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In peripheral countries, the lack of adequate urban planning associated with natural dynamics intensifies the existing vulnerabilities of the environment, causing physical and material losses. Therefore, this research aims to discuss the potential use of Environmental Protection Areas as a tool to drive urban growth with a low-impact development, helping to mitigate urban floods and bringing nature into the city landscape. The municipality of Maricá, located in the metropolitan region of Rio de Janeiro, Brazil, is taken as a case study. The method proposed to drive the regional environmental planning and management can be described as a three-stage method coupled with the adapted SWOT Matrix, following: the diagnosis, the prognosis, and the action plan. This process points to the definition of a Hydrological Interest Area that would allow not only the restoration of local vegetation and a better interaction of the population with the watercourses, but also the recovery of areas that have been gradually impacted by the urban expansion. The method presented in this research allows its application in different urban contexts, once it has the objective of recognizing the strengths, weaknesses, opportunities, and threats to allow the elaboration of sustainable actions and guidelines.

Abstract Background Predicting protein contacts solely based on sequence information remains a challenging problem, despite the huge amount of sequence data at our disposal. Mutual Information (MI), an information theory measure, has been extensively employed and modified to identify residues within a protein (intra-protein) that are in contact. More recently MI and its variants have also been used in the prediction of contacts between proteins (inter-protein). Methods Here we assess the predictive power of MI and variants for domain-domain contact prediction. We test original MI and these variants, which are called MIp, MIc and ZNMI, on 40 domain-domain test cases containing 10,753 sequences. We also propose and evaluate two new versions of MI that consider triangles of residues and the physiochemical properties of the amino acids, respectively. Results We found that all versions of MI are skewed towards predicting surface residues. Since domain-domain contacts are on the surface of each domain, we considered only surface residues when attempting to predict contacts. Our analysis shows that MIc is the best current MI domain-domain contact predictor. At 20% recall MIc achieved a precision of 44.9% when only surface residues were considered. Our triangle and reduced alphabet variants of MI highlight the delicate trade-off between signal and noise in the use of MI for domain-domain contact prediction. We also examine a specific “successful” case study and demonstrate that here, when considering surface residues, even the most accurate domain-domain contact predictor, MIc, performs no better than random. Conclusions All tested variants of MI are skewed towards predicting surface residues. When considering surface residues only, we find MIc to be the best current MI domain-domain contact predictor. Its performance, however, is not as good as a non-MI based contact predictor, i-Patch. Additionally, the intra-protein contact prediction capabilities of MIc outperform its domain-domain contact prediction abilities.

Abstract Background Chronic hemodialysis patients are at higher risk for acquiring hepatitis C virus (HCV). The prevalence varies among different countries and hemodialysis centers. Although guidelines for a comprehensive infection control program exist, the nosocomial transmission still accounts for the new cases of infection. The aim of this study was analyze the follow up of newly acquired acute hepatitis C cases, during the period from January 2002 to May 2005, in the Hemodialysis Center, located in the Southwest region of Parana State, Brazil and to analyze the effectiveness of the measures to restrain the appearance of new cases of acute hepatitis C. Methods Patients were analyzed monthly with anti-HCV tests and ALT measurements. Patients with ALT elevations were monitored for possible acute hepatitis C. Results During this period, 32 new cases were identified with acute hepatitis C virus infection. Blood screening showed variable ALT levels preceding the anti-HCV seroconversion. HCV RNA viremia by PCR analysis was intermittently and even negative in some cases. Ten out of 32 patients received 1 mcg/kg dose of pegylated interferon alfa-2b treatment for 24 weeks. All dialysis personnel were re-trained to strictly follow the regulations and recommendations regarding infection control, proper methods to clean and disinfect equipment were reviewed and HCV-positive patients were isolated. Conclusion Laboratory tests results showed variable ALT preceding anti-HCV seroconversion and intermittent viremia. The applied recommendations contributed importantly to restrain the appearance of new cases of acute hepatitis C in this center and the last case was diagnosed in May 2004.

(1) Background: The goal of this study was to analyze the reliability and validity of the Portuguese version of the SARC-F in older adults. (2) Methods: A total of 100 participants (77.1 ± 7.36 years, 73% women) were included in the study. In a first phase, the Portuguese SARC-F was adapted following the standardized forward-backward translation procedure, and internal consistency as well as inter-rater and test-retest reliability of the Portuguese SARC-F were analyzed. Secondly, clinical validation was evaluated by comparing the SARC-F total score with five operational definitions of sarcopenia and with other sarcopenia-related measurements. Discriminant validity, with respect to low muscle mass and strength and physical function were analyzed. (3) Results: The Portuguese SAR-F showed acceptable internal consistency (Cronbach α = 0.82), excellent inter-rater reliability (total score), and substantial to excellent test-retest reliability (ICC = 0.891 for the total score). Specificity ranged from 72.5% (FNIH) to 73.4 (IGWS), and negative predictive values went from 91.8% (EWGSOP1) to 97.3% (FNIH), but low sensitivity and positive predictive value were observed. The Portuguese SARC-F showed a moderate ability to discriminate people with low muscle strength (AUC = 0.78) and gait speed (AUC = 0.89). (4) Conclusions: The Portuguese SARC-F is a valid and reliable tool for ruling out sarcopenia in community-dwelling older adults and can discriminate between people with low handgrip strength and gait speed.

The main objective of extreme value theory is essentially the estimation of quantities related to extreme events. One of its main issues has been the estimation of the extreme value index (EVI), a parameter directly related to the tail weight of the distribution. Here we deal with the semi-parametric estimation of the EVI, for heavy tails. A recent class of EVI-estimators, based on the Lehmer's mean-of-order p (L p ), which generalizes the arithmetic mean, is considered. An asymptotic comparison at optimal levels performed in previous works has revealed the competitiveness of this class of EVI-estimators. A large-scale Monte-Carlo simulation study for finite simulated samples has been here performed, showing the behaviour of L p , as a function of p . A bootstrap adaptive choice of ( k , p ) , where k is the number of upper order statistics used in the estimation, and a second algorithm based on a stability criterion are computationally studied and applied to simulated and real data., Competing Interests: No potential conflict of interest was reported by the authors., (© 2019 Informa UK Limited, trading as Taylor & Francis Group.)

Background: Developments in image reconstruction techniques for planar imaging, also known as enhanced planar processing (EPP), enable the possibility to reconstruct planar scintigraphic images with low count statistics, providing the opportunity to reduce image acquisition time. In this study, the performance of EPP for oncologic half-time bone scintigraphy images was evaluated., Methods: The EPP software was evaluated for different imaging conditions using standardized phantom experiments. Additionally, 51 patients with prostate and breast cancer were prospectively included and underwent bone scintigraphy using a standard and half-time protocol. Independent reading was performed on three image types (standard, half-time non-processed, and half-time EPP) by three observers, scoring the number and anatomical location of lesions, image quality, and diagnostic confidence by which the definitive diagnosis was made., Results: EPP images had improved contrast and lower noise levels compared to the non-processed half-time images. It was determined that EPP images acquired at double scan speed had similar image quality to the standard non-processed images. There was substantial agreement with respect to diagnosis and diagnostic confidence based on all three image types between the observers. Image quality in the EPP images was higher with respect to the non-processed half-time images, and was comparable to the standard images., Conclusions: Diagnostic confidence was not affected by reduction in image acquisition time. There was substantial agreement between all three observers with respect to the diagnosis provided in all three image types. Subjective and objective image quality improved when half-time images were processed with EPP software.

Introduction: Governments across Europe want to promote healthy and active aging, as a matter of both public health and economic sustainability. Designing policies focused on the most vulnerable groups requires information at the individual level. However, a measure of healthy and active aging at the individual level does not yet exist., Objectives: This paper develops the Selfie Aging Index (SAI), an individual-level index of healthy and active aging. The SAI is developed thinking about a tool that would allow each person to take a selfie of her aging status. Therefore, it is based entirely on self-assessed indicators. This paper also illustrates how the SAI may look like in practice., Methods: The SAI is based on the Biopsychosocial Assessment Model (MAB), a tool for the multidimensional assessment of older adults along three domains: biological, psychological, and social. Indicators are selected and their weights determined based on an ordered probit model that relates the MAB indicators to self-assessed health, which proxies healthy and active aging. The ordered probit model predicts the SAI based on the estimated parameters. Finally, predictions are rescaled to the 0-1 interval. Data for the SAI development come from the Study of the Aging Profiles of the Portuguese Population and the Survey of Health, Aging, and Retirement in Europe., Results: The selected indicators are BMI, having difficulties moving around indoors and performing the activities of daily living, feeling depressed, feeling nervous, lacking energy, time awareness score, marital status, having someone to confide in, education, type of job, exercise, and smoking status. The model also determines their weights., Conclusion: Results shed light on various factors that contribute significantly to healthy and active aging. Two examples are mental health and exercise, which deserve more attention from individuals themselves, health-care professionals, and public health policy. The SAI has the potential to put the individual at the center of the healthy and active aging discussion, contribute to patient empowerment, and promote patient-centered care. It can become a useful instrument to monitor healthy and active aging for different actors, including individuals themselves, health-care professionals, and policy makers.

In past studies conducted by our group, riparin I (rip I) isolated from the green fruit of Aniba riparia presented antianxiety effects in mice, while its analogs rip II and III showed anxiolytic and antidepressant-like actions. This time around, we investigated a possible antidepressant activity of rip I using the forced swimming test (FST) and tail suspension test (TST) as predictive tests for antidepressant activity in rodents. In addition, the involvement of the monoaminergic system in this effect was also assessed. rip I was acutely administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at doses of 25 and 50 mg/kg. Results showed that rip I at both tested doses and administration routes produced a significant decrease in immobility time in FST and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an α₁ -adrenoceptor antagonist), yohimbine (1 mg/kg, i.p., an α₂ -adrenoceptor antagonist), SCH23390 (15 μg/kg, i.p., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p-chlorophenylalanine (100 mg/kg, an inhibitor of serotonin synthesis) or ritanserin (4 mg/kg, a serotonin 5-HT2(A)/2(C) receptor antagonist) blocked the anti-immobility effects elicited by rip I (50 mg/kg, p.o.) in the FST. Taken together, results indicate that rip I produces significant antidepressant-like activity in the FST and TST, and this effect seems to be dependent on its interaction with noradrenergic, dopaminergic and serotonergic systems., (© 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.)

Riparin II (RipII), an alkamide isolated from the green fruit of Aniba riparia, was tested in the various animal models of inflammation to investigate its anti-inflammatory activity. Male Wistar rats (180-240g) were treated with RipII by gavage at doses 25 or 50mg/kg, before initiating the inflammatory responses. The tests used were paw edema induced by carrageenan, dextran, histamine or serotonin; peritonitis induced by carrageenan and fMLP, as well as the measurement of MPO activity, TNF-α and Il-1β amount in the peritoneal fluid. In the animal models of carrageenan and dextran-induced paw edema, the animals treated with RipII showed lower edema than those of the control group. Treatment with RipII also reduced the paw edema induced by histamine but not serotonin. In the carrageenan-induced peritonitis model, treatment with RipII reduced leukocyte migration, the MPO activity and the amount of TNF-α and IL-1β in the peritoneal fluid. In summary, these results indicate that RipII has an anti-inflammatory activity in chemical models of acute inflammation. RipII might be directly or indirectly inhibiting the activity, production or release of pro-inflammatory mediators involved in the generation of the pain associated with inflammation., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Dehydrodieugenol, known as bis-eugenol, is a eugenol ortho dimer, and both compounds were able to exhibit anti-inflammatory and antioxidant activities in previous studies. Furthermore, eugenol showed antidepressant-like effect; however, the biological actions of bis-eugenol on experimental models for screening antidepressant activity are still unknown. The present study investigated a possible antidepressant-like activity of bis-eugenol in the forced swimming test (FST) and tail suspension test (TST) in mice and the involvement in the monoaminergic system in this effect. In addition, a neurochemical analysis on brain monoamines of mice acutely treated with bis-eugenol was also conducted. Bis-eugenol decreased the immobility time in the FST and TST without accompanying changes in ambulation in the open field test at 10 mg/kg, i.p.. Nevertheless, it induced ambulation at 25 and 50 mg/kg doses. The anti-immobility effect of bis-eugenol (10 and 50 mg/kg, i.p.) was prevented by pretreatment of mice with p-chlorophenylalanine (PCPA, 100 mg/kg, i.p., an inhibitor of serotonin synthesis, for four consecutive days), yohimbine (1 mg/kg, i.p., an α2-adrenoceptor antagonist), SCH23390 (15 μg/kg, s.c., a dopamine D1 receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist). Monoamines analysis using high-performance liquid chromatograph revealed significant increase in the 5-HT, NE and DA levels in brain striatum. The present study indicates that bis-eugenol possesses antidepressant-like activity in FST and TST by altering dopaminergic, serotonergic and noradrenergic systems function., (© 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.)

This research has been motivated by a real-life problem of a waste cooking oil collection system characterized by the existence of multiple depots with an outsourced vehicle fleet, where the collection routes have to be plan. The routing problem addressed allows open routes between depots, i.e., all routes start at one depot but can end at the same or at a different one, depending on what minimizes the objective function considered. Such problem is referred as a Multi-Depot Vehicle Routing Problem with Mixed Closed and Open Inter-Depot Routes and is, in this paper, modeled through a mixed integer linear programming (MILP) formulation where capacity and duration constraints are taken into account. The model developed is applied to the real case study providing, as final results, the vehicle routes planning where a decrease of 13% on mileage and 11% on fleet hiring cost are achieved, when comparing with the current company solution., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

In a previous study conducted by our group, riparin II (ripII) isolated from the green fruit of Aniba riparia presented antianxiety effects in mice. This study investigates a possible antidepressant activity of rip II using two predictive tests for antidepressant activity in rodents: the forced swimming test (FST) and tail suspension test (TST). Additionally, the mechanisms involved in the antidepressant-like effect in mice were also assessed. Rip II was acute administered by intraperitoneal (i.p.) and oral (p.o) routes to male mice at doses of 25 and 50 mg/kg. Results showed that ripII at both tested doses and administration routes produced a significant decrease of immobility time in FST and TST. The pretreatment of mice with prazosin (1 mg/kg, i.p., an α1-adrenoceptor antagonist), SCH23390 (15 μg/kg, i.p., a dopamine D1 receptor antagonist), sulpiride (50 mg/kg, i.p., a dopamine D2 receptor antagonist), p-chlorophenylalanine (100 mg/kg, an inhibitor of serotonin synthesis), or NAN-190 (0.5 mg/kg, a serotonin 5-HT1A receptor antagonist) completely blocked the anti-immobility effects elicited by riparin II (50 mg/kg, p.o.) in the FST. This study indicates that riparin II produces significant antidepressant-like activity in the forced swimming and TSTs, and this effect seems to be dependent on its interaction with noradrenergic, dopaminergic, and serotonergic systems., (© 2011 The Author Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.)

Background: Cardiac disorders are very common in individuals with chronic kidney disease and are associated with morbimortality., Objective: To evaluate cardiac alterations after kidney transplantation., Methods: We prospectively evaluated 40 patients with chronic kidney disease, immediately before and one month, three months and six months after kidney transplantation, using tissue Doppler echocardiographic study. The left ventricular mass, systolic and diastolic function parameters were analyzed., Results: The mean age was 31.6 years and 40% of patients were female. We observed a reduction in left ventricular diastolic diameter (52.23 to 49.95 mm, p = 0.021) and LV mass index (131.48 to 113.039 g/m2, p = 0.002) after kidney transplantation. The mean E/e' decreased in the third and sixth months after kidney transplantation, when compared to basal values (8.13 and 7.85 vs. 9.79, p <0.05). The ejection fraction increased from the first month after kidney transplantation compared to basal assessment (69.72% vs. 65.68%, p <0.05). The prevalence of diastolic dysfunction decreased 43% during the evaluated period. The basal ejection fraction and mean E/e' were associated with reduced LV mass index after kidney transplantation. The LV mass index at baseline, female sex and decrease in serum phosphorus were associated with a reduction in the mean E/e ' ratio after kidney transplantation., Conclusion: Kidney transplantation resulted in significant alterations in Doppler echocardiographic parameters of LV mass, systolic and diastolic function in patients with chronic kidney disease.

Cocaine is used worldwide and considered a public health problem. Relapse from addiction is one of the difficulties faced by cocaine users, and in most cases according to the period of abstinence, users may present symptoms such as anxiety or depression. To evaluate the anxiety-like behavior induced by different periods, rats were treated for 7 days with cocaine 20 mg/kg, i.p., and 24 h, 7 and 21 days after drug withdrawal were submitted to the elevated plus maze (EPM) and the open field (OF) tests. In different protocol, propranolol (10 mg/kg, i.p.), ondansetron (4 mg/kg, i.p.) and buspirone (5 mg/kg, i.p.) were administered once after 24 h and 7 days of abstinence from cocaine to evaluate possible reversal or attenuation of the symptoms caused by cocaine withdrawal. EPM results showed a reduction in all parameters after 24 h and 7 days of the last exposure to cocaine, indicating anxiety-like behavior. In the OF test, 24 h and 7 days of abstinence showed increased locomotor activity, while in the withdrawal 21 days the animals not alter the locomotor activity. The administration of propranolol, ondansetron or buspirone after a 24 h abstinence period reduced the animalś anxiety in the EPM, and in the OF all drugs were able to reduce locomotor activity. After abstinence 7 d, the drugs reduced locomotor activity in the OF, in the EMP propranolol and ondansetron reversed the anxiogenic effect induced by cocaine. These results suggest that the treatment of anxyogenic effects of abstinence from cocaine is dependent on the period of the withdrawal., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: The antipsychotic, hypnotic, myorelaxant and antioxidant effects of the essential oil of Alpinia zerumbet (EOAZ) were studied., Methods: EOAZ (50, 100 and 200 mg/kg i.p.) was administered once to mice for the determination of antipsychotic activity (evaluated by ketamine-induced hyperlocomotion), hypnotic activity (induced by sodium pentobarbital, 40 mg/kg i.p.), motor coordination (rotarod test), antioxidant effects (determination of lipid peroxidation and GSH levels), as well as alterations in nitric oxide levels (determination of nitrite content)., Key Findings: EOAZ at doses of 100 and 200 mg/kg prevented ketamine hyperlocomotion, as did haloperidol (0.2 mg/kg i.p). EOAZ at a dose of 200 mg/kg decreased sleep latency, while all doses increased sleeping time. There was no effect on motor coordination. The in-vitro antioxidant capacity of the oil caused a decrease in lipid peroxidation and increase in GSH levels. EOAZ also prevented the decrease in nitrite content caused by oxidative stress., Conclusions: The results suggest antipsychotic and antioxidant effects for the EOAZ that may have promising efficacy for the treatment of schizophrenia., (© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.)

The European Union directive for electric and electronic waste, published in 2003, enforced all European countries to meet some targets concerning the recycling and recovery of these products. This directive was transposed to the Portuguese legislation in 2004. Following this, a group of EEE producers set up an organization (Amb3e) whose mission was to design and manage a nationwide recovery network for WEEE, which will be the subject matter of this work. A generic MILP model is proposed to represent this network, which is applied to its design and planning, where the best locations for collection and sorting centres are chosen simultaneously with the definition of a tactical network planning. Several analyses are performed to provide further insights regarding the selection of these alternative locations. The results gave support to the company strategic expansion plans for a high number of centres to be opened and to their location near the major WEEE sources., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The aim of this study was to assess the effects of a synbiotic composed of Bifidobacterium animalis and fructooligosaccharides on female rats infected with Toxoplasma gondii. Female Wistar rats, treated or not with dexamethasone, were daily supplemented with synbiotics for 21 days. After 15 days of supplementation, the rats were orally infected with 10(4)T. gondii bradyzoites. Blood samples were collected to measure the levels of IFN-γ, IL-10 and T. gondii antibodies. All synbiotic-supplemented rats survived until the end of the experiment; however, non-supplemented dexamethasone-treated rats died between the fifth and the eighth days after T. gondii infection. Dexamethasone-treated rats supplemented with synbiotics (P<0.05) were capable of synthesizing IFN-γ, and this immunological response was essential to ensure their survival. In addition, brain cysts were found in one rat not supplemented with synbiotics. Results suggest that the synbiotic composed of B. animalis and fructooligosaccharides may be beneficial to toxoplasmosis control., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Recent studies have shown that some monoterpenes exert anxiolytic- and depressant-like actions, however, these effects from monoterpene 1,4-cineole are still unknown. This work aimed to study the effects of 1,4-cineole in classic animal models for depression- and anxiety-like behavior, specifically the elevated plus maze (EPM), hole board, open field, pentobarbital sleeping time, forced swimming, tail suspension and rota rod tests. 1,4-Cineole was administered orally to mice (100, 200 and 400 mg/kg), while diazepam (1 or 2 mg/kg) and imipramine (10 or 30 mg/kg) were used as standard drugs. 1,4-Cineole (400 mg/kg) modified all parameters observed in the EPM, while no significant variation was observed on general motor activity in the open-field test. In the hole-board assay, 1,4-cineole induced increase on the number of head dips. Forced swimming and tail suspension tests showed that cineole (200 and/or 400 mg/kg) was able to promote significant increase on the immobility time, while a decreased sleep latency was observed (200 and 400 mg/kg ) on the pentobarbital sleeping time. Cineole had no effect on the motor coordination of animals in the rota rod test. The results suggest that 1,4-cineole presents potential anxiolytic-like action consistent with possible general depression of the CNS., (2010 Elsevier Inc. All rights reserved.)

A growing body of evidence has pointed to the ionotropic glutamate N-methyl-d-aspartate receptor (NMDA) as an important player in the etiology of psychopathologies, including anxiety and major depression. Clinical findings suggest that ketamine may be used for the treatment of major depression. There is evidence that reactive oxygen species also play an important role in the pathogenesis of many diseases, particularly those which are neurological and psychiatric in nature. This study examined the behavioral and oxidative stress alterations after a single administration of ketamine (5, 10 and 20mg/kg i.p.) in mice. Ketamine presented a significant anxiogenic effect in the elevated plus-maze model of anxiety, also increasing locomotor activity. In the forced swimming and tail suspension tests, a significant decrease in immobility time after ketamine administration was observed. In addition to the behavioral changes induced by ketamine, this drug also increased lipid peroxidation, nitrite content and catalase activity, while decreased GSH levels in mice prefrontal cortex. In conclusion, our results confirm the antidepressant effects of ketamine, also showing a pro-oxidant effect of this drug., (2010 Elsevier Inc. All rights reserved.)

This study evaluated whether a synergy exists for the combined treatment with lycopene and synbiotic on early biomarkers of colon carcinogenesis. Male Wistar rats received a diet containing 300 mg/kg of lycopene and/or synbiotic (Bifidobacterium lactisplus oligofructose/inulin) or their combination 2 weeks before and during carcinogen treatment with 1,2-dimethylhydrazine (DMH). Twenty-four hours after the last DMH application, the colons were processed for immunohistochemical analysis of proliferating cell nuclear antigen (PCNA), p53 protein, hematoxylin-eosin staining for apoptosis analysis and genotoxicity of fecal water by comet assay. Eight weeks after the last DMH application, the colons were analyzed for development of classical aberrant crypt foci (ACF) and mucin-negative ACF. Treatment with lycopene, synbiotic or their combination significantly increased apoptosis, reduced the PCNA and p53 labeling indexes and the development of classical ACF and mucin-negative ACF. Furthermore, a lower genotoxicity of fecal water was also detected in the groups treated with the chemopreventive agents. An additive/synergistic effect of the combined treatment with lycopene/synbiotic was observed only for the fecal water genotoxicity and mucin-negative ACF parameters. These results indicate that an additive/synergistic of the combination of chemopreventive agents on the initiation phase of colon carcinogenesis can be detected using selective early biomarkers., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Oxidative stress (OS) has been related to cocaine's actions and also to numerous nervous system pathologies, including seizures. The purpose of this work was to determine the alterations in glutathione (GSH) content, nitrite/nitrate and MDA levels after cocaine-induced toxicity. Male Swiss mice were injected (i.p.) with cocaine 90 mg/kg and observed during 1h. After this cocaine overdose some animals presented status epilepticus (SE) while some died after seizures. These animals were divided in two groups, SE and death. A group with an association of the antioxidant Vitamin E (Vit E, 400mg/kg, i.p.) plus Coc 90 (Vit E plus Coc 90) was undertaken to assess the neuroprotective effect of Vit E. Neurochemical analyses were carried out in prefrontal cortex (PFC) and striatum (ST). GSH levels increased only after cocaine-induced death in both areas studied. Cocaine-induced SE has increased nitrite/nitrate content in PFC and ST, while after death the increase was only in PFC. MDA (the lipid peroxidation marker) was elevated after SE and death in ST and only after death in PFC. Antioxidant treatment significantly reduced the GSH, nitrite/nitrate in ST and MDA levels. Only nitrite/nitrate content in PFC has not been decreased by Vit E pretreatment. The results relate that oxidative stress occurs after cocaine-induced toxicity mainly after death indicating that probably the increase of OS in the animal's brain leads to seizures and death, also showing a protective effect of Vit E in this process. Together with previous results this study contributes to the knowledge of cocaine-induced toxicity and possible in the near future to the use of antioxidants in the prevention of cocaine-induced CNS toxicity., (2009 Elsevier Ltd. All rights reserved.)

The present study investigated the effects of isopulegol, a monoterpene alcohol, in PTZ-induced convulsions and verified possible involved mechanisms. Saline, isopulegol or diazepam were intraperitonealy injected 30 min before PTZ. The latency for development of convulsions and mortality, as well as the mortality protection percentage was recorded. For investigating the involvement of GABAergic system, flumazenil was utilized. The activity of antioxidant enzyme catalase as well as the levels of reduced glutathione and lipid peroxidation were measured in brain hippocampus. Similarly to diazepam, isopulegol significantly prolonged the latency for convulsions and mortality of mice. All animals were protected against mortality at higher dose of isopulegol. Flumazenil pretreatment decreased the prolongation of seizure latency induced by both diazepam and isopulegol, although it was not able to reverse the latency and protection percent for mortality. Isopulegol also significantly prevented PTZ-induced increase in lipid peroxidation, preserved catalase activity in normal levels, and prevented the PTZ-induced loss of GSH in hippocampus of mice. These results suggest that the anticonvulsant and bioprotective effects of isopulegol against PTZ-induced convulsions are possibly related to positive modulation of benzodiazepine-sensitive GABA(A) receptors and to antioxidant properties.

Objectives: Alpinia zerumbet, known in Brazil as colônia, is popularly used as a diuretic, antihypertensive, anti-ulcerogenic and sedative. Based on this, we have investigated the central effects of the essential oil isolated from A. zerumbet leaves., Methods: Mice were treated once with 50 or 100 mg/kg of the essential oil, intraperitoneally, 30 min before being submitted to behavioural models of: locomotor activity (open-field), catalepsy, anxiety (elevated plus maze), depression (forced swimming test and tail suspension tests) as well as apomorphine-induced stereotypy., Key Findings: Results showed a dose-related decrease on locomotor activity and apomorphine-induced stereotypy. There was a decrease to the order of 55% of the grooming behaviour with both doses studied. The essential oil 100 mg/kg increased cataleptic activity (167%) and the immobility time in the forced swimming and tail suspension tests. Pretreatment with haloperidol (0.2 mg/kg, i.p.) alone also decreased locomotion, increased cataleptic activity and immobility time in the tail suspension test. No alterations in the elevated plus maze test were registered., Conclusions: The essential oil of A. zerumbet leaves had depressant and possible antipsychotic activity, since it could reverse the stereotypy induced by apomorphine, presenting effects comparable with those obtained with haloperidol treatment.

The present study investigated whether isopulegol, a monoterpene present in essential oils of several aromatic plants, would be able to promote some gastroprotective effect and also verified the possible mechanisms involved in this action. For this study, ethanol- and indomethacin-induced gastric ulcer models in mice and histopathological assessment were used. The roles of NO, sulfhydryls (glutathione, GSH), ATP-sensitive K(+) channels (K(ATP) channels), and prostaglandins were also investigated. Isopulegol exhibited a dose-related gastroprotective effect against ethanol-induced lesions, while the pretreatment with glibenclamide and indomethacin [but not with N(G)-nitro-L-arginine methyl ester] were able to reverse this action. The pretreatment with isopulegol also restored GSH levels to normal levels and exhibited dose-related gastroprotective effect against indomethacin-induced ulcer. The results suggested that isopulegol presents significant gastroprotective effects in both ethanol- and indomethacin-induced ulcer models, which appear to be mediated, at least in part, by endogenous prostaglandins, K(ATP) channel opening, and antioxidant properties.

Isopulegol is a monoterpene alcohol intermediate in the preparation of (-)-menthol and it is present in the essential oils of various plants. This work presents behavioral effects of isopulegol in animal models of open field, elevated plus maze (EPM), rota rod, hole board, barbiturate-induced sleeping time, tail suspension and forced swimming tests in mice. Isopulegol was administered intraperitoneally to male mice at single doses of 25 and 50 mg/kg, while diazepam 1 or 2 mg/kg and imipramine 10 or 30 mg/kg were used as standard drugs. The results showed that, similar to diazepam (1 mg/kg), both doses of isopulegol significantly modified all the observed parameters in the EPM test, without alter the general motor activity in the open field test. In the same way, both doses of isopulegol increased the number of head dips in the hole-board test. Forced swimming and tail suspension tests showed that isopulegol (25 and 50 mg/kg) was able to induce a significant increase in the immobility time, in opposite to imipramine, a recognized antidepressant drug. There was a decrease in the sleep latency time and prolongation of the pentobarbital-induced sleeping time with both doses of Isopulegol. Different from diazepam (2 mg/kg), isopulegol (25 e 50 mg/kg) had no effect on the motor coordination of animals in the rota rod test. These results showed that isopulegol presented depressant- and anxiolytic-like effects.

In the present study were studied the antinociceptives properties of monoterpene R-(+)-limonene (LM) in chemical and thermal models of nociception in mice. The R-(+)-limonene was administered, intraperitoneally (i.p.), at doses of 25 and 50 mg/kg. The results showed significant inhibition produced on chemical nociception induced by intraperitoneal acetic-acid and in the second phase of subplantar formalin test, but did not manifest a significant effect in hot-plate test. The R-(+)-limonene-induced antinociception in second phase of formalin test was insensitive to naloxone (1 mg/kg, s.c.). It was also demonstrated that R-(+)-limonene (25, 50 mg/kg) neither significantly enhanced the pentobarbital-sleeping time nor impaired the motor performance in rota-rod test, indicating that the observed antinociception is unlikely to be due to sedation or motor abnormality. In conclusion it may be suggested that the R-(+)-limonene presented antinociceptive activity and that, probably, this action can be related with peripheral analgesia, but, not with the stimulation of opioids receptors.

This paper analyzes municipal management through managerial and manager practices in family health program offices in municipal health ministries and basic health clinics. Theoretically management and social relationship technologies are considered tools for the work carried out in the health care field, and they are also valuable instruments for change the micro-policy of the real work done in the health care domain. The methodological approach is qualitative and the research techniques used were the systematized direct observation as well as semi-structured interviews. The research subjects were the municipal health ministry managers, family health program coordinators and directors from four cities in the state of Maranhão. The results have shown that management is based on a traditional managerial style, characterized by a hard bureaucratic core. However, there is a trend for change because in practice, there are already signs which indicate the establishment of accountability and more caring relationships with respect to users and their families.

Chest roentgenogram of a sixty-year-old male patient, revealed a tumoral mass in the right lung, that was later demonstrated by transbronchial biopsy, to be a bronchogenic adenocarcinoma. There was no tomographic evidence of distant metastasis, however, in order to assess the mediastinal involvement for staging of the tumor, biopsies from the regional lymph nodes were obtained. Microscopic examination of the sample tissues failed to show any metastatic lesion, but, unexpectedly, revealed the presence of cicatricial granulomas in an advanced stage of fibrosis. They contained a few round, empty and collapsed corpuscles, limited by a thick PAS-positive, membrane. These structures were identified as adiaconidia of Emmonsia crescens, the etiological agent of human adiaspiromycosis. In the tissue sections, a large amount of carbon dust (anthracosis) was also seen.

A case of abdominal hydatidosis, without hepatic involvement, in a patient from the State of Acre is reported. The hydatid, already in degeneration and partially calcified, was discovered incidentally by a radiologic examination of the vertebral column, carried out for evaluating the state of an intervertebral disk prolapse. Although the images suggested a mesenteric tumor, attached to the intestinal wall, the finding of rostellar hooklets in the dense contents of the cyst, after surgical removal, revealed the parasitic nature of the lesion.

During an outbreak of yellow fever (rural form of the infection) occurred recently in the State of Goiás, Brazil, a patient, with clinical manifestations suggestive of the infection, died in the University Hospital of Brasilia, DF, on the fifth day from admission. Postmortem examination revealed, microscopically, the characteristic alterations of the infection, and discovered in the lungs and hilar lymph nodes round microrganisms identified as adiaconidia of Emmonsia parva var. crescens.

Mutagenicity in the urine of workers occupationally exposed to mineral oils and iron oxide particles and age matched workers only exposed to mineral oils was investigated using the Salmonella/mammalian microsome assay. Both groups of workers included smokers and non-smokers. Mutagenicity was significantly higher in the group of workers exposed to both mineral oils and iron oxide particles, the statistical significance of the difference being similar to that found when total non-smokers were compared with total smokers irrespective of occupational exposure. When only non-smokers of both groups of workers were compared, the extent of mutagenicity in the urine of workers exposed to iron oxide particles was still significantly higher, suggesting that smoking did not exhibit a significant enhancing effect on urinary mutagenicity of workers exposed to mineral oils and iron oxide particles, but instead seemed to enhance urinary mutagenicity similarly in both groups of workers. Whether or not this conclusion can be drawn may depend, among other factors, on the variability of the Ames assay. To cope with this particular problem, the possible usefulness of a mutagenicity factor is discussed.

Glycosides of flavonols such as quercetin, are found in the edible portions of most food vegetables. Flavonols present in plants as glycosides can be freed during fermentation. We have compared the DNA-damaging activity of quercetin, rutin (3-o-rutinoside of quercetin) and a fermented flavonoid-containing beverage, red wine, for different genetic end-points under different metabolic conditions. The genotoxicity of quercetin, rutin and commercial red wine has been studied for the induction of: (i) reverse mutation in the Ames assay; (ii) SOS functions in the SOS Chromotest; (iii) sister-chromatid exchanges (SCEs) in human lymphocytes. While in the Ames assay the mutagenicity of quercetin is enhanced by the presence of rat liver microsomal enzymes (S9) or the respective cytosolic fraction (S100), genotoxicity is reduced when the induction of SOS responses is assessed using the SOS Chromotest. Similarly, the induction of SCEs is lowered when testing in the presence of liver enzymes. Rutin has no activity whatsoever. Detection of activity of red wine in the three assays is not dependent upon hydrolysis by glycosidases and its content of quercetin accounts almost entirely for the levels of genotoxicity detected. The results suggest that the putative genotoxic metabolites of quercetin vary for different genetic end-points considered and that the metabolic fate of flavonoids might partly account for the conflicting data about their genotoxicity in vivo and carcinogenic activity.

Nil and Nilpy hamster cells exposed to temperatures of 44 degrees C to induce the heat-shock proteins survive such exposure for 2 h or more when incubated in Eagle's Minimum Essential Medium with 10% undialyzed fetal calf serum. If D-glucose and L-glutamine are withdrawn from the medium during heat treatment, nearly all the cells are killed by as little as 20 min at 44 degrees C. Several alpha-keto acids, pyruvate, alpha-ketobutyrate, oxaloacetate, and alpha-ketoglutarate, protect cells from the lethal action of the heat treatment in the absence of D-glucose and L-glutamine. L-Glucose and D-glutamine are without effect. Efforts to reverse lethal effects have not been successful.