The isoflavones mixture from Trifolium pratense L. protects HCN 1-A neurons from oxidative stress

Oxidative stress-induced neuronal cell death has been implicated in different neurological disorders and neurodegenerative diseases such as Alzheimer's disease and Parkinson's. Using the Alzheimer's disease-associated hydrogen peroxide (H(2)O(2)), we investigated the neuroprotective efficacy of a natural mixture of phytoestrogenic isoflavones (genistein, daidzein, biochanin A and formononetin) from Trifolium pratense L. (Red clover) against oxidative stress-induced cell death in human cortical cell line HCN 1-A maintained in culture. Neuronal viability was determined by MTT or trypan blue test and neuronal integrity by morphological analysis.The results obtained indicate that exposure of HCN 1-A cell cultures to hydrogen peroxide resulted in a concentration-dependent decrease in neuron viability. Concentration of H(2)O(2) ranging from 50 to 200 microg/ml were toxic to these cultures. A 24-hour pretreatment with 0.5, 1 and 2 microg/ml isoflavones extract significantly increased cell survival as evidenced by MTT or trypan blue test and significantly prevented the morphological disruption caused by H(2)O(2) as shown by microscopical inspection, indicating that neurons treated with isoflavones were protected from the cell death induced by H(2)O(2) exposure. These findings imply that the neuroprotective effect of isoflavones extract is partly associated with its antioxidant activity. Further, results of these investigations indicate that although isoflavones extract exert a neuroprotective effect, it do not promoted cortical neuron process outgrowth.     

Coupling of lactose molecules to the carrier protein hinders the spleen and bone marrow uptake of doxorubicin conjugated with human albumin.

Several attempts have been made to enhance doxorubicin (DOXO) concentrations in tumour cells by drug conjugation with human albumin (HSA). HSA-DOXO has the drawback of causing DOXO accumulation in spleen and bone marrow, with a consequent leucopoenia not produced when lactose molecules are coupled to the carrier protein. In the present experiments we demonstrated that the effect of HSA lactosamination is not a consequence of a more rapid disappearance from the bloodstream of the lactosaminated conjugate (L-HSA-DOXO), which is rapidly internalized by the liver through the asialoglycoprotein receptor, but is due to a hindered uptake by spleen and bone marrow cells caused by the coupled lactose molecules. Experiments in vitro showed that HSA-DOXO produced an inhibition of murine macrophage proliferation not caused by L-HSA-DOXO. This result can be explained by higher amounts of the former conjugate entering in these cells and suggests macrophages as the cell type responsible for the spleen and bone marrow internalization of HSA-DOXO hindered by lactose coupling. Importantly, lactosamination of HSA did not reduce the marked uptake of HSA-DOXO by chemically induced rat hepatocellular carcinoma. L-HSA-DOXO, by avoiding DOXO accumulation in bone marrow is an attractive candidate for clinical trials against tumors which were found to actively internalize this conjugate in laboratory animals, such as hepatocellular carcinoma.     

Self-expanding mesh stent for endoscopic palliation of rectal obstructing tumors: a preliminary report

Summary The endoscopic insertion of self-expanding mesh stents in four patients affected by obstructing rectal malignant tumors is reported. The preliminary experience shows that, in the short term, normal defecation was achieved, with no complications. Longer follow-up is necessary to evaluate the duration and the quality of the palliative effect.     

Intracerebroventricular injection of hemicholinium-3 prevents the ACTH-induced, but not the physostigmine-induced, reversal of hemorrhagic shock in rats

In rats bled to hypovolemic shock, the intracerebroventricular injection of hemicholinium-3 (20 micrograms/rat) completely prevented the shock reversal induced by the intravenous injection of ACTH (1-24) (160 micrograms/kg), but had no influence on the shock reversal induced by the intravenous injection of physostigmine (70 micrograms/kg). These data indicate that brain cholinergic neurons are involved in the anti-shock effect of ACTH-peptides, but not in that of centrally acting cholinergic drugs.     

Arecoline, but not haloperidol, induces changes in the permeability of the blood-brain barrier in the rat

The aim of the present study was to investigate the existence of alterations of the blood-brain barrier (BBB) permeability in rats injected with centrally acting drugs, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-alpha-aminoisobutyric acid. The intraperitoneal (i.p.) injection of the dopaminergic antagonist haloperidol (1 mg kg-1) did not modify the regional BBB permeability. When the cholinomimetic agent arecoline hydrobromide (6.25 mg kg-1) was injected i.p. into methylatropine-pretreated rats, it induced a significant decrease of Ki values within the frontal cortex, parietal cortex, striatum and brain-stem. Our findings emphasize two concepts: (1) centrally acting drugs, such as arecoline, can induce changes in the BBB permeability, through several mechanisms; (2) there is no predictable correlation of drug stimulation of specific brain neuronal pathways and changes in the permeability of the BBB.