Reaction mechanisms in irradiated, precipitated, and mesoporous silica.

A matrix EPR spectroscopy study of the low temperature γ radiolysis of precipitated (Zeosil) and mesoporous high surface silica has afforded evidence of the formation of trapped H-atoms, H-atom centers, siloxy radicals ≡Si-O(•), anomalous silyl peroxy radicals ≡Si-OO(•) with reduced g tensor anisotropy, siloxy radical-cations (≡Si-O-Si≡)(+•), E' centers, and two species from Ge impurity. Coordination of peroxyl radicals with diamagnetic ≡Si(+) centers is proposed and tested by DFT computations in order to justify the observed g tensor. Coordination of H-atoms to ≡Si(+) centers is also proposed for the structure of the H-atom centers as an alternative model not requiring the intervention of Ge, Sn, or CO impurities. The DFT method has been employed to assess the electronic structure of siloxy radical-cations and its similarity with that of the carbon radical-cation analogues; the results have prompted a revision of the structures proposed in the literature for ST1 and ST2 centers. The comparison between the two types of silica has afforded evidence of different radiolysis mechanisms leading to a greater yield of trapped H-atoms and H-atom centers in zeosil silica, which is reckoned with the 4-fold greater concentration of silanol groups. Parallel radiolysis experiments carried out by using both types of silica with polybutadiene oligomers as adsorbate have afforded evidence of free valence and energy migration phenomena leading to irreversible linking of polybutadiene chains onto silica. Reaction mechanisms are proposed based on the detection of SiO2-bonded free radicals whose structure has been defined by EPR.

Highly luminescent scintillating hetero-ligand MOF nanocrystals with engineered Stokes shift for photonic applications.

Large Stokes shift fast emitters show a negligible reabsorption of their luminescence, a feature highly desirable for several applications such as fluorescence imaging, solar-light managing, and fabricating sensitive scintillating detectors for medical imaging and high-rate high-energy physics experiments. Here we obtain high efficiency luminescence with significant Stokes shift by exploiting fluorescent conjugated acene building blocks arranged in nanocrystals. Two ligands of equal molecular length and connectivity, yet complementary electronic properties, are co-assembled by zirconium oxy-hydroxy clusters, generating crystalline hetero-ligand metal-organic framework (MOF) nanocrystals. The diffusion of singlet excitons within the MOF and the matching of ligands absorption and emission properties enables an ultrafast activation of the low energy emission in the 100 ps time scale. The hybrid nanocrystals show a fluorescence quantum efficiency of ~60% and a Stokes shift as large as 750 meV (~6000 cm-1), which suppresses the emission reabsorption also in bulk devices. The fabricated prototypal nanocomposite fast scintillator shows benchmark performances which compete with those of some inorganic and organic commercial systems.

Fluorinated porous organic frameworks for improved CO2 and CH4 capture.

A porous 3D selectively fluorinated framework (F-PAF1), robust yet flexible and with a surface area of 2050 m2 g-1, was synthesised by condensation of an ad hoc prepared fluorinated tetraphenylmethane (TPM) monomer to ensure homogenously distributed C-F dipoles in the swellable architecture. Tetradentate TPM was also the comonomer for the reaction with fluorinated difunctional monomers to obtain frameworks (FMFs) with a controlled amount of regularly spaced reorientable C-F dipoles. The isosteric heat of adsorption of CO2 was increased by 53% by even moderate C-F dipole insertion, with respect to the non-fluorinated frameworks. CO2/N2 selectivity was also increased up to a value of 50 for the difluoro-containing comonomer. Moreover, methane shows optimal interaction energies of 24 kJ mol-1.

Expandable porous organic frameworks with built-in amino and hydroxyl functions for CO2 and CH4 capture.

The synthesis of porous organic 3D frameworks, wherein amine, hydroxyl and Li-alkoxide functions were built directly on the monomer-unit carbon core, realizes improved interactions with target gases. CO2 was retained by the amine group with a remarkable energy of 54 kJ mol-1, while 2D MAS NMR provided rare evidence of amine-to-gas short-distance interactions. Frameworks containing hydroxyl and Li-alkoxide functions show optimal interaction energies with CH4 of up to 25 kJ mol-1. The light network of 3-branch building units ensures the expandability of the nano-sponges.

Porous dipeptide crystals as volatile-drug vessels.

Porous crystalline dipeptides absorb, reversibly from the gas phase, a series of volatile fluorinated ethers in use as anesthetics. Their vapor pressure was considerably reduced, with favorable guest capture and release. Variable channel sizes were customized for selective sorption and pressure thresholds were observed in the narrowest pores. 1H, 13C and 19F MAS NMR coupled with ab initio conformational analysis and grand canonical Monte Carlo simulations highlight the guest loading and arrangement adopted in the congruent nanochannels, suggesting how the anesthetics can accommodate in biochemical receptors.

CO2 regulates molecular rotor dynamics in porous materials.

A crystalline hydrogen-bonded framework with permanent porosity, built by rod-like struts and engineered to bear ultra-fast molecular rotors between two triple bonds, offers the possibility of controlling the rotational rates upon CO2 adsorption. CO2 enters the pores from the gas phase and reduces the rotational rates from the extremely fast regime of 107 Hz at 216 K to 105 Hz. The CO2-rotor interaction was evident from the 2H NMR response to the dynamics of the rotors in contact with CO2 in the crystal structure.

IL-13 induces serine phosphorylation of cPLA2 in mouse peritoneal macrophages leading to arachidonic acid and PGE2 production and blocks the zymosan-induced serine phosphorylation of cPLA2 and eicosanoid production.

In a recent investigation, we demonstrated that long-term treatment of macrophages with IL-13 enhances cPLA2 expression and modulates zymosan-stimulated AA mobilization. In the present study, we examine the ability of IL-13 to modify the cPLA2 activity and the AA mobilization of macrophages after a short-period of treatment. We demonstrate that in resting macrophages, IL-13 induces, through a MAP kinase-dependent process, (1) an increase of free AA release within 15 min, followed by increased PGE2 production and (2) a time-dependent serine phosphorylation of cPLA2. Conversely, in macrophages stimulated by zymosan, IL-13 added 30 min before zymosan inhibited the AA release and the serine phosphorylation of cPLA2 induced by the phagocytic agonist. In conclusion, these findings show for the first time that a Th2-type cytokine can upregulate cPLA2 activity and downregulate zymosan-induced AA metabolism. Thus, establishment of the connection between these two events may help to understand the complex regulatory role of IL-13 on the macrophage AA metabolism.

IL-13 increases the cPLA2 gene and protein expression and the mobilization of arachidonic acid during an inflammatory process in mouse peritoneal macrophages.

Pretreatment of mouse peritoneal macrophages with interleukin-13 (IL-13) potentiates the mobilization of arachidonic acid (AA) and the production of HETEs but does not affect the production of cyclooxygenase metabolites triggered by the suboptimal concentration of an inflammatory agonist (opsonized-zymosan). Cycloheximide suppresses these effects of IL-13 suggesting that de novo protein synthesis is involved. Indeed, IL-13 induces a time-dependent increase in the levels of cytosolic PLA2 (cPLA2) protein and mRNA. This study demonstrates a new pathway for IL-13 to modulate the inflammatory process in macrophages via modifications of cPLA2 expression and subsequent AA mobilization.

Cervicovaginal infections during pregnancy: epidemiological and microbiological aspects.

OBJECTIVE: The assessment of the association of cervicovaginal infections during pregnancy with preterm (pPROM) and term (PROM) premature rupture of membranes, preterm delivery, mid-trimester miscarriage and intrauterine death, and the definition of the risk factors that identify pregnant women who should have a cervicovaginal culture. METHODS: We retrospectively studied the relationship between pregnancy outcomes and cervicovaginal infections in 3217 pregnant women between January 1998 and December 1999. Microbiological assessment included Gram staining and specific cultures; bacterial vaginosis was diagnosed by Amsel's criteria. We also studied the medical, obstetric, sexual, demographic and social history of 11,212 pregnant women who underwent cervicovaginal culture between January 1992 and December 2001. RESULTS: Overall, 1425 of the 3217 cultures (44.3%) were positive. The micro-organisms most frequently found were: yeasts (44%), Ureaplasma urealiticum (29%); group B streptococcus (15%); and bacterial vaginosis (11%). Cervicovaginal cultures were found positive in 84.6% of pPROM, 55.0% of PROM, 50.8% of preterm deliveries, 43.8% of mid-trimester miscarriages, 31.4% of intrauterine deaths and in 33.5% of controls. Among the 11 212 cervicovaginal cultures considered in the second study, an overall 6301 (56.2%) were positive, 2711 (43%) in asymptomatic women. Cervicovaginal infections were associated with country of origin, age under 25 years, age at first intercourse under 15 years, more than ten partners, more than one partner in the past 6 months, prior abortions, past sexually transmitted diseases (STDs) and HIV infection. CONCLUSION: Cervicovaginal infections were significantly associated with PROM (p<0.0001), pPROM (p<0.0001) and preterm delivery (p<0.0001), but not with intrauterine death. The association with mid-trimester miscarriage approached statistical significance (p=0.06). The main risk factors for cervicovaginal infections were country of origin, age under 25 years, age at first intercourse under 15 years, more than ten partners, more than one partner in the past 6 months, prior abortions, past STDs and HIV infection.

Thermotropic behavior of dipalmitoylphosphatidylcholine-sulfatide liposomes.

The thermotropic behavior of multilamellar liposomes prepared from mixtures of sulfatide and dipalmitoylphosphatidylcholine has been studied by DTA calorimetry. The cooperative unit size and the enthalpy change of the main transition decrease concomitant with the increase of the sulfatide-phospholipid mole ratio. The origin of these effects and their dependence on the sulfatide content suggest that the in-plane distribution of sulfatide and the physical state of the lipid bilayer are affected by the sulfatide-phospholipid mole ratio.

Protein and lipid disturbances in rat liver microsomal membranes after bile duct ligation.

An analysis of proteins, phospholipids and cholesterol from liver microsomal membranes was performed in normal and post-cholestatic rats. Bile duct ligated rats showed a progressive decrease of these membrane constituents. Minor changes in peptide analysis, a marked decrease of phosphatidylcholine and phosphatidylinositol, disappearance of phosphatidylethanolamine and sphingomyelin, and a clear increment of phosphatidylserine was observed in post-cholestatic as compared to normal group. It was concluded that extra-hepatic cholestasis produces structural changes on the liver microsomes, particularly on phospholipid profile.

Pharmacological and biochemical characterization of cholecystokinin/gastrin receptors in developing rat pancreas. Age-related expression of distinct receptor glycoforms.

Cholecystokinin/gastrin receptors in the pancreas of newborn (3-day-old) rats are of type A, as in control mature rats, revealed by pharmacological analysis of specific 125I-Bolton-Hunter-reagent-labelled [Thr34,Ahx37]cholecystokinin(31-39) (Ahx, aminohexanoic acid) binding. Also, by 1 day post-partum, pancreatic cholecystokinin receptors were shown to be coupled to guanine-nucleotide-binding regulatory (G) proteins. Scatchard analysis of 125I-Bolton-Hunter-reagent-labelled [Thr34,Ahx37]cholecystokinin(31-39) binding to pancreatic membranes from rats at different times after birth showed a slight increase in the binding capacity of cholecystokinin receptors between days 3 and 14 and a sixfold increase in 21-day-old rats, with no change in receptor affinity during development. SDS/PAGE analysis of pancreatic membranes affinity labelled with the photoactivable ligand 125I-[2-(p-azidosalicylamido)-1,3'-dithiopropionate]-labelled [Thr34,Ahx37]cholecystokinin-(31-39) identified cholecystokinin receptors of 100-135 kDa in 3-day-old rats, 96-130 kDa in 7-day-old rats, 90-125 kDa in 10-day-old rats and 85-100 kDa in 14-day-old and 21-day-old rats, as found in control adult rats. Endo-beta-N-acetylglucosaminidase F treatment yielded a core protein of 42 kDa in all developmental stages. These findings are consistent with an age-related postnatal expression of distinct glycoforms of pancreatic cholecystokinin receptors. Furthermore, it was observed that the period 2-3 weeks after birth, characterized by stabilization of the mass of the cholecystokinin receptor, precedes the dramatic increase in the receptor number.

Interleukin-13 inhibits protein kinase C-triggered respiratory burst in human monocytes. Role of calcium and cyclic AMP.

Interleukin-13 (IL-13), a novel cytokine produced by activated lymphocytes modulates some monocyte functions, but no data is available concerning the signal transduction pathway. We show here, the inhibitory effect of IL-13 on 12-O-tetradecanoylphorbol-13-acetate (TPA)-triggered reactive oxygen intermediate production in human monocytes and the signals involved in this response. Our results show that IL-13 produces rapid and transient phosphoinositide hydrolysis and intracellular Ca2+ mobilization. Furthermore, IL-13 induces intracellular cAMP accumulation through inositol 1,4,5-trisphosphate-dependent Ca2+ mobilization. Metabolic inhibitors were used to relate the first steps in signaling pathways to the inhibitory effect of IL-13 on TPA-triggered reactive oxygen intermediate production. Indeed, inhibitors of phospholipase C (neomycin), intracellular Ca2+ mobilization (8-[N,N-diethylamino]-octyl 3,4,5-trimethoxybenzoate hydrochloride), adenylate cyclase (delta 9-tetrahydrocannabinol), and protein kinase A (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide) impair the IL-13 inhibitory response. Altogether these observations indicate that modulatory effect of IL-13 on the TPA-induced oxidative burst is the result of the intracellular cAMP accumulation through an inositol 1,4,5-trisphosphate-induced Ca2+ mobilization-dependent pathway.

IL-13 induces tyrosine phosphorylation of phospholipase C gamma-1 following IRS-2 association in human monocytes: relationship with the inhibitory effect of IL-13 on ROI production.

Here we analysed the involvement of tyrosine phosphorylation in the regulation of the initial molecular events induced by IL-13 to modulate TPA-triggered reactive oxygen intermediates (ROI) production. Our data indicate that treatment of monocytes with a protein tyrosine kinase inhibitor (herbimycin A) prevents IL-13-induced cAMP accumulation and subsequent ROI inhibition. We have previously demonstrated that cAMP accumulation depends on inositol phosphates hydrolysis (InsPs) and intracellular Ca2+ mobilisation. The inhibition of InsPs and intracellular Ca2+ release by herbimycin A suggests a primary role of tyrosine kinases upstream PLC activation. We further specify that IL-13 stimulates PLC-gamma 1 and IRS-2 tyrosine phosphorylation in human monocytes. We demonstrate for the first time that IL-13 induces the association of IRS-2 with PLC-gamma 1. We proposed here that PLC-gamma 1 is a new candidate recruited by IRS-2.

Detection and biochemical characteristics of the receptor for complexes of soluble CD14 and bacterial lipopolysaccharide.

Soluble CD14 (sCD14) has been found to bind LPS and mediate LPS activation of several cell types. It has been postulated that sCD14-LPS complexes induce cell responses by interacting with a cell surface structure, which, in turn, triggers cell activation. There has been no biochemical evidence, however, for a direct interaction of sCD14 with a cell surface structure, and the putative receptor has not been identified. To rigorously test this hypothesis, we studied the interaction of human rsCD14 with cells in the absence of serum and in the presence and the absence of LPS. We found 1) there was specific and saturable binding of 125I-sCD14, indicative of a typical receptor-ligand interaction, to several cell types, including endothelial cells, epithelial cells, astrocytes, and human monocytes; 2) specific binding to all the cell types and IL-6 induction in membrane-bound CD14 (mCD14)-negative cells occurred only when both sCD14 and LPS were present; 3) competitive displacement experiments of 125I-sCD14 binding to astrocytes and Scatchard plots revealed a binding of high affinity (Kd = 3.3 +/- 0.4 nM) and approximately 25,000 single class binding sites/cell; 4) the steady state for the association of 125I-sCD14 was obtained after 180-200 min; 5) chemical cross-linking experiments revealed the association of sCD14 with a binding structure of approximately 216 kDa; 6) binding of 125I-sCD14 to CD14-expressing cell transfectants was about 50% lower than that to nontransfected cells. Maximal binding, however, was recovered after removing mCD14, suggesting that the sCD14-LPS receptor may also interact with mCD14. These results provide direct biochemical evidence for the existence of a cell surface signal-mediating binding structure for LPS-bearing sCD14 and suggest that this structure may represent the signaling unit of the postulated multimeric LPS receptor in mCD14-bearing cells.

Weakness of mucosal barrier in portal hypertensive gastropathy of alcoholic cirrhosis. Effects of propranolol and enprostil.

BACKGROUND/AIMS: It has been suggested that the vulnerability of gastric mucosa is increased in patients with cirrhosis as a result of a PGE2 deficiency. Therefore, we evaluated whether PGE2 mucosal generation, and gastric potential difference - a reflection of the gastric mucosal barrier - were correlated to endoscopic features and whether these alterations could be alleviated. METHODS: The potential difference was measured before (basal) and after a stimulation test by aspirin. The serum levels of gastrin and glucagon were also determined. Finally, the effects of a 1-week administration of propranolol or enprostil were tested on potential difference. The endoscopic grade of portal hypertensive gastropathy was assessed according to McCormack et al. The results are presented respectively for controls, patients with mild gastropathy, and patients with severe gastropathy. Comparisons were made using variance or covariance analysis after adjustment with age. RESULTS: Basal potential difference was significantly different between the three groups: -30.6, -28.8, -24.9 mV, p <0.05, respectively. The effects of aspirin administration on potential difference parameters were significantly different between the three groups (irritability index: 35 +/- 25, 92 +/- 98, 114 +/- 74 mV2.min, p <0.05, respectively) when non-responders to aspirin were excluded. PGE2 mucosal generation was significantly increased in both the antrum (9.8, 19.5, 19.7 ng/mg proteins, p<0.05, respectively) and in the corpus (8.1, 14.0, 20.2 ng/mg proteins, p<0.05, respectively). PGE2 generation was not related to potential difference. Glucagon serum levels were related to the grade of gastropathy. A 1-week administration of 160 mg/d long-acting propranolol, 35 micro g/d enprostil or placebo did not significantly modify basal potential difference. CONCLUSIONS: Portal hypertensive gastropathy is characterized by a decreased potential difference proportional to the endoscopic severity. The gastric mucosa of patients with cirrhosis seems to be more susceptible to aspirin than that of healthy subjects. It appears that the role of PGE2 is controversial in portal hypertensive gastropathy. Propranolol and enprostil do not improve this decreased potential difference.