Protective and therapeutic effects of cannabis plant extract on liver cancer induced by dimethylnitrosamine in mice

Hepatocellular carcinomas will emerge as a major form of malignancy in the coming decades. When these tumors are in advanced stages, few therapeutic options are available. Therefore, it is essential to search for new treatment modalities to fight this disease.Aim: Evaluate the possible protective and therapeutic effects of Cannabis extract on dimethylnitrosamine (DMNA)-induced hepatocarcinogenicity in mice.Methods: Seventy-five male mice were divided into five groups of 15 each: group I mice received corn oil only as the control group; group II mice were injected intraperitoneally with DMNA (10 lg/kg body weight) weekly for 12 weeks; group III mice were pretreated orally with cannabis extract (0.5 ml/kg body weight) every other day for two weeks before the injection of DMNA, and continued until the end of the experiment (12 weeks); group IV mice were treated orally with cannabis extract every other day simultaneously with DMNA injection and continued until the end of the experiment; group V mice were treated orally with cannabis extract every other day after receiving the last intraperitoneal injection of DMNA. A real time PCR was used to quantify telomerase reverse transcriptase and caspase-8 m-RNA expression level. Results: As compared to the control group, mTERT mRNA expression level was significantly increased in group II. The gene in groups (III, IV, and V) was insignificantly higher than the control group but it was significantly decreased as compared to group II. The caspase-8 mRNA expression level was significantly decreased in all groups as compared to the control group. As compared to group II, caspase-8 mRNA level was significantly increased in group III. Conclusion: The protective effect of cannabis extract is more pronounced in group taking cannabis before DMNA. Cannabinoids might exert their anti-tumor effects by the direct induction of apoptosis and can decrease telomerase activity by inhibiting the expression of the TERT gene. Coordination between inhibition of telomerase activity and induction of apoptosis might be a potential therapeutic agent for cancer treatment. KEYWORDS Hepatocellular carcinoma; Cannabis; mTERT; Caspase-

Advancing the application of systems thinking in health:analysing the contextual and social network factors influencing the use of sustainability indicators in a health system - a comparative study in Nepal and Somaliland

BACKGROUND: Health systems strengthening is becoming a key component of development agendas for low-income countries worldwide. Systems thinking emphasizes the role of diverse stakeholders in designing solutions to system problems, including sustainability. The objective of this paper is to compare the definition and use of sustainability indicators developed through the Sustainability Analysis Process in two rehabilitation sectors, one in Nepal and one in Somaliland, and analyse the contextual factors (including the characteristics of system stakeholder networks) influencing the use of sustainability data. METHODS: Using the Sustainability Analysis Process, participants collectively clarified the boundaries of their respective systems, defined sustainability, and identified sustainability indicators. Baseline indicator data was gathered, where possible, and then researched again 2 years later. As part of the exercise, system stakeholder networks were mapped at baseline and at the 2-year follow-up. We compared stakeholder networks and interrelationships with baseline and 2-year progress toward self-defined sustainability goals. Using in-depth interviews and observations, additional contextual factors affecting the use of sustainability data were identified. RESULTS: Differences in the selection of sustainability indicators selected by local stakeholders from Nepal and Somaliland reflected differences in the governance and structure of the present rehabilitation system. At 2 years, differences in the structure of social networks were more marked. In Nepal, the system stakeholder network had become more dense and decentralized. Financial support by an international organization facilitated advancement toward self-identified sustainability goals. In Somaliland, the small, centralised stakeholder network suffered a critical rupture between the system's two main information brokers due to competing priorities and withdrawal of international support to one of these. Progress toward self-defined sustainability was nil. CONCLUSIONS: The structure of the rehabilitation system stakeholder network characteristics in Nepal and Somaliland evolved over time and helped understand the changing nature of relationships between actors and their capacity to work as a system rather than a sum of actors. Creating consensus on a common vision of sustainability requires additional system-level interventions such as identification of and support to stakeholders who promote systems thinking above individual interests