Crenças, atitudes e comportamentos de saúde e de risco de adictos em comunidades terapêuticas

Os comportamentos de saúde e de risco são comuns em toxicodependentes. Este trabalho foi conduzido no âmbito da análise descritiva da amostra, nomeadamente, caracterização sócio-demográfica e variáveis cognitivas, seguindo-se um segundo objectivo que consistiu na descrição dos comportamentos, crenças e atitudes face à saúde que os adictos apresentam. A amostra é constituída por 75 sujeitos, do sexo masculino, com uma média de idade de 34,07 anos. A metodologia utilizada caracteriza o estudo de quantitativo-correlacionai, uma vez que se pretende efectuar a descrição das características da amostra e os comportamentos de saúde e de risco que apresentam. Os resultados revelam que os adictos apresentam comportamentos de risco, logo, são menores os comportamentos de saúde adoptados durante os consumos. É necessário intervir nas várias áreas de saúde do adicto, nomeadamente, nas práticas sexuais, na prevenção de doenças, nos cuidados alimentares, na conduta rodoviária e na preocupação com o exercício físico-desportivo. /ABSTRACT: Health behaviors and risk factors are common in drug addicts. This work was conducted under the descriptive analysis, including socio-demographic and cognitive variables, followed by a second objective was to describe the altitudes, beliefs and altitudes towards health that addicts have. The sample consists of 75 subjects were mala, with a mean age of 34.07 years. The methodology characterizes the quantitative and correlational study, since we intend to perform the description of sample characteristics and health behaviors and risk they present. The results show that addicts exhibit risky behavior, so they are smaller health behaviors adopted during the intake. lt is necessary to intervene in several areas of health of the addict, including sexual practices, disease prevention, care food, conduct road and the concern that physical exercise I sports.

Delito y enfermedad mental: consumo de sustancias legales e ilegales

 Resumen  Palabras clave: drogas, psiquiatrización, medicalización, control social.AbstractThe article addresses the connections between medicalization and the prosecution of the consumption of substances called narcotics and their effects on the subject- a subject who, at the same time, is entitled to rights. Through the examination of six judicial warrants for compulsory admissions to a "psychiatric colony", the working of the interconnection between legal and psychiatric practices is analyzed. What is also analysed are the effects such interconnection has on the construction of a broader spectrum of action and intervention, both of the judiciary and the medical practices, beyond the framework of the statutory regulations upon which such admissions are based. From the examined material two main aspects come to light: firstly, the medical and mental-health arguments from which decisions about psychiatric hospital admissions in drug or alcohol abuse cases will be made. Secondly, there is also an indication of the purpose or objective of such hospital admissions. This paper also deals with the processes that Foucault calls "indefinite medicalization « and the real productions that go beyond therapeutic aspects, relating the effects of the former with the workings of the control of subjects through the different diagnoses categories of addicts, be it alcoholics or drug addicts.Keywords: drug, psychiatrization, medicalization, social control. 

Spatially defined peptidomimetics for pain relief and for targeted cancer therapy and diagnostics

Cancer is a disease that has plagued scientists for decades, and how to treat cancer and its complications are inevitable topics in current scientific research. Cancer pain is a major factor that reduces the quality of life of patients. Therefore, the development of analgesic agents with minimal adverse side effects, especially with low addiction, has attracted more and more attention. Among them, opioid analgesics are widely used to alleviate cancer pain and improve the quality of life of patients with advanced cancer, such as in the palliative therapy. Although peptide drugs are efficient, selective and safe, they have several unignorable disadvantages such as poor biological stability, rapid excretion, difficulty in penetrate blood brain barrier. In order to solve these problems, peptidomimetics were developed by introducing unnatural/modified amino acids, decorated peptide backbone, conformational restrictions and secondary structure mimics in peptide sequence. Compared with peptides, peptidomimetics have improved biological stability, increased bioavailability, high affinity and selectivity for receptor binding, and decreased adverse side effects. As the second part of this thesis, I explored the opportunity to design peptide-functionalized responsive biomaterials for the detection of cancer cell and the selective delivery of cytotoxic drugs. The conjugation of peptides with biomaterials enhanced the stability of the loaded drugs, improved targeted delivery, decreased side effects, and increased bioavailability. The precise and controllable drug delivery platform has profound application prospects in cancer treatment. Grafting specific peptides sequence on the surface of biomaterials can satisfy different drug delivery demands according to the characteristics of both peptides and biomaterials. For example, the introduction of tumor-targeting peptides can guide biomaterials into tumor lesions, and blood-brain barrier (BBB) shuttle peptides can lead biomaterials to penetrate the BBB, etc.

The role of Proteasome in the development, maintenance and management of Chronic Pain

In chronic pain, opioids represent the gold standard analgesics, but their use is hampered by the development of several side effects, as development of analgesic tolerance and opioid-induced hyperalgesia. Evidence showed that many molecular mechanisms (changes in opioid receptors, neurotransmitter release, and glia/microglia activation) are involved in their appearance, as well as in chronic pain. Recently, a crucial role has been proposed for oxidative stress and proteasome in chronic pain and in treatment-related side effects. To better elucidate these aspects, the aim of this PhD thesis was to investigate the effects of opioids on cell oxidative stress, antioxidant enzymatic machinery and proteasome expression and activity in vitro. Also, the involvement of proteasome in the development of chronic pain conditions was investigated utilizing an experimental model of oxaliplatin-induced neuropathy (OXAIN), in vivo. Data showed that morphine, fentanyl, buprenorphine and tapentadol alter differently ROS production. The ROS increasing effect of morphine is not shared by the other opioids, suggesting that the different pharmacological profile could influence this parameter. Moreover, these drugs produced different alterations of β2trypsin-like and β5chymotrypsin-like activities. In fact, while morphine and fentanyl increased the proteolytic activity after prolonged exposure, a different picture was observed for buprenorphine and tapentadol, suggesting that the level of MOR agonism could be strongly related with proteasome activation. In vivo studies revealed that rats treated with oxaliplatin showed a significant increase in β5, in the thalamus (TH) and somatosensory cortex (SSCx). Moreover, a selective up-regulation of β5 and LMP7 subunit gene expression was assessed in the SSCx. Furthermore, our study revealed that oprozomib, a selective β5 inhibitor normalized the spinal prodynorphin gene expression upregulation induced by oxaliplatin, and reverted mechanical/thermal allodynia and mechanical hyperalgesia in oxaliplatin-treated rats. These results underline the role of proteasome in the OXAIN and suggest new pharmacological targets to counteract it.

Evaluation of clinical implications correlate to genetic polymorphisms and pharmacokinetic of transdermal fentanyl

ABSTRACT Background:Strong opioids are the treatment of choice for moderate to severe cancer-related pain. Fentanyl is a synthetic opioid with high affinity for the μ-opioid receptor and is 75–100 times more potent than morphine. Fentanyl is metabolised rapidly, particularly in the liver and only 10% is excreted as intact substance. The use of CYP3A4 inhibitors and inducers, impaired liver function, and heating of the patch potentially influence fentanyl pharmacokinetics in a clinically relevant way. The influence of BMI and gender on fentanyl pharmacokinetics is questionable. Pharmacogenetic, may influence fentanyl pharmacokinetic and other factors have been studied but did not show significant and clinically relevant effects on fentanyl pharmacokinetic. Method: This is a biological interventional prospective, single-center study in 49 patients with solid or haematological neoplasm treated with transdermal fentanyl undergoing 5-step pharmacokinetic and pharmacogenetic withdrawals from administration of the fentanyl patch. Objective:to evaluate the pharmacokinetic and pharmacogenetic of transdermal fentanyl in relation to the patient's clinical response on pain Results: Sex was the only parameter with evidence of different distribution between responders and non-responders , showing a major chance for male to be responders than females. We found some correlation with pharmacokinetic parameters and sex, regarding adverse events and NRS correlation with BPI. NAT2 and UGT2B7 polymorphisms are associated with AUC and Cmax kinetics parameters, NAT2 and CYP4F2 showed some evidence of association with the fentanyl dosage and CYP2B6 polymorphism seemed to be correlate with side effects. Conclusion: Small sample size of study population make difficult do find some significant correlation between pharmacogenetic, pharmacokinetic and clinical response. Larger studies are needed to increase knowledge about response to opioid treatment in cancer patients to better individualized pain treatment.