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.
Analgesics, Opioid ; Animals ; Benzoxazines ; Brain ; Cannabinoids ; Central Nervous System ; Membranes ; Morpholines ; Naloxone ; Naltrexone ; Naphthalenes ; Narcotic Antagonists ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1 ; Receptors, Opioid ; Receptors, Opioid, delta ; Signal Transduction

No abstract available.
Hyperalgesia

Obesity, that is, having a body mass index (BMI) >30 kg/m2, has increased dramatically and became the most single most common preventable cause of death in South Korea. In the end, obesity results in metabolic syndrome, which includes abdominal obesity, increased triglycerides, decreased high-density lipoprotein, hypertension, and impaired glucose tolerance. Nonsurgical methods for obesity treatments include dietary therapy, exercise counseling, behavioral therapy, psychiatric therapy, and pharmacotherapy. Surgical methods for obesity treatments, laparoscopic gastric banding and Roux-en-Y gastric bypass, are commonly performed for obese patients, particularly those with a BMI of 40 kg/m2 or at BMI more than 30 kg/m2 with accompanying diseases related to metabolic syndrome such as hypertension, type 2 diabetes, hypercholesterolemia, asthma, angina, other cardiopulmonary diseases, infertility, polycystic ovary, urinary incontinence, severe arthritis, or Pickwickian syndrome. Preoperative evaluation for bariatric surgery should focus on airway management, sleep apnea history, use of a continuous positive airway pressure device, and comorbid systemic diseases. Special consideration and pharmacokinetic knowledge is needed for the choice and dose of the anesthetic agents as well as postoperative pain control, patient monitoring, fluid intake, and surgical complications. Obesity is a disease. Appropriate surgical intervention and peri-operative anesthetic care for bariatric surgery will increase the safety and satisfaction of obese patients and will finally provide a better quality of life for our society.
Airway Management ; Anesthesia ; Anesthetics ; Arthritis ; Asthma ; Bariatric Surgery ; Body Mass Index ; Cause of Death ; Continuous Positive Airway Pressure ; Counseling ; Exercise Therapy ; Female ; Gastric Bypass ; Glucose ; Humans ; Hypercholesterolemia ; Hypertension ; Infertility ; Lipoproteins ; Monitoring, Physiologic ; Obesity ; Obesity Hypoventilation Syndrome ; Obesity, Abdominal ; Ovary ; Pain, Postoperative ; Quality of Life ; Republic of Korea ; Sleep Apnea Syndromes ; Triglycerides ; Urinary Incontinence

BACKGROUND: Cannabinoid receptor agonists can reverse opioidinduced nausea and vomiting in animals, but have not yet been tested against opioid-induced pruritus. This study tests the hypothesis that a cannabinoid receptor agonist will prevent opioidinduced pruritus and evaluates if the use of a cannabinoid receptor agonist will increase the analgesic efficacy of opioids. METHODS: Various doses of fentanyl were injected subcutaneously in mice to obtain a dose-response curve with the use of a writhing test. To observe the analgesic potentiation of the cannabinoid agonist WIN55,212-2 in the writhing test, mice were pretreated with various concentrations of WIN55,212-2 (0.25, 0.5, 1.0, 2.0 mg/kg) 10 min prior to the injection of an ED50 dose of fentanyl, as determined from the dose-response curve. To observe the antipruritogenic effect of WIN55,212-2 in a scratching test, mice were pretreated with WIN55,212-2 (0.25, 0.5 mg/kg) 20 min prior to fentanyl injection. A CB1 receptor selective antagonist, AM251 (3 mg/kg), was used to confirm the cannabinoid receptor selectivity. RESULTS: The ED50 of fentanyl in the writhing test was 0.018 mg/kg (range, 0.011?0.025 mg/kg). A dose of 1 mg/kg WIN55,212-2 increased the analgesic efficacy of fentanyl significantly (P < 0.001), but doses of 0.25 mg/kg and 0.5 mg/kg did not increase the analgesic efficacy. A dose of 0.25 mg/kg WIN55,212-5 reduced the scratching response of fentanyl significantly (P < 0.001) and this action was a cannabinoid receptor selective response. CONCLUSIONS: These results demonstrate that 0.25 mg/kg WIN55,212-2 can prevent opioid-induced pruritus. The antipruritogenic activity of WIN55,212-2 occurs at CB1 receptors even if the analgesic efficacy of fentanyl cannot be increased.
Analgesics, Opioid ; Animals ; Cannabinoid Receptor Agonists ; Fentanyl ; Mice ; Nausea ; Piperidines ; Pruritus ; Pyrazoles ; Receptor, Cannabinoid, CB1 ; Receptors, Cannabinoid ; Vomiting

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.
Analgesics/administration & dosage/*pharmacology ; Animals ; Formaldehyde/toxicity ; Injections, Spinal ; Male ; Naltrexone/administration & dosage/analogs & derivatives/pharmacology ; Narcotic Antagonists/administration & dosage/*pharmacology ; Opioid Peptides/administration & dosage/*pharmacology ; Pain Measurement ; Rats ; Rats, Sprague-Dawley ; Receptors, Opioid/*agonists/drug effects

Perioperative opioid-induced hyperalgesia (OIH) can be defined as the "increased perception of pain after opioid-based anesthesia and surgery" since hyperalgesia is defined as "increased pain from a stimulus that normally provokes pain." OIH has been identified mainly after remifentanil-based anesthesia in surgical patients given the high dose and rapid withdrawal used. The mechanisms of OIH have been postulated mainly by the cellular-level adaptation in internalization of the receptors and downregulation of intracellular coupling, upregulation of spinal dynorphins, and activation of N-methyl-D-aspartate receptors have been postulated as well. The clinical aspects of OIH with various causes, especially remifentanil, have been investigated. Pros and cons related to remifentanil-induced hyperalgesia have been suggested. The dose and duration of remifentanil used in surgery and anesthesia can be the appropriate factors for OIH, including the way of setting for the control groups of those studies, and the methods for evaluating the pain. Opioids remain one of the most powerful pain killers for acute pain management. Opioids are sometimes necessary for perioperative analgesia, but OIH can be an unavoidable risk. Ongoing interest in OIH and the development of anesthesia optimized for its prevention will increase the quality of perioperative life.
Acute Pain ; Analgesia ; Analgesics, Opioid ; Anesthesia ; Down-Regulation ; Drug Tolerance ; Dynorphins ; Humans ; Hyperalgesia* ; Methods ; Receptors, N-Methyl-D-Aspartate ; Up-Regulation

BACKGROUND: The Pentax Airway Scope (AWS) is a video laryngoscope designed to facilitate tracheal intubation with a high-resolution image. The Pentax AWS has been reported to cause less hemodynamic stress than the Macintosh laryngoscope. The aims of this study are to investigate the differences in hemodynamic responses and norepinephrine concentrations to tracheal intubation between procedures using he Pentax AWS and the Macintosh laryngoscope. METHODS: Forty patients (American Society of Anesthesiologists class I-II, age range: 18-60 years) were randomly assigned to be intubated with either the Pentax AWS or the Macintosh laryngoscope while under general anesthesia. Routine monitoring, including invasive arterial blood pressure and bispectral index, were applied. Thiopental (4 mg/kg), fentanyl (1 microg/kg), midazolam (0.05 mg/kg), and rocuronium (0.6 mg/kg) were administered for anesthetic induction. Systolic, diastolic, and mean blood pressures and heart rates were recorded pre-intubation, immediately post-intubation (T0), and over the following 10 minutes at one minute intervals (T1, T2, T3, T4, T5em leaderT10). Patient blood was sampled for norepinephrine concentrations pre-intubation (baseline) and post-intubation (T1). Evidence of sore throat was evaluated 30 min and 24 hr after extubation. Data were transformed to % basal and expressed as mean +/- SD. RESULTS: The systolic, diastolic, and mean blood pressure, and heart rate at T0 and T4 were significantly different between the two groups. There was no significant difference in plasma norepinephrine between the two groups. The difference in incidence of sore throat was not significant between the two groups. CONCLUSIONS: Pentax-AWS for tracheal intubation has greater hemodynamic stability than the Macintosh blade laryngoscope.
Androstanols ; Anesthesia, General ; Arterial Pressure ; Blood Pressure ; Fentanyl ; Heart Rate ; Hemodynamics ; Humans ; Incidence ; Intubation ; Laryngoscopes ; Midazolam ; Norepinephrine ; Pharyngitis ; Plasma ; Thiopental

PURPOSE: This study attempts to evaluate the effect of lens cortex and nucleus remnants on posterior capsular opacification with method of the cell culture according to in vitro capsular bag model. METHODS: After bovine lens were isolated, we performed continuous curvilinear capsulorhexis and hydrodissectioin of the lens fiber mass. At this stage a tension ring was implanted and then the preparations placed in organ culture for up to 6 weeks. Lens cortex and nucleus material was added at the culture media in group 2, 3, 4, 5, 6 with amount of 1/16, 1/32, 1/64, 1/96, 1/128 of one lens volume. Group 1 was control group that was not added lens materials. Cell coverage of the posterior lens capsule was recorded and the capsules were examined, both pre-and post-coverage, for proliferative activity. RESULTS: After a lag period outgrowth was observed across the posterior capsule. The proliferative activity was greater at the groups that were added more amount of the lens cortex and nucleus material. CONCLUSIONS: it is important that we should not remain any lens cortex material remnant at cataract surgery.
Capsules ; Capsulorhexis ; Cataract ; Cell Culture Techniques ; Culture Media ; Epithelial Cells* ; Organ Culture Techniques

PURPOSE: The purpose of this study was to review intervention programs designed to promote mental health in multicultural children and adolescents living in Korea. METHODS: A systematic search with key words in Korean and English was conducted using 9 electronic databases. Twelve studies were included in the sample for systematic review and the Methodological Index for Non-Randomized Study (MINORS) was used to assess methodological rigor and quality of scientific evidence. RESULTS: Randomized controlled trials (RCTs) were used in 3 and quasi-experimental designs in nine studies. Interventions utilizing art therapy were found to be effective in improving school adjustment in these children, and in decreasing levels of depression and anxiety. Learning activities and self-image were not found to be effective. In all 12 studies discussion of the theory guiding the intervention was not included and all 12 studies were rated as having a high risk of bias based on MINORS criteria. CONCLUSION: Findings provide a basis for developing intervention programs to improve mental health in multicultural children and adolescents. Core strategies for promoting mental health in these children and adolescents include access to age and situational characteristics. For intervention effects, development of programs to improve self-esteem and resilience is important.
Adolescent ; Anxiety ; Art Therapy ; Bias (Epidemiology) ; Child ; Cultural Diversity ; Depression ; Humans ; Korea ; Learning ; Mental Health

Purpose: This study aimed to systematically evaluate the content and effect of using Korean mobile apps for mental health care as reported in previous studies. Methods: We conducted a systematic review according to PRISMA guidelines. Randomized controlled trials published up to May 2021 were searched in the PubMed, Cochrane Library, EMBASE, CINAHL, PsycINFO, RISS, KISS, and KoreaMed databases. We used the Cochrane risk-of-bias tool version 2 for randomized trials to evaluate the selected studies. Results: Out of 3,374 articles retrieved, 12 were selected. These studies included people with mental disorders (mood disorder, panic disorder, or obsessive-compulsive disorder), psychiatric symptoms (depression, anxiety, attention deficit, etc.), and people in specific groups (college students or nurses). The apps were based on cognitive-behavioral therapy, cognitive training, well-being cognition technique, or relaxation techniques. The apps were effective in reducing depression, anxiety, panic attacks, attention deficit, negative emotions, and dysfunctional attitudes, and boosting memory and positive emotions. Conclusion Mobile apps with well-established, theory-based content can serve as an effective intervention for managing several mental health symptoms. However, the scope of the research subjects and symptoms in Korea remains limited. Further studies with more varied populations and symptoms are required.