A call for urgent action to safeguard our planet and our health in line with the helsinki declaration.

In 2015, the Rockefeller Foundation-Lancet Commission launched a report introducing a novel approach called Planetary Health and proposed a concept, a strategy and a course of action. To discuss the concept of Planetary Health in the context of Europe, a conference entitled: "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki in December 2019. The conference participants concluded with a need for action to support Planetary Health during the 2020s. The Helsinki Declaration emphasizes the urgency to act as scientific evidence shows that human activities are causing climate change, biodiversity loss, land degradation, overuse of natural resources and pollution. They threaten the health and safety of human kind. Global, regional, national, local and individual initiatives are called for and multidisciplinary and multisectorial actions and measures are needed. A framework for an action plan is suggested that can be modified for local needs. Accordingly, a shift from fragmented approaches to policy and practice towards systematic actions will promote human health and health of the planet. Systems thinking will feed into conserving nature and biodiversity, and into halting climate change. The Planetary Health paradigm ‒ the health of human civilization and the state of natural systems on which it depends ‒ must become the driver for all policies.

Intermittent levosimendan treatment in patients with severe congestive heart failure.

OBJECTIVE: Levosimendan (LS) is a novel inodilator for the treatment of severe congestive heart failure (CHF). In this study, we investigated the potential long-term effects of intermittent LS treatment on the pathophysiology of heart failure. METHODS: Thirteen patients with modest to severe CHF received three 24-h intravenous infusions of LS at 3-week intervals. Exercise capacity was determined by bicycle ergospirometry, well-being assessed by Minnesota Living with Heart Failure Questionnaire (MLHFQ) and laboratory parameters of interest measured before and after each treatment. RESULTS: One patient experienced non-sustained periods of ventricular tachycardia (VT) during the first infusion and had to discontinue the study. Otherwise the LS infusions were well tolerated. Exercise capacity (VO2max) did not improve significantly during the study although symptoms decreased (P < 0.0001). Levels of plasma NT-proANP, NT-proBNP and NT-proXNP decreased 30-50% during each infusion (P < 0.001 for all), but the changes disappeared within 3 weeks. Although norepinephrine (NE) appeared to increase during the first treatment (P = 0.019), no long-term changes were observed. CONCLUSION: Intermittent LS treatments decreased effectively and repetitively plasma vasoactive peptide levels, but no carryover effects were observed. Patients' symptoms decreased for the whole study period although there was no objective improvement of their exercise capacity. The prognostic significance of these effects needs to be further studied.

Cytokines, interstitial collagen and ventricular remodelling in dilated cardiomyopathy.

BACKGROUND: Dilated cardiomyopathy (DCM) is associated with myocardial fibrosis, and proinflammatory cytokines may play a role in this. METHODS: N-terminal type I and III procollagen propeptides (PINP, PIIINP) and cross-linked telopeptide of type I collagen (ICTP) were measured from serum samples of 73 patients with DCM and 56 age and sex matched controls. Circulating cytokine levels were determined in DCM patients. RESULTS: Serum levels of PINP and PIIINP were lower in patients than in controls (p<0.05 and p=0.001). In patients with DCM, the levels of PIIINP and ICTP correlated significantly with each other (p<0.01), and the proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6), correlated positively with ICTP (p<0.001, p<0.05), PIIINP/PINP ratio (p<0.05, p<0.01) and left atrial size (p<0.01, p<0.05). Presence of atrial fibrillation was associated with lower serum PINP level and higher PIIINP/PINP ratio (p<0.05). CONCLUSIONS: Our results suggest that interstitial myocardial collagen metabolism is altered in DCM patients and regulated by proinflammatory cytokines. These changes in collagen metabolism are associated with presence of atrial fibrillation, but do not reflect left ventricular remodelling. Treatment with beta-blockers and inhibitors of the renin angiotensin aldosterone system seem to effectively inhibit overall type I and III collagen syntheses.

TK-GFP fusion gene virus vectors as tools for studying the features of HSV-TK/ganciclovir cancer gene therapy in vivo.

The fusion gene of herpes simplex virus thymidine kinase and green fluorescent protein (TK-GFP) was shown to be a versatile tool for examining the features of thymidine kinase/ganciclovir gene therapy in vitro. In this study, we used viral vectors carrying the fusion gene to characterize the aspects of this gene therapy form in rodent tumor models. Growth of subcutaneous 9L rat tumors transduced ex vivo with TK-GFP gene was prevented when ganciclovir (GCV) treatment was initiated immediately after tumor inoculation. Established tumors (>100 mm(3)), however, were untreatable despite the initial 55% proportion of TK-GFP positive cells. This was due to a rapid clearance of TK-GFP positive cells, but not GFP positive cells. Propidium iodide staining revealed that TK-GFP lentivirus vector was able to induce apoptosis/necrosis in 9L cells, as opposed to the respective GFP vector. Furthermore, when a subcutaneous nude mouse tumor model was used, the percentage of TK-GFP positive cells in vivo was maintained similarly as in cultured cells, suggesting contribution of a fully functional immune response to the disappearance of fusion gene positive cells. In vivo gene transfer studies: adenovirus TK-GFP vector injections resulted in about 25% gene transfer efficiency to 9L tumors and showed that their growth could be significantly reduced even when the tumor volumes were already >120 mm(3). Part of the effect was shown to be due to cytotoxicity of the vector. In summary, our results demonstrate the utility of TK-GFP fusion gene-carrying viral vectors in animal studies and show that readily detectable therapeutic genes can help us to understand the complicated nature of in vivo cancer gene therapy experiments.