Transdermal nicotine absorption handling e-cigarette refill liquids.

The concentrated nicotine in e-cigarette refill liquids can be toxic if inadvertently ingested or absorbed through the skin. Reports of poisonings due to accidental ingestion of nicotine on refill liquids are rapidly increasing, while the evaluation of nicotine dermally absorbed still lacks. For that reason we studied transdermal nicotine absorption after the skin contamination with e-liquid. Donor chambers of eight Franz diffusion cells were filled with 1 mL of 0.8 mg/mL nicotine e-liquid for 24 h. The concentration of nicotine in the receiving phase was determined by high-performance liquid chromatography (LOD:0.1 µg/mL). Nicotine was detectable in receiving solution 2 h after the start of exposure and increased progressively. The medium flux calculated was 4.82 ± 1.05 µg/cm(2)/h with a lag time of 3.9 ± 0.1 h. After 24 h, the nicotine concentration in the receiving compartment was 101.02 ± 22.35 µg/cm(2) corresponding to 3.04 mg of absorbed nicotine after contamination of a skin surface of 100 cm(2). Skin contamination with e-liquid can cause nicotine skin absorption: caution must be paid when handling refill e-liquids.

hr-HPV testing in the management of women with ASC-US+ and in the follow-up of women with cytological abnormalities and negative colposcopy. Recommendations of the Italian group for cervical cancer screening (GISCi).

Compared to spontaneous screening, an organized screening programme is characterized by the presence of protocols and recommendations for all stages including follow-up. Despite the availability of well-functioning screening programmes throughout the country, the follow-up protocol after an abnormal Pap test and negative colposcopy is not clearly defined in Italy, and there is no uniformity of indications. HPV testing for oncogenic human papillomavirus (hr-HPV) has a high negative predictive value (NPV) and high positive predictive value (PPV) for CIN2+ and its employment can reduce follow-up assessments. In order to provide indications about the management of women with ASC-US+ and the follow-up of women with cytological abnormalities and negative colposcopy, a literature analysis was carried out, taking into consideration European and American guidelines and good practice recommendations from the most important scientific associations and regulatory agencies. GISCi (Italian Group for Cervical Screening) drafted recommendations for the management of women with ASC-US, L-SIL, ASC-H, AGC, and H-SIL until their return to the routine screening interval. This protocol can be applied not only in the management of abnormal Pap smears in cytology-based programmes, but also in the management of abnormal Pap test triage after HPV positive test when HPV is the primary screening test. The protocols approved within the screening programmes must have an extensive consensus among all involved professionals, including any that women might meet outside the programme.

Job strain, effort-reward imbalance and ambulatory blood pressure: results of a cross-sectional study in call handler operators.

OBJECTIVES: To examine the association between two job stress models-the job strain (JDC) and the effort-reward imbalance (ERI) model-and ambulatory blood pressure monitoring in call handler operators. METHODS: Participants included 74 women (age, 34.9 ± 9.9 years) and 26 men (age 36.0 ± 10.8 years) who were monitored on 2 workdays for ambulatory blood pressure. Measures of both job stress models were related to blood pressure by the generalized estimating equations (GEE) method while adjusting for potential confounders (gender, age, cigarette smoking, alcohol consumption, educational level, marital status, time of day, and work schedule). RESULTS: Workshifts were associated with an increase of 3-4 and 14 mmHg in mean arterial pressure (MAP) compared with diurnal activities out of work and sleeping period, respectively (P < 0.001). Ambulatory blood pressure was also significantly related with work schedule preference: unpleasant work schedule was associated with an increase of 2 mmHg in MAP compared with pleasant work schedule (P = 0.013). In the ERI model, subjects scoring high in work stress have higher ambulatory blood pressure at work, at home, and during sleep. Work stress by time interaction was not longer significant when controlling for potential confounders: generalized estimating equations revealed that MAP was influenced by BMI (>25 vs. <25: 0.7 (0.2-1.1) mmHg), workshift preference (unpleasant vs. pleasant: 2 (0.4-3.6) mmHg), and time of day. Weak not significant relation was found between ABP and psychosocial factors evaluated by the JDC and ERI models. CONCLUSION: These results do not support work stress as a significant factor influencing ABP in a homogeneous group of call-handlers. Complementary information independently obtained from the two work stress models could provide more exhaustive explanations on the stress-related effects on blood pressure.

Corrigendum to "Drug Delivery Nanoparticles in Skin Cancers".

[This corrects the article DOI: 10.1155/2014/895986.].

Human skin penetration of silver nanoparticles through intact and damaged skin.

There is a growing interest on nanoparticle safety for topical use. The benefits of nanoparticles have been shown in several scientific fields, but little is known about their potential to penetrate the skin. This study aims at evaluating in vitro skin penetration of silver nanoparticles. Experiments were performed using the Franz diffusion cell method with intact and damaged human skin. Physiological solution was used as receiving phase and 70 microg/cm2 of silver nanoparticles coated with polyvinylpirrolidone dispersed in synthetic sweat were applied as donor phase to the outer surface of the skin for 24h. The receptor fluid measurements were performed by electro thermal atomic absorption spectroscopy (ETAAS). Human skin penetration was also determined by using transmission electron microscope (TEM) to verify the location of silver nanoparticles in exposed membranes. Median silver concentrations of 0.46 ng cm(-2) (range

In vitro absorption of metal powders through intact and damaged human skin.

The bioavailability of metals, which are known as important contact allergens, is decisive for the development and the maintenance of contact dermatitis. The aim of this study was to evaluate the percutaneous penetration of metal powders of cobalt (Co), nickel (Ni) and chromium (Cr) and the effect of skin lesions on skin absorption. In vitro permeation experiments were performed using the Franz diffusion cells with intact and damaged human skin. Physiological solution was used as receiving phase and metal powders (Co, Ni and Cr) dispersed in synthetic sweat at pH 4.5 were applied as donor phase to the outer surface of the skin for 24h. The amount of each metal permeating the skin was analysed by electro-thermal atomic absorption spectroscopy (ETAAS). Donor solution analysis demonstrated that metals were present as ions. Measurements of metals skin content were also exploited. Median Co and Ni concentrations found in the receiving phase were significantly higher when Co and Ni powders were applied on the abraded skin than after application on the intact skin (3566 and 2631ngcm(-2) vs. 8.4 and 31ngcm(-2), respectively). No significant difference was found in Cr permeation through intact and damaged skin. The measurement of metals skin content showed that Co, Ni and Cr concentrations were significantly higher in the damaged skin than in the intact skin. Co and Ni ions concentrations increased significantly when the donor solutions were applied on the damaged skin, while Cr ions concentrations did not increase. This study demonstrated that Co and Ni powders can permeate through damaged skin more easily than Cr powder, which has probably a stronger skin proteins binding capacity. Therefore, our results suggest that is necessary to prevent skin contamination when using toxic substances because a small injury to the skin barrier can significantly increase skin absorption.

Associations between two job stress models and measures of salivary cortisol.

PURPOSE: To investigate the association between two job stress models-the job demand-control model and the effort-reward imbalance model-and repeated measures of salivary cortisol among male and female call-centre operators. METHODS: Daily cortisol profiles consisting of seven time points were measured across two workdays and one leisure day to determine the cortisol awakening response and the cortisol output in the day in 104 volunteers. The employees completed two self-administered questionnaire--the Karasek's demand-control questionnaire and the Siegrist's effort-reward imbalance questionnaire-to assess psychosocial hazards at work. The relations between the perceived workload measures and salivary cortisol levels were analyzed by means of generalized estimating equations method after adjusting for potential confounders (gender, age, educational level, marital status, morning awakening time, sleep duration and quality, weekdays, work schedule, adherence to sampling procedure). RESULTS: The total cortisol amount excreted in the awakening period was positively associated with the job strain measures (high strain vs. low strain: 1.4 (2.4-0.3) nmol/l). In contrast, individuals scoring higher in effort-reward imbalance at work had both lower cortisol awakening response (high imbalance vs. low imbalance: -0.7 (-1.3 to -0.2) nmol/l) and lower diurnal secretory activity (-9.2 (-17.7 to -0.7) nmol/l). Gender, weekday and adherence to sampling schedule significantly influenced the cortisol excretion in the morning period. CONCLUSIONS: Our results indicate that the two work stress models differentially affect salivary cortisol output. This finding suggests that combining the information from two complementary job stress models results in improved knowledge on the psychobiological correlates of the psychosocial work environment.

Nanoparticle dermal absorption and toxicity: a review of the literature.

INTRODUCTION: Nanotechnologies are among the fastest growing areas of scientific research and have important applications in a wide variety of fields. The data suggest that in the future workers and consumers exposed to nanoparticles will significantly increase. DERMAL ABSORPTION AND TOXICITY OF NANOPARTICLES: At now there are gaps in understanding about the human and environmental risk that manufactured nanoparticles pose for occupational exposed people and for consumers. There is a need for assessing the health and environmental impacts, the nanoparticles life cycle, the human exposure routes, the behavior of nanoparticles in the body, and the risk for workers. Possible routes of entry into the body include inhalation, absorption through the skin or digestive tract, injection, and absorption or implantation for drugs delivery systems. In particular, dermal absorption and skin penetration of nanoparticles needs a better evaluation because few and contradictory data are present in the literature, mainly on titanium dioxide. CONCLUSIONS: There are limited data on carbon-based nanoparticles and very few data on other metal nanoparticles increasingly used in industry. The article reviews the literature on the percutaneous absorption of nanoparticles and their effect on skin.

Salivary cortisol and psychosocial hazards at work.

BACKGROUND: Experimental and clinical evidence suggest that stress can lead to ill-health through the disregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Studies to date have produced equivocal results likely due to different methodologies and failure to account for confounding factors. This investigation aimed to assess the relation between self-reported work-related stressors and salivary cortisol and to clarify the role of the potential confounders. METHODS: Thirty-six call-handlers completed a self-administered job content questionnaire and collected seven daily salivary samples on two workdays and a weekend. The diurnal salivary cortisol output was expressed as cortisol awakening response (CAR), and cortisol output in the rest of the day. Salivary cortisol data were normalized by means of square root transformation. The generalized estimating equations method was used to assess the relation between job strain and cortisol levels after adjusting for gender, weekdays and adherence to the sampling schedule. RESULTS: Job strain significantly influenced the total amount of cortisol response to waking (high strain vs. low strain: 1.1 (0.3-2.0) nmol/L). The cortisol response to waking showed gender-specific differences [women excreting greater cortisol than men: 1.1 (0.3-1.9) nmol/L], and weekday differences [workdays vs. weekend: 1.0 (0.3-1.6) nmol/L]. Non-compliance with the sampling protocol was associated with lower salivary cortisol than in adherent subjects. CONCLUSIONS: Our results provide further evidence for the HPA axis involvement in the physiological response to work stress. The measure of the CAR showed to be the sensitive index to assess the physiological response to psychosocial factors. Gender, weekday, and protocol compliance were confounding factors.

Obstetric outcomes in patients who have undergone excisional treatment for high-grade cervical squamous intra-epithelial neoplasia.

OBJECTIVE: To evaluate the relationships between excisional treatment for high-grade cervical intra-epithelial neoplasia (CIN2+) and obstetric outcomes in terms of preterm delivery risk, premature rupture of membrane (PROM) and type of delivery, and between pre-term delivery and the type of excisional technique (radio frequency excision, laser conization). METHODS: This was a retrospective study of the obstetric outcomes of 2316 women aged 25-45 years who underwent excisional treatment for CIN2+ at the Obstetric and Gynecological Clinic of Ospedale Maggiore della Carità in Novara and at the Obstetric and Gynecological Department of Ospedale Sant'Anna in Torino in the period 2005-2014 and were evaluated until April 2016, and 57,937 untreated women of the same age, from the same centers. RESULTS: After treatment, 320 women had at least one pregnancy leading to delivery after a mean of 3.35 years. Treatment significantly increased the risk of preterm delivery. Compared with no treatment, the risk of preterm birth was higher in women who had undergone treatment (33.13% vs. 6.60%). Techniques removing or ablating more tissue, such as large loop excision of the transformation zone, were associated with worse outcomes (OR 2.96, 95% IC 1.72-5.10). Smoking habits significantly increase the risk of preterm delivery in the treated women (OR 2.82, 95% IC 1.61-4.9). The risk of premature rupture of the membranes (PROM) (40% vs. 23.22%), the risk of preterm PROM (pPROM) (13.13% vs. 2.71%) and dystocic births (18.75% vs 4.48%) were also significantly increased after treatment. Caesarean sections were less frequent among the treated women (15.94% vs. 32.41%). CONCLUSIONS: Our findings reveal a relationship between cervical excisional treatment and pre-term delivery, PROM, and the method of delivery. In order to minimise risk and guarantee the best obstetric outcome, patient treatment and follow-up should be personalised.

In vitro transdermal absorption of Al2O3 nanoparticles.

Dermal exposure to Aluminium nanoparticles (AlNPs) can occur in occupationally- and non occupationally exposed- population, due to the use of Al salts-based antiperspirants. No AlNPs transdermal permeation data exists. Our study investigated in vitro the permeation of 30-60 nm Al2O3NPs dispersed in synthetic sweat (20 g/L) using excised human skin on Franz cells. Experiments were performed using intact (experiment 1) and needle-abraded skin (experiment 2). After 24 h traces of Al were detectable in receiving solution of exposed cells (35.0 ±â€¯6.0 ng/cm2 for intact and 88.5 ±â€¯34.2 ng/cm2 for damaged skin, mean and SD) and in blank cells (36.3 ±â€¯7.0 ng/cm2), without statistical significance (p = 0.08, Mann-Whitney test). The average amount of Al into intact and damaged skin samples was 3.96 ±â€¯0.20 µg/cm2 for intact and 4.36 ±â€¯0.47 µg/cm2 for damaged skin (p = 0.08). Al content was similar in epidermal and dermal layers of intact and damaged skin (1.95 ±â€¯0.13 µg/cm2 and 2.31 ±â€¯0.12 µg/cm2 epidermal, 2.01 ±â€¯0.25 µg/cm2 and 2.05 ±â€¯0.35 µg/cm2 dermal). Al is a trace element in human body and the amount found in receiving solutions could be due as background impurity. This data suggest a reassuring transdermal permeation profile for Al2O3NPs.

In vitro percutaneous absorption of chromium powder and the effect of skin cleanser.

The present study tried to investigate, using a synthetic sweat at pH 4.5, whether metallic chromium can pass through the skin (in vitro) and the effect of rapid skin decontamination with a common detergent. A suspension of chromium powder in synthetic sweat at pH 4.5 was prepared and shaken with a stirring plate at room temperature for 30 min. Human skin membranes were set up in Franz-diffusion cells and 1 ml of the freshly made suspension was applied to the outer surface of the skin for 24h. The tests were performed without and with decontamination using the cleanser 30 min after the start of exposure. The appearance of metal ions in the aqueous receptor phase was quantified by Electro Thermal Atomic Absorption Spectroscopy (ETAAS) and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES). Speciation analysis and measurements of chromium skin content were also performed. Chromium skin permeation was demonstrated in in vitro experiments using the Franz cell system, giving a permeation flux of 0.84+/-0.25 ng cm(-2)h(-1) and a lag time of 1.1+/-0.7h. The cleaning procedure stop Cr permeation but its concentration into the skin significantly increased (Mann-Whitney U test P<0.03). The results revealed that chromium applied as powder can pass through the skin and that decontamination, done after 30 min of exposure, prevent Cr skin permeation but increase Cr content into the skin.

Does metal porosity affect metal ion release in blood and urine following total hip arthroplasty? A short term study.

INTRODUCTION: The surface area of exposed metal in a trabecular-titanium acetabular component is wider compared to traditional-titanium implants. The purpose of this study is to establish if this increase in surface area can lead to a significant increase in systemic metal levels. METHODS: 19 patients with conventional acetabular component and 19 with trabecular-titanium cup were compared. Aluminum, Vanadium and Titanium in blood and urine were assessed before surgery and at intervals for 2 years. The samples were analysed using an inductively coupled plasma mass spectrometry. RESULTS: Patients with trabecular-titanium did not have significantly higher metal ion levels compared to patients with conventional cups up to 2 years. A trend over time was statistically significant in both blood and urine for aluminum and titanium concentrations. CONCLUSIONS: The three-dimensionality and the wide surface of the trabecular-titanium acetabular component did not affect metal ion release compared to traditional implants after 2 years.

In vitro permeation of palladium powders through intact and damaged human skin.

The use of palladium (Pd) has grown in the last decades, commonly used in automotive catalytic converters, jewellery and dental restorations sectors. Both general and working population can be exposed to this metal, which may act as skin sensitizer. This study investigated in vitro palladium powders permeation through excised intact and damaged human skin using the Franz diffusion cell method and the effect of rapid skin decontamination using sodium laureth-sulphate. 1 mL of a 10 min sonicated suspension made of 2.5 g of Pd powder in 50 mL synthetic sweat at pH 4.5 and room temperature was applied to the outer surface of the skin membranes for 24 h. Pd permeation, assessed by ICP-MS, was higher when damaged skin was used (p = 0.03). Final flux permeation values and lag times were 0.02 ±â€¯0.01 µg cm-2 h-1 and 6.00 ±â€¯3.95 h for intact, and 0.10 ±â€¯0.02 µg cm-2 h-1 and 2.05 ±â€¯1.49 h for damaged skin samples, respectively. Damaged skin protocol enhances Pd skin penetration inside dermal layer (p = 0.04), thus making the metal available for systemic uptake. Pd penetration (p = 0.02) and permeation (p = 0.012) through intact skin decreased significantly when a cleaning procedure was applied. This study demonstrates that after skin exposure to Pd powders a small permeation of the metal happen both through intact and damaged skin and that an early decontamination with a common cleanser can significantly decrease the final amount of metal available forsystemic uptake.

In vitro meningeal permeation of MnFe2O4 nanoparticles.

MnFe2O4 nanoparticles (NPs) are commonly produced in some occupational settings and may reach high concentration in activities such as arc-welding or ferroalloy metallurgy. Manganese is an essential cofactor in enzyme activities but it has been demonstrated that long-term exposure to excessive levels can lead to "manganism", a neurodegenerative disease resembling Parkinson features. Inhaled NPs deposit partially in pharynx and nasopharynx and may reach the central nervous system through the olfactory nerve, which is completely enveloped by the meningeal membranes throughout its course from the nasal cavity to the olfactory bulb or through the trigeminal nerves. This study investigated in vitro the transmeningeal absorption of 50 nm MnFe2O4NPs, using excised porcine meninges mounted on Franz diffusion cells. We tested two donor solutions: the first containing MnFe2O4NPs (2.0 g/L) and the second obtained by the ultrafiltration of the first one, in order to test only the NPs water soluble fraction. Each experiment was carried separately for 4 h. Results showed that no Mn flux permeation through the meninges occurred, since only trace of the metal was found in receivers solutions of cells exposed to MnFeNPs (5.5 ±â€¯2.2 ng/cm2), ultrafiltered solution (3.5 ±â€¯1.5 ng/cm2) and blank cells. (2.1 ±â€¯0.6 ng/cm2) (mean and SE). Differences did not reach the statistical significance. Our study shows - for the first time - that MnFe2O4NPs penetrate the meningeal membrane in a negligible amount, thus making unlikely the hypothesis of a transcellular and paracellular absorption through the olfactory nerve but not excluding the hypothesis of an active intraneuronal absorption.

In vitro percutaneous absorption of metal compounds.

It is well known that contact with metals can be responsible for allergic contact dermatitis; also, there is experimental evidence that nickel ions are readily available on the surface of used coins containing nickel and copper. The aim of this study was to prove that metal powders of nickel (Ni), cobalt (Co) and chromium (Cr) dispersed in synthetic sweat are oxidised into respective ions that can permeate the skin. Suspensions of 5 g of metal powder (Ni, Co and Cr) in 100 mL of synthetic sweat at pH 6.5 were prepared and shaken with a stirring plate at room temperature for 30 min. Human skin membranes were set up in Franz-diffusion cells and 2 mL of the freshly made suspension were applied to the outer surface of the skin for 24h. The appearance of metal ions in the aqueous receptor phase (NaCl 0.9%) was quantified by Electro Thermal Atomic Absorption Spectroscopy (ETAAS). Also, metals ions were analysed using Differential Pulse Polarography (DDP), Differential Pulse Voltammetry (DPV) and Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) techniques both in the receiving phase and in the donor solution to evaluate the presence of different ionic metallic species. DPP and DPV measurements of cobalt and nickel suspensions confirmed the presence of Co2+ and Ni2+ ions in concentration, respectively of 33.3+/-3.2 and 27.1+/-3.2 mg L(-1). Chromium ions concentration below 0.1 mg L(-1) were found in chromium suspensions bearing evidence of synthetic sweat inefficacy of oxidising chromium metal powder. Cobalt and nickel skin permeation was demonstrated in in vitro experiments using the Franz cell system giving a permeation flux of 0.0123+/-0.0054 microg cm(-2) h(-1) for cobalt and of 0.0165+/-0.00036 microg cm(-2) h(-1) for nickel and a lag time of 1.55+/-0.71 h for cobalt and of 14.56+/-0.56 for nickel. Chromium below 0.1 microg L(-1) was found in the receiving solutions. Our experiments demonstrated that metallic nickel and cobalt can be oxidised when suspended in synthetic sweat, while chromium would probably need stronger oxidising conditions. Metallic ions can permeate the skin and the Franz cell system showed that it is possible to measure a flux of ions through the skin for cobalt and nickel but not for chromium.

Skin contamination as pathway for nicotine intoxication in vapers.

Growing warnings on health effects related to electronic cigarettes have met inconclusive findings at present. This study analyzed the in vitro percutaneous absorption of nicotine resulting by skin contamination with two e-liquids (refill 1 and 2) containing nicotine at 1.8%. Donor chambers of 6 Franz cells for each refill liquid were filled with 1mL of nicotine e-liquid for 24h; at selected intervals, 1.5mL of the receptor solutions were collected for nicotine concentration analysis by mean gas chromatography-mass spectrometry (LOD: 0.01µg/mL). The experiment was repeated removing the nicotine donor solution after 10min from the application and rinsing the skin surface three times with 3.0mL of milliQ water. A total of 12 cells with 24h exposure and 12 cells washed were studied. The mean concentration of nicotine in the receiving phase at the end of the experiment was 54.9±29.5 and 30.2±18.4µg/cm2 for refill 1 and 2 respectively and significantly lower in washed cells (4.7±2.4 and 3.5±1.3µg/cm2). The skin absorption of nicotine can lead to minor health illness in vapers, while caution must be paid to dermal contamination by e liquids in children. The skin cleaning significantly reduced the transdermal absorption kinetic and intradermal deposition of nicotine.

Skin absorption of inorganic lead (PbO) and the effect of skin cleansers.

OBJECTIVE: The aim of this study was to investigate the percutaneous penetration of lead oxide (PbO) powder and the effect of rapid skin decontamination with two different detergents. METHODS: Franz cells were used to study in vitro PbO skin penetration through human skin during a 24-hour period. The tests were performed without or with decontamination using either Ivory Liquid soap or a new experimental cleanser 30 minutes after the start of exposure. RESULTS: We confirm that PbO can pass through the skin with a median penetration of 2.9 ng/cm (25-75th percentiles 0.35-6). The cleaning procedure using Ivory Liquid soap significantly increased skin penetration with a median value of 23.6 ng/cm (25-75th percentiles 12-47.1; Mann-Whitney U test, P = 0.0002), whereas the new experimental cleanser only marginally increased penetration (7.1 ng/cm). CONCLUSIONS: Our results indicate that it is necessary to prevent skin contamination from occurring because a short contact can increase skin content and penetration even if quickly followed by washing. This study demonstrated that PbO powder can pass through the skin and that skin decontamination done after 30 minutes of exposure did not decrease skin absorption occurring over 24 hours and stresses the need to prevent skin contamination when using toxic substances.

Surface properties and cell response of low metal ion release Ti-6Al-7Nb alloy after multi-step chemical and thermal treatments.

Ti-6Al-7Nb samples treated by innovative multi-step chemical and thermal processes were characterized in order to evaluate their surface properties and cell interaction. The main object was to asses if the treatments were effective in order to obtain a surface presenting at the same time bone-like apatite induction ability, low metal ion release, good cell response and high protein binding. The morphology, crystallographic structure, porosity and wettability of the treated materials were investigated, as well as their interaction with simulated body fluid during soaking for different times. Cytotoxicity, protein adsorption tests and in vitro fibroblast and osteoblast-like cell cultures were also performed.