Silymarin pretreatment protects against ethanol-induced memory impairment: Biochemical and histopathological evidence.

BACKGROUND: Ethanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear. METHODS: Twenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups. RESULTS: While the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters. CONCLUSION: The memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes.

The Fat1 cadherin is overexpressed and an independent prognostic factor for survival in paired diagnosis-relapse samples of precursor B-cell acute lymphoblastic leukemia.

Improved survival of patients with acute lymphoblastic leukemia (ALL) has emerged from identifying new prognostic markers; however, 20% of children still suffer recurrence. Previously, the altered expression of Fat1 cadherin has been implicated in a number of solid tumors. In this report, in vitro analysis shows that Fat1 protein is expressed by a range of leukemia cell lines, but not by normal peripheral blood (PB) and bone marrow (BM) cells from healthy donors. In silico analysis of expression of array data from clinical leukemias found significant levels of Fat1 transcript in 11% of acute myeloid leukemia, 29% and 63% of ALL of B and T lineages, respectively, and little or no transcript present in normal PB or BM. Furthermore, in two independent studies of matched diagnosis-relapse of precursor B-cell (preB) ALL pediatric samples (n=32 and n=27), the level of Fat1 mRNA expression was prognostic at the time of diagnosis. High Fat1 mRNA expression was predictive of shorter relapse-free and overall survival, independent of other traditional prognostic markers, including white blood cell count, sex and age. The data presented demonstrate that Fat1 expression in preB-ALL has a role in the emergence of relapse and could provide a suitable therapeutic target in high-risk preB-ALL.

Eugenol depresses synaptic transmission but does not prevent the induction of long-term potentiation in the CA1 region of rat hippocampal slices.

Using field potential recording in the CA1 region of the rat hippocampal slices, the effects of eugenol on synaptic transmission and long-term potentiation (LTP) were investigated. Population spikes (PS) were recorded in the stratum pyramidal following stimulation of stratum fibers. To induce LTP, eight episodes of theta pattern primed-bursts (PBs) were delivered. Eugenol decreased the amplitude of PS in a concentration-dependent manner. The effect was fast and completely reversible. Eugenol had no effect on PBs-induced LTP of PS. It is concluded that while eugenol depresses synaptic transmission it does not affect the ability of CA1 synapses for tetanus-induced LTP and plasticity.

The effect of cryopreservation on clonogenic capacity and in vitro expansion potential of umbilical cord blood progenitor cells.

BACKGROUND: Umbilical cord blood progenitor cells have been demonstrated to possess significant advantages over bone marrow in terms of proliferative capacity and immunologic reactivity. But the low number of hematopoeitic stem cells (HSC) is the most important limitation of its use. The ex vivo expansion of cord blood progenitor cells is the current strategy to overcome this problem. Furthermore, among the factors that enable successful cord blood transplantation is the ability to store and subsequently recover a sufficient number of viable cells. Since it would be costly to expand umbilical cord blood (UCB) progenitor cells, it is important to determine the feasibility and reproducibility of progenitor cell expansion after cryopreservation. We evaluated whether cryopreservation procedures might impair the clonogenic capacity and in vitro expansion of UCB. MATERIALS AND METHODS: We evaluated the cell viability, clonogenic capacity, CD34+38- content and in vitro expansion potential of progenitor cells from UCB (n = 10) separated mononuclear cells (MNC), before and after 1 month of cryopreservation by programmed rate freezing. RESULTS: Although cell viability decreased after cryopreservation (P < .05), there was no significant difference in CD34+ or CD34+38- absolute count, colonogenic capacity and in vitro expansion potential of cord blood progenitor cells (P > .05). CONCLUSIONS: Since the survival of CD34+ cells was greater than other elements, CD34+ cells seem more tolerant to cryopreservation than the other nucleated populations. Moreover in vitro expansion of UCB progenitor cells may be obtained following cryopreservation. Our results suggest that cryopreservation procedures do not impair the clonogenic capacity and in vitro expansion potential of cord blood stem/progenitor cells.