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Brain is susceptible to oxidative stress and it is associated with age-related brain dysfunction. Previously, we have pointed out a dramatic decrease of glutathione levels in the rat brain after acetaminophen (APAP) oral administration overdose. Silymarin (SM) is a mixture of bioactive flavonolignans isolated from Silybum marianum (L.) Gaertn., employed usually in the treatment of alcoholic liver disease and as anti-hepatotoxic agent in humans. In this study, we have evaluated the effect of SM on enzymatic and non enzymatic antioxidant defensive systems in rat brain after APAP-induced damage. Male albino Wistar rats were treated with SM (200 mg/kg/die orally) for three days, or with APAP single oral administration (3 g/kg) or with SM (200 mg/kg/die orally) for 3 days and APAP single oral administration (3 g/kg) at third day. Successively the following parameters were measured: reduced and oxidized glutathione (GSH and GSSG), ascorbic acid (AA), enzymatic activity variations of superoxide dismutase (SOD) and malondialdehyde levels (MDA). Our results showed a significant decrease of GSH levels, AA levels and SOD activity and an increase of MDA and GSSG levels after APAP administration. After SM administration GSH and AA significantly increase and SOD activity was significantly enhanced. In the SM+APAP group, GSH values significantly increase and the others parameters remained unchanged respect to control values. These results suggest that SM may to protect the SNC by oxidative damage for its ability to prevent lipid peroxidation and replenishing the GSH levels.

Iresine herbstii Hook. (Amaranthaceae) and Brugmansia arborea (L.) Lagerheim (Solanaceae) are used in the northern Peruvian Andes for magic-therapeutical purposes. The traditional healers use Iresine herbstii with the ritual aim to expel bad spirits from the body. Furthermore, Iresine herbstii was used in association with other plants, such as Trichocereus pachanoi Britt. et Rose, for divination, to diagnose diseases, and to take possession of another identity. Also, species of Brugmansia have been reported to be used during ritual practices for magical and curative purposes. Given the above evidence, the aim of the present study is to evaluate if the central effects of Iresine herbstii and Brugmansia arborea could be associated with interaction with SNC receptors. Two Iresine herbstii extracts (methanolic and aqueous) and one Brugmansia arborea aqueous extract were tested for in vitro affinity on 5-HT(1A), 5-HT(2A), 5-HT(2C), D1, D2, alpha(1), and alpha(2) receptors by radioligand binding assays. The biological materials for binding assay (cerebral cortex) were taken from male Sprague-Dawley rats. The extracts affinity for receptors is definite as inhibition percentage of radioligand/receptor binding and measured as the radioactivity of remaining complex radioligand/receptor. The data obtained for Iresine extracts have shown a low affinity for the 5-HT(1A) receptor and no affinity for 5-HT(2A) receptor. Otherwise the methanolic extract showed affinity for 5-HT(2C) receptor (IC(50): 34.78 microg/ml) and for D1 receptor (IC(50): 19.63 microg/ml), instead the Iresine aqueous extract displayed a lower affinity for D1 (48.3% at the maximum concentration tested) and a higher value of affinity for D2 receptors (IC(50): 32.08 microg/ml). The Brugmansia aqueous extract displayed affinity for D1 receptors (IC(50): 17.68 microg/ml), D2 receptors (IC(50): 15.95 microg/ml) and weak affinity for the serotoninergic receptors. None of the three extracts showed relevant affinity to the alpha(1), and alpha(2) receptors. The results of our experiments indicate that Iresine herbstii methanolic extract was able to interact with the central 5-HT(2C) and D1 receptors and Iresine herbstii aqueous extract showed affinity for D2 receptors, thus confirming their ritual use. Instead Brugmansia arborea was able to interact only with the central dopamine receptors tested. Parallel studies are currently in progress for evaluating the extracts affinity and active components towards these and other receptor types (GABAergic).

Experimental findings suggest that granulocyte-monocyte-colony stimulating factor (GM-CSF) synergistically interacts with interleukin-2 (IL-2) in generating an efficient antigen-specific immune response. We evaluated the toxicity, antitumour activity and immunobiological effects of human recombinant (hr)-GM-CSF and hr-IL-2 in 25 cancer patients who subcutaneously (s.c.) received hr-GM-CSF 150 microg/day for 5 days, followed by hrIL-2 s.c. for 10 days and 15 days rest. Two of the most common side-effects were bone pain and fever. Of the 24 patients evaluable for response, 3 achieved partial remission, 13 experienced stable disease, and 8 progressed. Cytokine treatment increased the number of monocytes, dendritic cells (DC), and lymphocytes (memory T cells) in the peripheral blood and enhanced the antigen-specific immunoreactivity of these patients. Our results show that the hr-GM-CSF and hr-IL-2 combination is active and well tolerated. Its biological activity may support tumour associated antigen (TAA)-specific anticancer immunotherapy by increasing antigen presenting cell (APC) activity and T cell immune competence in vivo.

Background: The risk of gastric carcinoma is increased in persons with a positive family history of the disease. Previous findings suggest that free radicals are involved in both the initiation and promotion of carcinogenesis. Objective: The aim of this study was to assess whether alterations in the antioxidant defense system of gastric mucosal cells in patients with gastric carcinoma are related to a positive family history. Methods: Glutathione peroxidase activity, oxidized glutathione, total glutathione, and malondialdehyde levels were assayed in patients with gastric carcinoma with and without a family history of the disease. A control group consisted of healthy volunteers. Results: The study enrolled 65 patients with gastric carcinoma: 35 with and 30 without a family history of the disease, as well as 30 control subjects. The level of glutathione peroxidase activity in tumor-free tissue samples from patients with a family history of gastric carcinoma was higher than in samples from those without such family history. Glutathione peroxidase activity was also significantly higher in neoplastic than in tumor-free tissue. There was no significant difference in glutathione peroxidase activity between neoplastic tissue samples taken from patients with and without a positive family history. Conclusions: The results appear to support the existence of an enzymatic imbalance caused by cellular initiation in patients with a family history of gastric carcinoma. This imbalance may lead to an altered response to free radical oxygen species and a consequent progressive increase in biologic damage.

Valeriana adscendens Trel. (Valerianaceae) is a psychoactive plant usually used in magical-therapeutic rituals in traditional practices of the Northern Peruvian Andes. Previous studies have been carried out on extracts of aerial parts in order to validate its traditional use. The results indicated that Valeriana adscendens exerts important effects on the central nervous system. Aim of the present study is to evaluate if the effects on the central nervous system of Valeriana adscendens extracts can be associated with interaction with some CNS receptors. In this work we examined affinity and selectivity of two Valeriana adscendens extracts (methanolic and aqueous) towards 5-HT(1A), 5-HT(2A), 5-HT(2C) serotononergic, D(1) and D(2) dopaminergic, alpha(1) and alpha(2) noradrenergic receptors by a preliminary binding screen. The results show weak affinity to 5-HT(1A) for the aqueous extract. Both extracts showed affinity for D(1) receptors, but only for the methanolic extract the IC(50) value was determinable (30.14 microg/ml). No affinity for 5-HT(2A), 5-HT(2C) serotononergic receptors, alpha(1) and alpha(2) noradrenergic receptors and D(2) receptors was recorded for the extracts.

A simple high-performance liquid chromatographic (HPLC) method for the determination of flufenamic acid in rat plasma is described. After liquid-liquid extraction, the drug is separated by HPLC on a 5-microns octadecylsilica column (Nucleosil C18) with ultraviolet detection at 280 nm. Linear calibration graphs for flufenamic acid were constructed from 0.5 to 15 micrograms/ml. The method has been applied to a pharmacokinetic study in animals.

To investigate the relationship between acetaminophen (APA) and calcium ion (Ca 2+ ) homeostasis within the glutathione (GSH) oxidation-reduction cycle, male rats were given APA (one buccal injection of 3 g/kg) and/or MK-801 (three intraperitoneal injections each of 0.2 mg/kg), a noncompetitive N-methyl-D-aspartate receptor antagonist. There were injection-vehicle control groups for all active drug groups; an additional control group received no injections (total of seven experimental groups; 134 rats). The brain tissue was examined 8 hours after administration of the drugs to determine the levels of GSH, APA, and protein. APA produced a 25% decrease in GSH that was strongly enhanced by the coadministration of MK-801 (49% decrease). MK-801 alone produced a 32% decrease in brain levels of GSH. This reduction of GSH is probably linked to the interference of Ca 2+ homeostasis and can be considered as a trigger for cell injury in oxidative stress.

The levels of the antioxidant glutathione were measured in several regions of the rat brain after oral administration of 3 gm/kg of acetaminophen. Acetaminophen affected the concentration of the reduced form of glutathione primarily in the hypothalamus (−20%), medulla oblongata (−14%), and cerebral cortex (−24%). This depletion, probably bound to Ca ++ homeostasis, is able to start a reversible or irreversible toxic process.

The administration of L-2-oxothiazolidin-4-carboxylic acid (OTC) and glutathione (GSH) to modulate total GSH levels was examined in 24 men with human immunodeficiency virus (HIV) and 10 healthy HIV-seronegative control subjects. The mean blood GSH concentration in the control subjects was 1.65 ± 0.287 μmol/ml while that in the HIV-seropositive patients was 0.61 ± 0.248 μmol/ml. The oral administration of OTC 25 mg/kg and the intramuscular administration of GSH 800 mg/day in the HIV-seropositive subjects markedly increased the total GSH levels. These results suggest that a systemic decrease in GSH levels could be one of the factors involved in the immunodeficiency of HIV-seropositive patients.