The role of the TP53 gene during rat tongue carcinogenesis induced by 4-nitroquinoline 1-oxide

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

Natriorexigenic effect of baclofen is reduced by AT(1) receptor blockade in the lateral parabrachial nucleus

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

Antidipsogenic effects of central adenosine-5'-triphosphate

Besides other physiological functions, adenosine-5'-triphosphate (ATP) is also a neurotransmitter that acts on purinergic receptors. In spite of the presence of purinergic receptors in forebrain areas involved with fluid-electrolyte balance, the effect of ATP on water intake has not been investigated. Therefore, we studied the effects of intracerebroventricular (icv) injections of ATP (100, 200 and 300 nmol/µL) alone or combined with DPCPX or PPADS (P1 and P2 purinergic antagonists, respectively, 25 nmol/µL) on water intake induced by water deprivation. In addition, the effect of icv ATP was also tested on water intake induced by intragastric load of 12% NaCl (2 mL/rat), acute treatment with the diuretic/natriuretic furosemide (20 mg/kg), icv angiotensin II (50 ng/µL) or icv carbachol (a cholinergic agonist, 4 nmol/µL), on sodium depletion-induced 1.8% NaCl intake, and on food intake induced by food deprivation. Male Holtzman rats (280-320 g, N = 7-11) had cannulas implanted into the lateral ventricle. Icv ATP (300 nmol/µL) reduced water intake induced by water deprivation (13.1 ± 1.9 vs saline: 19.0 ± 1.4 mL/2 h; P < 0.05), an effect blocked by pre-treatment with PPADS, but not DPCPX. Icv ATP also reduced water intake induced by NaCl intragastric load (5.6 ± 0.9 vs saline: 10.3 ± 1.4 mL/2 h; P < 0.05), acute furosemide treatment (0.5 ± 0.2 vs saline: 2.3 ± 0.6 mL/15 min; P < 0.05), and icv angiotensin II (2.2 ± 0.8 vs saline: 10.4 ± 2.0 mL/2 h; P < 0.05), without changing icv carbachol-induced water intake, sodium depletion-induced 1.8% NaCl intake and food deprivation-induced food intake. These data suggest that central ATP, acting on purinergic P2 receptors, reduces water intake induced by intracellular and extracellular dehydration.

Low Apgar scores at 5 minutes in a low risk population: maternal and obstetrical factors and postnatal outcome

OBJETIVO: Avaliar a associação entre índice de Apgar menor que sete no 5º minuto, os fatores pré-natais e resultados pós-natais. MÉTODOS: Trata-se de estudo retrospectivo com 27.252 recém-nascidos em maternidade escola com população de baixo risco obstétrico, de janeiro de 2003 a dezembro de 2010. Prontuários de todos os casos com índice de Apgar < 7 no 5º minuto (n = 121; - 0,4%) e de 363 casos com Apgar > 7 no 5º minuto, escolhidos ao acaso, foram revisados. Os principais desfechos estudados foram: óbito neonatal, insuficiência respiratória neonatal, necessidade de intubação orotraqueal e de unidade terapia intensiva (UTI) neonatal e encefalopatia hipóxico-isquêmica. RESULTADOS: Após análise de regressão múltipla, desacelerações tardias (DIP II) (OR: 2,4; IC95%: 1,4-4,1) e período expulsivo prolongado (OR: 3,3; IC 95%: 1,3-8,3) se associaram com Apgar < 7 no 5º minuto; assim como com insuficiência respiratória ao nascimento (OR: 3,0; IC 95%: 1,3-6,9), intubação traqueal (OR: 2,5; IC 95%: 1,2-4,8), necessidade de UTI neonatal (OR: 9,5; IC 95%: 6,7-16,8) e encefalopatia hipóxico-isquêmica (OR: 14,1; IC 95%: 3,6-54,7). Nenhuma outra variável prénatal se associou com Apgar < 7 no 5º minuto (p < 0,05). CONCLUSÃO: DIP II e período expulsivo prolongado estão associados com Apgar < 7 no 5º minuto em população obstétrica de baixo risco; situação essa relacionada com maior risco de insuficiência respiratória no parto, necessidade de suporte ventilatório e encefalopatia hipóxico-isquêmica.

alpha(1)-Adrenoceptors in proximal segments of tail arteries from control and reserpinised rats

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Effects of indoramin in rat vas deferens and aorta: concomitant alpha(1)-adrenoceptor and neuronal uptake blockade

1 the actions of the alpha(1)-adrenoceptor antagonist indoramin have been examined against the contractions induced by noradrenaline in the rat vas deferens and aorta taking into account a putative neuronal uptake blocking activity of this antagonist which could. result in self-cancelling actions.2 Indoramin behaved as a simple competitive antagonist of the contractions induced by noradrenaline in the vas deferens and aorta yielding pA(2) values of 7.38 +/- 0.05 (slope = 0.98 +/- 0.03) and 6.78 +/- 0.14 (slope = 1.08 +/- 0.06), respectively.3 When the experiments were repeated in the presence of cocaine (6 mu M) the potency (pA(2)) of indoramin in antagonizing the contractions of the vas deferens to noradrenaline was increased to 8.72 +/- 0.07 (slope = 1.10 +/- 0.05) while its potency remained unchanged in the aorta (pA(2) = 6.69 +/- 0.12; slope = 1.04 +/- 0.05).4 In denervated vas deferens, indoramin antagonized the contractions to noradrenaline with a potency similar to that found in the presence of cocaine (8.79 +/- 0.07; slope = 1.09 +/- 0.06).5 It is suggested that indoramin blocks alpha(1)-adrenoceptors and neuronal uptake in rat vas deferens resulting in Schild plots with slopes not different from unity even in the absence of selective inhibition of neuronal uptake. As a major consequence of this double mechanism of action, the pA(2) values for this antagonist are underestimated when calculated in situations where the neuronal uptake is active, yielding spurious pK(B) values.

Lemongrass effects on IL-1 and IL-6 production by macrophages

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

Effects of swimming training on bone mass and the GH/IGF-1 axis in diabetic rats

The aim of this study was to examine the influence of moderate swimming training on the GH/IGF-1 growth axis and tibial mass in diabetic rats. Male Wistar rats were allocated to one of four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced with alloxan (35 mg/kg b.w.). The training program consisted of a 1 h swimming session/day with a load corresponding to 5% of the b.w., five days/week for six weeks. At the end of the training period, the rats were sacrificed and blood was collected for quantification of the serum glucose, insulin, GH, and IGF-1 concentrations. Samples of skeletal muscle were used to quantify the IGF-1 pepticle content. The tibias were collected to determine their total area, length and bone mineral content. The results were analyzed by ANOVA with P < 0.05 indicating significance. Diabetes decreased the serum levels of GH and IGF-1, as well as the tibial length, total area and bone mineral content in the SD group (P < 0.05). Physical training increased the serum IGF-1 level in the TC and TD groups when compared to the sedentary groups (SC and SD), and the tibial length, total area and bone mineral content were higher in the TD group than in the SD group (P < 0.05). Exercise did not alter the level of IGF-1 in gastrocnemius muscle in nondiabetic rats, but the muscle IGF-1 content was higher in the TD group than in the SD group. These results indicate that swimming training stimulates bone mass and the GH/IGF-1 axis in diabetic rats. (c) 2006 Elsevier Ltd. All rights reserved.

Differential coronary resistance microvessel remodeling between type 1 and type 2 diabetic mice: Impact of exercise training

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

Three-dimensional structure of ribonuclease T-1 complexed with an isosteric phosphonate substrate analogue of GpU: Alternate substrate binding modes and catalysis

The X-ray crystal structure of a complex between ribonuclease T-1 and guanylyl(3'-6')-6'-deoxyhomouridine (GpcU) has been determined at 2.0 Angstrom resolution. This Ligand is an isosteric analogue of the minimal RNA substrate, guanylyl(3'-5')uridine (GpU), where a methylene is substituted for the uridine 5'-oxygen atom. Two protein molecules are part of the asymmetric unit and both have a GpcU bound at the active site in the same manner. The protein-protein interface reveals an extended aromatic stack involving both guanines and three enzyme phenolic groups. A third GpcU has its guanine moiety stacked on His92 at the active site on enzyme molecule A and interacts with GpcU on molecule B in a neighboring unit via hydrogen bonding between uridine ribose 2'- and 3'-OH groups. None of the uridine moieties of the three GpcU molecules in the asymmetric unit interacts directly with the protein. GpcU-active-site interactions involve extensive hydrogen bonding of the guanine moiety at the primary recognition site and of the guanosine 2'-hydroxyl group with His40 and Glu58. on the other hand, the phosphonate group is weakly bound only by a single hydrogen bond with Tyr38, unlike ligand phosphate groups of other substrate analogues and 3'-GMP, which hydrogen-bonded with three additional active-site residues. Hydrogen bonding of the guanylyl 2'-OH group and the phosphonate moiety is essentially the same as that recently observed for a novel structure of a RNase T-1-3'-GMP complex obtained immediately after in situ hydrolysis of exo-(S-p)-guanosine 2',3'-cyclophosphorothioate [Zegers et al. (1998) Nature Struct. Biol. 5, 280-283]. It is likely that GpcU at the active site represents a nonproductive binding mode for GpU [:Steyaert, J., and Engleborghs (1995) fur. J. Biochem. 233, 140-144]. The results suggest that the active site of ribonuclease T-1 is adapted for optimal tight binding of both the guanylyl 2'-OH and phosphate groups (of GpU) only in the transition state for catalytic transesterification, which is stabilized by adjacent binding of the leaving nucleoside (U) group.

Hydrothermal syntheses of ETS-10 like vanadosilicates using chiral organic molecules. Part I

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

Limits on anomalous trilinear gauge couplings from WW -> e(+)e(-), WW -> e(+/-)mu(-/+), and WW ->mu(+)mu(-) events from pp collisions at root s=1.96 TeV

Limits are set on anomalous WW gamma and WWZ trilinear gauge couplings using W+W--> e(+)nu(e)e(-)(nu) over bar (e), W+W--> e(+/-)nu(e)mu(-/+)nu(mu), and W+W-->mu(+)nu(mu)mu(-)(nu) over bar (mu) events. The data set was collected by the Run II D0 detector at the Fermilab Tevatron Collider and corresponds to approximately 250 pb(-1) of integrated luminosity at root s=1.96 TeV. Under the assumption that the WW gamma couplings are equal to the WWZ couplings and using a form factor scale of Lambda=2.0 TeV, the combined 95% C.L. one-dimensional coupling limits from all three channels are -0.32

Search for R-parity violating supersymmetry via the LL(E)over-bar couplings lambda(121), lambda(122) or lambda(133) in p(p)over-bar collisions at root s=1.96 TeV

A search for gaugino pair production with a trilepton signature in the framework of R-parity violating supersymmetry via the couplings; lambda(121), lambda(122), or lambda(133) is presented. The data, corresponding to an integrated luminosity of L approximate to 360 pb(-1), were collected from April 2002 to August 2004 with the D0 detector at the Fermilab Tevatron Collider, at a center-of-mass energy of root s = 1.96 TeV. This analysis considers final states with three charged leptons with the flavor combinations eel, mu mu l, and ee tau (l = e or mu). No evidence for supersymmetry is found and limits at the 95% confidence level are set on the gaugino pair production cross section and lower bounds on the masses of the lightest neutralino and chargino are derived in two supersymmetric models. (c) 2006 Elsevier B.V. All rights reserved.

Z gamma production and limits on anomalous ZZ gamma and Z gamma gamma couplings in pp collisions at root s=1.96 TeV

We present a study of eey and mu mu gamma events using 1109 (1009) pb-(1) of data in the electron (muon) channel, respectively. These data were collected with the DO detector at the Fermilab Tevatron pp collider at Is = 1.96 TeV. Having observed 453 (515) candidates in the eey (jtAy) final state, we measure the Z gamma production cross section for a photon with transverse energy ET > 7 GeV, separation between the photon and leptons Delta Rey > 0.7, and invariant mass of the di-lepton pair Mee > 30 GeV/(2)(c), to be 4.96 0.30(stat. + syst.) zE 0.30(lumi.) pb, in agreement with the Standard Model prediction of 4.74 0.22 pb. This is the most precise Zy cross section measurement at a hadron collider. We set limits on anomalous trilinear Zyy and ZZy gauge boson couplings of -0.085 < h(30)(y) < 0.084, -0.0053 < h(40)(y) < 0.0054 and -0.083 < h(30)(Z) < 0.082, 30 40 30 -0.0053 < h(40)(Z) < 0.0054 at the 95% C.L. for the form-factor scale A = 1.2 TeV. 40 Published by Elsevier B.V.