Repeated exposure of adolescent rats to oral methylphenidate does not induce behavioral sensitization or cross-sensitization to nicotine

Several lines of evidence indicate that the use of stimulant drugs, including methylphenidate (MPD), increases tobacco smoking. This has raised concerns that MPD use during adolescence could facilitate nicotine abuse. Preclinical studies have shown that repeated treatment with an addictive drug produces sensitization to that drug and usually cross-sensitization to other drugs. Behavioral sensitization has been implicated in the development of drug addiction. We examined whether repeated oral MPD administration during adolescence could induce behavioral sensitization to MPD and long-lasting cross-sensitization to nicotine. Adolescent male Wistar rats were treated orally with 10 mg/kg MPD or saline (SAL) from postnatal day (PND) 27 to 33. To evaluate behavioral sensitization to MPD in adolescent rats (PND 39), the SAL pretreated group was subdivided into two groups that received intragastric SAL (1.0 mL/kg) or MPD (10 mg/kg); MPD pretreated rats received MPD (10 mg/kg). Cross-sensitization was evaluated on PND 39 or PND 70 (adulthood). To this end, SAL- and MPD-pretreated groups received subcutaneous injections of SAL (1.0 mL/kg) or nicotine (0.4 mg/kg). All groups had 8 animals. Immediately after injections, locomotor activity was determined. The locomotor response to MPD challenge of MPD-pretreated rats was not significantly different from that of the SAL-pretreated group. Moreover, the locomotor response of MPD-pretreated rats to nicotine challenge was not significantly different from that of the SAL-pretreated group. This lack of sensitization and cross-sensitization suggests that MPD treatment during adolescence does not induce short- or long-term neuroadaptation in rats that could increase sensitivity to MPD or nicotine.

Psychometric properties of the Child Health Assessment Questionnaire (CHAQ) applied to children and adolescents with cerebral palsy

Background: Cerebral palsy (CP) patients have motor limitations that can affect functionality and abilities for activities of daily living (ADL). Health related quality of life and health status instruments validated to be applied to these patients do not directly approach the concepts of functionality or ADL. The Child Health Assessment Questionnaire (CHAQ) seems to be a good instrument to approach this dimension, but it was never used for CP patients. The purpose of the study was to verify the psychometric properties of CHAQ applied to children and adolescents with CP. Methods: Parents or guardians of children and adolescents with CP, aged 5 to 18 years, answered the CHAQ. A healthy group of 314 children and adolescents was recruited during the validation of the CHAQ Brazilian-version. Data quality, reliability and validity were studied. The motor function was evaluated by the Gross Motor Function Measure (GMFM). Results: Ninety-six parents/guardians answered the questionnaire. The age of the patients ranged from 5 to 17.9 years (average: 9.3). The rate of missing data was low(< 9.3%). The floor effect was observed in two domains, being higher only in the visual analogue scales (<= 35.5%). The ceiling effect was significant in all domains and particularly high in patients with quadriplegia (81.8 to 90.9%) and extrapyramidal (45.4 to 91.0%). The Cronbach alpha coefficient ranged from 0.85 to 0.95. The validity was appropriate: for the discriminant validity the correlation of the disability index with the visual analogue scales was not significant; for the convergent validity CHAQ disability index had a strong correlation with the GMFM (0.77); for the divergent validity there was no correlation between GMFM and the pain and overall evaluation scales; for the criterion validity GMFM as well as CHAQ detected differences in the scores among the clinical type of CP (p < 0.01); for the construct validity, the patients' disability index score (mean: 2.16; SD: 0.72) was higher than the healthy group ( mean: 0.12; SD: 0.23)(p < 0.01). Conclusion: CHAQ reliability and validity were adequate to this population. However, further studies are necessary to verify the influence of the ceiling effect on the responsiveness of the instrument.

KeaA, a Dictyostelium kelch-domain protein that regulates the response to stress and development

Background: The protein kinase YakA is responsible for the growth arrest and induction of developmental processes that occur upon starvation of Dictyostelium cells. yakA-cells are aggregation deficient, have a faster cell cycle and are hypersensitive to oxidative and nitrosoative stress. With the aim of isolating members of the YakA pathway, suppressors of the death induced by nitrosoative stress in the yakA-cells were identified. One of the suppressor mutations occurred in keaA, a gene identical to DG1106 and similar to Keap1 from mice and the Kelch protein from Drosophila, among others that contain Kelch domains. Results: A mutation in keaA suppresses the hypersensitivity to oxidative and nitrosoative stresses but not the faster growth phenotype of yakA-cells. The growth profile of keaA deficient cells indicates that this gene is necessary for growth. keaA deficient cells are more resistant to nitrosoative and oxidative stress and keaA is necessary for the production and detection of cAMP. A morphological analysis of keaA deficient cells during multicellular development indicated that, although the mutant is not absolutely deficient in aggregation, cells do not efficiently participate in the process. Gene expression analysis using cDNA microarrays of wild-type and keaA deficient cells indicated a role for KeaA in the regulation of the cell cycle and pre-starvation responses. Conclusions: KeaA is required for cAMP signaling following stress. Our studies indicate a role for kelch proteins in the signaling that regulates the cell cycle and development in response to changes in the environmental conditions.

Low nanomolar concentration of mercury chloride increases vascular reactivity to phenylephrine and local angiotensin production in rats

Exposure to mercury at nanomolar level affects cardiac function but its effects on vascular reactivity have yet to be investigated. Pressor responses to phenylephrine (PHE) were investigated in perfused rat tail arteries before and after treatment with 6 nM HgCl2 during 1 h,,in the presence (E+) and absence (E-) of endothelium, after L-NAME (10(-4) M), indomethacin (10(-5) M), enalaprilate (1 mu M), tempol (1 mu M) and deferoxamine (300 mu M) treatments. HgCl2 increased sensitivity (pD(2)) without modifying the maximum response (Em) to PHE, but the pD(2) increase was abolished after endothelial damage. L-NAME treatment increased pD(2) and Emax. However, in the presence of HgCl2, this increase was smaller, and it did not modify Emax. After indomethacin treatment, the increase of pD(2) induced by HgCl2 was maintained. Enalaprilate, tempol and deferoxamine reversed the increase of pD(2) evoked by HgCl2. HgCl2 increased the angiotensin converting enzyme (ACE) activity explaining the result obtained with enalaprilate. Results suggest that at nanomolar concentrations HgCl2 increase the vascular reactivity to PHE. This response is endothelium mediated and involves the reduction of NO bioavailability and the action of reactive oxygen species. The local ACE participates in mercury actions and depends on the angiotensin 11 generation. (c) 2007 Elsevier Inc. All rights reserved.

Leptospiral TlyC is an extracellular matrix-binding protein and does not present hemolysin activity

The role of TlyA, TlyB and TlyC proteins in the biology of Leptospira is still uncertain. Although these proteins have been considered as putative hemolysins, we demonstrate that leptospiral recombinant TlyB and TlyC do not possess hemolytic activity. However, further experiments showed that TlyC is a surface-exposed protein that seems to bind to laminin, collagen IV and fibronectin. The expression of both proteins was detected both in vitro and in vivo. Our findings suggest that TlyB and TlyC are not directly involved in hemolysis, and that TlyC may contribute to Leptospira binding to extracellular matrix (ECM) during host infection. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

The efficacy of a highly concentrated fluoride dentifrice on bovine enamel subjected to erosion and abrasion

Background. Researchers have proposed the use of fluoride for the prevention of enamel wear; however, only limited information is available about the impact of fluoridated dentifrices. Because tooth wear is a well-recognized dental problem, the authors conducted an in situ, ex vivo study to assess the efficacy of a highly concentrated fluoride dentifrice on bovine enamel subjected to erosion and abrasion. Methods. The authors conducted a double-blind, crossover in situ study consisting of three phases (seven days each). In each phase, the authors tested one of the dentifrices (5,000 parts per million fluoride [F]; 1,100 ppm F; no F). They performed erosive challenges with the use of cola drink (60 seconds, four times per day) and abrasive challenges via toothbrushing (30 seconds, four times per day). The authors determined the enamel loss via profilometry. Results. The authors tested the data by using two-way analysis of variance (P <.05). For the erosion-plus-abrasion condition, the study results showed that enamel wear was significantly higher than that with erosion alone. The findings showed no significant differences between the dentifrices regarding enamel wear. Conclusions. Within the in situ, ex vivo conditions of this study, the authors concluded that the highly concentrated fluoride dentifrice did not have a protective effect on enamel against erosion and erosion plus toothbrushing abrasion. Clinical Implications. Patients at risk of developing enamel erosion should benefit from preventive measures other than fluoride dentifrice, because even a highly concentrated fluoride dentifrice does not appear to prevent enamel erosion.

Neuronal Expression of Cd36, Cd44, and Cd83 Antigen Transcripts Maps to Distinct and Specific Murine Brain Circuits

Cells recruited by the innate immune response rely on surface-expressed molecules in order to receive signals from the local environment and to perform phagocytosis, cell adhesion, and others processes linked to host defense. Hundreds of surface antigens designated through a cluster of differentiation (CD) number have been used to identify particular populations of leukocytes. Surprisingly, we verified that the genes that encode Cd36 and Cd83 are constitutively expressed in specific neuronal cells. For instance, Cd36 mRNA is expressed in some regions related to circuitry involved in pheromone responses and reproductive behavior. Cd44 expression, reanalyzed and detailed here, is associated with the laminar formation and midline thalamic nuclei in addition to striatum, extended amygdala, and a few hypothalamic, cortical, and hippocampal regions. A systemic immune challenge was able to increase Cd44 expression quickly in the area postrema and motor nucleus of the vagus but not in regions presenting expressive constitutive expression. In contrast to Cd36 and Cd44, Cd83 message was widely distributed from the olfactory bulb to the brain stem reticular formation, sparing the striatopallidum, olivary region, and cerebellum. Its pattern of expression nevertheless remained strongly associated with hypothalamic, thalamic, and hindbrain nuclei. Unlike the other transcripts, Cd83 mRNA was rapidly modulated by restraint stress. Our results indicate that these molecules might play a role in specific neural circuits and present functions other than those attributed to leukocyte biology. The data also suggest that these surface proteins, or their associated mRNA, could be used to label neurons in specific circuits/regions. J. Comp. Neurol. 517:906-924, 2009. (C) 2009 Wiley-Liss, Inc.

Determination of the susceptibility of Rhipicephalus (Boophilus) microplus (Acari: Ixodidae) to ivermectin and fipronil by Larval Immersion Test (LIT) in Uruguay

Rhipicephalus (Boophilus) microplus is an important cattle pest in Uruguay, and the law regulates its control. It is resistant to organophosphates, synthetic pyrethroids and, as recently discovered, to fipronil. Resistance to macrocyclic lactones (MLs) and amitraz have not been documented; however, veterinarians and farmers have reported treatment failures. The objective of the present work was to study the susceptibility of cattle tick strains from different Uruguayan counties to ivermectin (IVM) and fipronil by using the Larval Immersion Test (LIT). The Mozo strain was used as the susceptible reference strain. From 2007 to 2009, twenty-eight tick populations were collected from different cattle farms with and without history of IVM or fipronil use. A probit analysis estimated dose-mortality regressions, lethal concentrations (LC), and confidence intervals. The resistance ratio (RR) was determined at the LC(50) and LC(90) estimates. To classify a tick population in relation to resistance, three categories based on a statistical analysis of LC and RR between field populations and Mozo strains were defined: susceptible (no differences), incipient resistance (differences and RR(50) < 2) and resistant (differences and RR(50) >= 2). Eighteen field populations were tested with IVM and five of them presented a RR(50) range between 1.35 and 1.98 and the LC(50/90), which is statistically different from the Mozo strain (incipient resistance). However, the RR(90) increases >= 2 in four of the populations, confirming that tick resistance to IVM is emergent. The low RR values obtained could be a result of a low frequency of treatments with IVM. Twenty-seven tick populations were tested with fipronil and six were diagnosed as resistant according to the LIT. Cross-resistance was not observed between fipronil and IVM on these tick populations. The current study presents different R. (B.) microplus populations with an incipient resistance to IVM, and indicates that the fipronil tick resistance is restricted to certain areas in Uruguay. (c) 2011 Elsevier B.V. All rights reserved.

Adherence to cervical and breast cancer programs is crucial to improving screening performance

Introduction: Cervical and breast cancer are the most common malignancies among women worldwide. Effective screening can facilitate early detection and dramatically reduce mortality rates. The interface between those screening patients and patients most needing screening is complex, and women in remote areas of rural counties face additional barriers that limit the effectiveness of cancer prevention programs. This study compared various methods to improve compliance with mass screening for breast and cervical cancer among women in a remote, rural region of Brazil. Methods: In 2003, a mobile unit was used to perform 10 156 mammograms and Papanicolaou smear tests for women living in the Barretos County region of Sao Paulo state, Brazil (consisting of 19 neighbouring cities). To reach the women, the following community outreach strategies were used: distribution of flyers and pamphlets; media broadcasts (via radio and car loudspeakers); and community healthcare agents (CHCAs) making home visits. Results: The most useful intervention appeared to be the home visits by healthcare agents or CHCAs. These agents of the Family Health Programme of the Brazilian Ministry of Health reached an average of 45.6% of those screened, with radio advertisements reaching a further 11.9%. The great majority of the screened women were illiterate or had elementary level schooling (80.9%) and were of 'poor' or 'very poor' socioeconomic class (67.2%). Conclusions: Use of a mobile screening unit is a useful strategy in developing countries where local health systems have inadequate facilities for cancer screening in underserved populations. A multimodal approach to community outreach strategies, especially using CHCAs and radio advertisements, can improve the uptake of mass screening in low-income, low-educational background female populations.

Afferent Connections to the Rostrolateral Part of the Periaqueductal Gray: A Critical Region Influencing the Motivation Drive to Hunt and Forage

Previous studies have shown that a particular site in the periaqueductal gray (PAG), the rostrolateral PAG, influences the motivation drive to forage or hunt. To have a deeper understanding on the putative paths involved in the decision-making process between foraging, hunting, and other behavioral responses, in the present investigation, we carried out a systematic analysis of the neural inputs to the rostrolateral PAG (rlPAG), using Fluorogold as a retrograde tracer. According to the present findings, the rlPAG appears to be importantly driven by medial prefrontal cortical areas involved in controlling attention-related and decision-making processes. Moreover, the rlPAG also receives a wealth of information from different amygdalar, hypothalamic, and brainstem sites related to feeding, drinking, or hunting behavioral responses. Therefore, this unique combination of afferent connections puts the rlPAG in a privileged position to influence the motivation drive to choose whether hunting and foraging would be the most appropriate adaptive responses. Copyright (C) 2009 Sandra Regina Mota-Ortiz et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Electrochemical impedance spectroscopy investigation of the electrochemical behaviour of copper coated with artificial patina layers and submitted to wet and dry cycles

Due to rain events historical monuments exposed to the atmosphere are frequently submitted to wet and dry cycles. During drying periods wetness is maintained in some confined regions and the corrosion product layer, generally denominated patinas, builds up and gets thicker. The aim of this study is to use electrochemical impedance spectroscopy (EIS) to investigate the electrochemical behaviour of pure copper coated with two artificial patina layers and submitted either to continuous or to intermittent immersion tests, this latter aiming to simulate wet and dry cycles. The experiments were performed in 0.1 mol dm(-3) NaCl solution and in artificial rainwater containing the most significant pollutants of the city of Sao Paulo. The results of the continuous immersion tests in the NaCl solution have shown that the coated samples behave like a porous electrode with finite pore length. On the other hand, in the intermittent tests a porous electrode response with semi-infinite pore length can be developed. The results were interpreted based on the model of de Levie and a critical comparison with previous interpretations reported in the literature for similar systems is presented. (C) 2011 Elsevier Ltd. All rights reserved.

Preslaughter mortality of broilers in relation to lairage and season in a subtropical climate

The preslaughter handling and transport of broilers are stressful operations that might affect welfare and meat quality and could increase numbers of deaths before slaughter. However, the influence of thermal factors during transportation and lairage at slaughterhouses is complex in subtropical regions, where increasing temperature and high RH are the major concerns regarding animal survival before slaughter. In this study we assessed the influence of a controlled lairage environment on preslaughter mortality rates of broiler chickens that were transported during different seasons of the year and had varying lairage times in the subtropical climate. Preslaughter data from 13,937 broiler flocks were recorded daily during 2006 in a commercial slaughterhouse in southeastern Brazil. The main factors that influenced daily mortality rate were mean dry bulb temperature and RH, lairage time, daily periods, density of broilers per crate, season of the year, stocking density per lorry, transport time, and distance between farms and slaughterhouse. A holding area at the slaughterhouse with environmental control was assessed. Using a double GLM for mean and dispersion modeling, the seasons were found to have significant effects (P < 0.05) on average mortality rates. The highest incidence was observed in summer (0.42%), followed by spring (0.39%), winter (0.28%), and autumn (0.23%). A decrease of preslaughter mortality of broilers during summer (P < 0.05) was observed when the lairage time was increased, mainly after 1 h of exposure to a controlled environment. Thus, lairage for 3 to 4 h in a controlled lairage environment during the summer and spring is necessary to reduce the thermal load of broiler chickens.

Biochemical responses of the ethylene-insensitive Never ripe tomato mutant subjected to cadmium and sodium stresses

In order to further address the known interaction between ethylene and components of the oxidative system, we have used the ethylene-insensitive Never ripe (Nr) tomato (Solanum lycopersicum L) mutant, which blocks ethylene responses. The mutant was compared to the control Micro-Tom (MT) cultivar subjected to two stressful situations: 100 mM NaCl and 0.5 mM CdCl(2). Leaf chlorophyll, lipid peroxidation and antioxidant enzyme activities in roots, leaves and fruits, and Na and Cd accumulation in tissues were determined. Although we verified a similar growth pattern and Na and Cd accumulation for MT and Nr, the mutant exhibited reduced leaf chlorophyll degradation following stress. In roots and leaves, the patterns of catalase (CAT), glutathione reductase (GR), ascorbate peroxidase (APX), guaiacol peroxidase (GPOX), superoxide dismutase (SOD) enzyme activity as well as malondialdehyde (MDA) and hydrogen peroxide (H(2)O(2)) production under the stressful conditions tested were very similar between MT and Nr mutant. However, Nr fruits showed increased H(2)O(2) production, reduced and enhanced APX activity in NaCl and CdCl(2), respectively, and enhanced GPOX in NaCl. Moreover, through non-denaturing PAGE, a similar reduction of SOD I band intensity in both, control MT and Nr mutant, treated with NaCl was observed. In leaves and fruits, a similar SOD activity pattern was observed for all periods, genotypes and treatments. Overall the results indicate that the ethylene signaling associated with NR receptor can modulate the biochemical pathways of oxidative stress in a tissue dependent manner, and that this signaling may be different following Na and Cd exposure. (C) 2011 Elsevier B.V. All rights reserved.

Antioxidant response of Nicotiana tabacum cv. Bright Yellow 2 cells to cadmium and nickel stress

Plant cell cultures are a suitable model system for investigation of the physiological mechanisms of tolerance to environmental stress. We have determined the effects of Cd (0.1 and 0.2 mM CdCl(2)) and Ni (0.075 and 0.75 mM NiCl(2)) on Nicotiana tabacum L. cv. Bright Yellow (TBY-2) cell suspension cultures over a 72-h period. Inhibition of growth, loss of cell viability and lipid peroxidation occurred, in general, only when the TBY-2 cells were grown at 0.2 mM CdCl(2) and at 0.75 mM NiCl(2). At 0.1 mM CdCl(2), a significant increase in growth was determined at the end of the experiment. Increases in the activities of all of the four enzymatic antioxidant defence systems tested, were induced by the two concentrations of Cd and Ni, but at different times during the period of metal exposure. Overall, the cellular antioxidant responses to Cd and Ni were similar and were apparently sufficient to avoid oxidative stress at the lower concentrations of Cd and Ni. The activities of glutathione reductase and glutathione S-transferase increased early but transiently, whereas the activities of catalase and guaiacol peroxidase increased in the latter half of the experimental period. Therefore it is likely that the metabolism of reduced glutathione was enhanced during the initial onset of the stress, while catalase and guaiacol-type peroxidase appeared to play a more important role in the antioxidant response once the stress became severe.

Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling

Vieira RP, de Andrade VF, Duarte AC, dos Santos AB, Mauad T, Martins MA, Dolhnikoff M, Carvalho CR. Aerobic conditioning and allergic pulmonary inflammation in mice. II. Effects on lung vascular and parenchymal inflammation and remodeling. Am J Physiol Lung Cell Mol Physiol 295: L670-L679, 2008. First published August 29, 2008; doi: 10.1152/ajplung.00465.2007.-Recent evidence suggests that asthma leads to inflammation and remodeling not only in the airways but also in pulmonary vessels and parenchyma. In addition, some studies demonstrated that aerobic training decreases chronic allergic inflammation in the airways; however, its effects on the pulmonary vessels and parenchyma have not been previously evaluated. Our objective was to test the hypothesis that aerobic conditioning reduces inflammation and remodeling in pulmonary vessels and parenchyma in a model of chronic allergic lung inflammation. Balb/c mice were sensitized at days 0, 14, 28, and 42 and challenged with ovalbumin ( OVA) from day 21 to day 50. Aerobic training started on day 21 and continued until day 50. Pulmonary vessel and parenchyma inflammation and remodeling were evaluated by quantitative analysis of eosinophils and mononuclear cells and by collagen and elastin contents and smooth muscle thickness. Immunohistochemistry was performed to quantify the density of positive cells to interleukin (IL)-2, IL-4, IL-5, interferon-gamma, IL-10, monocyte chemotatic protein (MCP)-1, nuclear factor (NF)-kappa B p65, and insulin-like growth factor (IGF)-I. OVA exposure induced pulmonary blood vessels and parenchyma inflammation as well as increased expression of IL-4, IL-5, MCP-1, NF-kappa B p65, and IGF-I by inflammatory cells were reduced by aerobic conditioning. OVA exposure also induced an increase in smooth muscle thickness and elastic and collagen contents in pulmonary vessels, which were reduced by aerobic conditioning. Aerobic conditioning increased the expression of IL-10 in sensitized mice. We conclude that aerobic conditioning decreases pulmonary vascular and parenchymal inflammation and remodeling in this experimental model of chronic allergic lung inflammation in mice.