RESUMO
Así como planteamos en la primera entrega de esta serie de artículos de actualización sobre la obesidad, resulta urgente revisar el abordaje tradicional que la comunidad médica le ofrece a las personas con cuerpos gordos. En este segundo artículo desarrollaremos en profundidad diferentes alternativas terapéuticas para los pacientes que desean bajar de peso:plan alimentario, actividad física, tratamiento farmacológico y cirugía metabólica. (AU)
As we proposed in the first issue of this series of articles, it is urgent to review the traditional approach that the medical community offers to people with fat bodies. This second article will develop different therapeutic alternatives for patients who want to lose weight: eating plans, physical activity, pharmacological treatment, and metabolic surgery. (AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Exercício Físico , Bupropiona/administração & dosagem , Dieta , Sobrepeso/terapia , Cirurgia Bariátrica , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Naltrexona/administração & dosagem , Obesidade/terapia , Índice de Massa Corporal , Bupropiona/efeitos adversos , Receptor do Peptídeo Semelhante ao Glucagon 1/administração & dosagem , Estilo de Vida Saudável , Preconceito de Peso , Alimento Processado , Naltrexona/efeitos adversosRESUMO
Objetive: Overweight and obesity represent a global epidemic of increasing prevalence associated with an increase in morbidity and mortality. In clinical trials, the combination of naltrexone/bupropion (NB), together with a hypocaloric diet and exercise, was superior to placebo in achieving a sustained reduction of body weight (BW). The purpouse of our investigation was to evaluate the clinical benefit of NB in reallife conditions. Methods: Ambispective and observational research, in a 225 patient's cohort with obesity, or overweight plus related comorbidities, under usual medical care and 16-week follow-up period. The management of the patients was under the usual conditions of practice, therefore, the performance of any diagnostic or therapeutic procedure was not imposed. Results: Unlike clinical trials, we included patients > 65 years old, with a body mass index (BMI) > 45 kg/m2, and type 2 diabetes mellitus (T2DM). NB was associated with significant reduction of baseline BMI (-3.1 kg/m2, IC 95%: -2.8 to -3.4, p < 0.0001) was observed, and 65% of the patients achieved a ≥5% reduction of their BW, despite lower medication compliance and the use of lower doses than the ones recommended. Conclusion: NB was effective and well tolerated to induce an initial reduction in BW. These results were similar to those reported in clinical trials in the same follow-up period, and even better than the ones observed in retrospective, real-life trials.
Objetivo: El sobrepeso y la obesidad representan una epidemia global de prevalencia creciente, asociada con aumento de la morbilidad y la mortalidad. En los ensayos clínicos centrales, la combinación de naltrexona/bupropion (NB), junto con una dieta hipocalórica y ejercicio, fue superior al placebo para lograr una reducción sostenida del peso corporal (PC). El propósito de nuestra investigación fue evaluar el beneficio clínico de la NB en pacientes con sobrepeso/obesidad en las condiciones de la vida real. Métodos: Investigación ambispectiva y observacional, en una cohorte de 225 pacientes con obesidad o sobrepeso más comorbilidades relacionadas, bajo atención médica habitual y un seguimiento de 16 semanas. El abordaje de los pacientes fue en las condiciones habituales de la práctica, por lo tanto, no se impuso la realización de procedimiento diagnóstico o terapéutico alguno. Resultados: A diferencia de los ensayos clínicos, se incluyeron pacientes > 65 años, con un índice de masa corporal (IMC) > 45 kg/m2 y diabetes mellitus tipo 2 (DBT2). La combinación NB se asoció con una reducción significativa del IMC inicial (-3.1 kg/m2; intervalo de confianza del 95% [IC 95%]: -2.8 a -3.4, p < 0.0001) y el 65 % de los pacientes logró una reducción ≥ 5% de su PC, a pesar de tener menor cumplimiento del tratamiento y del uso de dosis inferiores a las recomendadas. Conclusión: La combinación NB fue efectiva y bien tolerada para inducir una reducción inicial del PC. Estos resultados fueron similares a los informados en ensayos clínicos en el mismo período de seguimiento, e, incluso, mejores que los observados en estudios retrospectivos de la práctica clínica real.
Assuntos
Farmacologia , Bupropiona , Sobrepeso , Naltrexona , ObesidadeRESUMO
Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)
Assuntos
Pseudomixoma Peritoneal/tratamento farmacológico , Aporfinas/uso terapêutico , Retinoides/uso terapêutico , Dexametasona/uso terapêutico , Cálcio , Amilorida/uso terapêutico , Metilação/efeitos dos fármacos , Mucinas/efeitos dos fármacos , Naltrexona/uso terapêuticoRESUMO
Abstract Introduction Fibromyalgia is a complex, generalized, and diffuse chronic musculoskeletal pain. Pharmacological approaches are widely used to relieve pain and increase quality of life. Low-Dose Naltrexone (LDN) was shown to increase the nociceptive threshold in patients with fibromyalgia. Transcranial Direct Current Stimulation (tDCS) is effective for pain management. Objective The purpose of this study was to evaluate the analgesic and neuromodulatory effects of a combination of LDN and tDCS in patients with fibromyalgia. Methods This was a randomized, double-blinded, parallel, placebo/sham-controlled trial (NCT04502251; RBR-7HK8N) in which 86 women with fibromyalgia were included, and written informed consent was obtained from them. The patients were allocated into four groups: LDN + tDCS (n = 21), LDN + tDCS Sham (n = 22), placebo + tDCS (n = 22), and placebo+tDCS Sham (n = 21). The LDN or placebo (p.o.) intervention lasted 26 days; in the last five sessions, tDCS was applied (sham or active, 20 min, 2 mA). The following categories were assessed: sociodemographic, Visual Analog Pain Scale (VAS), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), Fibromyalgia Impact Questionnaire (FIQ), Beck Depression Inventory (BDI-II), Profile of Chronic Pain Scale (PCP:S), Pain Pressure Threshold (PPT), and Conditioned Pain Modulation (CPM). Blood samples were collected to analyze BDNF serum levels. Results At baseline, no significant difference was found regarding all measurements. VAS pain was significantly reduced in the LDN + tDCS (p = 0.010), LDN + tDCS Sham (p= 0.001), and placebo+tDCS Sham (p= 0.009) groups. In the PCP:S, the LDN+tDCS group showed reduced pain frequency and intensity (p= 0.001), effect of pain on activities (p= 0.014) and emotions (p= 0.008). Depressive symptoms reduced after all active interventions (p > 0.001). Conclusion Combined LDN+tDCS has possible benefits in reducing pain frequency and intensity; however, a placebo effect was observed in pain using VAS, and further studies should be performed to analyze the possible association.
Assuntos
Humanos , Feminino , Fibromialgia , Estimulação Transcraniana por Corrente Contínua , Qualidade de Vida , Método Duplo-Cego , Dor Crônica/tratamento farmacológico , NaltrexonaRESUMO
OBJECTIVES: The current study covers a secondary revision of the guidelines for the pharmacotherapy of schizophrenia issued by the Korean Medication Algorithm for Schizophrenia (KMAP-SCZ) 2001, specifically for co-existing symptoms and antipsychotics-related side-effects in schizophrenia patients. METHODS: An expert consensus regarding the strategies of pharmacotherapy for positive symptoms of schizophrenia, co-existing symptoms of schizophrenia, and side-effect of antipsychotics in patients with schizophrenia was retrieved by responses obtained using a 30-item questionnaire. RESULTS: For the co-existing symptoms, agitation could be treated with oral or intramuscular injection of benzodiazepine or antipsychotics; depressive symptoms with atypical antipsychotics and adjunctive use of antidepressant; obsessive-compulsive symptoms with selective serotonin reuptake inhibitors and antipsychotics other than clozapine and olanzapine; negative symptoms with atypical antipsychotics or antidepressants; higher risk of suicide with clozapine; comorbid substance abuse with use of naltrexone or bupropion/ varenicline, respectively. For the antipsychotics-related side effects, anticholinergics (extrapyramidal symptom), propranolol and benzodiazepine (akathisia), topiramate or metformin (weight gain), change of antipsychotics to aripiprazole (hyperprolactinemia and prolonged QTc) or clozapine (tardive dyskinesia) could be used. CONCLUSION: Updated pharmacotherapy strategies for co-existing symptoms and antipsychotics-related side effects in schizophrenia patients as presented in KMAP-SCZ 2019 could help effective clinical decision making of psychiatrists as a preferable option.
Assuntos
Humanos , Antidepressivos , Antipsicóticos , Aripiprazol , Benzodiazepinas , Antagonistas Colinérgicos , Tomada de Decisão Clínica , Clozapina , Consenso , Depressão , Di-Hidroergotamina , Tratamento Farmacológico , Injeções Intramusculares , Metformina , Naltrexona , Propranolol , Psiquiatria , Esquizofrenia , Inibidores Seletivos de Recaptação de Serotonina , Transtornos Relacionados ao Uso de Substâncias , Suicídio , VareniclinaRESUMO
The Korean Ministry of Food and Drug Safety has approved three anti-obesity drugs for long-term management in the past decade. In addition, since 2019, bariatric surgery has been financially supported by National Health Insurance Service in Korea. In this review, the mechanisms of action and the clinical implications of the recently approved anti-obesity drugs, lorcaserin, naltrexone/bupropion, and liraglutide are explained. Lorcaserin stimulates proopiomelanocortin (POMC)/cocaine- and amphetamine-regulated transcript (CART) neurons and inhibits neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons, which results in the activation of melanocortin 3/4 receptors. Naltrexone/bupropion stimulates POMC neurons through bupropion; this stimulation is augmented by blocking the autoinhibitory mechanism of POMC with naltrexone. The hypophagic effect of liraglutide is mediated through the direct activation of POMC/CART neurons and the indirect suppression of NPY/AgRP neurons through γ-aminobutyric acid-dependent signaling, with adjunctive suppression of the mesolimbic dopamine reward system. In addition to liraglutide, another glucagon-like peptide-1 receptor agonist, semaglutide, is expected to be added to the list of anti-obesity drugs in the near future. In patients with obesity and high cardiovascular risk, lorcaserin was considered neutral and liraglutide was considered favorable, whereas inconclusive results were obtained for naltrexone/bupropion.
Assuntos
Humanos , Fármacos Antiobesidade , Cirurgia Bariátrica , Bupropiona , Dopamina , Receptor do Peptídeo Semelhante ao Glucagon 1 , Coreia (Geográfico) , Liraglutida , Naltrexona , Programas Nacionais de Saúde , Neurônios , Neuropeptídeo Y , Obesidade , Pró-Opiomelanocortina , RecompensaRESUMO
Clinical studies published over the past two decades have consistently demonstrated the therapeutic efficacy and safety of anti-craving medications. To use anti-craving agents more effectively in clinical settings, it is important to set clear treatment goals. Because alcoholic patients have lost control of drinking alcohol, it is recommended to set ‘abstinence’ as a goal rather than ‘controlled drinking’. Indeed, the therapeutic effects of anti-craving medication are higher when abstinence is set as the target. On the other hand, if abstinence is the sole criterion, it is difficult to elicit the motivation of a patient who lacks motivation in clinical practice. In the case of patients who have not yet gained insight, the initial goal might be set to gradually reduce the amount of alcohol consumed and prevent at-risk heavy drinking. Even in this case, anti-craving can help clinically. To increase the effectiveness of anti-craving medications, it is best to start at least four to seven days after the patient has stopped drinking. If the patient has alcohol withdrawal symptoms, they should be treated first.
Assuntos
Humanos , Alcoólicos , Fissura , Ingestão de Líquidos , Mãos , Motivação , Naltrexona , Síndrome de Abstinência a Substâncias , Usos TerapêuticosRESUMO
Naltrexone is a competitive antagonist of μ, δ, and κ opioid receptors. Naltrexone has been investigated for use an as anti-obesity agent in both the general population and in patients with severe mental illness, including schizophrenia. In patients with schizophrenia, however, potential psychotic symptoms due to adverse effects of naltrexone have not been investigated. Our case study, a relevant case report, and some related articles suggest that naltrexone might be associated with the emergence of visual hallucinations, which clinicians should be aware of.
Assuntos
Humanos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Alucinações , Naltrexona , Antagonistas de Entorpecentes , Receptores Opioides , EsquizofreniaRESUMO
This study aimed to investigate the protective effect of salvinorin A on the cerebral pial artery after forebrain ischemia and explore related mechanisms. Thirty Sprague-Dawley rats received forebrain ischemia for 10 min. The dilation responses of the cerebral pial artery to hypercapnia and hypotension were assessed in rats before and 1 h after ischemia. The ischemia reperfusion (IR) control group received DMSO (1 µL/kg) immediately after ischemia. Two different doses of salvinorin A (10 and 20 µg/kg) were administered following the onset of reperfusion. The 5th, 6th, and 7th groups received salvinorin A (20 µg/kg) and LY294002 (10 µM), L-NAME (10 μM), or norbinaltorphimine (norBIN, 1 μM) after ischemia. The levels of cGMP in the cerebrospinal fluid (CSF) were also measured. The phosphorylation of AKT (p-AKT) was measured in the cerebral cortex by western blot at 24 h post-ischemia. Cell necrosis and apoptosis were examined by hematoxylin-eosin staining (HE) and TUNEL staining, respectively. The motor function of the rats was evaluated at 1, 2, and 5 days post-ischemia. The dilation responses of the cerebral pial artery were significantly impaired after ischemia and were preserved by salvinorin A treatment. In addition, salvinorin A significantly increased the levels of cGMP and p-AKT, suppressed cell necrosis and apoptosis of the cerebral cortex and improved the motor function of the rats. These effects were abolished by LY294002, L-NAME, and norBIN. Salvinorin A preserved cerebral pial artery autoregulation in response to hypercapnia and hypotension via the PI3K/AKT/cGMP pathway.
Assuntos
Animais , Masculino , Ratos , Artérias Cerebrais/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Diterpenos Clerodânicos/farmacologia , Transdução de Sinais , Artérias Cerebrais/fisiopatologia , Isquemia Encefálica/tratamento farmacológico , Morfolinas/administração & dosagem , Cromonas/administração & dosagem , Ratos Sprague-Dawley , GMP Cíclico/líquido cefalorraquidiano , GMP Cíclico/metabolismo , NG-Nitroarginina Metil Éster , Diterpenos Clerodânicos/antagonistas & inibidores , Modelos Animais de Doenças , Naltrexona/administração & dosagem , Naltrexona/análogos & derivadosRESUMO
BACKGROUND: Severe pruritus is a challenging condition, and it is more difficult to deal with in older patients due to their limitations in taking oral medication because of underlying diseases, possible interaction with concurrent medications, and poor general condition. OBJECTIVE: We evaluated the efficacy and safety of naltrexone (Revia®), an opioid antagonist, in elderly patients with severe pruritus that was not easily controlled with conventional antipruritics. METHODS: Eighteen patients were enrolled, with a mean age of 73 years. They additionally received 50 mg of naltrexone per day for an average of 2 months. RESULTS: Using the visual analogue scale, 13 (72.2%) of 18 patients showed a "much improved" condition, reporting more than a 50% decrease in pruritus intensity. Sixteen (88.9%) showed symptomatic improvement, and only 2 (11.1%) had persistent pruritus. Five patients reported side effects including insomnia, fatigue, constipation, and anorexia. However, reactions were either limited to the first 2 weeks or well managed. CONCLUSION: Naltrexone could be an effective and safe alternative treatment option to control severe pruritus in older patients.
Assuntos
Idoso , Humanos , Anorexia , Antipruriginosos , Constipação Intestinal , Fadiga , Naltrexona , Prurido , Distúrbios do Início e da Manutenção do SonoRESUMO
Autism spectrum disorder (ASD) is characterized by persistent deficits within two core symptom domains: social communication and restricted, repetitive behaviors. Although numerous studies have reported psychopharmacological treatment outcomes for the core symptom domains of ASD, there are not enough studies on fundamental treatments based on the etiological pathology of ASD. Studies on candidate medications related to the pathogenesis of ASD, such as naltrexone and secretin, were conducted, but the results were inconclusive. Oxytocin has been identified as having an important role in maternal behavior and attachment, and it has been recognized as a key factor in the social developmental deficit seen in ASD. Genetic studies have also identified associations between ASD and the oxytocin pathway. As ASD has its onset in infancy, parents are willing to try even experimental or unapproved treatments in an effort to avoid missing the critical period for diagnosis and treatment, which can place their child in an irreversible state. While therapeutic application of oxytocin for ASD is in its early stages, we have concluded that oxytocin would be a promising therapeutic substance via a thorough literature review focusing on the following: the relationship between oxytocin and sociality; single nucleotide polymorphisms as a biological marker of ASD; and validity verification of oxytocin treatment in humans. We also reviewed materials related to the mechanism of oxytocin action that may support its potential application in treating ASD.
Assuntos
Criança , Humanos , Transtorno Autístico , Transtorno do Espectro Autista , Período Crítico Psicológico , Diagnóstico , Comportamento Materno , Naltrexona , Ocitocina , Pais , Patologia , Polimorfismo de Nucleotídeo Único , Secretina , Mudança Social , BiomarcadoresRESUMO
Polydipsia in schizophrenic patients is not uncommon, but a frequently underdiagnosed condition. The etiology of polydipsia remains unclear, and its complications can be life-threatening, while often being difficult to manage it. We report a case of a successfully treated chronic schizophrenic patient with polydipsia. The patient was male, 47-year-old, suffering 27-years of residual schizophrenia who had been consuming more than 10 L of water per day, and is complicated by hyponatremia. He was treated with irbesarten 300 mg and naltrexone 50 mg in the setting of closed ward. He consumed less than 3.5 L of water per day and serum sodium levels seemed to be stable following discharge from the closed ward. We suggest that irbesartan and naltrexone may have beneficial effects for treating polydipsia, and future prospective and well-controlled studies are to be performed.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Hiponatremia , Naltrexona , Polidipsia , Estudos Prospectivos , Esquizofrenia , Sódio , ÁguaRESUMO
<p><b>OBJECTIVE</b>To observe the effects of κ-opioid receptor agonist U50, 488H on myocardial ischemia and reperfusion injury and related mechanism.</p><p><b>METHODS</b>Rats were randomly divided into sham operation, myocardial ischemia and reperfusion(I/R, 30 min ischemia followed by 120 min reperfusion), and MI/R+U50, 488H (1.5 mg/kg) and I/R+U50, 488H+ selective κ-opioid receptor antagonist Nor-BNI (2 mg/kg, n = 8 each). The infarction size and the incidence of ventricular arrhythmias were observed.Real-time PCR and DAB staining were used to define the myocardium Toll-like receptor 4(TLR4) expression. Myeloperoxidase level, TNF-α induction and the expression of NF-κB were also examined in rats.</p><p><b>RESULTS</b>After I/R, the expressions of myocardial TLR4 and NF-κB increased significantly both in ischemia area and area at risk. Compared with I/R, κ-opioid receptor stimulation with U50, 488H significantly attenuated the expressions of TLR4 and NF-κB and reduced myeloperoxidase (MPO) levels, myocardial TNF-α production, myocardial infarct sizes and the incidence of ventricular arrhythmias and arrhythmia score (2.9 ± 0.7 vs. 4.4 ± 0.9, P < 0.05) , above effects of U50, 488H were partly abolished by co-treatment with Nor-BNI.</p><p><b>CONCLUSION</b>These data provide evidence for the first time that κ-opioid receptor stimulation could attenuate myocardial I/R injury via downregulating TLR4/NF-κB signaling in rats.</p>
Assuntos
Animais , Ratos , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida , Farmacologia , Arritmias Cardíacas , Síndrome de Brugada , Doença do Sistema de Condução Cardíaco , Doença da Artéria Coronariana , Regulação para Baixo , Sistema de Condução Cardíaco , Anormalidades Congênitas , Infarto do Miocárdio , Isquemia Miocárdica , Metabolismo , Miocárdio , NF-kappa B , Naltrexona , Ratos Sprague-Dawley , Receptores Opioides kappa , Fisiologia , Traumatismo por Reperfusão , Transdução de Sinais , Receptor 4 Toll-Like , Fisiologia , Fator de Necrose Tumoral alfaRESUMO
The purpose of this study was to investigate the differences in subjective acute effects of alcohol and naltrexone among those who prefer spicy food to varying degrees. Acute biphasic alcohol effects scale (BAES), visual analogue scale for craving (VAS-C), blood alcohol concentration (BAC) and food preference scale were measured in 26 men. Repeated measures ANOVA (2 preference groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in naltrexone condition (N+) (P<0.001), but not in non-naltrexone condition (N-). Furthermore, repeated measures ANOVA (2 drug groupsx4 time blocks) on the stimulative subscale of BAES revealed a significant group by block interaction in strong preference for spicy food (SP) (P<0.001), but not in lesser preference for spicy food (LP). The paired t-test revealed that significant suppression of the stimulative subscale of BAES was observed at 15 min (P<0.001) and 30 min (P<0.001) after drinking when N+ compared with N- in SP. For those who prefer spicy food, the stimulative effect of acute alcohol administration was suppressed by naltrexone. This result suggests that the effect of naltrexone may vary according to spicy food preference.
Assuntos
Adulto , Humanos , Masculino , Adulto Jovem , Consumo de Bebidas Alcoólicas/efeitos adversos , Alcoolismo/tratamento farmacológico , Capsaicina/farmacologia , Preferências Alimentares/efeitos dos fármacos , Naltrexona/efeitos adversos , Antagonistas de Entorpecentes/efeitos adversos , Inquéritos e Questionários , Fármacos do Sistema Sensorial/farmacologiaRESUMO
Alcoholism is becoming one of the most serious issues in Korea. The purpose of this review article was to understand the present status of the treatment system for alcoholism in Korea compared to the United States and to suggest its developmental direction in Korea. Current modalities of alcoholism treatment in Korea including withdrawal treatment, pharmacotherapy, and psychosocial treatment are available according to Korean evidence-based treatment guidelines. Benzodiazepines and supportive care including vitamin and nutritional support are mainly used to treat alcohol withdrawal in Korea. Naltrexone and acamprosate are the drugs of first choice to treat chronic alcoholism. Psychosocial treatment methods such as individual psychotherapy, group psychotherapy, family therapy, cognitive behavior therapy, cue exposure therapy, 12-step facilitation therapy, self-help group therapy, and community-based treatment have been carried out to treat chronic alcoholism in Korea. However, current alcohol treatment system in Korea is not integrative compared to that in the United States. To establish the treatment system, it is important to set up an independent governmental administration on alcohol abuse, to secure experts on alcoholism, and to conduct outpatient alcoholism treatment programs and facilities in an open system including some form of continuing care.
Assuntos
Humanos , Dissuasores de Álcool/uso terapêutico , Alcoolismo/economia , Benzodiazepinas/uso terapêutico , Naltrexona/uso terapêutico , Psicoterapia , República da Coreia , Taurina/análogos & derivadosRESUMO
Sexual violence crime causes severe trauma to victim's family as well as the victim, and its aftereffect which is hard to be healed can last for the entire lifetime. And thus plenty of social cost is incurred due to the crime. It has long been reported that paraphilia is associated with sexual offenders and sexual violence. In this study, the previous foreign data on the psychiatric medication used for sexual offender or paraphilia were summarized for the first time in Korea, and the possibility of medication in Korea was examined. As for the drugs used for sexual offender or paraphilia, SSRI was most frequently reported and besides that, tricyclic antidepressant, antipsychotics, antiepileptic drugs, mirtazapine, and naltrexone were reported.
Assuntos
Humanos , Anticonvulsivantes , Antipsicóticos , Crime , Criminosos , Coreia (Geográfico) , Mianserina , Naltrexona , Transtornos Parafílicos , Delitos SexuaisRESUMO
BACKGROUND: WIN55212-2 is a synthetic cannabinoid agonist and selective to cannabinoid 1 (CB1) receptors, which are distributed mainly in the central nervous system. Opioid receptors and CB1 receptors have several similarities in terms of their intracellular signal transduction mechanisms, distributions, and pharmacological action. Several studies have therefore sought to describe the functional interactions between opioids and cannabinoids at the cellular and behavioral levels. The present study investigated agonist-stimulated [35S]GTPgammaS binding by WIN55212-2 in rat brain membranes and determined the antagonism by selective opioid antagonists at the level of receptor-ligand interaction and intracellular signal transduction. METHODS: Sprague-Dawley rats (male, n = 20) were euthanized for the preparation of brain membranes. In agonist-stimulated [35S]GTPgammaS binding by WIN55212-2, the values of EC50 and maximum stimulation (% over basal) were determined in the absence or presence of the micro, kappa and delta opioid receptor antagonists naloxone (20 nM), norbinaltorphimine (3 nM), and naltrindole (3 nM), respectively. Ke values for opioid antagonist inhibition in the absence or presence of each opioid receptor antagonist were calculated using the following equation: [nanomolar antagonist] / (dose ratio of EC50 - 1). RESULTS: In WIN55212-2-stimulated [35S]GTPgammaS binding in the rat brain membranes, the values of EC50 and maximum stimulation (% over basal) were 154 +/- 39.5 nM and 27.6 +/- 5.3% over basal, respectively. Addition of selective opioid antagonists did not produce a significant rightward shift in the WIN55212-2 concentration-response curve, and Ke values were not applicable. CONCLUSIONS: Our results suggest that the functional activity of WIN55212-2-stimulated [35S]GTPgammaS binding was not affected by opioid antagonists in the rat brain membranes. Although the exact mechanism remains unclear, our results may partially elucidate their actions.
Assuntos
Animais , Ratos , Analgésicos Opioides , Benzoxazinas , Encéfalo , Canabinoides , Sistema Nervoso Central , Membranas , Morfolinas , Naloxona , Naltrexona , Naftalenos , Antagonistas de Entorpecentes , Ratos Sprague-Dawley , Receptor CB1 de Canabinoide , Receptores Opioides , Receptores Opioides delta , Transdução de SinaisRESUMO
PURPOSE: Nociceptin/orphanin FQ (N/OFQ) as an endogeneous hexadecapeptide is known to exert antinociceptive effects spinally. The aims of this study were to demonstrate the antinociceptive effects of i.t. N/OFQ and to investigate the possible interaction between N/OFQ and endogenous opioid systems using selective opioid receptor antagonists in rat formalin tests. MATERIALS AND METHODS: I.t. N/OFQ was injected in different doses (1-10 nmol) via a lumbar catheter prior to a 50 microL injection of 5% formalin into the right hindpaw of rats. Flinching responses were measured from 0-10 min (phase I, an initial acute state) and 11-60 min (phase II, a prolonged tonic state). To observe which opioid receptors are involved in the anti-nociceptive effect of i.t. N/OFQ in the rat-formalin tests, naltrindole (5-20 nmol), beta-funaltrexamine (1-10 nmol), and norbinaltorphimine (10 nmol), selective delta-, micro- and kappa-opioid receptor antagonists, respectively, were administered intrathecally 5 min after i.t. N/OFQ. RESULTS: I.t. N/OFQ attenuated the formalin-induced flinching responses in a dose-dependent manner in both phases I and II. I.t. administration of naltrindole and beta-funaltrexamine dose-dependently reversed the N/OFQ-induced attenuation of flinching responses in both phases; however, norbinaltorphimine did not. CONCLUSION: I.t. N/OFQ exerted an antinociceptive effect in both phases of the rat-formalin test through the nociceptin opioid peptide receptor. In addition, the results suggested that delta- and micro-opioid receptors, but not kappa-opioid receptors, are involved in the antinociceptive effects of N/OFQ in the spinal cord of rats.
Assuntos
Animais , Masculino , Ratos , Analgésicos/administração & dosagem , Formaldeído/toxicidade , Injeções Espinhais , Naltrexona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Peptídeos Opioides/administração & dosagem , Medição da Dor , Ratos Sprague-Dawley , Receptores Opioides/agonistasRESUMO
PURPOSE: To investigate the effect of the opioid blocker naltrexone in the inflammatory response in acute pancreatitis (AP). METHODS: Acute pancreatitis was induced in anesthetized male Wistar rats by retrograde injection of 2.5% sodium taurocholate diluted in 0.5ml saline into the main pancreatic duct. Animals were randomized to the following experimental groups: Control Group (n=9): animals received an intraperitoneal injection of saline solution (0.5ml), 15 minutes before the induction of AP. Naltrexone Group (n=9): animals received an intraperitoneal injection of naltrexone 0.5ml (15 mg/kg), 15 minutes before induction of AP. Peritoneal levels of TNF-α and serum levels of IL-6 and amylase were determined The volume of the ascitic fluid was also evaluated. Myeloperoxidase (MPO) activities were analyzed in homogenates of pulmonary tissue. RESULTS: There were no significant differences in the ascitic fluid volume, nor in TNF-a and IL-6 levels in the naltrexone group compared to controls. Treatment with naltrexone did not affect the lung MPO activity compared to control group. CONCLUSIONS: The opioid receptors don't play an important role in the pathogenesis of the inflammatory response in acute pancreatitis. If opioids affect leukocytes inflammatory signaling, there are no major implications in the pathogenesis of acute pancreatitis.
OBJETIVO: Investigar o efeito do bloqueador opióide naltrexone na resposta inflamatória da pancreatite aguda. METODOS: Pancreatite aguda foi induzida em ratos machos Wistar, através de injeção retrógada de solução de taurocolato de sódio a 2,5% nos ductos pancreáticos. Os animais foram alocados em dois grupos: Grupo controle (n=9) animais receberam 0,5 ml de solução salina intra-peritonial 15 minutos antes da indução da pancreatite aguda e Grupo naltrexone (n=9) animais receberam naltrexone (15mg/kg de peso), em 0,5 ml de volume final por via intraperitoneal, 15 minutos antes da indução da pancreatite aguda. Foram avaliados o volume de ascite, os níveis séricos de amilase e IL-6, assim como TNF-α peritoneal e a atividade da mieloperoxidase (MPO) no tecido pulmonar. RESULTADOS: Não foram encontradas diferenças significantes nos parâmetros analisados entre o grupo que recebeu solução salina e o que recebeu naltrexone . CONCLUSÕES: Os receptores opióides não desempenham papel importante na resposta inflamatória sistêmica associada à pancreatite aguda. Se os opioides alteram a sinalização inflamatória nos leucócitos está ação não se reflete na patogênese da pancreatite aguda.
Assuntos
Animais , Masculino , Ratos , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Pancreatite/etiologia , Receptores Opioides/fisiologia , Doença Aguda , Amilases/sangue , Modelos Animais de Doenças , /sangue , Pancreatite/metabolismo , Peroxidase/análise , Distribuição Aleatória , Ratos Wistar , Receptores Opioides/antagonistas & inibidores , Ácido Taurocólico , Fator de Necrose Tumoral alfa/análiseRESUMO
<p><b>OBJECTIVE</b>To investigate the effect of DADLE, a δ-opioid receptor agonist, on the proliferation of human liver cancer HepG2 cells and explore the mechanism involving PKC pathway.</p><p><b>METHODS</b>HepG2 cells were treated with DADLE at different doses (0.01, 0.1, 1.0 and 10 µmol/L). Cell viability was determined using methyl thiazolyl terazolium (MTT) assay. The expression of PKC mRNA and p-PKC protein were examined by RT-PCR and Western blot assay. After treated separately with DADLE plusing NAL or PMA, the cell cycle of HepG2 cells was analyzed by flow cytometer. MTT was used to detect their proliferation capacity and Western blot was used to examine the p-PKC expression. The growth inhibitory rate of HepG2 cells treated with DADLE and cis-diammine dichloridoplatinum (CDDP) was analyzed.</p><p><b>RESULTS</b>DADLE at different concentrations showed an inhibitory effect on the proliferation of HepG2 cells though inhibiting the expression of PKC mRNA and p-PKC protein. The results of flow cytometry showed that compared with the control group, the percentage of S + G(2)/M cells in DADLE-treated group was lowered by 3.94% (P < 0.01). Meanwhile, after treated with NAL and PMA, the percentage was elevated by 3.22% and 3.63%, respectively (P < 0.01). The MTT and Western blot assays showed that compared with the control group, the values of A570 and p-PKC protein levels in the HepG2 cells of DADLE-treated group were significantly decreased (P < 0.01). After treatment with NAL and PMA, the values of A570 and p-PKC protein levels were elevated significantly (P < 0.01). The growth inhibitory rate of DADLE + CDDP group was 79.9%, significantly lower than 25.2% and 43.2% of the DADLE and CDDP groups, respectively.</p><p><b>CONCLUSIONS</b>Activation of δ-opioid receptor by DADLE inhibits the apoptosis of human liver cancer HepG2 cells. The underlying mechanism may be correlated with PKC pathway. DADLE can enhance the chemosensitivity of HepG2 cells to CDDP.</p>