Renal denervation in an animal model of diabetes and hypertension: Impact on the autonomic nervous system and nephropathy

Background: The effects of renal denervation on cardiovascular reflexes and markers of nephropathy in diabetic-hypertensive rats have not yet been explored. Methods: Aim: To evaluate the effects of renal denervation on nephropathy development mechanisms (blood pressure, cardiovascular autonomic changes, renal GLUT2) in diabetic-hypertensive rats. Forty-one male spontaneously hypertensive rats (SHR) similar to 250 g were injected with STZ or not; 30 days later, surgical renal denervation (RD) or sham procedure was performed; 15 days later, glycemia and albuminuria (ELISA) were evaluated. Catheters were implanted into the femoral artery to evaluate arterial pressure (AP) and heart rate variability (spectral analysis) one day later in conscious animals. Animals were killed, kidneys removed, and cortical renal GLUT2 quantified (Western blotting). Results: Higher glycemia (p < 0.05) and lower mean AP were observed in diabetics vs. nondiabetics (p < 0.05). Heart rate was higher in renal-denervated hypertensive and lower in diabetic-hypertensive rats (384.8 +/- 37, 431.3 +/- 36, 316.2 +/- 5, 363.8 +/- 12 bpm in SHR, RD-SHR, STZ-SHR and RD-STZ-SHR, respectively). Heart rate variability was higher in renal-denervated diabetic-hypertensive rats (55.75 +/- 25.21, 73.40 +/- 53.30, 148.4 +/- 93 in RD-SHR, STZ-SHR-and RD-STZ-SHR, respectively, p < 0.05), as well as the LF component of AP variability (1.62 +/- 0.9, 2.12 +/- 0.9, 7.38 +/- 6.5 in RD-SHR, STZ-SHR and RD-STZ-SHR, respectively, p < 0.05). GLUT2 renal content was higher in all groups vs. SHR. Conclusions: Renal denervation in diabetic-hypertensive rats improved previously reduced heart rate variability. The GLUT2 equally overexpressed by diabetes and renal denervation may represent a maximal derangement effect of each condition.

Activation of endogenous p53 by combined p19Arf gene transfer and nutlin-3 drug treatment modalities in the murine cell lines B16 and C6

Background: Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma. In our previous work, we constructed the pCLPG retroviral vector where transgene expression is controlled by p53 through a p53-responsive promoter. The use of this vector to introduce p19Arf into tumor cells that harbor p53wt should yield viral expression of p19Arf which, in turn, would activate the endogenous p53 and result in enhanced vector expression and tumor suppression. Since nutlin-3 can activate p53 by blocking its interaction with mdm2, we explored the possibility that the combination of p19Arf gene transfer and nutlin-3 drug treatment may provide an additive benefit in stimulating p53 function. Methods: B16 (mouse melanoma) and C6 (rat glioma) cell lines, which harbor p53wt, were transduced with pCLPGp19 and these were additionally treated with nutlin-3 or the DNA damaging agent, doxorubicin. Viral expression was confirmed by Western, Northern and immunofluorescence assays. p53 function was assessed by reporter gene activity provided by a p53-responsive construct. Alterations in proliferation and viability were measured by colony formation, growth curve, cell cycle and MTT assays. In an animal model, B16 cells were treated with the pCLPGp19 virus and/or drugs before subcutaneous injection in C57BL/6 mice, observation of tumor progression and histopathologic analyses. Results: Here we show that the functional activation of endogenous p53wt in B16 was particularly challenging, but accomplished when combined gene transfer and drug treatments were applied, resulting in increased transactivation by p53, marked cell cycle alteration and reduced viability in culture. In an animal model, B16 cells treated with both p19Arf and nutlin-3 yielded increased necrosis and decreased BrdU marking. In comparison, C6 cells were quite susceptible to either treatment, yet p53 was further activated by the combination of p19Arf and nutlin-3. Conclusions: To the best of our knowledge, this is the first study to apply both p19Arf and nutlin-3 for the stimulation of p53 activity. These results support the notion that a p53 responsive vector may prove to be an interesting gene transfer tool, especially when combined with p53- activating agents, for the treatment of tumors that retain wild-type p53.

Respiratory allergy to Blomia tropicalis: Immune response in four syngeneic mouse strains and assessment of a low allergen-dose, short-term experimental model

Background: The dust mite Blomia tropicalis is an important source of aeroallergens in tropical areas. Although a mouse model for B. tropicalis extract (BtE)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol. Objectives: This work had two objectives. The first was to study the anti-B. tropicalis allergic responses in different mouse strains using a short-term model of respiratory allergy to BtE. This study included the comparison of the allergic responses elicited by BtE with those elicited by ovalbumin in mice of the strain that responded better to BtE sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low BtE doses. Methods: Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 mu g of BtE on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 mu g of BtE. A/J mice, that were the best responders to BtE sensitization, were used to compare the B. tropicalis-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of BtE. Results: Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-BtE IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with BtE induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low BtE dose (10 mu g per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose BtE immunization, for the development of allergy-associated immune and lung inflammatory responses. Conclusions: The described short-term model of BtE-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and BtE induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of BtE.

Development of a DNA-dosimeter system for monitoring the effects of solar-ultraviolet radiation

Solar radiation sustains and affects all life forms on Earth. In recent years, the increase in environmental levels of solar-UV radiation due to depletion of the stratospheric ozone layer, as a result of anthropogenic emission of destructive chemicals, has highlighted serious issues of social concern. This becomes still more dramatic in tropical and subtropical regions, where the intensity of solar radiation is higher. To better understand the impact of the harmful effects of solar-UV radiation on the DNA molecule, we developed a reliable biological monitoring system based on the exposure of plasmid DNA to artificial UV lamps and sunlight. The determination and quanti. cation of different types of UV photoproducts were performed through the use of specific DNA repair enzymes and antibodies. As expected, a significant number of CPDs and 6-4PPs was observed when the DNA-dosimeter system was exposed to increasing doses of UVB radiation. Moreover, CPDs could also be clearly detected in plasmid DNA when this system was exposed to either UVA or directly to sunlight. Interestingly, although less abundant, 6-4PPs and oxidative DNA damage were also generated after exposure to both UVA and sunlight. These results confirm the genotoxic potential of sunlight, reveal that UVA may also produce CPDs and 6-4PPs directly in naked DNA and demonstrate the applicability of a DNA-dosimeter system for monitoring the biological effects of solar-UV radiation.

Aspergillus nidulans as a biological system to detect the genotoxic effects of mercury fumes on eukaryotes

Mercury (Hg) pollution is one of the most serious environmental problems. Due to public concern prompted by the symptoms displayed by people who consumed contaminated fish in Minamata, Japan in 1956, Hg pollution has since been kept under constant surveillance. However, despite considerable accumulation of knowledge on the noxious effects of ingested or inhaled Hg, especially for humans, there is virtually nothing known about the genotoxic effects of Hg. Because increased mitotic crossing over is assumed to be the first step leading to carcinogenesis, we used a sensitive short-term test (homozygotization index) to look for DNA alterations induced by Hg fumes. In one Aspergillus nidulans diploid strain (UT448//UT184), the effects of the Hg fumes appeared scattered all over the DNA, causing 3.05 times more recombination frequencies than the mean for other strains. Another diploid (Dp II- I//UT184) was little affected by Hg. This led us to hypothesize that a genetic factor present in the UT184 master strain genome, close to the nicB8 genetic marker, is responsible for this behavior. These findings corroborate our previous findings that the homozygotization index can be used as a bioassay for rapid and efficient assessment of ecotoxicological hazards.

Association of Trypanosoma vivax in extracellular sites with central nervous system lesions and changes in cerebrospinal fluid in experimentally infected goats

Changes in cerebrospinal fluid (CSF) and anatomical and histopathological central nervous system (CNS) lesions were evaluated, and the presence of Trypanosoma vivax in CNS tissues was investigated through PCR. Twelve adult male goats were divided into three groups (G): G1, infected with T. vivax and evaluated during the acute phase; G2, infected goats evaluated during the chronic phase; and G3, consisting of non-infected goats. Each goat from G1 and G2 was infected with 1.25 x 10(5) trypomastigotes. Cerebrospinal fluid (CSF) analysis and investigation of T. vivax was performed at the 15(th) day post-infection (dpi) in G1 goats and on the fifth day after the manifestation of nervous system infection signs in G2 goats. All goats were necropsied, and CNS fragments from G1 and G2 goats were evaluated by PCR for the determination of T. vivax. Hyperthermia, anemia and parasitemia were observed from the fifth dpi for G1 and G2, with the highest parasitemia peak between the seventh and 21(st) dpi. Nervous system infection signs were observed in three G2 goats between the 30(th) and 35(th) dpi. CSF analysis revealed the presence of T. vivax for G2. Meningitis and meningoencephalitis were diagnosed in G2. PCR were positive for T. vivax in all the samples tested. In conclusion, T. vivax may reach the nervous tissue resulting in immune response from the host, which is the cause of progressive clinical and pathological manifestations of the CNS in experimentally infected goats.

AMBIVALENT IMPLICATIONS OF HEALTH CARE INFORMATION SYSTEMS: A STUDY IN THE BRAZILIAN PUBLIC HEALTH CARE SYSTEM

This article evaluates social implications of the ""SIGA"" Health Care Information System (HIS) in a public health care organization in the city of Sao Paulo. The evaluation was performed by means of an in-depth case study with patients and staff of a public health care organization, using qualitative and quantitative data. On the one hand, the system had consequences perceived as positive such as improved convenience and democratization of specialized treatment for patients and improvements in work organization. On the other hand, negative outcomes were reported, like difficulties faced by employees due to little familiarity with IT and an increase in the time needed to schedule appointments. Results show the ambiguity of the implications of HIS in developing countries, emphasizing the need for a more nuanced view of the evaluation of failures and successes and the importance of social contextual factors.

The Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System (CATT-BRAMS) - Part 2: Model sensitivity to the biomass burning

We describe an estimation technique for biomass burning emissions in South America based on a combination of remote-sensing fire products and field observations, the Brazilian Biomass Burning Emission Model (3BEM). For each fire pixel detected by remote sensing, the mass of the emitted tracer is calculated based on field observations of fire properties related to the type of vegetation burning. The burnt area is estimated from the instantaneous fire size retrieved by remote sensing, when available, or from statistical properties of the burn scars. The sources are then spatially and temporally distributed and assimilated daily by the Coupled Aerosol and Tracer Transport model to the Brazilian developments on the Regional Atmospheric Modeling System (CATT-BRAMS) in order to perform the prognosis of related tracer concentrations. Three other biomass burning inventories, including GFEDv2 and EDGAR, are simultaneously used to compare the emission strength in terms of the resultant tracer distribution. We also assess the effect of using the daily time resolution of fire emissions by including runs with monthly-averaged emissions. We evaluate the performance of the model using the different emission estimation techniques by comparing the model results with direct measurements of carbon monoxide both near-surface and airborne, as well as remote sensing derived products. The model results obtained using the 3BEM methodology of estimation introduced in this paper show relatively good agreement with the direct measurements and MOPITT data product, suggesting the reliability of the model at local to regional scales.

Multistability and Self-Similarity in the Parameter-Space of a Vibro-Impact System

The dynamics of a dissipative vibro-impact system called impact-pair is investigated. This system is similar to Fermi-Ulam accelerator model and consists of an oscillating one-dimensional box containing a point mass moving freely between successive inelastic collisions with the rigid walls of the box. In our numerical simulations, we observed multistable regimes, for which the corresponding basins of attraction present a quite complicated structure with smooth boundary. In addition, we characterize the system in a two-dimensional parameter space by using the largest Lyapunov exponents, identifying self-similar periodic sets. Copyright (C) 2009 Silvio L.T. de Souza et al.

Precise measurements of direct CP violation, CPT symmetry, and other parameters in the neutral kaon system

We present precise tests of CP and CPT symmetry based on the full data set of K -> pi pi decays collected by the KTeV experiment at Fermi National Accelerator Laboratory during 1996, 1997, and 1999. This data set contains 16 x 10(6) K -> pi(0)pi(0) and 69 x 10(6) K -> pi(+)pi(-) decays. We measure the direct CP violation parameter Re(epsilon'/epsilon) = (19.2 +/- 2.1) x 10(-4). We find the K(L) -> K(S) mass difference Delta m = (5270 +/- 12) x 10(6) (h) over tilde s(-1) and the K(S) lifetime tau(S) = (89.62 +/- 0.05) x 10(-12) s. We also measure several parameters that test CPT invariance. We find the difference between the phase of the indirect CP violation parameter epsilon and the superweak phase: phi(epsilon) - phi(SW) =(0.40 +/- 0.56)degrees. We measure the difference of the relative phases between the CP violating and CP conserving decay amplitudes for K -> pi(+)pi(-) (phi(+-)) and for K -> pi(0)pi(0) (phi(00)): Delta phi = (0.30 +/- 0.35)degrees. From these phase measurements, we place a limit on the mass difference between K(0) and (K) over bar (0): Delta M < 4.8 x 10(-19) GeV/c(2) at 95% C.L. These results are consistent with those of other experiments, our own earlier measurements, and CPT symmetry.

Microwave Zero-Resistance States in a Bilayer Electron System

Magnetotransport measurements on a high-mobility electron bilayer system formed in a wide GaAs quantum well reveal vanishing dissipative resistance under continuous microwave irradiation. Profound zero-resistance states (ZRS) appear even in the presence of additional intersubband scattering of electrons. We study the dependence of photoresistance on frequency, microwave power, and temperature. Experimental results are compared with a theory demonstrating that the conditions for absolute negative resistivity correlate with the appearance of ZRS.

Quantum Hall Effect near the Charge Neutrality Point in a Two-Dimensional Electron-Hole System

We study the transport properties of HgTe-based quantum wells containing simultaneously electrons and holes in a magnetic field B. At the charge neutrality point (CNP) with nearly equal electron and hole densities, the resistance is found to increase very strongly with B while the Hall resistivity turns to zero. This behavior results in a wide plateau in the Hall conductivity sigma(xy) approximate to 0 and in a minimum of diagonal conductivity sigma(xx) at nu = nu(p) - nu(n) = 0, where nu(n) and nu(p) are the electron and hole Landau level filling factors. We suggest that the transport at the CNP point is determined by electron-hole ""snake states'' propagating along the nu = 0 lines. Our observations are qualitatively similar to the quantum Hall effect in graphene as well as to the transport in a random magnetic field with a zero mean value.

Role of dipolar interactions in a system of Ni nanoparticles studied by magnetic susceptibility measurements

The role of dipolar interactions among Ni nanoparticles (NPs) embedded in an amorphous SiO(2)/C matrix with different concentrations has been studied performing ac magnetic susceptibility chi(ac) measurements. For very diluted samples, with Ni concentrations < 4 wt % Ni or very weak dipolar interactions, the data are well described by the Neacuteel-Arrhenius law. Increasing Ni concentration to values up to 12.8 wt % Ni results in changes in the Neacuteel-Arrhenius behavior, the dipolar interactions become important, and need to be considered to describe the magnetic response of the NPs system. We have found no evidence of a spin-glasslike behavior in our Ni NP systems even when dipolar interactions are clearly present.

Classical and quantum magnetoresistance in a two-subband electron system

We observe a large positive magnetoresistance in a bilayer electron system (double quantum well) as the latter is driven by the external gate from double to single layer configuration. Both classical and quantum contributions to magnetotransport are found to be important for explanation of this effect. We demonstrate that these contributions can be separated experimentally by studying the magnetic-field dependence of the resistance at different gate voltages. The experimental results are analyzed and described by using the theory of low-field magnetotransport in the systems with two occupied subbands.

Critical behavior of the magnetization in the spin-gapped system NiCl(2)-4SC (NH(2))(2)

We report accurate magnetization measurements on the spin-gap compound NiCl(2)-4SC (NH(2))(2) around the low portion of the magnetic induced phase ordering. The critical density of the magnetization at the phase boundary is analyzed in terms of a Bose-Einstein condensation (BEC) of bosonic particles, and the boson interaction strength is obtained as upsilon(0)=0.61 meV. The detailed analysis of the magnetization data across the transition leads to the conclusion for the preservation of the U(1) symmetry, as required for BEC. (c) 2009 American Institute of Physics. [DOI: 10.1063/1.3055265]