The structure of hyperalkaline aqueous solutions containing high concentrations of gallium--a solution X-ray diffraction and computational study.

Highly concentrated alkaline NaOH-Ga(OH)3 solutions with 1.18 M ≤ [Ga(III)]T ≤ 2.32 M and 2.4 M ≤ [NaOH]T ≤ 4.9 M (where the subscript T denotes total or analytical concentrations) have been prepared and investigated by solution X-ray diffraction and also by ab initio quantum chemical calculations. The data obtained are consistent with the presence of only one predominant Ga(III)-bearing species in these solutions, which is the tetrahedral hydroxo complex Ga(OH)4(-). This finding is in stark contrast to that found for Al(III)-containing solutions of similar concentrations, in which, besides the monomeric complex, an oxo-bridged dimer was also found to form. From the solution X-ray diffraction measurements, the formation of the dimeric (OH)3Ga-O-Ga(OH)3(2-) could not unambiguously be shown, however, from the comparison of experimental IR, Raman and (71)Ga NMR spectra with calculated ones, its formation can be safely excluded. Moreover, higher mononuclear stepwise hydroxo complexes, like Ga(OH)6(3-), which have been claimed to exist by others in the literature, were not possible to experimentally detect in these solutions with any of the spectroscopic techniques used.

Periodontal ligament and gingival fibroblasts from periodontitis patients are more active in interaction with Porphyromonas gingivalis.

BACKGROUND AND OBJECTIVE: Inflammatory responses of host cells to oral pathogenic bacteria, such as Porphyromonas gingivalis, are crucial in the development of periodontitis. Host cells, such as periodontal ligament and gingival fibroblasts, from periodontitis patients may respond to P. gingivalis in a different manner compared with cells from healthy persons. The aim of this study was to investigate inflammatory responses to viable P. gingivalis by periodontal ligament and gingival fibroblasts from periodontitis patients and healthy control subjects. MATERIAL AND METHODS: Primary periodontal ligament and gingival fibroblasts from periodontitis patients (n=14) and healthy control subjects (n=8) were challenged in vitro with viable P. gingivalis. Gene expression of Toll-like receptors (TLRs) 1, 2, 4, 6, 7 and 9, CD14, nuclear factor-κB1 and its putative inhibitor NF-κB inhibitor-like protein1, and of interleukin-1ß, interleukin-6, interleukin-8, tumour necrosis factor-α, monocyte chemotactic protein-1 and regulated upon activation, normal T-cel expressed, and secreted, were assessed by real-time PCR. RESULTS: Periodontal ligament fibroblasts from periodontitis patients had a higher mRNA expression of TLR1, TLR4, TLR7 and CD14, and a lower expression of NFKBIL1, both before and after P. gingivalis challenge. In contrast, gingival fibroblasts from periodontitis patients had stronger induction of TLR1, TLR2 and TLR7 by P. gingivalis. Cytokine responses were not different between patients and control subjects. Interestingly, periodontal ligament, but not gingival, fibroblasts from P. gingivalis culture-positive persons responded more strongly to P. gingivalis than periodontal ligament fibroblasts from P. gingivalis-negative persons. CONCLUSION: Periodontal ligament and gingival fibroblasts respond to P. gingivalis in a different manner and may play different roles in periodontitis. Both subsets of fibroblasts from patients appear more active in interaction with P. gingivalis. Moreover, periodontal ligament fibroblasts from P. gingivalis-positive donors are more responsive to an in vitro P. gingivalis challenge.

Comparison of the Ca2+ complexing properties of isosaccharinate and gluconate - is gluconate a reliable structural and functional model of isosaccharinate?

The calcium complexation and acid-base properties of α-d-isosaccharinate (Isa-) in neutral and in (hyper)alkaline solutions have been investigated via potentiometric titrations, multinuclear NMR, ESI-MS and quantum chemical calculations. Isa- is the primary alkaline degradation product of cellulose, and may be present in radioactive waste repositories and therefore, it could contribute to the mobilization of radioactive nuclei. Because of its limited availability, d-gluconate (Gluc-) is commonly used as a structural and functional model of Isa-. Therefore, the thermodynamic and structural data obtained for Isa- were compared with those of Gluc-. The formation constants of the CaIsa+ and CaGluc+ complexes present in neutral solutions are practically identical, but the binding sites are in different positions and the CaIsa20 solution species cannot be detected. The stepwise formation constant of the CaIsaH-10 complex (forming in alkaline medium) is somewhat larger than that of CaGlucH-10, which is in line with the observation that IsaH-12- is a stronger base than GlucH-12-. The most striking difference is that, unlike Gluc-, Isa- does not form polynuclear complexes with Ca2+. The structural reason for this is that the alcoholate groups on C2 and C3 adjacent to the carboxylate moiety on Gluc- are able to simultaneously bind Ca2+, making the formation of polynuclear Ca-complexes possible. On Isa-, only the alcoholate on C2 is involved, while the other one on C6 is not (supposedly for steric reasons). In conclusion, during the interactions of Gluc- and Isa- with Ca2+, differences rather than similarities prevail.

Characterization of complexes formed between [Me2Sn(IV)]2+ and carboxymethylcelluloses.

Complexes formed between carboxymethylcellulose (CMC) and the [Me(2)Sn(IV)]2+ cation have been prepared in the solid state and characterized by FTIR and Mössbauer spectroscopy. The complexes contained CMC with varying molar weight and degree of carboxylation, and the complexes were isolated both from acidic and from neutral solutions at varying metal-to-ligand ratios. The characteristic vibration bands of the ligands were identified from their pH-dependent FTIR spectra. In the organotin(IV) complexes obtained at pH approximately 2, the -COO- moieties were found to be coordinated in a monodentate manner, and the band characteristic of the protonated (unbound) -COO- group(s) was also identified. The broad -OH band can be interpreted as the sum of the contributions of the alcoholic -OH groups of the anhydroglucose units and the mixed organotin aqua complexes. In complexes obtained at pH approximately 7, the broad -OH band significantly sharpens, which is probably due to the metal-ion induced deprotonation and subsequent coordination of the alcoholic -OH groups. At the same time, -COO- groups are also involved in the coordination of the metal ions, resulting in a complicated network that forms through inter- and intramolecular bridges. Quadrupole splitting (/Delta(exp)/) values observed by Mössbauer spectroscopy revealed that the valence state of tin is four in all of the complexes. The /Delta(exp)/ values were compared with the calculated ones, obtained from the pqs theory. From these data, trigonal bipyramidal (Tbp) and octahedral (Oh) geometries have been suggested for the complexes obtained. It has also been concluded that the structure of the complexes prepared depends mainly on the pH of the solution, and it is relatively insensitive to the other parameters, like molar mass or degree of carboxylation of the ligand, or the metal-to-ligand ratio in the reaction mixture.

Ursodeoxycholate stabilizes phospholipid-rich membranes and mimics the effect of cholesterol: investigations on large unilamellar vesicles.

Ursodeoxycholate is used to treat primary biliary cirrhosis and is incorporated into hepatocyte plasma membranes. Its steroid nucleus binds to the apolar domain of the membrane, in a similar position to cholesterol. Therefore the question arises whether ursodeoxycholate has a similar effect on membrane structure and stability as cholesterol. Using differential scanning calorimetry the thermotropic behavior of egg phosphatidylcholine and dimyristoylphosphatidylcholine were studied after incubation with cholesterol or ursodeoxycholate. Large unilamellar vesicles were prepared with cholesterol contents of 0-50%. Following incubation of these vesicles with different amounts of ursodeoxycholate, vesicle stability in a gravitational field was investigated by measuring the phospholipid and cholesterol release. Vesicle size was studied by laser light scattering after incubation with cheno- and ursodeoxycholate, and the release of entrapped carboxyfluorescein was measured by means of fluorescence spectroscopy. Increasing cholesterol diminished the enthalpy of the phase transition in the membrane. Ursodeoxycholate decreased the enthalpy of the phase transition at even lower concentrations. Lipid release from vesicles in a high gravitational field diminished with increasing cholesterol content of the vesicles. Ursodeoxycholate had a comparable effect, which increased as the cholesterol content of the vesicles was decreased. Chenodeoxycholate damaged vesicles, whereas ursodeoxycholate did not. Cholesterol and ursodeoxycholate (below its critical micellar concentration) decreased the carboxyfluorescein release from vesicles induced by chenodeoxycholate. Thus like cholesterol, ursodeoxycholate is incorporated into phospholipid model membranes and reduces the change in enthalpy of the gel to liquid-crystalline phase transition. Like cholesterol ursodeoxycholate also maintains membrane stability and prevents membrane damage induced by mechanical and chemical stress.

Curcumin and its analogue induce apoptosis in leukemia cells and have additive effects with bortezomib in cellular and xenograft models.

Combination therapy of bortezomib with other chemotherapeutics is an emerging treatment strategy. Since both curcumin and bortezomib inhibit NF-κB, we tested the effects of their combination on leukemia cells. To improve potency, a novel Mannich-type curcumin derivative, C-150, was synthesized. Curcumin and its analogue showed potent antiproliferative and apoptotic effects on the human leukemia cell line, HL60, with different potency but similar additive properties with bortezomib. Additive antiproliferative effects were correlated well with LPS-induced NF-κB inhibition results. Gene expression data on cell cycle and apoptosis related genes, obtained by high-throughput QPCR, showed that curcumin and its analogue act through similar signaling pathways. In correlation with in vitro results similar additive effect could be obsereved in SCID mice inoculated systemically with HL60 cells. C-150 in a liposomal formulation given intravenously in combination with bortezomib was more efficient than either of the drugs alone. As our novel curcumin analogue exerted anticancer effects in leukemic cells at submicromolar concentration in vitro and at 3 mg/kg dose in vivo, which was potentiated by bortezomib, it holds a great promise as a future therapeutic agent in the treatment of leukemia alone or in combination.

The ionic product of water in concentrated tetramethylammonium chloride solutions.

The ionic product of water, pK(w) = - log[H(+)][OH(-)] has been determined in aqueous solutions of tetramethylammonium chloride over the concentration range of 0.1-5.5 M at 25 degrees C using high-precision glass electrode potentiometric titrations. pK(w) data relating to aqueous potassium and sodium chlorides at ionic strengths up to 5 M are markedly lower than the tetramethylammonium chloride results. These differences are almost certainly due to weak associations between potassium and (especially) sodium and hydroxide ions.

[Comparative study of superoxide production of monocytes in primary biliary cirrhosis]. / A monocyták szuperoxid termelésének összehasonlító vizsgálata primer biliaris cirrhosisban.

Monocytes appear to play a role in immunological abnormalities observed in primary biliary cirrhosis (PBC). Monocytes not only produce fibroproliferative factors, such as IL-1, TNF, and PDGF but also produce superoxide anion which can directly damage tissues, and thus may lead to fibrosis. The aim of this study was to compare the superoxide production in monocytes obtained from 12 control persons, 9 patients with non biliary cirrhosis, 6 untreated PBC patients, 6 patients with gallstones under urso- and chenodeoxycholicacid (Lithofalk) treatment and 32 PBC patients under ursodeoxycholicacid (UDCA) therapy. Monocytes were isolated and the production of superoxide anions with and without phorbol-myristate-acetate (PMA) stimulation was determined. In two occasion, the monocytes from control patients were preincubated with 10, 50, 100 microM UDCA. Unstimulated monocytes from PBC patients under UDCA therapy produce an average 43% more and the PMA stimulated monocytes an average 42% more superoxide than monocytes from the control or from the other cirrhotic patients. The UDCA preincubation did not influence the superoxide production of monocytes obtained from control patients. These findings suggest that the increased activity of monocytes may also play a role in liver damage and fibrosis in PBC.

Review: Endothelial progenitor cells in pregnancy and obstetric pathologies.

Since their discovery, endothelial progenitor cells (EPCs) have generated considerable interest in vascular biology. They are a heterogeneous population of cells that exist in both the fetus and adult, and are mobilized to support de novo vessel formation or encourage vascular health. This review summarizes our understanding of these cells in pregnancy, paying particular attention to their physiological role in placental development and the uterus, alongside their involvement in related obstetric pathologies.

Physico-chemical characterization and in vitro/in vivo evaluation of loratadine:dimethyl-ß-cyclodextrin inclusion complexes.

A tricyclic, piperidine derivative of antihistamines, loratadine, which belongs in class II of the Biopharmaceutical Classification System, was investigated. It is an ionizable drug, whose solubility depends on the gastrointestinal pH, and the bioavailability is therefore very variable. Inclusion complexes were prepared by kneading method, containing loratadine (LOR) and dimethyl-ß-cyclodextrin (DIMEB) in two different molar ratios in an attempt to achieve better dissolution and therefore the better bioavailability of loratadine. The formation and physicochemical properties of the inclusion complexes were investigated by means of dissolution tests, pH-dependent solubility studies, electrospray ionization mass spectrometry and diffusion-ordered 1H NMR spectroscopy. The in vivo efficiency of the complexes was examined in rat animal experiments to confirm the better in vitro dissolution. The instrumental examinations proved the presence of total complexes in 1:1 ratio in both compositions. However, the in vitro pH-dependent solubility results, the in vivo blood levels and the greater pharmacological effect prove that excess DIMEB is needed to achieve the pH-independent and complete solubility of LOR, and therefore better and more consistent bioavailability.

Endothelial progenitor cells: their potential in the placental vasculature and related complications.

Endothelial progenitor cells (EPCs) have received significant attention in recent times. A role for EPCs has been suggested in a range of pathologies and some recent studies of EPCs in pregnancy have been published. This review provides a guide to the confusing field of EPCs. Attention is paid to their phenotyping, as although elementary this remains a highly debated topic. The current understanding of different subtypes and physiological role of EPCs in the placenta, fetus and adult are also considered. An overview is given as to role of EPC's in the pathophysiology of different disease states and the possible therapeutic and diagnostic applications expected from EPC-related research in obstetrics.

The combined use of enamel matrix proteins and a tetracycline-coated expanded polytetrafluoroethylene barrier membrane in the treatment of intra-osseous defects.

OBJECTIVES: The purpose of this split-mouth study was to evaluate the clinical response of enamel matrix proteins (EMPs, Emdogain Gel in intra-osseous defects with or without a combined application of a tetracycline-coated expanded polytetrafluoroethylene barrier membrane (e-PTFE, Gore-Tex). METHODS: Twelve pairs of intra-osseous periodontal defects in 11 patients received the application of EMPs on the exposed root surface (EMP). One of the two defects received randomly, as an adjunct to EMP treatment, a tetracycline-coated e-PTFE membrane (MEMP). At baseline, 6- and 12-month probing pocket depth (PPD), clinical attachment level (CAL) and probing bone level (PBL) were measured. RESULTS: After 12 months, the EMP defects showed a significant mean PPD reduction of 2.86+/-0.75 mm, a mean gain in CAL of 1.28+/-2.04 mm, a mean PBL gain of 1.63+/-1.21 mm and a mean increase of recession (REC) of 1.56+/-2.30 mm. The MEMP defects showed a significant mean PPD reduction of 3.02+/-1.55 mm, a mean gain in CAL of 1.65+/-1.29 mm, a mean PBL gain of 1.58+/-1.92 mm and a mean increase of REC of 1.38+/-1.63 mm. Except for significantly more post-operative discomfort at the MEMP sites, no significant differences were found between EMP and MEMP defects. CONCLUSION: Within the limits of this study, it is concluded that in the treatment of intra-osseous defects with EMP, the adjunctive use of a tetracycline-coated e-PTFE membrane failed to show more gain of CAL and PBL.

Effect of electrophilic and nucleophilic substituents on the protonation microequilibria of tyrosine derivatives.

The microscopic protonation constants of 10 tyrosine-like, unusual amino acids used in the syntheses of opioid peptides have been determined by using a combined pH-metric-spectrophotometric method, at 0.10 mol dm-3 (NaCl) ionic strength and 25.0 degrees. The role of the different electrophilic and nucleophilic substituents on the individual basicity of the aliphatic amine and phenolic hydroxylate basic centers is discussed in detail. The interactivity parameters between these two groups correlate fairly well with the structure of the skeleton and the distance between the two basic centers, but they were found to be substituent-independent. This finding made it possible to extend the calculations to compounds having non-overlapping protonation equilibria.

Cholecystitis, gallstones and free radical reactions in human gallbladder.

BACKGROUND: The relationship between biophysical and biochemical processes of gallbladder bile and free radical reactions is still not known. The aim of our study was to investigate the correlation between free radical production and the degree of inflammation in gallbladder. MATERIAL AND METHODS: The degree of chronic cholecystitis was determined by observing the number of infiltrating lymphocytes and the mucosal epithelial change. The free radical reaction products were determined by measuring the chemiluminescent light intensity, the malondialdehyde (MDA) and dien concentration of bile. RESULTS: The content of free radical reaction products, like MDA and diene in bile slightly decreased with the severity of cholecystitis. The size of stones inversely correlated with the severity of inflammation. The chemiluminescent light intensity showed correlation with bilirubin concentration. Between 501 (mol/l range the bilirubin gave significantly higher chemiluminescent light intensity, than in the lower and in the higher concentration range. In this bilirubin concentration range diene concentration correlated inversely with chemiluminescent light intensity, while MDA concentration elevated with the bilirubin concentration. CONCLUSION: Correlation was found between the number of stones and the degree of cholecystitis which may indicate that free radical products are incorporated into the stones and do not stay in solution. The high chemiluminescent light intensity of the bile at the 501-1300 (mol/l bilirubin concentration range means that bilirubin participates at this concentration most reactively in free radical reactions. These results suggest, that there is a correlation between free radical reactions, gallstone formation and the degree of cholecystitis.

An investigation of the lead(II)-hydroxide system.

A detailed investigation of the Pb(II)/OH(-) system has been made in NaClO(4) media at 25 degrees C. Combined UV-vis spectrophotometric-potentiometric titrations at [Pb(II)](T) < or = 10 microM using a long path length cell detected only four mononuclear hydroxide complexes. The values of log beta(1)(q)(), for the equilibria Pb(2+)(aq) + qH(2)O <--> Pb(OH)(q)()((2)(-)(q)()()+)(aq) + qH(+)(aq), were -7.2, -16.1, -26.5, and -38.0 for q = 1-4, respectively, at ionic strength I = 1 M (NaClO(4)). Similar results were obtained at I = 5 M (NaClO(4)). No evidence was found for higher order complexes (q > 4) even at very high [OH(-)]/[Pb(II)] ratios, nor for polynuclear species at [Pb(II)](T) < or = 10 microM. Measurements using (207)Pb-NMR and Raman spectroscopies and differential pulse polarography (DPP) provided only semiquantitative confirmation. The mononuclear Pb(OH)(q)()((2)(-)(q)()()+)(aq) complexes are the only hydrolyzed species likely to be significant under typical environmental and biological conditions.

Perfusate oncotic pressure during cardiopulmonary bypass. Optimum level as determined by metabolic acidosis, tissue edema, and renal function.

Current practice with respect to the use of a dilutional prime for cardiopulmonary bypass (CPB) varies widely, and the safe lower limit of perfusate protein content has not been defined. We studied this question in 75 rabbits subjected to a 1-hour CPB with a perfusate colloid osmotic pressure (COP) ranging from 26 to 4 mm Hg. Metabolic acidosis was inversely related to COP; acid-base equilibrium is thus best maintained with a high perfusate protein content. Tissue edema rapidly increased at COP levels below 16 mm Hg, i.e. with a protein level less than 4.2 g%. Urinary excretion during CPB was antagonized by the COP, the reason being that glomerular filtration rate was proportional to the difference between perfusion pressure and COP. The safety margin for renal function during CPB thus widens with a decreasing perfusate protein content. We conclude that the optimum levels of perfuste oncotic pressure and protein content during experimental cardiopulmonary bypass are 16 mm Hg and 4.2 g%.

Late epigastric incisional hernias following laparoscopic cholecystectomy.

By the introduction of laparoscopic cholecystectomy a new "gold standard" procedure became a routinely performed operation in the field of biliary tract surgery. Thus, the incision related early and late complications are thought to diminish, especially the formation of incisional hernias. Five patients had been referred to our department suffering from chronic incisional hernias following laparoscopic cholecystectomy. All of the hernias were located to the site of the epigastric trocar. The contents of the hernias proved to be omentum. The documentation's of the laparoscopic cholecystectomies revealed the extraction of thick walled gallbladders that contain large stones, and the wounds through which the extraction was performed had not been closed. Taking into consideration the fact of the "Chimney Effect" caused by the desufflation of the pneumoperitoneum at the end of the laparoscopic operation, bowel or omentum can easily escape through the relatively large wound formed during the extraction of the gallbladder, resulting in the formation of incisional hernias. This can be avoided by the complete desufflation and the prompt closure of the wound.

Free radical reactions in the gallbladder.

The changes in the composition of bile can lead to the process of it's crystallization in the gallbladder. In bile model it was shown that inflammation with the generation of reactive oxygen metabolites may induce and influence the cholesterol monohydrate crystal formation within supersaturated bile. The aim of this study was to investigate the ability to detect traces of reactive oxygen metabolites, thiobarbituric acid reactive compounds and dien, in order to compare cholesterol and bilirubin contents in bile and serum during different conditions of inflammation in the gallbladder's wall. In every bile sample a reference to free radical reaction was found. There was an increase in MDA during higher degree of inflammation in the gallbladder, but no alteration in the dien content was observed. In case of common bile duct stones the bilirubin in the serum and in the gallbladder was parallelly high, but in other cases there were no significant correlation. In an occluded gallbladder with hydrops the content of protein was significantly higher in 85% of the cholesterol stones. As a conclusion, free radical reactions in the wall of gallbladder as well as in bile can induce gallstone formation. Further studies are needed to clarify the time which is sufficient to change the composition of bile and the degree of inflammation which lead to the onset of stone formation.