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Approximately 1 in 6 infants are born prematurely each year. Typically, these infants spend 25 days in the Neonatal Intensive Care Unit (NICU) where they experience 10-18 painful and inflammatory procedures each day. Remarkably, pre-emptive analgesics and/or anesthesia are administered less than 30% of the time. Unalleviated pain during the perinatal period is associated with permanent decreases in pain sensitivity, blunted cortisol responses and high rates of neuropsychiatric disorders. To date, the mechanism(s) by which these long-term changes in stress and pain behavior occur, and whether such alterations can be prevented by appropriate analgesia at the time of injury, remains unclear. We have previously reported in rats that inflammation experienced on the day of birth permanently upregulates central opioid tone, resulting in a significant reduction in adult pain sensitivity. However, the impact on early life pain on anxiety- and stress-related behavior and HPA axis regulation is not known. Therefore the goal of this dissertation was to determine the long-term impact of a single neonatal inflammatory pain experience on adult anxiety- and stress-related responses. Neuroanatomical changes in stress-associated neurocircuits were also examined. As the endogenous pain control system and HPA axis are in a state of exaggerated developmental plasticity early in postnatal life, and these systems work in concert to respond to noxious or aversive stimuli, this dissertation research aimed to answer the following questions: (1) Does neonatal injury produce deficits in adult stress-related behavior and alter stress-related neuroanatomy through an opioid-dependent mechanism? (2) Does neonatal injury alter receptor systems regulating the activation and termination of the stress response in adulthood? (3) Are stress- and pain-related neurotransmitters altered within the first week following early life pain? (4) Is early activation of the pain system necessary for the long-term changes in anxiety- and stress-related behavior? Together these studies demonstrate the degree, severity and preventability of the long-term deficits in stress responding associated with a single painful experience early in life. The goal of this research is to promote change in the treatment of infant pain in the NICU to reduce long-term sensory and mental health complications associated with prematurity.

A reduction in voluntary feed intake is a major factor in the lost productivity of grazing lambs infected by gastrointestinal parasites yet the mechanisms involved are poorly understood. Potential pathways involved in parasite-induced feed intake depression were investigated in lambs with minimal previous exposure to parasites and artificially infected by the small intestinal parasite Trichostrongylus colubriformis. Six in vivo experiments were conducted on lambs housed in individual pens or metabolism crates with similar feeding and experimental procedures. In Experiment 1 (Chapter 4) the effect of T. colubriformis infection on short term feed intake in lambs and of some pharmacological agents on feed intake depression were investigated. Prior to and for the duration of infection, lambs were fed once per day and feed intake recorded at regular intervals over the day (8 h). Following the onset of feed intake depression in the infected group (9 weeks after commencing dosing), all animals were treated with an analgesic (codeine phosphate per os), an anti-inflammatory agent (indomethacin per os), a CCK antagonist (L364-718 by subcutaneous injection) or saline (control) in a replicated Latin square design (n = 8). Although the pattern of feed consumption was similar in infected and non-infected lambs, average daily intake was reduced 32 % and short term intake (recorded at 10 minute intervals for the first hour of feeding, 15 minute intervals for the second hour and hourly for the next 6 hours of feeding) reduced 40 % by infection. This identified the key component by which intake was depressed and enabled the use of a short term intake model and short duration of action compounds to identify the pathways involved in intake depression in this sequence of experiments. None of the pharmacological treatments increased intake in the infected group. These results suggest a reduction in the rate of consumption due to reduced hunger signals, rather than change of meal eating patterns, is the major cause of feed intake depression. Specific conclusions about the pathways investigated using the pharmacological agents could not be obtained. Experiment 2 (Chapter 5) was designed to investigate the roles of pain and osmolality on feed intake depression. Digesta samples collected prior to and during parasite infection and before and after feeding had similar osmolalities (240-260 mosmol/l) which indicated that feeding or infection had no effect on osmolality of digesta. Following the onset of feed intake depression in infected animals, all animals were treated in a Latin square design (n = 4) with no treatment, saline, local anaesthetic (xylocaine) or analgesic (codeine phosphate) solution 15 minutes before feeding, by slow injection into the duodenum. There was no effect of these treatments on food intake. In the second part of the experiment, hyperosmotic solutions (mannitol and NaCI) markedly depressed short term intake in non-infected animals, suggesting a role for osmoreceptors in intake regulation. However these effects were not blocked by local anaesthetic so the depressed intake may have resulted from generalised malaise rather than from specific osmoreceptor effects. In Experiment 3 (Chapter 6) the role of peripheral CCK on intake depression was examined by a dose-response study utilising the CCK antagonist, loxiglumide. Intravenous injection of 5, 10 or 20 mg/kg LW of loxiglumide to infected lambs 10-15 minutes before feeding (n = 6) had no effect on feed intake at any of the dose levels. In experiment 4 (Chapter 7) loxiglumide was infused intravenously for 10 minutes (30 mg/kg/h) before feeding and for the first 2 h (10 mg/kg/h) after feed was offered to minimise any effect of the rate of clearance of loxiglumide on the lack of feed intake response. As well, the rate of marker disappearance from the abomasum was recorded in both infected and non-infected animals. Continuous infusion of loxiglumide did not attenuate parasite induced intake depression nor did it have any effect on abomasal emptying. Abomasal volume was reduced by infection (66.3 vs 162 ml) as was the fractional outflow rate (2.2 vs 2.8 ml/min) but these differences were accounted for by the lower level of feed intake in the infected animals. In Experiment 5 (Chapter 8) brotizolam, a benzodiazepine appetite stimulant, thought to act on the hypothalamus, was administered in a dose-response study to infected and non-infected animals (n = 4) immediately prior to feeding or following termination of the first meal (45 minutes after feeding) and the feed intake response recorded. Brotizolam elevated both the short term (0-0.75 h), daily (22 h) intake and all time intervals in the first 5 h after feeding in infected and non-infected animals when administered after the first meal but when administered prior to feeding elevated intake only over the first 6 h of feeding. In both cases the magnitude of the response was greater in infected animals than in non-infected animals. Brotizolam appeared to increase the rate of eating without having a major impact on meal eating patterns when administered before feeding. Where administration was after the first meal, the effect was due to an "extra" meal being consumed. These findings showed that infected animals can respond to central stimulators of intake although the mechanism of the response is not known. Opioids were implicated in intake depression as the rate of intake rather than meal patterns appeared to be the major parameter depressed under parasitism. This was examined in experiment 6 (Chapter 9) where animals (n = 6) were fasted for 26 h or not fasted, then treated with saline (control), brotizolam (intake stimulant) or naloxone (opioid antagonist) immediately prior to feeding. Fasting stimulated feed intake in the short term (100 % increase in 75 min) and over the day (12 % increase) in both infected and non-infected animals. Following fasting, infected animals ate a similar amount of feed to the non-infected, fasted animals and more than the non-infected, non-fasted animals. The signals resulting from a one day fast were sufficient in the short term to override parasite induced mechanisms causing feed intake depression. Naloxone suppressed the intake stimulatory effects of a 26 h fast in both infected and non-infected animals, which supports a role for endogenous opioids as hunger signals. Where animals were not fasted, naloxone reduced intake only in the non-infected animals which suggested endogenous opioid levels may be lower in infected animals than in non-infected animals. In the final experiment (Experiment 7, Chapter 10) the role of central hunger and satiety mechanism were investigated. Infected and non-infected animals (n = 6) were treated with naloxone or saline by intravenous injection, or saline and met-enkephalinamide (an opioid analogue) by intracerebral infusion, or naloxone and the opioid analogue simultaneously to investigate the role of central opioids in feed intake depression. To determine the role of CCK induced satiety signals on feed intake at a central level, loxiglumide and CCK were infused separately and in combination for 30 minutes prior to feeding and for the first 60 minutes of feed on offer, into a lateral cerebral ventricle of the brain of infected and control animals (n = 6). The opioid analogue tended to increase intake in infected animals but the effect was not significant probably because the dose used was too low to elicit a response in sheep. Naloxone depressed intake only in the infected animals, which conflicted with the results of Experiment 4. As a consequence these results were inconclusive because of the single low dose of opioid analogue used and the conflicting naloxone responses. CCK alone depressed intake by 39-52 % only in infected animals and this effect of the 90 minute infusion was evident over the 8 h short term recording period. Loxiglumide attenuated the feed intake depressive effects of CCK in the infected animals to the extent that intake was elevated above control levels. Loxiglumide alone was an intake stimulant in both infected and non-infected animals. Intake was increased over the entire 8 h but mostly in the second hour when intake was increased by 188 % in infected animals and by 16 % in the non-infected animals and resulted in almost continuous eating. These results showed loxiglumide will temporarily block the effect of parasite infection on feed intake in sheep when administered centrally and the fact that it blocked the effects of exogenous CCK on intake indicated that the effect is mediated via CCK receptors. In conclusion GIT parasite infection reduced both short term and daily feed intake apparently by a change in rate of intake rather than any alteration in meal patterns. It was further suggested that anyone of a number of potential peripheral pathways, including changes to osmolality, gut emptying, pain and inflammation of the gut, alone is not involved in anorexia in sofar as the compounds used could block these factors and the results support the idea that intake depression is mediated via a central mechanism. Intake in infected animals responded to a much greater extent when fasting, i.c.v. loxiglumide or brotizolam were employed. Feed intake thus appears to be regulated through the same mechanisms in infected and non-infected animals. The results from compounds affecting the central mechanism suggest central CCK receptors are important in parasite induced anorexia, possibly by changing the onset of satiety or by interacting with endogenous opioids to reduce the rate of feed intake. Secondly reduced endogenous opioids may be causing the reduction in the rate of feed consumption alone or as a result of other interactions. It was concluded that intake in parasitised animals could be increased to that of control animals by employing procedures and compounds thought to act on the hypothalamus.

Submitted by Johnny Rodrigues (johnnyrodrigues@ufcg.edu.br) on 2018-04-11T15:06:17Z No. of bitstreams: 1 LEONARDO FALCÃO FEITOSA - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2258061 bytes, checksum: cdc233909fd365937aacd1ef5fa7c2cd (MD5) / Made available in DSpace on 2018-04-11T15:06:17Z (GMT). No. of bitstreams: 1 LEONARDO FALCÃO FEITOSA - DISSERTAÇÃO PPG-CEMat 2014..pdf: 2258061 bytes, checksum: cdc233909fd365937aacd1ef5fa7c2cd (MD5) Previous issue date: 2014-12-29 / Na terapia medicamentosa convencional o fármaco é administrado através de uma forma farmacêutica e produz um nível tecidual do fármaco que não se mantêm dentro da faixa terapêutica por um período prolongado de tempo. Desta forma, o êxito do tratamento vai depender de vários fatores como dosagens precisas e frequentes em horários específicos pré-determinados e adesão do paciente à terapêutica de modo que, a não obediência ao esquema terapêutico, pode resultar em utilização do fármaco em faixa não efetiva ou em níveis tóxicos Devido a grande problemática da manutenção de níveis séricos de fármacos no organismo humano, principalmente quando se tratam se fármacos relacionados ao tratamento de dores de moderadas a intensa, este trabalho propõe o desenvolvimento de membranas porosas a base de quitosana, que é um polímero natural biocompatível, capazes de promover a liberação controlada de fentanil. As matrizes obtidas foram caracterizadas por: MO, MEV, EDS, FTIR, DRX, Ensaio de Intumescimento, Ensaio de Biodegradação e Ensaio de Citotoxicidade. Por MO e MEV verificou-se uma superfície com poros aparentemente interconectados. A partir da análise por EDS pode-se verificar os elementos componentes da quitosana e do fármaco. Por FTIR e DRX notou-se a não alteração dos grupos funcionais e cristalinidade, respectivamente, do material devido a incorporação do fármaco. Baseado nos ensaios de intumescimentos e biodegradação verificou-se a capacidade de controlar as variáveis: razão de intumescimento e taxa de degradação exclusivamente pela variação da concentração de quitosana na membrana porosa. Verificou-se no ensaio de citotoxicidade que as membranas, mesmo com a incorporação do fármaco, não apresentaram citotoxicidade. Baseado nos resultados obtidos pôde-se concluir que é possível sintetizar uma matriz polimérica com promissoras propriedades para carrear fármaco e para testes in vivo. / In conventional medical therapy the drug is administered via a dosage form and produces a tissue level of the drug that is not maintained within the therapeutic range over an extended period of time. Thus, the success of the treatment will depend on several factors such as accurate and frequent dosing at predetermined specific times and patient adherence to therapy so that the non-compliance to the treatment regimen can result in use of the drug in not effective range or toxic levels Due to the great problem of maintaining serum levels of drugs in the human body, especially in the case if drugs related to the treatment of moderate to severe pain, this paper proposes the development of porous membranes chitosan base, which is a biocompatible natural polymer, capable of promoting the controlled release of fentanyl. The matrices obtained were characterized by: OM, SEM, EDS, FTIR, XRD, Swelling test, biodegradation test and Cytotoxicity Assay. For OM and SEM there was apparently a surface with interconnected pores. From the EDS analysis can verify the elements of chitosan and drug. FTIR and XRD noted not to change functional groups of crystallinity and, respectively, of the material due to the incorporation of the drug. Based on swellings and biodegradation tests verified the ability to control the following variables: swelling ratio and degradation rate solely by varying the concentration of the chitosan porous membrane. It was found that the cytotoxicity assay the membranes, even with the incorporation of the drug did not show cytotoxicity. Based on the results obtained it was concluded that it is possible to synthesize a polymer matrix with promising properties to adduce drug and in vivo tests.

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O consumo de drogas e álcool constitui cada vez mais um problema social e de saúde pública, pelas consequências negativas que provocam no desenvolvimento emocional e físico dos indivíduos. Existem poucas referências na literatura avaliando o uso destas substâncias por portadores de doença falciforme (DF). Estes pacientes apresentam crises álgicas severas, recorrentes, frequentemente controladas por opióides. O comprometimento da qualidade de vida predispõe a ocorrência de transtornos psiquiátricos não-psicóticos, como depressão por exemplo, tornando o grupo vulnerável ao uso abusivo de substâncias. Objetivos: avaliar o consumo de álcool e drogas em pacientes portadores de DF acompanhados pelo Centro de Referência de Doença Falciforme (CRAF) do Hospital de Clínicas de Porto Alegre (HCPA), estimar o percentual de pacientes em tratamento da doença falciforme que fazem uso abusivo de álcool e drogas, e colaborar com o estudo que avaliará a efetividade de um centro de referência multidisciplinar para esta população. Métodos: estudo transversal, de uma amostra de conveniência, com 139 pacientes portadores de DF acompanhados no CRAF do HCPA. Resultados: a prevalência do uso abusivo foi de 1,5% para o álcool e 3,0% para o tabaco, e não se identificou o uso abusivo de outras substâncias, inclusive opióides. O padrão para o uso de substâncias não foi influenciado pela exposição ou por transtornos psiquiátricos não-psicóticos. Conclusão: São necessários mais estudos para reforçar estes achados, mas demonstra-se a segurança do uso de analgésicos opióides para o manejo das crises dolorosas apresentadas pelos portadores de DF. / Drug abuse is increasingly becoming a social and public health problem, because of the negative consequences that such abuse causes on the emotional and physical development of individuals. There are few references in the literature evaluating the use of these substances by individuals with sickle cell disease (SCD). These patients have severe and recurrent pain crises, frequently needing opioids drugs to control it. The compromised quality of life can predispose this population to the occurrence of non-psychotic psychiatric disorders such as depression, making them vulnerable to substance abuse. Objectives: To evaluate the level of consumption of alcohol and drugs in patients with SCD followed by Sickle Cell Disease Reference Center (CRAF) at Hospital de Clínicas de Porto Alegre; to estimate the percentage of patients in treatment of SCD who abuse alcohol and drugs, and to collaborate with the study evaluating the effectiveness of the CRAF. Methods: cross-sectional study of a convenience sample of 139 patients with SCD treated at CRAF. Results: the prevalence of abusive use of the studied population was 1.5% for alcohol and 3.0% for tobacco, and no abusive use of any other substance, including opioids, was identified. It was verified that the pattern for substance use was not influenced by exposure to substances or the presence of non-psychotic psychiatric disorders. Conclusion: More studies are needed to reinforce these findings, but they suggested that the use of opioid analgesics for the management of SCD painful crises is safe and do not induces substance abuse.

Submitted by MARIA EULÁLIA BALEOTTI null (mabaleotti@yahoo.com.br) on 2017-05-06T05:24:22Z No. of bitstreams: 1 Maria Eulalia Baleotti - Unesp - Dissertação versão final _M1_ _T1_.pdf: 975486 bytes, checksum: 875b7d0e99029d3a312012a165ce439c (MD5) / Rejected by Luiz Galeffi (luizgaleffi@gmail.com), reason: Solicitamos que realize uma nova submissão seguindo a orientação abaixo: O arquivo submetido não contém o certificado de aprovação. Corrija esta informação e realize uma nova submissão com o arquivo correto. Agradecemos a compreensão. on 2017-05-08T16:42:03Z (GMT) / Submitted by MARIA EULÁLIA BALEOTTI null (mabaleotti@yahoo.com.br) on 2017-05-09T02:13:09Z No. of bitstreams: 1 Maria Eulalia Baleotti - Unesp - Dissertação versão final _M1_ _T1_.pdf: 1404968 bytes, checksum: ed93838350a715d82b43c32074f22275 (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-05-10T17:49:28Z (GMT) No. of bitstreams: 1 baleotti_ma_me_assis.pdf: 1404968 bytes, checksum: ed93838350a715d82b43c32074f22275 (MD5) / Made available in DSpace on 2017-05-10T17:49:28Z (GMT). No. of bitstreams: 1 baleotti_ma_me_assis.pdf: 1404968 bytes, checksum: ed93838350a715d82b43c32074f22275 (MD5) Previous issue date: 2017-03-07 / Fármacos antidepressivos como os inibidores seletivos de recaptação de serotonina (ISRSs; exemplos: fluoxetina e escitalopram) são drogas de primeira escolha no tratamento dos Transtornos de Ansiedade Generalizada (TAG) e do Transtorno do Pânico (TP). No entanto, apesar de eficazes na terapêutica, esses fármacos apresentam limitações no seu uso, tais como: os efeitos desejados ocorrem somente após administração crônica, em torno de 3 a 4 semanas após o início do tratamento; a proporção relativamente alta de pacientes que não respondem à medicação e o frequente aumento nos níveis de ansiedade desse pacientes no início do tratamento, levando à descontinuidade do uso destas drogas. Nesse sentido, há grande interesse na busca de novas estratégias de tratamento, identificando outros sistemas de neurotransmissão que possam estar relacionados à etiologia e, consequentemente, ao tratamento desses transtornos de ansiedade. Estudos prévios apontaram o envolvimento de opioides endógenos na modulação da ansiedade. Mais especificamente em relação ao TP, já se constatou que mecanismos opioides favorecem a atividade inibitória da serotonina em neurônios da Substância Cinzenta Periaquedutal Dorsal (SCPD) que modulam a fuga/pânico, possivelmente por meio da formação de heterodímeros entre receptores 5-HT1A e μ-opioide. Com base em tais aspectos, o presente estudo teve por objetivo investigar o efeito da Buprenorfina, um agonista parcial de receptores µ-opioide e antagonista de receptores κ-opioide, sobre a manifestação de comportamentos defensivos relacionados com o TAG e com o TP. O uso de agonistas parciais justifica-se pela possibilidade de atenuar efeitos adversos sobrevindos do uso contínuo de agonistas plenos para os receptores µ-opioide, tais como a euforia, a tolerância e a dependência. Para isto, foram conduzidos dois experimentos utilizando ratos Wistar, seguindo-se em cada um deles dois tipos de avaliação: Teste de analgesia, como parâmetro da eficácia do fármaco e testes comportamentais Labirinto em T Elevado (LTE), Campo Aberto e Transição Claro-Escuro. No primeiro experimento foi implantado cirurgicamente um adesivo de Buprenorfina (5mg) entre a pele e o tecido subcutâneo, cujas avaliações foram conduzidas 27 horas após o implante. No segundo experimento utilizou-se um extrato liofilizado da Buprenorfina a partir dos adesivos, em 3 doses diferentes: 1,5 mg/kg; 3,0 mg/kg; 6,0 mg/kg. Todas as avaliações ocorreram 10 minutos após as injeções intraperitoneais. Os resultados mostraram que a Buprenorfina nas doses e vias estudadas desinibiu o comportamento de esquivas inibitórias no LTE e o comportamento motor dos ratos no Teste do Campo Aberto, mas não afetou as fugas no LTE e nem outras manifestações comportamentais no Teste de Transição Claro-Escuro, exceto no implante do adesivo, quando se observou ansiólise nesse teste. Na administração por via IP, esses resultados ocorreram em todos os testes, mas somente na reexposição, 24 horas após a primeira avaliação comportamental. Em conclusão, a Buprenorfina nas doses e vias estudadas apresentou efeito analgésico e desinibiu o comportamento de esquivas e o comportamento motor dos ratos, mas não afetou as fugas, o que indica seu envolvimento na modulação de comportamentos defensivos apenas relacionados com a manifestação da ansiedade generalizada. Nesta dissertação, para maior aprofundamento do tema, foi inicialmente apresentada uma fundamentação teórica geral sobre as variáveis sob foco de investigação. Na sequência, foi exposto um artigo contendo uma fundamentação teórica mais específica, a descrição metodológica, bem como a análise e discussão dos resultados dos experimentos realizados. / Antidepressant drugs such as the selective serotonin reuptake inhibitors (SSRI; examples: fluoxetine and escitalopram) are first choice drugs for treating Generalized Anxiety Disorders (GAD) and Panic Disorder (PD). However, in spite of being therapeutically effective, such drugs present use limitations, such as: the desired effects occur only after chronic administration, within 3 to 4 weeks after the beginning of treatment; a relatively high proportion of patients who do not respond to the drug and the frequent increase of anxiety levels of such patients at the beginning of the treatment, leading to discontinuity in the use of such drugs. Along these lines, there is a great interest in the search of new treatment strategies, identifying other neurotransmission systems which may be related to the etiology and, consequently, to the treatment of such anxiety disorders. Previous studies pointed to the involvement of endogenous opioids in anxiety modulation. More specifically in relation to PD, one has found out that opioid mechanisms favor the inhibitory activity of serotonin in periaqueductal grey matter (dPAG) neurons which modulate escape/panic, probably by means of the formation of heterodimers between 5-HT1A and μ-opioide receptors. Based on such features, this study was carried out aiming at investigating buprenorfine effects, a partial μ-opioide receptor agonist and κ- opioidereceptor antagonist, on the manifestation of defensive behaviors related to GAD and PD. The use of partial agonists is justified by the possibility of attenuating adverse effects occurred after the continuous use of full agonists for μ- opioidereceptors, such as euphoria, tolerance and dependence. Therefore, two experiments werecarread out using Wistar rat, each one followed by two assessment types: analgesia test, as efficiency parameter of the drug and behavioral tests the elevated T-maze (ETM), Open Field and Light-Dark Transition. In the first experiment was surgically implanted a buprenorfine patch (5 mg) between the skin and the subcutaneous tissue, whose assessments were carried out 27 hours after the implantation. In the second experiment was used a buprenorfine extract based on the patches, with three different doses: 1.5 mg/kg; 3.0 mg/kg; 6.0 mg/kg. All the assessments were carried out 10 minutes after the intra-peritoneal injections. The results showed that buprenorfine administered in the studied doses and means uninhibited the inhibiting escape behavior in LTE and the motor behavior of rat in the Open Field Test, but did not affect escapes in LTE nor in other behavioral manifestations in the Light-Dark Transition Test, with the exception of the patch implant, when we were observed anxiolysis in this test. In the IP administration, such results occurredin all the tests, but only in the re-exposure, 24 hours after the first behavioral assessment. In conclusion, buprenorfine administered in doses and methods produced analgesic effect and impaired of the avoidance, but did not affected the escapes, which shows the involvement of this drug in the modulation of defensive behaviors only related whit manifestation of generalized anxiety. In this dissertation, presented a general theoretical foundation on the variables focused on the investigation and afterwards, a paper with a more specific theoretical foundation, the methodological description, as well as the analysis and discussion of the results yielded in the conducted experiments.

O consumo de drogas e álcool constitui cada vez mais um problema social e de saúde pública, pelas consequências negativas que provocam no desenvolvimento emocional e físico dos indivíduos. Existem poucas referências na literatura avaliando o uso destas substâncias por portadores de doença falciforme (DF). Estes pacientes apresentam crises álgicas severas, recorrentes, frequentemente controladas por opióides. O comprometimento da qualidade de vida predispõe a ocorrência de transtornos psiquiátricos não-psicóticos, como depressão por exemplo, tornando o grupo vulnerável ao uso abusivo de substâncias. Objetivos: avaliar o consumo de álcool e drogas em pacientes portadores de DF acompanhados pelo Centro de Referência de Doença Falciforme (CRAF) do Hospital de Clínicas de Porto Alegre (HCPA), estimar o percentual de pacientes em tratamento da doença falciforme que fazem uso abusivo de álcool e drogas, e colaborar com o estudo que avaliará a efetividade de um centro de referência multidisciplinar para esta população. Métodos: estudo transversal, de uma amostra de conveniência, com 139 pacientes portadores de DF acompanhados no CRAF do HCPA. Resultados: a prevalência do uso abusivo foi de 1,5% para o álcool e 3,0% para o tabaco, e não se identificou o uso abusivo de outras substâncias, inclusive opióides. O padrão para o uso de substâncias não foi influenciado pela exposição ou por transtornos psiquiátricos não-psicóticos. Conclusão: São necessários mais estudos para reforçar estes achados, mas demonstra-se a segurança do uso de analgésicos opióides para o manejo das crises dolorosas apresentadas pelos portadores de DF. / Drug abuse is increasingly becoming a social and public health problem, because of the negative consequences that such abuse causes on the emotional and physical development of individuals. There are few references in the literature evaluating the use of these substances by individuals with sickle cell disease (SCD). These patients have severe and recurrent pain crises, frequently needing opioids drugs to control it. The compromised quality of life can predispose this population to the occurrence of non-psychotic psychiatric disorders such as depression, making them vulnerable to substance abuse. Objectives: To evaluate the level of consumption of alcohol and drugs in patients with SCD followed by Sickle Cell Disease Reference Center (CRAF) at Hospital de Clínicas de Porto Alegre; to estimate the percentage of patients in treatment of SCD who abuse alcohol and drugs, and to collaborate with the study evaluating the effectiveness of the CRAF. Methods: cross-sectional study of a convenience sample of 139 patients with SCD treated at CRAF. Results: the prevalence of abusive use of the studied population was 1.5% for alcohol and 3.0% for tobacco, and no abusive use of any other substance, including opioids, was identified. It was verified that the pattern for substance use was not influenced by exposure to substances or the presence of non-psychotic psychiatric disorders. Conclusion: More studies are needed to reinforce these findings, but they suggested that the use of opioid analgesics for the management of SCD painful crises is safe and do not induces substance abuse.

A estimulação opioidérgica decorrente do tratamento com morfina em fêmeas reprodutoras gera efeitos moleculares e comportamentais tardios diferenciados de acordo com o estado fisiológico no momento do tratamento. Trabalhos prévios têm demonstrado um importante papel da substância cinzenta periaquedutal (PAG) neste fenômeno. Assim, investigou-se a expressão dos receptores opióides centrais, por meio de estudos da atividade dos seus genes e da presença dos respectivos produtos protéicos. Possíveis modulações decorrentes do uso agudo e crônico de agonistas dos receptores de opióides na PAG durante os períodos de gestação ou lactação no comportamento maternal em ratas também foram investigadas. Os resultados mostraram que a expressão dos receptores opióides na PAG em fêmeas é modulada tanto pelo estado fisiológico como por desafios farmacológicos com possíveis implicações para o comportamento maternal. / Morphine-induced opioidergic stimulation leads to tardive molecular and behavioral changes in female rats. Previous works have demonstrated a role for the periaqueductal grey (PAG) on opioid-mediated behavioral selection during lactation. This study was designed to investigate the maternal behavior and the physiological and pharmacological modulation of the expression of opioid receptors. The results showed that PAG opioid gene expression is modulated both by physiological status and pharmacological treatments. These data may have implications for maternal behavior.