Probing the binding of the coumarin drugs using peptide fragments of DNA gyrase B protein

Bacterial DNA gyrase, has been identified as the target of several antibacterial agents, including the coumarin drugs. The coumarins inhibit the gyrase action by competitive binding to the ATP-binding site of DNA gyrase B (GyrB) protein. The high in vitro inhibitory potency of coumarins against DNA gyrase reactions has raised interest in studies on coumarin-gyrase interactions. In this context, a series of low-molecular weight peptides, including the coumarin resistance-determining region of subunit B of Escherichia coli gyrase, has been designed and synthesized. The first peptide model was built using the natural fragment 131-146 of GyrB and was able to bind to novobiocin (K a = 1.8 ± 0.2 × 105/M) and ATP (Ka = 1.9 ± 0.4 × 103/M). To build the other sequences, changes in the Arg136 residue were introduced so that the binding to the drug was progressively reduced with the hydrophobicity of this residue (Ka = 1.3 ± 0.1 × 105/M and 1.0 ± 0.2 × 105/M for Ser and His, respectively). No binding was observed for the change Arg136 to Leu. In contrast, the binding to ATP was not altered, independently of the changes promoted. On the contrary, for peptide-coumarin and peptide-ATP complexes, Mg2+ appears to modulate the binding process. Our results demonstrate the crucial role of Arg 136 residue for the stability of coumarin-gyrase complex as well as suggest a different binding site for ATP and in both cases the interactions are mediated by magnesium ions. Copyright Blackwell Munksgaard, 2005.

Influence of arginine vasopressin receptor and nitric oxide on the water, sodium intake and arterial blood pressure induce by angiotensin injected into third ventricle of the brain

As several structures of the central nervous system are involved in the control of hydromineral and cardiovascular balance we investigated whether the natriorhexigenic and pressor response induced by the injection of ANG II into the 3rd V could be mediated by vasopressinergic and nitrergic system. Male Holtzman rats weighing 200-250 g with cannulae implanted into the 3rd V were used. The drugs were injected in 0.5 μL over 30-60 sec. Controls were injected with a similar volume of 0.15 M NaCl. ANGII increased the water intake vs control. AVPA injected into 3rd V prior to ANGII decreased the dipsogenic effect of ANGII. L-arginine also decreased the water intake induced by ANGII. AVPA plus L-arginine inhibit the water intake induced by ANGII. 7NIT injected prior to ANGII potentiated the dipsogenic effect of ANGII. Pre-treatment with ANGII increased the sodium ingestion vs control. AVPA decreased the ANGII effect in sodium intake. L-arginine also decreased the natriorhexigenic effect of ANGII. The combination of L-arginine and AVPA inhibit the sodium intake induced by ANGII. 7NIT injected prior to ANGII potentiated the sodium intake induced by ANGII. ANGII induced an increase in Mean Arterial Pressure (MAP) vs control. AVPA and L-arginine induced a decreased in the pressor effect of ANGII. The combination of L-arginine and AVPA inhibit the pressor effect of ANGII. 7NIT injected prior to ANGII into 3rd V potentiated the pressor effect of ANGII. These data suggest that arginine vasopressin V 1 receptors and Nitric Oxide (NO) within the circumventricular structures may be involved in sodium intake and pressor response induced by the activation of ANGII receptors within the circumventricular neurons. These studies revealed the involvement of sodium appetite by utilizing the angiotensinergic, vasopressinergic and nitrergic system in the central regulation of blood pressure. © 2006 Asian Network for Scientific Information.

Weight loss and surface roughness of hard chairside reline resins after toothbrushing: Influence of postpolymerization treatments

Purpose: To evaluate the effect of 2 postpolymerization treatments on toothbrushing wear (weight loss) and surface roughness of 3 autopolymerized reline resins-Duraliner II (D) (Reliance Dental), Kooliner (K) (Coe Laboratories), and Tokuso Rebase Fast (T) (Tokuyama Dental)-and 1 heat-polymerized resin, Lucitone 550 (L) (Dentsply International). Materials and Methods: Specimens (40 x 10 x 2mm) of each material (n = 24) were prepared and divided into 3 groups: control (no postpolymerization treatment); water bath (immersion in water at 55°C); and microwave (microwave irradiation). Specimens were dried until constant weight was achieved and the surface roughness (Ra) was measured. Tests were performed in a toothbrush machine using 20,000 strokes of brushing at a weight of 200 g, with the specimens immersed in 1:1 dentifrice/water slurry. Specimens were reconditioned to constant weight and the weight loss (mg) and surface roughness were evaluated. Data were analyzed by 2-way analysis of variance and followed by Tukey test (α = .05). Results: In the control group, the weight loss of materials D and T was lower (P < .05) than that of L. No differences among materials were found after postpolymerization treatments (P > .05). The weight loss of material T (control = 0.5 mg) was significantly increased (P < .05) after postpolymerization treatments (water bath = 1.9 mg; microwave = 1.8 mg). For materials K and T, the toothbrushed surface roughness was higher (P < .05) after microwave and waterbath postpolymerization treatments. Material L showed increased surface roughness after microwave postpolymerization treatment. Conclusion: The toothbrushing wear resistance of L was not superior to the reline resins. The postpolymerization treatments did not improve the toothbrushing wear resistance of the materials and produced an increased surface roughness for materials L, K, and T.

Degree of conversion and molecular weight of one denture base and three reline resins submitted post-polymerization treatments

The effect of post-polymerization treatments (MW-microwave irradiatron and WB-water-bath) on the degree of conversion (DC) of three reline resins (Ufi Gel hard-U, Kooliner-K, and Tokuso Rebase Fast-T) and one denture base resin (Lucitone 550-L), submitted to two polymerization cycles (LS-short and LL-long), was evaluated by using FT-Raman spectroscopy (n = 5). The molecular weight (Mw) of the powder of all materials and of K polymerized specimens (control; MW; and WB; n = 3) was analyzed using GPC. DC data were analyzed using Kruskal-Wallis test (α = .05). For control specimens, there were no significant differences between U (68%) and LL (77%) and among LL, K (81%), and T (84%). LS (92%) had the highest DC (P<0.05). Only material K exhibited an increased DC after WB (P<0.05). All powders had Mw from 4.0 × 105 to 6.5 × 105 and narrow Mw distributions (2.1 to 3.6). Polymerization and post-polymerization produced K specimens with Mw similar to that of K powder.

Effects of nitric oxide and arginine vasopressin on sodium intake induced by central angiotensin II. Part 2

We study the effects of angiotensin receptors antagonists, arginine vasopressin receptor antagonist, L-arginine and L-NAME, injected into supraoptic nucleus of the hypothalamus (SON) on sodium intake induced by the injection of angiotensin II (ANGII). Holtzman rats weighing 200-250 g with canulae implanted into the SON were used. The drugs were injected in 0.5 μL over 30-60 sec. Sodium intake after injection of saline SAL+SAL 0.15 M NaCl was 0.10±00.1 mL 2 h -1; SAL+ANGII injected into SON increased sodium intake. Losartan injected prior to ANGII into SON decreased sodium intake induced by ANGII. PD123319 injected prior to ANGII produced no changes in sodium intake induced by ANGII. AVPA receptor V 1 antagonist injected prior to ANGII reduced sodium intake with a less intensity than losartan. L-arginine injected prior to ANGII decreases sodium intake at a same intensity than losartan. L-NAME injected prior to ANGII potentiated sodium intake induced by ANGII. Losartan injected simultaneously with L-arginine prior to ANGII blocked the natriorexigenic effect of ANGII. These results confirm the importance of SON in the control of sodium intake. Also suggest that both AT 1 and arginine vasopressin V 1 receptors interact with nitrergic pathways within the SON influencing the sodium metabolism by changing sodium appetite induced by ANGII. © 2007 Asian Network for Scientific Information.

The influence of ovariectomy, simvastatin and sodium alendronate on alveolar bone in rats

Bisphosphonates are currently used in the treatment of many diseases involving increased bone resorption such as osteoporosis. Statins have been widely used for the treatment of hypercholesterolemia and recent studies have shown that these drugs are also capable of stimulating bone formation. The purpose of this study was to evaluate thel influence of an estrogen deficient state and the effects of simvastatin and sodium alendronate therapies on alveolar bone in female rats. Fifty-four rats were either ovariectomized (OVX) or sham operated. A month later, the animals began to receive a daily dose of simvastatin (SIN - 25 mg/kg), sodium alendronate (ALN - 2 mg/kg) or water (control) orally. Thirty-five days after the beginning of the treatment, the rats were sacrificed and their left hemimandibles were removed and radiographed using digital X-ray equipment. The alveolar radiographic density under the first molar was determined with gray-level scaling and the values were submitted to analysis of variance (α = 5%). Ovariectomized rats gained more weight (mean ± standard deviation: 20.06 ± 6.68%) than did the sham operated animals (12.13 ± 5.63%). Alveolar radiographic density values, expressed as gray levels, were lowest in the OVX-water group (183.49 ± 6.47), and differed significantly from those observed for the groups receiving alendronate (sham-ALN: 193.85 ± 3.81; OVX-ALN: 196.06 ± 5.11) and from those of the sham-water group (193.66 ± 4.36). Other comparisons between groups did not show significant differences. It was concluded that the ovariectomy reduced alveolar bone density and that alendronate was efficient for the treatment of this condition.

The effects of up to 240 days of tacrolimus therapy on the gingival tissues of rats - A morphological evaluation

Background: Tacrolimus, an immunosuppressive drug used in organ transplantation, has been reported not to induce gingival overgrowth. However, prevalence studies are limited, and the methods used for assessing gingival overgrowth varies among studies. Objective: The purpose of this study was to evaluate the effects of up to 240 days of tacrolimus therapy on gingival tissues of rats. Materials and methods: Rats were treated for 60, 120, 180 and 240 days with daily subcutaneous injections of 1 mg/kg body weight of tacrolimus. After histological processing, the oral and connective tissue, volume densities of fibroblasts (Vf), collagen fibers (Vcf) and other structures (Vo) were assessed in the region of the lower first molar. Results: After 60 and 120 days of treatment with tacrolimus, gingival overgrowth was not observed. The gingival epithelium, connective tissue, as well as the values for Vf, Vcf, and Vo were similar to those of the control rats (P > 0.05). After 180 and 240 days of the treatment, gingival overgrowth was associated with a significant increase in the gingival epithelium and connective tissue as well as an increase in the V f and Vcf (P < 0.05). Conclusions: Within the limits of the experimental study, it may be concluded that the deleterious side effects of tacrolimus on the gingival tissues of rats may be time-related. © 2007 Blackwell Munksgaard All rights reserved.

Management of vomplex systems: Modeling the biological pest control

The aim of this paper is to study the cropping system as complex one, applying methods from theory of dynamic systems and from the control theory to the mathematical modeling of the biological pest control. The complex system can be described by different mathematical models. Based on three models of the pest control, the various scenarios have been simulated in order to obtain the pest control strategy only through natural enemies' introduction. © 2008 World Scientific Publishing Company.

The role of coarse intermetallics in the localized corrosion behaviour of AA 2024-T3 in low concentrated chloride media

Aluminium alloy (AA) 2024-T3 is an important engineering material due to its widespread use in the aerospace industry. However, it is very prone to localized corrosion attack in chloride containing media, which has been mainly associated to the presence of coarse intermetallics (IMs). In this work the corrosion behaviour of aluminium alloy 2024-T3 in low concentrated chloride media was investigated using microscopy and electrochemical methods. SEM observations have shown that intermetallics with the same nominal composition present heterogeneous reaction rates, and that both types of coarse IMs normally found in the AA 2024-T3 microstructure corrode. Moreover, EDS analyses have shown important compositional changes in the corroded IMs, evidencing the selective corrosion of their more active constituents and the onset of an intense oxygen peak, irrespective to the IM nature. TEM/EDS observations on non-corroded samples have evidenced the heterogeneous composition within the IMs. On the other hand, the results of the electrochemical investigations, in accordance with the SEM/EDS observations, have evidenced that IMs corrosion dominates the electrochemical response of the alloy during the first hours of immersion in the test electrolyte. © 2009 by NACE International.

Weight vector estimation of circular arrays of antennas using Artificial Neural Networks

This paper presents a model for the control of the radiation pattern of a circular array of antennas, shaping it to address the radiation beam in the direction of the user, in order to reduce the transmitted power and to attenuate interference. The control of the array is based on Artificial Neural Networks (ANN) of the type RBF (Radial Basis Functions), trained from samples generated by the Wiener equation. The obtained results suggest that the objective was reached.

Development and application of a highly selective biomimetic sensor for detection of captopril, an important ally in hypertension control

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

Air-assistance and low volume application to control of asian rust on soybean crop

Currently, one of factors that cause the production cost increase of soybean crop is the pesticide application. The most important disease in soybean crop is Asian rust, caused by Phakopsora pachyrhizi Sydon & P. Sydon fungus, which can cause significant loss of the production. Therefore, this work aimed at evaluation of different spraying techniques on the spray deposits and some parameters of soybean crop: grain size, weight of 1 000 seeds and the crop productivity. Two experiments were carried out in the experimental area of FCA/UNESP (Faculdade de Ciencias Agronomicas/Universidade Estadual Paulista Julio de Mesquita Filho) - Botucatu, S P, Brazil, in soybean crop, Conquista variety, in the 2007/2008 season. In the first experiment, three air levels (0, 9 and 29 km/h of the air speed generated by fan) with flat fan nozzle XR 8002 with a spray volume of 130 l/ha were compared with a rotating nozzle - using low volume oily - LVO at 40 l/ha of spray volume. The second experiment was carried out under the same conditions as the previous experiment, including a control treatment (untreated plants). The disease severity was evaluated using a diagrammatic scale with a visual evaluation of the disease on 15 leaves of each plot. The grades varied between 0.6 and 78.5% of the disease severity. The use of air assistance when compared with the rotating system nozzle did not show significant differences for spray deposits on adaxial and abaxial surface of the leaves in bottom part of the plant. The air assistance with maximum air speed (29 km/h) increased the productivity with respect of the other treatments.

Bridgeless interleaved boost PFC converter with variable duty cycle control

This paper proposes a bridgeless boost interleaved PFC (power factor correction) converter with variable duty cycle control. The application of bridgeless technique causes reduction of conduction losses, while the interleaving technique of converters cells allows division of efforts in semiconductor devices and reduction of weight and volume of the input EMI filter. The use of variable duty cycle control has the functions of regulating the output voltage and eliminating the low order harmonic components that appears in the input current of the common interleaved power factor converters working in Discontinuous Conduction Mode (DCM). The simulation results of the proposed converter presented high power factor and a good transient response in relation to the output voltage regulation in presence of high load variations and supply voltage variations. © 2011 IEEE.

AC-DC three-phase multipulse converter with boost DC-DC stage and constant hysteresis control

This work proposes a new three-phase multipulse rectifier based on the delta autotransformer connection with DC-DC Boost stages and constant hysteresis control which has the objective of providing a reliable DC bus for on-board applications, electric motor drives and similars, always considering power quality issues. Thus, the proposal presents 0.99 power factor, 6% harmonic distortions in the currents from the mains and enhanced magnetic core utilization, which results in low weight and volume for the overall converter. The proposed control technique uses the simple constant hysteresis concept, thus leading to a low-cost but effective and reliable strategy. © 2011 IEEE.

Risk factors for low birth weight in Botucatu city, SP state, Brazil: A study conducted in the public health system from 2004 to 2008

Background: Low birth weight (LBW), defined as birth weight less than 2500 g, has a complex etiology and may be a result of premature interruption of pregnancy or intrauterine growth restriction. The objective of this study was to provide information on determinants of LBW and contribute to the understanding of the problem in Brazil. Methods. A case-control study was conducted in Botucatu city, SP state, Brazil. The study population consisted of 2 groups with 860 newborns in each group as follows: low weight newborns (LWNB) and a control group (weight ≤ 2500 g). Secondary data from 2004 to 2008 were collected using the Live Birth Certificate (LBC) and records from medical charts of pregnant women in Basic Health Units (BHU) and in the Public University Hospital (UH). Variables were as follows: maternal socio-demographic characteristics, pregnancy and birth conditions including quality of prenatal care according to 3 criteria. They were based on parameters established by the Ministry of Health (MH), one of them, the modified Kessner Index. The multivariable analysis by logistic regression was used to evaluate the association between variables and LBW. Results: According to the analysis, the factors associated with LBW were as follows: prematurity (OR = 56.98, 95% CI 29.52-109.95), twin pregnancy (OR = 20.00, 95% CI 6.25-100.00), maternal smoking (OR = 2.12, 95% CI 1.33-3.45), maternal malnourishment (OR = 2.30, 95% CI 1.08-5.00), maternal obesity (OR = 2.30, 95% IC 1.18-4.48), weight gain during pregnancy less than 5 kg (OR = 2.63, 95% CI 1.35-5.00) and weight gain during pregnancy more than 15 kg (OR = 2.26, 95% CI 1.16-4.41). Adequacy of prenatal care visits adjusted to gestational age was less frequent in the LBW group than in the control group (68.7% vs. 80.5%, x 2 p < 0.001). According to the modified Kessner Index, 64.4% of prenatal visits in the LWNB group were adequate. Conclusion: LWNB are a quite heterogeneous group of infants concerning their determinants and prevention actions against LBW and the follow-up of these infants have also been very complex. Therefore, improvement in the quality of care provided should be given priority through concrete actions for prevention of LBW. © 2012 Fonseca et al; licensee BioMed Central Ltd.