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Mumps is a vaccine-preventable infectious disease diffuse worldwide. The implementation of mumps vaccination reduced largely the spread of infection. On 11,327 Medical School students the prevalence of mumps positive antibodies was evaluated according to dose/doses of vaccine, year of birth and sex. Compliance to mumps vaccine was low in students born before 1990 but increased consistently after this year, above all compliance to two doses, due to the implementation of the vaccine offer. Positivity of mumps antibodies is significantly (p &lt, 0.0001) lower in students vaccinated once (71.2%) compared to those vaccinated twice (85.4%). In addition, students born after 1995, largely vaccinated twice, showed a seropositivity near to 90%. Further, females had a significantly (p &lt, 0.0001) higher proportion of positive antibodies after vaccination than males, both one (74.6% vs. 64.7%) and two doses (86.8% vs. 82.9%). Finally, seropositivity after two vaccine doses remains high (86.1%) even 15 years after the second dose. In conclusion, the research highlighted that vaccination against mumps reaches a good level of coverage only after two doses of vaccine persisting at high levels over 15 years and induces a more significant response in females.

Measles is a very contagious infectious disease, and vaccination is the only medical aid to counter the spread of the infection. The aim of this study was to evaluate the influence of vaccination schedule and type of vaccine, number of doses, and sex on the immune response. In a population of Italian medical students (8497 individuals born after 1980 with certificate of vaccination and quantitative measurement of antibodies against measles), the prevalence of positive antibodies to measles and antibody titer was measured. Vaccination schedule such as number of doses and vaccine type (measles alone or combined as measles, mumps and rubella (MMR)) and sex were the variables considered to influence the immune response. The vaccination schedule depends on the year of birth: students born before 1990 were prevalently vaccinated once and with measles vaccine alone (not as MMR). One dose of vaccine induces a significantly (p &lt, 0.0001) higher positive response and antibody titer than two doses, in particular when measles alone is used (p &lt, 0.0001). Females have a significantly higher percentage of positive response (p = 0.0001) than males but only when the MMR formulation was used. Multiple linear regression confirms that sex significantly influences antibody titer when only MMR is used, after one (p = 0.0002) or two (p = 0.0060) doses. In conclusion, vaccination schedule and, partially, sex influence immune response to measles vaccination. Most notably, the measles vaccine alone (one dose) is more effective than one and two doses of MMR.

The burden of hepatitis B virus (HBV) infection is a serious public health problem all over the world. Vaccination remains the most effective prevention measure, and safe and effective HBV vaccines have been available since 1982. Health care workers (HCWs) vaccinated against HBV and prospectively followed up for at least 14 years were classified by their antibody titers after primary vaccination as: poor responders (10–99 mIU/mL), moderate responders (100–999 mIU/mL), and good responders (≥1000 mIU/mL). The incidence of antibody loss was calculated for 1000 person-years and the anti-HBs persistence was calculated. The analysis concerned 539 HCWs: 494 good responders (91.7%), 37 moderate responders (6.9%), and eight poor responders (1.5%). The incidence of anti-HBs loss was 52.1 per 1000 person-years for the poor responders, 11.3 per 1000 person-years for the moderate responders, and 1.4 per 1000 person-years for the good responders. The mean persistence of anti-HBs differed significantly between the three groups, being: 19.2 years (95% CI: 15.6–22.8), 25.4 years (95% CI: 23.0–27.9), and 31.0 years (95% CI: 30.5–31.5) for the poor, moderate and good responders, respectively. In conclusion, our findings demonstrate a good persistence of protective anti-HBs titers in HCWs exposed to occupational risk for up to 30 years after a primary vaccination cycle (even without a booster dose) if their titer was initially higher than 100 mIU/mL.

Objective: Rubella is a very diffusive but relatively benign infectious disease unless contracted during pregnancy, when it causes congenital rubella syndrome. The aim of this research was to determine the prevalence and titer of antirubella antibodies in a population of future healthcare workers (students at the school of medicine).Methods: The cohort consisted of 11,022 students who underwent antibody analysis after the presentation of a vaccine certificate.Results: Vaccination compliance was very high, particularly in younger students (born after 1995), reaching almost 100% (at least one dose). Unvaccinated students born before 1990 had high seropositivity (>95%), but this percentage dropped to zero among the youngest students. Variables affecting antibody titer included year of birth and sex. Considering only vaccinated students, a greater antibody response was observed if the vaccine was administered between 8 and 10 years of age. Female sex was associated with more significant (p < 0.0001) positivity and higher antibody titer after one and two doses. However, this difference appeared less consistent in relation to year of birth.Conclusions: The studied population exhibited excellent vaccination compliance, high seropositivity, and high antibody titer. Vaccine and immune coverage were higher than what is deemed necessary to achieve herd immunity.

The aim of this study was to evaluate the levels of As, Be, Bi, Cd, Co, Cr, Cu, Hg, Mn, Ni, Pb, Se, Tl, V, and Zn, by inductively coupled plasma-mass spectrometry (ICP-MS) in the urine of two groups of patients with two different types of metal-on-metal (MoM) total hip prostheses (ASR DePuy&reg, group A, 25 patients, total Met-Met System Lima&reg, group B, 28 patients). The determination of metals reflected a steady-state release (group A: 9 years after surgery and group B: 6 years after surgery). The results obtained confirmed the increase of Co and Cr urinary levels in both group when compared with the reference values for the general population adopted by the Italian Society of Reference Values (SIVR). In particular, Co and Cr levels exceeded the threshold values in urine, respectively, of 30 &mu, g and 21 &micro, g, adjusted to creatinine based on the threshold in whole blood of 7 &mu, g/L proposed by the Medicines and Healthcare Products Regulatory Agency (MHRA). Regarding the other investigated metals, significantly higher values were found in Group A than in Group B. These differences could be due to the type of hip prosthesis implanted, the longer period of time since the implantation, as well as many other factors such as diet, age, drug consumption, physical activity, or presence of dental fillings. The continuous monitoring over the years of metal concentrations in patients carrying a prosthesis could be useful to better identify the sources of these metals.

Hepatitis B virus (HBV) infection is one of the major infectious hazards for health-care workers (HCWs) because of the frequency of percutaneous exposures to blood or body fluids. For this reason, all HCWs should be vaccinated, including students in medicine and health professional degree programs. The aim of this study was to assess the immune coverage to anti-HBV vaccine and long-lasting protective titres of anti-HBs antibodies in female and male students to evaluate gender-related differences in response to HBV vaccination. Data relative to anti-HBs antibody titre, sex, age, and age at vaccination were collected and analyzed from 5291 Italian students (1812 males and 3479 females) of the graduate courses at the School of Medicine, who underwent the mandatory health surveillance of workers exposed to biological risk. The results indicated that gender affects the immune response to HBV vaccine, particularly evident in the case of females vaccinated after one year of age who exhibited a statistically significant (p = 0.0023) 1.21-fold increase in median antibody titre with respect to males. Our findings could contribute to the optimization of HBV vaccination schedules in health surveillance of HCWs.

Non-occupational lead poisoning is not rare, mainly occurring in domestic situations in children, but also in adults. Lead poisoning was observed in a 65 years-old woman non-exposed to risk that caught our attention with a diagnostic suspicion of acute intermittent porphyria according to recurrent episodes of abdominal pain and neuropathy of upper limbs. Acute intermittent porphyria was excluded by a laboratory investigation that showed instead severe lead poisoning. After several thorough examinations of the domestic environment, the source of intoxication has been detected in some cooking pots that released high concentrations of lead. Ethylenediamine tetracetic acid disodium calcium therapy (three cycles) reduced consistently blood lead concentration and, after one year, neuropathy was almost entirely recovered.

Total hip arthroplasty (THA) with metal-on-metal (MoM) bearings have shown problems of biocompatibility linked to metal ion release at the local level causing an adverse reaction to metal debris (ARMD) and at a systemic level. The aim of this study was to evaluate clinical and radiological outcomes, and metal ion concentrations in the blood and urine of patients who underwent THA with the LIMA Met-Met hip system. Patients with ceramic-on-ceramic (CoC) bearings were included as a control group. In this study, 68 patients were enrolled: 34 with MoM THAs and 34 with CoC THAs. Patients were evaluated clinically (Harris Hip Score, SF-36) and radiologically at a median of 7.4 years after surgery. Whole blood and urinary cobalt and chromium levels were also assessed. Both types of implants were comparable in terms of clinical and functional results. Ion levels were significantly higher in the MoM group compared with CoC group 7 years after surgery. No correlations were found between metal ion levels and patient demographics, functional and radiological outcomes, and prosthesis features. Patient monitoring is thus advised to establish if prosthesis revision is necessary, especially in the case of MoM THA.

The purpose of the study is to evaluate the urinary levels of free 2,5-hexanedione (2,5-HD) in Italian subjects non-occupationally exposed to n-hexane, in order to define background values in non-occupational settings. The study was carried out on 99 subjects of the general population. The analysis of free 2,5-HD was performed by gas chromatography-mass spectrometry. Personal information about the subjects was ascertained by means of a self-administered questionnaire. The urinary levels of free 2,5-HD were in the range of &lt, 12.0&ndash, 77.9 &micro, g/L (5th&ndash, 95th percentiles). The urinary excretion of the metabolite did not seem to be influenced by gender, age, smoking habit or area of residence. Statistically significant differences (p = 0.03) were found between the free 2,5-HD urinary levels according to the vehicular traffic intensity within the area of residence and to body mass index of subjects. The background levels of free 2,5-HD found in this study could contribute to the definition of reference values of general population non-occupationally exposed and could be useful to the toxicologists and industrial hygienists to determine whether workers have been exposed to higher levels of n-hexane than the general population.

Health care workers (HCWs) are prone to a heavy psycho-physical workload. Health promotion programs can help prevent the onset of chronic and work-related diseases. The aim of the STI-VI &lsquo, before-and-after&rsquo, study, with assessments scheduled at 6 and 12 months, was to improve the lifestyle of HCWs with at least one cardiovascular risk factor. A tailored motivational counseling intervention, focusing on dietary habits and physical activity (PA) was administered to 167 HCWs (53 males, 114 females). BMI, waist circumference, blood pressure, and cholesterol, triglyceride, and blood glucose levels were measured before and after the intervention. The 6-month results (total sample and by gender) showed a marked effect on lifestyle: PA improved (+121.2 MET, p = 0.01), and diets became more similar to the Mediterranean model (+0.8, p &lt, 0.001). BMI dropped (&minus, 0.2, p &lt, 0.03), and waist circumference improved even more (&minus, 2.5 cm, p &lt, 0.001). Other variables improved significantly: total and LDL cholesterol (&minus, 12.8 and &minus, 9.4 mg/dL, p &lt, 0.001), systolic and diastolic blood pressure (&minus, 4.4 and &minus, 2.5 mmHg, p &lt, blood glucose (&minus, 1.5 mg/dL, p = 0.05), and triglycerides (significant only in women), (&minus, 8.7 mg/dL, p = 0.008), but HDL cholesterol levels dropped too. If consolidated at 12 months, these results indicate that our intervention can help HCWs maintain a healthy lifestyle and work ability.

In this paper, we focused on the analysis of the effects mediated by different cyclic dithiocarbamic ligands (DTC) on three classes of antiproliferative coordination compounds, namely, Ru(III) complexes with the general formulae [Ru(DTC)3] and [Ru2(DTC)5]Cl, and the neutral Cu(II) derivatives of the type [Cu(DTC)2]. In particular, we present the synthesis and characterization of a library of total 23 coordination compounds containing Ru(III) or Cu(II) as the biologically-active metal center and two or more dithiocarbamato (DTC) ligands derived from cyclic amines (aliphatic or aromatic). Several techniques including elemental analysis, X-ray crystallography, ESI-MS, 1H-NMR spectroscopy, FT-IR and UV-Vis spectrophotometry were used to characterize the compounds, which highlighted the different electronic behaviors generated by the substituents within the DTC moiety. Moreover, the synthesized compounds were tested for their stability in order to investigate their antiproliferative activity against 3 human cancer cell lines, namely, HeLa, HepG2 and HepG2/SB3. In particular, HepG2/SB3 was chosen for its aggressiveness due to upregulation of the anti-apoptotic protein SerpinB3. Finally, the most promising compounds are studied in terms of log P. Overall, the results reveal the drug-likeness of some of the derivatives of copper(II) and ruthenium(III).

Automobiles are an important source of carbon dioxide (CO 2 ) and other greenhouse gases (GHG) involved in climate change and human health impairment. Correct information on the environmental impact of cars in terms of CO 2 emissions and fuel consumption is necessary in car advertisements. The purpose of this paper is to evaluate the completeness of information on CO 2 emissions and fuel consumption in car advertisements according to the 1999/94/EC European Directive. We examined 902 car advertisements published in a monthly Italian car magazine searching for data on CO 2 emissions and fuel consumption according to 1999/94/EC Directive and also on further characteristics, such as type of car, engine size and power, power supply and compliance with European anti-pollution legislation. Our data showed only partial adherence to the statutory provisions of 1999/94/EC Directive: data on CO 2 emissions and fuel consumption were published with a high frequency, but they were referred to the specific car advertised in only a low percentage of ads, with relevant differences among car manufacturers. This makes difficult to compare the CO 2 emissions and fuel consumption of different cars to potential buyers. Full adherence to all provisions of the abovementioned Directive by all car manufacturers is desirable to provide consumers comprehensive and transparent information on the environmental performance of cars. The easiest and most effective way for a full and correct application of 1999/94/EC Directive is the introduction in ads of a label, similar to that currently in use for refrigerators and tires, reporting for each car advertised the official fuel consumption and official specific CO 2 emissions figures.

The American Conference of Governmental Industrial Hygienists (ACGIH) has classified oak dust as a human carcinogen (A1), based on increased sinus and nasal cancer rates among exposed workers. The aims of this study were to investigate the use of gallic acid (GA) as a chemical marker of occupational exposure to oak dusts, to develop a high-performance liquid chromatography-diode array detector method to quantify GA and to apply the method in the analysis of oak dust samples collected in several factories.A high-performance liquid chromatography method was developed to detect GA in oak wood dust. The method was tested in the field, and GA was extracted from inhalable oak wood dust collected using the Institute of Occupational Medicine inhalable dust sampler in the air of five woodworking plants where only oak wood is used.A total of 57 samples with dust concentrations in the range of 0.27-11.14 mg/m(3) were collected. Five of these samples exceeded the Italian threshold limit value of 5 mg/m(3), and 30 samples exceeded the ACGIH TLV of 1 mg/m(3). The GA concentrations were in the range 0.02-4.18 µg/m(3). The total oak dust sampled was correlated with the GA content with a correlation coefficient (r) of 0.95.The GA in the tannic extracts of oak wood may be considered a good marker for this type of wood, and its concentration in wood dust sampled in the work environment is useful in assessing the true exposure to carcinogenic oak dust.

Transition metals offer many possibilities in developing potent chemotherapeutic agents. They are endowed with a variety of oxidation states, allowing for the selection of their coordination numbers and geometries via the choice of proper ligands, leading to the tuning of their final biological properties. We report here on the synthesis, physico-chemical characterization, and solution behavior of two gold(III) pyrrolidinedithiocarbamates (PDT), namely [Au(III)Br2(PDT)] and [Au(III)Cl2(PDT)]. We found that the bromide derivative was more effective than the chloride one in inducing cell death for several cancer cell lines. [Au(III)Br2(PDT)] elicited oxidative stress with effects on the permeability transition pore, a mitochondrial channel whose opening leads to cell death. More efficient antineoplastic strategies are required for the widespread burden that is cancer. In line with this, our results indicate that [Au(III)Br2(PDT)] is a promising antineoplastic agent that targets cellular components with crucial functions for the survival of tumor cells.

It has been suggested that high-frequency audiometry (HFA) could represent a useful preventive measure in exposed workers. The aim was to investigate the effects of age, ultrasound and noise on high-frequency hearing thresholds. We tested 24 industrial ultrasound-exposed subjects, 113 industrial noise-exposed subjects and 148 non-exposed subjects. Each subject was tested with both conventional-frequency (0.125–8 kHz) and high-frequency (9–18 kHz) audiometry. The hearing threshold at high frequency deteriorated as a function of age, especially in subjects more than 30 years old. The ultrasound-exposed subjects had significantly higher hearing thresholds than the non-exposed ones at the high frequencies, being greatest from 10 to 14 kHz. This hearing loss was already significantly evident in subjects with exposure

Blood metal ion levels in 72 patients with large head metal-on-metal hip arthroplasty were studied to determine the correlation between the values measured in whole blood and urine. Urinary cobalt and chromium levels of 30μg and 21μg, respectively, adjusted to creatinine were found to correspond to the 7μg/l cut-off value that has been accepted in whole blood. Cobalt and chromium levels in whole blood and urine both significantly correlated with increased acetabular component inclination angle over 50 degrees and pain scores. There was no correlation with socket anteversion angle or femoral head diameter. The data support the use of urinary measurement of metal ions adjusted to creatinine to monitor patients with large head metal-on-metal total hip arthroplasty.

To assess the clinical relevance of a semi-quantitative measurement of human cytomegalovirus (HCMV) DNA in renal transplant recipients within the typical clinical context of a developing country where virtually 100% of both receptors and donors are seropositive for this virus, we have undertaken HCMV DNA quantification using a simple, semi-quantitative, limiting dilution polymerase chain reaction (PCR). We evaluated this assay prospectively in 52 renal transplant patients from whom a total of 495 serial blood samples were collected. The samples scored HCMV positive by qualitative PCR had the levels of HCMV DNA determined by end-point dilution-PCR. All patients were HCMV DNA positive during the monitoring period and a diagnosis of symptomatic infection was made for 4 of 52 patients. In symptomatic patients the geometric mean of the highest level of HCMV DNAemia was 152,000 copies per 10(6) leukocytes, while for the asymptomatic group this value was 12,050. Symptomatic patients showed high, protracted HCMV DNA levels, whereas asymptomatic patients demonstrated intermittent low or moderate levels. Using a cut-off value of 100,000 copies per 10(6) leukocytes, the limiting dilution assay had sensitivity of 100%, specificity of 92%, a positive predictive value of 43% and a negative predictive value of 100% for HCMV disease. In this patient group, there was universal HCMV infection but relatively infrequent symptomatic HCMV disease. The two patient groups were readily distinguished by monitoring with the limiting dilution assay, an extremely simple technology immediately applicable in any clinical laboratory with PCR capability.

Viral load measurements may predict whether human papillomavirus (HPV) type 16 infections may become persistent and eventually lead to cervical lesions. Today, multiple PCR methods exist to estimate viral load. We tested three protocols to investigate viral load as a predictor of HPV clearance. We measured viral load in 418 HPV16-positive cervical smears from 224 women participating in the Ludwig–McGill Cohort Study by low-stringency PCR (LS-PCR) using consensus L1 primers targeting over 40 known HPV types, and quantitative real-time PCR (qRT-PCR) targeting the HPV16 E6 and L1 genes. HPV16 clearance was determined by MY09/11 and PGMY PCR testing on repeated smears collected over 5 years. Correlation between viral load measurements by qRT-PCR (E6 versus L1) was excellent (Spearman’s rank correlation, ρ = 0.88), but decreased for L1 qRT-PCR versus LS-PCR (ρ = 0.61). Viral load by LS-PCR was higher for HPV16 and related types independently of other concurrent HPV infections. Median duration of infection was longer for smears with high copy number by all three PCR protocols (log rankP

a b s t r a c t The environmental and biological monitoring of benzene exposure is crucial to prevent the toxic effects of this solvent in workers. The degree of correlation, however, between the two and of different biomark- ers among them varies, particularly at low levels of exposure, depending on various factors, including variability in metabolizing enzymes and smoking habits. To investigate these further, a cohort of 28 petrochemical workers (6 smokers and 22 non smokers) was monitored throughout ten consecutive days, on two occasions, two years apart, by collecting in total 173 environmental and biological samples. The airborne benzene levels, the urinary t,t-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA) concentrations, and the glutathione S-transferases (GST) M1 and T1 genotypes were measured. S-PMA was the only metabolite statistically correlated with airborne benzene levels (r = 0.447, P < 0.0001), par- ticularly in non smokers (r = 0.667, P < 0.0001), the smoking habit being the only variable influencing metabolite excretion. Finally, a reduced S-PMA excretion was found to be associated with the GSTT1, but not the GSTM1, null genotype. In conclusion, the results show that S-PMA, but not t,t-MA, is able to mon- itor exposure to low benzene concentrations and confirm that the GSTT1 null genotype has a significant influence on metabolite excretion. The influence of the GSTT1 null genotype, however, was low, even when studying each subject with several urine samples.

An issue yet to be addressed, in the investigation of the xenobiotic toxicity, is a detailed characterization of the sex differences in toxicological responses. The 'sex issue' is particularly significant in nephrotoxicology as the kidney is a relevant target organ for xenobiotics and few studies have approached this subject in the past. There is a strong need to improve our understanding regarding the influence of sex in toxicology, given their increased requirement to establish the limits of exposure to chemicals in the environment and at work.In this review, the authors provide the reader with the current knowledge of sex differences in kidney toxicity for rats and mice. To make the review easier to consult, these studies have been organized according to the class of xenobiotic.From the analysis of the present knowledge emerges a dramatic need for information on sex differences in xenobiotics toxicity. Although animals are reasonably good predictors of adverse renal effects in patients, there is need to identify alternative methods (e.g. in vitro/ex vivo) to better study sex differences in organ toxicity.

During the last decade, our research group has prepared a number of metal dithiocarbamato derivatives of Pt, Pd and Au that were expected to resemble the main features of cisplatin together with higher activity, improved selectivity and bioavailability, and lower side-effects. Furthermore, we have already published the synthesis, characterization and in vitro cytotoxicity studies of novel ruthenium(III) dithiocarbamato complexes such as [RuL(3)] monomers (11) and α-[Ru(2)L(5)]Cl dimers (12) with five different dithiocarbamate ligands. As both the monomer and the dinuclear complexes have shown significant antitumor activity in different human tumor cell lines, we decided to widen the characterization studies and to analyse thoroughly their behavior in physiological-like medium by UV-visible and CD spectroscopy. In the present paper we report on the crystal structure of [Ru(DMDT)(3)], [Ru(PDT)(3)] and [Ru(ESDT)(3)] complexes and we determine the spin state of the paramagnetic Ru(III) by means of Evans' method. Then, we discuss in detail the UV-visible spectral data of the complexes in different medium. All the studied complexes are stable in dimethyl sulfoxide, and show low solubility in phosphate buffered saline solution, particularly the monomer species, even at low concentration, while increased solubility for both types of complexes have been found in the presence of bovine serum albumin (BSA). Moreover, no changes on the coordination sphere of the metal, as well as no direct interaction between the BSA protein and the complex have been identified by UV-visible spectroscopy. However, some conformational changes on the BSA structure, induced by the ruthenium(III) complexes have been confirmed by CD spectroscopy, indicating a probable secondary electrostatic interaction between the metal complex and the peptide. In addition, no significant interaction has been demonstrated with the components of Dulbecco's Modified Eagle's Medium, used for the in vitro assays.

Little is known concerning the sensitivity of aged rats to xenobiotics inducing kidney damage. To increase this knowledge, the age-dependent response of the kidney to hexachloro-1 : 3-butadiene (HCBD) or potassium dichromate (chromate) was investigated. Rats were treated at different ages with a single dose of segment-specific nephrotoxicants of the proximal tubule, chosen on the basis of their specificity for S(3) and for S(1)-S(2) segments, respectively. The toxicological impact of these xenobiotics has been evaluated through biochemical and genomic markers, and histopathological investigation of kidney samples. HCBD treatment induced tubular necrosis of the S(3) segment of the proximal tubule associated with changes of toxicological markers unrelated to the age. In contrast, chromate treatment induced an increased kidney damage related to the rat age. In fact, histopathological investigation revealed that at 1 month of age tubular vacuolar degeneration was seen affecting S(1)-S(2) segments of the proximal tubule, whereas at 3 months of age tubular necrosis occurred in the same segments associated with tubular dilation of the distal portions. Consistently, biochemical analysis confirmed a direct correlation among genomic and biochemical marker variability and animal age. Altogether, the results show that during aging there is an increased sensitivity of kidney to chromate but not to HCBD-induced damage and evidence differential age-related selectivity of rats for nephrotoxic compounds. Significance for human risk assessment is discussed.

In the present research a novel operative strategy of health surveillance with a reduced number of serologic tests is proposed. The approach consists to identify sub-populations with high predictable serological profile that makes the serological tests unnecessary. The study is focused on assays done to detect the response against hepatitis A, which in Italy displays low/intermediate endemicity. Receiver operating characteristics analysis performed on data from documented and self-reported vaccination information of a cohort of students from Padua University Medical School confirmed that anti-hepatitis A antibodies measurement might be avoided in subjects younger than 30 years with negative documented or self-reported history of vaccination or subjected to current vaccination schedule.

[RuCl 3 · n H 2 O] and Na( trans- [RuCl 4 (DMSO) 2 ]) were reacted with 1-pyrrolidinedithiocarbamate (PDT), its S -methyl ester (PDTM), and N , N -dimethylcarbamodithioic acid methyl ester (DMDTM) in water or methanol in order to obtain the corresponding Ru(III) derivatives. Once isolated and purified, the complexes were characterized by means of elemental analysis, conductivity measurements, FT-IR and 1 H NMR spectroscopy, ion electrospray mass spectrometry (ESI-MS), and thermal analyses. The crystal structure of mer -[Ru(DMDTM)(DMSO)Cl 3 ] has been also determined by X-ray crystallography. In vitro cytotoxic activity of all the synthesized complexes was eventually evaluated on some selected human tumor cell lines.

Background Vaccination for hepatitis B virus has been mandatory in Italy since 1991 for newborns but not for workers exposed to biologic fluids. Methods The immunologic status against hepatitis B virus was investigated in 827 paramedical students of Padua University Medical School. The students were subdivided according to sex and 2 age groups: 24 years of age or less and older than 24 years because subjects aged 24 years or less were probably included in the Italian vaccination mandatory period. Results Subjects born during the mandatory period showed a large compliance to vaccination (94.9%) and without statistically significant difference between males and females compared with the oldest students (67.6%). Conclusion The prevention at work is a matter of public health, not an individual sensitivity. For this reason, the devices to prevent accidents and diseases should be mandatory for all exposed subjects.

Renal tissue biomarkers (glutamine synthetase and p-aminohippuric acid uptake) were studied in male and female rats after treatment with hexachloro-1,3-butadiene. Reduced glutathione content also was also determined in liver and kidney. Histopathological examination (light microscopy) was then performed. The aim was to define sex differences in nephrotoxic effects caused by the solvent injected i.p. at 50, 100 and 200 mg kg(-1) dose. The rats were sacrificed 24 and 48 h after treatment; after 24 h a significant (P < 0.05) dose-dependent depletion of liver reduced glutathione was observed in male rats only; after 48 h male and female rats showed a significant (P < 0.05) increase at 50 and 100 mg kg(-1) doses. Reduced glutathione in the kidney was increased in male but not in female rats 24 and 48 h after treatment. Glutamine synthetase activity in renal tissue showed a significant (P < 0.05) dose-dependent decrease 24 and 48 h after treatment in both sexes, but is was significantly (P < 0.05) greater in female rats after 48 h. p-Aminohippuric acid uptake in renal cortical slices appeared significantly (P < 0.05) decreased in both sexes at the higher dose 24 h after treatment but this was significantly (P < 0.05) greater in female rats. A further significant (P < 0.05) impairment was observed after 48 h in males treated with a 200 mg kg(-1) dose. In addition, a slight but significant (P < 0.05) loss of p-aminohippuric acid uptake was observed 48 h after treatment with a 100 mg kg(-1) dose in both sexes. Light microscopy showed that the pars recta of the proximal tubule was mainly affected and tubular damage increased according to dose and time, involving the inner medulla and cortex. In conclusion, female rats show a significantly earlier and higher susceptibility of the kidney to toxic effects of hexachloro-1,3-butadiene.

Cisplatin is an important antineoplastic agent, but dose-limiting nephrotoxicity and the occurrence of cellular resistance prevent its potential efficacy. Moreover, cisplatin is known to be carcinogenic and genotoxic in mammalian cells and this feature is of a special interest due to the risk of inducing secondary malignancies. There is a great interest in developing new platinum agents that have broad spectrum of antitumor activity and reduced toxicity. We have recently synthesized a novel platinum(II) coordination complex containing a pyridine nucleus and a dithiocarbamate moiety as ligands, [Pt(ESDT)(Py)Cl], in order to obtain an agent with more favorable therapeutic indices than cisplatin. In this study, the new platinum(II) complex was tested for its cytotoxicity, by MTT assay, on various human cancer cell lines also including different cisplatin-resistant cells endowed with different mechanisms of resistance. On human peripheral blood lymphocytes we evaluated the genotoxic potential of [Pt(ESDT)(Py)Cl] via micronuclei and SCE detection. We also performed in vivo experiments with the purpose of investigating the antitumor and nephrotoxic effects of the new platinum(II) complex. The antitumor activity was studied in ascitic or solid Ehrlich carcinoma bearing mice while nephrotoxicity was monitored in male Wistar rats by means of histopathological findings of renal specimens and of biochemical investigation on urinary parameters (GS and NAG activities and of TUP excretion) of urine samples. The results reported here indicate that [Pt(ESDT)(Py)Cl] showed a remarkable in vitro antitumor activity (with IC50 values about twofold as low as those of cisplatin), moreover, it markedly circumvented the acquired cisplatin resistance in selected human cancer cells. The analysis of the cytogenetic damage in normal cells clearly attested that the new dithiocarbamate complex, tested at equitoxic concentrations, is less genotoxic than cisplatin. Chemotherapy in Ehrlich carcinoma bearing mice with [Pt(ESDT)(Py)Cl] was significantly better tolerated than that with cisplatin. Against the ascitic tumor, [Pt(ESDT)(Py)Cl], showed an activity noticeably higher than that of cisplatin in increasing the life span of treated animals (% T/C = 190 and 129, respectively). In solid-tumor-bearing mice, [Pt(ESDT)(Py)Cl] induced a tumor size reduction very close to that observed with the reference compound. Finally, our findings obtained from the nephrotoxicity studies demonstrated [Pt(ESDT)(Py)Cl] was not nephrotoxic, contrary to cisplatin which caused a notorious acute proximal tubular damage. In summary, [Pt(ESDT)(Py)Cl] may be considered as a new platinum(II) complex with remarkable antitumor activity and low nephrotoxicity and genotoxicity compared with cisplatin.

Fluoride, a main metabolite, and one degradation product of sevoflurane (SEV), called Compound A, are known to cause kidney effects in experimental animals. Other than in volunteers and patients, no research is available on exposed workers. The possible effects on the kidney in workers exposed in surgical areas were studied.Subjects exposed to SEV and nitrous oxide (N(2)O) in surgical areas (N = 61) using open (N = 25) or semi-closed (N = 36) circuits were submitted to biological monitoring. The same biological indices were determined in 43 controls also. Sevoflurane (SEVU), nitrous oxide (N(2)OU), total urinary proteins (TUP), N-acetyl-beta-D-glucosaminidase (NAGU), and glutamine synthetase (GSU) were measured in urine.The mean values of environmental exposure were 31.3 ppm (range 0.9-111.6 ppm) for N(2)O and 0.28 ppm (range 0-1.88 ppm) for SEV. Exposed subjects had significantly higher excretion of TUP; a higher, not significant, excretion of GSU was also observed in subjects using open circuits. A significant correlation was found in all exposed subjects between NAGU and SEVU (r = 0.303, P0.05), GSU and N(2)OU (r = 0.382, P0.01) and, especially, GSU and SEVU (r = 0.650, P0.001). These correlations appeared to be influenced by the use of open circuits; infact, NAGU was well correlated to N(2)OU (r = 0.770, P0.001) and SEVU (r = 0.863, P0.001); GSU to N(2)OU (r = 0.468, P0.05) and SEVU (r = 0.735, P0.001).Results show that no relevant effect on the kidney is present for the levels of exposure studied. Nevertheless, correlation between dose and response urinary indices supports that SEV, other than N(2)O, may influence kidney function, especially when open circuits are used.