Yttrium and aluminium complexes bearing dithiodiolate ligands: synthesis and application in cyclic ester polymerization.

Yttrium and aluminium complexes of two dithiodiolate ligands that feature different bridges (CF3)2C(OH)CH2SRSCH2C(OH)(CF3)2 (L(1)-H2, R = CH2CH2 and L(2)-H2, R = C6H4) were synthesized in good yields by reacting tris(silylamide)yttrium or trimethylaluminium with one equivalent of the proligand. All complexes were characterized by NMR and elemental analysis, and single-crystal X-ray structural analysis was also performed for one of the yttrium complexes. The catalytic activities of the four complexes in the ring-opening polymerization of ε-caprolactone and rac-lactide have been investigated. Furthermore, DOSY experiment and DFT calculations have been carried out to determine the structure of the isopropoxo derivative of the complex L(2)Y amide.

Carbon nanotubes: Properties, biomedical applications, advantages and risks in patients and occupationally-exposed workers.

Since the beginning of the 21st century, carbon-based nanomaterials (CNTs) have been introduced in pharmacy and medicine for drug delivery system in therapeutics. CNTs have proved able to transport a wide range of molecules across membranes and into living cells; therefore, they have attracted great interest in biomedical applications such as advanced imaging, tissue regeneration, and drug or gene delivery. Although there are many data on the advantages in terms of higher efficacy and less adverse effects, several recent findings have reported unexpected toxicities induced by CNTs. The dose, shape, surface chemistry, exposure route, and purity play important roles in these differential toxicities. Mapping these risks as well as understanding their molecular mechanisms is a crucial step in the development of any CNT-containing nanopharmaceuticals. This paper seeks to provide a comprehensive review of all articles published on cellular response to CNTs, underlining their therapeutic applications and possible toxicity in patients and occupationally exposed workers.

Occupational Exposure to Chromium of Assembly Workers in Aviation Industries.

Aircraft are constructed by modules that are covered by a "primer" layer, which can often contain hexavalent chromium [Cr(VI)], known carcinogen to humans. While the occupational exposure to Cr(VI) during aircraft painting is ascertained, the exposure assessment of assembly workers (assemblers) requires investigations. Three biological monitoring campaigns (BM-I,II,III) were performed in an aviation industry, on homogeneous groups of assemblers (N = 43) and controls (N = 23), by measuring chromium concentrations in end-shift urine collected at the end of the working week and the chromium concentration difference between end- and before-shift urines. BM-I was conducted on full-time workers, BM-II was performed on workers after a 3-4 day absence from work, BM-III on workers using ecoprimers with lower Cr(VI) content. Samples were analyzed by atomic absorption spectroscopy and mean values were compared by T-test. Even if Cr concentrations measured during BM-I were lower than Biological Exposure Indices by ACGIH, statistically significant differences were found between urinary Cr concentrations of workers and controls. Despite 3-4 days of absence from work, urinary chromium concentrations measured during BM-II were still higher than references from nonoccupationally exposed populations. In the BM-III campaign, the obtained preliminary results suggested the efficacy of using ecoprimers. The healthcare of workers exposed to carcinogenic agents follows the principle of limiting the exposure to "the minimum technically possible". The obtained results evidence that assemblers of aviation industries, whose task does not involve the direct use of primers containing Cr(VI), show an albeit slight occupational exposure to Cr(VI), that must be carefully taken into consideration in planning suitable prevention measures during risk assessment and management processes.

Evaluation by environmental monitoring of pesticide absorption in farm workers of 18 Italian tomato cultivations.

Tomato cultivation farms of Southern Italy were investigated in order to evaluate the general working conditions and the levels of exposure of farm workers to pesticides, during the mixing/loading and the application of pesticides on fields. Information on working modalities, personal protective equipment, etc. was collected using a questionnaire. Inhaling and cutaneous exposure levels were measured, and the estimated pesticide total absorbed dose was compared with Admissible Daily Intakes (ADIs). Field treatments were mainly carried out by using sprayers with open cab tractors, and, in 57.9 percent of cases, the pesticide mixture was manually prepared by mixing pesticides in a pail, often without using gloves (59.5 percent). The estimated pesticides absorbed doses varied in the range 0.56-2630.31 mg (mean value, 46.9 mg), and 20 percent of the measured absorbed doses exceeded ADIs. The findings obtained in the 18 examined farms show a worrying situation, suggesting the investigation of many more farms, so that a statistically significant picture of tomato cultivations in Southern Italy could be formed. Besides, the planning of training courses aimed to increase workers consciousness about health risks and how they can be prevented is advisable.

Biomarker discovery by plasma proteomics in familial Brugada Syndrome.

Brugada Syndrome (BS) is a polygenic inherited cardiac disease characterized by life-threatening arrhythmias and high incidence of sudden death. In this study, two-dimensional gel electrophoresis (2D-PAGE) coupled to mass spectrometry (LC-MS/MS) was used to investigate specific changes in the plasma proteome of BS patients and family members sharing the same gene mutation (SCN5AQ1118X), with the aim to identify novel disease biomarkers. Our data demonstrate that the levels of several proteins were significantly altered in BS patients compared with controls. In particular, apolipoprotein E, prothrombin, vitronectin, complement-factor H, vitamin-D-binding protein, voltage-dependent anion-selective channel protein 3 and clusterin were considerably increased in plasma sample of BS patients, whereas alpha-1-antitrypsin, fibrinogen and angiotensinogen were considerably decreased; moreover, post-translational modifications of antithrombin-III were detected in all affected individuals. On the light of these results, we hypothesize that these proteins might be considered as potential markers for the identification of disease status in BS.

[HFR-AEQUILIBRIUM and intradialytic cardiovascular stability: results of the first multicenter study in Lazio]. / HFR-AEQUILIBRIUM e stabilità cardiovascolare intradialitica: risultati del primo studio multi-centrico laziale.

Intradialytic hypotension (IDH) is a still-frequent and poorly-understood complication of haemodialysis. Haemofiltration has recently been shown to reduce the phenomenon of IDH. HFR-Aequilibrium adds to traditional HFR and is, in practice, a variant comprising endogenous re-infusion of haemodiafiltration with dialysate sodium concentration and ultrafiltration rate profiles elaborated by the 'Profiler' plasma sodium biofeedback system, and measurement of plasma sodium via the on-line Natrium sodium sensor.

Nanotech revolution for the anti-cancer drug delivery through blood-brain barrier.

Nanotechnology-based drug delivery was born as a chance for pharmaceutical weapons to be delivered in the body sites where drug action is required. Specifically, the incorporation of anti-cancer agents in nanodevices of 100-300 nm allows their delivery in tissues that have a fenestrated vasculature and a reduced lymphatic drainage. These two features are typical of neoplastic tissues and, therefore, allow the accumulation of nanostructured devices in tumours. An important issue of anti-cancer pharmacological strategies is the overcoming of anatomical barriers such as the bloodbrain- barrier (BBB) that protects brain from toxicological injuries but, at the same time, makes impossible for most of the pharmacological agents with anti-cancer activity to reach tumour cells placed in the brain and derived from either primary tumours or metastases. In fact, only highly lipophilic molecules can passively diffuse through BBB to reach central nervous system (CNS). Another possibility is to use nanotechnological approaches as powerful tools to across BBB, by both prolonging the plasma half-life of the drugs and crossing fenestrations of BBB damaged by brain metastases. Moreover, modifications of nanocarrier surface with specific endogenous or exogenous ligands can promote the crossing of intact BBB as in the case of primary brain tumours. This aim can be achieved through the binding of the nanodevices to carriers or receptors expressed by the endothelial cells of BBB and that can favour the internalization of the nanostructured devices delivering anti-cancer drugs. This review summarizes the most meaningful advances in the field of nanotechnologies for brain delivery of drugs.

[Managment of tuberculosis in an University of Campania]. / La gestione di casi di tubercolosi in un'Azienda Ospedaliera Universitaria Campana.

Tuberculosis (TBC) is an infectious disease with the highest mortality and morbidity by single pathogen, affecting about one third of worldwide population. Although Mantoux test is the most used, IGRA (Interferon-gamma Release Assays) tests seem to give good results for presumptive diagnosis of active or latent tuberculosis. From June 2011 to June 2012 we made about 1,000 visits for TBC prevention among the exposed to biological risks of our University. The management of suspected latent or active tuberculosis infection was carried out in collaboration with the pulmonologist, assessing the risk of contagion among exposed or affected operators. Health surveillance protocol and judgements of suitability for specific task were made not only in consideration of worker health, but also considerating the possible risk for patients, since this disease is a major problem for public health.

[Functional changes in human peripheral neutrophils in workers with different exposure to noxious agents]. / Valutazione delle modifiche funzionali dei neutrofili in lavoratori esposti a xenobiotici.

Free radicals have a role in interaction between occupational exposure to multiple agents and biological systems; peripheral neutrophils (PMNs) are a source of free radicals and other reactive oxygen species. PMN's activity was evaluated by chemiluminescence assays referring to different noxious agents exposure levels. Two office workers groups were recruited: first one was exposed to several agents, control group was composed by lower exposure workers. Intra and extracellular chemiluminescence evaluation was performed to obtain radical species information. Stimulated PMNs from exposed subjects respond to the stimuli less than unexposed, and can be suggested as chronic exposure markers to noxious agents.

[Evaluation in vitro of the cardiotoxic effects of 5-fluorouracil for the prevention of cardiovascular damage in health workers occupationally exposed]. / Valutazione in vitro degli effetti cardiotossici da 5-fluorouracile per la prevenzione dei danni cardiovascolari negli operatori sanitari professionalmente esposti.

The occupational exposure to antineoplastic drugs in health care workers determines a risk of absorption through inhalation of vapors or skin contact with drops. Even if many data confirm the cardiotoxicity of anthracyclines, is not clear the evidence of cytotoxicity of 5-Fluorouracil, thoug in a percent of patients receiving this chemotherapy, there is the presence of heart pain, aspecific ECG disorders and induction of coronary disease. This experimental study wants to analyze on the H9c2 cardiomyocyte cell model the effects of 5-Fluorouracil, commonly used in hospital realities of the South Italy, for the prevention of the possible cardiovascular damage in workers occupationally exposed.

[Human health effects of ultrafine particles]. / Effetti dell'inquinamento da particolato ultrafine sulla salute umana.

Epidemiologic and clinical studies have linked elevated concentrations of ambient ultrafine particles (UFPs) to adverse health effects. In particular, has been demonstrated an association between UFPs exposure and occurrence of acute respiratory infections, lung cancer, chronic chronic obstructive pulmonary diseases and cardiovascular diseases. Although the biological mechanisms behind these associations are not fully understood, the results of in vitro toxicological research have shown that UFPs induces several types of adverse cellular effects, including cytotoxicity, mutagenicity, DNA oxidative damage and stimulation of proinflammatory cytokine production. In this reviewer are summarized the results of the recent epidemiological and toxicological studies on adverse health effects from exposure to UFPs.

Morbi mortalidad por infecciones en pacientes con leucemia linfoblástica aguda: recaida en inducción / Infection associated morbidity and mortality in children with relapsed acute limphoblastic leukemia during induction therapy

Los pacientes con Leucemia Linfoblástica Aguda (LLA) recaída reciben quimioterapia (QMT) intensa que produce neutropenia severa y prolongada que condiciona mayor frecuencia de infecciones. Con el fin de evaluar las características clínicas de las infecciones en estos pacientes con neutrepenia y fiebre (NF) luego de la QMT de inducción se realizó un análisis retrospectivo de estos episodios de NF. La QMT de inducción incluyó 10 días de prednisona 100 mg/m2 VO y altas dosis de QMT de 6 días de duración. Recibieron esta QMT 98 pacientes en el período comprendido entre septiembre de 1994 y Diciembre de 2002. De los 96 pacientes evaluables el 73 eran varones y la edad media fue de 110.5 meses. E 28 eran mayores de 12 años. El 64 tenían catéter implantable. el 77 eran eutróficos y el 21 obesos. Presentaron NF 86 pacientes (90). El 29 tuvo sepsis. Todos los episodios de NF cumplieron criterios de alto riesgo. La media de días de internación fue 19.5. El 19 de los niños requirió en Unidad de Cuidados Intensivos (UCI). Recibieron asistencia respiratoria mecánica (ARM) el 16 de los niños. El 52 de los niños tuvo bacteriemia, donde prevalecieron los cocos Gram positivos (29) seguido de bacilos Gram negativos (22). Ochenta y cinco por ciento de los episodios presentaron foco clínico de infección y prevalecieron el foco pulmonar (33.3) y la mucositis oral (32.3). Fallecieron 9 pacientes (9.4). Todas las muertes fueron debidas a sepsis no controlada. La edad mayor a 12 años fue la única variable estadísticamente significtiva relacionada con la mortalidad (OR 6.3, IC 951.4-27.3; p<0.01). La presencia de foco perianal, enteral y el infiltrado pulmonar se asociaron con la presencia de sepsis. Los pacientes con NF luego de la inducción de LLA recaída tienen alta tasa de mortalidad relacionada con la infección, perticularmente la sepsis. En este grupo de pacientes es necesario extremar los cuidados posteriores a la QMT.

[Matrix metalloproteinases: new effect biomarkers in the occupational exposure of toxic agents]. / Le metalloproteasi: nuovi biomarkers di effetto nell'esposizione professionale ad agenti tossici.

Matrix metalloproteinases belong to a growing family of proteases controlled by specific tissue inhibitors, involved in tissutal flogosis, wound healing, cancer invasion and metastasis. We developed an in vitro model to screen for potential toxic compounds in professional exposure. Human keratinocytes (HaCat) were used as target cells while matrix metalloproteinases (MMP) were selected as responders, developing and in vitro model of allergic dermatitis. The chemical agents: potassium dichromate and nickel sulphate as positive teste, because represent the main etiological agents of allergic dermatitis. Nickel contact at very low concentrations (10(-5), 10(-6) M) induced upregulation of MMP-2 and IL-8 mRNA production; chromium contact at very low concentrations killed all cells. Actually, our in vitro research is based on analysis of cytotoxic effects of xenobiotics on human lung fibroblasts; simultaneously we verified serum increasing in vivo of MMP-9, determinated in workers serum, exposed to anesthetic gas (fluorane). In only six exposed workers we observed MMP9 increasing over than normal range. Actually, we are continuing our research on a more representative sample.

Intestinal permeability is decreased in anorexia nervosa.

Malnutrition and absence of exogenous luminal nutrients in the gastrointestinal tract affect intestinal permeability (IP) leading to an increased penetration of substances that passively cross intestinal epithelium via intercellular pathways. We hypothesised that an increase in IP could occur in patients with anorexia nervosa because of their prolonged fasting and chronic malnutrition. Therefore, we assessed IP in 14 drug-free anorexic women and 19 drug-free age-matched healthy women by means of the lactulose/mannitol (LA/MA) test. To this purpose, after an overnight fast, subjects ingested an oral solution containing 5 g lactulose and 2 g mannitol in 100 ml water. Urine specimens were collected immediately before and 30, 60, 120, 180, 240 and 300 min after the ingestion of the sugar solution. Urinary lactulose and mannitol were determined by high-performance anion exchange chromatography coupled with pulsed amperometric detection. We found that IP, as expressed by the 5-h LA/MA excretion ratio, was significantly decreased in anorexic women because of a lower urinary recovery of lactulose. Moreover, in patients, the time course of lactulose excretion significantly differs from healthy controls. These results do not confirm our hypothesis of increased IP in anorexia nervosa. Since IP reflects the anatomo-functional status of intestinal mucosa, the present findings support the idea that changes in the anatomo-physiology of intestinal mucosa occur in anorexia nervosa.

Thromboxane A(2) regulation of endothelial cell migration, angiogenesis, and tumor metastasis.

Prostaglandin endoperoxide H synthases and their arachidonate products have been implicated in modulating angiogenesis during tumor growth and chronic inflammation. Here we report the involvement of thromboxane A(2), a downstream metabolite of prostaglandin H synthase, in angiogenesis. A TXA(2) mimetic, U46619, stimulated endothelial cell migration. Angiogenic basic fibroblast growth factor (bFGF) or vascular endothelial growth factor (VEGF) increased TXA(2) synthesis in endothelial cells three- to fivefold. Inhibition of TXA(2) synthesis with furegrelate or CI reduced HUVEC migration stimulated by VEGF or bFGF. A TXA(2) receptor antagonist, SQ29,548, inhibited VEGF- or bFGF-stimulated endothelial cell migration. In vivo, CI inhibited bFGF-induced angiogenesis. Finally, development of lung metastasis in C57Bl/6J mice intravenously injected with Lewis lung carcinoma or B16a cells was significantly inhibited by thromboxane synthase inhibitors, CI or furegrelate sodium. Our data demonstrate the involvement of TXA(2) in angiogenesis and development of tumor metastasis.

Lymph node mapping and sentinel lymph node biopsy for evaluation of axillary lymph node status in early invasive breast cancer. Our experience.

The Authors show their preliminary experience with the sentinel lymph node biopsy (SLNB) in clinical early invasive breast cancer (T1N0). During a period of 15 months, forty-two patients were submitted to SLNB upon Tc99-colloid albumin injection and SLN identification by lymphoscintigraphy. The middle number of lymph nodes found in the SLNB was 1 (1-3), whereas the middle number of lymph nodes identified in level I/II ALND specimens was 15. The SLN was identified with success in all cases (100%). The axilla was positive for metastasis in 4/42 cases. The SLN was positive in all four cases in which nodal metastasis was identified. The negative predictive value of SLN was 100%. The SLN was the only site of metastasis in 3/4 cases. The SLN pathological status accurately reflected the lymphatic basin status, but further investigation is needed to define the optimal timing of colloid injection and method of examination of the SLN.

Diabetic vascular disease and hypertension.

There is increasing evidence that essential hypertension is associated with a panoply of metabolic abnormalities. Included in these abnormalities are insulin resistance, dyslipidemia, enhanced coagulation, and decreased fibrinolytic activity, microalbuminuria, and platelet abnormalities and endothelial dysfunction. Visceral obesity appears to be the most common and predictive underlying factor for all of these metabolic abnormalities accompanying hypertension as well as increased cardiovascular disease (CVD) risk. As the prevalence of obesity is increasing, there is cause for concern that CVD increases will parallel this risk factor, particularly in especially high-risk populations, such as African-American women. Other important risk factors, such as increased oxidative stress, may require special therapeutic strategies, including the use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin blockers as cornerstones of antihypertensive drug therapy.

Infecciones asociadas a catéteres implantables / Infections related to implantable venous devices

Durante el período comprendio entre diciembre de 1991 y noviembre de 1993 fueron analizados 216 catéteres implantados en 208 pacientes con enfermedades hemato-oncológicas. Las enfermedades de base que predominaron fueron: leucemia (114), tumores sólidos (64) y linfoma (16). El sitio más frecuente de colocación de los catéteres fue la vena más yugular externa (76 por ciento). Se registraron 13 infecciones y 21 bacteriemias asociadas a catéter. Los microorganismos más frecuentemente aislados fueron candida sp y Staphylococus coagulasa negativo. El tiempo de permanencia del catéter osciló entre 7 y 622 días con un total acumulado de 60918 días. las tasas de infección y bacteriemia asociadas a catéter fueron de 0.22 y 0.41 cada 1000 días de uso, respectivamente. El 37 por ciento de los catéteres tuvieron que ser removidos, siendo la infección la causa más frecuente. La tasa de infección de nuestros pacientes fue baja; ésto remarca que el manejo organizado y normalizado de estos catéteres redunda en una menor tasa de infección.