It has not been well established whether the oxidative stress found in cancer patients results from an increased production of oxidants in the body or from a failure of physiological antioxidant ...systems. To further investigate this question, we have assessed the blood levels of reactive oxygen species as a marker of free radicals producing oxidative stress and the most relevant of the physiological body enzymes counteracting reactive oxygen species, namely glutathione peroxidase and superoxide dismutase. We also investigated serum levels of proinflammatory cytokines and IL-2. All of these parameters were studied in relation to the most important clinical index of disease progression--namely, the Eastern Cooperative Oncology Group (ECOG) Performance Status (PS). We also tested the reducing ability of different antioxidant agents on reactive oxygen species levels by measuring the increase in glutathione peroxidase activity and the reduction of serum levels of IL-6 and TNF-alpha.
We carried out an open nonrandomized study on 28 advanced stage cancer patients (stage III, 10.7% and stage IV, 89.3%) with tumors at different sites. The patients were divided into 5 groups, and a different antioxidant treatment was administered to each group. The antioxidants were alpha lipoic acid 200 mg/day orally; N-acetylcysteine 1800 mg/day i.v. or carboxycysteine-lysine salt 2.7 g/day orally; amifostine 375 mg/day i.v.; reduced glutathione 600 mg/day i.v.; and a combination of vitamin A 30,000 IU/day orally, vitamin E 70 mg/day orally, and vitamin C 500 mg/day orally. The antioxidant treatment was administered for 10 consecutive days.
We found that all but one of the antioxidants tested were effective in reducing reactive oxygen species levels, and two of them (cysteine-containing compounds and amifostine) had the additional effect of increasing glutathione peroxidase activity. Comprehensively, the antioxidant treatment was found to have an effect on both reactive oxygen species levels and glutathione peroxidase activity. The antioxidant treatment also reduced the serum levels of IL-6 and TNF-alpha. Patients in both ECOG PS 0-1 and ECOG PS 2-3 responded to antioxidant treatment.
In the present study we tested the ability of different antioxidant agents, used alone or in combination, to reduce the reactive oxygen species (ROS) levels and to increase the glutathione peroxidase ...(GPx) activity. Moreover, we tested the ability of such antioxidant agents to reduce the serum levels of proinflammatory cytokines IL-6 and TNF f . Fifty-six advanced stage cancer patients with tumors at different sites were included in the study: they were mainly stage III (12.5%) and stage IV (82.1%). The study was divided into two phases. In the 1 st phase 28 patients were divided into five groups and a single different antioxidant agent was administered to each group. The selected antioxidant agents were: alpha lipoic acid or carboxycysteine-lysine salt, amifostine, reduced glutathione, vitamin A plus vitamin E plus Vitamin C. In the 2 nd phase of the study 28 patients were divided into five groups and a combination of two different antioxidant agents was administered to each group. The antioxidant treatment was administered for 10 consecutive days. The patients were studied at baseline and after antioxidant treatment. Our results show that all single antioxidants tested were effective in reducing the ROS levels and three of them in increasing GPx activity, too. Among the combinations of antioxidant agents, three were effective in reducing ROS, while three were effective in increasing GPx activity (arm 4 was effective in both instances). Comprehensively, the "antioxidant treatment" was found to be effective both on ROS levels and GPx activity. Moreover, the antioxidant treatment was able to reduce serum levels of IL-6 and TNF f . Furthermore, a correlation was shown between the Eastern Cooperative Oncology Group Performance Status of patients and blood levels of ROS, GPx activity, serum levels of proinflammatory cytokines.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
On the eastern flank of Etna volcano, movements along the NNW–SSE trending normal faults of the Timpe system generate recurrent, low magnitude very shallow seismic events that induce noteworthy ...ground surface effects. The Timpe system is the on-land extension of the Hyblean–Malta fault system, which is the likely source of the 1693 Maw 7.4 earthquake.
Frequent creep phenomena occur both associated with seismic events and/or volcanic eruptions, and independent from them. These surface deformations are mainly confined in the eastern sector of the volcano apparatus and result from the interaction between regional tectonics and local volcano-tectonic processes.
The widespread diffusion of cultural sites in this region even before the Greek civilisation testifies to the complex relationship of humans with a restless violent nature. Many Greek authors and myths refer to the frightening eruptions and earthquakes of Etna, but, at the same time, Strabo underlines the extreme fertility of the land due to the volcanic ash, and the quality of the local wine. So notwithstanding the evident risk, this region is one of the most densely inhabited regions of Sicily. Coseismic surface ruptures and creep are responsible for damaging effects on buildings, roads, railways and lifelines, including the water supply network.
To reduce the environmental risk from faulting, APAT—Italian Agency for Environment Protection and for Technical Services—has compiled a georeferenced database, where capable faults, extract from ITHACA (Italy Hazard from Capable Faults) catalogue, and water supply and other environmentally sensible networks are overlapped to pinpoint zones of expected damage. This tool is fundamental in land planning and during an emergency, as seen during the 2002 Santa Venerina earthquake when the environmental agency needed to quickly verify the integrity of the water distribution and sewage networks.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A rock avalanche deposit was investigated in order to understand the chronological evolution of geological hazards and to evaluate the interaction of the triggering geodynamic processes in the valley ...Val Viola, Italian Alps. The deposit is situated west of the Alpe Dosdé, in a permafrost area with deep-seated gravitational deformations (DSGD) along a tectonic line. Based on its geomorphologic context, the rock avalanche was first interpreted as a result of slope stress release without exact timing. This hypothesis was tested by measuring the
10Be exposure date of quartz from one boulder from the rock avalanche. The age of 7430±460 years places the event in the early Holocene. The timing of the last deglaciation was constrained using the inner late glacial moraine of a moraine doublet in the valley Alpe Dosdé situated at an altitude between 2140 and 2120
m a.s.l. west of the rock avalanche. The
10Be concentrations of quartz yield minimum exposure ages of 11,480±670 and 10,850±820 years. Different proposals for potential triggering factors of the rock avalanche include (a) melting of the local valley glacier and slope stress release in the Val Viola, likely to play a minor role as trigger, because of the time delay between the deglaciation and the rock avalanche event. More likely are (b) enhanced crustal seismicity induced by post-glacial regional isostatic glacial rebound coupled with tectonic stress or/and (c) climate conditions with higher temperatures around 7430±460 years, resulting in an upwards movement of the permafrost limit and destabilization of the rock walls.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A rock avalanche deposit was investigated in order to understand the chronological evolution of geological hazards and to evaluate the interaction of the triggering geodynamic processes in the valley ...Val Viola, Italian Alps. The deposit is situated west of the Alpe Dosde, in a permafrost area with deep-seated gravitational deformations (DSGD) along a tectonic line. Based on its geomorphologic context, the rock avalanche was first interpreted as a result of slope stress release without exact timing. This hypothesis was tested by measuring the super(10Be exposure date of quartz from one boulder from the rock avalanche. The age of 7430+/-460 years places the event in the early Holocene. The timing of the last deglaciation was constrained using the inner late glacial moraine of a moraine doublet in the valley Alpe Dosde situated at an altitude between 2140 and 2120 m a.s.l. west of the rock avalanche. The ) super(1)0Be concentrations of quartz yield minimum exposure ages of 11,480+/-670 and 10,850+/-820 years. Different proposals for potential triggering factors of the rock avalanche include (a) melting of the local valley glacier and slope stress release in the Val Viola, likely to play a minor role as trigger, because of the time delay between the deglaciation and the rock avalanche event. More likely are (b) enhanced crustal seismicity induced by post-glacial regional isostatic glacial rebound coupled with tectonic stress or/and (c) climate conditions with higher temperatures around 7430+/-460 years, resulting in an upwards movement of the permafrost limit and destabilization of the rock walls.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The Pollino Range is the southernmost segment of the Southern Apennines at the boundary with the Calabrian Arc. While several strong earthquakes (magnitude 6.5–7.0) have occurred in nearby regions, ...the Pollino area has no known historical record of seismic events of magnitude > 5. We carried out an aerial photograph interpretation and a field survey of the Pollino fault (the major Quaternary normal fault of the area) in order to characterize geologically the seismic potential of this structure. We dug two sets of trenches across fault scarps within the apecies of latest Pleistocene to Holocene alluvial fans at the Masseria Quercia Marina (MQM) and Grotta Carbone (GC) sites, in the central segment of the southern Pollino Range front. At both sites we identified two surface faulting events affecting the alluvial fan deposits and two overlying colluvial units of historical age. The penultimate event produced a vertical offset of 80–90 cm at GC and 50–60 cm at MQM; while the last event produced a vertical offset of 40–50 cm at GC and few centimeters of offset at MQM. Detailed geomorphological field observations suggest that the two historical earthquakes reactivated the entire length of the Masseria Marzano-Civita segment of the Pollino fault (rupture length about 18 km). For events in this range of rupture length and vertical displacement, comparison with surface faulting earthquakes in the Apennines (and abroad) indicates a magnitude of 6.5–7.0. Therefore, the maximum potential earthquake and the seismic hazard of the Pollino area are significantly larger than that suggested by the available historical seismic catalogue.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In the present open non-randomized phase II study we looked for effectiveness, safety, tolerability and costs of locally applied GM-CSF in preventing or treating mucositis in patients receiving ...chemotherapy or chemoradiotherapy for head and neck cancer. In addition to clinical mucositis scoring system, the effects of treatment with GM-CSF were evaluated by its impact on patient quality of life and by laboratory immunological assays such as serum proinflammatory cytokines, IL-2 and leptin. The trial was designed to assess the effectiveness of local GM-CSF treatment in two different settings: i) prophylaxis of mucositis; ii) treatment of mucositis. Prophylaxis was chosen for chemoradiotherapy treatments of high mucosatoxic potential, while curative treatment was reserved for chemotherapy or chemoradiotherapy treatments of lesser potential of inducing mucositis. From January 1998 to December 2001, 68 patients entered the study. The great majority of patients of both groups had head and neck cancer, were stage IV, PS ECOG 0-1, were habitual smokers and were treated with chemotherapy and concomitant (or sequential) chemoradiotherapy. Forty-six patients were included in the 'prophylactic' setting and 22 patients in the 'curative' setting. The main findings of our study are: only 50% of patients included in the 'prophylactic' setting developed mucositis; the duration of oral mucositis from appearance until complete remission was significantly shorter in the 'prophylactic' than in the 'curative' setting; the mean grade of oral mucositis at baseline, on day 3 of therapy and on day 6 of therapy was significantly lower in the 'prophylactic' than in the 'curative' setting; 24 (55.82%) patients in the 'prophylactic' setting had grade 3/4 oral mucositis at baseline compared to 25 (80.60%) patients in the 'curative' setting (p=0.048). Thirteen (30.23%) patients in the 'prophylactic' setting had grade 3/4 oral mucositis on day 3 of therapy compared to 19 (61.29%) patients in the 'curative' setting (p=0.015); 'prophylactic' setting was able to shorten grade 3/4 oral mucositis to grade 0/1 more effectively than the 'curative' one on day 6 of therapy (p=0.05). The present clinical trial is to date by far the largest study assessing the effectiveness of topical GM-CSF and it is the first study comparing the efficacy of topical GM-CSF in the 'prophylactic' setting, i.e., with the aim to prevent the chemoradiotherapy-induced oral mucositis, with that in the 'curative' treatment, i.e., the therapy for established oral mucositis. The topical application of GM-CSF was demonstrated to be effective for oral mucositis induced by chemotherapy and chemoradiotherapy regimens. Moreover, the 'prophylactic' setting was demonstrated to be more effective than the 'curative' one.
The primary aim of this study was to find whether any association exists between serum levels of proinflammatory cytokines, mainly IL-6, and the most important comprehensive geriatric assessment ...(CGA) variables such as functional status, cognitive functions and nutrition in a population of elderly cancer patients. The secondary aims were to find whether any difference existed between: i) age groups, ii) performance status scores, iii) patients who had lost weight versus those who had not. Eighty-four elderly patients with advanced cancer were included in the study (stage III 15.4%, and stage IV 72.6%). Serum levels of IL-6 and CRP were significantly higher in elderly than in the other adult cancer patients. Among the CGA variables investigated, the most affected were functional status assessed by IADL, cognitive functions by MMSE and nutrition. The ECOG PS was shown to be significantly associated with all the dimensions of CGA investigated: poor PS (>/=2) corresponded to severe disabilities. As for the relationship of serum IL-6 with CGA variables, the strongest correlations were between IL-6 and functional status assessed by both Katz ADL (p=0.0003), IADL (p=0.0070) and nutrition (p=0.0013). Moreover, we observed an association, although not statistically significant, between functional disability (ADL and IADL) and high IL-6 levels in individuals with weight loss. IL-6 levels seem to be independently associated with all CGA variables investigated in the present study in a population of elderly cancer patients. Because the most important CGA variables, in particular functional status, have been observed to be strongly associated with survival, the present study, confirming our previously reported ones, suggests that IL-6 may be a reliable marker of disease outcome and supports the feasibility of using IL-6 as a sensitive outcome marker in studies based on novel approaches aiming at modifying age- and cancer-related biologic mechanisms.
