瘦素/阿片促黑素细胞皮质素原/神经肽Y信号在胃转流术治疗2型糖尿病中的作用

目的 探讨瘦素(Leptin)、神经肽Y(NPY)、阿片促黑素细胞皮质素原(POMC)信号通路在胃转流手术治疗2型糖尿病中的作用及机制.方法采用20只成年SD雄性大鼠成功建立2型糖尿病大鼠模型,随机分为糖尿病非手术对照组(NO组,n=10)和糖尿病手术组[Roux-en-Y胃旁路术(RYGB)组,n=10],另外再选10只正常大鼠作为正常对照组(NC组),对手术组实施胃转流手术,分别于术前、术后检测各组大鼠血糖(GLU)、总胆固醇(TCH)及甘油三酯(TG)、Leptin水平,每天定时监测大鼠饮水量、饮食量以及体质量的变化,术后第4周取大鼠下丘脑,检测下丘脑中NPY、POMC mRNA的表达水平.结果术后第4周,RYGB组大鼠血糖、血脂以及进食、水量已接近正常水平,Leptin和NPY mRNA水平分别由术前的(4.58±0.37)μg/L、1.89 ±0.24降低到(3.10±0.38) μg/L、0.95±0.19(P＜0.01),而POMC mRNA水平则由术前的0.78±0.26升高至1.70±0.31(P＜0.01).结论 胃转流手术可以改善2型糖尿病的血糖水平,Leptin可能通过NPY、POMC神经元信号调节2型糖尿病的能量代谢平衡,提示Leptin与下丘脑NPY、POMC调节通路可能在胃转流手术后2型糖尿病病情缓解过程中发挥重要作用.     

吗啡对外周刺激诱导的大鼠海马CA1区长时程增强(LTP)的抑制作用

目的观察吗啡急性中枢应用,对外周电刺激坐骨神经诱导的海马CA1区LTP及海马痛觉调制作用的影响,并探讨其可能的机制。方法25只雄性SD大鼠200～260g,随机分为5组。单刺激坐骨神经,各组侧脑室给药后给予强直刺激,观察场电位的变化。结果单刺激坐骨神经可在海马CA1区诱导出场电位(21.43±4.54)μV,其潜伏期较长(169.94±14.65)ms及阈值较高(平均15V),据此,推断是C类纤维诱发的;强直刺激后海马CA1区可出现持续时间在2h以上LTP现象;中、大剂量吗啡侧脑室注射可抑制海马CA1区LTP,纳洛酮可阻断这种作用。结论LTP是海马痛觉调制的生物学机制之一,阿片受体在其中起重要作用。吗啡对C-类纤维诱导的海马CA1区LTP的抑制作用可能通过阿片受体实现。     

NMDA antagonist modulation of morphine antinociception in female vs. male rats

NMDA antagonists may be useful for their potential to increase or prolong opioid analgesia while attenuating the development of opioid tolerance and dependence. The purpose of this study was to determine whether there are sex differences in NMDA antagonist modulation of morphine antinociception. Adult female and male Sprague–Dawley rats were injected s.c. with saline or one dose of MK-801 (0.005, 0.01, 0.02, or 0.04 mg/kg), dextromethorphan (5, 10, or 20 mg/kg), or LY235959 (0.5, 1.0, or 2.0 mg/kg) in combination with saline or one dose of morphine (1.8, 3.2, or 5.6 mg/kg), and tested on the 50 °C hotplate and tail withdrawal assays 15–120 min post-injection. At the doses examined, only LY235959 produced any antinociception when administered alone. MK-801 attenuated morphine antinociception on both assays, but only at sporadic (inconsistent) dose-combinations. Dextromethorphan increased morphine antinociception on the hotplate but not tail withdrawal assay, at all three morphine doses in males, but only the higher morphine doses in females. In contrast, LY235959 modulated morphine antinociception on both assays; the lowest dose attenuated, and higher doses enhanced morphine antinociception, but the particular morphine doses and assay in which these effects occurred depended on the sex of the subject. Thus, all three NMDA antagonists modulated morphine antinociception in female and male rats, but the direction of this modulation depended on the particular antagonist examined, the nociceptive test, the dose of antagonist and of morphine, and time post-injection.     

Hepatitis C infection and psychiatric burden in two imprisoned cohorts: Young offenders and opioid-maintained prisoners

Prisoners constitute a considerable gap in the hepatitis C virus (HCV) tested population. The present study examined HCV prevalence in imprisoned opioid-maintained patients (OMT-P) and adolescents and young adults (AYA, 14–26 years). In addition, HCV testing and treatment provision, knowledge of HCV status and psychiatric comorbidity were assessed. Data collection took place in six Austrian prisons. Participants were N = 133 for OMT-P (78% male, mean age 35.7 years) and N = 71 for AYA (100% male, mean age 19.8 years). Analysis of HCV serology was conducted. Psychiatric comorbidity and addiction severity were assessed applying standardized questionnaires and interviews. Antibodies were detected in 74.4% of OMT-P, and in 45.0% HCV infection was confirmed. Only one AYA was infected with HCV. None of the participants was receiving treatment for HCV. Eleven percent of OMT-P (50.7% of AYA) did not know their HCV status, and 14.3% of OMT-P (36.6% of AYA) had not been tested in prison. Among OMT-P, lifetime IDU [OR = 330.33, CI = 25.91–4433.20] and age at first IDU [OR = 0.90, CI = 0.82–0.98] significantly predicted HCV status. In both samples, a high prevalence of affective disorders was observed. Despite the high prevalence of HCV among opioid-dependent detainees, the unique opportunities for comprehensive testing and treatment of HCV are substantially underutilized. This is in stark contrast to the UN Basic Principles for the Treatment of Prisoners.     

Kratom policy: The challenge of balancing therapeutic potential with public safety

Kratom (Mitragyna speciosa) is a tree-like plant indigenous to Southeast Asia. Its leaves, and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mitragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported “kratom” products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mitragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom.