Antileukemia Activity and Mechanism of Platinum(II)-Based Metal Complexes.

Transition metal complexes have continued to constitute an appealing class of medicinal compounds since the exceptional discovery of cisplatin in the late 1960s. Pt(II)-based complexes are endowed with a broad range of biological properties, which are mainly exerted by targeting DNA. In this study, we report a significant biological investigation into and computation analyses of four Pt(II)-complexes, namely, LDP-1-4, synthesized and characterized according to previously reported procedures. Molecular-modelling studies highlighted that the top two LDP compounds (i.e., LDP-1 and LDP-4) might bind to both matched and mismatched base pair sites of the oligonucleotide 5'-(dCGGAAATTACCG)2-3', supporting their anticancer potential. These two complexes displayed noteworthy cytotoxicity in vitro (sub-micromolar-micromolar range) against two leukaemia cell lines, i.e., CCRF-CEM and its multi-drug-resistant counterpart CEM/ADR5000, and remarkable anti-angiogenic properties (in the sub-micromolar range) evaluated in an in vivo model, i.e., a chick embryo chorioallantoic membrane (CAM) assay.

New Insights on Phytochemical Features and Biological Properties of Alnus glutinosa Stem Bark.

Alnus glutinosa (namely black alder or European alder) is a tree of the Betulaceae family widely spread through Europe, Southeastern Asia, the Caucasus mountains, and Western Siberia. Its bark is traditionally used for medicinal purposes as an astringent, cathartic, febrifuge, emetic, hemostatic, and tonic, suggesting that it may contain bioactive compounds useful to counteract inflammation. The aim of this study was to investigate the phytochemical profile of A. glutinosa stem bark extract (AGE) by LC-DAD-ESI-MS/MS analysis and to validate some biological activities such as antioxidant, anti-inflammatory and anti-angiogenic properties by in vitro and in vivo models (chick chorioallantoic membranes and zebrafish embryos), that can justify its use against inflammatory-based diseases. The AGE showed a high total phenols content expressed as gallic acid equivalents (0.71 g GAE/g of AGE). Diarylheptanoids have been identified as the predominant compounds (0.65 g/g of AGE) with oregonin, which alone constitutes 74.67% of the AGE. The AGE showed a strong and concentration-dependent antioxidant (IC50 0.15-12.21 µg/mL) and anti-inflammatory (IC50 5.47-12.97 µg/mL) activity. Furthermore, it showed promising anti-angiogenic activity, inhibiting both the vessel growth (IC50 23.39 µg/egg) and the release of an endogenous phosphatase alkaline enzyme (IC50 44.24 µg/embryo). In conclusion, AGE is a promising source of antioxidant, anti-inflammatory and angio-modulator compounds.

Design, Synthesis, and in Vitro Evaluation of 4-(4-Hydroxyphenyl)piperazine-Based Compounds Targeting Tyrosinase.

Melanin biosynthesis is enzymatically regulated by tyrosinase (TYR, EC 1.14.18.1), which is efficiently inhibited by natural and synthetic phenols, demonstrating potential therapeutic application for the treatment of several human diseases. Herein we report the inhibitory effects of a series of (4-(4-hydroxyphenyl)piperazin-1-yl)arylmethanone derivatives, that were designed, synthesised and assayed against TYR from Agaricus bisporus (AbTYR). The best inhibitory activity was predominantly found for compounds bearing selected hydrophobic ortho-substituents on the aroyl moiety (IC50 values in the range of 1.5-4.6 µM). They proved to be more potent than the reference compound kojic acid (IC50 =17.8 µM) and displayed competitive mechanism of inhibition of diphenolase activity of AbTYR. Docking simulation predicted their binding mode into the catalytic cavities of AbTYR and the modelled human TYR. In addition, these compounds displayed antioxidant activity combined with no cytotoxicity in MTT tests. Notably, the best inhibitor affected tyrosinase activity in α-MSH-stimulated B16F10 cells, thus demonstrating anti-melanogenic activity.

Ziziphus lotus (L.) Lam. as a Source of Health Promoting Products: Metabolomic Profile, Antioxidant and Tyrosinase Inhibitory Activities.

The methanolic extract of the stem bark of a wild species of jujube, Ziziphus lotus (L.) Lam., growing in Sicily, was chemically and biologically investigated. The chemical profile was defined by UHPLC-HR-ESI-Orbitrap/MS analysis whereas antioxidant and tyrosinase inhibitory activities were investigated by in vitro assays. The extract showed a high total phenolic and flavonoid content (TPC=271.65 GAE/g and TFC=188.11 RE/g extract). Metabolomic analysis revealed a rich phytocomplex characterized by phenols, cyclopeptide alkaloids, and triterpenoid saponins, some of which here detected for the first time. The mushroom tyrosinase inhibition assay displayed that the methanolic extract efficiently inhibits the monophenolase and diphenolase activity. Furthermore, the extract showed a strong ability to scavenge DPPH, a good Fe3+ reducing antioxidant power, in addition to a Fe2+ chelating activity. Taken together, these results suggest possible novel applications of wild jujube stem bark as a source of potential skin-care agents with several uses in pharmaceutical and cosmetic industries.

[Mobbing: between personality traits and organizational-managerial characteristics of the occupational environment]. / Mobbing: tra struttura di personalità e caratteristiche organizzativo-- gestionali dell'ambiente lavorativo.

UNLABELLED: INTRODUCTION. The relationship between stressful events in the workplace and their effect on health is the subject of numerous studies where the phenomenon of"Mobbing" has become of increasing interest in Social Psychiatry and Occupational Medicine. The aim of this study is to evaluate the relationship between mobbing, occupational stress and personality structure in a group of persons who consulted the "Work Adaptation Disorders Centre" at the Institute of Occupational Medicine between December 2008 and June 2010 for mobbing-related issues. METHODS: Referring to Leymann Inventory of Psychological Terrorization (LIPT), H. Ege, Occupational Stress Indicator (OSI), Minnesota Multiphasic Personality Inventory 2 (MMPI-2), it has been possible to assess situations of harassment, the sources and the effects of work stress, as well as personality traits in the study group. RESULTS: The results showed that high levels of occupational stress and inadequate coping strategies can lead to depressive, hysterical and paranoid manifestations. CONCLUSIONS: Although the relationship between mobbing, occupational stress and personality traits still remains controversial, there is an association between perception of adverse behaviour and mental health, regardless of the subject's ability to cope with stressful life events. The data seem to confirm that the prevention of bullying must be implemented by the work organization and by handling interpersonal conflicts in the work context.

Chlamydophila psittaci seropositivity and serum levels of soluble intercellular adhesion molecule-1 in farmers.

Chlamydophila infection is known as an occupational hazard to veterinarians, farmers, poultry workers. Serum levels of the soluble Intercellular Adhesion Molecule-1 (sIC AM-1), is associated with C. seropositivity. Since no data about IC AM-1 levels and C. psittaci infection are known, the aim of this work was to assess if chronic persistent C. psittaci infection constantly stimulates the expression of sIC AM-1, independent of the characteristic symptoms of ornithosis. C. psittaci seropositivity and serum concentrations of sIC AM-1 were investigated in 30 farmers and 20 age-matched healthy public employees as controls. Increased serum sIC AM-1 levels were found in the group of farmers exposed to infectious risk compared to controls, and the serum concentrations of sIC AM-1 was significantly correlated with a high IgG titre against C. psittaci. It is therefore possible to suggest a sIC AM-1 measurement for use as a tool to verify the development of C. psittaci chronic infection in an occupational setting.

Serologic investigation of the prevalence of Chlamydophila psittaci in occupationally-exposed subjects in eastern Sicily.

The aim of the study was to investigate the occurrence of serum antibodies to C. psittaci in workers at 8 stock farms located in a rural area of eastern Sicily. Serum samples from 188 workers and 160 controls were tested for immunoglobulin IgA, IgG and IgM direct against C. psittaci by microimmunofluorescent test (MIF). Seropositive subjects were defined as those with IgG titres of 1:16-1:256, and seronegative subjects as those whose titre was <1:16. To rule out the presence of cross reactive antibodies, testing was also performed for C. trachomatis and C. pneumoniae. A total of 28 (14.9%) subjects studied met the criteria for seropositivity to C. psittaci. Two of the 188 (1.06%) had an IgG titre of 1:32, 16 (8.51%) an IgG titre of 1: 64, 6 (3.19%) an IgG titre of 1:128 and 4 subjects (2.12%) demonstrated an antibody titre of 1:256. The high prevalence rate of C. psittaci antibodies among farmers suggests that this infection is spread in those subjects living in areas with an high percentage employed in rearing activities. The authors stress the importance of carrying out health surveillance in subjects working in close contact with animals receptive to infection, and confirm the need to adopt a serological test, such as MIF as a preventive measure for activities at risk.

[Burnout and occupational stress in nurses]. / Burnout e stress lavorativo in infermieri professionali.

BACKGROUND: In the last few years there has been a growing interest in the psychosocial work environment of health care workers, since they are both at high risk of burnout, role conflict and job dissatifaction. Burnout, as a type of prolonged response to chronic job-related stress, has a special significance in health care settings, where staff experience both psychological--emotional and physical stress. OBJECTIVES: The present study investigated the interrelationship between burnout, occupational stress and personality characteristics in a sample of 120 nurses employed in the Infectious Diseases Department and the Department of Medical Oncology of two major hospitals in Messina, Italy. METHODS: Three questionnaire surveys were administered: The Maslach Burnout Inventory (MBI) to estimate the job stress level, Occupational Stress Inventory to measure occupational stress and the Comrey Personality Scale to identify major personality characteristics. RESULTS: The results showed a significant statistical diference regarding the burnout levels in the two groups under study, with a higher burnout level in the Medical Oncology staff with respect to the Infectious Diseases Staff. The latter group also showed a higher occupational stress compared to the second group, with a significant statistical difference regarding "stress sources", coping strategies" and psychological health". Concerning the CPS results, some personality characteristics, as predictors for burnout syndrome, were found in the Medical Oncology staff. CONCLUSIONS: The study results underline the importance of the role ofpsychosocial work environment and the interrelationships between burnout, occupational stress and psychosomatic health in health care workers. In addition, in order to reduce a burnout risk, the Authors suggest improving the psychosocial work environment as a preventive measure.

Relationship of blood lead levels to blood pressure in exhaust battery storage workers.

Several researches has focused the hypothesis that low blood lead levels could be associated with an increased risk of hypertension. To assess the relation between occupational lead exposure and elevated blood pressure a group of 27 workers, age range from 27 to 62 years, mean (SD) 36.52 (+/- 8.16) yr; length of employment mean (DS) 2.97 (+/- 1.67) yr, were recruited as study subjects. The following variables were measured: blood lead concentration (BPb), delta-Aminolevulinic Acid Dehydratase (ALAD) activity, Zinc Protoporphirin (ZPP), creatinine, hematocrit, Body Mass Index (BMI) and Systolic Blood Pressure (SBP) and Diastolic Blood (DBP) Pressure. The results showed that long term occupational exposure was related to a slight increase of systolic and diastolic blood pressure among workers who had been exposed to higher level of lead with respect to workers exposed to lower level of lead. Furthermore, blood lead concentration (BPb) and ZPP resulted higher among workers exposed to higher level of ambient lead, while in the same group of workers ALAD activity resulted more inhibited. The authors concluded long term cumulative lead exposure can significantly increase blood pressure in low level Pb exposed workers.

Modification of interleukin-15 serum levels in workers exposed to chemotherapeutic agents.

Cytostatic anticancer drugs are known as carcinogenic, mutagenic, and teratogenic risk factors for health care workers occupationally exposed. It has been demonstrated that the administration of interleukin-15 in rat models of colon carcinoma protects against chemotherapy-induced gastrointestinal toxicities. We found that occupational exposure to chemotherapeutic antiblastic agents in vivo modified circulating levels of interleukin-15 in 17 health care workers exposed to antineoplastic drugs in relation to their jobs and in as many healthy age- and sex-matched subjects. Health care workers displayed significantly higher circulating interleukin-15 levels compared to their age-matched controls. If this increase representing an anticancer response remains to be established, these findings strengthen the idea of a therapeutic use of interleukin-15 in the field of cancer.

[Serologic investigation on the prevalence of Leptospira spp infection in occupationally exposed subjects]. / Indagine sierologica sulla prevalenza di infezione da Leptospira spp in soggetti occupazionalmente esposti.

BACKGROUND: Leptospirosis is a worldwide zoonotic infection with a high in tropical regions. OBJECTIVE: The aim of the present survey was to verify the occurrence of diffusion of leptospirosis infections in Eastern Sicily, in some groups (6 veterinarians, 34 farmers and 28 abattoir workers), who were considered at high occupational risk. METHODS: Serologic investigation were performed using the immunological method (Martin Petit test); the Leptospira serovars considered were: ictero-haemorrhagiae (Bianchi 1); canicola (Alarik); pomona (Mezzano 1); grippo-typhosa (Moskva V); bratislava (Riccio 2); sejroe (Topino 1); hardjo (Hardjoprajitno); saxkoebing (Mus 24). RESULTS: Contagion was observed in 16 subjects out of 68 (23.5%), and the anti-leptospira antibodies detected were canicola, hardjo, sejroe grippo-typhosa e ictero-haemorrhagiae. CONCLUSIONS: The authors stress the importance carrying out periodic health surveillance in subjects working in wet and contaminated environments or who are continuously in contact with animals receptive to infections. The present study also confirms the need to adopt preventive measures such as vaccines, and control programs for activities at high risk.