Implications of the 2018 Canadian Cannabis Act: Should regulation differ for medicinal and non-medicinal cannabis use?⋆

The regulatory framework for access to medical cannabis has been established in Canada since 2001, with the number of patients seeking access growing substantially over the years. With the novel enactment of the Cannabis Act in October 2018, Canada now maintains two distinct mechanisms for accessing cannabis - one for medical cannabis and the other for non-medical cannabis. With two regulatory access mechanisms in place, questions have arisen in the country as to the necessity of maintaining regulatory separation and the integrity of the medical access framework. A single framework would remove the gate-keeping function that the medical profession currently holds, streamlining processes and simplifying the current regulatory landscape. This approach has been advocated for by the Canadian Medical Association, despite objections from multiple stakeholders. Critical questions arise should the medical access framework be dissolved into a single, non medical-based regulatory framework. Insurance coverage, control mechanisms, market incentives, and patient obligations represent some examples of these issues. This paper will expand upon these considerations and highlight why maintaining two separate access mechanismss best serves the Canadian public. As medicinal cannabis continues to be liberated in international jurisdictions, this paper can help to illuminate the current status of medical cannabis in Canada, and provide insights to those from other countries on our current approach and domestic challenges.     

Influence of renal nerves on renal function during development

The present review summarizes recent studies describing the role of renal sympathetic innervation in the regulation of renal function during development. The afferent renal innervation appears early during fetal life and probably precedes the development of efferent renal nerves. There is suggestive evidence that renal nerves are required for the proper development of the kidney and that neurotrophic growth factors play an important role in renal embryogenesis and in renal tubular differentiation. Renal sympathetic innervation modulates renal hemodynamics early during development. Renal nerve stimulation during -adrenoceptor blockade produces renal vasodilation in fetal and newborn animals but not in adults. Unlike the effect of renal nerves on fetal renal hemodynamics which is observed in the young fetus, the role of renal sympathetic nerves in modulating fluid and electrolyte homeostasis seems to develop during late gestation. Recent studies have also shown that renal nerves play an important role in regulating renin secretion during the transition from fetal to newborn life. For example, renal denervation during fetal life suppressed the physiological rise in plasma renin activity associated with delivery and decreased renal renin mRNA levels after birth. Taken together, these studies suggest that renal nerves influence fetal renal development and that the influence of renal sympathetic innervation on renal hemodynamics and function changes with maturation.     

The microanatomy of canine islets of Langerhans: implications for intra-islet regulation

Summary In recent years models for the internal (intra-islet) regulation of hormone secretion have been proposed to explain how different islet cells might regulate each other by means of their respective secretory peptides. Models that emphasize the importance of a directed intra-islet blood flow and sequence of perfusion of islet cells rely on a certain type of islet microanatomy and vascular supply. The experimental studies underlying these models have partly been performed in dogs. To extend the incomplete morphological knowledge of the canine endocrine pancreas both canine islets of Langerhans and extrainsular cells have been analysed in immunostained serial semithin (0.5 m) sections. In addition to their occurrence within islets of Langerhans, all endocrine cell types are also found at extrainsular sites (about 9% of all endocrine cells) where they are distributed in different quantities among the epithelial lining of exocrine acini or excretory ducts and the connective tissue. There are continuous transitions from single extrainsular cells to small mono-and polycellular cell groups to islets. In a comprehensive analysis of whole islets, including computer-assisted three-dimensional reconstructions, the size, shape and vascularization of the islets as well as their cellular composition and the microtopology of islet cells have been studied. We have found marked intra-and inter-islet heterogeneities of the parameters investigated that are not compatible with concepts of a uniform and directed vascular perfusion of the various islet cell populations. Instead, their paracrine regulation may occur primarily via hormonal secretion into the intercellular spaces or vascular hormonal delivery to adjacent cells.     

In vivo induction of HLA molecules in patients with myeloproliferative syndrome during IFNα treatment

Summary Eighteen patients with myeloproliferative syndrome (14 with chronic myeloid leukemia, four with essential thrombocytosis) were investigated for modulation of HLA antigens on peripheral blood lymphocytes, monocytes, and hematopoietic precursors during IFN therapy as a sign of potentially increased immune recognition of malignant cells. After 1 month of IFN therapy, an increased number of monocytes and hematopoietic precursor cells, but not of lymphocytes, expressed HLADQ antigens. In addition, a strong induction of HLA class-I antigens was found on both hematopoietic progenitors and normal peripheral blood mononuclear cells. With daily injections of IFN in the first month of therapy stimulation continuously increased, suggested a major effect of IFNa on hematopoietic progenitors with sustained enhanced expression of HLA class-I antigens during differentiation of myelomonocytic cells. HLA class-I antigen expression was consistently augmented by IFN in all patients, irrespective of their hematological response.This work was supported by theElse Übelmesser Stiftung and theDeutsche Forschungsgemeinschaft, Sonderforschungsbereich 120, projects A3 and D4     

子宫内膜癌细胞中孕激素受体的多因素调节

目的　通过体外实验研究雌激素、孕激素、胰岛素 /胰岛素样生长因子Ⅰ (Insulin -likegrowthfactorⅠ ,IGF -Ⅰ )对内膜癌细胞中孕激素受体 (Progesteronereceptor,PR )亚型表达的调节 ,探讨内膜癌细胞中PR亚型表达的意义。方法　体外培养高分化子宫内膜癌细胞Ishikawa ,按实验目的分别加入雌激素、孕激素、雌激素孕激素联合、胰岛素及IGF -Ⅰ刺激 2 4h、 4 8h后 ,采用Westernblot方法测定各个条件下内膜癌细胞中两种孕激素受体亚型的表达。结果　内膜癌细胞Ishikawa在自然状态下 ,PR -A和PR -B均阳性表达 ;细胞经血清限制后 ,总PR及两种亚型都明显下调。雌激素可以上调细胞中PR -A和PR -B表达水平 ,但在高血清时明显。孕激素单独或雌、孕激素联合应用在 4 8h时都可以降低Ishikawa细胞中PR表达。胰岛素 /IGF -Ⅰ在 2 4h时可以上调PR -B水平 ,4 8h时此上调作用消失。结论　①雌激素对PR的上调作用与血清浓度有关 ,血清中可能含有雌激素作用所需要的某些因子 ;②孕激素对内膜癌细胞Ishikawa中PR有下调作用 ;③胰岛素 /IGF -Ⅰ可以上调内膜癌细胞中PR表达 ,主要是PR -B表达 ,但此作用持续时间短     

食管鳞癌中pRb2/p130、Cdk4和c-myc的表达及意义

目的:探讨pRb2/p130、Cdk4和c-myc在食管鳞癌中的表达及意义。方法:应用Immuno-Bridge+免疫组化法检测了pRb2/p130、Cdk4和c-myc在60例食管鳞癌中的表达水平,用χ2检验分析它们与临床病理指标及它们三者之间相互关系,用Kaplan-Meier方法绘制生存曲线并进行生存分析,Cox比例风险模型作预后分析。结果:食管鳞癌中pRb2/p130的低表达与癌组织分化程度、TNM分期、淋巴结转移、浸润深度有关;Cdk4的高表达与癌组织的分化程度、TNM分期、淋巴结转移相关;c-myc的高表达与淋巴结转移相关;Kaplan-Meier生存分析表明pRb2/p130高表达组(+)的各期的生存率均高于低表达组(-);Cox比例风险模型分析显示pRb2/p130、淋巴结转移、癌组织分化程度是食管鳞癌的独立预后指标。结论:食管鳞癌中存在pRb2/p130的低表达以及Cdk4和c-myc的高表达,促进了细胞的生长和肿瘤的发展,是食管癌发生发展中的重要事件。     

Threshold and non-threshold chemical carcinogens: A survey of the present regulatory landscape

For the proper regulation of a carcinogenic material it is necessary to fully understand its mode of action, and in particular whether it demonstrates a threshold of effect. This paper explores our present understanding of carcinogenicity and the mechanisms underlying the carcinogenic response. The concepts of genotoxic and non-genotoxic and threshold and non-threshold carcinogens are fully described. We provide summary tables of the types of cancer considered to be associated with exposure to a number of carcinogens and the available evidence relating to whether carcinogenicity occurs through a threshold or non-threshold mechanism. In light of these observations we consider how different regulatory bodies approach the question of chemical carcinogenesis, looking in particular at the definitions and methodologies used to derive Occupational Exposure Levels (OELs) for carcinogens. We conclude that unless proper differentiation is made between threshold and non-threshold carcinogens, inappropriate risk management measures may be put in place - and lead also to difficulties in translating carcinogenicity research findings into appropriate health policies. We recommend that clear differentiation between threshold and non-threshold carcinogens should be made by all expert groups and regulatory bodies dealing with carcinogen classification and risk assessment.     

美国马里兰州医院支付体系及其启示

自1977年以来,美国马里兰州医院体系一直执行统一的收费标准,称之为All-payer system。该支付体系最大特点是:对于在同一医院就诊的患者,无论其是否参与任何形式的保险,都按照统一的支付标准向医院支付费用。其优点在于通过政府主导方式对医院体系面临的市场失灵的风险以及医院承担的重要社会责任需消耗的成本进行补偿,有效控制医院成本并促进效率提高。