Gelatin/polyethylene glycol-loaded magnesium hydroxide nanocomposite to attenuate acetylcholinesterase, neurotoxicity, and activation of GPR55 protein in rat models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease marked by mitochondrial dysfunction, amyloid-ß (Aß) aggregation, and neuronal cell loss. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for insulin receptors in diabetes therapy, but GPR55's role in AD is still unidentified. Gelatin (GE) and polyethylene glycol (PEG) polymeric hydrogels are commonly used in the drug delivery system. Therefore, the aim of the present study was the preparation of magnesium hydroxide nanocomposite using Clitoria ternatea (CT) flower extract, GE, and PEG (GE/PEG/Mg(OH)2NCs) by the green precipitation method. The synthesized GE/PEG/Mg(OH)2NCs were used to determine the effect of GPR55 activation of intracerebroventricular administration on streptozotocin (ICV-STC)-induced cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive deficits. The GE/PEG/Mg(OH)2NCs were administered following bilateral ICV-STC administration (3 mg/kg) in experimental rats. Neurobehavioral assessments were performed using a Morris water maze (MWM) and a passive avoidance test (PA). Cholinergic and antioxidant activity, oxidative stress, and mitochondrial complex activity were estimated in the cortex and hippocampus through biochemical analysis. Inflammatory markers (TNF-α, IL-6, and IL-1ß) were determined using the ELISA method. Our study results demonstrated that the GE/PEG/Mg(OH)2NCs treatment significantly improved spatial and non-spatial memory functions in behavioral studies. Moreover, the treatment with GE/PEG/Mg(OH)2NCs group significantly attenuated cholinergic dysfunction, oxidative stress, and inflammatory markers, and also highly improved anti-oxidant activity (GSH, SOD, CAT, and GPx) in the cortex and hippocampus regions. The western blot results suggest the activation of the GPR55 protein expression through GE/PEG/Mg(OH)2NCs. The histopathological studies showed clear cytoplasm and healthy neurons, effectively promoting neuronal activity. Furthermore, the molecular docking results demonstrated the binding affinity and potential interactions of the compounds with the AChE enzyme. In conclusion, the GE/PEG/Mg(OH)2NCs treated groups showed reduced neurotoxicity and have the potential as a therapeutic agent to effectively target AD.

Calcareous deposit formation under cathodic polarization and marine biocalcifying bacterial activity.

CaCO3 precipitation can occur through bacterial activity (biomineralization) but can also take place in abiotic conditions in seawater at a steel surface under cathodic polarization. In this work, we used two biocalcifying bacterial strains: Pseudoalteromonas sp. and Virgibacillus halodenitrificans isolated in a previous work from marine environment for their ability to induce CaCO3 precipitation. Motility experiments were performed to evaluate the bacterial behaviour in the absence or presence of an applied electric current of -600 µA/cm2 in a solid medium. As no alteration of bacterial growth or CaCO3 crystal formation were observed, we studied both strains in liquid cultures at different applied currents densities: -100, -200 and -600 µA/cm2. The deposits formed on the cathode surface were characterized by µ-Raman spectroscopy and X-ray diffraction. The strain ability to biocalcify in the presence of electric current, in the liquid medium, was evaluated by monitoring bacterial growth, pH evolution, CaCO3 production and metabolic characterization for 7 days. Our results show that neither bacterial growth, enzymatic pathways or CaCO3 production were altered by the electric current. Moreover, bacterial activity modified drastically the nature of the compounds formed on the cathode surface. It favoured Mg-containing calcite, hindering the formation of both aragonite and brucite.

Hepatoprotective effect of combination of L-carnitine and magnesium-hydroxide in nonalcoholic fatty liver disease patients: a double-blinded randomized controlled pilot study.

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) still has no accepted pharmacological therapy. Even though monotherapy of L-carnitine or magnesium supplementation exhibits an essential beneficial role in NAFLD treatment, and despite that new NAFLD treatment strategies focus on combination therapies, the combination of L-carnitine with magnesium has not yet been examined in NAFLD patients. We aimed to assess the efficacy of L-carnitine in combination with magnesium in NAFLD patients. PATIENTS AND METHODS: Double-blinded, randomized controlled trial with 22 NAFLD participants who were randomized to either control group receiving placebo for the first 8 weeks and an additional 8 weeks with CIRRHOS product (2 gr L-carnitine and 150 mg magnesium) or treatment group receiving CIRRHOS product for 16 weeks. Weight, serum aspartate aminotransferase (AST), alanine transaminase (ALT) and C-reactive protein (CRP) levels were measured monthly. Lipid profile and serum insulin levels were monitored at baseline and at week 16 of treatment. Shear-wave elastography was used to evaluate liver stiffness (LS). RESULTS: While AST and ALT levels decreased progressively over 16 weeks of treatment in the treatment group, AST and ALT levels of the control group were increased modestly or unaffected. AST and ALT levels of the treatment group decreased by 25% (p=0.9) and 20% (p=0.1) respectively, compared to AST and ALT levels at baseline. However, serum CRP levels, insulin levels, lipid profile and LS were not affected by treatment. CONCLUSIONS: Our findings suggest that L-carnitine with magnesium supplementation could be a potential therapy for NAFLD. However, further studies with a larger population and high-sensitivity diagnostic parameters for early stages of NAFLD are needed to elucidate L-carnitine and magnesium efficacy in NAFLD.

Nano-Mg(OH)2-induced proliferation inhibition and dysfunction of human umbilical vein vascular endothelial cells through caveolin-1-mediated endocytosis.

Nano-Mg(OH)2 is efficiently used in pollutant adsorption and removal due to its high adsorption capability, low-cost, and recyclability. A recent research from our group showed that Mg(OH)2 nanoflakes are not evidently internalized by cancer cells and are not cytotoxic. But the biocompatibility and potential toxicity of nano-Mg(OH)2 in a normal biological system are largely unclear. Nanoparticles could affect the function of endothelial cells, and endothelial dysfunction represents an early sign of lesion within the vasculature. Here, we applied the human umbilical vein vascular endothelial cells (HUVECs) as an in vitro model of the endothelium to study the cytotoxicity of nano-Mg(OH)2. Our results showed that nano-Mg(OH)2 at 200 µg/ml impaired proliferation and induced dysfunction of HUVECs, but did not result in cell necrosis and apoptosis. Transmission electron microscopy images and immunofluorescence results showed that the nano-Mg(OH)2 could enter HUVECs through caveolin-1-mediated endocytosis. Nano-Mg(OH)2 at high concentrations decreased the level of caveolin-1 and increased the activity of endothelial nitric oxide synthase (eNOS), thus leading to the production of excess nitric oxide (NO). In this work, we provide the cell damage concentrations of nano-Mg(OH)2 nanoparticles, and we propose a mechanism of injury induced by nano-Mg(OH)2 in HUVECs.

Cell rescue by nanosequestration: reduced cytotoxicity of an environmental remediation residue, Mg(OH)2 nanoflake/Cr(VI) adduct.

Some nanomaterials, such as Mg(OH)2 nanoflakes, are heavily used in pollutant adsorption and removal. Residues from these environmental remediations are potential hazardous materials. Safety evaluations of these materials are needed for environmental protection and human health. Although nanotoxicity has been widely investigated in recent years, research on the toxicity of nanoparticle/pollutant adducts has been rather inadequate. Here, we report the cellular perturbations and cytotoxicity of nano-Mg(OH)2/Cr(VI) adducts as a case study to elucidate how nanoparticle/pollutant adducts impact human cells. We found that Mg(OH)2 nanoflakes barely enter cells, while desorbed Cr(VI) anions enter cells, generate ROS, induce cell apoptosis, and cause cytotoxicity. This cytotoxicity is only a fraction of the cytotoxicity of free Cr(VI) because nano-Mg(OH)2 particles are able to retain more than half of their Cr(VI) anions.

Protein interactions with nanosized hydrotalcites of different composition.

Nanosized hydrotalcite-like compounds (HTlc) with different chemical composition were prepared and used to study protein adsorption. Two soft proteins, myoglobin (Mb) and bovine serum albumin (BSA), were chosen to investigate the nature of the forces controlling the adsorption and how these depend on the chemical composition of the support. Both proteins strongly interact with HTlc exhibiting in most cases a Langmuir-type adsorption. Mb showed a higher affinity for Nickel Chromium (NiCr-HTlc) than for Nickel Aluminum (NiAl-HTlc), while for BSA no significant differences between supports were found. Adsorption experiments in the presence of additives showed that proteins exhibited different types of interactions onto the same HTlc surface and that the adsorption was strongly suppressed by the addition of disodium hydrogen phosphate (Na(2)HPO(4)). Atomic force microscopy images showed that the adsorption of both proteins onto nanoparticles was followed by the aggregation of biocomposites, with a more disordered structure for BSA. Fluorescence measurements for adsorbed Mb showed that the inorganic nanoparticles induced conformational changes in the biomolecules; in particular, the interactions with HTlc surface quenched the tryptophan fluorescence and this process was particularly efficient for NiCr-HTlc. The adsorption of BSA onto the HTlc nanoparticles induced a selective quenching of the exposed fluorescent residues, as indicated by the blue-shift of the emission spectra of tryptophan residues and by the shortening of the fluorescence decay times.

Hybridization of sugar alcohols into brucite interlayers via a melt intercalation process.

We report the preparation of organic-brucite (BR) hybrids using harmless sugar alcohols (xylitol, XYL, and sorbitol, SOR). Since XYL and SOR are solid materials at room temperature, the hybridization was investigated by comparing two separate methods, hydrothermal treatment and melt mixing. BR-sugar alcohol hybrids were successfully prepared by a melt intercalation method at 175 °C. X-ray diffraction and Fourier transform infrared spectroscopy analyses indicated that organic molecules were intercalated into the brucite layers, overcoming the barrier of hydroxyl bonds between the BR layers. Moreover, X-ray photoelectron spectroscopy and thermal analyses showed that the intercalated materials at 175 °C resulted in the formation of covalent Mg-O-C bond linkages on the interlayer surface of BR.

Layered double hydroxide nanoparticles as target-specific delivery carriers: uptake mechanism and toxicity.

Layered double hydroxides (LDHs), also known as anionic nanoclays or hydrotalcite-like compounds, have attracted a great deal of interest for their potential as delivery carriers. In this article, we describe the cellular uptake behaviors and uptake pathway of LDHs in vitro and in vivo, which can not only explain the mechanism by which high efficacy of biomolecules delivered through LDH nanocarriers could be obtained, but also provide novel strategies to enhance their delivery efficiency. Toxicological effects of LDHs in cell lines and in animal models are also present, aiming at providing critical information about their toxicity potential, which should be carefully considered for their biomedical application. Understanding the uptake behaviors, uptake mechanism and toxicity of LDHs in terms of dose-response relationship, diverse physicochemical properties and interaction with different biological systems is important to optimize delivery efficiency as well as biocompatibility.

Adsorption and separation of proteins by a synthetic hydrotalcite.

In this study, the potential use of a synthetic Mg/Al hydrotalcite (layered double hydroxide) as a novel chromatography material for protein purification was investigated. The hydrotalcite is present in its carbonate form and is characterized by an Al/Mg-ratio of 1.85. Zetapotential measurements confirm a positive surface potential up to pH 10 suggesting applicability as anion exchanger. The binding of model proteins covering a broad range of isoelectric points and molecular weights was performed at different pH-values under batch conditions to evaluate the binding behaviour of the hydrotalcite. Furthermore, static binding capacities were exemplarily determined for hemoglobin and human serum albumin. Additionally, the adsorption and elution of hemoglobin was studied under dynamic conditions. The binding behaviour of the hydrotalcite was compared to commercially available anion exchangers and was found to be a function of pH, depending on the model protein. Variant adsorption behaviour is explained by further interactions like hydrogen bonds and by an unequal charge distribution over the protein surfaces. The hydrotalcite reveals high adsorption capacities under static (260 mg/g) as well as under dynamic conditions (88 mg/g at 34 cm/h; 61 mg/g at 340 cm/h). With appropriate buffers like 500 mM carbonate (pH 10) the adsorbed proteins can be nearly completely desorbed making regeneration possible. Due to the binding and elution properties it is concluded, that the hydrotalcite can serve anion exchange material for chromatographic protein separations.

Wet air oxidation and catalytic wet air oxidation for dyes degradation.

BACKGROUND, AIM, AND SCOPE: Textile industry produces wastewater which contributes to water pollution since it utilizes a lot of chemicals. Preliminary studies show that the wastewater from textile industries contains grease, wax, surfactant, and dyes. The objective of this study was to determine the treatment efficiency of the nickel catalysts supported on hydrotalcites in three-dye model compounds and two types of wastewater. MATERIALS AND METHODS: Hydrotalcites were employed to prepare supported nickel catalysts by wetness impregnation technique. Metal loadings from 1 to 10 wt% were tested. Catalysts were characterized by several techniques. They were tested in a catalytic wet air oxidation of three dyes and two wastewaters with different origins. RESULTS AND DISCUSSION: It could be observed that the higher the metal content, the lower the BET area, possibly due to sintering of Ni and the consequent blocking of the pores by the metal. In addition, metallic dispersion was also higher when the metal content was lower. Dye conversion was more than 95% for every catalyst showing no differences with the nickel content. A high degree of dye conversion was achieved. Wet air oxidation (WAO) and catalytic wet air oxidation (CWAO) processes have been proved to be extremely efficient in TOC removal for wastewaters. CONCLUSIONS: The CWAO process can be used to remove dyes from wastewater. Three different dyes were tested showing satisfactory results in all of them. TOC degradation and dye removal in the presence of the catalyst were effective. Also, the HTNi catalyst is very active for organic matter and toxicity removal in wastewaters.

Transesterification of triglycerides in high and low quality oil feeds over an HT2 hydrotalcite catalyst.

The use of a heterogeneous catalyst, in the transesterification reaction of refined and acidic cottonseed oil for the production of methyl-esters (biodiesel) has been studied. The basic Mg-Al-CO3 hydrotalcite catalyst used showed a high activity for methanolysis and esterification reactions in a refined and an acidic cottonseed oil as well as in a representative high water content animal fat feed. The experiments were performed in a temperature range between 180 and 210 degrees C, in a batch reactor. The methanol to vegetable oil molar ratio was 6 to 1, while the catalyst concentration was fixed at 1 wt.% of the oil mass. Non-calcined and calcined forms of the catalyst were tested. The activity of the calcined catalyst was lower than the initial activity of the non-calcined catalytic system but it appeared the same with the reused non-calcined system.

Anionic clays for sunscreen agent safe use: photoprotection, photostability and prevention of their skin penetration.

The use of sunscreen preparations is recently growing and their efficacy and safety must be taken into account since they are applied on the skin frequently and for many hours. Exposition to sunlight, in fact, can cause sunscreen photodegradation and determine their decrease in UV protection often with the occurrence of allergic and/or toxic degradation products. A high photostability is hence very important for their effectiveness and safety. The aim of this work is to obtain new sunscreen formulations stabilized by intercalating PABA, within the lamellar structures of two kinds of hydrotalcite. PABA was chosen as model sunscreen because of its high photoinstability and photosensitizing properties that nowadays bar its utilization. Both intercalated products showed an increased protection range and, in one case, an improved sunscreen photostability. Sunscreen release from creams containing intercalated or free PABA was evaluated as well. The very low or negligible sunscreen release, obtained from the intercalated product loaded formulations, resulted in a lack of a close contact between skin and filter with the consequence that cutaneous reactions and allergy problems are eliminated. The use of these materials resulted in a good strategic technological approach in order to increase efficacy and safety of solar products.

In end-stage renal failure, does infection lead to elevated plasma aluminium and neurotoxicity? Implications for monitoring.

The well-described long-term effects of sustained exposure to aluminium in patients with end-stage renal failure (ESRF) are a result of uptake and storage of aluminium, leading to cellular toxicity. A case is presented suggesting that this aluminium may be mobilizable, and indicating the consequence of such release. A patient on haemodialysis (HD) presented acutely with infection, a raised CRP, decreased conscious level, impaired cognition and agitation. Subsequent neurological recovery over six to seven days appeared to follow the return of markedly elevated plasma aluminium concentrations to basal (i.e. from 25.2 micromol/L to 2.5 micromol/L; reference range < 0.5 micromol/L), coupled with a resolution of the infection. The patient was on long-term aludrox therapy 3 g/day, and showed relative resistance to the exogenous hormone erythropoietin, resulting in a refractory anaemia and suggesting aluminium toxicity. A series of HD patients (n = 5) presenting with bacteraemia, not on aludrox, showed no appreciable rise in the plasma aluminium mean of 1.3 micromol/L (SD 0.9; range 0.6-2.0 micromol/L). We suggest that infection can result in release of tissue aluminium, leading to acutely elevated plasma aluminium concentrations and signs of neurotoxicity. The amount of tissue storage and resultant aluminium release seemed to be related to the use of aluminium hydroxide as a phosphate binder.

Can a hydroxide ligand trigger a change in the coordination number of magnesium ions in biological systems?

Density functional (B3LYP) calculations indicate that a hydroxide ligand is capable of triggering a reduction in the coordination number of Mg(2+) ions from 6 to 5. Since this could be quite relevant in the mode of action of magnesium-containing enzymes (especially hydrolases in which a metal-bound hydroxide species is believed to play a crucial role), we have performed a systematic deprotonation study of biologically relevant magnesium complexes. We explicitly calculated the preferred coordination number of [MgL(1)(x)L(2)(y)L(3)(z)](2)(-)(n) species at the B3LYP/aug-cc-pVTZ level of theory. L(1), L(2), and L(3) represent combinations of water, hydroxide, carboxylate (models Glu and Asp), ammonia ligands (models Lys and His residues), and fluoride ions. As expected, Mg(2+) exclusively prefers an octahedral coordination geometry with H(2)O, HCO(2)(-), or NH(3). Surprisingly, one hydroxide ligand triggers a change to a trigonal bipyramidal geometry. The isoelectronic fluoride ion behaves similarly. When two OH(-) are present, a tetrahedral coordination geometry is preferred. We postulate that a hydroxide (in addition to its role as an active nucleophile) could be employed by magnesium-containing enzymes to trigger a differential coordination behavior.

An interesting case of osteomalacia due to antacid use associated with stainable bone aluminum in a patient with normal renal function.

Antacids containing aluminum and magnesium hydroxide are widely used nonprescription agents for treatment of gastritis and peptic ulcer disease. One of the side effects of these antacids is that they bind phosphate in the gut, resulting in its malabsorption. Short-term use, consistent with the directions on the manufacturer's label, is safe and effective for most patients. Heavy chronic use, even when within label, can cause serious skeletal impairment. This report concerns the case of a 39-year-old pharmacist who self-mediated for peptic ulcer disease with high doses of a potent antacid containing aluminum and magnesium hydroxide. The patient consumed over 18 kg of elemental aluminum and 15 kg of elemental magnesium over 8 years of antacid use. This treatment resulted in the clinical syndrome of severe osteomalacia due to profound phosphate depletion. Bone biopsy revealed stainable aluminum deposits along 27.6% of the total bone surface, which is a unique observation in a patient with normal renal function. Treatment included withdrawing the antacid and supplementation with phosphate, calcium, and vitamin D. She experienced marked subjective and objective improvement with this regimen. This included a striking increase in her bone mineral density occurring over the 2-year follow-up period. This case documents that long-term antacid therapy, even when used by patients with normal renal function and within the manufacturer's label recommendations, can lead to severe phosphate depletion, osteomalacia, and toxic accumulation of aluminum and magnesium. This clinical syndrome was readily treated by withdrawal of the antacid and with calcium and phosphate supplementation. Physicians recommending treatment with these compounds or learning of their patient's self-medication with them should inform the patient of the potential serious side effects these agents can cause when used chronically at maximally recommended doses.

Development of a drug delivery system for the treatment of periodontal disease based on bioerodible poly(ortho esters).

Poly(ortho esters) prepared by the condensation of 1,2,6-hexanetriol and an alkyl orthoacetate are viscous, semisolid materials at room temperature that can be injected using a blunt needle. When tetracycline was incorporated into these materials, complete release occurred within about 24 hours, but when small amounts of Mg(OH)2 were incorporated into the polymer release could be extended to many weeks, and a loading of 0.5 wt% resulted in sustained release of about 10 days. When adhesion was tested using bovine teeth, cohesive failure of the pure polymer occurred at a force of about 392 mN cm-2 and cohesive failure of a polymer incorporating 10 wt% tetracycline and 1 wt% (Mg(OH)2 occurred at about 118 mN cm-2. The combination of injectability, dentoadhesiveness and ability to control accurately the release of incorporated antibiotics makes these materials promising candidates for bioerodible delivery systems useful in the treatment of periodontitis. Toxicological studies are currently in progress.

Pharmacokinetics of cefpodoxime proxetil and interactions with an antacid and an H2 receptor antagonist.

Cefpodoxime proxetil is a new oral esterified cephem antibiotic with a broad antibacterial spectrum. The dissolution of cefpodoxime proxetil is pH dependent. The objectives of this study were to characterize the pharmacokinetics of cefpodoxime proxetil in two different oral doses and to examine possible interactions with an antacid, aluminum magnesium hydroxide (Maalox 70), and an H2 receptor antagonist, famotidine. Two studies involving the same 10 healthy volunteers were performed. In the first study, cefpodoxime proxetil was administered in two doses, 0.1 and 0.2 g. In the second study, two interventions were performed in a randomized crossover design. For one intervention, the volunteers were pretreated with 40 mg of famotidine 1 h before 0.2 g of cefpodoxime proxetil was administered. In the second trial, participants were given 10 ml of Maalox 70 2 h and 10 ml of Maalox 70 15 min before they received 0.2 g of cefpodoxime proxetil. Serum and urine concentrations were determined by high-performance liquid chromatography. For the statistical evaluation, these data were tested by using the pharmacokinetics of 0.2 g of cefpodoxime proxetil from the first study. The maximum concentrations were 1.19 +/- 0.32 mg/liter after 0.1 g of cefpodoxime proxetil and 2.54 +/- 0.64 mg/liter after 0.2 g of cefpodoxime proxetil. The elimination half-lives were 149 min for 0.1 g and 172 min for 0.2 g of cefpodoxime proxetil. The total increase in the area under the concentration-time curve (AUC) was dose dependent. Combination with Maalox 70 caused a reduction in the AUC from 14.0 +/- 3.9 to 8.44 +/- 1.85 mg.h/liter. After famotidine, the AUC decreased to 8.36 +/- 2.0 mg . h/liter. Corresponding changes were registered for the maximum concentration of drug in serum, 24-h urine recovery, and the time to maximum concentration of drug serum. Cefpodoxime proxetil was well tolerated without any seriously adverse drug reactions.

Prevention of hyperparathyroidism in patients on maintenance dialysis by intravenous 1-alpha-hydroxyvitamin D3 in association with Mg(OH)2 as sole phosphate binder. A randomized comparative study with the association CaCO3 +/- Mg(OH)2.

The purpose of this study is to evaluate the place of intravenous 1 alpha-hydroxyvitamin D3 (1 alpha-OH-D3) in the prevention of radiologically obvious hyperparathyroidism (HPT) in patients on maintenance dialysis while excluding aluminium phosphate binder and using a dialysate calcium concentration of 1.62 mmol which keeps the intradialytic calcium balance neutral. Therefore, 47 patients without subperiosteal resorption and previously treated by oral CaCO3 and if necessary Mg(OH)2 as phosphate binder while their dialysate calcium had a Ca level of 1.62 and a Mg level of 0.2 mmol/l were randomized into a control group of 24 who were maintained on the same treatment and an experimental group of 23. This group discontinued CaCO3 and received intravenous 1 alpha-OH-D3 after each dialysis at increasing doses up to 4 micrograms and increased Mg(OH)2 as their sole phosphate binder. When plasma Ca increased above 2.7 mmol/l, the dose of 1 alpha-OH-D3 was decreased. When plasma PO4 increased above 2 mmol/l, the dose of Mg(OH)2 was increased to the highest dose not inducing diarrhea, hypermagnesemia (less than 2 mmol/l) or hyperkalemia (less than 6 mmol/l). In case of persistent hyperphosphatemia, the dose of 1 alpha-OH-D3 was decreased. Since mean plasma alkaline phosphatase was normal, HPT was monitored on the plasma concentration of 1-84 PTH for which a previous histological study showed that frank osteitis fibrosa was present only when they were above 70 pg/ml, i.e. (about twice the upper limit of the normal value). Before the study, plasma PTH was below this limit in 16 patients of the CaCO3 group and in 14 patients of the 1 alpha-OH-D3 group. After 6 months, they remained below this limit in all patients except 2 of each group. Plasma PTH was initially above 70 pg/ml in 8 of the CaCO3 and did not change significantly throughout the study, 2 patients having at 6 months a PTH level below 70 pg/ml. In contrast with intravenous 1 alpha-OH-D3, all the 9 patients with initial frank HPT decreased their PTH levels after 2 months, the levels being below 70 pg/ml in 6 cases. However, because of hypercalcemia and/or of hyperphosphatemia in spite of a highest tolerable dose of Mg(OH)2, 1 alpha-OH-D3 doses had to be decreased down to 0.4 microgram per dialysis at the 6th month so that at 6 months 6 of 9 patients had their PTH levels above 70 pg/ml, a number comparable to that of patients treated with CaCO3 (6 of 8).(ABSTRACT TRUNCATED AT 400 WORDS)