg/ml for 500 ng, p < 0.005; 20.5 ± 1.3 vs 12.3 ± 1.1 for 1,000 ng, p < 0.001, and 19.5 ± 2.0 vs. 10.6 ± 1.1 pg/ml for 2,000 ng, p < 0.0008). Despite these findings, no differences in blood Ca²⁺ could be detected between treated animals and controls. The following conclusions can be inferred from the foregoing: Systemic administration of rIL-1β to rats induced a dose-dependent fall in circulating PTH without altering calcemia, calling into question the biological relevance of the former finding. Although the recorded PTH depression may indeed not have been severe enough to cause hypocalcemia, it can be hypothesized that osteoclast activation by rIL-1β would enhance bone mineral release into the pool compensating for depressed PTH activity.

Rat stomach ECL-cell histidine decarboxylase activity is suppressed by ergocalciferol but unaffected by parathyroid hormone and calcitonin

The ECL cells are peptide hormone-producing cells, rich in histamine and chromogranin A (CGA)-derived peptides, that operate under the control of gastrin. Gastrin and the ECL cells form a functional unit, the gastrin–ECL-cell axis. The aims of the present study were to examine (1) if calcitonin (CT), parathyroid hormone (PTH) and vitamin D affect the gastrin–ECL-cell axis (by measuring the activity of the histamine-forming enzyme, histidine decarboxylase (HDC), and the expression of HDC mRNA and CGA mRNA in the ECL cells), and (2) if activation of the gastrin–ECL-cell axis affects the parathyroid glands (by measuring plasma PTH and mRNA expression). We also examined the possibility that the oxyntic mucosa harbours vitamin D receptors. Fasted rats received intravenous infusion of PTH and CT with or without gastrin. PTH raised the blood Ca 2+ concentration, whereas CT infusion lowered it. Plasma PTH rose in response to CT, while serum gastrin remained unaffected. ECL-cell HDC was activated by gastrin but not by CT and PTH. Five daily subcutaneous injections of large amounts of ergocalciferol raised the blood Ca 2+ concentration, while reducing the oxyntic mucosal HDC activity and the expression of HDC and CGA mRNA. The serum gastrin concentration was not affected. The findings are in line with the idea that the gastrin–ECL-cell axis can be suppressed by vitamin D or by vitamin D-dependent mechanisms. Western blot analysis revealed the presence of vitamin D receptor immunoreactivity and reverse transcription PCR detected vitamin D receptor gene expression in the rat oxyntic mucosa. Hypergastrinemia was induced by daily peroral treatment with the H +/K +-ATPase inhibitor, omeprazole, for 2 weeks or by continuous subcutaneous infusion of gastrin for 7 days. Elevated serum gastrin concentration was associated with increased HDC activity and increased HDC and CGA mRNA expression in the oxyntic mucosa. There was no elevation of plasma PTH or PTH mRNA expression in the parathyroid gland.

Calcitonin Cells in the Intestine of Goldfish and a Comparison of the Number of Cells among Saline-Fed, Soup-Fed, or High Ca Soup-Fed Fishes

Calcitonin-immunoreactive cells were found in the intestine of goldfish. These cells were distributed mainly in the anterior part of the intestine, dispersed in the intestinal epithelium. The nucleus was located in the basal portion of the serosal side, and the cytoplasm was elongated to the luminal side. From the anterior part of the intestine, cDNA fragments with the same nucleotide sequence as that of the goldfish calcitonin gene were amplified by RT–PCR method. After administration of one of three kinds of solutions (saline, consommé soup, or high Ca consommé soup) into the digestive tract of the goldfish, the number of those cells was the largest in the consommé group at 6 h after ingestion, although blood Ca levels were the highest in the high Ca consommé group. The function of calcitonin cells in the intestine may be to restrain the acute absorption of nutrients and not to control blood Ca levels.

Effectiveness of calcium chloride in increasing blood calcium concentrations of periparturient dairy cows.

Calcium chloride supplements such as gels and drench were studied to determine their effectiveness for increasing blood serum Ca concentrations in periparturient dairy cows. Multiparous, pregnant Holstein dairy cows (n = 36) were assigned to one of four treatments. After calving, cows in four treatments received basal diet and two doses of either control inert gel (CON), gel containing CaCl2 and vitamins (CVG), gel containing CaCl2 and minerals (CMG), or CaCl2 as drench containing vitamins (CVD). The first dose was given within 2 h after calving and the second dose 12 h after the first dose. Each dose provided .07, 54.5, 56.0, and 33.2 g of elemental Ca in CON, CVG, CMG, and CVD treatments, respectively. Blood samples were collected at 0, 15, 30, 60, 180, and 360 min after each oral dose. The blood serum Ca concentrations were 6.26, 7.56, 6.20, and 5.96 mg/dL during the pretreatment period and deviated -13.5, 7.1, 9.3, and 18.1% from pretreatment levels at 18 h after the first dose in CON, CVG, CMG, and CVD treatments, respectively. The average changes in serum P from pretreatment levels were not different among treatments. Serum Mg concentrations remained below the pretreatment levels in all four treatments. Blood serum beta-hydroxybutyrate during the first 2 wk and milk yields during the first 4 wk of lactation were the same in all treatments. Three cases of clinical milk fever were observed in CON treatment and one case in CVD treatment. The oral supplements of CaCl2 as gel or drench increased the blood Ca levels in periparturient dairy cows. Increased supply of Ca through oral supplements of CaCl2 may prevent milk fever in cows that are marginally hypocalcemic.

Evidence that peroral calcium does not activate the gastrin-ECL-cell axis in the rat

The ECL cells are histamine- and pancreastatin-secreting endocrine cells in the oxyntic mucosa, thought to release a blood Ca 2+-lowering peptide hormone upon stimulation by gastrin. Previously, we have shown that the ECL cells do not respond to perturbations in blood Ca 2+. In the present study, we examine if Ca 2+ in the gastric lumen will affect the activity of the gastrin-ECL-cell axis. Freely fed or food deprived (48 h) rats were given an oral load of CaCl 2 (or NaCl), and the blood Ca 2+ concentration was monitored. The serum gastrin concentration at sacrifice, 3 h after ingestion of CaCl 2, was measured together with two parameters of ECL cell activity: the oxyntic mucosal histidine decarboxylase (HDC) activity and the serum pancreastatin concentration. The circulating concentrations of calcitonin and parathyroid hormone (PTH) were also measured. Oral CaCl 2 raised the blood Ca 2+ in a dose-dependent manner. The two highest doses (which caused damage to the oxyntic mucosa) raised the serum gastrin concentration and the HDC activity in both fed and fasted rats; the serum pancreastatin concentration remained unaffected. Oral CaCl 2 raised the serum calcitonin concentration and lowered the serum PTH concentration. The effects of high doses of oral CaCl 2 on the serum gastrin concentration and on the oxyntic mucosal HDC activity could be reproduced by a high dose of NaCl. Thus the effects are probably not due to Ca 2+ per se. We conclude that the gastrin-ECL-cell axis in the rat does not respond to peroral Ca 2+. Since the ECL cells do not respond to either circulating or peroral Ca 2+ they are unlikely to secrete a calciotropic hormone.

Effect of anionic salts in concentrate mixture and calcium intake on some blood and urine minerals, acid-base balance and feed intake of dry pregnant cows on grass silage based feeding

Twelve Ayrshire and eight Friesian cows were randomly assigned to one of four prepartum diets in a 2 x 2 factorially designed experiment to determine the effect of anionic diet and calcium (Ca) intake on Ca metabolism, acid-base status and feed intake of grass silage based diets during the dry period. Four diets provided either 34 g or 74 g total dietary Ca/day, and were either anionic or cationic. Dietary cation-anion balance (DCAB), calculated as milliequivalents [(Na+ + K+) - (Cl- + S2-)], was -247 mEq/kg dry matter (DM) in the low DCAB group and +34 mEq/kg DM in the high DCAB group. DCAB was formulated using NH4Cl, (NH4)2SO4 and MgCl2 as anionic salts. Cows received grass silage (5.2 kg DM), hay (0.9 kg DM) and concentrate mixture (1.6 kg DM) until calving. Blood and urine samples were collected 4, 3, 2 and 1 week before the expected calving date, at calving, the day after calving and 1 week following calving. The results indicate that the reduction of cation-anion balance induced mild metabolic acidosis and increased the ability of the cow to maintain blood Ca concentration. However, DCAB should be higher since urinary pH decreased markedly (&lt; 6) and so remarkable changes in some blood electrolyte concentrations were noticed.;