Chlorophyll and pheophytin protonated and deprotonated ions: Observation and theory.

Pheophytin a and chlorophyll a have been investigated by electrospray mass spectrometry in the positive and negative modes, in view of the importance of the knowledge of their properties in photosynthesis. Pheophytin and chlorophyll are both observed intensely in the protonated mode, and their main fragmentation route is the loss of their phytyl chain. Pheophytin is observed intact in the negative mode, while under collisions, it is primarily cleaved beyond the phytyl chain and loses the attaching propionate group. Chlorophyll is not detected in normal conditions in the negative mode, but addition of methanol solvent molecule is detected. Fragmentation of this adduct primarily forms a product (-30 amu) that dissociates into dephytyllated deprotonated chlorophyll. Semi-empirical molecular dynamics calculations show that the phytyl chain is unfolded from the chlorin cycle in pheophytin a and folded in chlorophyll a. Density functional theory calculations have been conducted to locate the charges on protonated and deprotonated pheophytin a and chlorophyll a and have found the major location sites that are notably more stable in energy by more than 0.5 eV than the others. The deprotonation site is found identical for pheophytin a and the chlorophyll a-methanol adduct. This is in line with experiment and calculation locating the addition of methanol on a double bond of deprotonated chlorophyll a.

QM/MM study of l-lactate oxidation by flavocytochrome b2.

In this work, we have performed molecular dynamics simulations using a hybrid Quantum Mechanics/Molecular Mechanics (QM/MM) scheme to study the mechanism of l-lactate oxidation by flavocytochrome b2 (Fcb2). Our results obtained at the QM(AM1)/MM level have been improved by single-point corrections using density functional theory (DFT) methods. Free energy surfaces have been calculated in the framework of the hydride transfer hypothesis. This mechanism involves the transfer of the lactate hydroxyl proton to H373 while the substrate αH atom is transferred as a hydride to the flavin mononucleotide (FMN) prosthetic group anchored in the active site. Four different systems have been modeled: wild-type enzyme considering R289 in a distal or a proximal conformation observed in crystal structures and the D282N and Y254L variants (with R289 in a distal position). Simulation results highlight the influence of the environment on the catalytic mechanism by describing a step-wise process in the WT enzyme with R289 in a distal position and a concerted mechanism for the other systems. In the step-wise mechanism, the hydride transfer to flavin can occur only after a proton transfer from substrate to H373. Modifications of the electrostatic field around l-lactate or H373 disfavor the highly charged complex resulting from this proton transfer. Simulations of the Y254L variant also reveal some effect of steric changes.

Electron transfer within a reaction path model calibrated by constrained DFT calculations: application to mixed-valence organic compounds.

The quantum dynamics of electron transfer in mixed-valence organic compounds is investigated using a reaction path model calibrated by constrained density functional theory (cDFT). Constrained DFT is used to define diabatic states relevant for describing the electron transfer, to obtain equilibrium structures for each of these states and to estimate the electronic coupling between them. The harmonic analysis at the diabatic minima yields normal modes forming the dissipative bath coupled to the electronic states. In order to decrease the system-bath coupling, an effective one dimensional vibronic Hamiltonian is constructed by partitioning the modes into a linear reaction path which connects both equilibrium positions and a set of secondary vibrational modes, coupled to this reaction coordinate. Using this vibronic model Hamiltonian, dissipative quantum dynamics is carried out using Redfield theory, based on a spectral density which is determined from the cDFT results. In a first benchmark case, the model is applied to a series of mixed-valence organic compounds formed by two 1,4-dimethoxy-3-methylphenylene fragments linked by an increasing number of phenylene bridges. This allows us to examine the coherent electron transfer in extreme situations leading to a ground adiabatic state with or without a barrier and therefore to the trapping of the charge or to an easy delocalization.

Study of the docking of competitive inhibitors at a model of tyrosinase active site: insights from joint broken-symmetry/Spin-Flip DFT computations and ELF topological analysis.

Following our previous study (Piquemal et al., New J. Chem., 2003, 27, 909), we present here a DFT study of the inhibition of the Tyrosinase enzyme. Broken-symmetry DFT computations are supplemented with Spin-Flip TD-DFT calculations, which, for the first time, are applied to such a dicopper enzyme. The chosen biomimetic model encompasses a dioxygen molecule, two Cu(II) cations, and six imidazole rings. The docking energy of a natural substrate, namely phenolate, together with those of several inhibitor and non-inhibitor compounds, are reported and show the ability of the model to rank the most potent inhibitors in agreement with experimental data. With respect to broken-symmetry calculations, the Spin-Flip TD-DFT approach reinforces the possibility for theory to point out potent inhibitors: the need for the deprotonation of the substrates, natural or inhibitors, is now clearly established. Moreover, Electron Localization Function (ELF) topological analysis computations are used to deeply track the particular electronic distribution of the Cu-O-Cu three-center bonds involved in the enzymatic Cu(2)O(2) metallic core (Piquemal and Pilmé, J. Mol. Struct.: Theochem, 2006, 77, 764). It is shown that such bonds exhibit very resilient out-of-plane density expansions that play a key role in docking interactions: their 3D-orientation could be the topological electronic signature of oxygen activation within such systems.

[Endoscopic polypectomy in benign adenoma and in early colo-rectal lesions]. / La polipectomia endoscopica negli adenomi benigni e nelle lesioni "early" del colon-retto.

The Authors report their results in 219 patients who underwent endoscopic polypectomy for benign adenomatous polyps and early colorectal cancer. This is safe and curative technique associated with low-risk of complications and in an ideal therapy to prevent the development of colorectal cancer. In fact, nowadays, dysplasia-carcinoma sequence has been described. All polyps were histologically identified and the grade of dysplasia always detected.

[Endoscopic ligation in the prevention of hemorrhage after polypectomy: our experience]. / La legatura transendoscopica nella profilassi dell'emorragia dopo polipectomia: nostra esperienza.

The Authors report their experience with the use of the Olympus Endoloop HX-20L for the prevention of haemorrhages after endoscopic polypectomy. They emphasize the utility of this therapeutic device that will find its right application only in a well selected group of patients.

Abdominal Takayasu's aortitis, the middle aortic syndrome and atherosclerosis. A critical review.

To review the current status of clinical, pathological and arteriographic aspects of abdominal Takayasu's aortitis (TA). Personal experience with 86 patients with TA and review of the literature is the basis of this report. The diagnostic significance of primary versus secondary atherosclerosis is described in this communication and the arteriographic differential diagnostic guidelines are provided to separate abdominal TA from abdominal atherosclerosis.

Efficacy of triple therapy with PPI or H2 antagonist versus the elimination of helicobacter pylori

O Helicobacter pylori tem sido considerado importante fator nas doencas gastroduodenais e o esquema chamado triplice e o que mais se aceita no momento para a sua terapeutica. Neste estudo incluiram-se 14 pacientes portadores de gastrite cronica, 30 com ulcera gastrica e 16 com ulcera duodenal. Foram divididos em 2 grupos homogeneos para tratamento clinico, cada um com esquema bem definido: grupo A - claritromicina 250mg/2, tinidazol 250mg/2 e omeprazole 20mg em caso de gastrite e 40mg em caso de ulcera; grupo B - mesmos antibioticos e ranitidina respectivamente nas doses de 150 e 300mg. O periodo de tratamento foi de 7 dias para gastrites e 4 semanas para ulceras. Atraves de endoscopia e biopsia realizadas 30 dias depois do termino do tratamento, os 30 casos do grupo A tiveram erradicacao completa do Helicobacter pylori e cicatrizacao das ulceras. No grupo B, apenas 3 casos nao tiveram eliminacao do Helicobacter pylori. Concluiu-se que o uso de bloqueadores H2 no lugar de inibidores da bomba protonica tambem permite a obtencao de sucesso terapeutico

[Precise mucostatic primary impression taking in the edentulous mandible. Hemi-arch method]. / Prise d'empreinte primaire mucostatique précise chez l'édenté total mandibulaire. Méthode par hémi-arcade.

The author has shown that any impression material and its support in the mouth must be more malleable than the material used for the object to be reproduced. From a fall mandibular arch the impression of both sides, left and right, are taken successively by hemi-impressions without impression trays. Two individual half impression trays are made, placed in the mouth and are joined together using an auto-polymerizing resin. The resulting individual tray permits to make a perfect mucostatic impression. This method, far from taking more time, is a time saver, since the touch-ups to the individual tray and then to the finished prosthesis are practically non-existent or considerably reduced.

Accuracy of radiographic differentiation of bacterial from nonbacterial pneumonia.

The chest roentgenogram is an accepted tool for the diagnosis of pneumonia. Little information is available, however, addressing the ability of physicians to distinguish bacterial from nonbacterial pneumonias by examination of the chest roentgenogram. Five different observers evaluated 36 chest films from patients with pneumonia who had a laboratory proven etiologic diagnosis. The sensitivity of roentgenogram diagnosis of bacterial pneumonia ranged from 42-58 percent. When clinical and laboratory data were provided to the observers the sensitivity ranged from 42-92 percent. This study indicates that chest film examination is too insensitive to be useful for the selection of patients who have bacterial pneumonia from those whose pneumonia is non-bacterial.

Pneumonia in pediatric outpatients: cause and clinical manifestations.

The cause and clinical manifestations of pneumonia were studied in 98 pediatric outpatients. A viral diagnosis was established in 38 (39%) of the 98 patients, and a bacterial diagnosis in 19 (19%). Ten (53%) of the 19 patients with bacterial pneumonia had a concurrent viral infection. No clinical, laboratory, or radiographic findings that would reliably differentiate viral from bacterial infection were identified. This study suggests that bacterial pneumonia is more common in pediatric outpatients than previously reported, and that the clinical, laboratory, and radiographic findings in patients with bacterial infection may be indistinguishable from findings in patients with viral infection.

Epiglottitis in the adolescent.

Acute epiglottitis is rare in adolescents. Respiratory compromise may not occur early. Physicians should consider this diagnosis in their adolescent patients who complain of pain and dysphagia, with or without visible pharyngitis. Airway maintenance is paramount. The antibiotic used should include coverage for Hemophilus influenzae, type B. The case presented here illustrates these points.