Langmuir films containing ibuprofen and phospholipids

This study shows the incorporation of ibuprofen, an anti-inflammatory drug, in Langmuir monolayers as cell membrane models. Significant effects were observed for dipalmitoyl phosphatidyl choline (DPPC) monolayers with relevant changes in the elasticity of the monolayer. Dipalmitoyl phosphatidyl glycerol (DPPG) monolayers were affected by small concentrations of ibuprofen, from 1 to 5 mol%. For both types of monolayer, ibuprofen could penetrate into the hydrophobic part of the monolayer, which was confirmed with polarization-modulated infrared reflection–absorption spectroscopy (PM-IRRAS). Brewster angle microscopy (BAM) images showed that ibuprofen prevents the formation of large domains of DPPC. The pharmacological action should occur primarily with penetration of ibuprofen via electrically neutral phospholipid headgroups of the membrane.

Assessment of variance components in nonlinear mixed-effects elliptical models

The issue of assessing variance components is essential in deciding on the inclusion of random effects in the context of mixed models. In this work we discuss this problem by supposing nonlinear elliptical models for correlated data by using the score-type test proposed in Silvapulle and Silvapulle (1995). Being asymptotically equivalent to the likelihood ratio test and only requiring the estimation under the null hypothesis, this test provides a fairly easy computable alternative for assessing one-sided hypotheses in the context of the marginal model. Taking into account the possible non-normal distribution, we assume that the joint distribution of the response variable and the random effects lies in the elliptical class, which includes light-tailed and heavy-tailed distributions such as Student-t, power exponential, logistic, generalized Student-t, generalized logistic, contaminated normal, and the normal itself, among others. We compare the sensitivity of the score-type test under normal, Student-t and power exponential models for the kinetics data set discussed in Vonesh and Carter (1992) and fitted using the model presented in Russo et al. (2009). Also, a simulation study is performed to analyze the consequences of the kurtosis misspecification.

Beneficial effects of Anadenanthera colubrina (Vell.) Brenan extract on the inflammatory and nociceptive responses in rodent models

Ethnopharmacological relevance:Anadenantheracolubrina (Vell.) Brenan,popularlyknownas “angico”, is a plantthathasbeenwidelyusedinfolkmedicineduetoitsanti-inflammatory property.Toevaluatethe pharmacological activitiesofthisplant,studieswereperformedonitsantinociceptiveandanti- inflammatoryproperties. Materials andmethods: The AEof Anadenantheracolubrina, madefromthebark,wasusedinrodentsvia oral route(p.o.),at100,200,and400mg/kginclassicalmodelsofnociception(aceticacid-induced writhing andhot-platetest)andinflammation evokedbycarrageenan(e.g.,pawedema,peritonitis,and synovitis). Results: The aceticacid-inducedabdominalwrithesinmiceweresignificantly reduced(Po0.001)by oral treatmentwiththeextract(100,200,and400mg/kg),buttheextractdidnotsignificantly increase the latencyinthenociceptivehot-platetest. Anadenantheracolubrina aqueousextractreduced significantly theedemaand,besides,diminishedthemieloperoxidaseactivity(200and400mg/kg, Po0.01).Thecarrageenan-inducedperitonitiswassignificantly reduced(Po0.05) bytheaqueous extractat100,200,and400mg/kg.Theaqueousextract(200mg/kg)reducesthesynovialleukocyte infiltration oncarrageenan-inducedsynovitisinrats(Po0.01),butfailedtosignificantly affectjoint swelling andimpairedmobility. Conclusions: Weshowforthe first timethattheanti-inflammatory andperipheralantinociceptive activities of Anadenantheracolubrina are consistent,atleastinpart,withtheuseofthisplantinpopular medicine practices.

Effects of abiotic factors on growth and chemical defenses in cultivated clones of Laurencia dendroidea J. Agardh (Ceramiales, Rhodophyta)

Laurencia dendroidea shows high inter- and intrapopulation variability in the amount of the sesquiterpene elatol, caused by genetic variation as well as environmental factors. To test the independent effect of physical and nutritional conditions, the growth and the levels of elatol in L. dendroidea clones were evaluated under different conditions of temperature, salinity, irradiance, and culture medium in the laboratory. Growth of L. dendroidea was clearly affected by all these factors, but elatol levels were influenced only by temperature and salinity. Better conditions for growth did not produce a similar effect on elatol production in L. dendroidea, contradicting the carbon/nutrient balance and growth/differentiation balance models. On the contrary, severe conditions of temperature and salinity promoted a decrease in elatol levels, as predicted by the environmental stress model. Our results using clones indicated that abiotic factors clearly take part in fostering chemical variations observed in natural populations, in addition to genetic factors, and can promote differential susceptibility of plant specimens to natural enemies.

Inhibition of iNOS induces antidepressant-like effects in mice: Pharmacological and genetic evidence

Recent evidence has suggested that systemic administration of non-selective NOS inhibitors induces antidepressant-like effects in animal models. However, the precise involvement of the different NOS isoforms (neuronal-nNOS and inducible-iNOS) in these effects has not been clearly defined yet. Considering that mediators of the inflammatory response, that are able to induce iNOS expression, can be increased by exposure to stress, the aim of the present study was to investigate iNOS involvement in stress-induced behavioral consequences in the forced swimming test (FST), an animal model sensitive to antidepressant drugs. Therefore, we investigated the effects induced by systemic injection of aminoguanidine (preferential iNOS inhibitor), 1400W (selective iNOS inhibitor) or n-propyl-L-arginine (NPA, selective nNOS inhibitor) in mice submitted to the FST. We also investigated the behavior of mice with genetic deletion of iNOS (knockout) submitted to the FST. Aminoguanidine significantly decreased the immobility time (IT) in the FST. 1400W but not NPA, when administered at equivalent doses considering the magnitude of their Ki values for iNOS and nNOS, respectively, reduced the IT, thus suggesting that aminoguanidine-induced effects would be due to selective iNOS inhibition. Similarly, iNOS KO presented decreased IT in the FST when compared to wild-type mice. These results are the first to show that selective inhibition of iNOS or its knockdown induces antidepressant-like effects, therefore suggesting that iNOS-mediated NO synthesis is involved in the modulation of stress-induced behavioral consequences. Moreover, they further support NO involvement in the neurobiology of depression. This article is part of a Special Issue entitled 'Anxiety and Depression'. (C) 2011 Elsevier Ltd. All rights reserved.

Effects of pregabalin on behavioral alterations induced by ketamine in rats

Objective: The aim of this study is to investigate the effects of pregabalin on the behavior of rats under the influence of ketamine, an NMDA receptor antagonist that mimics the symptoms of schizophrenia. Methods: Rats were injected with saline or 25 mg/kg ketamine intraperitoneally. After that, behavior modifications were investigated by the evaluation of stereotypy and hyperlocomotion, after treating rats with pregabalin (at doses of 30 mg/kg or 100 mg/kg) or placebo (saline solution). Results: The administration of pregabalin reduced ketamine-induced hyperlocomotion. However, neither doses of pregabalin had a significant effect on ketamine-induced stereotypy. Conclusion: This is the first study to investigate the effects of pregabalin using an animal model of psychosis. Furthermore, our results indicate that behavioral changes induced by ketamine in rats can be reversed with the use of pregabalin, suggesting its potential to treat psychotic symptoms.

Bone marrow cells of swine: collection and separation

Bone marrow is a source of stem cells for greater and easier access, which is widely studied as a provider of hematopoietic and mesenchymal cells for various purposes, mainly therapeutic by the advances in research involving cell therapy. The swine is an animal species commonly used in the pursuit of development of experimental models. Thus, this study aimed to standardize protocol for collection and separation of bone marrow in swines, since this species is widely used as experimental models for various diseases. Twelve animals were used, which underwent bone marrow puncture with access from the iliac crest and cell separation by density gradient followed by a viability test with an average of 98% of viable cells. Given our results, we can ensure the swine as an excellent model for obtaining and isolation of mononuclear cells from bone marrow, stimulating several studies addressing the field of cell therapy. Microsc. Res. Tech., 2012. (C) 2012 Wiley Periodicals, Inc.

Effects of selective bile duct ligation on liver parenchyma in young animals: histologic and molecular evaluations

Background/Purpose: The mechanisms of increased collagen production and liver parenchyma fibrosis are poorly understood. These phenomena are observed mainly in children with biliary obstruction (BO), and in a great number of patients, the evolution to biliary cirrhosis and hepatic failure leads to the need for liver transplantation before adolescence. However, pediatric liver transplantation presents with biliary complications in 20% to 30% of cases in the postoperative period. Intra-or extrahepatic stenosis of bile ducts is frequent and may lead to secondary biliary cirrhosis and the need for retransplantation. It is unknown whether biliary stenosis involving isolated segments or lobes may affect the adjacent nonobstructed lobes by paracrine or endocrine means, leading to fibrosis in this parenchyma. Therefore, the present study aimed to create an experimental model of selective biliary duct ligation in young animals with a subsequent evaluation of the histologic and molecular alterations in liver parenchyma of the obstructed and nonobstructed lobes. Methods: After a pilot study to standardize the surgical procedures, weaning rats underwent ligation of the bile ducts of the median, left lateral, and caudate liver lobes. The bile duct of the right lateral lobe was kept intact. To avoid intrahepatic biliary duct collaterals neoformation, the parenchymal connection between the right lateral and median lobes was clamped. The animals were divided into groups according to the time of death: 1, 2, 3, 4, and 8 weeks after surgical procedure. After death, the median and left lateral lobes (with BO) and the right lateral lobe (without BO [NBO]) were harvested separately. A group of 8 healthy nonoperated on animals served as controls. Liver tissues were subjected to histologic evaluation and quantification of the ductular proliferation and of the portal fibrosis. The expressions of smooth muscle alpha-actin (alpha-SMA), desmin, and transforming growth factor beta 1 genes were studied by molecular analyses (semiquantitative reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction, a quantitative method). Results: Histologic analyses revealed the occurrence of ductular proliferation and collagen formation in the portal spaces of both BO and NBO lobes. These phenomena were observed later in NBO than BO. Bile duct density significantly increased 1 week after duct ligation; it decreased after 2 and 3 weeks and then increased again after 4 and 8 weeks in both BO and NBO lobes. The portal space collagen area increased after 2 weeks in both BO and NBO lobes. After 3 weeks, collagen deposition in BO was even higher, and in NBO, the collagen area started decreasing after 2 weeks. Molecular analyses revealed increased expression of the alpha-SMA gene in both BO and NBO lobes. The semiquantitative and quantitative methods showed concordant results. Conclusions: The ligation of a duct responsible for biliary drainage of the liver lobe promoted alterations in the parenchyma and in the adjacent nonobstructed parenchyma by paracrine and/or endocrine means. This was supported by histologic findings and increased expression of alpha-SMA, a protein related to hepatic fibrogenesis. (C) 2012 Elsevier Inc. All rights reserved.

Reducing the parameter space for unparticle-inspired models using white dwarf masses

Based on astrophysical constraints derived from Chandrasekhar's mass limit for white dwarfs, we study the effects of the model on the parameters of unparticle-inspired gravity, on scales Lambda(U) > 1 TeV and d(U) approximate to 1.

Using occupancy models to investigate space partitioning between two sympatric large predators, the jaguar and puma in central Brazil

Coexistence of sympatric species is mediated by resource partitioning. Pumas occur sympatrically with jaguars throughout most of the jaguar's range but few studies have investigated space partitioning between both species. Here, camera trapping and occupancy models accounting for imperfect detection were employed in a Bayesian framework to investigate space partitioning between the jaguar and puma in Emas National Park (ENP), central Brazil. Jaguars were estimated to occupy 54.1% and pumas 39.3% of the sample sites. Jaguar occupancy was negatively correlated with distance to water and positively correlated with the amount of dense habitat surrounding the camera trap. Puma occupancy only showed a weak negative correlation with distance to water and with jaguar presence. Both species were less often present at the same site than expected under independent distributions. Jaguars had a significantly higher detection probability at cameras on roads than at off-road locations. For pumas, detection was similar on and off-road. Results indicate that both differences in habitat use and active avoidance shape space partitioning between jaguars and pumas in ENP. Considering its size, the jaguar is likely the competitively dominant of the two species. Owing to its habitat preferences, suitable jaguar habitat outside the park is probably sparse. Consequently, the jaguar population is likely largely confined to the park, while the puma population is known to extend into ENP's surroundings. (C) 2011 Deutsche Gesellschaft fur Saugetierkunde. Published by Elsevier GmbH. All rights reserved.

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increased the percentage of HT29 cells in the G(0)/G(1) phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.

Homogeneity assessment of a station climate series (1933-2005) in the Metropolitan Area of Sao Paulo: instruments change and urbanization effects

This work assessed homogeneity of the Institute of Astronomy, Geophysics and Atmospheric Sciences (IAG) weather station climate series, using various statistical techniques. The record from this target station is one of the longest in Brazil, having commenced in 1933 with observations of precipitation, and temperatures and other variables later in 1936. Thus, it is one of the few stations in Brazil with enough data for long-term climate variability and climate change studies. There is, however, a possibility that its data may have been contaminated by some artifacts over time. Admittedly, there was an intervention on the observations in 1958, with the replacement of instruments, for which the size of impact has not been yet evaluated. The station transformed in the course of time from rural to urban, and this may also have influenced homogeneity of the observations and makes the station less representative for climate studies over larger spatial scales. Homogeneity of the target station was assessed applying both absolute, or single station tests, and tests relatively to regional climate, in annual scale, regarding daily precipitation, relative humidity, maximum (TMax), minimum (TMin), and wet bulb temperatures. Among these quantities, only precipitation does not exhibit any inhomogeneity. A clear signal of change of instruments in 1958 was detected in the TMax and relative humidity data, the latter certainly because of its strong dependence on temperature. This signal is not very clear in TMin, but it presents non-climatic discontinuities around 1953 and around 1970. A significant homogeneity break is found around 1990 for TMax and wet bulb temperature. The discontinuities detected after 1958 may have been caused by urbanization, as the observed warming trend in the station is considerably greater than that corresponding to regional climate.

Effects of diazepam on BOLD activation during the processing of aversive faces

This study aimed to measure, using fMRI, the effect of diazepam on the haemodynamic response to emotional faces. Twelve healthy male volunteers (mean age = 24.83 +/- 3.16 years), were evaluated in a randomized, balanced-order, double-blind, placebo-controlled crossover design. Diazepam (10 mg) or placebo was given 1 h before the neuroimaging acquisition. In a blocked design covert face emotional task, subjects were presented with neutral (A) and aversive (B) (angry or fearful) faces. Participants were also submitted to an explicit emotional face recognition task, and subjective anxiety was evaluated throughout the procedures. Diazepam attenuated the activation of right amygdala and right orbitofrontal cortex and enhanced the activation of right anterior cingulate cortex (ACC) to fearful faces. In contrast, diazepam enhanced the activation of posterior left insula and attenuated the activation of bilateral ACC to angry faces. In the behavioural task, diazepam impaired the recognition of fear in female faces. Under the action of diazepam, volunteers were less anxious at the end of the experimental session. These results suggest that benzodiazepines can differentially modulate brain activation to aversive stimuli, depending on the stimulus features and indicate a role of amygdala and insula in the anxiolytic action of benzodiazepines.

Effects of the antimycobacterial compound 2-phenoxy-1-phenylethanone on rat hepatocytes and formation of metabolites

Context: Neolignans are usually dimers formed by oxidative coupling of allyl and propenyl phenols, and the neolignan analogue, 2-phenoxy-1-phenylethanone (LS-2) is a promising antimycobacterial compound showing very weak cytotoxicity in mammalian cells and lack of acute toxicity in murine models. Objectives: To investigate the mechanism of action of LS-2 in rat hepatocytes by evaluating the activity levels of enzymes related to oxidation status and drug-metabolizing activity. Materials and methods: Hepatocytes were treated with LS-2 from 0.05 up to 1 mM, for 24 and 48 h, and reduced glutathione (GSH), lipid peroxidation and cytochrome P450 enzyme (CYP450) activity were assayed. A homologous series of phenoxazone ethers were used as substrates to measure the enzymatic profile. The biotransformation of LS-2 was studied in hepatocytes by gas chromatography-mass spectrometry (GC-MS) for detection and analysis of possible metabolites. Results: Hepatocytes treated with LS-2 up to 1 mM for 24 or 48 h did not induce the formation of GSH and lipid peroxidation. O-Dealkylation activities of the isoenzymes CYP4501A1, CYP4501A2, CYP4502B1 and CYP4502B2 were also not detected in the hepatocytes treated with LS-2 for 24 or 48 h. Discussion and conclusion: The results indicate that LS-2 or its two detected metabolites, 2-phenoxy-1-phenylethanol and 2,4-(2-hydroxy-2-phenylethoxy) phenol, are not cytotoxic to rat hepatocytes. These compounds maintain a balance between the production of pro-oxidant agents and their respective antioxidant systems. The data show that enzymes related to oxidation status and drug-metabolizing activities are not involved in the mechanism of action of LS-2.

H-1 low- and high-field NMR study of the effects of plasma treatment on the oil and water fractions in crude heavy oil

The chemical and physical properties of a Brazilian heavy oil submitted to plasma treatment were investigated by H-1 low-and high-field nuclear magnetic resonance (NMR) combined to the characterization of rheological properties, thermogravimetry and measurement of basic sediments and water (BSW) content. The crude oil was treated in a dielectric barrier discharge plasma reactor, using natural gas, CO2 or H-2 as working gas. The results indicated a large drop in the water content of the plasma-treated samples as compared to the crude oil, giving rise to a reduction in the viscosity. No significant chemical change was produced in the oil portion itself, as observed by H-1 NMR. The water contents determined by H-1 low-field NMR analyses agreed well with those obtained by BSW, indicating the low-field NMR methods as a useful tool for following the effects of plasma treatments on heavy oils, allowing the separation of the effects caused on the water and oil fractions. (C) 2011 Elsevier Ltd. All rights reserved.