**8. References**

604 Pharmacology

was tested in dose range of 10, 50, 100 µg/106 cells. 10 µg extract contains 0.002 µg lectin + 0.01 µg viscotoxin, 50 µg extract contains 0.01 µg lectin + 0.05 µg viscotoxin, 100 µg extract

Dosage of Vincristine in the therapy for multiple myeloma: In combination with other chemotherapeutic agents as a part of the VAD regimen 0.4 mg/day intravenously (400 µg/day). In these experimental studies Vincristine was applied in dose range of 10, 50, 100 µg/106 cells. The effects of Vincristine on the proliferation and the apoptosis/necrosis were in each cell line without dose dependence. This means that these doses lay in a saturation

The efficient dose range for VAQuFrF lies between 50 and 100 µg/106 cells (0.01µg lectin + 0.05 µg viscotoxin and 0.02 µg lectin + 0.1 µg viscotoxin). These date concern the cell lines LP-1, RPMI-8226 and COLO-677. For cell lines OPM-2, KMS-12-BM the dose range lies higher. In

Our findings suggest that the in vivo effective (active) dose for VAQuFrF will be about 10-

1. **Viscum album** (VA) QuFrF extract contains two active components: mistletoe lectins (I,

**lectin(s)** or **viscotoxin** or **both?** Further study is planned to clarify this **question.** 

viscotoxin in 10 mg/ml **(ratio between lectin and viscotoxin: 0.2).**

3. To investigate more human multiple myeloma cell lines.

VAQuFrF extract in a higher dose range.

**Question**: Which component is responsible for the effects of this extract? Is this the

The non-fermented preparation from VAQuFrF extract contains 2 µg lectin and 10 µg

The **ratio between lectin and viscotoxin from the fermented preparations is 0.06** respectively **0.08.** The fermented preparations are used either alone or in combination with chemo /radiotherapy in the treatment of tumour patients. The extract presented in this study is an experimental drug that is not yet used in the treatment of tumour patients. 2. The results presented in this study indicated that VAQuFrF could effect the membrane expression of IL-6 receptor by antagonism. **Question:** Is this substance a competitive- or a non-competitive antagonist? Additional experiments will give answer to this

To investigate **tumour cells isolated from bone marrow** of patients with multiple

4. To investigate the anti-proliferative and apoptotic/necrotic effects of Vincristine in a lower dose range, respectively the anti-proliferative and apoptotic/necrotic effects of

The measurements of the parameters were carried out in the laboratory of the Society of Cancer Research (Arlesheim, Switzerland). The idea of this study is based on the findings of the author. As principal investigator she wrote the study protocol and co-ordinated the study. The evaluation of the results, the writing and the completion of this manuscript were

not supported from the Society of Cancer Research and from any foundation.

range. It is planned to investigate the effects of Vincristine in a lower dose range.

MOLP-8 cell line VAQuFrF inhibits the proliferation more effectively than Vincristine.

contains 0.02 µg lectin + 0.1 µg viscotoxin.

20 times higher than that of Vincristine.

**6. Future research** 

II, III) and viscotoxins**.** 

(important) **question.** 

**7. Acknowledgements** 

myeloma.


**1. Introduction** 

**27** 

*Slovenia* 

**Ethanol Toxicity in the Brain:** 

*Department of Pharmacology and Experimental Toxicology* 

*University of Ljubljana, Faculty of Medicine,* 

Metoda Lipnik-Štangelj

**Alteration of Astroglial Cell Function** 

Ethanol consumption has for a long time been associated with brain damage. Experimental studies and necropsy examinations of chronic alcoholics have shown a variety of structural and functional alterations in the neurons as well as in the glial cells. Such alterations are seen also in children with the alcoholic foetal syndrome. Ethanol is known to be a teratogen. Its abusage can result as dysfunction of the central nerve system (CNS), growth deficiency and facial malformation in the fetus, and behavioural, learning, sensory and motor disabilities (Barret et al., 1996; González & Salido, 2009; Šarc & Lipnik-Štangelj, 2009a). Chronic ethanol consumption in the adult is also intimately associated with brain atrophy. Accumulating evidence indicates that ethanol-induced neurobehavioral dysfunctions may be related to disruptions in the patterns of neuronal and glial developments such as depression of neurogenesis, aberrant migration of neurons and alterations in late gliogenesis and neurogenesis. These changes can further reduce the populations of cortical neurons and glial cells, trigger the biochemical alterations in glial cells and deleterious consequences for neuronal-glial interactions, and eventually lead to damage or apoptosis of these cells

(González & Salido, 2009; Šarc & Lipnik-Štangelj, 2009b; Sofroniew & Vinters, 2010).

et al., 2001; Halassa et al., 2007; Sofroniew & Vinters, 2010).

significant object of toxicological evaluation.

As the most abundant type of glial cells in the brain, astrocytes provide metabolic and trophic support to neurons, modulate synaptic activities and have a strong capacity to scavenge oxidants and suppress cellular apoptosis. However, when the capacity of cells to eliminate the oxidants is overwhelmed, overproduction of reactive oxygen species (ROS) can cause morphological and functional alterations in the cells, including cellular Ca2+ homeostasis and some active molecules tightly associated with neuronal activity (Allansson

Although astrocytes are more resistant than neurons to the oxidative and neurotoxic stresses and to the chemical and toxic damages in the surrounding environment, any impairment of astrocytes can dramatically affect neuronal functions. The ethanol-induced detrimental alterations of astrocytes would lead to perturbances in neuron–astroglia interactions and developmental defects of the brain (González & Salido, 2009; Šarc & Lipnik-Štangelj, 2009b). Given this important role of astroglial cells in neuronal functioning, they have become a

