Surviving adversity: Exploring the presence of Lunularia cruciata (L.) Dum. on metal-polluted mining waste.

The tailings dump of Barraxiutta (Sardinia, Italy) contains considerable concentrations of heavy metals and, consequently, is scarcely colonized by plants. However, wild populations of the liverwort Lunularia cruciata (L.) Dum. form dense and healthy-looking carpets on this tailing dump. L. cruciata colonizing the tailing dump was compared with a control population growing in a pristine environment in terms of: (i) pollutant content, (ii) photochemical efficiency, and (iii) volatile secondary metabolites in thalli extracts. L. cruciata maintained optimal photosynthesis despite containing considerable amounts of soil pollutants in its thalli and had higher sesquiterpene content compared to control plants. Sesquiterpenes have a role in plant stress resistance and adaptation to adverse environments. In the present study, we propose enhanced sesquiterpenes featuring Contaminated L. cruciata as a defence strategy implemented in the post-mining environment.

Effectiveness of a combined UV-C and ozone treatment in reducing healthcare-associated infections in hospital facilities.

BACKGROUND: Hospital-acquired infections pose an ongoing threat to patient safety due to the presence of multi-drug-resistant organisms (MDROs) and other pathogens such as Clostridioides difficile which are dependent on thorough and effective cleaning and disinfection by personnel. METHODS: This study evaluated the influence of UV-C air treatment: the air in the room was sanitized by UV-C and redirected into the room. In addition, ozone was released into the room to treat actual surfaces in low-risk areas such as hospital gyms, and high- to medium-risk areas such as hospital rooms. To this aim, a portable device designed for treating the environment air was tested against nine bacterial strains including Aspergillus spp. and Clostridioides spp. RESULTS: The use of UV-C air treatment during daily operations and ozone treatment achieved at least a 2-log10 pathogen reduction except for Clostridioides spp. CONCLUSION: Effective prevention of C. difficile normally requires the use of combined approaches that include chemical compounds and disinfection agents whose toxicity can be harmful not only to patients but also to healthcare personnel. Thus, the proposed no-touch device may be evaluated in future research to assess the needed requirements for its possible and full implementation in hospitals.

Quantitative and qualitative features of acute phase-adverse events following SARS-CoV-2 vaccination in a large sample of people with multiple sclerosis.

INTRODUCTION: Few data are available on adverse events (AE) associated to vaccines in persons with multiple sclerosis (pwMS). AIMS: to study the incidence of acute phase AE (AP-AE) related to SARS-CoV-2 mRNA vaccines in pwMS compared to a control group, and to analyze the association between AP-AE and disease modifying treatments (DMT). METHODS: This was a cross-sectional study on 438 PwMS and 481 age- and sex-matched subjects not affected by dysimmune diseases that underwent two doses of SARS-CoV-2 mRNA BNT162b2 vaccine (Pfizer/BioNtech). RESULTS: Two hundred and twenty five (51.4%) pwMS complained of ≥1 AP-AE after the first dose, 269 (61.4%) after the second dose. A logistic regression analysis revealed that only pwMS on Fingolimod and Ocrelizumab did not show a higher risk of developing AP-AE. The likelihood to present with ≥1 AP-AE, after correcting for age and sex, was significantly higher in pwMS than controls. CONCLUSIONS: This study reports qualitative and quantitative features of AP-AE associated with the first and second doses of SARS-CoV-2 vaccine in a large sample of pwMS. The only risk factor identified for developing AP-AE is female gender. AntiCD-20 monoclonal antibodies and S1P inhibitors are associated with a lower risk of AP-AE occurrence.

In vitro evaluation of the wound healing activity of Drypetes klainei stem bark extracts.

ETHNOPHARMACOLOGICAL RELEVANCE: Drypetes klainei Pierre ex Pax is used in Cameroon by Baka Pygmies in the wound healing process and for the treatment of burns. AIM OF THE STUDY: To validate the traditional use of D. klainei Pierre ex Pax stem bark extracts through the evaluation of their antimicrobial properties and their ability to improve wound healing process in fibroblast cell cultures. MATERIALS AND METHODS: The antimicrobial properties of D. klainei extracts were evaluated against Staphylococcus aureus ATCC 6538, Streptococcus pyogenes ATCC 19615, Escherichia coli ATCC 10536, Candida albicans ATCC 10231, on the basis of the minimum inhibitory concentration (MIC) and the minimum bactericidal-fungicidal concentration (MBC-MFC) by the macrodilution method. The extracts abilities to accelerate wound healing were studied on murine and human fibroblasts in terms of cell viability and migration (scratch wound-healing assay). RESULTS: All the extracts were non-toxic against the selected microorganisms at the tested concentrations, and significantly improve wound healing process in vitro, compared to untreated controls. However, the defatted methanol extract was active at lower concentrations, compared to the water extract. CONCLUSIONS: The ability of both water and defatted methanol extracts to accelerate scratch wound closure in fibroblast cultures may support the traditional use of D. klainei stem bark in the treatment of skin lesions (such as burns) even if no antimicrobial activity was evidenced.

Three conventional-drug combination (ifosfamide, carboplatin, etoposide--ICE regimen) in advanced non-small cell lung cancer (NSCLC).

Fifty consecutive patients with stage IIIB-IV non-small cell lung cancer (NSCLC) received the ICE regimen at intermediate doses (ifosfamide 1 g/m2, carboplatin 120 mg/m2, etoposide 80 mg/m2, day 1 to 3, q.4 weeks, for a maximum of 6 cycles). Overall 2 complete response (CR) and 10 partial response (PR) (overall response, OR: 24%, 95% C.I. 14-37%) were observed. An additional 7 patients had stable disease (SD) lasting more than 6 months, therefore a clinical benefit (CR+PR+SD >6 mos) was achieved in 19 patients (38%). Median time-to-progression (TTP) was 7 months and median overall survival (OS) was 11 months; 1- and 2-year survival rates were 36% and 10%. The ICE regimen was well tolerated and devoid of any cardiac, hepatic or neurologic toxicity. Moderate nausea and vomiting were easily manageable, grade 2 alopecia was universal, while hematological toxicity was mild (grade 2 leuko- and thrombocytopenia). Due to its efficacy and safety profile, this 3-drug regimen can be considered for routine community use.

Four-day infusion of fluorouracil plus vinorelbine as salvage treatment of heavily pretreated metastatic breast cancer.

AIMS: Anthracyclines-taxanes containing regimens are widely used for breast cancer treatment both in neoadjuvant-adjuvant setting and in metastatic disease. Recently high-dose chemotherapy (HDC) with autologous stem cell support has been introduced as adjuvant treatment for high-risk primary breast cancer and for selected subsets of women with metastatic disease. Therefore, salvage treatment for previously treated patients with progressive disease becomes even more problematic. A regimen of continuous infusion of fluorouracil (FU) and vinorelbine (VNR) has been evaluated in heavily pretreated metastatic breast cancer patients. PATIENTS AND METHODS: Forty-eight women, median age 52 years, with previously treated breast cancer entered the study. All but one received more than one line of prior systemic chemotherapy for metastatic disease. Furthermore 14 women had undergone HDC with peripheral blood progenitor cells transplantation in adjuvant setting (6 pts), or metastatic disease (8 pts). Treatment consisted of four-day infusion of FU (1000 mg/m2/day) plus VNR (20 mg/m2/i.v. day 1 and 5), recycled every 3 weeks for a total of six courses. Drugs administration was discontinued for G4 toxicity, tumor progression or patient's refusal. RESULTS: Twenty PR and four CR for an overall response rate of 50% (95%C.I. 36-64%) were recorded. The therapeutic efficacy of the tested regimen was documented both in patients unresponsive to previous anthracyclines-taxanes combinations and in those relapsing after HDC. The median duration of response was 9 months and median survival 16 months. One third of patients experienced Grade-3 stomatitis-mucositis, hematological toxicity was mild and no cardiac toxicity was observed. Twenty-five women (52%) suffered from infusion-related phlebitis (in half of patients a central venous device was necessary at some point of the treatment program). CONCLUSIONS: The combination of FU infusion and VNR i.v. is an effective salvage treatment for heavily pretreated metastatic breast cancer patients, and may represent a valid alternative when other cytotoxic regimens are not feasible.

Somatic mutations at the T-cell antigen receptor in antineoplastic drug-exposed populations: comparison with sister chromatid exchange frequency.

OBJECTIVE: The objective of this study was to assess the genetic effect of occupational exposure to antineoplastic agents. METHOD: The influence of occupational handling of cytotoxic drugs was investigated by monitoring the frequency of sister chromatid exchanges (SCE), the percentage of cells with high frequencies of SCE (high-frequency cells, HFC), and the frequency of somatic mutation at the T-cell receptor (TCR) locus in mononuclear cells of exposed hospital nurses. These parameters were also measured in healthy donors and in cancer patients at the time of the diagnosis and following the administration of high doses of cytotoxic drugs requiring stem cell support. RESULTS: Our results show that (a) SCE and HFC values in occupationally exposed nurses do not differ from controls, (b) patients with newly diagnosed cancer or following chemotherapy show a number of SCE comparable to those of healthy donors, but a significantly different percentage of HFC, (c) cigarette smokers of all categories studied show higher frequencies of SCE and HFC as compared to nonsmokers, but the differences are not statistically significant, (d) the mutation frequency at the TCR locus in oncology nurses is higher, but not significantly different from the frequency in the control group, and (e) the increase of mutation frequency is statistically significant and seems to be dose dependent in patients treated with high-dose chemotherapy. CONCLUSIONS: Our data suggest that SCE frequency and HFC percentage are not reliable indicators of exposure to possible mutagenic/carcinogenic effects of antineoplastic drugs; on the contrary, our observations indicate that anticancer therapy induces somatic mutations at the TCR locus and suggest an association between exposure to cytotoxic agents and the increase in somatic mutations.

Phase II study with ifosfamide, carboplatin, etoposide (ICE regimen) at intermediate dosage for advanced non small cell lung cancer (NSCLC).

We have evaluated the combination of ifosfamide, carboplatin and etoposide (ICE regimen) along with mesna in 26 previously untreated patients with non small cell lung cancer (NSCLC). Thirteen stage III B and 13 stage IV patients received intermediate doses of ifosfamide (1000 mg/m2), carboplatin (120 mg/m2) and etoposide (120 mg/m2) given intravenously on day 1 to 3 every 4 weeks. Except for one patient who experienced grade 3 transient thrombocytopenia no major events of hematological or systemic toxicity were observed. Response rate (27%, 95% C.I., 10 to 44%), median duration of response (9 months, range 6-15), and survival (9.5 months, range 2-44+) were comparable to those achieved with conventional cisplatin-containing regimens. Our ICE combination, as compared to standard or high dose schedules appears effective, safe, well tolerated, and devoid of severe hematological toxicity.

Environmental and urinary reference values as markers of exposure to hydrocarbons in urban areas.

A study using individual dosimetry to evaluate the daily inhaled dose of sixteen aromatic and aliphatic hydrocarbons in three groups of primary school children, living in three Italian towns with 50,000 inhabitants or less, (Treviglio-Lombardy; Poggibonsi-Tuscany; Valenza-Piedmont) is presented. The simultaneous use of two passive samplers (radial diffusion) for each child, for a 24 h period, determined both the indoor and indoor + outdoor environmental reference concentrations. We measured the urinary levels of benzene, toluene, ethylbenzene and xylenes for each child and hence determined the urinary reference values for BTEX. We also considered the possibility of using benzene in urine as a biomarker of environmental exposure of the general population to this xenobiotic. We evaluated how both the environmental and biological measures were influenced by the presence of smokers in the surveyed children's houses. For the group of children living in Poggibonsi, we considered the influence of the living area and the traffic density on environmental concentrations of benzene (indoor and indoor + outdoor).

Urinary mercapturic acid diastereoisomers in rats subchronically exposed to styrene and ethanol.

Styrene is stereoselectively oxidized by cytochrome P450 to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers of styrene oxide can be conjugated with glutathione (GSH) to both (R)- and (S)-diastereoisomers of the specific mercapturic acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). Several investigations have indicated different toxic potential of the (R)- and (S)-configurations of styrene oxide and its GSH- and N-acetyl-conjugates. In this study the mercapturic acid diastereoisomers were measured in the urine of rats exposed to styrene in combination with ethanol, a good inducer of styrene metabolism. Male Sprague-Dawley rats were given an isocaloric liquid diet containing ethanol (5% w/v) for 3 weeks. Starting from the 2nd week, the animals were also exposed to styrene vapours (300 ppm, 6 h/day, 5 days/week) in a dynamic exposure chamber. Both the (R)- and (S)-diastereoisomers of the M1 and M2 as well as the conventional biomarkers, mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured in urinary samples. Approximately 30 and 25% reduction of the levels of brain non-protein sulfhydryls (NPS) was observed in the animals given styrene and ethanol, respectively, while the combined ethanol and styrene treatment resulted in a 60% decrease. Ethanol consumption also resulted in higher urinary levels of the M1-R, M1-S and M2 metabolites associated with increased M1-R/S ratio and higher urinary MA excretion compared to animals treated with styrene. These results suggest that the urinary mercapturic acid diastereoisomers may be used as a noninvasive tool to examine stereoselective patterns of styrene metabolism in vivo, as well as their alterations caused by ethanol. These compound-specific mercapturic acids may also be valuable indicators of styrene-induced disorders of GSH homeostasis in nonaccessible organs.

Direct antiproliferative effect of triptorelin on human breast cancer cells.

We investigated the effect of Triptorelin (Decapeptyl, DEC) alone or combined with Tamoxifen (TAM) or Medroxyprogesterone acetate (MPA) in human breast cancer cells. DEC did not affect the growth of estrogen-insensitive MDA-MB-231 cells, while it inhibited the estrogen-stimulated proliferation of MCF-7 and CG-5 cells. No amplification of growth inhibition induced by TAM or MPA was determined by DEC. Progesterone receptor levels of CG-5 cells were significantly enhanced by DEC in the presence of 17 beta-estradiol (E2) with respect to those in control and E2-treated cells.