Conformational analyses and docking studies of a series of 5-nitrofuran- and 5-nitrothiophen-semicarbazone derivatives in three possible binding sites of trypanothione and glutathione reductases

To explore three possible binding sites of trypanothione and glutathione reductase, namely, the active, the dimer interface and the coenzyme NADPH binding site, a series of eight compounds, nitrofurans and nitrothiophenes derivatives, were docked, using their crystallographic and modeled conformations. Docking results showed that, for both families and both enzymes, compounds are more likely to bind in the interface site, even though there is some probability of binding in the active site. These studies are in agreement with experimental data, which suggest that these class of compounds can act either as uncompetitive or mixed type inhibitors, and also with the finding that there is an alpha-helix which connects the active with the interface site, thus allowing charge transference between them. (c) 2005 Elsevier B.V. All rights reserved.

Structure, microstructure and dielectric properties of 100-x(Bi0.5Na0.5)TiO3-x[SrTiO3] composites ceramics

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

Effects of bovine Herpesvirus Type 5 on development of in vitro-produced bovine embryos

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

Notes on beta-deformations of the pure spinor superstring in AdS(5) x S-5

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

Susceptibility of neuron-like cells derived from bovine Wharton's jelly to bovine herpesvirus type 5 infections

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

Treatment of rat nephrotoxic nephritis. Use of 5-fluorouracil or methotrexate-5-fluorouracil association

To evaluate the effect of 5-fluorouracil (F) and methotrexate-5-fluorouracil association (MTX-F) on nephrotoxic nephritis, seven groups of 10 rats were inoculated with anti-rat glomerular basement membrane serum (AGBMS); five groups were treated with different doses of F, beginning on the 2nd or the 6th day, one group with MTX-F beginning on the 2nd day and one group (control) with distilled water. Twenty-four hour proteinuria was determined weekly until the 71st day. The kidneys were examined histologically and by immunofluorescence. The group treated with F (1.3 mg/100 g body weight) developed a severe glomerulonephritis similar to the control group; (b) the groups treated with F (2.0 mg/100 g body weight) or with MTX-F showed progressively lower proteinuria, less severe histological changes and less intense fluorescence due to autologous antibodies. The best results were observed in the MTX-F group and in the F group treated from the 6th day. These groups presented at the 71st day proteinuria of 84 and 91 mg as compared to 312 mg in the control group, and minimal histological lesions as compared to glomerulosclerosis and tubular atrophy in the control group. We concluded that either F or MTX-F produced significant improvement of nephrotoxic nephritis due to inhibition of autologous antibody production.

Hysteroscopic myomectomy in a submucous fibroid near from tubal ostia and 5 mm from the serosa: A case report from the Endoscopy Service of Ginendo-RJ

This is a case report of a 27-year-old white woman, nuliparous, single, who presented a heavy menstrual flow with clots, dysmenorrhoea and anaemia. Gynaecological examination of the uterus revealed anteverted position, mobility, no pain, slight enlargement and right displacement. Magnetic resonance imaging of the pelvis showed a 29-mm submucous fibroid with intramural component more than 50%, type 2, in the posterior wall, with a 5-mm distance from serosa. In office hysteroscopy, a 30-mm submucous fibroid with an intramural component with more than 50%, type 2, near around 5 mm from left tubal ostia, classified in STEP-W submucous fibroids classification as score 6, group II, was noted. GnRH analogue was indicated for 3 months before intervention to treat anaemia. The patient was submitted to hysteroscopic myomectomy with direct mobilisation technique, with the fibroid completely removed without complications in a surgery which lasted for 52 min and 20 s. © 2008 Springer-Verlag.

Persistent efficacy of 3.5% doramectin compared to 3.15% ivermectin against gastrointestinal nematodes in experimentally-infected cattle in Brazil

The present study aimed to evaluate the persistent efficacy of a 3.5% doramectin* (700μg/kg) formulation compared to 3.15% ivermectin** (630μg/kg) treatment, administered subcutaneously at a dose of 1mL/50kg body weight in cattle experimentally infected with gastrointestinal nematodes. Seventy-two male crossbred Holstein cattle that were negative for helminth infection were divided into nine groups. Treatments of 3.5% doramectin (Groups 2, 4, 6 and 8) and 3.15% ivermectin (Groups 3, 5, 7 and 9) were administered on days 49, 42, 35 and 28 prior to challenge with infectious nematode larvae (L3). Animals in the control group (Group 1) received saline solution on day 49 before challenge. Beginning on day zero, each animal received 50mL orally of a mixed culture containing approximately 3,000 third stage larvae (L3) of Haemonchus (60%), Oesophagostomum (20%), Cooperia (15%) and Trichostrongylus (5%) for seven consecutive days, resulting in a total challenge of 21,000 larvae/animal. Due to the large number of cattle, autopsies were performed between days 28 and 35 after the last day of inoculation. The formulation containing doramectin (700 mcg/kg) achieved persistent efficacy against H. placei and C. punctata for 49 and 35days, respectively. The persistent efficacy of ivermectin (630 mcg/kg) against H. placei lasted for 49days, but this treatment was ineffective against C. punctata. Both formulations demonstrated persistent efficacy against T. axei for 49days. The persistent efficacy of doramectin (700 mcg/kg) and ivermectin (630 mcg/kg) lasted for 49 and 42days against O. radiatum, respectively. © 2012 Elsevier Ltd.

Cannabidiol administration into the bed nucleus of the stria terminalis alters cardiovascular responses induced by acute restraint stress through 5-HT1A receptor

Systemic administration of cannabidiol (CBD) is able to attenuate cardiovascular responses to acute restraint stress through activation of 5-HT1A receptors. Previous results from our group suggest that the bed nucleus of the stria terminalis (BNST) is involved in the antiaversive effects of the CBD. Moreover, it has been proposed that synapses within the BNST influence restraint-evoked cardiovascular changes, in particular by an inhibitory influence on the tachycardiac response associated to restraint stress. Thus, the present work investigated the effects of CBD injected into the BNST on cardiovascular changes induced by acute restraint stress and if these effects would involve the local activation of 5-HT1A receptors. The exposition to restraint stress increased both blood pressure and heart rate (HR). The microinjection of CBD (30 and 60nmol) into the BNST enhanced the restraint-evoked HR increase, in a dose-dependent manner, without affecting the pressor response. The selective 5-HT1A receptor antagonist WAY100635 by itself did not change the cardiovascular responses to restraint stress, but blocked the effects of CBD. These results showed that CBD microinjected into the BNST enhanced the HR increase associated with acute restraint stress without affecting the blood pressure response. Although these results are not in agreement with those observed after systemic administration of CBD, they are similar to effects observed after reversible inactivation of the BNST. Moreover, similar to the effects observed after systemic administration, CBD effects in the BNST seem to depend on activation of 5-HT1A receptors. © 2012 Elsevier B.V. and ECNP.

Synthesis, cytotoxic activity and DNA interaction of Pd(II) complexes bearing N′-methyl-3,5-dimethyl-1-thiocarbamoylpyrazole

A new series of complexes of general formulae [PdX2(tmdmPz)] {X = Cl (1), Br (2), I (3), SCN (4); tmdmPz = N′-methyl-3,5-dimethyl-1- thiocarbamoylpyrazole} have been synthesized and characterized by elemental analysis, molar conductivities, IR, 1H and 13C{ 1H} NMR spectroscopy. In these complexes, the tmdmPz coordinates to Pd(II) center as a neutral N,S-chelating ligand. The geometries of the complexes have been optimized with the DFT method. Cytotoxicity evaluation against LM3 (mammary adenocarcinoma) and LP07 (lung adenocarcinoma) cell lines indicated that complexes 1-4 were more active than cisplatin. The binding of the complexes with a purine base (guanosine) was investigated by 1H NMR and mass spectrometry, showing that the coordination of guanosine occurs through N7. Electrophoretic DNA migration studies showed that all of them modify the DNA tertiary structure. © 2013 Elsevier Ltd. All rights reserved.

Timed artificial insemination programs during the summer in lactating dairy cows: Comparison of the 5-d Cosynch protocol with an estrogen/progesterone-based protocol

The objective of this study was to compare a GnRH-based to an estrogen/progesterone (E2/P4)-based protocol for estrous cycle synchronization and fixed timed artificial insemination (TAI), both designed for synchronization of ovulation and to reduce the period from follicular emergence until ovulation in cows with a synchronized follicular wave. A total of 1,190 lactating Holstein cows (primiparous: n = 685 and multiparous: n = 505) yielding 26.5 ± 0.30 kg of milk/d at 177 ± 5.02 d in milk were randomly assigned to receive one of the following programs: 5-d Cosynch protocol [d -8: controlled internal drug release (CIDR) + GnRH; d -3: CIDR removal + PGF2α; d -2: PGF2α; d 0: TAI + GnRH] or E2/P4 protocol (d -10: CIDR + estradiol benzoate; d -3: PGF2α; d -2: CIDR removal + estradiol cypionate; d 0: TAI). Rectal temperature and circulating progesterone (P4) were measured on d -3, -2, 0 (TAI), and 7. The estrous cycle was considered to be synchronized when P4 was ≥1.0 ng/mL on d 7 in cows that had luteolysis (P4 ≤0.4 ng/mL on d 0). To evaluate the effects of heat stress, cows were classified by number of heat stress events: 0, 1, and 2-or-more measurements of elevated body temperature (≥39.1°C). Pregnancy success (pregnancy per artificial insemination, P/AI) was determined at d 32 and 60 after TAI. The cows in the 5-d Cosynch protocol had increased circulating P4 at the time of PGF2α injection (2.66 ± 0.13 vs. 1.66 ± 0.13 ng/mL). The cows in the E2/P4 protocol were more likely to be detected in estrus (62.8 vs. 43.4%) compared with the cows in the 5-d Cosynch protocol, and expression of estrus improved P/AI in both treatments. The cows in the 5-d Cosynch protocol had greater percentage of synchronized estrous cycle (78.2%), compared with cows in the E2/P4 protocol (70.7%). On d 60, the E2/P4 protocol tended to improve P/AI (20.7 vs. 16.7%) and reduced pregnancy loss from 32 to 60 d (11.0 vs. 19.6%), compared with the 5-d Cosynch protocol. In cows with their estrous cycle synchronized, the E2/P4 protocol had greater P/AI (25.6 vs. 17.7%) on d 60 and lower pregnancy loss from 32 to 60 d (6.7 vs. 21.7%) compared with cows in the 5-d Cosynch protocol. Follicle diameter affected pregnancy loss from 32 to 60 d only in the cows in the 5-d Cosynch protocol, with smaller follicles resulting in greater pregnancy loss. Pregnancy per AI at d 60 was different between protocols in the cows with 2 or more measurements of heat stress (5-d Cosynch = 12.2% vs. E2/P4 = 22.8%), but not in the cows without or with 1 heat stress measurement. In conclusion, the 5-d Cosynch protocol apparently produced better estrous cycle synchronization than the E2/P4 protocol but did not improve P/AI. The potential explanation for these results is that increased E2 concentrations during the periovulatory period can improve pregnancy success and pregnancy maintenance, and this effect appears to be greatest in heat-stressed cows when circulating E2 may be reduced. © 2013 American Dairy Science Association.

Bovine herpesvirus type 5 infection regulates Bax/BCL-2 ratio

Bovine herpesvirus 5 (BoHV-5) is an α-herpesvirus that causes neurological disease in young cattle and is also occasionally involved in reproductive disorders. Although there have been many studies of the apoptotic pathways induced by viruses belonging to the family Herpesviridae, there is little information about the intrinsic programmed cell death pathway in host-BoHV-5 interactions. We found that BoHV-5 is able to replicate in both mesenchymal and epithelial cell lines, provoking cytopathology that is characterized by cellular swelling and cell fusion. Viral antigens were detected in infected cells by immunofluorescence assay at 48 to 96 h post-infection (p.i.). At 48 to 72 h p.i., anti-apoptotic BCL-2 antigens were found at higher levels than Bax antigens; the latter is considered a pro-apoptotic protein. Infected cells had increased BCL-2 phenotype cells from 48 to 96 h p.i., based on flow cytometric analysis. At 48 to 96 h p.i., Bax mRNA was not expressed in any of the infected cell monolayers. In contrast, BCL-2 mRNA was found at high levels at all p.i. in both types of cells. BoHV-5 replication apparently modulates BCL-2 expression and gene transcription, enhancing production of virus progeny. © FUNPEC-RP.