Pharmacology and Therapeutic Potential of Sigma1 Receptor Ligands

Sigma (σ) receptors, initially described as a subtype of opioid receptors, are now considered unique receptors. Pharmacological studies have distinguished two types of σ receptors, termed σ1 and σ2. Of these two subtypes, the σ1 receptor has been cloned in humans and rodents, and its amino acid sequence shows no homology with other mammalian proteins. Several psychoactive drugs show high to moderate affinity for σ1 receptors, including the antipsychotic haloperidol, the antidepressant drugs fluvoxamine and sertraline, and the psychostimulants cocaine and methamphetamine; in addition, the anticonvulsant drug phenytoin allosterically modulates σ1 receptors. Certain neurosteroids are known to interact with σ1 receptors, and have been proposed to be their endogenous ligands. These receptors are located in the plasma membrane and in subcellular membranes, particularly in the endoplasmic reticulum, where they play a modulatory role in intracellular Ca2+ signaling. Sigma1 receptors also play a modulatory role in the activity of some ion channels and in several neurotransmitter systems, mainly in glutamatergic neurotransmission. In accordance with their widespread modulatory role, σ1 receptor ligands have been proposed to be useful in several therapeutic fields such as amnesic and cognitive deficits, depression and anxiety, schizophrenia, analgesia, and against some effects of drugs of abuse (such as cocaine and methamphetamine). In this review we provide an overview of the present knowledge of σ1 receptors, focussing on σ1 ligand neuropharmacology and the role of σ1 receptors in behavioral animal studies, which have contributed greatly to the potential therapeutic applications of σ1 ligands

Flexibilidad psicológica y autoabandono del tabaco

The prevalence of smoking in the general population remains high in spite of the extended acknowledgement of the well-documented health consequences of smoking and potential benefits of quitting. Only a minority of smokers who attempt to quit seeks professional treatment, yet most of the research on smoking cessation focuses on such form of quitting. Research on self-quitting is scarce, although most smokers who successfully quit, do so on their own. Recently, research has evidenced that psychological flexibility, a core concept in Acceptance and Commitment Therapy, is an important variable in predicting successful behavioral change in many clinically relevant areas. The goal of this study was to analyze the relationship between psychological flexibility and successful self-quitting from smoking. 277 participants who had attempted to quit on their own (217 successfully abstinent and 60 still smoking) provided information on their smoking history, quit attempts, nicotine dependence, and demographics, and were assessed with the Acceptance and Action Questionnaire-II. Abstinence status was measured through self-reports of continuous abstinence and confirmed by concentrations of expired carbon monoxide below 8 ppm. Results show a statistically significant difference (t= -8, 775; p <.01) for the AAQ-II scores of successful (M= 18.39, SD= 7.76) and unsuccessful self-quitters (M= 27.17; SD= 6.88). Only 26% participants with high level of psychological inflexibility quitted successfully, compared to 94% participants with low levels of psychological inflexibility. These results show clear evidence that psychological flexibility is associated to successful self-quitting, and suggest that this variable could facilitate success in attempts to stop smoking without professional help. Implications and limitations of this study are discussed

Trends and outcome of neoadjuvant treatment for rectal cancer: A retrospective analysis and critical assessment of a 10-year prospective national registry on behalf of the Spanish Rectal Cancer Project

Introduction: Preoperative treatment and adequate surgery increase local control in rectal cancer. However, modalities and indications for neoadjuvant treatment may be controversial. Aim of this study was to assess the trends of preoperative treatment and outcomes in patients with rectal cancer included in the Rectal Cancer Registry of the Spanish Associations of Surgeons. Method: This is a STROBE-compliant retrospective analysis of a prospective database. All patients operated on with curative intention included in the Rectal Cancer Registry were included. Analyses were performed to compare the use of neoadjuvant/adjuvant treatment in three timeframes: I)2006–2009; II)2010–2013; III)2014–2017. Survival analyses were run for 3-year survival in timeframes I-II. Results: Out of 14, 391 patients, 8871 (61.6%) received neoadjuvant treatment. Long-course chemo/radiotherapy was the most used approach (79.9%), followed by short-course radiotherapy ± chemotherapy (7.6%). The use of neoadjuvant treatment for cancer of the upper third (15-11 cm) increased over time (31.5%vs 34.5%vs 38.6%, p = 0.0018). The complete regression rate slightly increased over time (15.6% vs 16% vs 18.5%; p = 0.0093); the proportion of patients with involved circumferential resection margins (CRM) went down from 8.2% to 7.3%and 5.5% (p = 0.0004). Neoadjuvant treatment significantly decreased positive CRM in lower third tumors (OR 0.71, 0.59–0.87, Cochrane-Mantel-Haenszel P = 0.0008). Most ypN0 patients also received adjuvant therapy. In MR-defined stage III patients, preoperative treatment was associated with significantly longer local-recurrence-free survival (p < 0.0001), and cancer-specific survival (p < 0.0001). The survival benefit was smaller in upper third cancers. Conclusion: There was an increasing trend and a potential overuse of neoadjuvant treatment in cancer of the upper rectum. Most ypN0 patients received postoperative treatment. Involvement of CRM in lower third tumors was reduced after neoadjuvant treatment. Stage III and MRcN + benefited the most

Curso sobre zoonosis

Centro de Informacion y Documentacion Cientifica (CINDOC). C/Joaquin Costa, 22. 28002 Madrid. SPAIN / CINDOC - Centro de Informaciòn y Documentaciòn CientìficaSIGLEESSpai

Lipid profile of immunocastrated, castrated male and female pigs

RESUMO A presente pesquisa foi realizada com o objetivo de avaliar os níveis de colesterol, extrato etéreo, perfil de ácidos graxos e o índice aterogênico e trombogênico da gordura intramuscular de suínos machos imunocastrados em relação às fêmeas e aos machos castrados cirurgicamente. Utilizaram-se 45 animais, com peso inicial de 25,2±2,8kg, distribuídos em delineamento inteiramente ao acaso, com três tratamentos (machos castrados, machos e fêmeas imunocastrados) e três repetições de cinco animais cada. Os animais foram abatidos a 90,3±2,7kg. As amostras de Longissimus dorsi foram coletadas, liofilizadas e analisadas quanto ao perfil de ácidos gordos, colesterol e extrato etéreo. Não foram observadas diferenças (P>0,05) para nenhuma das variáveis analisadas entre a gordura intramuscular de machos castrados cirurgicamente, machos imunocastrados e fêmeas. A imunocastração não alterou os níveis intramusculares de extrato etéreo, colesterol, composição de ácidos graxos ou o índice aterogênico e trombogênico do Longissimus dorsi