Effect of histamine H2-receptor antagonist on the phosphorus-binding abilities of calcium carbonate and calcium lactate in hemodialysis patients.
The effect of histamine H2-receptor antagonist (famotidine) on the phosphorus-binding abilities of calcium carbonate and calcium lactate were examined in 13 chronic hemodialysis patients. In seven patients receiving calcium carbonate, famotidine (20 mg/d) was given because of gastroduodenal disorders, and calcium carbonate was replaced with calcium lactate as a phosphorus binder after 4 wk of treatment with famotidine. With the 4-wk administration of famotidine accompanied by calcium carbonate, the serum phosphorus level increased from 6.3+/-0.9 to 7.1+/-0.5 mg/dl (P<0.05). However, with the substitution of calcium lactate, the serum phosphorus level decreased significantly when compared to that before substitution (6.3+/-0.2 and 6.0+/-0.9 mg/dl after 4 and 8 wk of substitution, respectively), despite continued administration of famotidine. Serum calcium, creatinine, alkaline phosphatase, high sensitive parathyroid hormone, blood urea nitrogen, arterial blood pH, and bicarbonate were not significantly altered during the trial period. In six control patients treated with calcium carbonate alone, there were no statistical changes in serum calcium and phosphorus levels after substitution of calcium lactate for calcium carbonate. These results suggest that famotidine significantly affects the phosphorus-binding ability of calcium carbonate, but not that of calcium lactate. A careful observation of changes in the serum phosphorus level should be required in hemodialysis patients receiving calcium carbonate and histamine H2-receptor antagonists. Calcium lactate may be useful as a phosphorus binder in such hemodialysis patients. (+info)
New treatment of dry eye: the effect of calcium ointment through eyelid skin delivery.
AIM: To demonstrate the efficacy of a petrolatum based calcium ointment applied to the lower lid skin in the management of dry eye. METHODS: In a controlled double masked study, the effects of water free petrolatum ointment containing calcium carbonate (10% w/w) on tear functional factors and ocular surface vital staining in dry eye patients were observed. Petrolatum without calcium carbonate served as control. Patients were instructed to place ointment to the lower lid skin twice a day. Evaluation of subjective complaints, fluorescein and rose bengal staining patterns, blink rate, tear evaporation and tear break up time (BUT) were performed before and 3 months after treatment. In order to demonstrate the movement of petrolatum from the skin to the tear film, petrolatum containing 1% sodium fluorescein was placed on the lower lid of four healthy volunteers, and the concentration of fluorescein in the tear film was followed up to 6 hours using an anterior fluorometer. RESULTS: Subjective symptoms significantly improved in both the calcium group (p=0.001) and control (p=0.012), while only the calcium group demonstrated a significant improvement in fluorescein (p=0.043), rose bengal (p=0.021) scores, and blink rate (p=0.004). Tear evaporation also significantly decreased in both the calcium group (p=0.0004) and control (0.043). BUT did not improve in either group. CONCLUSION: Petrolatum based calcium ointment significantly improved symptoms, tear dynamics, and ocular surface staining in dry eye patients. However, some of the therapeutic effects may be due to lipids in the petrolatum vehicle. Petrolatum applied to the lower lid skin is an effective drug delivery system for slowly releasing drugs to the ocular surface. (+info)
Calcium use increases risk of calciphylaxis: a case-control study.
OBJECTIVE: To investigate the risk factors for the development of calciphylaxis in renal failure, a poorly understood and often fatal condition characterized by calcium deposition in tissues. DESIGN: Retrospective case-control study. SETTING: University hospital peritoneal dialysis center. PATIENTS: Eight continuous ambulatory peritoneal dialysis (CAPD) patients with calciphylaxis were identified in a 3-year period. We matched up to five controls for dialysis modality and length of time on dialysis with each case. STATISTICS: Multivariate conditional logistic regression analysis for matched case-controls. MAIN OUTCOME MEASURES: Laboratory data and demographics were collected as well as cumulative calcium and vitamin D ingestion over the year prior to disease onset. RESULTS: All the patients were female, versus only 38% (14/37) of controls (p < 0.0001). While not statistically significant, a majority of the patients were diabetic [62.5% (5/8) vs 32% (12/37)]. Peak and average levels of serum calcium, phosphate, calcium x phosphate product, parathyroid hormone (PTH), albumin, iron, total iron-binding capacity (TIBC), and ferritin were not significantly different in cases compared with controls. The use of calcitriol alone or with calcium carbonate was not found to be a significant risk factor for the development of calciphylaxis. In a multivariate analysis, iron intake seemed to be protective, contrary to previous reports, while the use of calcium carbonate was associated with a strong trend to increased risk of calciphylaxis development (odds ratio = 1.029/g and 1.011/g calcium ingested per month, at 1 and 2 - 3 months prior to calciphylaxis development; p = 0.0556 and 0.0565, respectively). CONCLUSION: These data, although limited by the small numbers of index cases, suggest that calcium ingestion is a risk factor for calciphylaxis. The increased use of calcium salts as a phosphate binder in recent years might explain the apparent increased incidence of calciphylaxis in our and other centers. The preponderance of female diabetics among cases reported elsewhere was confirmed in our study. (+info)
A method of microinjection: delivering monoclonal antibody 1223 into sea urchin embryos.
In this paper, a simpler method of microinjecting sea urchin embryos without using the conventional microinjection chamber designed by Kiehart is reported. A trough was made on a surface of 0.6% agarose gel dissolved in artificial sea water. Approximately fifty hatched embryos could be loaded in the trough and, consequently, swimming embryos were trapped in the trough. Monoclonal antibody (mAB) 1223 which blocks spiculogenesis in vitro was delivered into the blastocoels of sea urchin embryos to test whether this antibody inhibits spiculogenesis in vivo and also, whether this new technique is effective for the microinjection of the sea urchin embryos. The embryos were injected with mAB1223 at the hatched blastula, early mesenchyme blastula and early gastrula stages, and 63%, 90% and 97% of the embryos did not form spicules at the late gastrula stage, respectively. Therefore, mAB1223 was shown to also block spiculogenesis in vivo. From the fact that spiculogenesis occurred at a lower rate when mAB1223 was injected at the hatched blastula stage than at later stages, it may be speculated that endogenous proteases degraded the injected antibodies. Using this technique, extracellular events in the blastocoel or the function of certain molecules expressed in blastocoel can be easily investigated in vivo. (+info)
Molecular cloning and ultrastructural localization of the core protein of an eggshell matrix proteoglycan, ovocleidin-116.
The role of avian eggshell matrix proteins in shell formation is poorly understood. This calcitic biomaterial forms in a uterine fluid where the protein composition varies during the initial, calcification, and terminal phases of eggshell deposition. A specific antibody was raised to a 116-kDa protein, which is most abundant in uterine fluid during active eggshell calcification. This antiserum was used to expression screen a bacteriophage cDNA library prepared using mRNA extracted from pooled uterine tissue harvested at the midpoint of eggshell calcification. Plasmids containing inserts of differing 5'-lengths were isolated with a maximum cDNA sequence of 2.4 kilobases. Northern blotting and reverse transcriptase-polymerase chain reaction demonstrated that the 2. 35-kilobase message was expressed in a uterine-specific manner. The hypothetical translational product from the open reading frame corresponded to a novel 80-kDa protein, which we have named ovocleidin-116. After removal of the predicted signal peptide, its N-terminal sequence corresponded almost exactly with that determined from direct microsequencing of the 116-kDa uterine protein (this work) and with that previously determined for the core protein of a 120-kDa eggshell dermatan sulfate proteoglycan (Corrino, D. A., Rodriguez, J. P., and Caplan, A. I. (1997) Connect. Tissue Res. 36, 175-193). Ultrastructural colloidal gold immunocytochemistry of ovocleidin-116 demonstrated its presence in the organic matrix, in small vesicles found throughout the mineralized palisade layer, and the calcium reserve assembly of the mammillary layer. Ovocleidin-116 thus is a candidate molecule for the regulation of calcite growth during eggshell calcification. (+info)
A new matrix protein family related to the nacreous layer formation of Pinctada fucata.
We have isolated a new matrix protein family (N16) which is specific to the nacreous layer of the Japanese pearl oyster, Pinctada fucata, and have cloned and characterized the cDNAs coding for the components. Analysis of the deduced amino acid sequence revealed that N16 showed no definitive homology with other proteins. The in vitro studies of the crystallization clarified that N16 induced aragonite crystals when fixed on the substrate but inhibited crystal formation without it. The aragonite crystals showed platy morphology different from those formed inorganically, and long intervals of incubation resulted in crystalline layers highly similar to the nacreous layer. (+info)
Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Durham Renal Osteodystrophy Study Group.
Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. BACKGROUND: In the management of patients with mild secondary hyperparathyroidism, it is not known whether calcium supplementation alone is sufficient to correct abnormalities in bone and mineral metabolism or if calcitriol is needed in either physiologic oral or intravenous pharmacologic doses. METHODS: This was a 40-week prospective nonmasked trial of 52 patients [parathyroid hormone (PTH) 150 to 600 pg/mL] who were randomized to receive escalating doses of either calcium carbonate (CaCO3) alone (calcium group, N = 11), daily oral calcitriol (oral group, N = 20), or intermittent intravenous calcitriol (IV group, N = 21). The groups were compared with regard to changes in serum intact PTH, serum bone-specific alkaline phosphatase (BAP), incidence of hypercalcemia (>10.5 mg/dL), and hyperphosphatemia (>6.5 mg/dL). RESULTS: PTH levels decreased in all groups (P < 0.01, paired t-test). In the calcium group, PTH (mean +/- SEM) decreased from 325 +/- 46.2 to 160 +/- 44.5 pg/mL. In the oral group, it decreased from 265 +/- 26.4 to 125 +/- 23.7 pg/mL, and in the IV group, it decreased from 240 +/- 27.7 to 65 +/- 10.0 pg/mL. Upon analysis of covariance, controlling for the initial PTH level, we found no differences in the PTH response between the groups (P > 0.10). In contrast, the BAP concentration increased from 20.7 +/- 7.6 to 27.5 +/- 7.0 microg/L in the calcium group (P = 0.17), decreased from 20. 6 +/- 3.9 to 17.8 +/- 4.5 microg/L in the oral group (P = 0.26), and from 19.1 +/- 2.6 to 10.6 +/- 1.1 microg/L in the IV group (P = 0. 007). Serum calcium increased significantly in all groups from 8.4 +/- 0.25 to 9.0 +/- 0.28, 8.5 +/- 0.16 to 9.2 +/- 0.27, and 8.7 +/- 0.16 to 9.4 +/- 0.18 mg/dL in the calcium, oral, and IV groups, respectively (P = NS difference between groups). Serum phosphorus was significantly lower in the calcium group throughout the study (P = 0.02). Hypercalcemic episodes were 2.0 +/- 0.8, 3.0 +/- 0.6, and 3. 4 +/- 0.6 per patient-year (P > 0.10), and hyperphosphatemic episodes were 0.9 +/- 0.56, 4.2 +/- 0.79 and 4.9 +/- 0.84 in the calcium, oral, and IV groups, respectively (P < 0.01). CONCLUSION: In mild secondary hyperparathyroidism, all three strategies are effective. High-dose CaCO3 alone may be sufficient to control PTH with a favorable side-effect profile, but calcitriol appears to have additional suppressive effects on bone that are greater following the intravenous route of administration and may increase the risk of adynamic bone disease. (+info)
Mechanism of calcite crystal growth inhibition by the N-terminal undecapeptide of lithostathine.
Pancreatic juice is supersaturated with calcium carbonate. Calcite crystals therefore may occur, obstruct pancreatic ducts, and finally cause a lithiasis. Human lithostathine, a protein synthesized by the pancreas, inhibits the growth of calcite crystals by inducing a habit modification: the rhombohedral (10 14) usual habit is transformed into a needle-like habit through the (11 0) crystal form. A similar observation was made with the N-terminal undecapeptide (pE(1)R(11)) of lithostathine. We therefore aimed at discovering how peptides inhibit calcium salt crystal growth. We solved the complete x-ray structure of lithostathine, including the flexible N-terminal domain, at 1.3 A. Docking studies of pE(1)R(11) with the (10 14) and (11 0) faces through molecular dynamics simulation resulted in three successive steps. First, the undecapeptide progressively unfolded as it approached the calcite surface. Second, mobile lateral chains of amino acids made hydrogen bonds with the calcite surface. Last, electrostatic bonds between calcium ions and peptide bonds stabilized and anchored pE(1)R(11) on the crystal surface. pE(1)R(11)-calcite interaction was stronger with the (11 0) face than with the (10 14) face, confirming earlier experimental observations. Energy contributions showed that the peptide backbone governed the binding more than did the lateral chains. The ability of peptides to inhibit crystal growth is therefore essentially based on backbone flexibility. (+info)