INJECTION OF RAMIPRIL INTO THE LATERAL VENTRICLE INTERFERES WITH THE DRINKING RESPONSE INDUCED BY PHARMACOLOGICAL AND NATURAL THIRST STIMULI

We investigated the effects of ramipril, an angiotensin I-converting enzyme (ACE) inhibitor, on water intake by male Holtzman rats (250-300 g) with cannulae implanted into the lateral ventricle. Intracerebroventricular (icv) injection of ramipril (1 mu g/mu l) significantly reduced drinking in response to subcutaneous (sc) injection of isoprenaline (100 mu g/kg) from 8.49 +/- 0.69 to 2.96 +/- 0.36 ml/2 h, polyethyleneglycol (PEG) (30% w/v, 10 ml/kg) from 9.51 +/- 2.20 to 1.6 +/- 0.34 ml/2 h or water deprivation for 24 h from 12.61 +/- 0.83 to 5.10 +/- 1.37 ml/2 h. Ramipril had no effect on water intake induced by cellular dehydration produced by sc injection of hypertonic saline (2 M NaCl). These results are consistent with the hypothesis that ramipril acts as an ACE-blocking agent in the brain. The possibility that ramipril is transformed to ramiprilat, the active drug, by the brain is suggested.

AC impedance study of Ni, Fe, Cu, Mn doped ceria stabilized zirconia ceramics

Doped zirconia has been used in electronic applications in the cubic crystalline phase. Ceria-stabilized tetragonal zirconia presents high toughness and can also be applied as solid electrolytes. The tetragonal phase of zirconia can be stabilized at room temperature with ceria in a broad range of composition. However, CeO2-ZrO2 has low sinterability. so it is important to investigate the effect of sintering dopants. In this study the effect of iron, copper. manganese and nickel was investigated. The dopants such as iron and copper lowered the sintering temperature from 1600 degreesC down to 1450 degreesC, with a percentage of tetragonal phase retained at room temperature higher than 98% and also with an increase of the electrical conductivity. The electrical conductivity was measured using impedance spectroscopy. The grain boundary contribution was determined and the activation energy associated with the ionic conduction was 1.04 eV. The dopants can also promote a grain boundary cleanliness verified by blocking effect measurement. (C) 2001 Elsevier B.V. Ltd. All rights reserved.

THE USE OF AMPPD AS AN ALTERNATIVE SUBSTRATE FOR AP-MEDIATED DETECTION OF NONRADIOLABELED DNA PROBES IN EUCALYPTUS-SALIGNA

We present a non-radioactive alternative to Southern's (J. Mol. Biol. 98: 503-517, 1975) DNA-DNA hybridization technique. The use of AMPPD - Disodium 3-(4-Methoxyspiro {1,2-dioxetane-3,2'tricyclo[3.3.1.1(3,7)]decan}-4-yl)phyenyl phosphate as an alternative substrate for AP-mediated detection of digoxigenin-11 dUTP-labeled probes made possible the simple and nonhazardous reuse of blots. We used 0.8 % agarose gels containing 30 mug per lane of Eucalyptus saligna DNA, digested with Eco RI, electrophoresed and blotted on to nylon membranes (Hybond-N, Amersham, UK), using the Southern blotting procedure, and UV irradiated for one minute for DNA fixation. The hybridizations were carried out overnight with digoxigenin labeled random inserts of E. saligna DNA by using the Genius Kit (Boehringer Mannheim). Detection of the DNA-DNA hybrids was performed in the presence of 0.5% blocking agent and the substrates NBT/BCIP were replaced by 0.26 mM AMPPD in the final alkaline assay buffer (50 mul/cm2). After membrane incubation for five minutes at room temperature in a sealed plastic bag, the AMPPD solution was retrieved and stored at 4-degrees-C for reuse. A Kodak X-BRAF QA-S film was pressed firmly onto the bag containing the wet membrane, exposed for two to six hours and then developed. After use, the probes were stripped off and the blots reutilized, three times so far, with the same results.

Chloroquine is therapeutic in murine experimental model of paracoccidioidomycosis

Chloroquine, due to its basic properties, has been shown to prevent the release of iron from holotransferrin, thereby interfering with normal iron metabolism in a variety of cell types. We have studied the effects of chloroquine on the evolution of experimental paracoccidioidomycosis by evaluating the viable fungal recovery from lung, liver and spleen from infected mice and H2O2, NO production, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-10 levels and transferrin receptor (TfR) expression from uninfected and infected peritoneal macrophages. Chloroquine caused a significant decrease in the viable fungal recovery from all organs tested, during all periods of evaluation. Peritoneal macrophages from chloroquine-treated infected mice showed higher H2O2 production and TfR expression, and decreased levels of NO, endogenous and stimulated-TNF-alpha, IL-6 and IL-10 during the three evaluated periods. However, despite its suppressor effects on the macrophage function, the chloroquine therapeutic effect upon murine paracoccidioidomycosis was probably due to its effect on iron metabolism, blocking iron uptake by cells, and consequently restricting iron to fungus growth and survival.

Interaction between vitamin K nutriture and bacterial overgrowth in hypochlorhydria induced by omeprazole

Subjects taking a hydrogen pump blocking agent (omeprazole) develop bacterial overgrowth of the small intestine. We tested the hypothesis that this bacterial overgrowth produces menaquinones, which would meet the Vitamin requirement in situations of vitamin K deficiency. In a crossover-type design, 13 healthy Volunteers eating a phylloquinone-restricted diet for 35 d were randomly assigned to take omeprazole during the first period of study or starting on day 15 until the end of the study. Coagulation times, serum osteocalcin [total osteocalcin and undercarboxylated osteocalcin (ucOC)], plasma phylloquinone, urinary gamma-carboxyglutamic acid, and plasma undercarboxylated prothrombin (PIVKA-II) were measured. Plasma phylloquinone concentrations declined 82% with dietary phylloquinone restriction (P < 0.05) and were not significantly different in the period when the diet was combined with omeprazole treatment (P > 0.05), the mean value for PIVKA-II during the phylloquinone-restricted diet significantly increased 5.7-fold from baseline (P < 0.05); however, the combination of omeprazole treatment and the phylloquinone-restricted diet significantly reduced PIVKA-II values by 21% (P < 0.05) compared with the diet period alone. There were no alterations in total or percentage ucOC concentrations during the phylloquinone-restricted diet or during the period of diet plus omeprazole treatment. Our data support the hypothesis that bacterial overgrowth results in the synthesis and absorption of menaquinones. These menaquinones contribute to vitamin K nutriture during dietary phylloquinone restriction, but not enough to restore normal vitamin K status.

Development and characterization of an equine behaviour chamber and the effects of amitraz and detomidine on spontaneous locomotor activity

This report describes the development of a behaviour chamber and the validation of the chamber to measure locomotor activity of a horse, Locomotor activity was detected by four Mini-beam sensors and recorded on a data logger every 5 min for 22 h. Horses were more active during daytime than in the evening, which was at least partially related to human activity in their surroundings. To validate the ability of the chambers to detect changes in activity, fentanyl citrate and xylazine HCl, agents well-characterized as a stimulant and a depressant, respectively, were administered to five horses. Fentanyl citrate (0.016 mg/kg) significantly increased locomotor activity which persisted for 30 min, Xylazine HCl (1 mg/kg) significantly reduced locomotor activity for 90 min. Amitraz produced a dose-dependent decrease in locomotor activity, lasting 75 min for the 0.05 mg/kg dose, 120 min for the 0.10 mg/kg dose, and 180 min for the 0.15 mg/kg dose, In a separate experiment, yohimbine administration immediately reversed the sedative effect of amitraz, This suggests there is a similarity in the mode of action of amitraz, xylazine and detomidine, as yohimbine acts primarily by blocking central alpha 2-adrenoceptors that are stimulated by agents like xylazine, There was also a significant decrease in locomotor activity following injection of detomidine (0.02, 0.04 and 0.08 mg/kg) for 1.5, 3.5 and 5.0 h, respectively, the locomotor chamber is a useful, sensitive and highly reproducible tool for measuring spontaneous locomotor activity in the horse, which allows investigators to determine an agent's average time of onset, duration and intensity of effect on movement.

Row-column response surface designs

Factorial experiments are widely used in industry to investigate the effects of process factors on quality response variables. Many food processes, for example, are not only subject to variation between days, but also between different times of the day. Removing this variation using blocking factors leads to row-column designs. In this paper, an algorithm is described for constructing factorial row-column designs when the factors are quantitative, and the data are to be analysed by fitting a polynomial model. The row-column designs are constructed using an iterative interchange search, where interchanges that result in an improvement in the weighted mean of the efficiency factors corresponding to the parameters of interest are accepted. Some examples illustrating the performance of the algorithm are given.

THEORY OF ELECTRICAL CHARACTERISTICS OF A SCHOTTKY-BARRIER HAVING EXPONENTIALLY DISTRIBUTED IMPURITY STATES AND METAL-INSULATOR METAL STRUCTURES

The metal-insulator or metal-amorphous semiconductor blocking contact is still not well understood. Here, we discuss the steady state characteristics of a non-intimate metal-insulator Schottky barrier. We consider an exponential distribution (in energy) of impurity states in addition to impurity states at a single energy level within the depletion region. We present analytical expressions for the electrical potential, field, thickness of depletion region, capacitance, and charge accumulated in the depletion region. We also discuss ln I versus V(ap) data. Finally, we compare the characteristics in three cases: (i) impurity states at only a single energy level; (ii) uniform energy distribution of impurity states; and (iii) exponential energy distribution of impurity states.In general, the electrical characteristics of Schottky barriers and metal-insulator-metal structures with Schottky barriers depend strongly on the energy distribution of impurity states.

THEORY OF NON-STEADY-STATE ELECTRICAL CHARACTERISTICS OF METAL-INSULATOR-METAL STRUCTURES WITH SCHOTTKY BARRIERS AND UNIFORMLY DISTRIBUTED INTERFACE IMPURITY STATES

The metal-insulator (or amorphous semiconductor) blocking contact is still not well understood. In the present paper, we discuss the non steady state characteristics of Metal-lnsulator-Metal Structure with non-intimate blocking contacts (i.e. Metal-Oxide-Insulator-Metal Structure). We consider a uniform distribution (in energy) of impurity states in addition to impurity states at a single energy level within the depletion region. We discuss thermal as well as isothermal characteristics and present expressions for the temperature of maximum current (T-m) and a method to calculate the density of uniformly distributed impurity states. The variation of mobility with electrical field has also been considered. Finally we plot the theoretical curves under different conditions. The present results are closing into available experimental results.

Difference variance dispersion graphs for comparing response surface designs with applications in food technology

Variance dispersion graphs have become a popular tool in aiding the choice of a response surface design. Often differences in response from some particular point, such as the expected position of the optimum or standard operating conditions, are more important than the response itself. We describe two examples from food technology. In the first, an experiment was conducted to find the levels of three factors which optimized the yield of valuable products enzymatically synthesized from sugars and to discover how the yield changed as the levels of the factors were changed from the optimum. In the second example, an experiment was conducted on a mixing process for pastry dough to discover how three factors affected a number of properties of the pastry, with a view to using these factors to control the process. We introduce the difference variance dispersion graph (DVDG) to help in the choice of a design in these circumstances. The DVDG for blocked designs is developed and the examples are used to show how the DVDG can be used in practice. In both examples a design was chosen by using the DVDG, as well as other properties, and the experiments were conducted and produced results that were useful to the experimenters. In both cases the conclusions were drawn partly by comparing responses at different points on the response surface.

Consolidation and break-up of the South American platform in southeastern Brazil: Tectonothermal and denudation histories

The different tectonic stages that occurred at the end of the Proterozoic and during the Phanerozoic have an important bearing on the tectonothermal history of the South American Platform and its consolidation. Geochronological data (U/Pb monazite, Ar-40/Ar-39 whole rock) and apatite fission-track analysis, from Precambrian rocks of the southeastern Brazilian coastline, permit the modeling of a long-term thermal history of the crust and constrain variable denudation rates.Using these data, a temperature-time diagram reflects a period of accelerated exhumation during the end of the Brasiliano Orogeny, followed by long stability and reactivation of the platform during the Rifting Phase of the South Atlantic Ocean.U/Pb zircon and monazite (blocking temperature of ca. 650degreesC) data from a series of igneous bodies suggest that a tangential and transpressional tectonic regime occurred between 625 and 610 Ma. During the following escape tectonics, between 610 and 590 Ma the exhumation process indicates cooling rates of ca. 12degreesC/Ma. Ar-40/Ar-39 biotite ages between 540 and 510 Ma (ca. 300degreesC) and a corrected fission-track age on apatites (100degreesC) of 480 Ma indicate an exhumation event related to block tectonics with huge vertical displacement along shear zones.A long stabilization phase, with low exhumation, and cooling rate around 0.25degreesC/Ma was recorded from the Cambro/Ordovician to the Mesozoic. At 65 Ma an acceleration of the exhumation through denudation and reworking of the South American surface with cooling rate of 1.5degreesC/Ma is observed.The uplift of the Mantiqueira and Serra do Mar mountain ranges along the southeast Brazilian coastline works as a climatic barrier provoking lateral erosional processes causing long-term scarp retreat, combined with intense, but progressive denudation towards the continent. A denudation of 2.5 to 4 km was calculated for such processes. This lateral retreat of escarpments and flexural response can provide important insights regarding marginal isostatic uplift and the evolution of offshore sedimentary basins of southeast Brazil.

A new shadow-ring device for measuring diffuse solar radiation at the surface

A new shadow-ring device for measuring diffuse solar radiation at the surface is presented. In this device the seasonal variation of shadow is followed by moving the detector horizontally. This unique characteristic facilitates its application for long and continuous periods of time. The blocking effect caused by the ring and other related geometric properties are formulated considering the diffuse solar radiation isotropic. The correction factor, shadow size, and ring-detector distance are derived as a function of radius and width of the ring, sun position, and local latitude. The largest blocking occurs during summer, when the ring-detector distance and the shadow width are the smallest, and it is compensated by a smaller blocking effect in the winter period. The performance of the new device is verified comparing daily values of diffuse solar radiation measured simultaneously with a similar device from Kipp & Zonen, Inc. The results show a very good agreement (within 2.5%) between both devices. The new device was also able to reproduce the radiometric properties of the local atmosphere based on 3-yr-long measurements of direct solar radiation using a pyrheliometer. The new device can be applied to estimate daily values of diffuse solar radiation at the surface in the range of 30degreesN-30degreesS with results comparable to other similar apparatuses.

New attachment achieved by guided tissue regeneration using a bioresorbable polylactic acid membrane in dogs

Created periodontal defects in dogs were randomly assigned for experimental (Guidor bioresorbable membranes) or control (conventional therapy) treatment the results showed that the new connective issue attachment was significantly greater in test sites than in controls. This new attachment averaged 2.79 +/- 0.74 mm and 1.47 +/- 0.20 mm at test and control sites, respectively (P < 0.05). Epithelial downgrowth was also reduced in the test sites (P < 0.05). No differences in bone response were found. The bioresorbable barrier was effective in blocking gingival epithelial downgrowth and connective tissue proliferation, promoting new attachment according to the principles of guided tissue regeneration.

Signaling path of the action of AVP on distal K+ secretion

Background. Previous studies from our laboratory have shown that luminal perfusion with arginine vasopressin (AVP) stimulates distal tubule secretory potassium flux (J(K)) via V1 receptors (Am J Physiol 278: F809- F816, 2000). In the present work, we investigate the cell signaling mechanism of this process.Methods. In vivo stationary microperfusion was performed in rat cortical distal tubules and luminal K was measured using double K+ resin/reference microelectrodes.Results. In control conditions, J(K) was 0.71 +/- 0.05 nmol. cm(-2).second(-1); this process was inhibited (14%) by 10(-5) mol/L 8-bromo-cyclic adenosine monophosphate (cAMP), and increased by 35% with 10(-8) mol/L phorbol ester [phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C (PKC)]. During luminal perfusion with 10(-11) mol/L AVP, J(K) increased to 0.88 +/- 0.08 nmol. cm(-2).seconds(-1). In the presence of 10(-11) mol/L AVP, J(K) was not affected by 10(-4) mol/L H89, a blocker of protein kinase A (PKA), but was inhibited (45%) by 10(-5) mol/L staurosporine, an inhibitor of PKC, and by 41% during perfusion with 5 x 10(-5) mol/L of the cell Ca2+ chelator bis (2-aminophenoxy) ethane-tetraacetic acid (BAPTA). In order to study the role of Ca2+-dependent K channels in the luminal hormonal action, the tubules were perfused with 5 mmol/L tetraethylammonium chloride (TEA) or 10(-7) mol/L iberiotoxin, in the presence of AVP, and JK was significantly reduced by both agents. Iberiotoxin reduced AVP-stimulated J(K) by 36.4%, and AVP-independent J(K) (after blocking V1 receptors) by only 16%.Conclusion. The results suggest that the luminal V1-receptor effect of AVP on J(K) was mediated by the phospholipase C (PLC)/ Ca2+/PKC signaling path and not by adenylate cyclase/cAMP/PKA, therefore probably acting on maxi-potassium channels.

Initial Development and Characterization of PLGA Nanospheres Containing Ropivacaine

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