SSRIs in the course of COVID-19 pneumonia: Evidence of effectiveness of antidepressants on acute inflammation. A retrospective study.

INTRODUCTION: Relationships between inflammation and mood have been observed in terms of pro-inflammatory effects induced by depressive conditions and, in parallel, by an antidepressant-induced favorable effect on the recovery of inflammatory states. Selective serotonin reuptake inhibitor (SSRI) drugs were hypothesized to improve the prognosis of COVID-19 pneumonia, a typical acute inflammation, in terms of decreased mortality rate and pro-inflammatory cytokine serum levels. METHODS: The medical records of COVID-19 pneumonia inpatients at Careggi University Hospital (Florence) were analyzed for prognosis and Interleukin 6 (IL-6) after admission for over a period of 22 months. Medical records of patients treated at admission and not discontinued until discharge with an SSRI or with vortioxetine were identified. Two groups, one treated with antidepressants, the other not treated, were evaluated according to the mentioned parameters. Multiple linear regression and logistic regression were performed. RESULTS: The entire sample composed of 1236 records (recovered patients 77.1%, deceased patients 22.9%). The treated group (n = 107) had a better prognosis than the untreated group in spite of age and comorbidity both being greater than in the untreated group. Correspondingly, IL-6 levels in the treated group were significantly lower (p < 0.01) than the levels in the untreated group, in every comparison. CONCLUSIONS: Outcomes of this study support the hypothesis of the favorable influence of some antidepressants on the prognosis of COVID-19, possibly mediated by IL-6 modulation. Reduction in acute inflammation induced by the action of antidepressants was confirmed.

Can selective serotonin reuptake inhibitors/serotonin and norepinephrine reuptake inhibitor antidepressants decrease the "cytokine storm" in the course of COVID-19 pneumonia?

BACKGROUND: Lots of research has been conducted to fight COVID-19 since the outbreak of the pandemic in 2020. The role of "cytokine storm" in the pathogenesis of COVID-19 pneumonia is well known. Relationship between interleukins and depression is still subject matter of the research, but a correlation between interleukin-6 and depressive disorders is proven by now. The aim of this study is to verify differences among interleukin-6 blood levels of inpatients treated with selective serotonin reuptake inhibitors and/or serotonin and norepinephrine reuptake inhibitor before and during hospitalization and of inpatients not treated with these drugs. METHODS: This is an observational study performed during the first wave of SARS Cov-2 pandemic in Italy for three months. The hospitalized patients of Internal Medicine wards and Infectious and Tropical Diseases ward of Azienda Ospedaliero-Universitaria Careggi of Florence for COVID-19 pneumonia have been divided into two subgroups (treated / not treated with antidepressants). Patients admitted to Intensive Care Unit previously have been excluded. Each patient has been evaluated concerning demographic, clinical and therapeutic features. The first dosage of interleukin-6 detected during hospitalization has been noticed. RESULTS: The entire sample included 402 patients and 8.5% (N.=34) had been treated with an antidepressant of the two considered categories before admission until discharge from hospital. Significant lower levels of interleukin-6 of recovered patients of the treated subgroup have been highlighted as compared to recovered patients of not-treated subgroup (12.1 vs. 25.4 P<0.001). These results have been pointed out in spite of higher mean age and more serious comorbidities of the treated subgroup. Nevertheless, the incidence of severe acute respiratory distress syndrome is significantly lower in the subgroup of patients with antidepressant treatment (20.6% vs. 43.2% P<0.02) as well as endotracheal intubation employment (0.0% vs. 11.7% P<0.04). The rate of deceased patients of treated-subgroup is not significantly lower than the rate of not-treated subgroup (23.5% vs. 26.4% P=0.13). CONCLUSIONS: During COVID-19 pneumonia, the production of interleukin-6 seems to be modulated in presence of antidepressant therapy. Further proofs and broader surveys are necessary.

Transcatheter aortic valve intervention in hospitals without cardiac surgery departments: a future scenario?

Transcatheter Aortic Valve Intervention (TAVI) was introduced in early 2000 to offer treatment to inoperable patients with severe aortic valve stenosis. In a couple of decades, the procedure resulted effective and safe also in patients with intermediate to low risk for surgery; therefore, due to the progressive ageing of the population, the clinical need for TAVI is continuously increasing and is hardly met by the availability of the procedure, the so-called "TAVI capacity". As a result, many patients encounter difficulties in being referred to TAVI centers or face long waiting list times, thus risking severe adverse events (including death) before the procedure is performed. Although contemporary guidelines and consensus documents recommend that TAVI should be only performed in hospitals with active cardiac surgery departments, starting TAVI programs also in interventional cardiac laboratories without on-site cardiac surgery could represent a way to increase TAVI capacity, thus leading to a greater number of patients being treated in less time. On the other side of the coin, such a strategy may jeopardize patient safety in case of periprocedural complications needing bailout surgery and may lead to a suboptimal multidisciplinary Heart Team evaluation. This review aims to assess and discuss available clinical data and implementation of TAVI programs in hospitals without on-site active cardiac surgery departments considering the growing unmet clinical need and technical advancement of TAVI platforms, yet not overlooking the recommendation of international scientific societies.

Serum sodium alterations in SARS CoV-2 (COVID-19) infection: impact on patient outcome.

OBJECTIVE: Hyponatremia is the most common electrolyte disorder in hospitalized patients and occurs in about 30% of patients with pneumonia. Hyponatremia has been associated with a worse outcome in several pathologic conditions The main objective of this study was to determine whether serum sodium alterations may be independent predictors of the outcome of hospitalized COVID-19 patients. DESIGN AND METHODS: In this observational study, data from 441 laboratory-confirmed COVID-19 patients admitted to a University Hospital were collected. After excluding 61 patients (no serum sodium at admission available, saline solution infusion before sodium assessment, transfer from another hospital), data from 380 patients were analyzed. RESULTS: 274 (72.1%) patients had normonatremia at admission, 87 (22.9%) patients had hyponatremia and 19 (5%) patients had hypernatremia. We found an inverse correlation between serum sodium and IL-6, whereas a direct correlation between serum sodium and PaO2/FiO2 ratio was observed. Patients with hyponatremia had a higher prevalence of non-invasive ventilation and ICU transfer than those with normonatremia or hypernatremia. Hyponatremia was an independent predictor of in-hospital mortality (2.7-fold increase vs normonatremia) and each mEq/L of serum sodium reduction was associated with a 14.4% increased risk of death. CONCLUSIONS: These results suggest that serum sodium at admission may be considered as an early prognostic marker of disease severity in hospitalized COVID-19 patients.

Compassionate use of JAK1/2 inhibitor ruxolitinib for severe COVID-19: a prospective observational study.

Overwhelming inflammatory reactions contribute to respiratory distress in patients with COVID-19. Ruxolitinib is a JAK1/JAK2 inhibitor with potent anti-inflammatory properties. We report on a prospective, observational study in 34 patients with COVID-19 who received ruxolitinib on a compassionate-use protocol. Patients had severe pulmonary disease defined by pulmonary infiltrates on imaging and an oxygen saturation ≤ 93% in air and/or PaO2/FiO2 ratio ≤ 300 mmHg. Median age was 80.5 years, and 85.3% had ≥ 2 comorbidities. Median exposure time to ruxolitinib was 13 days, median dose intensity was 20 mg/day. Overall survival by day 28 was 94.1%. Cumulative incidence of clinical improvement of ≥2 points in the ordinal scale was 82.4% (95% confidence interval, 71-93). Clinical improvement was not affected by low-flow versus high-flow oxygen support but was less frequent in patients with PaO2/FiO2 < 200 mmHg. The most frequent adverse events were anemia, urinary tract infections, and thrombocytopenia. Improvement of inflammatory cytokine profile and activated lymphocyte subsets was observed at day 14. In this prospective cohort of aged and high-risk comorbidity patients with severe COVID-19, compassionate-use ruxolitinib was safe and was associated with improvement of pulmonary function and discharge home in 85.3%. Controlled clinical trials are necessary to establish efficacy of ruxolitinib in COVID-19.

Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study.

BACKGROUND: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. OBJECTIVE: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. METHODS: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. RESULTS: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. CONCLUSIONS: Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.

Long-Term Follow-Up of Transcatheter Aortic Valve Implantation With Portico Versus Evolut Devices.

New-generation devices such as Evolut and Portico have provided favorable results in patients who underwent transcatheter aortic valve implantation (TAVI) for aortic stenosis, but their comparative effectiveness remains debated, despite its relevance when envisioning TAVI in low-risk patients. We evaluated the safety and efficacy of 2 leading TAVI devices (Evolut and Portico) used by the same team of experienced TAVI operators, focusing on long-term outcomes, including major adverse events (i.e., the composite of death, stroke, myocardial infarction, major vascular complication, or major bleeding). Unadjusted and propensity score-adjusted analyses were carried out. A total of 233 patients were included, 119 (51.1%) receiving Evolut and 114 (49%) Portico. Baseline and procedural data showed significant between-device differences, including functional class, surgical risk, chronic obstructive pulmonary disease, renal function, transesophageal guidance, device size, postdilation, and procedural time (all p <0.05). Yet, acute and in-hospital outcomes were not significantly different (all p >0.05). Follow-up status was ascertained in 228 (98%) patients after 15.0 ± 7.6 months. Unadjusted analysis showed similar rates of major adverse events, as well as the individual risk of death, stroke, myocardial infarction, major vascular complication, major bleeding, and pacemaker implantation (all p >0.05). Even at propensity score-adjusted analysis outcomes were not significantly different with Evolut and Portico (all p >0.05). In conclusion, Evolut and Portico devices yield similarly favorable results at long-term follow-up when used by experienced TAVI operators.

Meta-Analysis of Head-to-Head Comparison of Intracoronary Versus Intravenous Adenosine for the Assessment of Fractional Flow Reserve.

Intravenous (IV) infusion of adenosine represents the gold standard for measuring fractional flow reserve (FFR). However, IV adenosine is more expensive and time-consuming compared with intracoronary (IC) boluses of adenosine. We conducted a meta-analysis of studies comparing IC with IV adenosine for FFR assessment in the same coronary lesions. We searched for studies comparing IC with IV adenosine and reporting absolute FFR values or rate of abnormal FFR for both routes. Prespecified subgroup analysis was performed to appraise studies using low-dose (<100 µg) or high-dose IC adenosine (≥100 µg). We retrieved 11 studies amounting to 587 patients and 621 lesions. Six studies evaluated low-dose IC boluses (15 to 80 µg) and 5 studies high-dose boluses (120 to 600 µg). Absolute FFR values were slightly, yet significantly lower with IV adenosine compared with IC adenosine (mean difference 0.02, 95% confidence interval [CI] 0.00 to 0.03, p = 0.02). This difference, however, did not translate into a significant difference in the rate of abnormal FFR between IC and IV adenosine (hazard ratio 0.93, 95% CI 0.76 to 1.13, p = 0.57); moreover, no statistically significant difference was observed between low-dose and high-dose IC adenosine subgroups. Adverse events were less frequent with IC adenosine compared with IV adenosine (risk ratio 0.17, 95% CI 0.07 to 0.43, p <0.001). In conclusion, IC administration of adenosine, although inducing a slightly lower amount of hyperemia compared with IV infusion of adenosine, yields a similar diagnostic accuracy in identifying hemodynamically significant coronary stenosis and is better tolerated by the patients.

Outcomes of early invasive treatment strategy in elderly patients with non-ST elevation acute coronary syndromes.

BACKGROUND: As benefits of revascularization in non-ST elevation acute coronary syndromes (NSTEACSs) in the elderly are still unproven, we sought to assess the association between invasive or conservative management of NSTEACS and short-, mid- and long-term mortality or composite outcome of all-cause mortality and myocardial infarction in a cohort of consecutive elderly patients. METHODS AND RESULTS: Consecutive NSTEACS patients older than 75 years discharged between 2006 and 2010 from a single intensive cardiac care unit, and managed with invasive or conservative strategy according to available guidelines were retrospectively surveyed. By multivariate regression and sensitivity analysis, crude and adjusted mortality and composite outcome were estimated at prespecified time points of short-term (in-hospital or 30 days mortality), mid-term (T1: 31 days to 6 months), and long-term (T2: 31 days to 12 months). A total of 453 patients (median age 80 years, 47% men) were evaluated; 301 (66.5%) underwent invasive treatment. Invasive was associated with significantly lower risk of short- [odds ratio (OR) 0.28, 95% confidence interval (CI) 0.12-0.67, P = 0.004], mid- (OR 0.33, 95% CI 0.16-0.67, P = 0.003) and long-term mortality (OR 0.34, 95% CI 0.20-0.58, P < .0001). Invasive strategy was also associated with nonsignificant lower short- (OR 0.55, 95% CI 0.28-1.07, P = 0.077), and highly significant lower mid- (OR 0.52, 95% CI 0.34-0.81, P = 0.003) and long-term adjusted cumulative composite outcome rate (OR 0.68, 95% CI 0.46-0.98, P = 0.004). CONCLUSION: In NSTEACS elderly patients, invasive strategy is independently associated with lower short-, mid- and long-term mortality and composite outcome.

The micronucleus assay in mammalian cells in vitro to assess health benefits of various phytochemicals.

We evaluated the protective effects of Gentiana lutea extracts (GLEx) and 6-Gingerol (6-G) on clastogenicity of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 7,12-dimethylbenz(α) anthracene (DMBA) in vitro on HepG2 cells using the frequencies of induced micronuclei (MN) as the end point. Pre-, post- and simultaneous treatments with GLEx or 6-G and the carcinogens were carried out. Both GLEx post- and simultaneous treatments reduced the frequencies of MN induced by MNNG and DMBA. Probably this effect is due to an increase of cytostasis and a physico-chemical interaction between GLEx and DMBA under simultaneous treatment. Pre- and simultaneous treatments with 6-G significantly reduced the yield of MNNG-induced micronuclei without affecting % of cytostasis. Simultaneous treatment with 6-G plus DMBA resulted in reduction in the frequency of MN and an increase in cytotoxicity compared to sample treated alone with DMBA, whereas a post-treatment, caused a significant decrease in the yield of MN compared with DMBA alone without any cytotoxic effect. These results are compared with our earlier data obtained in the same system with other phytochemicals. It is concluded that for a critical evaluation of the protective effects of phytochemicals, both the influence on the induced MN and induced cytostasis have to be considered.

Role of chromatin structure modulation by the histone deacetylase inhibitor trichostatin A on the radio-sensitivity of ataxia telangiectasia.

At present, a lot is known about biochemical aspects of double strand breaks (DBS) repair but how chromatin structure affects this process and the sensitivity of DNA to DSB induction is still an unresolved question. Ataxia telangiectasia (A-T) patients are characterised by very high sensitivity to DSB-inducing agents such as ionising radiation. This radiosensitivity is revealed with an enhancement of chromosomal instability as a consequence of defective DNA repair for a small fraction of breaks located in the heterochromatin, where they are less accessible. Besides, recently it has been reported that Ataxia Telangiectasia Mutated (ATM) mediated signalling modifies chromatin structure. In order to study the impact of chromatin compaction on the chromosomal instability of A-T cells, the response to trichostatin-A, an histone deacetylase inhibitor, in normal and A-T lymphoblastoid cell lines was investigated testing its effect on chromosomal aberrations, cell cycle progression, DNA damage and repair after exposure to X-rays. The results suggest that the response to both trichostatin-A pre- and continuous treatments is independent of the presence of either functional or mutated ATM protein, as the reduction of chromosomal damage was found also in the wild-type cell line. The presence of trichostatin-A before exposure to X-rays could give rise to prompt DNA repair functioning on chromatin structure already in an open conformation. Differently, trichostatin-A post-treatment causing hyperacetylation of histone tails and reducing the heterochromatic DNA content might diminish the requirement for ATM and favour DSBs repair reducing chromosomal damage only in A-T cells. This fact could suggest that trichostatin-A post-treatment is favouring the slow component of DSB repair pathway, the one impaired in absence of a functionally ATM protein. Data obtained suggest a fundamental role of chromatin compaction on chromosomal instability in A-T cells.

Evaluation of the effects of ellagic acid (EA) on 7,12-dimethylbenz(α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo.

We evaluated the protective effects of EA, a promising dietary constituent against degenerative diseases, on the clastogenic action of the model carcinogen DMBA in vitro on human hepatoma cells (HepG2) and in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments with EA and the carcinogen were carried out in vitro. Simultaneous treatment with EA caused a statistically significant increase of DMBA induced MN, suggesting a direct interaction between the two agents. No significant reduction in DMBA induced MN was found by pre- or post treatment with EA. Similar effects were observed in the toxicity assay. In in vivo experiments, EA pre-treatment did not affect the frequencies of MN in PCEs of bone marrow induced by DMBA. A good correlation was found between in vitro and in vivo experiments. Our results did not reveal any clear indication on the efficacy of EA on the induction of micronuclei by DMBA. EA by itself did not show any harmful effects.

A clinical and angiographic study of the XIENCE V everolimus-eluting coronary stent system in the treatment of patients with multivessel coronary artery disease: the EXECUTIVE trial (EXecutive RCT: evaluating XIENCE V in a multi vessel disease).

OBJECTIVES: This study sought to investigate the efficacy and performance of the XIENCE V everolimus-eluting stent (EES) (Abbott Vascular, Santa Clara, California) in the treatment of de novo coronary lesions in patients with 2- to 3-vessel multivessel coronary artery disease (MV-CAD). BACKGROUND: Drug-eluting stents (DES) have emerged as an alternative to conventional coronary artery bypass surgery in patients with MV-CAD although first-generation DES yielded inferior efficacy and safety compared with surgery. METHODS: Prospective, randomized (1:1), multicenter feasibility trial was designed to assess angiographic efficacy of EES compared with the TAXUS paclitaxel-eluting stent (PES) in 200 patients, and a prospective, open-label, single-arm, controlled registry was designed to analyze the clinical outcome of EES at 1-year follow-up in 400 MV-CAD patients. For the randomized trial, the primary endpoint was in-stent late loss at 9 months. For the registry, the primary endpoint was a composite of all-cause death, myocardial infarction, and ischemia-driven target vessel revascularization at 12 months. RESULTS: The primary endpoint per single lesion was significantly lower in the EES group compared with the PES group (-0.03 ± 0.49 mm vs. 0.23 ± 0.51 mm, p = 0.001). Similar results were observed when analyzing all lesions (0.05 ± 0.51 mm vs. 0.24 ± 0.50 mm, p < 0.001). Clinical outcome at 1 year yielded a composite of major adverse cardiac events of 9.2% in the single-arm registry, and 11.1% and 16.5% in the EES and PES randomized groups, respectively (p = 0.30). CONCLUSIONS: The EXECUTIVE trial was a randomized pilot trial dedicated to the comparison of the efficacy of 2 different DES among patients with 2- to 3-vessel MV-CAD. The study shows lower in-stent late loss at 9 months with the EES XIENCE V compared with the PES TAXUS Libertè, and a low major adverse cardiac event rate at 1 year in patients with 2-to 3-vessel MV-CAD. (EXECUTIVE [EXecutive RCT: Evaluating XIENCE V in a Multi Vessel Disease]; NCT00531011).

Effect of blueberries (BB) on micronuclei induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and 7,12-dimethylbenz(a)anthracene (DMBA) in mammalian cells, assessed in in vitro and in vivo assays.

The protective effect of blueberry (BB) on the clastogenic effects of MNNG and DMBA was evaluated with the induced micronucleus (MN) frequency as a biomarker, both in vitro and in vivo. Human hepatoma HepG2 cells, which contain most of the metabolic activating enzymes was used for the in vitro test. MN frequencies were determined in binucleated cells generated by blocking cytokinesis by use of cytochalasin-B. The MN frequency in vivo was determined in polychromatic erythrocytes (PCEs) from the bone marrow of treated mice. BB by itself was not toxic both in vivo and in vitro. There was no evidence of a potential physico-chemical interaction between BB and the test carcinogens in vitro. Pre-treatment with BB reduced the MN frequency induced by MNNG. But, simultaneous treatment and post-treatment with BB did not affect the frequency of MNNG-induced MN. BB did not affect the frequency of DMBA-induced MN in vitro under any test condition. Under in vivo conditions, BB reduced the frequencies of MNNG- and DMBA-induced MN in PCEs, but in the case of the protective effect of BB against DMBA a dramatic reduction in the percentage of PCEs was observed, suggesting increased cytotoxicity.

Exposure to polycyclic aromatic hydrocarbons in women from Poland, Serbia and Italy--relation between PAH metabolite excretion, DNA damage, diet and genotype (the EU DIEPHY project).

Exposure of the general population to polycyclic aromatic hydrocarbons (PAH) is ubiquitous. The aim of this study was to analyze biomarkers associated with the uptake of PAH in 428 non-smoking women from Lodz (Poland), Viterbo (Italy), Belgrade (Serbia) and from the Pancevo area, where the petrochemical complex was destroyed by the air raids in 1999. Urinary excretion of PAH metabolites was lowest in Italian women, intermediary for Serbian and highest in Polish women, who predominantly excreted hydroxy phenanthrenes as metabolites of phenanthrene. Bulky DNA adduct levels were highest in Italian and Polish women. Genotype or PAH ambient air levels could not explain the dissimilarities between the study groups with respect to biomarker patterns, which probably reflected differences in life style-associated factors.

A comparative study of the anticlastogenic effects of chlorophyllin on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or 7,12-dimethylbenz (α) anthracene (DMBA) induced micronuclei in mammalian cells in vitro and in vivo.

Chlorophyllin (CHL), a water soluble derivative of chlorophyll has been shown to have both anticarcinogenic and antigenotoxic properties. We evaluated the protective effects of CHL (25µM in vitro, 4 and 100mg/kg. b.w.) on the clastogenic action of two model carcinogens, MNNG and DMBA (25µM and 2µM respectively) in vitro on human hepatoma cells (HepG2) and (40mg and 25mg/Kg/b.w. respectively) in vivo on bone marrow of mice, using the frequencies of induced micronuclei as the end point. Pre-, post- and simultaneous treatments with CHL and the carcinogen were carried out in vitro. With MNNG, only simultaneous treatment with CHL was effective in reducing the frequencies of MN, suggesting a direct interaction between CHL and MNNG. A statistically significant reduction in of DMBA induced MN was found by pre-or post treatment with CHL while a reduction (not significant) was observed by simultaneous treatment. In in vivo experiments, CHL pre-treatment did not affect the frequencies of MN in PCEs of bone marrow induced by MNNG or DMBA. However, increased the toxic effect of DMBA (reduction in percent of PCEs) was accompanied by a reduction in the induced frequencies of MN. CHL was not clastogenic in both in vitro and in vivo tests. It can be concluded that (a) CHL has a protective effect against MNNG and DMBA. This effect is dependent upon the protocol employed in in vitro experiments. In vivo, CHL did not have a protective effect against MNNG and DMBA. A protective effect of CHL against DMBA was evident only at high toxic levels.

Protective effect of ellagic acid (EA) on micronucleus formation induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in mammalian cells, in in vitro assays and in vivo.

The beneficial effects of fruits and vegetables with respect to age-related diseases such as diabetes, atherosclerosis and several types of cancer are widely recognized and confirmed by several epidemiological studies. A possible approach for evaluating the protective potential of promising diet constituents is to evaluate their beneficial effect with respect to a set of biomarkers that are indicative of a potential risk for developing degenerative diseases. Among the numerous biomarkers of the effect of food-related carcinogens and for the assessment of the degree of risk for disease, chromosomal damage detection is very predictive. The aim of this study was to test antigenotoxic effect of ellagic acid (EA) both in in vitro and in vivo studies, in combination with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), a methylating agent. EA, a naturally occurring and widely distributed plant phenol, has been intensively studied but with conflicting results, depending on the endpoints considered and the experimental material employed. In vitro and in vivo studies differ in their experimental schedule: in the in vitro study pre- and post-treatments and simultaneous treatments with EA were performed, while in the in vivo study only pre-treatment was carried out. The results of this study clearly demonstrate a protective action of EA with respect to MNNG-induced micronuclei and cell proliferation both in vitro and in vivo. The lack of effect in the post-treatment in in vitro experiments excludes a possible effect of EA on DNA-repair systems. On the other hand, consumption of EA can have a protective action against primary DNA damage induced by oxidative stress.

Study on X-ray-induced apoptosis and chromosomal damage in G2 human lymphocytes in the presence of pifithrin-α, an inhibitor of p53.

The aim of this study is to investigate the role of the cell-cycle phase in cells exposed to radiation and chemicals in relation to the cellular response. The analysis was focused on the G2 cell-cycle phase, exploring the impact of p53 inhibition in human lymphocytes irradiated with X-rays in the presence or absence of pifithrin-α (PFT-α), a p53-specific inhibitor. Lymphocytes, 44h after stimulation to proliferate, were X-irradiated with 0.5Gy both in the presence or the absence of PFT-α and post-treated with a pulse of 5-bromodeoxyuridine (BrdUrd) to distinguish cells in the S- or G2-phase at the moment of irradiation. At early sampling times after X-ray exposure the following parameters were analysed: cellular proliferation, apoptosis, chromosomal aberrations and p53 expression. The results show an enhancement of apoptotic cells in G2 at early sampling times after irradiation and no differences in terms of chromosomal aberration induction both in cells treated with X-rays alone and in cells treated with X-rays plus PFT-α. Expression of p53 was not detectable at all recovery times. The results suggest a p53-independent apoptotic pathway acting at early times after X-ray exposure in G2 lymphocytes. Furthermore, the same yield of X-ray-induced chromatid breaks was observed both in the presence or absence of PFT-α implying that in G2 X-irradiated lymphocytes this inhibitor of the p53 protein does not affect DNA repair.