Reações de Cp'(CO)2MnPPH2H com CH3COCl e CH3S(O)2Cl em THF/trietilamina: evidências da primeira estabilização por complexação de um fósforo-homólogo das sulfonamidas

Cp'Mn(CO)3 (Cp'=h5-C5H4-CH 3) reacts with P(C6H5)2H in THF to give Cp'(CO)2MnPPh2H (Ph = Phenyl) (1), by substitution of one CO ligand. The reaction of 1 with CH3COCl and CH3S(O)2Cl in the presence of triethylamine occurs under electrophilic substitution on the diphenylphosphan ligand to yield the acetyl- and sulfonylphosphane complexes of manganese(I) Cp'(CO)2MnPPh2COCH3 (2) and Cp'(CO)2MnPPh2S(O)2 CH3 (3). The complex stabilisation of these molecules, wich are hitherto unknown in the free state, is only accomplished by blocking the free electron pair on phosphorus by coordination. The new complexes 1, 2 and 3 were analysed by IR, ¹H-NMR and 31P-MNR spectroscopy and their similar structures are discusssed.

Desenvolvimento de um detector piezelétrico para cromatógrafo a gás interfaceado a microcomputador

A piezoelectric detector based on a commercial quartz crystal of 3.57MHz is shown. A PTFE cell attached to the GC-column outlet holds the polymer-coated crystal, whose terminals were removed. Two TTL oscillators (reference and sensor) are used and the beating of their frequencies is monitored through a home-made counter card inserted in a microcomputer. The original thermal conductivity detector was also interfaced, but through a 12-bit analog-to-digital converter. In spite of the well-known fact that QCM has low sensitivity at high temperatures, results show significant peak deformation for low temperatures. In addition, the phenomenon is also dependent on the chemical composition of the absorbent film besides instantaneous partial pressure and chemical composition of the analyte.

Role of Membrane Transporters, P-Glycoprotein and Mrp1, in The Placental Transfer of Drugs With Special Reference to Saquinavir and Quetiapine

Drug transporting membrane proteins are expressed in various human tissues and blood-tissue barriers, regulating the transfer of drugs, toxins and endogenous compounds into or out of the cells. Various in vitro and animal experiments suggest that P-glycoprotein (P-gp) forms a functional barrier between maternal and fetal blood circulation in the placenta thereby protecting the fetus from exposure to xenobiotics during pregnancy. The multidrug resistance-associated protein 1 (MRP1) is a relatively less studied transporter protein in the human placenta. The aim of this study series was to study the role of placental transporters, apical P-gp and basal MRP1, using saquinavir as a probe drug, and to study transfer of quetiapine and the role of P-gp in its transfer in the dually perfused human placenta/cotyledon. Furthermore, two ABCB1 (encoding P-gp) polymorphisms (c.3435C>T, p.Ile1145Ile and c.2677G>T/A, p.Ala893Ser/Thr) were studied to determine their impact on P-gp protein expression level and on the transfer of the study drugs. Also, the influence of the P-gp protein expression level on the transfer of the study drugs was addressed. Because P-gp and MRP1 are ATP-dependent drug-efflux pumps, it was studied whether exogenous ATP is needed for the function of ATP-dependent transporter in the present experimental model. The present results indicated that the addition of exogenous ATP was not necessary for transporter function in the perfused human placental cotyledon. Saquinavir and quetiapine were both found to cross the human placenta; transplacental transfer (TPTAUC %) for saquinavir was <0.5% and for quetiapine 3.7%. Pharmacologic blocking of P-gp led to disruption of the blood-placental barrier (BPB) and increased the placental transfer of P-gp substrate, saquinavir, into the fetal circulation by 6- to 8-fold. In reversed perfusions P-gp, MRP1 and possibly OATP2B1 had a negligible role in the fetal-to-maternal transfer of saquinavir. The TPTAUC % of saquinavir was about 100-fold greater from the fetal side to the maternal side compared with the maternal-to-fetal transfer. P-gp activity is not likely to modify the placental transfer of quetiapine. Higher P-gp protein expression levels were associated with the variant allele 3435T, but no correlation was found between the TPTAUC % of saquinavir and placental P-gp protein expression. The present results indicate that P-gp activity drastically affects the fetal exposure to saquinavir, and suggest that pharmacological blockade of the P-gp activity during pregnancy may pose an increased risk for adverse fetal outcome. The blockade of P-gp activity could be used in purpose to obtain higher drug concentration to the fetal side, for example, in prevention (to decrease virus transfer to fetal side) or in treating sick fetus.

VAP-1 in Leukocyte Trafficking

The extravasation of leukocytes from the blood stream into the tissues is a prerequisite for adequate immune surveillance and immune reaction. The leukocyte movement from the bloodstream into the tissues is mediated by molecular bonds. The bonds are formed between adhesion molecules on endothelial cells and their counterparts expressed on leukocytes. Vascular adhesion protein-1 (VAP-1) is an endothelial adhesion molecule mediating leukocyte interactions with endothelium. It is also an enzyme having semicarbazide sensitive amine oxidase (SSAO) activity. The SSAOactivity catalyses deamination of primary amines into corresponding aldehyde and during the enzymatic reaction hydrogen peroxide and ammonia are produced. The aim of this study was to investigate the relationship between the adhesive and enzymatic activities of VAP-1. The role of VAP-1 in leukocyte traffic was studied in vivo under normal and pathological conditions in VAP-1 deficient mice. The results from in vitro flow-based assays indicated that VAP-1 uses both SSAOactivity and its adhesive epitope to bind leukocytes, and both are perquisites for VAP-1 mediated adhesion. Furthermore, in vivo results demonstrated that leukocyte trafficking was impaired in vivo by deleting VAP-1 or inhibiting SSAO-activity. There was impairment in lymphocyte recirculation as well as leukocyte accumulation into the inflamed area. Moreover, the VAP-1 deficient mice did not show generalized defects in antimicrobial responses, whereas significant reduction in tumor progression and neovascularization was observed. These results indicate that VAP-1 could be used as a target in anti-adhesive therapies either by blocking its adhesive epitope with antibodies or by inhibiting its SSAO-activity using inhibitors. Moreover, targeting of VAP-1 may provide a new way of inhibiting neovascularization in tumors.

Aplicação de técnicas eletroquímicas no estudo da dissolução oxidativa da covelita (CuS) por Thiobacillus ferrooxidans

Among the copper sulphides, chalcopyrite (CuFeS2), covellite (CuS) and chalcocite (Cu2S) are the most important source of minerals for copper mining industry. The acknowledge of behaviour of these sulphides related with bacterial leaching process are essential for optimization procedures. Despite of its importance, covellite has not deserved much interest of researchers regarding this matter. In this work it was studied the oxidation of covellite by the chemolithotrophic bacterium Thiobacillus ferrooxidans by using electrochemical techniques, such as open circuit potentials with the time and cyclic voltammetry. The experiments were carried out in acid medium (pH 1.8), containing or not Fe2+ as additional energy source, and in different periods of incubation; chemical controls were run in parallel. The results showed that a sulphur layer is formed spontaneously due the acid attack, covering the sulphide in the initial phase of incubation, blocking the sulphide oxidation. However, the bacterium was capable to oxidize this sulphur layer. In the presence of Fe2+ as supplemental energy source, the corrosion process was facilitated, because ocurred an indirect oxidation of covellite by Fe3+, which was produced by T. ferrooxidans oxidation of the Fe2+ added in the medium.

Agentes antiasmáticos modernos: antagonistas de receptores de leucotrienos cisteínicos

In the early 1990s numerous clinical trials with antileukotriene drugs confirmed the hypothesis that cysteinyl leukotrienes are important bronchoconstrictor agents in asthma. Newly released"antiasthmatic medications include antileukotriene agents which function either by blocking the interaction of leukotrienes with receptors or by inhibiting leukotriene synthesis. Representatives of cysteinyl leukotriene receptors antagonists are zafirlukast (7), montelukast (8) and pranlukast (9). The bronchodilator efficacy and antiinflammatory property of antileukotriene drugs provided the main impetus behind their introduction as the first novel class of asthma therapy in more than 20 years.

Um modelo para a superfície líquida no estudo da dinâmica do espalhamento de Xe e Ne pelo esqualano

In this work we present a theoretical model to investigate the scattering of Xe and Ne by a liquid squalane surface. The liquid surface is modeled as a grid of harmonic oscillators with frequencies adjusted to experimental vibration as frequencies of the liquid squalane and the atom-surface interaction potential is modeled by a Lennard-Jones function. The three dimensional description of the dynamics of the process which occurs at the gas-liquid interface is obtained by the classical trajectory method. The general characteristics of the dynamics of the scattering process are in good agreement with experimental data.

Síntese e caracterização de nanocompósitos Ni: SiO2 processados na forma de filmes finos

We have produced nanocomposite films of Ni:SiO2 by an alternative polymeric precursor route. Films, with thickness of ~ 1000 nm, were characterized by several techniques including X-ray diffraction, scanning electron microscopy, atomic force microscopy, flame absorption atomic spectrometry, and dc magnetization. Results from the microstructural characterizations indicated that metallic Ni-nanoparticles with average diameter of ~ 3 nm are homogeneously distributed in an amorphous SiO2 matrix. Magnetization measurements revealed a blocking temperature T B ~ 7 K for the most diluted sample and the absence of an exchange bias suggesting that Ni nanoparticles are free from an oxide layer.

Morphological and Magnetic Properties of Superparamagnetic Carbon-Coated Fe Nanoparticles Produced by Arc Discharge.

Spherical carbon coated iron particles of nanometric diameter in the 5-10 nm range have been produced by arc discharge at near-atmospheric pressure conditions (using 5-8·10 4 Pa of He). The particles exhibit a crystalline dense iron core with an average diameter 7.4 ± 2.0 nm surrounded by a sealed carbon shell, shown by transmission electron microscopy (TEM), selected-area diffrac- tion (SAED), energy-dispersive X-ray analysis (STEM-EDX) and electron energy loss spectroscopy (EELS). The SAED, EDX and EELS results indicate a lack of traces of core oxidized phases showing an efficient protection role of the carbon shell. The magnetic properties of the nanoparticles have been investigated in the 5-300 K temperature range using a superconducting quantum interference device (SQUID). The results reveal a superparamagnetic behaviour with an average monodomain diameter of 7.6 nm of the nanoparticles. The zero field cooled and field cooled (ZFC-FC)magnetization curves show a blocking temperature (TB)at room temperature very suitable for biomedical applications (drug delivery, magnetic resonance imaging-MRI-, hyperthermia).

Feedback-related Brain Potential Activity Complies with Basic Assumptions of Associative Learning Theory

Feedback-related negativity (FRN) is an ERP component that distinguishes positive from negative feedback. FRN has been hypothesized to be the product of an error signal that may be used to adjust future behavior. In addition, associative learning models assume that the trial-to-trial learning of cueoutcome mappings involves the minimization of an error term. This study evaluated whether FRN is a possible electrophysiological correlate of this error term in a predictive learning task where human subjects were asked to learn different cueoutcome relationships. Specifically, we evaluated the sensitivity of the FRN to the course of learning when different stimuli interact or compete to become a predictor of certain outcomes. Importantly, some of these cues were blocked by more informative or predictive cues (i.e., the blocking effect). Interestingly, the present results show that both learning and blocking affect the amplitude of the FRN component. Furthermore, independent analyses of positive and negative feedback event-related signals showed that the learning effect was restricted to the ERP component elicited by positive feedback. The blocking test showed differences in the FRN magnitude between a predictive and a blocked cue. Overall, the present results show that ERPs that are related to feedback processing correspond to the main predictions of associative learning models. ■

On the structure of cooperative and competitive solutions for a generalized assignment game

We study cooperative and competitive solutions for a many- to-many generalization of Shapley and Shubik (1972)'s assignment game. We consider the Core, three other notions of group stability and two al- ternative definitions of competitive equilibrium. We show that (i) each group stable set is closely related with the Core of certain games defined using a proper notion of blocking and (ii) each group stable set contains the set of payoff vectors associated to the two definitions of competitive equilibrium. We also show that all six solutions maintain a strictly nested structure. Moreover, each solution can be identified with a set of ma- trices of (discriminated) prices which indicate how gains from trade are distributed among buyers and sellers. In all cases such matrices arise as solutions of a system of linear inequalities. Hence, all six solutions have the same properties from a structural and computational point of view.

Dinâmica complexa no sistema bromato/hipofosfito/acetona/manganês e ferroína

New chemical systems have been recently designed for the study of complex phenomena such as oscillatory dynamics in the temporal domain and spatiotemporal pattern formation. Systems derived from oscillators based on the chemistry of bromate are the most extensively studied, with the celebrated Belousov-Zhabotinsky (BZ) reaction being the most popular example. Problems such as the formation of bubbles (CO2) and solid precipitate in the course of the reaction and the occurrence of simply short-lived oscillations under batch conditions are very common and, in some cases, compromise the use of some of these systems. It is investigated in this paper the dynamic behavior of the bromate/hypophosphite/acetone/dual catalyst system, which has been sugested as an interesting alternative to circumvent those inconvenients. In this work, manganese and ferroin are employed as catalysts and the complete system (BrO3-/H2PO2-/acetone/Mn(II)-ferroin) is studied under batch conditions. Temporal symmetry breaking was studied in a reactor under agitation by means of simultaneous records of the potential changes of platinum and Ag/AgBr electrodes, both measured versus a reversible hydrogen electrode. Additionally, spatio-temporal formation of target patterns and spiral waves were obtained when the oscillating mixture was placed in a quasi two-dimensional reactor.

Targeting striatal metabotropic glutamate receptor type 5 in Parkinson's disease: bridging molecular studies and clinical trials

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed primarily on neurons and glial cells modulating the effects of glutamatergic neurotransmission. The pharmacological manipulation of these receptors has been postulated to be valuable in the management of some neurological disorders. Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for Parkinson's disease (PD) has been proposed, especially to manage the adverse symptoms associated to chronic treatment with classical PD drugs. Thus, the specific pharmacological blocking of mGlu5 receptors constitutes one of the most attractive non-dopaminergic-based strategies for PD management in general and for the L-DOPA-induced diskynesia (LID) in particular. Overall, we provide here an update of the current state of the art of these mGlu5 receptor-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Orthotopic PC-3 Tumor Xenografts in Studies on Prostate Cancer Growth and Metastasis

Prostate cancer is generally a slowly developing disease. However, some cancers develop into an aggressive, metastasic and consequently life-threatening state. The mechanisms of prostate cancer spread are still mainly unidentified but hormones and growth factors are known to been involved. The forming of new blood vessels i.e. angiogenesis is crucial for tumor growth. Blood vessels and lymphatic vessels are also prominent routes for metastasis. Both angiogenic and lymphangiogenic factors are overexpressed in prostate cancer. We established an in vivo model to study the factors effecting human prostate cancer growth and metastasis. Tumors were produced by the orthotopic inoculation of PC-3 prostate cancer cells into the prostates of immunodeficient mice. Like human prostate tumors, these tumors metastasized to prostate-draining lymph nodes. Treatment of the mice with the bisphosphonate alendronate known to decrease prostate cancer cell invasion in vitro inhibited metastasis and decreased tumor growth. Decreased tumor growth was associated with decreased angiogenesis and increased apoptosis of tumor cells. To elucidate the role of angiogenesis in prostate cancer progression, we studied the growth of orthotopic PC-3 tumors overexpressing fibroblast growth factor b (FGF8b) known to be expressed in human prostate cancer. FGF8b increased tumor growth and angiogenesis, which were both associated with a characteristic gene expression pattern. To study the role of lymphangiogenesis, we produced orthotopic PC-3 tumors overexpressing vascular endothelial growth factor C (VEGF-C). Blocking of VEGF-C receptor (VEGFR3) completely inhibited lymph node metastasis whereas overexpression of VEGF-C increased tumor growth and angiogenesis. VEGF-C also increased lung metastases but, surprisingly, decreased spread to lymph nodes. This suggests that the expanded vascular network was primarily used as a route for tumor spreading. Finally, the functionality of the capillary network in subcutaneous FGF8b-overexpressing PC-3 tumors was compared to that of tumors overexpressing VEGF. Both tumors showed angiogenic morphology and grew faster than control tumors. However, FGF8b tumors were hypoxic and their perfusion and oxygenation was poor compared with VEGF tumors. This suggests that the growth advantage of FGF8b tumors is more likely due to stimulated proliferation than effective angiogenesis. In conclusion, these results show that orthotopic prostate tumors provide a useful model to explore the mechanisms of prostate cancer growth and metastasis.

Integração numérica de leis de velocidade diferenciais com o uso do SCILAB

In this work, we applied the free open source SCILAB software for the numerical integration of differential rate law equations to obtain the concentration profiles of chemical species involved in the kinetics of some complex reactions. An automated method was applied to construct the system of ordinary differential equations (ODE) from the postulated chemical models. The solutions of the ODEs were obtained numerically by standard SCILAB functions. We successfully simulated even complex chemical systems such as pH oscillators. This communication opens up the possibility of using SCILAB in simulations and modeling by our chemistry undergraduate students.