Post-resistance exercise hypotension in spontaneously hypertensive rats is mediated by nitric oxide

1. Postexercise hypotension (PEH) plays an important role in the non-pharmacological treatment of hypertension. It is characterized by a decrease in blood pressure (BP) after a single bout of exercise in relation to pre-exercise levels. 2. The present study investigated the effect of a single session of resistance exercise, as well as the effect of nitric oxide (NO) and the autonomic nervous system (ANS), in PEH in spontaneously hypertensive rats (SHR). 3. Catheters were inserted into the left carotid artery and left jugular vein of male SHR (n = 37) for the purpose of measuring BP or heart rate (HR) and drug or vehicle administration, respectively. Haemodynamic measurements were made before and after acute resistance exercise. The roles of NO and the ANS were investigated by using N(G)-nitro-L-arginine methyl ester (L-NAME; 15 mg/kg, i.v.) and hexamethonium (20 mg/kg, i.v.) after a session of acute resistance exercise. 4. Acute resistance exercise promoted a pronounced reduction in systolic and diastolic BP (-37 +/- 1 and -8 +/- 1 mmHg, respectively; P < 0.05), which was suppressed after treatment with L-NAME. The reduction in systolic BP caused by exercise (-37 +/- 1 mmHg) was not altered by the administration of hexamethonium (-38 +/- 2 mmHg; P > 0.05). After exercise, the decrease in diastolic BP was greater with hexamethonium (-26 +/- 1 mmHg; P < 0.05) compared with the decrease caused by exercise alone. 5. The results suggest that acute resistance exercise has an important hypotensive effect on SHR and that NO plays a crucial role in this response.

Motor perseveration during an ""A not B"" task in children with intellectual disabilities

This study was designed to identify perseverative reaching tendencies in children with intellectual disabilities (ID), over a period of 1 year, by using a version of the Piagetian ""A not B"" task modified by Smith, Thelen, Titzer, and McLin (1999). Nine children (4.8 years old at the beginning of the study) with intellectual disabilities (ID) (eight with mild ID; one with moderate ID) were assessed every 3 months for approximately 1 year, totaling four assessments. The results indicate that in a majority of the cases perseveration was resilient, and that the visual system decoupled from the reaching, especially towards the later assessment periods at the end of the year. Across assessment periods variability seemed to increase in each trial (A1 through B2) for reached target. These individuals, vulnerable to distraction and attention and to short-term memory deficits, are easily locked into rigid modes of motor habits. They are susceptible to perseveration while performing simple task contexts that are typically designed for 10- to 12-month-old, normally-developing infants, therefore creating strong confinements to stable, rigid modes of elementary forms of behavior. (C) 2009 Elsevier B.V. All rights reserved.

Lifecycle assessment of fuel ethanol from sugarcane in Brazil

This paper presents the lifecycle assessment (LCA) of fuel ethanol, as 100% of the vehicle fuel, from sugarcane in Brazil. The functional unit is 10,000 km run in an urban area by a car with a 1,600-cm(3) engine running on fuel hydrated ethanol, and the resulting reference flow is 1,000 kg of ethanol. The product system includes agricultural and industrial activities, distribution, cogeneration of electricity and steam, ethanol use during car driving, and industrial by-products recycling to irrigate sugarcane fields. The use of sugarcane by the ethanol agribusiness is one of the foremost financial resources for the economy of the Brazilian rural area, which occupies extensive areas and provides far-reaching potentials for renewable fuel production. But, there are environmental impacts during the fuel ethanol lifecycle, which this paper intents to analyze, including addressing the main activities responsible for such impacts and indicating some suggestions to minimize the impacts. This study is classified as an applied quantitative research, and the technical procedure to achieve the exploratory goal is based on bibliographic revision, documental research, primary data collection, and study cases at sugarcane farms and fuel ethanol industries in the northeast of SA o pound Paulo State, Brazil. The methodological structure for this LCA study is in agreement with the International Standardization Organization, and the method used is the Environmental Design of Industrial Products. The lifecycle impact assessment (LCIA) covers the following emission-related impact categories: global warming, ozone formation, acidification, nutrient enrichment, ecotoxicity, and human toxicity. The results of the fuel ethanol LCI demonstrate that even though alcohol is considered a renewable fuel because it comes from biomass (sugarcane), it uses a high quantity and diversity of nonrenewable resources over its lifecycle. The input of renewable resources is also high mainly because of the water consumption in the industrial phases, due to the sugarcane washing process. During the lifecycle of alcohol, there is a surplus of electric energy due to the cogeneration activity. Another focus point is the quantity of emissions to the atmosphere and the diversity of the substances emitted. Harvesting is the unit process that contributes most to global warming. For photochemical ozone formation, harvesting is also the activity with the strongest contributions due to the burning in harvesting and the emissions from using diesel fuel. The acidification impact potential is mostly due to the NOx emitted by the combustion of ethanol during use, on account of the sulfuric acid use in the industrial process and because of the NOx emitted by the burning in harvesting. The main consequence of the intensive use of fertilizers to the field is the high nutrient enrichment impact potential associated with this activity. The main contributions to the ecotoxicity impact potential come from chemical applications during crop growth. The activity that presents the highest impact potential for human toxicity (HT) via air and via soil is harvesting. Via water, HT potential is high in harvesting due to lubricant use on the machines. The normalization results indicate that nutrient enrichment, acidification, and human toxicity via air and via water are the most significant impact potentials for the lifecycle of fuel ethanol. The fuel ethanol lifecycle contributes negatively to all the impact potentials analyzed: global warming, ozone formation, acidification, nutrient enrichment, ecotoxicity, and human toxicity. Concerning energy consumption, it consumes less energy than its own production largely because of the electricity cogeneration system, but this process is highly dependent on water. The main causes for the biggest impact potential indicated by the normalization is the nutrient application, the burning in harvesting and the use of diesel fuel. The recommendations for the ethanol lifecycle are: harvesting the sugarcane without burning; more environmentally benign agricultural practices; renewable fuel rather than diesel; not washing sugarcane and implementing water recycling systems during the industrial processing; and improving the system of gases emissions control during the use of ethanol in cars, mainly for NOx. Other studies on the fuel ethanol from sugarcane may analyze in more details the social aspects, the biodiversity, and the land use impact.

Experimental investigation on the dynamic behaviour of a railway vehicle travelling through a turnout

Track critical locations with respect to the railway vehicle safety are the passages through the turnouts. The purpose of this investigation is to evaluate the safety of a railway vehicle crossing a turnout. In this study, the topography of a track turnout lay-out has been experimentally measured, and its geometric properties were synthesised. Results show that a constant wavelength vehicle oscillation occurs on the switches in the turnout and that the maximum lateral force at 65 km/h is almost 65% greater than those at low speeds (under 30 km/h).

Instrumented indentation testing of an epoxy adhesive used in automobile body assembling

Instrumented indentation has been used to investigate the mechanical properties of BETAMATE 1496 (R) Epoxy adhesive. The properties of the adhesive were analyzed by measuring its hardness and its Young`s modulus in samples extracted from six different positions of the front door of a commercial passenger vehicle in two phases of processing: after application of the adhesive in the door assembling (""pre-cured"" state) and after final cure in the painting oven (""cured"" state). Special attention was given to setting the optimal parameters (""creep"" time and unloading time step) for the instrumented indentation testing for the present application. Young`s modulus values around 1.1 +/- 0.2 GPa and hardness values around 0.15 +/- 0.05 GPa were obtained for all samples, irrespective of the variation of the indentation parameters in the testing procedure and of the relative position of the adhesive in the door frame in both states. (C) 2008 Elsevier Ltd. All rights reserved.

Effects of 7-Epiclusianone on Streptococcus mutans and Caries Development in Rats

The aim of this study was to evaluate the effects of 7-epiclusianone (7-epi) on specific virulence attributes of Streptococcus mutans in vitro and on development of dental caries in vivo. 7-Epi was obtained and purified from fruits of Rheedia brasiliensis. We investigated its influence on surface-adsorbed glucosyltransferase (Gtf) B activity, acid production, and viability of S. mutans in biofilms, as well as on caries development using a rodent model. 7-Epi (100 mu g/mL) significantly reduced the activity of surface-adsorbed GtfB (up to 48.0 +/- 1.8 of inhibition at 100 mu g/mL) and glyco-lytic pH-drop by S. mutans in biofilms (125 and 250 mu g/mL) (vs. vehicle control, p < 0.05). In contrast, the test compound did not significantly affect the bacterial viability when compared to vehicle control (15% ethanol, p > 0.05). Wistar rats treated topically with 7-epi (twice daily, 60-s exposure) showed significantly smaller number of and less severe smooth-and sulcal-surface carious lesions (p < 0.05), without reducing the S. mutans viable population from the animals` dental biofilms. In conclusion, the natural compound 7-epiclusianone may be a potentially novel pharmacological agent to prevent and control dental caries disease.

Endophytic population of Pantoea agglomerans in citrus plants and development of a cloning vector for endophytes

Harmless bacteria inhabiting inner plant tissues are termed endophytes. Population fluctuations in the endophytic bacterium Pantoea agglomerans associated with two species of field cultured citrus plants were monitored over a two-year period. The results demonstrated that populations of P. agglomerans fluctuated in Citrus reticulata but not C. sinensis. A cryptic plasmid pPA3.0 (2.9 kb) was identified in 35 out of 44 endophytic isolates of P. agglomerans and was subsequently sequenced. The origins of replication were identified and nine out of 18 open reading frames (ORFs) revealed homology with described proteins. Notably, two ORFs were related to cellular transport systems and plasmid maintenance. Plasmid pPA3.0 was cloned and the gfp gene inserted to generate the pPAGFP vector. The vector was introduced into P. agglomerans isolates and revealed stability was dependent on the isolate genotype, ninety-percent stability values were reached after 60 hours of bacterial cultivation in most evaluated isolates. In order to definitively establish P. agglomerans as an endophyte, the non-transformed bacterium was reintroduced into in vitro cultivated seedlings and the density of inner tissue colonization in inoculated plants was estimated by bacterium re-isolation, while the tissue niches preferred by the bacterium were investigated by scanning electronic microscopy (SEM). Cells from P. agglomerans (strain ARB18) at similar densities were re-isolated from roots, stems and leaves and colonization of parenchyma and xylem tissues were observed. Data suggested that P. agglomerans is a ubiquitous citrus endophyte harboring cryptic plasmids. These characteristics suggest the potential to use the bacterium as a vehicle to introduce new genes in host plants via endophytic bacterial transformation.

Paclitaxel associated with cholesterol-rich nanoemulsions promotes atherosclerosis regression in the rabbit

A cholesterol-rich nanoemulsion (LDE) that resembles LDL binds to the LDL receptors and after injection into the blood stream may concentrate in cells with LDL receptor overexpression, as occurs in neoplasias and other proliferative processes. Thus, LDE can be used as vehicle to target drugs against those cells. The current study was designed to verify in rabbits whether LDE concentrates in the lesioned rabbit artery and whether a paclitaxel derivative, paclitaxel oleate, associated to LDE could reduce the atherosclerotic lesions. Sixteen male New Zealand rabbits were fed a 1% cholesterol diet for 60 days. Starting from day 30 under cholesterol feeding, eight animals were treated with four weekly intravenous injections of LDE-paclitaxel (4 mg/kg) and eight with four weekly intravenous saline solution injections for additional 30 days. On day 60, the animals were sacrificed for analysis. The uptake of LDE labeled with [C-14]-cholesteryl oleate by the aortic arch of cholesterol-fed rabbits was twice as much that observed in animals fed only regular chow. LDE-paclitaxel reduced the lesion areas of cholesterol-fed animals by 60% and intima-media ratio fourfold and inhibited the macrophage migration and the smooth muscle cell proliferation and invasion of the intima. LDE-paclitaxel treatment had no toxicity. In conclusion, LDE-paclitaxel produced pronounced atherosclerosis regression without toxicity and has shown remarkable potential in cardiovascular therapeutics. (c) 2008 Published by Elsevier Ireland Ltd.

Spectrophotometric determination of fenoterol hydrobromide in pharmaceutical preparations

A simple spectrophotometric method has been developed,for the determination of fenoterol hydrobromide (FH) in tablets, drops and syrup, as the only active principle and associated with ibuprofen. The method is based on the oxidative coupling reaction of the FH with 3-methyl-2-benzothiazolinone hydrazone (MBTH) and ceric sulphate as oxidant reagent. The mixture of the drug, MBTH and ceric sulfate, in acid medium, produces a red brown color compound, with absorption maximum at 475 nm. The calibration curve was linear over a concentration range from 3.0 to 12.0 mu g/mL, with correlation coefficient of 0.9998. The different experimental parameters affecting the development and stability of the color compound were carefully studied and optimized. The method was applied successfully to assay FH in dosage forms and simulated samples. The coefficient of variation was from 0.25 % to 0.82 % and average recoveries of the standard from 98 % to 102 %. The excipients (tablets and drops) did not interfere in the analysis and the results showed that method can be used for determination of the FH isolated or associated with ibuprofen with precision, accuracy and specificity. In case of syrup, the interference in the analysis suggests a possible reaction between vehicle components with MBTH.

Effects of chlorogenic acid on neutrophil locomotion functions in response to inflammatory stimulus

Aim of the study: Species of Lychnophora are used in Brazilian folk medicine as analgesic and anti-inflammatory agents. Chlorogenic acid (CGA) and their analogues are important components of polar extracts of these species, as well in several European and Asian medicinal plants. Some of these phenolic compounds display anti-inflammatory effects. In this paper we report the isolation of CGA from Lychnophora salicifolia and its effects on functions involved in neutrophils locomotion. Materials and methods: LC-MS(n) data confirmed the presence of CGA in the plant. Actions of CGA were investigated on neutrophils obtained from peritoneal cavity of Wistar rats (4h after 1% oyster glycogen solution injection; 10 ml), and incubated with vehicle or with 50, 100 or 1000 mu M CGA in presence of lipopolysaccharide from Escherichia coil (LPS, 5 mu g/ml). Nitric oxide (NO; Griess reaction); prostaglandin E(2) (PGE(2)), interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha [TNF-alpha; enzyme-linked immunosorbent assay (EIA)]; protein (flow cytometry) and gene (RT-PCR) expression of L-selectin, beta(2)integrin and platelet-endothelial cell adhesion molecule-1 (PECAM-1) were quantified. In vitro neutrophil adhesion to primary culture of microvascular endothelial cell (PMEC) and neutrophil migration in response to formyl-methionil-leucil-phenilalanine (fMLP, 10(-8)M, Boyden chamber) was determined. Results: CGA treatment did not modify the secretion of inflammatory mediators, but inhibited L-selectin cleavage and reduced beta(2) integrin, independently from its mRNA synthesis, and reduced membrane PECAM-1 expression: inhibited neutrophil adhesion and neutrophil migration induced by fMLP. Conclusions: Based on these findings, we highlight the direct inhibitory actions of CGA on adhesive and locomotion properties of neutrophils, which may contribute to its anti-inflammatory effects and help to explain the use of Lychnophora salicifolia as an anti-inflammatory agent. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Lercanidipine reduces matrix metalloproteinase-2 activity and reverses vascular dysfunction in renovascular hypertensive rats

Increased expression/activity of matrix metalloproteinases (MMPs), especially MMP-2, plays a role in the vascular alterations induced by hypertension, and increased oxidative stress is a major factor activating MMPs. Here, we hypothesized that lercanidipine, a calcium channel blocker, could attenuate the increases in oxidative stress and MMP-2 expression/activity in the two-kidney, one-clip (2K-1C) hypertensive rats. Sham-operated or 2K-1C hypertension rats were treated with lercanidipine 2.5 mg/kg/day (or vehicle) starting three weeks after hypertension was induced. Systolic blood pressure was monitored weekly. After five weeks of treatment, aortic rings were isolated to assess endothelium-dependent and independent relaxations. Quantitative morphometry of structural changes in the aortic wall were studied in hematoxylin/eosin sections. Aortic MMP-2 levels were determined by gelatin zymography. Aortic MMP-2/tissue inhibitor of metalloproteinases (TIMP)-2 mRNA levels were determined by quantitative real-time RT-PCR. Plasma thiobarbituric acid reactive substances concentrations were determined using a fluorometric method. Lercanidipine attenuated 2K-1C hypertension (224 12 versus 183 11 mm Hg in 2K-1C rats and 2K-1C + Lercandipine rats, respectively; P < 0.01) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Increased MMP-2 and Pro-MMP-2 levels were found in the aortas of 2K-1C rats (all P < 0.05). Lercandipine attenuated 2K-1C-induced increases in MMP-2 by more than 60% and blunted 2K-1C-induced increases in oxidative stress (both P < 0.001). While hypertension-induced significant aortic wall hypertrophy and approximately 9-fold increases in the ratio of MMP-2MMP-2 mRNA expression (both P < 0.05), lercandipine did not affect these changes. These results suggest that lercanidipine produces antihypertensive effects and reverses the endothelial dysfunction associated with 2K-1C hypertension, probably through mechanisms involving antioxidant effects leading to lower MMP-2 activation. (C) 2008 Elsevier B.V. All rights reserved.

Antioxidant treatment reduces matrix metalloproteinase-2-induced vascular changes in renovascular hypertension

Mounting evidence indicates that structural and functional vascular changes associated with two-kidney, one-clip (2K-1C) hypertension result, at least in part, from altered activity of matrix metalloproteinases (MMPs). Because MMPs are upregulated by increased formation of reactive oxygen species (ROS), we hypothesized that antioxidant approaches could attenuate the increases in MMP-2 expression/activity and the vascular dysfunction and remodeling associated with 2K-1C hypertension. Sham-operated or 2K-1C hypertensive rats were treated with tempol 18 mg/kg/day or apocyanin 25 mg/kg/day (or vehicle). Systolic blood pressure was monitored weekly. After 8 weeks of treatment, aortic rings were isolated to assess endothelium-dependent and -independent relaxation. Quantitative morphometry of structural changes in the aortic wall was studied in hematoxylin/eosin sections. Aortic and systemic ROS levels were measured using dihydroethidine and thiobarbituric acid-reactive substances, respectively. Aortic MMP-2 levels and activity were determined by gelatin and in situ zymography, fluorimetry, and immunohistochemistry. Tempol and apocyanin attenuated 2K-1C hypertension (181 +/- 20.8 and 192 +/- 17.6 mm Hg, respectively, versus 213 +/- 18 mm Hg in hypertensive controls; both p<0.05) and prevented the reduction in endothelium-dependent vasorelaxation found in 2K-1C rats. Tempol, but not apocyanin (p>0.05), prevented the vascular remodeling found in 2K-1C rats (all p<0.01). Tempol was more effective than apocyanin in attenuating hypertension-induced increases in oxidative stress (both p<0.05), MMP-2 levels, and MMP-2 activity in hypertensive rats (all p<0.05). Our results suggest that antioxidant approaches decrease MMP-2 upregulation and attenuate the vascular dysfunction and remodeling during 2K-1C hypertension. (C) 2009 Elsevier Inc. All rights reserved.

Photophysical studies and in vitro skin permeation/retention of Foscan (R)/nanoemulsion (NE) applicable to photodynamic therapy skin cancer treatment.

In this work we evaluated the photophysical and in vitro properties of Foscan (R), a second-generation photosensitizer drug (PS) widely used in systemic clinical protocols for cancer therapy based on Photodynamic Therapy (PDT). We employed biodegradable nanoemulsions (NE) as a colloidal vehicle of the oil/water (o/w) type focusing in topical administration of Foscan (R) and other photosensitizer drugs. This formulation was obtained and stabilized by the methodology described by Tabosa do Egito et al.,(30) based on the mixture of two phases: an aqueous solution and an organic medium consisting of nonionic surfactants and oil. The photodynamic potential of the drug incorporated into the NE was studied by steady-state and time-resolved spectroscopic techniques. We also analyzed the in vitro biological behavior carried out in mimetic biological environment protocols based on the animal model. After topical application in a skin animal model, we evaluated the Foscan (R)/NE diffusion flux into the skin layers (stratum corneum and epidermis + dermis) by classical procedures using Franz Diffusion cells. Our results showed that the photophysical properties of PS were maintained after its incorporation into the NE when compared with homogeneous organic medium. The in vitro assays enabled the determination of an adequate profile for the interaction of this system in the different skin layers, with an ideal time lag of 6 h after topical administration in the skin model. The Foscan (R) diffusion flux (J) was increased when this PS was incorporated into the NE, if compared with its flux in physiological medium. These parameters demonstrated that the NE can be potentially applied as a drug delivery system (DDS) for Foscan (R) in both in vitro and in vivo assays, as well as in future clinical applications involving topical skin cancer PDT.

In Vivo Evaluation of the Photoprotective Efficacy of O-1/W/O-2 Multiple Emulsions with Andiroba Oil (Carapa guianensis)

Stable multiple emulsions containing andiroba oil and sunscreen have been formulated. These were prepared using the two-step procedure. The formulations were characterized and their stability over the time was evaluated by centrifugation, macroscopic, and microscopic analyses, and rheological measurements. The photoprotective efficacy of the O/W and O1/W/O2 containing or not andiroba oil was evaluated by in vivo sun protection factor determination according to the FDA method. The formulations exhibited good stability during 30 days after preparation at different temperatures. These presented pseudoplastic flow behaviour and thixotropy. The increase of in vivo SPF value was not observed when andiroba oil was incorporated into emulsions containing ethylhexyl methoxycinnamate. These multiple emulsions can be utilized as an interesting topical vehicle.

O/W Nanoemulsion After 15 Years of Preparation: A Suitable Vehicle for Pharmaceutical and Cosmetic Applications

The application of nanoemulsions is due to have good stability, uniform spreading and enhance active penetration upon skin. Nanometer emulsions can be obtained by low-energy emulsification method. The required hydrophilic and lipophilic balance indicates the better balance of emulsifier for optimum system emulsification. Emulsion stability is evidently controlled for the properties of the adsorbed layer formed in the surface of its globules, know as potential zeta. The aim of this work was to evaluate the oil/water nanoemulsion of formulation obtained after 15 years of preparation. The results suggested that the nanoemulsion have performed stability for many years.