Pharmacokinetics and pharmacodynamics of the glucagon-like peptide-1 analog liraglutide in healthy cats

Glucagon-like peptide-1 (GLP-1) is an intestinal hormone that induces glucose-dependent stimulation of insulin secretion while suppressing glucagon secretion. Glucagon-like peptide-1 also increases beta cell mass and satiation while decelerating gastric emptying. Liraglutide is a fatty-acid derivative of GLP-1 with a protracted pharmacokinetic profile that is used in people for treatment of type II diabetes mellitus and obesity. The aim of this study was to determine the pharmacokinetics and pharmacodynamics of liraglutide in healthy cats. Hyperglycemic clamps were performed on days 0 (HGC) and 14 (LgHGC) in 7 healthy cats. Liraglutide was administered subcutaneously (0.6 mg/cat) once daily on days 8 through 14. Compared with the HGC (mean +/- standard deviation; 455.5 +/- 115.8 ng/L), insulin concentrations during LgHGC were increased (760.8 +/- 350.7 ng/L; P = 0.0022), glucagon concentrations decreased (0.66 +/- 0.4 pmol/L during HGC vs 0.5 +/- 0.4 pmol/L during LgHGC; P = 0.0089), and there was a trend toward an increased total glucose infused (median [range] = 1.61 (1.11-2.54) g/kg and 2.25 (1.64-3.10) g/kg, respectively; P = 0.087). Appetite reduction and decreased body weight (9% +/- 3%; P = 0.006) were observed in all cats. Liraglutide has similar effects and pharmacokinetics profile in cats to those reported in people. With a half-life of approximately 12 h, once daily dosing might be feasible; however, significant effects on appetite and weight loss may necessitate dosage or dosing frequency reductions. Further investigation of liraglutide in diabetic cats and overweight cats is warranted. (C) 2015 Elsevier Inc. All rights reserved.

Pharmacology of the glucagon-like peptide-1 analog exenatide extended-release in healthy cats

Exenatide extended-release (ER) is a microencapsulated formulation of the glucagon-like peptide 1-receptor agonist exenatide: It has a protracted pharmacokinetic profile that allows a once-weekly injection with comparable efficacy to insulin with an improved safety profile in type II diabetic people. Here, we studied the pharmacology of exenatide ER in 6 healthy cats. A single subcutaneous injection of exenatide ER (0.13 mg/kg) was administered on day 0. Exenatide concentrations were measured for 12 wk. A hyperglycemic clamp (target = 225 mg/dL) was performed on days 7 (clamp I) and 21 (clamp II) with measurements of insulin and glucagon concentrations. Glucose tolerance was defined as the amount of glucose required to maintain hyperglycemia during the clamp. Continuous glucose monitoring was performed on weeks 0, 2, and 6 after injection. Plasma concentrations of exenatide peaked at 1 h and 4 wk after injection. Comparing clamp I with clamp II, fasting blood glucose decreased (mean standard deviation = 11 8 mg/dL, P = 0.02), glucose tolerance improved (median [range] +33% 14%-138%], P = 0.04), insulin concentrations increased (+36.5% [-9.9% to 274.1%], P = 0.02), and glucagon concentrations decreased (-4.7% [0%-12.1%], P = 0.005). Compared with preinjection values on continuous glucose monitoring, glucose concentrations decreased and the frequency of readings <50 mg/dL increased at 2 and 6 wk after injection of exenatide ER. This did not correspond to clinical hypoglycemia. No other side effects were observed throughout the study. Exenatide ER was safe and effective in improving glucose tolerance 3 wk after a single injection. Further evaluation is needed to determine its safety, efficacy, and duration of action in diabetic cats. (C) 2015 Elsevier Inc. All rights reserved.

Reaction of pentacarbonyliron with a nitrogen heterocycle. X-ray crystal structure of bis[(carbonyl)(quinoline-2-thiolate-N,S)]iron(II)

The monomeric compound bis[(carbonyl)(quinoline-2-thiolate-N,S)]iron(II) was synthesized and studied by IR and Mossbauer spectroscopy, cyclic voltammetry and X-ray diffraction. The molecule has two terminal carbonyl groups and two quinoline-2-thiolate anions coordinated as N,S-donor chelates, and the iron atom shows an octahedral coordination geometry.

An analog implementation of radial basis function network appropriate for transducer linearizer

A circuit for transducer linearizer tasks have been designed and built using discrete components and it implements by: a Radial Basis Function Network (RBFN) with three basis functions. The application in a linearized thermistor showed that the network has good approximation capabilities. The circuit advantages is the amplitude, width and center.

Effect of some surfactants on the chemiluminescent reactions of bis(2,4,6-trichlorophenyl)oxalate and bis(2-nitrophenyl)oxalate with hydrogen peroxide

The chemiluminescent reactions of bis(2,4,6-trichlorophenyl)oxalate (TCPO) and bis(2-nitrophenyl)oxalate (2-NPO) with hydrogen peroxide in acetonitrile/water micellar systems (anionic, cationic, and non-ionic) and gamma-cyclodextrin were studied in the presence of fluoranthene or 9,10-diphenylanthracene, imidazole, and two buffer solutions, HTRIS+/TRIS and H2PO4-/HPO42-. The relative chemiluminenscence (CL) intensity is higher in the presence of the cationic (DDAB, CTAC, DODAC, and OTAC), anionic (SDS), and non-ionic (Tween 80) surfactants. In the presence of some non-ionic surfactants (Brij 35, Brij 76, and Tween 20), the CL intensity was partially quenched compared with the reaction with no surfactant. The sensitivity for hydrogen peroxide determination in the range 0.01 x 10(-4) to 1.0 x 10(-4) mol L-1, considering the slope of the calibration curves (maximum peak height of CL vs. concentration), improved with the introduction of DDAH, CTAB, and SDS in HTRIS+/TRIS buffer.

Unraveling the Mysterious Role of Palladium in Feigl bis(dimethylglyoximate)nickel(II) Spot Tests by Means of Confocal Raman Microscopy

The add protection effect promoted by traces of PdCl2 in [Ni(dmgH)(2)] spot tests was elucidated from confocal Raman microscopy imaging, which revealed the formation of protecting layers of [Pd(dmgH)(2)] closing the extremities of the [Ni(dmgH)(2)] filaments.

Analog of the susceptibility spectrum for levitation forces between a superconductor and a permanent magnet

We report on the measurements of both vertical and lateral levitation forces between a permanent magnet NdFeB and a polycrystalline YBa4Cu6O7-delta superconductor. The analysis of the obtained results revealed an interesting correlation between the behavior of the forces in the field-cooled and zero-field-cooled regimes, resembling the structure of the so-called susceptibility spectrum chi ''(chi'). Such force-force diagrams can be useful for identifying flux distribution structure inside a superconducting material. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.4743006]

Spectroscopic characterization and crystal structure of cis-Bis(N-(2-benzoyl)-N ',N '-diphenylthioureato-k O-2,S)nickel(II)

The title compound [Ni(C20H15N2OS)(2)] is prepared by the reaction of metal acetate with the corresponding acylthiourea derivative. The complex is characterized by elemental analysis, IR, H-1 and C-13 NMR, and its structure is determined by single crystal X-ray diffraction. The Ni(II) ion is coordinated by the S and O atoms of two N-benzoyl-N',N'-diphenylthiourea ligands in a slightly distorted square-planar coordination geometry. The two O and two S atoms are mutually cis to each other. The substance crystallizes triclinic (P-1 space group) with cell dimensions a = 10.7262(9) , b = 12.938(3) , c = 14.2085(12) , alpha = 74.650(4)A degrees, beta = 78.398(4)A degrees, gamma = 68.200(5)A degrees, and two formula units in the unit cell. The structure is very close to the related N-(2-furoyl) Ni complex reported previously.

Synthesis, Characterization and Biological Activities of a Bidentate Schiff Base Ligand: N,N '-Bis(1-phenylethylidene)ethane-1,2-diamine and its Transition Metals (II) Complexes

Schiff base ligand: N,N'-bis(1-phenylethylidene)ethane-1,2-diamine (L), was derived from acetophenone and ethylenediamine by condensation and its complexes (1-5) were prepared with Pb2+, Ni2+, Co2+, Cu2+ and Cd2+ metal ions. Their structures were characterized by FAB-MS, IR spectra, elemental analyses and molar conductance. The octahedral geometry of the complexes was proposed by electronic spectra and magnetic moment data. The conductivity data showed that the complexes have non-electrolytic nature. The complexes (1-5) have higher in vitro antimicrobial activity than the Schiff base ligand (L). In the nuclease activity, the complexes cleave DNA as compared to control DNA in the presence of H2O2.

Thermal Analysis and Raman Spectra of Different Phases of the Ionic Liquid Butyltrimethylammonium Bis(trifluoromethylsulfonyl)imide

The ionic liquid butyltrimethylammonium bis(trifluoromethylsulfonyl)imide, [C4C1C1C1N][Tf2N], is a glass-forming liquid that exhibits partial crystallization depending on the cooling rate. Differential scanning calorimetry (DSC) indicates crystallization at T-c = 227 K, melting at T-m = 258 K, glass transition at T-g similar to 191 K, and also cold crystallization at T-cc similar to 219 K. Raman spectroscopy shows that the crystalline structure obtained by slow cooling is formed with [Tf2N](-) in cisoid conformation, whereas [Tf2N](-) in transoid conformation results from fast cooling. No preferred conformation of the butyl chain of the [C4C1C1C1N](+) cation is favored by slow or fast cooling of [C4C1C1C1N][Tf2N]. Low-frequency Raman spectroscopy shows that crystalline domains developing in the supercooled liquid result in a glacial state made of a mixture of crystallites and amorphous phase. However, these crystalline structures obtained by slow cooling or cold crystallization are not the same because anion-cation interactions promote local structures with distinct conformations of the [Tf2N](-) anion.

Biorremediação de solo contaminado por isobutanol, Bis-2-etil-hexilftalato e Di-isodecilftalato

Embora os ftalatos sejam um dos poluentes mais frequentemente encontrados no meio ambiente, há escassez de dados na literatura sobre biorremediação de solos tropicais contaminados por esses compostos. Por esse motivo, este estudo avaliou a biorremediação de um solo contaminado com os plastificantes DEHP (Bis-2-etilhexilftalato), DIDP (Di-isodecilftalato) e álcool isobutílico, por uma indústria no Estado de São Paulo. A biorremediação ocorreu pela utilização de microrganismos presentes no solo e pela adição de inóculo adaptado em reator em fase de lama. O reator foi monitorado durante 120 dias, sendo corrigida apenas a umidade do solo. Os resultados indicaram que a biodegradação dos ftalatos seguiu uma cinética de primeira ordem e a biorremediação ocorreu na faixa de pH entre 7,4 e 8,4 e temperaturas entre 17 e 25 ºC, com eficiência de remoção de contaminantes acima de 70 %. Após 120 dias, o teor de DEHP estava abaixo de 4 mg kg-1, limite estipulado pela legislação brasileira para solo de uso residencial.

Magnetic Ionic Liquids Produced by the Dispersion of Magnetic Nanoparticles in 1-n-Butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf2)

This paper reports on the advancement of magnetic ionic liquids (MILs) as stable dispersions of surface-modified gamma-Fe2O3, Fe3O4, and CoFe2O4 magnetic nanoparticles (MNPs) in a hydrophobic ionic liquid, 1-n-butyl 3-methylimidazolium bis(trifluoromethanesulfonyl)imide (BMI.NTf2). The MNPs were obtained via coprecipitation and were characterized using powder X-ray diffraction, transmission electron microscopy, Raman spectroscopy and Fourier transform near-infrared (FT-NIR) spectroscopy, and magnetic measurements. The surface-modified MNPs (SM-MNPs) were obtained via the silanization of the MNPs with the aid of 1-butyl-3[3-(trimethoxysilyl)propyl]imidazolium chloride (BMSPI.Cl). The SM-MNPs were characterized by Raman spectroscopy and Fourier trail: form infrared attenuated total reflectance (FTIR-ATR) spectroscopy and by magnetic measurements. The FTIR-ATR spectra of the SM-MNPs exhibited characteristic absorptions of the imidazolium and those of the Fe-O-Si-C moieties, confirming the presence of BMSPI.Cl on the MNP surface. Thermogravimetric analysis (TGA) showed that the SM-MNPs were modified by at least one BMSPI.Cl monolayer. The MILs were characterized using Raman spectroscopy, differential scanning calorimetry (DSC), and magnetic measurements. The Raman and DSC results indicated an interaction between the SM-MNPs and the IL. This interaction promotes the formation of a supramolecular structure close to the MNP surface that mimics the IL structure and is responsible for the stability of the MIL. Magnetic measurements of the MILs indicated no hysteresis. Superparamagnetic behavior and a saturation magnetization of similar to 22 emu/g could be inferred from the magnetic measurements of a sample containing 50% w/w gamma-Fe2O3 SM-MNP/BMI-NTf2.

Analysis of temperature variation influence on the analog performance of 45 degrees rotated triple-gate nMuGFETs

This work presents the analog performance of n-type triple-gate MuGFETs with high-k dielectrics and TiN gate material fabricated in 45 degrees rotated SOI substrates comparing their performance with standard MuGFETs fabricated without substrate rotation. Different fin widths are studied for temperatures ranging from 250 K up to 400 K. The results of transconductance, output conductance, transconductance over drain current ratio, intrinsic voltage gain and unit-gain frequency are studied. It is observed that the substrate rotation improves the carrier mobility of narrow MuGFETs at any temperature because of the changing in the conduction plane at the sidewalls from (1 1 0) to (1 0 0). For lower temperatures, the improvement of the carrier mobility of rotated MuGFETs is more noticeable as well as the rate of mobility improvement with the temperature decrease is larger. The output conductance is weakly affected by the substrate rotation. Although this improvement in the transconductance of rotated MuGFETs is negligibly transferred to the intrinsic voltage gain, the unity-gain frequency of rotated device is improved due to the larger carrier mobility in the entire range of temperatures studied. (C) 2011 Elsevier Ltd. All rights reserved.

Analog circuit synthesis performing fast Pareto frontier exploration and analysis through 3D graphs

This paper presents a technique for performing analog design synthesis at circuit level providing feedback to the designer through the exploration of the Pareto frontier. A modified simulated annealing which is able to perform crossover with past anchor points when a local minimum is found which is used as the optimization algorithm on the initial synthesis procedure. After all specifications are met, the algorithm searches for the extreme points of the Pareto frontier in order to obtain a non-exhaustive exploration of the Pareto front. Finally, multi-objective particle swarm optimization is used to spread the results and to find a more accurate frontier. Piecewise linear functions are used as single-objective cost functions to produce a smooth and equal convergence of all measurements to the desired specifications during the composition of the aggregate objective function. To verify the presented technique two circuits were designed, which are: a Miller amplifier with 96 dB Voltage gain, 15.48 MHz unity gain frequency, slew rate of 19.2 V/mu s with a current supply of 385.15 mu A, and a complementary folded cascode with 104.25 dB Voltage gain, 18.15 MHz of unity gain frequency and a slew rate of 13.370 MV/mu s. These circuits were synthesized using a 0.35 mu m technology. The results show that the method provides a fast approach for good solutions using the modified SA and further good Pareto front exploration through its connection to the particle swarm optimization algorithm.

Self-potential signals from an analog biogeobattery mode

A tank experiment was conducted to check if self-potential (SP) signals can be generated when buried organic matter is wire-connected to a near-surface, oxygen-rich, sediment layer. This experiment demonstrated that once wired, there was a flux of electrons (hence an electric current) between the lower and upper layers of the sandbox with the system responding as a large-scale microbial fuel cell (a type of bioelectrochemical system). An electric current was generated by this process in the wire and the SP method was used to monitor the associated electric potential distribution at the top of the tank.. The electric field was controlled by the flux of electrons through the wire, the oxidation of the organic matter, the reduction of oxygen used as a terminal electron acceptor, and the distribution of the DC resistivity in the tank. The current density through the wire was limited by the availability of oxygen and not by the oxidation of the organic matter. This laboratory experiment incorporated key elements of the biogeobattery observed in some organic-rich contaminant plumes. This analogy includes the generation of SP signals associated with a flux of electrons, the capacity of buried organic matter in sustaining anodic reactions, network resistance connecting terminal redox reactions spatially separated in space, and the existence of anodic secondary coupled reactions. A resistivity tomogram of the tank, after almost a year in operation, suggests that oxidative processes triggered by this geobattery can be imaged with this method to determine the radius of influence of the bioelectrochemical system.