Time-dependent increases in ouabain-sensitive Na(+), K(+)-ATPase activity in aortas from diabetic rats: The role of prostanoids and protein kinase C

Aims: Na(+), K(+)-ATPase activity contributes to the regulation of vascular contractility and it has been suggested that vascular Na(+), K(+)-ATPase activity may be altered during the progression of diabetes; however the mechanisms involved in the altered Na(+), K(+)-ATPase activity changes remain unclear. Thus, the aim of the present study was to evaluate ouabain-sensitive Na(+), K(+)-ATPase activity and the mechanism(s) responsible for any alterations on this activity in aortas from 1- and 4-week streptozotocin-pretreated (50 mg kg(-1), i.v.) rats. Main methods: Aortic rings were used to evaluate the relaxation induced by KCl (1-10 mM) in the presence and absence of ouabain (0.1 mmol/L) as an index of ouabain-sensitive Na(+), K(+)-ATPase activity. Protein expression of COX-2 and p-PKC-beta II in aortas were also investigated. Key findings: Ouabain-sensitive Na(+), K(+)-ATPase activity was unaltered following 1-week of streptozotocin administration, but was increased in the 4-week diabetic aorta (27%). Endothelium removal or nitric oxide synthase inhibition with L-NAME decreased ouabain-sensitive Na(+), K(+)-ATPase activity only in control aortas. In denuded aortic rings, indomethacin. NS-398, ridogrel or Go-6976 normalized ouabain-sensitive Na(+), K(+)-ATPase activity in 4-week diabetic rats. In addition, COX-2 (51%) and p-PKC-beta II (59%) protein expression were increased in 4-week diabetic aortas compared to controls. Significance: In conclusion, diabetes led to a time-dependent increase in ouabain-sensitive Na(+), K(+)-ATPase activity. The main mechanism involved in this activation is the release of TxA(2)/PGH(2) by COX-2 in smooth muscle cells, linked to activation of the PKC pathway. (C) 2010 Elsevier Inc. All rights reserved.

Vanadium complexes with thiosemicarbazones: Synthesis, characterization, crystal structures and anti-Mycobacterium tuberculosis activity

The development of more efficient anti-tuberculosis drugs is of interest. Three oxovanadium(IV) and three cis-dioxovanadium(V) complexes with thiosemicarbazone derivatives bearing moieties with different lipophilicity have been prepared and had their inhibitory activity against Mycobacterium tuberculosis H(37)Rv ATCC 27294 evaluated. The analytical methods used by the complexes` characterization included IR, EPR, (1)H, (13)C and (51)V NMR spectroscopies, elemental analysis, cyclic voltammetry, magnetic susceptibility measurement and single crystal X-ray diffractometry. [VO(acac)(aptsc)], [VO(acac)(apmtsc)] and [VO(acac)(apptsc)] (acac = acetylacetonate; Haptsc = 2-acetylpyridinethiosemicarbazone; Hapmtsc = 2-acetylpyridine-N(4)-methyl-thiosemicarbazone and Happtsc = 2-acetylpyridine-N(4)-phenyl-thiosemicarbazone) are paramagnetic and their EPR spectra are consistent with the monoanionic N,N,S-tridentate coordination of the thiosemicarbazone ligands, resulting in octahedral structures of rhombic symmetry and with the oxidation state +IV for the vanadium atom. As result of oxidation of the vanadium(IV) complexes above, the diamagnetic cis-dioxovanadium(V) complexes [VO(2)(aptsc)[, [VO(2)(apmtsc)[ and [VO(2)(apptsc)] are formed. Their (1)H, (13)C and (51)V NMR spectra were acquired and support a distorted square pyramidal geometry for them, in accord with the solid state X-ray structures determined for [VO(2)(aptsc)] and [VO(2)(apmtsc)]. In general, the vanadium compounds show comparable or larger anti-M. tuberculosis activities than the free thiosemicarbazone ligands, with MIC values within 62.5-1.56 (mu g/mL). (C) 2008 Elsevier Ltd. All rights reserved.

Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity

The aim of this study was to identify a candidate drug for the development of anti-tuberculosis therapy from previously synthesized compounds based on the thiosemicarbazones, semicarbazones, dithio-carbazates and hydrazide/hydrazones compounds. The minimal inhibitory concentration (MIC) of these compounds against Mycobacterium tuberculosis was determined. Their in vitro cytotoxicity to J774 cells (IC(50)) was determined to establish a selectivity index (SI) (SI = IC(50)/MIC). The best compounds were the thiosemicarbazones (2, 3 and 4) and the hydrazide/hydrazones (14, 15, 16 and 18). The results are comparable to or better than those of ""first line"" or ""second line"" drugs commonly used to treat TB, suggesting these compounds as anti-TB drug candidates. (C) 2010 Elsevier Masson SAS. All rights reserved.

Anti-Helicobacter pylori activity and oxidative burst inhibition by the naphthoquinone 5-methoxy-3,4-dehydroxanthomegnin from Paepalanthus latipes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Anti-Helicobacter pylori activity and immunostimulatory effect of extracts from Byrsonima crassa Nied. (Malpighiaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Anti-Mycobacterium tuberculosis activity of fungus Phomopsis stipata

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Synthesis and in vitro anti Mycobacterium tuberculosis activity of a series of phthalimide derivatives

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Thiosemicarbazones, semicarbazones, dithiocarbazates and hydrazide/hydrazones: Anti-Mycobacterium tuberculosis activity and cytotoxicity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Vanadium complexes with thiosemicarbazones: Synthesis, characterization, crystal structures and anti-Mycobacterium tuberculosis activity

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of anti-Mycobacterium tuberculosis activity of Campomanesia adamantium (Myrtaceae)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Secretory IgA-Fc alpha receptor interaction modulating phagocytosis and microbicidal activity by phagocytes in human colostrum of diabetics

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Hypoglycaemic and antioxidant effects of onion, Allium cepa: dietary onion addition, antioxidant activity and hypoglycaemic effects on diabetic rats

The purpose of the present study was to discover the relative potency of onion, Allium cepa, with respect to its hypoglycaemic and hypolipidaemic effects on the diabetic situation, and the association of these effects with the potential against oxidative stress. Male Wistar rats were divided into four groups. A normal control ( group A), and a non-diabetic group ( group B) were treated daily with 1 ml A. cepa solution (0.4 g A. cepa/rat). Groups C and D were made diabetic by an intraperitoneal injection of streptozotocin (STZ) ( 60 mg/kg body weight) in citrate buffer ( pH 6.3). These animals ( groups C and D) were the STZ diabetic control and STZ diabetic rats with onion intake, respectively. Onion increased the fasting serum high-density lipoprotein levels, and demonstrated alleviation of hyperglycaemia in STZ diabetic rats. The hypoglycaemic and hypolipidaemic actions of A. cepa were associated with antioxidant activity, since onion decreased superoxide dismutase activities while no increased lipid hydroperoxide and lipoperoxide concentrations were observed in diabetic rats treated with A. cepa.

Inhibition of myotoxic activity of Bothrops asper myotoxin II by the anti-trypanosomal drug surarnin

Suramin, a synthetic polysulfonated compound, developed initially for the treatment of African trypanosomiasis and onchocerciasis, is currently used for the treatment of several medically relevant disorders. Suramin, heparin, and other polyanions inhibit the myotoxic activity of Lys49 phospholipase A(2) analogues both in vitro and in vivo, and are thus of potential importance as therapeutic agents in the treatment of viperid snake bites. Due to its conformational flexibility around the single bonds that link the central phenyl rings to the secondary amide backbone, the symmetrical suramin molecule binds by an induced-fit mechanism complementing the hydrophobic surfaces of the dimer and adopts a novel conformation that lacks C2 symmetry in the dimeric crystal structure of the suramin-Bothrops asper myotoxin II complex. The simultaneous binding of suramin at the surfaces of the two monomers partially restricts access to the nominal active sites and significantly changes the overall charge of the interfacial recognition face of the protein, resulting in the inhibition of myotoxicity. (c) 2005 Elsevier Ltd. All rights reserved.

Anti-proliferative and cytotoxic activity of pentadactylin isolated from Leptodactylus labyrinthicus on melanoma cells

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)