Pharmacokinetics of Ferrous Sulphate (Tardyferon®) after Single Oral Dose Administration in Women with Iron Deficiency Anaemia.

Iron-containing preparations available on the market vary in dosage, salt, and chemical state of iron contained in the preparation, as well as in the iron delivery process (immediate or prolonged-release). The present study aimed at characterizing the serum pharmacokinetics of iron in non pregnant women with iron deficiency anaemia (IDA) following a single oral administration of a prolonged-release ferrous sulphate tablet. This multicenter, single dose, open-label study was conducted in 30 women aged between 18 and 45 years with IDA. A single 160 mg oral dose of ferrous sulphate was given as 2 tablets of 80 mg of Tardyferon(®) under fasting conditions. Blood samples were collected before dosing and until 24 h post-dosing. Serum iron concentrations were determined using a routine colorimetric analytical method. Pharmacokinetic parameters were determined from the serum concentration profiles using a non compartmental approach. Serum profiles showed elevated levels of iron up to 12 h after drug intake. The median time to maximum serum concentrations (Tmax) occurred 4 h post-dosing. Between 2 and 8 h post-dosing, mean serum iron concentrations fluctuated by only 20%. Additionally, C8h and C12h represented on average 78.6% and 47.5% of the Cmax, respectively. This study demonstrates that a single oral dose of 160 mg Tardyferon(®) administered under fasting condition to 30 women with IDA leads to an optimal long-lasting release of iron in the gastrointestinal tract in the targeted population. This allows the attainment and maintenance of elevated serum iron levels for up to 12 h after administration.

Cellular localization, binding sites, and pharmacologic effects of TFF3 in experimental colitis in mice.

Trefoil factors (TFFs) are essential for protection and restitution of the gastrointestinal mucosa but many aspects of TFF biology are unclear. Our aim was to compare the localization of endogenous TFFs and binding sites for injected TFF3 in the colon of healthy and colitic mice and to study the effect of TFF3 on dextrane sulfate sodium (DSS)-induced colitis in mice. Expression of endogenous TFF1-3 was examined by in situ hybridization and immunohistochemistry, and the distribution of intravenously, intraperitoneally, and subcutaneously administered (125)I-TFF3 by autoradiography and gamma-counting. The effect of systemically administered TFF3 on DSS-induced colitis was assessed. We found increased expression of endogenous TFF3 and increased binding of injected (125)I-TFF3 in the colon of animals with DSS-induced colitis. The distribution of intraperitoneally and subcutaneously administered (125)I-TFF3 was comparable. Systemic administration of the peptides reduced the severity of colitis. Expression of endogenous TFF3 and binding of systemically administered TFF3 are increased in DSS-induced colitis. Systemic administration of TFF3 attenuates the disease. These findings suggest a role of TFF3 in mucosal protection.

Adsorption of human salivary mucin MG1 onto glow-discharge plasma treated acrylic resin surfaces.

It has been suggested that altering the surface properties of acrylic resin material may change the nature of the adsorbed pellicle affecting denture retention and microbial adherence. This study aimed at evaluating the adsorption of salivary high molecular-weight mucins, a major component of denture pellicle, onto modified acrylic resin surfaces. (Poly) methylmethacrylate specimens were treated by glow discharge plasma technique, using hydrophilic 2-Hydroxyethylmethacrylate monomer or oxygen (O(2)) gas and hydrophobic Hexamethyldisiloxane monomer, at different discharge powers. Acrylic samples were incubated with high-molecular weight mucin, MG1 purified from saliva, the adsorbed fractions were transferred to nitrocellulose membranes by slot-blot technique, stained by periodic acid-Schiff and colour intensities were analysed by a colour densitometer. Higher amounts of mucins were adsorbed on all the surfaces modified by glow-discharge plasma treatment. Within the limitations of this study, it was concluded that glow-discharge plasma altered the surfaces of acrylic resin denture base materials and significantly increased the adsorption of high molecular-weight mucins at varying levels depending on plasma parameters.

Mucoadhesive thiolated chitosans as platforms for oral controlled drug delivery: synthesis and in vitro evaluation.

The aim of the present study was to evaluate the influence of the degree of modification and the polymer chain length on the mucoadhesive properties and the swelling behavior of thiolated chitosan derivatives obtained via a simple one-step reaction between the polymer and 2-iminothiolane. The conjugates differing in molecular mass of the polymer backbone and in the amount of immobilized thiol groups were compressed into tablets. They were investigated for their mucoadhesive properties on freshly excised porcine mucosa via tensile studies and the rotating cylinder method. Moreover, the swelling behavior of these tablets in aqueous solutions was studied by a simple gravimetric method. The obtained results demonstrated that the total work of adhesion of chitosan-TBA (=4-thio-butyl-amidine) conjugates can be improved by an increasing number of covalently attached thiol groups; a 100-fold increase compared to unmodified chitosan was observed for a medium molecular mass chitosan-TBA conjugate exhibiting 264 microM thiol groups per gram polymer. Also, the polymer chain length had an influence on the mucoadhesive properties of the polymer. The medium molecular mass polymer displayed a fourfold improved adhesion on the rotating cylinder compared to the derivative of low molecular mass. These results contribute to the development of new delivery systems exhibiting improved mucoadhesive properties.

Calcium dependency of adrenergic and muscarinic cholinergic stimulation of mucin release from dog submandibular gland cells.

Stimulation of muscarinic cholinergic, alpha-adrenergic and beta-adrenergic receptors elicited mucin release from dispersed dog submandibular cells. The secretory response to acetylcholine was much more pronounced than to adrenergic agonists, and largely dependent on the presence of extracellular Ca2+, but the dependency on extracellular Na+ was slight. Ionomycin also stimulated mucin release. In rat submandibular cells, neither muscarinic cholinergic agonists nor ionomycin were as effective mucosecretagogues as beta-adrenergic agonists. alpha-Adrenoceptor-mediated release was decreased by chelating extracellular Ca2+ with EGTA. The beta-adrenoceptor-mediated response was diminished by extensive exposure of cells to EGTA, due at least in part to the requirement of Ca2+ for beta-adrenoceptor stimulation of cAMP formation. 8-br-cAMP stimulated 45Ca2+ release from cells preloaded with 45Ca2+. The 8-br-cAMP-induced mucin release was eliminated in ionomycin-pretreated cells, but not inhibited by chelating extracellular Ca2+ and by the treatment of the cells with TMB-8 or in the cells loaded with BAPTA. These results suggest that not only the adrenergic system but also the muscarinic cholinergic system may participate in the regulation of mucin release in dog submandibular gland, and also provide the possibility that, in addition to a cAMP-mediated mechanism, Ca(2+)-dependent mechanisms may be involved in mucosecretion in dog submandibular acini.

Coadsorption onto hydroxyapatite of human salivary mucins and phosvitin, a phosphoprotein from egg yolk.

The adsorption of human salivary mucins (HWSM, 0.4 mg/ml) onto hydroxyapatite (HAP) was studied in the presence of varying amounts of the phosphoprotein phosvitin by three different procedures. a. Preadsorption of HWSM onto HAP for 20 h, followed by 4 h coadsorption with phosvitin, resulted in a decrease of 50% in HWSM binding to HAP with 0.3 mg/ml phosvitin and a complete desorption with 1.0 mg/ml phosvitin. b. Preincubation of HAP with phosvitin for 20 h, followed by 4 h coadsorption with HWSM, resulted in decrease of 50% in HWSM binding to HAP with 0.15 mg/ml phosvitin and the adsorption of HWSM was prevented completely with 1.0 mg/ml phosvitin. c. Simultaneous incubation of HWSM and phosvitin gave the least adsorption of HWSM to HAP: a decrease of 50% with as little as 0.025 mg/ml phosvitin and a nearly complete desorption with 0.3 mg/ml phosvitin. Similarly, the adsorption of phosvitin was strongly inhibited by HWSM after either simultaneous adsorption or preadsorption with HWSM. However, after preincubation of HAP with phosvitin, desorption of phosvitin by HWSM was not achieved. Release of phosphate increased by preadsorption with HWSM followed by incubation with phosvitin, but was lowered by about 50% after preadsorption with phosvitin. After simultaneous incubation of HAP with both species, the adsorption did not result in release of phosphate ions. Calcium release was only substantial when phosvitin was in excess in solution. The smallest release of calcium ions was observed when HAP was preincubated with phosvitin, followed by coadsorption with HWSM.