Fundação de Amparo a Pesquisa no Estado do Rio Grande do Sul / Opioids are the most common drugs prescribed worldwide for alleviating moderate to severe pain. However, the use of opioids is associated with the development of tolerance to the analgesic effect and potential adverse effects, such as paradoxical hyperalgesia, withdrawal syndrome and constipation. An important target for morphine-induced analgesia is the blockade of voltage-gated calcium channels (VGCCs). However, the participation of VGCCs in the tolerance and adverse effects caused by morphine is poorly understood. Thus, the present study was conducted in order to evaluate the possible actions of Phα1β, a peptide inhibitor of VGCCs purified from the venom of the Phoneutria nigriventer spider on the antinociceptive and adverse effects produced by single or repeated administration of morphine. It was evaluated the effect of intrathecal injection Phα1β (0.01-30 pmol/site) on mechanical and heat hyperalgesia, tolerance, withdrawal syndrome and constipation induced throught single (10 mg/kg) or repeated (increasing doses, 3 times a day, for 3 consecutive days) subcutaneous treatment of morphine in C57BL/6 mice. We observed that a single administration of morphine was able to reduce heat but not mechanical nociception as well as decrease gastrointestinal transit. The antinociception, but not the constipation, caused by a single injection of morphine was slightly increased by an intrathecal injection of Phα1β. Repeated treatment with morphine caused not only tolerance to its antinociceptive effect but also induced paradoxical heat and mechanical hyperalgesia, withdrawal syndrome and constipation. Phα1β was able to reverse the tolerance, withdrawal syndrome, mechanical and heat hyperalgesia and constipation induced by repeated morphine treatment. Finally, the effects produced by the native form of Phα1β were fully mimicked by a recombinant version of this peptide in naïve mice. Our results suggest that Phα1β is effective in potentiating the analgesia as well as in reducing tolerance and the adverse effects induced by morphine, indicating its potential use as an adjuvant drug in combination with opioids. / Os opióides são os medicamentos mais comuns prescritos em todo o mundo para aliviar as dores moderadas a intensas. No entanto, a utilização de opióides está associada com o desenvolvimento de tolerância ao efeito analgésico e de efeitos adversos, tais como hiperalgesia paradoxal, síndrome de abstinência e constipação. Um alvo importante para a analgesia induzida pela morfina é o bloqueio dos canais de cálcio regulados por voltagem (CCRV). Porém pouco se sabe sobre o papel desses canais na tolerância e nos efeitos adversos produzidos pela morfina. Assim, o presente estudo foi realizado com o intuito de avaliar as possíveis ações da Phα1β, um inibidor peptídico dos CCRVs purificado do veneno da aranha Phoneutria nigriventer, sobre os efeitos antinociceptivos e adversos produzidos pela administração única ou repetida de morfina. Foi avaliado o efeito da administração intratecal da Phα1β (0.01-30 pmol/site) sobre a hiperalgesia térmica e mecânica, tolerância, síndrome de abstinência e constipação induzidos pelo tratamento único (10 mg/kg) ou repetido (doses crescentes, 3 vezes ao dia, durante três dias) de morfina por via subcutânea em camundongos C57BL/6. Observamos que uma única administração de morfina foi capaz de reduzir a nocicepção térmica mas não a mecânica em camundongos, bem como reduzir o trânsito gastrointestinal. A antinocicepção, mas não a constipação, causada por uma única dose de morfina foi levemente aumentada pela administração intratecal da Phα1β. O tratamento repetido com morfina não causou somente tolerância analgésica como também induziu hiperalgesia, síndrome de abstinência e constipação. A Phα1β foi capaz de reverter a tolerância, a síndrome de abstinência, a hiperalgesia mecânica e térmica e a constipação induzidas pelo tratamento repetido de morfina. Finalmente, os efeitos produzidos pela forma nativa Phα1β foram totalmente mimetizados por uma versão recombinante do presente peptídeo. Em conclusão, nossos resultados sugerem que a Phα1β é efetiva em potencializar a analgesia, bem como, reduzir a tolerância e os efeitos adversos induzidos pela morfina. Desta maneira, a Phα1β apresenta um uso potencial como uma droga adjuvante na terapia opióide.

Opioid use disorder (OUD) impacts 5.6 million people in the US. Buprenorphine (BUP) is a commonly prescribed opioid medication used to treat OUD, including in pregnant women. However, opioid use during pregnancy is associated with poorer infant outcomes including reduced fetal growth, neurodevelopmental deficits, and neonatal opioid withdrawal syndrome (NOWS). Recent clinical data suggests that providing mothers with a lower dose of BUP may result in fewer negative outcomes in infants. Here, a preclinical rodent model of low-dose perinatal BUP exposure was used to study offspring health outcomes in the neonate, juvenile, and adolescent offspring. Dams were given clinically relevant doses of BUP prior to and throughout gestation, and continuing through weaning to mimic human doses and exposure. Although the lowest BUP dose still elicited signs of NOWS in offspring, there were fewer negative effects on overall brain morphology across the early lifespan than that of the higher BUP dose compared to controls.

DUBOVÁ, T. Rehabilitation of family drug addicted parents. Key words: Abstinence - oriented treatment, Dependance syndrome, Dysfunctional family, Rehabilitation of family, Resocialization, Withdrawal syndrome This thesis addresses the issue of drug addiction and parenting. It focuses on society's view on drug addicted parents and briefly defines the concept of addiction. The core work is the rehabilitation of these families and its various forms. It describes the role of professional institutions that deal with protecting the interests of the child and work with drug addicted parents and contributes to the rehabilitation of the family. The work also includes specific aspects of women's drug addiction and the consequences of substance use during pregnancy on the child. At the end of the theoretical chapter is devoted to professional institutions and their programs to work with the family. The practical part of this thesis includes three case studies that describe families of drug addicted parents and the way their efforts to restore or maintain the family.

La adicción es un trastorno crónico de la conducta caracterizado por la búsqueda y el consumo compulsivos de la droga, la pérdida de control para limitar dicho consumo, a aparición de un estado emocional negativo cuando el acceso a la droga está impedido y la recaída en el proceso incluso tras largos períodos de abstinencia. El sistema dopaminérgico mesolímbico cortical ha sido propuesto como la principal base neurobiológica de la adicción, sin embargo existen otros sistemas de neurotransmision que participan en la consolidación del proceso adictivo.El sistema endocannabinoide, a traves del receptor CB1, participa en las propiedades adictivas de diferentes drogas de abuso como el delta9-tetrahidrocannabinol, la nicotina y la morfina. Sin embargo, hasta el momento de iniciar este trabajo, pocos estudios han demostrado una clara implicación del sistema endocannabinoide en las propiedades reforzantes de los psicoestimulantes. Mediante el uso de ratones CB1 knockout, hemos demostrado que el receptor CB1 participa en la eficacia reforzante de la cocaína. Además, la presencia de dicho receptor es necesaria para los procesos de consolidación de una conducta operante mantenida por la autoadministración de cocaína. Este estudio demuestra la importancia de dicho receptor CB1 en las propiedades adictivas de la cocaína, confirmando que el sistema endocannabinoide es un sustrato común para la adicción de drogas de abuso. Por otra parte, el sistema purinérgico modula numerosos sistemas de neurotransmisión en el SNC. La estrecha relación a nivel celular y funcional entre los receptores de adenosina y los receptores dopaminérgicos proporciona evidencias de que el sistema purinérgico podría modular los sistemas de recompensa. Utilizando diferentes modelos animales, hemos demostrado que los receptores de adenosina A2A son necesarios para que las propiedades adictivas de las drogas de abuso como los cannabinoides, los opioides, la nicotina y los psicoestimulantes se produzcan de un modo completo.Nuestros estudios nos permiten afirmar que ambos sistemas, el cannabinoide y el purinérgico podría suponer la existencia de nuevos sistemas de modulación común de los procesos adictivos. Asi, sería de gran interés desarrollar nuevas estrategias de bloqueo de los receptores A2A y CB1 para atenuar e incluso prevenir el desarrollo de la adicción. / Drug addiction is a chronically relapsing disorder that is defined by a compulsion to take the drug intake, a loss of control in limiting intake and a withdrawal-negative affect state when the access to the drug is interrupted. Mesolimbic dopaminergic system has been proposed as a fundamental neurobiological substrate for drug addiction. However, there is evidence for other neurotransmitter systems involved in the consolidation of the addictive process. The endocannabinoid system, through the activation of CB1 receptor, participates in the addictive properties of different drugs of abuse such as delta9-tetrahydrocannabinol, morphine and nicotine. Nevertheless, few studies have revealed an important implication of CB1 receptor in the reinforcing properties of psychostimulants. By using CB1 knockout mice, we have demonstrated that CB1 receptor participates in the reinforcing efficacy of cocaine. Moreover, this receptor is necessary for the consolidation processes involved in cocaine maintained intravenous self-administration. Therefore, this study reveals an essential role of CB1 receptor in cocaine addictive properties, confirming that the endocannabinoid system is a common substrate of addiction to drugs of abuse.On the other hand, the purinergic system modulates different neurotransmitter systems in the CNS. Adenosine receptors are closely related to dopaminergic receptors at both cellular and functional levels, suggesting that purinergic system could modulate the reward systems. By using different animal models, we have demonstrated that A2A adenosine receptors are necessary for the development of the addictive properties of drugs of abuse such as opioids, cannabinoids, nicotine and cocaine. Our studies suggest that both cannabinoid and purinergic systems could represent new and common modulatory systems of addictive processes. Thus, it would be of interest to develop new therapeutic targets blocking CB1 and A2A receptors to attenuate the development of addiction.

No description available.

This study examined healthcare professionals’ perceptions on feeding difficulties experienced by infants with NOWS, the involvement of SLP in care, knowledge and experience levels of professionals, and trends in education and follow up care. A 34-question survey was developed to obtain data from participants involved in the care of exposed infants using the secure webbased RedCap™ platform. Nonparametric inferential statistics and descriptive analysis were used to interpret data. Feeding difficulties in infants exposed were reported by all respondents with SLP involvement reported by 42.2%. Results found that 51.9% of respondents were confident in their ability to educate families about feeding difficult with 60% reported inadequate time to provide education. Discharge follow up was inconsistent amongst facilities. The study supports early involvement of SLPs to address feeding difficulties and improve education.

This study was designed to understand the meaning of the lived experiences of incarcerated male juveniles who had committed drug-related crimes and to suggest guidelines for their rehabilitation with specific reference to their health care needs. In order to achieve these objectives, the researcher used Parse’s (1998) Theory of Human Becoming as a theoretical framework for the study and Parse’s (1998, 2005) phenomenological-hermeneutic research method. This study was restricted to three juvenile correctional centres in the Gauteng province, Republic of South Africa (RSA). A sample of 15 male juveniles (5 at each of the three juvenile correctional centres) was used for the purpose of individual dialogical engagements with the participants. Focus group interview sessions were held with two groups (5 members per group) at two identified juvenile correctional centres. A qualitative content analysis according to methods recommended by Graneheim and Lundman (2004) was performed on the data that was collected from the individual dialogical-engagements and the focus group interviews. The researcher attempted to elucidate the meanings that the participants attached to their experiences of incarceration as narrated by them and analysed the data according to Parse’s (1998; 2005) phenomenological-hermeneutic method comprising of extraction-synthesis and heuristic interpretation. The findings of this research confirm that problems of drug abuse and criminal activity represent a multifaceted, complex and often intractable phenomenon. The research also confirmed that the participants suffer from a variety of emotional and psychological problems such as depression, anxiety, fear, guilt, remorse, regret and a craving for the drugs that they had abused before their incarceration. It appears that the participants find it extremely difficult to deal effectively with these disorders on their own and that they are generally averse to asking for professional help and assistance. Interventions to alleviate these problems are crucial for the success of the current rehabilitation programmes being pursued in the correctional centres where the participants are accommodated. / Health Studies / D. Litt. et Phil. (Health Studies)

This diploma thesis explores the phenomenon of formation and development of alcohol dependence. In the first series focuses on the historical description, which demonstrates considerable anchored in the life of our ancestors already. It also defines the concept of addiction, its causes and consequences, whether psychological, medical or social. Its objective is to describe the possibilities of social work in this phenomenon. defines therefore primarily targets and understanding of social work and consequently specifics of client alcoholism. An important element is the role of the social worker in the client's motivation to change, which uses Nešpor's model of spontaneous changes in motivation. Then, on the basis of available social services selects several most suitable, which can help to improve the client's situation. Has an essential role in this issue also primary prevention, ie it discusses the methodology, target groups, focusing on adolescents and the focus is on the firm role of the family. Finally contains some official documents on primary prevention, which are discussed current issues of primary prevention practice and subsequent survey, mapping aspect of social workers on the incidence risk of alcohol dependence among adolescents attending social facilities.

The aim of this thesis is to draw attention to the serious problem of drug addiction among adolescents who are abusing addictive substances or marijuana. This increasingly important issue is discussed a lot, but very often neglected by the society. This thesis provides definitions and characteristics of individual drugs and their effects on adolescents. The need for prevention and treatment of adolescent clients is emphasized, alongside with the family support, which is often crucial. In the practical part, the author of the thesis focuses on organizations that are critically important in this field. These organizations focus on prevention, counseling services, social inclusion and treatment facilities (inpatient and outpatient services), etc. Their characteristics and methods of client treatment are described. Furthermore, in this work the author presents a survey that confirms the findings of some detailed quantitative research papers. The main findings are that drug abuse is a major problem of this century and also a burden on society, especially on the adolescents themselves. The solution is very complicated and time consuming, but everyone can contribute by not being indifferent to this problem.

This study was designed to understand the meaning of the lived experiences of incarcerated male juveniles who had committed drug-related crimes and to suggest guidelines for their rehabilitation with specific reference to their health care needs. In order to achieve these objectives, the researcher used Parse’s (1998) Theory of Human Becoming as a theoretical framework for the study and Parse’s (1998, 2005) phenomenological-hermeneutic research method. This study was restricted to three juvenile correctional centres in the Gauteng province, Republic of South Africa (RSA). A sample of 15 male juveniles (5 at each of the three juvenile correctional centres) was used for the purpose of individual dialogical engagements with the participants. Focus group interview sessions were held with two groups (5 members per group) at two identified juvenile correctional centres. A qualitative content analysis according to methods recommended by Graneheim and Lundman (2004) was performed on the data that was collected from the individual dialogical-engagements and the focus group interviews. The researcher attempted to elucidate the meanings that the participants attached to their experiences of incarceration as narrated by them and analysed the data according to Parse’s (1998; 2005) phenomenological-hermeneutic method comprising of extraction-synthesis and heuristic interpretation. The findings of this research confirm that problems of drug abuse and criminal activity represent a multifaceted, complex and often intractable phenomenon. The research also confirmed that the participants suffer from a variety of emotional and psychological problems such as depression, anxiety, fear, guilt, remorse, regret and a craving for the drugs that they had abused before their incarceration. It appears that the participants find it extremely difficult to deal effectively with these disorders on their own and that they are generally averse to asking for professional help and assistance. Interventions to alleviate these problems are crucial for the success of the current rehabilitation programmes being pursued in the correctional centres where the participants are accommodated. / Health Studies / D. Litt. et Phil. (Health Studies)