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The activity principle of the mistletoe (Viscum album L.) phytotherapeutics could be considered as combined cytotoxic and "biological response modifying" activities (increasing host defense against cancer) that result from the activities of the plant lectins and the other biologically relevant substances. We found before that the aqueous extract Isorel, produced by Novipharm GmbH (Pörtschach, Austria) from the entire plant (planta tota) of fresh mistletoe under standardized conditions with bioassay validated batch consistency, can be valuable in experimental adjuvant cancer therapy increasing efficiency of cyclophosphamide chemotherapy. In current study we found that Isorel increases the reactivity of the tumor-bearing mice lymphocytes to the mitogens (ConA and LPS) in vitro, thus indicating its immune stimulating effects for the cancer-immunosuppressed lymphocytes. Moreover, Isorel inhibited the incorporation of 3H-labelled amino acids (protein synthesis) in various malignant cell lines. For the growth inhibition mostly higher MW components were responsible, although even less than 500 Da components were also active. We further analyzed the effects of drug application in vicinity of tumor (murine mammary carcinoma) and compared it with systemic effects. The animals carried mammary carcinoma in both hind limbs and were also injected with tumor cells i.v. to develop artificial lung metastases. Isorel was applied only at the right side (in the limb distal from the tumor) and caused persistent and almost complete inhibition of the tumor growth for 2/7 animals. Anticancer effects were less pronounced on the contralateral side tumors, although tumor growth rate was transiently reduced for some mice. Histology revealed that Isorel treatment, both at the side of tumor and systemically, increased the incidence of apoptosis and necrosis in the tumors, while reduction of mitosis was noticed only for the tumors in vicinity of the tumor exposed to Isorel. Finally, animals treated with Isorel had, on the average, three times less lung metastases than the controls. Thus, we conclude that both local and systemic effects of the application of Isorel could be of benefit for the tumor-bearing organism resulting in immunomodulation combined with tumor growth inhibition and reduction of metastases. According to the in vitro results, antitumorous effects could be the result not only of the mistletoe lectins and the other high MW factors, but also of the very low MW (< 500 Da) substances that deserve further analyses.

Numerous findings indicate that specific plant lectins acting against cancer could be major active components of Viscum album extracts, although activity of low molecular weight components (peptides, carbohydrates and alkaloids) might be as essential for the beneficial activity of the plain plant extracts, too. Thus, active principle of Viscum album extracts is still not understood, and is difficult to be analysed because of the complex composition of the extracts and uncertainty of the standardised effectiveness (batch consistency) of the extracts. The aims of this study were to compare the concentration dependent effects of the pure mistletoe lectin (ML-1) with the fresh plant Viscum album extract (Isorel) and its different MW components on the in vitro growth of ConA stimulated lymphocytes, on the growth and tumorigenicity (artificial lung metastases development) of murine melanoma B16F10 cells, and to compare concentration dependent effects of the different types of the Viscum album extracts in vitro (applying novel type of MTT assay). The results obtained indicate that the effects of Isorel used at high dose could be result of toxic activity of the mistletoe lectins ("ML-1 like" activity). Unlike ML-1, if used at low concentrations, Isorel selectively inhibited tumor cells, due the activity of the low MW components. On the other hand, the number of tumor nodules was reduced (in comparison to the control) equally in the lungs of mice injected with B16F10 cells pre-treated in vitro with the plain Viscum album extract or any of its modifications or ML-1. Hence, it is supposed that the beneficial therapeutic effects of Isorel might result from the combined biological activity of the high and the low MW components not lectins only. Similarly, in MTT assay low concentrations of all types of the Viscum album extract showed stronger inhibiting activity for B16F10 and HeLa cells than pure ML-1. According to these results we propose a standardisation of aqueous Viscum album extracts by comparing their and ML-1 concentration dependent activity on the tumor cells in vitro applying MTT bioassay described which should be relevant for further evaluation of their active principle and for improvement of biotherapy of cancer.

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Klinički zavod za rehabilitaciju i ortopedska pomagala Kliničkog bolničkog centra Zagreb Medicinskog fakulteta Sveučilišta u Zagrebu SažetakKvaliteta zdravstvene skrbi i bolesnikova sigurnost dio su profesionalne etike zdravstvenih djelatnika. Zdravstvena skrb odvija se prema biopsihosocijalnom modelu u kojem bolesnikova sigurnost i bolesnik u središtu predstavljaju područje prioritetnog interesa za sustav, gledajući ne samo s medicinskog nego i sa socioekonomskog aspekta. Sigurnost bolesnika višedimenzionalan je standard u kvaliteti zdravstvene zaštite. Podložna promjenama u svojoj višedimenzionalnosti, bolesnikova sigurnost područje je koje zahtijeva razumijevanje, praćenje i razvoj. Standardi kvalitete zdravstvene zaštite jasno su određeni u definiciji te načinu primjene, no kultura unutar zdravstvenih organizacija nije u potpunosti razvijena, što utječe i na bolesnikovu sigurnost kao najpouzdaniju mjeru kvalitete zdravstvenog sustava. Za uspostavu bolesnikove sigurnosti nije nužno važna financijska potpora, već prije svega predanost zdravstvenog djelatnika procesu skrbi, kao individue s potrebnim znanjem i vještinama iz područja sigurnosti bolesnika. Formalna naobrazba zdravstvenih profesija važna je za uspostavu i održivost kulture bolesnikove sigurnosti, a razina njezine uspješnosti i/ili učinkovitosti odražava se u kvaliteti zdravstvene skrbi. Uz kontinuirano unaprjeđenje kvalitete inherentno je obrazovanje usklađeno s potrebama u zdravstvenom sustavu.