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1.
J Pediatr ; 208: 287-289, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30885644

RESUMO

Although recommended, most children are not routinely screened for lipid abnormalities and diabetes. We report a pilot of universal screening for diabetes, lipid abnormalities, and hypertension in the middle-school setting. Of 45 children screened, 34.8% had lipid or hemoglobin A1c abnormalities and 2 had hemoglobin A1c values in the diabetes range.


Assuntos
Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Adolescente , Índice de Massa Corporal , Peso Corporal , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Feminino , Hemoglobina A Glicada/análise , Humanos , Hipertensão/complicações , Lipídeos/sangue , Masculino , Programas de Rastreamento , Projetos Piloto , Risco , Serviços de Saúde Escolar , Instituições Acadêmicas
2.
Inorg Chem ; 57(11): 6491-6502, 2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29745653

RESUMO

The first-row transition-metal(II) dithiolates M(SAriPr4)2 [AriPr4 = C6H3-2,6-(C6H3-2,6-iPr2)2; M = Cr (1), Mn (3), Fe (4), Co (5), Ni (6), and Zn (7)] and Cr(SArMe6)2 [2; ArMe6 = C6H3-2,6-(C6H2-2,4,6-Me3)2] and the ligand-transfer reagent (NaSAriPr4)2 (8) are described. In contrast to their M(SAriPr6)2 (M = Cr, Mn, Fe, Co, Ni, and Zn; AriPr6 = C6H3-2,6-(C6H2-2,4,6-iPr3)2) congeners, which differ from 1 and 3-6 in having p-isopropyl groups on the flanking aryl rings of the terphenyl substituents, compounds 1 and 4-6 display highly bent coordination geometries with S-M-S angles of 109.802(2)° (1), 120.2828(3)° (4), 91.730(3)° (5), and 92.68(2)° (6) as well as relatively close metal-flanking aryl ring η6 interactions with metal-centroid distances of 2.11477(6) Å (1), 1.97188(3) Å (2), 2.15269(6) Å (4), 1.62058(9) Å (5), and 1.724(8) Å (6). However, the d5 (Mn) and d10 (Zn) complexes 3 and 7 display linear or near-linear coordination with no close metal-ligand distances. The nonlinear geometries of 1 and 4-6 also contrast with those of their AriPr4-substituted alkoxo and amido congeners, which have strictly linear coordination. Complexes 1-7 were synthesized by the reaction of the lithium or sodium thiolate salt with the metal dihalide or, in the case of 3, by the reaction of the thiol with the amido complex Mn[N(SiMe3)2]2. All compounds were characterized by electronic spectroscopy, X-ray crystallography, and magnetic measurements using Evans' method and SQUID magnetometry. It was concluded that, despite the large bulk of the AriPr4 substituents, the absence of p-isopropyl groups on the flanking rings of the ligand permits close secondary metal-flanking ring distances. The compounds are characterized by more intense colors and display magnetic moments that are generally lower than the spin-only values, in agreement with the covalent character of the close metal-flanking ring η6 interactions.

3.
Bioorg Med Chem ; 24(15): 3267-75, 2016 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-27301675

RESUMO

One of the hurdles in the discovery of antibiotics is the difficulty of linking antibacterial compounds to their cellular targets. Our laboratory has employed a genome-wide approach of over-expressing essential genes in order to identify cellular targets of antibacterial inhibitors. Our objective in this project was to develop and validate a more sensitive disk diffusion based platform of target identification (Target Identification Platform for Antibacterials version 2; TIPA II) using a collection of cell clones in an Escherichia coli mutant (AS19) host with increased outer membrane permeability. Five known antibiotics/inhibitors and 28 boron heterocycles were tested by TIPA II assay, in conjunction with the original assay TIPA. The TIPA II was more sensitive than TIPA because eight boron heterocycles previously found to be inactive to AG1 cells in TIPA assays exhibited activity to AS19 cells. For 15 boron heterocycles, resistant colonies were observed within the zones of inhibition only on the inducing plates in TIPA II assays. DNA sequencing confirmed that resistant clones harbor plasmids with fabI gene as insert, indicating that these boron heterocycles all target enoyl ACP reductase. Additionally, cell-based assays and dose response curved obtained indicated that for two boron heterocycle inhibitors, the fabI cell clone in AG1 (wild-type) host cells exhibited at least 11 fold more resistance under induced conditions than under non-induced conditions. Moreover, TIPA II also identified cellular targets of known antibacterial inhibitors triclosan, phosphomycin, trimethoprim, diazaborine and thiolactomycin, further validating the utility of the new system.


Assuntos
Compostos de Boro/química , Compostos Heterocíclicos/química , Compostos de Boro/farmacologia , Sistemas de Liberação de Medicamentos/métodos , Escherichia coli/efeitos dos fármacos , Compostos Heterocíclicos/farmacologia
4.
Angew Chem Int Ed Engl ; 54(44): 12914-7, 2015 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-26332337

RESUMO

The characterization of the unstable Ni(II) bis(silylamide) Ni{N(SiMe3 )2 }2 (1), its THF complex Ni{N(SiMe3 )2 }2 (THF) (2), and the stable bis(pyridine) derivative trans-Ni{N(SiMe3 )2 }2 (py)2 (3), is described. Both 1 and 2 decompose at ca. 25 °C to a tetrameric Ni(I) species, [Ni{N(SiMe3 )2 }]4 (4), also obtainable from LiN(SiMe3 )2 and NiCl2 (DME). Experimental and computational data indicate that the instability of 1 is likely due to ease of reduction of Ni(II) to Ni(I) and the stabilization of 4 through dispersion forces.

5.
Chem Biodivers ; 11(9): 1381-97, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25238079

RESUMO

A set of 2-acylated 2,3,1-benzodiazaborines and some related boron heterocycles were synthesized, characterized, and tested for antibacterial activity against Escherichia coli and Mycobacterium smegmatis. By high-field solution NMR, the heretofore unknown class of 2-acyl-1-hydroxy-2,3,1-diazaborines has been found to be able to exist in several interconvertable structural forms along a continuum comprised of an open hydrazone a, a monomeric B-hydroxy diazaborine b, and an anhydro dimer c. X-Ray crystallography of one of the anhydro dimers, 17c, revealed it to have an unprecedented structure featuring a double intramolecular O→B chelation. The crystal structure of another compound, 37, showed it to be based on a new pentacyclic B heterocycle framework. Nine compounds were found to possess activities against E. coli, and two others were active against M. smegmatis. The finding that these two contain isoniazid covalently embedded in their structures suggests that they might possibly be acting as prodrugs of this well-known antituberculosis agent in vivo.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Compostos de Boro/química , Compostos de Boro/farmacologia , Acilação , Antibacterianos/síntese química , Compostos de Boro/síntese química , Cristalografia por Raios X , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Mycobacterium smegmatis/efeitos dos fármacos , Espectroscopia de Prótons por Ressonância Magnética , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier
6.
J Am Chem Soc ; 136(25): 9173-80, 2014 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-24874837

RESUMO

Mono- and bis-terphenyl complexes of molybdenum and tungsten with general composition M2(Ar')(O2CR)3 and M2(Ar')2(O2CR)2, respectively (Ar' = terphenyl ligand), that contain carboxylate groups bridging the quadruply bonded metal atoms, have been prepared and structurally characterized. The new compounds stem from the reactions of the dimetal tetracarboxylates, M2(O2CR)4 (M = Mo, R = H, Me, CF3; M = W, R = CF3) with the lithium salts of the appropriate terphenyl groups (Ar' = Ar(Xyl2), Ar(Mes2), Ar(Dipp2), and Ar(Trip2)). Substitution of one bidentate carboxylate by a monodentate terphenyl forms a M-C σ bond and creates a coordination unsaturation at the other metal atom. Hence in M2(Ar')2(O2CR)2 complexes the two metal atoms have formally a low coordination number and an also low electron count. However, the unsaturation seems to be compensated by a weak M-C(arene) bonding interaction that implicates one of the aryl substituents of the terphenyl central aryl ring, as revealed by X-ray studies performed with some of these complexes and by theoretical calculations.

7.
Chem Commun (Camb) ; 48(33): 3954-6, 2012 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-22419994

RESUMO

New quadruply bonded dimolybdenum complexes of the terphenyl ligand Ar(Xyl(2)) (Ar(Xyl(2)) = C(6)H(3)-2,6-(C(6)H(3)-2,6-Me(2))(2)) have been prepared and structurally characterized. The steric hindrance exerted by the Ar(Xyl(2)) groups causes the Mo atoms to feature unsaturated four-coordinate structures and a formal fourteen-electron count.

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