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Effect of growth hormone or chromium picolinate on swine metabolism and inflammatory cytokine production after endotoxin challenge exposure.

OBJECTIVE: To determine whether recombinant porcine somatotropin (PST) or chromium picolinate (CrP) affected cytokine production and metabolism in swine after endotoxin challenge exposure. ANIMALS: 20 Poland China X Landrace pigs, 5/group. PROCEDURE: Pigs were given CrP-supplemented feed at body weight of 20 kg; PST treatment began at 60 kg, and both treatments continued through body weight of 90 kg. At 90 kg, pigs were challenge exposed with 20 micrograms of lipopolysaccharide (LPS)/kg of body weight. Blood samples were obtained at various times through 24 hours after LPS challenge exposure. RESULTS: In all pigs not given PST, glucose concentration decreased 2 to 4 hours after LPS. In PST-treated pigs, blood glucose concentration was decreased at 6 to 8 hours after LPS. Plasma insulin concentration paralleled changes in glucose concentration. Nonesterified fatty acid concentration was high 2 to 24 hours after LPS in pigs not given PST and at 6 to 24 h in PST-treated pigs. Plasma urea nitrogen concentration was high at 6 to 24 hours after LPS in pigs not given PST. The urea nitrogen values in PST-treated pigs were lower at all times. Serum aspartate transaminase activity was high 6 to 24 hours after LPS in pigs not given PST, whereas PST treatment prevented the increase in this enzyme activity. In untreated (PST) pigs, plasma bilirubin (total and direct) concentrations were high 4 to 8 hours after LPS and returned to normal at 24 hours. The PST- and CrP-treated pigs maintained normal plasma bilirubin concentrations. Interleukin 6 activity was unaffected by CrP and PST treatments. Treatment with CrP and PST decreased the tumor necrosis factor alpha response to LPS, compared with that in control pigs. CONCLUSIONS: PST, and to a lesser extent CrP, provide protection against the adverse metabolic effects of LPS-induced septic shock.

Analysis of Variance↗

Suspected chromium picolinate-induced rhabdomyolysis.

Rhabdomyolysis results from skeletal muscle injury and release of muscle cell contents into plasma. A number of etiologic factors have been reported for the condition, including strenuous exercise, weight lifting, trauma, seizure, sepsis, and alcohol and drug abuse. Hundreds of drugs also reportedly cause rhabdomyolysis. A 24-year-old body builder developed the disease after ingesting 1200 microg of chromium picolinate (6-24 times the daily recommended allowance of 50-200 microg) over 48 hours. We believe this to be the first reported case of chromium-induced rhabdomyolysis.

Adult↗

Investigation of Coordinational Properties of Europium(III) Complexes with Picolinic Acid Using Eu(III) Excitation Spectroscopy.

The 7F0 --> 5D0 excitation spectra of Eu(III) complexed with picolinic acid were investigated using Eu(III) excitation spectroscopy. Six overlapping peaks are seen in the excitation spectra, indicating the formation of six species. The structures of the six species are proposed here and described in terms of both coordination by carboxylate and N-chelation. Copyright 1999 Academic Press.

Journal Article↗

Metallomicellar Catalysis Hydrolysis of p-Nitrophenyl Picolinate Catalyzed by Copper(II), Nickel(II), and Zinc(II) Complexes of Long Alkyl Pyridine Ligands in Micellar Solution.

The ternary complex kinetic model for metallomicellar catalysis has been proposed in this paper. The catalytic effects of bivalent metal ion (Cu(2+), Zn(2+), and Ni(2+)) complexes of long alkyl pyridine ligands upon the hydrolysis of p-nitrophenyl picolinate (PNPP) have been studied kinetically in aqueous buffer of pH ranging from 5.0 to 8.5 at 30 degrees C. The effect of pH on the reactivity is discussed. The results indicate that the metallomicelles formed by pyridine ligands promote the hydrolysis of PNPP, and the order is Cu(II) system>Ni(II) system>Zn(II) system. A stereochemical modification of the complex in the CTAB micelle is suggested as a likely explanation for the observed phenomena. Copyright 2000 Academic Press.

Journal Article↗

Metallomicellar Catalysis Cleavage of p-Nitrophenyl Picolinate Catalyzed by Binuclear Metal Complexes Coordinating Tripeptide in CTAB Micellar Solution.

The catalytic hydrolysis of p-nitrophenyl picolinate (PNPP) by Cu(II) and Zn(II) complexes coordinating tripeptide were studied kinetically by observing the rates of release of p-nitrophenol in the buffered micellar solution at 25 degrees C and different pH values. The experimental results indicate that 1 : 2 ligand : metal ion complexes in CTAB micellar solution are the active species in the reaction, and the complexes, especially that with Cu(II), efficiently catalyze the hydrolysis of PNPP. As a result, a kinetic model of binuclear metal complex catalysis involving a ternary complex in CTAB micellar solution is proposed to analyze the kinetic behavior of catalysis, and thus, relative kinetic and thermodynamic parameters are obtained. The results predict that the catalytic reaction by metallomicelle with binuclear complex involves a bifunctional mechanism. Copyright 2001 Academic Press.

Journal Article↗

Metallomicellar catalysis: catalytic cleavage of p-nitrophenyl picolinate by Cu2+ complex of 4-chloride-2,6-bis(N-hydroxyethylaminomethyl)-benzophenol in micellar solution.

The hydrolysis of p-nitrophenyl picolinate (PNPP) catalyzed by the Cu(II) complex of 4-chloride-2,6-bis(N-hydroxyethylaminomethyl)-benzophenol was investigated kinetically by observing the rates of release of p-nitrophenol in the presence of three surfactants, which are hexadecyltrimethylammonium bromide, n-lauroylsarcosine sodium, and polyoxyethylene23 lauryl ether, at different pH and 25 degrees C. The scheme for the reaction involving a ternary complex comprising ligand, metal ion, and substrate in a micelle was established, and the relative kinetic and thermodynamic parameters were determined, including first-order rate constant (kN), association constant (Ks) for ternary complex, and pKa for the hydroxide ion of the ternary complex. The reaction mechanism was discussed.

Journal Article↗

Stable water-oil emulsions from the new insoluble surfactant sodium 5-(1-dodecylaminocarbonyl) picolinate.

The new compound sodium 5-(1-dodecylaminocarbonyl) picolinate (NaDPA) has been prepared and found to have the unusual surfactant property of forming stable water-oil (w/o) emulsions in the presence of water and a variety of organic liquids. A study of droplet size (diameters=0.1-1.0 mm) as a function of the amount of surfactant used shows that a near constant coverage of surfactant molecules exists at the water-oil interface and that the interface is made up of multiple layers. The structure of NaDPA, with its multiple hydrogen-bonding possibilities, probably contributes to the observed stability of the emulsions. The emulsions are made up of droplets that are stable for months and can be filled with dyes, buffers, and solutions of high ionic strength.

Journal Article↗

DNA binding mode of the cis and trans geometries of new antitumor nonclassical platinum complexes containing piperidine, piperazine, or 4-picoline ligand in cell-free media. Relations to their activity in cancer cell lines.

The global modification of mammalian and plasmid DNAs by novel platinum compounds, cis- or trans-[PtCl(2)(NH(3))(Am)], where Am = NH(3), nonplanar heterocycle piperidine, piperazine, or aromatic planar heterocycle 4-picoline, was investigated in cell-free media using various biochemical and biophysical methods. These modifications have been compared with the activity of these new compounds in several tumor cell lines including those resistant to antitumor cis-diamminedichloroplatinum(II) (cisplatin). The results show that the replacement of the NH(3) group in cisplatin by the heterocyclic ligands does not considerably affect the DNA binding mode of this drug. Cytotoxicity studies have revealed that the replacement lowers the activity of the platinum compound in both sensitive and resistant cell lines. It has been suggested that the reduced activity of these analogues of cisplatin is associated with some features of the damaged DNA and/or its cellular processing. Alternatively, the reduced activity of the analogues of cisplatin might also be due to the factors that do not operate directly at the level of the target DNA, such as intracellular platinum uptake. In contrast to the analogues of cisplatin, the replacement of one ammine group by the heterocyclic ligand in its clinically ineffective trans isomer (transplatin) results in a radical enhancement of its activity in tumor cell lines. Importantly, this replacement also markedly alters the DNA binding mode of transplatin. The results support the view that one strategy of how to activate the trans geometry in bifunctional platinum(II) compounds including circumvention of resistance to cisplatin may consist of a chemical modification of the ineffective transplatin that results in an increased stability of its intrastrand cross-links in double-helical DNA and/or in an increased efficiency to form interstrand cross-links.

Animals↗

[Mn2(saltmen)2Ni(pao)2(L)2](A)2 with L=pyridine, 4-picoline, 4-tert-butylpyridine, N-methylimidazole and A=ClO4-, BF4-, PF6-, ReO4-: a family of single-chain magnets.

A series of single-chain magnets, [Mn2(saltmen)2Ni(pao)2(L)2](A)2 (saltmen(2-)=N,N'-(1,1,2,2-tetramethylethylene) bis(salicylideneiminate), pao-=pyridine-2-aldoximate; A-=ClO4- with L=4-picoline; 2, 4-tert-butylpyridine; 3, N-methylimidazole; 4, and L=pyridine with A-=BF4-; 5, PF6-; 6, ReO4-; 7), was prepared by reactions between MnIII dimer units, i.e., [Mn2(saltmen)2(H2O)2](A)2 (A-=ClO4-, BF4-, PF6-) or Mn2(saltmen)2(ReO4)2, and NiII monomeric units, i.e., Ni(pao)2(L)2, in methanol/water media. The crystal structures of 4, 6, and 7 were established by single-crystal X-ray crystallography. These three compounds are isostructural with [Mn2(saltmen)2Ni(pao)2(py)2](ClO4)2 (1) (Clérac, R.; Miyasaka, H.; Yamashita, M.; Coulon, C. J. Am. Chem. Soc. 2002, 124, 12837) and crystallize in monoclinic space group C2/c. The linear arrangement of MnIII dimer units and NiII building blocks leads to an alternating chain having a repeating unit, [-(O)2-Mn-ON-Ni-NO-Mn-]. The chains are well separated with the nearest interchain intermetallic distance of 10.36 A for 4, 10.51 A for 6, and 10.30 A for 7, and there is no significant pi-pi interchain interaction between ligands. The void space between the chains is occupied by counteranions, which control the three-dimensional organization of the chains. The X-ray diffraction analysis (XRD) on a powder sample was also performed for all compounds. The XRD patterns for 1, 2, and 4-7 are very similar, emphasizing the isostructural nature of these materials although they have individually slight different interchain distances. Inversely, the XRD pattern for 3 reveals a completely different shape being indicative of the peculiar crystal packing compared to the others. Nevertheless, the one-dimensional nature of the structure is also kept in 3 as indicated by magnetic measurements. The whole family of compounds exhibits quasi-identical magnetic behavior compared to that described for 1. Above 30 K, the heterometallic chain can be described as an assembly of antiferromagnetically coupled Mn...Ni....Mn trimers (via oximate bridge, -24.2 K<J(Mn-Ni)/kB<-20.8 K) connected through Mn...Mn ferromagnetic interaction (via the phenolate bridge, J(Mn-Mn)/kB approximately +0.7 K), assuming a ferromagnetic chain with S=3 units. In the low temperature region, combined ac and dc magnetic measurements revealed for the whole series the systematic presence of a magnet behavior exhibiting coercivity and slow relaxation of magnetization below 3.5 K. This behavior was analyzed on the basis of Glauber's theory for an Ising one-dimensional system which predicts an activated dependence (Arrhenius law) of the relaxation time: tau=tau0 exp(Delta/kBT). Similar values of tau0 approximately 1x10(-10) s and Delta/kB approximately 70 K have been found along the series. The described compounds constitute the first example of the rational design of a single-chain magnet family and clearly demonstrate the unique behavior of these heterometallic chains independently of their interchain environments.

Journal Article↗

Structural, Spectroscopic, and Magnetochemical Characterization of the Trinuclear Vanadium(III) Carboxylates [V(3)O(O(2)CR)(6)L(3)](ClO(4)) (R = Various Groups; L = Pyridine, 4-Picoline, 3,5-Lutidine).

Synthetic procedures are described that allow access to the [V(3)O(O(2)CR)(6)L(3)](ClO(4)) (R = various groups; L = pyridine (py), 4-picoline (pic) or 3,5-lutidine (lut)) family of complexes. Treatment of VCl(3)(THF)(3) with NaO(2)CR (R = Me, Et) in RCO(2)H/py, pic/MeCN, or CH(2)Cl(2) solution followed by addition of NBu(n)(4)ClO(4) leads to isolation of [V(3)O(O(2)CR)(6)L(3)](ClO(4)) salts in 47-95% yields. A similar procedure for R = C(6)H(5), C(6)H(4)-p-OMe, C(6)H(3)-m-Me(2), and C(6)H(4)-p-Cl but omitting addition of NaO(2)CR provides the corresponding benzoate or substituted-benzoate derivatives in 24-56% yields. The X-ray structure of [V(3)O(O(2)CEt)(6)(pic)(3)](ClO(4)) (4) shows the anion to consist of a [V(3)O](7+) triangular fragment with a &mgr;(3)-O(2)(-) ion in the V(3) plane; each triangular edge is bridged by two EtCO(2)(-) groups in their familiar syn,syn modes, and there is a terminal pic group on each V(III) completing distorted octahedral geometries at the metal atoms. The cation has imposed C(2) symmetry (isosceles V(3) triangle), the C(2) axis passing through one V atom and the central &mgr;(3)-O atom, but has D(3)(h)() virtual symmetry (equilateral V(3) triangle). Complex 4 crystallizes in monoclinic space group C2/c with the following unit cell dimensions at -171 degrees C: a = 13.935(2) Å, b = 18.323(2) Å, c = 17.470(2) Å, beta = 95.55(1) degrees, V = 4439.7 Å(3), Z = 4. The structure was solved using 2657 unique reflections with F > 3sigma(F) and refined on F to conventional R (R(w)) values of 0.058 (0.066). Variable-temperature, solid-state magnetic susceptibility measurements were made on complex 1 in the 5.01-280 K region in a 1 kG magnetic field. The effective magnetic moment (&mgr;(eff)) per V(3) unit decreases gradually from 4.64 &mgr;(B) at 280 K to 1.76 &mgr;(B) at 5.01 K. The data were fit to the theoretical expression for an isosceles V(III)(3) complex, and the fitting parameters were J = -18.0(7) cm(-)(1), J' = -10.4(4) cm(-)(1), and g = 1.985, with TIP held constant at 600 x 10(-)(6) cm(3) mol(-)(1); J' refers to the unique exchange interaction within the isosceles triangle. The ground state of complex 1 thus has S = 0.

Journal Article↗

Density functional calculation of the 2D potential surface and deuterium isotope effect on 13C chemical shifts in picolinic acid N-oxide. Comparison with experiment.

2D free energy surfaces V = V(rOH, rO...O) for the intramolecular H-bond in the title compound were calculated by the DFT method and used in the calculation of primary and secondary chemical shifts of the compound dissolved in chloroform and acetonitrile. Solvent effects were accounted for by the SCRF/PCM method. The corresponding two-dimensional chemical shift surfaces with included solvent reaction field were obtained using the Continuous Set of Gauge Transformations approach at the B3LYP/6-311+G(2d,2p) level of theory. The chemical shifts were estimated as quantum averages along the two internal coordinates in the hydrogen bond and along several vibrational levels according to the Boltzmann distribution at room temperature. Fairly good agreement between the experimental and calculated isotope effects was obtained. 1D and 2D NMR spectra of solutions of picolinic acid N-oxide and its deuterated analogue were recorded and assigned.

Journal Article↗

Electrochemical determination of dopamine using a poly(2-picolinic acid) modified glassy carbon electrode.

A poly(2-picolinic acid) chemically modified electrode (CME) for the determination of dopamine (DA) by cyclic voltammetry is described. Compared with a bare glassy carbon electrode, the CME exhibits a 200 mV shift of the oxidation potential of DA in the cathodic direction and a marked enhancement of the current response. In pH 7.0 buffer solution, a linear calibration graph is obtained over the range from 2.5 x 10(-7) to 1.0 x 10(-5) mol dm-3 with a correlation coefficient of 0.998. The detection limit is 3.0 x 10(-8) mol dm-3. The modified electrode eliminated efficiently the interference from ascorbic acid (AA) when present in a 150-fold concentration ratio. It also showed excellent stability and reproducibility.

Cardiotonic Agents↗

Inclusion compounds of binaphthol with picolines: structures, selectivity and kinetics of desolvation.

The crystal structures of the inclusion compounds formed between the host 2,2'-dihydroxy-1,1'-binaphthyl and the three picoline isomers have been elucidated and their lattice energies calculated. The selectivities of enclathration by the host have been measured by competition experiments. The thermal stabilities and activation energies of desolvation of the compounds have been determined. The kinetics of desolvation are correlated to the structures.

Journal Article↗