The antitumor activity of the organometallic ruthenium(II)-arene complexes, RuCl(2)(eta(6)-arene)(PTA), (arene = p-cymene, toluene, benzene, benzo-15-crown-5, 1-ethylbenzene-2,3-dimethylimidazolium tetrafluoroborate, ethyl benzoate, hexamethylbenzene; PTA = 1,3,5-triaza-7-phosphaadamantane), abbreviated RAPTA, has been evaluated. In vitro biological experiments demonstrate that these compounds are active toward the TS/A mouse adenocarcinoma cancer cell line whereas cytotoxicity on the HBL-100 human mammary (nontumor) cell line was not observed at concentrations up to 0.3 mM, which indicates selectivity of these ruthenium(II)-arene complexes to cancer cells. Analogues of the RAPTA compounds, in which the PTA ligand is methylated, have also been prepared, and these prove to be cytotoxic toward both cell lines. RAPTA-C and the benzene analogue RAPTA-B were selected for in vivo experiments to evaluate their anticancer and antimetastatic activity. The results show that these complexes can reduce the growth of lung metastases in CBA mice bearing the MCa mammary carcinoma in the absence of a corresponding action at the site of primary tumor growth. Pharmacokinetic studies of RAPTA-C indicate that ruthenium is rapidly lost from the organs and the bloodstream.

The ruthenium-based drug NAMI-A, characterised by its selectivity against solid tumour metastases, promotes TGF-β1-dependent fibrosis and the reduction of the release of MMPs in the primary tumour. The aim of the study was to examine the interaction of NAMI-A with TGF-β1 in the process of metastasis formation. NAMI-A (1) affects the secretion of TGF-β1 in metastatic MDA-MB-231 cells rather than in non-tumorigenic HBL-100 cells, (2) prevails over TGF-β1 with regard to the invasive capacity of the treated cells, and (3) contrasts integrin-dependent migration stimulated by TGF-β1. It, thus, appears that the effects of NAMI-A on cell invasion and migration are best summarised as an interference with TGF-β1 and a reduction of its activity in these events. At a molecular level, the similar activity of NAMI-A and TGF-β1 on RhoA GTPase supports its interaction with cell surface integrins while TGF-β1 can activate it by interaction with its TGFβR receptor. The inhibition of TGF-β1-induced migration of MDA-MB-231 cells by NAMI-A cannot simply be attributed to a modulation of the Smad2 and p38MAPK pathways. In conclusion, the effects of NAMI-A on the biological role of TGF-β1 in cancer metastasis are insufficient to attribute the responsibility for the anti-metastatic activity of the ruthenium-based drug to this target alone.

Objective: Exposure to high altitude reduces oxygen supply to the central nervous system and may cause neuropsychological impairment. Aim of our study was to evaluate changes in neuropsychological performances of normal subjects when exposed to high and very high altitude, i.e. to conditions representing an experimental model for investigating cognitive functional changes occurring in clinical conditions characterized by reduced brain oxygen supply, such as obstructive sleep apnea or hypertension-related cerebrovascular damage.Design and Method: Forty-five normal subjects participating in the Himalaya's HIGHCARE expedition underwent an extensive neuropsychological and psychodiagnostic assessment at sea level (SL), at 3500 m and at 5400 m altitudes. Different cognitive domains were investigated with paper and pencil tools as well as with computerized tests (X50 eye-tracking device). Psychological status was assessed by clinical checklists.Results: While classic paper and pencil tests did not detect major changes with altitude, better cognitive performances scores were obtained in normoxia and at 3500 m than at 5400 m for computerized psychomotor (keyboard reaction times, KRT) and eye reaction times (ERT): KRT SL vs 5400 m 0.59 AE 0.15 sec vs 0.67 AE 0.17 sec (p < 0.04); KRT SL vs 3500 m 0.59 AE 0.15 sec vs 0.62 AE 0.17 sec (n.s.); KRT 3500 m vs 5400 m 0.62 AE 0.17 sec vs 0.67 AE 0.17 sec (n.s.). ERT SL vs 5400 m 0.44 AE 0.06 sec vs 0.46 AE 0.04 sec (p < 0.001); ERT SL vs 3500m 0.44 AE 0.06 sec vs 0.42 AE 0.05 sec (p < 0.007); ERT 3500m vs 5400m 0.42 AE 0.05 sec vs 0.46 AE 0.04 sec (p < 0.02).ERT were positively related to respiratory rate (RR) (r = 0.53, P < 0.0007). Gender differences were detected, with women having a better performance than men on psychomotor efficiency (% KRT responses) at 5400 m (p < 0.001).Conclusions: High altitude exposure induces specific alterations in cognitive functions, with significant impairment in cognitive performances at 5400m. Our data suggest that computerized tests used for the assessment could be more sensitive than paper and pencil ones, being able to detect even minimal hypoxia-induced changes in cognitive functions. Thus they might be useful in highlighting mild cognitive changes also in hypertensive patients with increased cerebrovascular risk.Objective: Left ventricular hypertrophy (LVH) has been increasingly recognized as a risk factor for stroke. Characterization of blood pressure (BP) using the 24-hour ambulatory blood pressure monitoring (ABPM) is superior to casual measurement in predicting cardiovascular target organ damage in patients with arterial hypertension. We aimed to determine the relationship between LVH and ABPM in patients after acute ischemic stroke.Design and method: We studied 80 subjects with acute ischemic stroke who underwent 24-h ABPM and cross-sectional and M-mode echocardiography. After six month a new ABPM was undergone. Patients were divided into two groups by presence and absence of LVH. Results:We included 40 patients with LVH and 40 patient...

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