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[PMID]:28589736
[Au] Autor:Zupancic O; Rohrer J; Thanh Lam H; Grießinger JA; Bernkop-Schnürch A
[Ad] Endereço:a Department of Pharmaceutical Technology, Institute of Pharmacy , Leopold-Franzens-University Innsbruck , Innsbruck , Austria.
[Ti] Título:Development and in vitro characterization of self-emulsifying drug delivery system (SEDDS) for oral opioid peptide delivery.
[So] Source:Drug Dev Ind Pharm;43(10):1694-1702, 2017 Oct.
[Is] ISSN:1520-5762
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIM: In this study, self-emulsifying drug delivery system (SEDDS) for oral delivery of opioid peptide dalargin were developed and characterized in vitro. METHODS: Dalargin lipophilicity was increased by O-esterification of tyrosine OH group, hydrophobic ion pairing, or a combination thereof. Distribution coefficients (log D) of lipidized dalargin derivatives were determined. Then, dalargin was incorporated in chosen SEDDS, namely SEDDS-1, composed of 50% Capmul 907, 40% Cremophor EL, and 10% propylene glycol and comparatively more lipophilic SEDDS-2 composed of 30% Captex 8000, 30% Capmul MCM, 30% Cremophor EL, and 10% propylene glycol. Additionally, SEDDS were characterized regarding droplet size, polydispersity index (PDI), cloudy point, physical stability and stability against pancreatic lipase. Furthermore, mucus permeating properties of SEDDS and their ability to protect the incorporated dalargin against proteolysis by trypsin, α-chymotrypsin, elastase, simulated gastric fluid (SGF), and simulated intestinal fluid (SIF) were evaluated. RESULTS: The highest dalargin drug payload of 4.57% in SEDDS-2 was achieved when dalargin palmitate (pDAL) was ion paired with sodium dodecyl sulfate (SDS) in molar ratio 1:1. Moreover, SEDDS-1 and SEDDS-2 had a narrow droplet size distribution with average droplet sizes of 42.1 and 33.1 nm with PDI of 0.042 and 0.034, respectively. Lipolysis study showed that within 30 min 78.5% of SEDDS-1 and 92.1% of SEDDS-2 were digested. In addition, both SEDDS exhibited mucus permeating properties as well as a protective effect against enzymatic degradation by trypsin, α-chymotrypsin, elastase, SGF and SIF. CONCLUSION: The results of this study suggest that the developed SEDDS could be considered for oral opioid peptide delivery.
[Mh] Termos MeSH primário: Caprilatos/química
Quimotripsina/química
Sistemas de Liberação de Medicamentos/métodos
Emulsões/química
Glicerídeos/química
Lipídeos/química
Muco/química
Peptídeos Opioides/química
Polietilenoglicóis/química
Propilenoglicol/química
[Mh] Termos MeSH secundário: Administração Oral
Disponibilidade Biológica
Peptídeos Opioides/administração & dosagem
Peptídeos Opioides/farmacologia
Solubilidade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Caprylates); 0 (Emulsions); 0 (Glycerides); 0 (Lipids); 0 (Opioid Peptides); 30IQX730WE (Polyethylene Glycols); 39279-69-1 (cremophor); 6DC9Q167V3 (Propylene Glycol); EC 3.4.21.1 (Chymotrypsin); EC 3.4.21.1 (alpha-chymotrypsin); VFU0OU98LO (monooctanoin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171020
[Lr] Data última revisão:
171020
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170608
[St] Status:MEDLINE
[do] DOI:10.1080/03639045.2017.1338722


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[PMID]:28583844
[Au] Autor:Bedini A; Baiula M; Vincelli G; Formaggio F; Lombardi S; Caprini M; Spampinato S
[Ad] Endereço:Department of Pharmacy and Biotechnology, University of Bologna, Irnerio 48, 40126 Bologna, Italy.
[Ti] Título:Nociceptin/orphanin FQ antagonizes lipopolysaccharide-stimulated proliferation, migration and inflammatory signaling in human glioblastoma U87 cells.
[So] Source:Biochem Pharmacol;140:89-104, 2017 Sep 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Glioblastoma is among the most aggressive brain tumors and has an exceedingly poor prognosis. Recently, the importance of the tumor microenvironment in glioblastoma cell growth and progression has been emphasized. Toll-like receptor 4 (TLR4) recognizes bacterial lipopolysaccharide (LPS) and endogenous ligands originating from dying cells or the extracellular matrix involved in host defense and in inflammation. G-protein coupled receptors (GPCRs) have gained interest in anti-tumor drug discovery due to the role that they directly or indirectly play by transactivating other receptors, causing cell migration and proliferation. A proteomic analysis showed that the nociceptin receptor (NOPr) is among the GPCRs significantly expressed in glioblastoma cells, including U87 cells. We describe a novel role of the peptide nociceptin (N/OFQ), the endogenous ligand of the NOPr that counteracts cell migration, proliferation and increase in IL-1ß mRNA elicited by LPS via TLR4 in U87 glioblastoma cells. Signaling pathways through which N/OFQ inhibits LPS-mediated cell migration and elevation of [Ca ] require ß-arrestin 2 and are sensitive to TNFR-associated factor 6, c-Src and protein kinase C (PKC). LPS-induced cell proliferation and increase in IL-1ß mRNA are counteracted by N/OFQ via ß-arrestin 2, PKC and extracellular signal-regulated kinase 1/2; furthermore, the contributions of the transcription factors NF-kB and AP-1 were investigated. Independent of LPS, N/OFQ induces a significant increase in cell apoptosis. Contrary to what was observed in other cell models, a prolonged exposure to this endotoxin did not promote any tolerance of the cellular effects above described, including NOPr down-regulation while N/OFQ loses its inhibitory role.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Antineoplásicos/farmacologia
Glioblastoma/tratamento farmacológico
Peptídeos Opioides/farmacologia
Fator 6 Associado a Receptor de TNF/agonistas
Receptor 4 Toll-Like/antagonistas & inibidores
beta-Arrestina 2/agonistas
[Mh] Termos MeSH secundário: Apoptose/efeitos dos fármacos
Astrócitos/efeitos dos fármacos
Astrócitos/imunologia
Astrócitos/metabolismo
Astrócitos/patologia
Sinalização do Cálcio/efeitos dos fármacos
Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Proliferação Celular/efeitos dos fármacos
Regulação Neoplásica da Expressão Gênica
Glioblastoma/imunologia
Glioblastoma/metabolismo
Glioblastoma/patologia
Seres Humanos
Interleucina-1beta/agonistas
Interleucina-1beta/antagonistas & inibidores
Interleucina-1beta/genética
Interleucina-1beta/metabolismo
Ligantes
Lipopolissacarídeos/antagonistas & inibidores
Lipopolissacarídeos/toxicidade
Proteínas de Neoplasias/agonistas
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/metabolismo
Proteínas do Tecido Nervoso/agonistas
Proteínas do Tecido Nervoso/antagonistas & inibidores
Proteínas do Tecido Nervoso/metabolismo
Interferência de RNA
Receptores Opioides/agonistas
Receptores Opioides/genética
Fator 6 Associado a Receptor de TNF/antagonistas & inibidores
Fator 6 Associado a Receptor de TNF/genética
Fator 6 Associado a Receptor de TNF/metabolismo
Receptor 4 Toll-Like/agonistas
Receptor 4 Toll-Like/genética
Receptor 4 Toll-Like/metabolismo
beta-Arrestina 2/antagonistas & inibidores
beta-Arrestina 2/genética
beta-Arrestina 2/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ARRB2 protein, human); 0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Antineoplastic Agents); 0 (IL1B protein, human); 0 (Interleukin-1beta); 0 (Ligands); 0 (Lipopolysaccharides); 0 (Neoplasm Proteins); 0 (Nerve Tissue Proteins); 0 (Opioid Peptides); 0 (Receptors, Opioid); 0 (TLR4 protein, human); 0 (TNF Receptor-Associated Factor 6); 0 (Tifab protein, human); 0 (Toll-Like Receptor 4); 0 (beta-Arrestin 2); 0 (lipopolysaccharide, Escherichia coli O111 B4); 0 (nociceptin receptor); 7AYI9N34FF (nociceptin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170607
[St] Status:MEDLINE


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[PMID]:28574391
[Au] Autor:Gorgiladze T; Nozadze I; Abzianidze E; Tsagareli M
[Ad] Endereço:1Tbilisi State Medical University; 2Beritashvili Center for Experimental Biomedicine, Tbilisi Georgia.
[Ti] Título:NON-STEROIDAL ANTI-INFLAMMATORY DRUGS'S ANTINOCICEPTION MEDIATED BY THE OPIOID MECHANISM IN THE NUCLEUS RAPHE MAGNUS.
[So] Source:Georgian Med News;(265):99-104, 2017 Apr.
[Is] ISSN:1512-0112
[Cp] País de publicação:Georgia (Republic)
[La] Idioma:eng
[Ab] Resumo:It has been established that the midbrain periaqueductal gray matter (PAG) and rostral ventro-medial medulla (RVM) are involved in the descending pain control system. The latter involves the midline nucleus raphe magnus (NRM) and adjacent reticular formation. These brain structures are is one of important parts of CNS circuit that controls nociceptive transmission at the level of spinal cord. Here we report that microinjection of commonly used non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac, ketorolac, metamizol, and xefocam into the NRM produces strong antinociception which is mediated by the opioid mechanism. The experiments were carried out on experimental and control (saline) white albino male rats. Animals were implanted with a guide cannula in the NRM and tested for antinociception following microinjection of NSAIDs into the NRM in the tail flick (TF) and hot plate (HP) tests. The analysis of variance (ANOVA) with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluation. The obtained data show that microinjection of these NSAIDs into the NRM produced antinociception as revealed by a latency increase in the tail-flick (TF) and hot plate (HP) latencies compared to the saline control microinjected into the same nucleus. Furthermore, we definitely showed that pre-treatment with opioid antagonist naloxone in the NRM diminishes NSAID-induced antinociception expressing in significant decrease in TF and HP latencies (P<0.001). The present findings support the concept that antinociceptive effects of NSAIDs are mediated via an endogenous opioid system possibly involving the descending pain modulatory circuit.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Naloxona/farmacologia
Antagonistas de Entorpecentes/farmacologia
Nociceptividade/efeitos dos fármacos
Núcleo Magno da Rafe/efeitos dos fármacos
Peptídeos Opioides/metabolismo
[Mh] Termos MeSH secundário: Animais
Diclofenaco/farmacologia
Dipirona/farmacologia
Cetorolaco/farmacologia
Masculino
Microinjeções
Núcleo Magno da Rafe/fisiologia
Piroxicam/análogos & derivados
Piroxicam/farmacologia
Ratos
Tempo de Reação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Narcotic Antagonists); 0 (Opioid Peptides); 13T4O6VMAM (Piroxicam); 144O8QL0L1 (Diclofenac); 36B82AMQ7N (Naloxone); 6429L0L52Y (Dipyrone); ER09126G7A (lornoxicam); YZI5105V0L (Ketorolac)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170603
[St] Status:MEDLINE


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[PMID]:28318942
[Au] Autor:Adamska-Bartlomiejczyk A; Janecka A; Szabó MR; Cerlesi MC; Calo G; Kluczyk A; Tömböly C; Borics A
[Ad] Endereço:Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
[Ti] Título:Cyclic mu-opioid receptor ligands containing multiple N-methylated amino acid residues.
[So] Source:Bioorg Med Chem Lett;27(8):1644-1648, 2017 04 15.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:In this study we report the in vitro activities of four cyclic opioid peptides with various sequence length/macrocycle size and N-methylamino acid residue content. N-Methylated amino acids were incorporated and cyclization was employed to enhance conformational rigidity to various extent. The effect of such modifications on ligand structure and binding properties were studied. The pentapeptide containing one endocyclic and one exocyclic N-methylated amino acid displayed the highest affinity to the mu-opioid receptor. This peptide was also shown to be a full agonist, while the other analogs failed to activate the mu opioid receptor. Results of molecular docking studies provided rationale for the explanation of binding properties on a structural basis.
[Mh] Termos MeSH primário: Analgésicos Opioides/química
Analgésicos Opioides/farmacologia
Peptídeos Opioides/química
Peptídeos Opioides/farmacologia
Receptores Opioides mu/agonistas
Receptores Opioides mu/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Aminoácidos/química
Aminoácidos/farmacologia
Animais
Ciclização
Seres Humanos
Ligantes
Metilação
Simulação de Acoplamento Molecular
Peptídeos Cíclicos/química
Peptídeos Cíclicos/farmacologia
Ratos
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acids); 0 (Analgesics, Opioid); 0 (Ligands); 0 (Opioid Peptides); 0 (Peptides, Cyclic); 0 (Receptors, Opioid, mu)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171124
[Lr] Data última revisão:
171124
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170321
[St] Status:MEDLINE


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[PMID]:28318893
[Au] Autor:Adamska-Bartlomiejczyk A; De Marco R; Gentilucci L; Kluczyk A; Janecka A
[Ad] Endereço:Department of Biomolecular Chemistry, Faculty of Medicine, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
[Ti] Título:Design and characterization of opioid ligands based on cycle-in-macrocycle scaffold.
[So] Source:Bioorg Med Chem;25(8):2399-2405, 2017 Apr 15.
[Is] ISSN:1464-3391
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The study reports on a series of novel cyclopeptides based on the structure Tyr-[d-Lys-Phe-Phe-Asp]NH , a mixed mu and kappa opioid receptor agonist with low nanomolar affinity, in which Phe residue was substituted by cyclic amino acids, such as Pro or its six-membered surrogates, piperidine-2-, 3- or 4-carboxylic acids (Pip, Nip and Inp, respectively). All derivatives exhibited high mu- and moderate delta-opioid receptor affinity, and almost no binding to the kappa-opioid receptor. Conformational analysis suggested that the cis conformation of the peptide bond Phe -Xaa influences receptor selectivity through the control of the position of Phe side chain. The results substantiate the use of the cycle-macrocyle scaffolds for fine-tuning receptor selectivity.
[Mh] Termos MeSH primário: Compostos Macrocíclicos/química
Peptídeos Opioides/química
[Mh] Termos MeSH secundário: Ligantes
Simulação de Dinâmica Molecular
Peptídeos Opioides/metabolismo
Receptores Opioides delta/metabolismo
Receptores Opioides mu/metabolismo
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Macrocyclic Compounds); 0 (Opioid Peptides); 0 (Receptors, Opioid, delta); 0 (Receptors, Opioid, mu)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170907
[Lr] Data última revisão:
170907
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170321
[St] Status:MEDLINE


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[PMID]:28097916
[Au] Autor:Mollica A; Pelliccia S; Famiglini V; Stefanucci A; Macedonio G; Chiavaroli A; Orlando G; Brunetti L; Ferrante C; Pieretti S; Novellino E; Benyhe S; Zador F; Erdei A; Szucs E; Samavati R; Dvrorasko S; Tomboly C; Ragno R; Patsilinakos A; Silvestri R
[Ad] Endereço:a Dipartimento di Farmacia , Università di Chieti-Pescara "G. d'Annunzio" , Chieti , Italy.
[Ti] Título:Exploring the first Rimonabant analog-opioid peptide hybrid compound, as bivalent ligand for CB1 and opioid receptors.
[So] Source:J Enzyme Inhib Med Chem;32(1):444-451, 2017 Dec.
[Is] ISSN:1475-6374
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cannabinoid (CB) and opioid systems are both involved in analgesia, food intake, mood and behavior. Due to the co-localization of µ-opioid (MOR) and CB1 receptors in various regions of the central nervous system (CNS) and their ability to form heterodimers, bivalent ligands targeting to both these systems may be good candidates to investigate the existence of possible cross-talking or synergistic effects, also at sub-effective doses. In this work, we selected from a small series of new Rimonabant analogs one CB1R reverse agonist to be conjugated to the opioid fragment Tyr-D-Ala-Gly-Phe-NH . The bivalent compound (9) has been used for in vitro binding assays, for in vivo antinociception models and in vitro hypothalamic perfusion test, to evaluate the neurotransmitters release.
[Mh] Termos MeSH primário: Peptídeos Opioides/farmacologia
Piperidinas/farmacologia
Pirazóis/farmacologia
Receptor CB1 de Canabinoide/metabolismo
Receptores Opioides/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Ligantes
Camundongos
Peptídeos Opioides/química
Peptídeos Opioides/metabolismo
Piperidinas/metabolismo
Pirazóis/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ligands); 0 (Opioid Peptides); 0 (Piperidines); 0 (Pyrazoles); 0 (Receptor, Cannabinoid, CB1); 0 (Receptors, Opioid); RML78EN3XE (rimonabant)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170228
[Lr] Data última revisão:
170228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170119
[St] Status:MEDLINE
[do] DOI:10.1080/14756366.2016.1260565


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[PMID]:28073587
[Au] Autor:Graeff FG
[Ad] Endereço:Institute of Neuroscience and Behavior - INeC, Avenida do Café, 2450, 14050-220 Ribeirão Preto, SP, Brazil; Neurobiology of Emotion Research Centre (NAP-NuPNE), University of Sao Paulo, Ribeirao Preto, Brazil. Electronic address: hegog@hotmail.com.
[Ti] Título:Translational approach to the pathophysiology of panic disorder: Focus on serotonin and endogenous opioids.
[So] Source:Neurosci Biobehav Rev;76(Pt A):48-55, 2017 May.
[Is] ISSN:1873-7528
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Panic patients experience recurrent panic attacks. Two main neurochemical hypotheses have been proposed to explain this vulnerability. The first suggests that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organizes defensive reactions to cope with proximal threats as well as of sympathomotor control areas of the rostral ventrolateral medulla that generate neurovegetative symptoms of the panic attack. The second proposes that endogenous opioids buffer panic attacks in normal subjects, and their deficit results in heightened sensitivity to suffocation and separation anxiety in panic patients. Experimental results obtained in rat models of panic indicate that serotonin interacts synergistically with endogenous opioids in the dorsal periaqueductal gray through 5-HT1A and µ-opioid receptors to inhibit proximal defense and, supposedly, panic attacks. These findings allow reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology. They also indicate that endogenous opioids are likely to participate in the panicolytic action of antidepressants and suggest that exogenous opioids may be useful for treating panic patients resistant to conventional pharmacotherapy.
[Mh] Termos MeSH primário: Transtorno de Pânico
[Mh] Termos MeSH secundário: Analgésicos Opioides
Animais
Seres Humanos
Peptídeos Opioides
Pânico
Substância Cinzenta Periaquedutal
Serotonina
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Analgesics, Opioid); 0 (Opioid Peptides); 333DO1RDJY (Serotonin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170112
[St] Status:MEDLINE


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[PMID]:28067727
[Au] Autor:Rizvi SJ; Iskric A; Calati R; Courtet P
[Ad] Endereço:aArthur Sommer Rotenberg Suicide and Depression Studies, St. Michael's Hospital bDepartment of Psychiatry, Institute of Medical Science, University of Toronto, Toronto, Canada cINSERM U1061; La Colombière Hospital, University of Montpellier, Montpellier, France.
[Ti] Título:Psychological and physical pain as predictors of suicide risk: evidence from clinical and neuroimaging findings.
[So] Source:Curr Opin Psychiatry;30(2):159-167, 2017 Mar.
[Is] ISSN:1473-6578
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE OF REVIEW: Suicide is a multidimensional clinical phenomenon with complex biological, social and psychological risk factors. Therefore, it is imperative for studies to focus on developing a unified understanding of suicide risk that integrates current clinical and neurobiological findings. A recent line of research has implicated different classifications of pain in understanding suicide risk, including the concepts of psychache and pain tolerance. Although psychache is defined as the experience of unbearable psychological pain, pain tolerance refers to the greatest duration or intensity of painful stimuli that one is able to bear. This review will focus on integrating current clinical and neurobiological findings by which psychache and pain tolerance confer suicide risk. RECENT FINDINGS: Results indicate that psychache has been identified as a significant risk factor for suicide and that psychache may be associated with the neurocircuitry involved in the modulation of physical pain. Converging evidence has also been found linking pain tolerance to self-injurious behaviours and suicide risk. The experience of psychache and physical pain in relation to other predictors of suicide, including reward processing, hopelessness and depression, are further discussed. SUMMARY: Future research examining the pain-suicide connection is required to understand the mechanism behind clinically relevant risk factors for suicide, which can ultimately inform the construction of empirically supported suicide risk assessment and intervention techniques.
[Mh] Termos MeSH primário: Dor Crônica/psicologia
Estresse Psicológico/psicologia
Suicídio/psicologia
[Mh] Termos MeSH secundário: Encéfalo/fisiopatologia
Mapeamento Encefálico
Caráter
Dor Crônica/fisiopatologia
Depressão/fisiopatologia
Depressão/psicologia
Seres Humanos
Imagem por Ressonância Magnética
Transtornos Mentais/complicações
Transtornos Mentais/fisiopatologia
Transtornos Mentais/psicologia
Rede Nervosa/fisiopatologia
Peptídeos Opioides/fisiologia
Limiar da Dor/fisiologia
Medição de Risco
Comportamento Autodestrutivo/fisiopatologia
Comportamento Autodestrutivo/psicologia
Estatística como Assunto
Estresse Psicológico/fisiopatologia
Suicídio/prevenção & controle
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Opioid Peptides)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170110
[St] Status:MEDLINE
[do] DOI:10.1097/YCO.0000000000000314


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[PMID]:28000999
[Au] Autor:Palmisano M; Mercatelli D; Caputi FF; Carretta D; Romualdi P; Candeletti S
[Ad] Endereço:Department of Pharmacy and Biotechnology, Alma Mater Studiorum - University of Bologna, Bologna, Italy.
[Ti] Título:N/OFQ system in brain areas of nerve-injured mice: its role in different aspects of neuropathic pain.
[So] Source:Genes Brain Behav;16(5):537-545, 2017 Jun.
[Is] ISSN:1601-183X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Several studies showed that chronic pain causes reorganization and functional alterations of supraspinal brain regions. The nociceptin-NOP receptor system is one of the major systems involved in pain control and much evidence also suggested its implication in stress, anxiety and depression. Therefore, we investigated the nociceptin-NOP system alterations in selected brain regions in a neuropathic pain murine model. Fourteen days after the common sciatic nerve ligature, polymerase chain reaction (PCR) analysis indicated a significant decrease of pronociceptin and NOP receptor mRNA levels in the thalamus; these alterations could contribute to the decrease of the thalamic inhibitory function reported in neuropathic pain condition. Nociceptin peptide and NOP mRNA increased in the anterior cingulate cortex (ACC) and not in the somatosensory cortex, suggesting a peculiar involvement of this system in pain regulating circuitry. Similarly to the ACC, an increase of nociceptin peptide levels was observed in the amygdala. Finally, the pronociceptin and NOP mRNAs decrease observed in the hypothalamus reflects the lack of hypothalamus-pituitary-adrenal axis activation, already reported in neuropathic pain models. Our data indicate that neuropathic pain conditions affect the supraspinal nociceptin-NOP system which is also altered in regions known to play a role in emotional aspects of pain.
[Mh] Termos MeSH primário: Giro do Cíngulo/metabolismo
Neuralgia/metabolismo
Peptídeos Opioides/metabolismo
Receptores Opioides/metabolismo
Nervo Isquiático/lesões
[Mh] Termos MeSH secundário: Tonsila do Cerebelo/metabolismo
Tonsila do Cerebelo/fisiologia
Animais
Giro do Cíngulo/fisiologia
Masculino
Camundongos
Neuralgia/fisiopatologia
Peptídeos Opioides/genética
Receptores Opioides/genética
Córtex Somatossensorial/metabolismo
Córtex Somatossensorial/fisiologia
Tálamo/metabolismo
Tálamo/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Opioid Peptides); 0 (Receptors, Opioid); 0 (nociceptin receptor); 7AYI9N34FF (nociceptin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161222
[St] Status:MEDLINE
[do] DOI:10.1111/gbb.12365


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[PMID]:27838394
[Au] Autor:Kononenko O; Bazov I; Watanabe H; Gerashchenko G; Dyachok O; Verbeek DS; Alkass K; Druid H; Andersson M; Mulder J; Svenningsen ÅF; Rajkowska G; Stockmeier CA; Krishtal O; Yakovleva T; Bakalkin G
[Ad] Endereço:Department of Pharmaceutical Biosciences, Uppsala University, Uppsala 751 24, Sweden; State Key Lab for Molecular Biology, Bogomoletz Institute of Physiology, Kiev 01024, Ukraine.
[Ti] Título:Opioid precursor protein isoform is targeted to the cell nuclei in the human brain.
[So] Source:Biochim Biophys Acta;1861(2):246-255, 2017 02.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Neuropeptide precursors are traditionally viewed as proteins giving rise to small neuropeptide molecules. Prodynorphin (PDYN) is the precursor protein to dynorphins, endogenous ligands for the κ-opioid receptor. Alternative mRNA splicing of neuropeptide genes may regulate cell- and tissue-specific neuropeptide expression and produce novel protein isoforms. We here searched for novel PDYN mRNA and their protein product in the human brain. METHODS: Novel PDYN transcripts were identified using nested PCR amplification of oligo(dT) selected full-length capped mRNA. Gene expression was analyzed by qRT-PCR, PDYN protein by western blotting and confocal imaging, dynorphin peptides by radioimmunoassay. Neuronal nuclei were isolated using fluorescence-activated nuclei sorting (FANS) from postmortem human striatal tissue. Immunofluorescence staining and confocal microscopy was performed for human caudate nucleus. RESULTS: Two novel human PDYN mRNA splicing variants were identified. Expression of one of them was confined to the striatum where its levels constituted up to 30% of total PDYN mRNA. This transcript may be translated into ∆SP-PDYN protein lacking 13 N-terminal amino acids, a fragment of signal peptide (SP). ∆SP-PDYN was not processed to mature dynorphins and surprisingly, was targeted to the cell nuclei in a model cellular system. The endogenous PDYN protein was identified in the cell nuclei in human striatum by western blotting of isolated neuronal nuclei, and by confocal imaging. CONCLUSIONS AND GENERAL SIGNIFICANCE: High levels of alternatively spliced ∆SP-PDYN mRNA and nuclear localization of PDYN protein suggests a nuclear function for this isoform of the opioid peptide precursor in human striatum.
[Mh] Termos MeSH primário: Núcleo Caudado/metabolismo
Núcleo Celular/metabolismo
Peptídeos Opioides/metabolismo
Isoformas de Proteínas/metabolismo
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Aminoácidos/metabolismo
Animais
Linhagem Celular Tumoral
Dinorfinas/metabolismo
Encefalinas/metabolismo
Feminino
Regulação da Expressão Gênica/fisiologia
Inativação Gênica/fisiologia
Seres Humanos
Masculino
Meia-Idade
Precursores de Proteínas/metabolismo
RNA Mensageiro/metabolismo
Ratos
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Amino Acids); 0 (Enkephalins); 0 (Opioid Peptides); 0 (Protein Isoforms); 0 (Protein Precursors); 0 (RNA, Messenger); 74913-18-1 (Dynorphins); 93443-35-7 (preproenkephalin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171019
[Lr] Data última revisão:
171019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161114
[St] Status:MEDLINE



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