Allergic acute coronary syndrome: a case report with a concise review.

Occurrence of chest pain during an allergic reaction is a typical manifestation of the Kounis syndrome, defined in 1991 by Nicholas Kounis and George Zavras as an "allergic angina", whose clinical course can range from a simple coronary spasm without troponin elevation to an acute myocardial infarction with all the possible complications, including sudden cardiac death. The full pathogenetic mechanisms are still not fully understood, and this is one of the reasons why it is underestimated in the emergency practice; on the other hand, an immediate identification and an appropriate treatment could prevent the occurrence of the most serious consequences. In this article we report the case study of a patient with Kounis syndrome and we review the literature on this uncommon disease; it is fundamental to consider Kounis syndrome as a possible cause of chest pain in patients admitted in the emergency department with an ongoing allergic reaction.

Development of a Novel Wearable Ring-Shaped Biosensor.

We report on the preliminary results obtained out of a wearable module designed to be encompassed within a ring-shaped system aimed at providing healthcare services. The module is composed of two sensors for the measuring of Galvanic Skin Response (GSR) and Heart Rate Variability (HRV). A first device validation was carried out by involving four subjects who were asked to perform tasks providing different stress-related statuses. A comparison of physiological parameters measured by the module with those measured by a commercial HRV-GSR sensor chosen as gold standard was made. Two out of the three HRV parameters and all of the GSR parameters measured with the module resulted consistent (mostly differing less than 10%) with the same parameters measured by the gold standard. The work reported in this paper set a milestone for the realization of a system exploiting sensor fusion to provide active ageing, stress detection, activity recognition and e-health services has been achieved.

Safety and efficacy of low doses of diclofenac on acute pain in the emergency setting.

Diclofenac is the most widely prescribed non-steroidal anti-inflammatory drug worldwide. Data collected during the last 10 years reported a dose-duration dependent increasing of cardiovascular risk associated with the use of diclofenac, supporting the evidence of a close association with the degree of COX-2 inhibition achieved in vivo. Nevertheless, the amplitude of cardiovascular risk associated with the administration of diclofenac at low doses and for the short-term duration is still poorly defined. Indeed, data did not show a clear and strong increasing of the risk for daily doses of 75 and of 50 mg. Concerning duration, while the identification of a safe temporal window is less defined, some studies reported an absence or a very low risk when the exposure is shorter than 30 days. Today, new low-dosage diclofenac formulations are available, allowing to reduce the systemic exposure, the degree of COX-2 inhibition and possibly the risk of occurrence of cardiovascular events. This is the reason why those new formulations may represent the ideal drug for the management of pain in the emergency setting.

Influence of dietary fat and carbohydrates proportions on plasma lipids, glucose control and low-grade inflammation in patients with type 2 diabetes-The TOSCA.IT Study.

PURPOSE: The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the study was to explore the association of different proportions of fat and carbohydrates of the diet-within the ranges recommended by different guidelines-with metabolic risk factors. METHODS: We studied 1785 people with type 2 diabetes, aged 50-75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured. RESULTS: Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (p < 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (p < 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake. CONCLUSIONS: In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.

Redox-active and redox-silent compounds: synergistic therapeutics in cancer.

Tumours exhibit higher basal levels of reactive oxygen species (ROS) and altered redox environment compared to normal cells. Excessive level of ROS can be toxic to these cells, thus they become more vulnerable to damage by further ROS insults induced by pharmacological agents. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Therefore, abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. Many redox-modulating agents have been developed. The redox-active system epitomised by ascorbate-driven quinone redox cycling, and the group of redox-silent vitamin E analogues represented by α-tocopheryl succinate have been shown to induce selective cancer cell death in different types of cancer. These compounds synergistically act by destabilising organelles like mitochondria, unleashing their apoptogenic potential, which results in efficient death of malignant cells and suppression of tumour growth. Consistent with this notion, clinical trials that aim to examine the therapeutic performance of novel redox-modulating drugs in cancer patients are currently under way.

Effects of potential neurotoxic pesticides on hearing loss: a review.

Several pesticides are supposed to be neurotoxic for humans, consequently, they may also affect the auditory system. This review analyzes human and experimental animal studies testing the hypothesis that exposure to pesticides is associated with hearing loss. The literature on this topic is still sparse and methodological limitations of some papers evaluated are identified. As a whole, available data indicate a possible ototoxic action of pesticides, but alternative hypotheses could not be ruled out, also considering some confounders, such as the co-exposure to noise. Therefore, further studies are necessary in order to clarify the association between pesticides exposure and hearing loss. While awaiting more evidence, for precautionary action we recommend considering pesticides as possible ototoxic agents, in particular for vulnerable targets, such as pregnant women and children during early development.

Influence of night-shift and napping at work on urinary melatonin, 17-ß-estradiol and clock gene expression in pre-menopausal nurses.

Night-workers experience disruption of the sleep-wake cycle and light at night which may increase breast cancer risk by suppressing the nocturnal melatonin surge, resulting in higher levels of circulating estrogens. Night-work may also deregulate peripheral clock genes which have been found to be altered in breast cancer. This study investigated urinary 6-sulfatoxymelatonin (aMT6s), serum 17-beta-estradiol levels in premenopausal shift nurses at the end of the night-shift compared to a control group of daytime nurses. Peripheral clock gene expression in lymphocytes were also investigated. All participants were sampled in the follicular phase of the menstrual cycle. The effect of nurses’ ability to take a short nap during the night-shift was also explored. The shift-work group had significantly lower aMT6s levels than daytime nurses independently of a nap. Night-shift napping significantly influences 17-beta-estradiol levels resulting in higher outcomes in nurses who do not take a nap compared to napping group and daytime workers. Peripheral clock genes expression investigated was not significantly different among the groups. Our findings suggest that shift nurses experience changes in aMT6s levels after a night-shift. Napping habits influence 17-beta-estradiol levels at the end of a night-shift. These findings might be related to the increased cancer risk reported in night-shift workers and suggest that a short nap during night-shifts may exert a positive effect.

Regulated ATF5 loss-of-function in adult mice blocks formation and causes regression/eradication of gliomas.

Glioblastomas are among the most incurable cancers. Our past findings indicated that glioblastoma cells, but not neurons or glia, require the transcription factor ATF5 (activating transcription factor 5) for survival. However, it was unknown whether interference with ATF5 function can prevent or promote regression/eradication of malignant gliomas in vivo. To address this issue, we created a mouse model by crossing a human glial fibrillary acidic protein (GFAP) promoter-tetracycline transactivator mouse line with tetracycline operon-dominant negative-ATF5 (d/n-ATF5) mice to establish bi-transgenic mice. In this model, d/n-ATF5 expression is controlled by doxycycline and the promoter for GFAP, a marker for stem/progenitor cells as well as gliomas. Endogenous gliomas were produced with high efficiency by retroviral delivery of platelet-derived growth factor (PDGF)-B and p53-short hairpin RNA (shRNA) in adult bi-transgenic mice in which expression of d/n-ATF5 was spatially and temporally regulated. Induction of d/n-ATF5 before delivery of PDGF-B/p53-shRNA virus greatly reduced the proportion of mice that formed tumors. Moreover, d/n-ATF5 induction after tumor formation led to regression/eradication of detectable gliomas without evident damage to normal brain cells in all 24 mice assessed.

[Sinonasal carcinoma and exposure to wood and leather dust: analysis of 36 cases]. / Neoplasie naso-sinusali da esposizione occupazionale a polveri di legno e cuoio: analisi retrospettiva di 36 casi.

In order to define the best strategies of prevention and diagnosis of sinonasal cancer, the aim of our study was the investigation of the etiological and prognostic factors related to 36 cases. The enrolled cases were composed mostly of men working in the footwear industry, with a mean age of 63.7 years and mean exposure of 34.6 years. The period between the start of exposure and the appearance of the neoplasm was of 44.6 years, the time between the onset of symptoms and diagnosis was of 10.8 months. Our results suggest that a diagnosis within 6 months after the onset of symptoms is associated with a lower tumor stage, a better survival and to a lower rate of recurrence. Nasal obstruction (58.3%) and epistaxis (52.7%) are the main initial symptoms. In order to obtain an early diagnosis, in addition to periodic clinical controls, a proper information of workers is required.

[Expression of thrombomodulin in malignant pleural mesothelioma]. / Espressione della trombomodulina nel mesotelioma maligno della pleura.

The malignant mesothelioma (MM) is often complicated by thromboembolic episodes, with thrombomodulin (TM) playing a role in the anti-coagulant process. We analyzed TM expression in biopsies of MM patients and in normal mesothelial tissue. The role of DNA methylation-associated gene silencing in TM expression was investigated. A correlation between low TM expression and high level of TM promoter methylation was found in MM biopsies. Low expression of TM was restored in MM cells by their treatment with 5-aza-2'-deoxycytidine while the epigenetic agent did not affect TM expression in Met-5A cells. Methylation of the TM promoter is responsible for silencing of TM expression in MM tissue.

alpha-Tocopheryl succinate promotes selective cell death induced by vitamin K3 in combination with ascorbate.

BACKGROUND: A strategy to reduce the secondary effects of anti-cancer agents is to potentiate the therapeutic effect by their combination. A combination of vitamin K3 (VK3) and ascorbic acid (AA) exhibited an anti-cancer synergistic effect, associated with extracellular production of H(2)O(2) that promoted cell death. METHODS: The redox-silent vitamin E analogue alpha-tocopheryl succinate (alpha-TOS) was used in combination with VK3 and AA to evaluate their effect on prostate cancer cells. RESULTS: Prostate cancer cells were sensitive to alpha-TOS and VK3 treatment, but resistant to AA upto 3.2 mM. When combined, a synergistic effect was found for VK3-AA, whereas alpha-TOS-VK3 and alpha-TOS-AA combination showed an antagonist and additive effect, respectively. However, sub-lethal doses of AA-VK3 combination combined with a sub-toxic dose of alpha-TOS showed to induce efficient cell death that resembles autoschizis. Associated with this cell demise, lipid peroxidation, DNA damage, cytoskeleton alteration, lysosomal-mitochondrial perturbation, and release of cytochrome c without caspase activation were observed. Inhibition of lysosomal proteases did not attenuate cell death induced by the combined agents. Furthermore, cell deaths by apoptosis and autoschizis were detected. CONCLUSION: These finding support the emerging idea that synergistic combinations of some agents can overcome toxicity and other side-effects associated with high doses of single drugs creating the opportunity for therapeutically relevant selectivity.

Use of oxycodone in polytrauma patients: the "Gemelli" experience.

INTRODUCTION: This is the first study investigating the effect of oxycodone in polytrauma patients. The management of pain in polytrauma patients has become a very relevant issue. Nonsteroidal anti-inflammatory drugs (NSAIDs) represent the most used drugs in polytrauma patients, even though their use is associated with an increased hemorrhagic risk. Previous studies have demonstrated the efficacy of oxycodone for the treatment of acute pain. The aim of this study was to assess the efficacy of oxycodone administration in polytrauma patients, with minor injuries. PATIENTS AND METHODS: 15 polytrauma patients (10 males, mean age 40 +/- 13 years; 5 females, mean age 49 +/- 26 years) were admitted to the Emergency Department of the Catholic University, A. Gemelli Hospital in Rome, Italy. All patients underwent physical examination, FAST ultrasound, total body CT scanning and blood tests. Three patients had multiple costal fractures, three had pelvic fracture, two had tibial fracture, five had vertebral fractures, one patient had clavicle fracture and ulnar fracture, one patient a severe trauma of the left leg, which required amputation. Five patients also reported minor head trauma, with a Glasgow Coma Score (GCS) 15. All patients reported abdominal trauma, while none of them had severe thoracic or kidney damage. Patients with head trauma also underwent a second CT head scanning 12 hours after admission, which excluded the occurrence of cerebral damage. All patients were then treated with oral administration of oxycodone 10 mg two times per day (bid) for 3 days. Pain intensity, before and after the administration of oxycodone, was evaluated using a scale ranging from 0 to 10. RESULTS: The mean pain score at admission was 8 +/- 0.7. All patients reported significant pain improvement after the administration of oxycodone (8 +/- 0.7 vs 1.8 +/- 0.9; p < 0.0001). A dosage increase of oxycodone from 20 to 40 mg bid was required in only one patient with a clavicle fracture. The main side effects were light-headache (5 patients), constipation (4 patients) and nausea (3 patients). CONCLUSIONS: These data indicate that oxycodone is a safe and effective drug for pain relief in polytrauma patients without severe thoracic, kidney or brain damage.

Effect of lead on the levels of some immunoregulatory cytokines in occupationally exposed workers.

Lead (Pb) may affect humoral and cellular immunity, acting on lymphocytes as well as on granulocytes and monocytes. Cytokines and nitric oxide (NO) play a central role in the immune balance. In this study, plasma levels of nitrites and nitrates (NOx), IL2, IL4, IL6, IL10, TNF-alpha and INF-gamma, were measured in healthy workers with very low (Pb-B=3.2-18.0 microg/dL) and low (Pb-B=9.1-46.0 microg/dL) Pb-exposure compared to non-exposed workers. Low Pb-exposed workers (Pb-B=9.1 -46.0 microg/ dL) were found to have significantly higher plasma IL-10 levels, and tendentially higher plasma TNF-alpha levels compared to non-exposed workers. This is the first report of a significant increase of plasma IL-10 levels in Pb-exposed workers. Plasma IL-10 increase was influenced by blood Pb levels even after correction for main confounding factors. No difference was found in plasma NOx levels between Pb-exposed and non-exposed workers, which is in agreement with previous findings exclusively regarding groups in the general population. Low Pb-exposure can induce an increase of pro-inflammatory cytokines, such as TNF-alpha, with a consequent increase of other cytokines, such as IL-10, considered a T cell cross-regulatory factor, suggesting possible interference of Pb in the system of immunophlogosis.

Efficacy of the MCHR1 antagonist N-[3-(1-{[4-(3,4-difluorophenoxy)phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847) in mouse models of anxiety and depression following acute and chronic administration is independent of hippocampal neurogenesis.

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that plays a role in the modulation of food intake and mood. In rodents, the actions of MCH are mediated via the MCHR1 receptor. The goal of this study was to investigate the effects of acute (1 h) and chronic (28 days) p.o. dosing of a novel MCHR1 antagonist, N-[3-(1-{[4-(3,4-difluorophenoxy)-phenyl]methyl}(4-piperidyl))-4-methylphenyl]-2-methylpropanamide (SNAP 94847), in three mouse models predictive of antidepressant/anxiolytic-like activity: novelty suppressed feeding (NSF) in 129S6/SvEvTac mice and light/dark paradigm (L/D) and forced swim test (FST) in BALB/cJ mice. A significant increase in the time spent in the light compartment of the L/D box was observed in response to acute and chronic treatment with SNAP 94847. An anxiolytic/antidepressant-like effect was found in the NSF test after acute and chronic treatment, whereas no effect was observed in the FST. Because neurogenesis in the dentate gyrus has been shown to be a requirement for the effects of antidepressants in the NSF test, we investigated whether neurogenesis was required for the effect of SNAP 94847. We showed that chronic treatment with SNAP 94847 stimulated proliferation of progenitors in the dentate gyrus. The efficacy of SNAP 94847 in the NSF test, however, was unaltered in mice in which neurogenesis was suppressed by X-irradiation. These results indicate that SNAP 94847 has a unique anxiolytic-like profile after both acute and chronic administration and that its mechanism of action is distinct from that of selective serotonin reuptake inhibitors and tricyclic antidepressants.

[Report on the incidence of accidents and occupational diseases in the sector of waste disposal]. / Rapporto sulla frequenza degli infortuni e delle malattie professionali nel settore smaltimento dei rifiuti.

Waste management is continuously evolving, moreover, lack of resources and environmental hygiene issues have given more importance to recycling, establishing the basis of an increased risk in these workers. The aim of this study was to provide a description of occupational health of Italian waste workers in order to highlight key points for ad hoc interventions. Data about injuries and professional disease were extracted from the Italian National Labour Insurance Institute (INAIL) Waste work is a well-known cause of occupational accidents, however occupational disease appear to be less-known with many "unclassified" events. While new researches are needed in order to clarify these emerging issues, education could be the key to assure the waste workers health safety.

[Biomarkers for prevention and early diagnosis of malignant pleural mesothelioma]. / Utilizzo di biomarkers nella prevenzione e diagnosi precoce del Mesotelioma Maligno della pleura.

Improved detection methods for diagnosis of asymptomatic malignant pleural mesothelioma (MPM) are essential for an early and reliable detection and treatment of this disease. Thus, focus has been on finding tumour markers in the blood. 94 asbestos-exposed subjects, 22 patients with MM, and 54 healthy subjects were recruited for evaluation of the significance of 8-hydroxy-2'-deoxy-guanosine (80HdG) in white blood cells and plasma concentrations of soluble mesothelin-related peptides (SMRPs), angiogenic factors (PDGFbeta, HGF, bFGF, VEGFbeta), and matrix proteases (MMP2, MMP9, TIMP1, TIMP2) for potential early detection of MM. The area under ROC curves (AUC) indicates that 80HdG levels can discriminate asbestos-exposed subjects from controls but not from MPM patients. Significant AUC values were found for SMRP discriminating asbestos-exposed subjects from MPM patients but not from controls. VEGFbeta can significantly differentiate asbestos-exposed subjects from control and cancer groups. No diagnostic value was observed for MMP2, MMP9, TIMP1, TIMP2. The sensitivity and specificity results of markers were calculated at defined cut-offs. The combination of 80HdG, VEGFbeta and SMRPs best distinguished the individual groups, suggesting a potential indicator of early and advanced MPM cancers. The combination of blood biomarkers and radiographic findings could be used to stratify the risk of mesothelioma in asbestos-exposed populations.

[Study of a population exposed to occupational stress: correlation among psychometrics tests and biochemical-immunological parameters]. / Studio di una popolazione esposta a stress occupazionale: correlazione tra tests psicometrici e parametri biochimico-immunologici.

A longitudinal study was carried out to evaluate the effect of psycho-physical and occupational stress on some biochemical and immunological parameters. The study was aimed to the identification of new and reliable method for the identification of subjects at high risk of occupational stress. 101 nurses which were working at several departments were enrolled. A blood sample was collected from all subjects after have filled the questionnaires at the time T0 and at the followed time points of 4 months (T1), 8 months (T2) and 12 months (T3). The self-reported questionnaires were: Rating Scale for Rapid Stress Assessment (VRS), General Health Questionnaire to 12 items (GHQ-12) Multidimensional Scale of Perceived Social Support (MSPSS) and a questionnaire on the occupational satisfaction (SOD). Haemachrome glycaemia, homocysteine, cortisol, lymphocyte numbers and their subtypes (CD4, CD8, CD19, NK CD56, NK CD57), NK activity and inflammatory cytokines were evaluated. A high reliability has been found between the psychometric tests. Correlations between biochemical and immunological variables were performed by Pearson coefficients and multiple regression analysis. Subjects with elevated value of stress evaluated as VRS and GHQ-12 score showed an altered immune response. A reduction of NK CD57 and IL-6 content better characterize the occupational satisfaction.

[Mercury toxicity: trace element interactions and detoxification activity by L-arginine]. / Tossicità del mercurio: interazione con gli elementi essenziali in tracce e ruolo della L-arginina nel processo di detossificazione.

Mercury (Hg) exposure makes happen disease to humans and animals spreading in all body compartments, especially in liver and kidney. In these ones, copper, zinc, manganese and iron were investigated to assess perturbation of essential metals' homeostasis due to Hg chronic intoxication. Because L-arginine, is able to induce beneficial influence on immunologic functions on mice intoxicated with Hg, we also studied the efficiency of detoxification process before and after treatment with this aminoacid. Adding L-arginine to diet of the intoxicated mice we achieved a good restoration to normal homeostatic conditions.

[Low back pain in VDT operators: importance of sports activities]. / Disturbi muscoloscheletrici lombari in addetti al VDT: influenza dell'attività sportiva svolta nel tempo libero.

Video display terminal (VDT) operators are required to maintain a sitting position for extended periods of time. This transverse study assessed the prevalence of lumbar musculoskeletal disorders (low back pain, LBP) in a population of VDT operators and related results to occupational factors and other interfering variables. Data were collected using questionnaires administered to 210 public employees. LBP was defined and evaluated using the Standardized Nordic Questionnaire. The prevalence of LBP was 58.4%; it correlated significantly with the female sex, spinal disorders, sleep disturbances and stress levels. There was a significant negative correlation with exercise and sports activities and with leisure time computer use. Multiple logistic regression adjusted for age and body mass index yielded an LBP odds ratio of 0.19 (C.I.95% 0.07-0.51) for sport-practicing subjects. At least one hour of exercise weekly was the cut-off for a significant reduction in LBP prevalence. The proportion of lumbar musculoskeletal symptoms was not significantly different in VDT operators and the general population. None of the occupational variables considered correlated with development of LBP. The occupational physician should recommend VDT operators to devote some leisure time to exercise.