Biomimetic proteolipid vesicles for targeting inflamed tissues.

A multitude of micro- and nanoparticles have been developed to improve the delivery of systemically administered pharmaceuticals, which are subject to a number of biological barriers that limit their optimal biodistribution. Bioinspired drug-delivery carriers formulated by bottom-up or top-down strategies have emerged as an alternative approach to evade the mononuclear phagocytic system and facilitate transport across the endothelial vessel wall. Here, we describe a method that leverages the advantages of bottom-up and top-down strategies to incorporate proteins derived from the leukocyte plasma membrane into lipid nanoparticles. The resulting proteolipid vesicles-which we refer to as leukosomes-retained the versatility and physicochemical properties typical of liposomal formulations, preferentially targeted inflamed vasculature, enabled the selective and effective delivery of dexamethasone to inflamed tissues, and reduced phlogosis in a localized model of inflammation.

Biodegradable silicon nanoneedles delivering nucleic acids intracellularly induce localized in vivo neovascularization.

The controlled delivery of nucleic acids to selected tissues remains an inefficient process mired by low transfection efficacy, poor scalability because of varying efficiency with cell type and location, and questionable safety as a result of toxicity issues arising from the typical materials and procedures employed. High efficiency and minimal toxicity in vitro has been shown for intracellular delivery of nuclei acids by using nanoneedles, yet extending these characteristics to in vivo delivery has been difficult, as current interfacing strategies rely on complex equipment or active cell internalization through prolonged interfacing. Here, we show that a tunable array of biodegradable nanoneedles fabricated by metal-assisted chemical etching of silicon can access the cytosol to co-deliver DNA and siRNA with an efficiency greater than 90%, and that in vivo the nanoneedles transfect the VEGF-165 gene, inducing sustained neovascularization and a localized sixfold increase in blood perfusion in a target region of the muscle.

[Mapping of carcinogens in the chemical production industry in the province of Ferrara]. / Mappatura degli agenti cancerogeni in comparti produttivi della provincia di Ferrara.

This study consists in the reconnaissance of the carcinogenic risk in some processing in Ferrara. The main object is to know, to estimate and to verify the diffusion of the carcinogenic substances and to estimate the number of the exposed or potentially exposed workers. The study has interested the synthesis chemistry and polymer production, woodworking, welding on stainless steel and chromium conversion coating and chrome electroplating. The research has involved 54 factories and 436 workers estimated exposed or potentially exposed to carcinogenic substances. The survey has consisted of inspections in the working places, collection of exposure data, control of the precautionary measures and exposure determination in the case of stainless steel welding. The smallest factories had less knowledge of the risk and for this reason it is necessary to keep constant attention.

Does the body give the brain an attentional boost? Examining the relationship between attentional and cardiac gating.

Studies on mind-body interactions have largely focused on how mental states modulate bodily physiological responses. Increasing evidence suggests that bodily states also modulate mental states. Here we investigated how both may be integrated in the brain at the resolution of a heartbeat, examining how phasic fluctuations of peripheral blood pressure and central attentional resources combine to influence cognition. We examined the effects of cardiac phase on the performance of two simultaneous tasks: a go/no-go letter detection task where targets were concurrently presented on background faces and a short-term memory face discrimination task. Short-term memory for the background face was better when the initial face was encoded during the systole rather than diastole phase and when it was paired with a target rather than a distractor. There was no significant interaction between cardiac phase and letter detection. These data suggest that peripheral blood pressure and central attention independently regulate cognitive performance.

[Occupational exposure and chronic heart failure severity]. / Esposizione professionale e gravità dello scompenso cardiaco cronico.

Chronic heart failure (CHF) is characterized by the inability of the heart to supply the body with sufficient amount of blood for metabolic and circulatory needs. The main risk factors for CHF development are: hypertension, type 2 diabetes, obesity, smoking, chronic kidney diseases. Many occupational exposures, such as extremes of heat or cold temperatures, prolonged exposure to noise, vibrations, pesticides, can contribute to etiology of this disease. The aim of our study was to evaluate if work can affect CHF severity. We analyzed retrospectively the first 76 smokers aged over 65 years who presented to the outpatient Clinic of Chronic Heart Failure. The patients were divided in 4 groups based on their previous job: white-collars, farmers, steelworkers and subjects performing different occupational activities (hairdressers, firemen, masons). Our results showed that farmers had a reduced left ventricular ejection fraction compared with white-collars (p = 0.0045) although NYHA class and the presence/absence of CHF risk factors were not different between the two groups. This data suggests that the farmer job could be associated with the severity of CHF.

Time and space evolution of transport properties in agarose-chondrocyte constructs.

During the development of de novo synthesized cartilage tissue engineered constructs, transport and biophysical properties are expected to change in time and space. Monitoring and control of the evolution of these parameters are of crucial importance to process biohybrid constructs in vitro. The aim of this work was to measure fluid and macromolecular transport and evolution of mechanical properties of tissue-engineered cartilage constructs as a function of culture time and extracellular matrix (ECM) production. It was found, in agreement with other literature reports, that mechanical and fluid transport properties of the constructs correlated well with time of culture and glycosaminoglycan (GAG) content. Further, diffusion coefficients of 2 probes, dextran (500 kDa) and bovine serum albumin (BSA), correlated well with GAG production. Diffusion coefficients (D) were measured with high spatial and temporal resolution by fluorescent recovery after photobleaching (FRAP). Diffusivity steadily decreases with time while it does not vary through the thickness of the specimen. On the basis of these results, an empirical relationship between diffusion coefficient and GAG content was proposed for the 2 probes analyzed. The results of this study provide useful information to optimize and control the tissue culture process in vitro.

[Lung cancer in a female non-smoker with occupational exposure to asbestos: a case report]. / Tumore polmonare in donna non fumatrice con esposizione professionale ad amianto: descrizione di un caso clinico.

BACKGROUND: Until recently, asbestos was widely used in a variety of industrial processes. Workers exposed to asbestos may develop lung and pleural diseases such as asbestosis, lung cancer, benign pleural effusion, pleural plaques and mesothelioma. OBJECTIVE: To describe a clinical case of lung cancer in a female non-smoker with occupational exposure to asbestos. METHODS: The clinical and occupational history was based on the information kindly provided by the Occupational Unit of the National Health Service and on the case history of a hospital admittance in 2001, when the patient underwent surgery for lung cancer. RESULTS: The patient worked for 6 years in an asbestos manufacturing industry where she was exposed to high concentrations of asbestos, and then worked for 14 years in a sugar refinery only during the summer. She had benign pleural effusion, pleural plaques, asbestosis and lung cancer. CONCLUSIONS: We concluded that a six-year exposure to high doses of asbestos may induce lung cancer and asbestosis in a female non-smoker.

Biomimetic carriers mimicking leukocyte plasma membrane to increase tumor vasculature permeability.

Recent advances in the field of nanomedicine have demonstrated that biomimicry can further improve targeting properties of current nanotechnologies while simultaneously enable carriers with a biological identity to better interact with the biological environment. Immune cells for example employ membrane proteins to target inflamed vasculature, locally increase vascular permeability, and extravasate across inflamed endothelium. Inspired by the physiology of immune cells, we recently developed a procedure to transfer leukocyte membranes onto nanoporous silicon particles (NPS), yielding Leukolike Vectors (LLV). LLV are composed of a surface coating containing multiple receptors that are critical in the cross-talk with the endothelium, mediating cellular accumulation in the tumor microenvironment while decreasing vascular barrier function. We previously demonstrated that lymphocyte function-associated antigen (LFA-1) transferred onto LLV was able to trigger the clustering of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells. Herein, we provide a more comprehensive analysis of the working mechanism of LLV in vitro in activating this pathway and in vivo in enhancing vascular permeability. Our results suggest the biological activity of the leukocyte membrane can be retained upon transplant onto NPS and is critical in providing the particles with complex biological functions towards tumor vasculature.

[Occupational exposure to respiratory irritants and chronic obstructive pulmonary disease]. / Esposizione professionale ad agenti irritanti e sviluppo di broncopneumopatia cronica ostruttiva (BPCO).

Cigarette smoking and occupational exposure to respiratory irritants are the major riskfactors for chronic obstructive pulmonary disease (COPD), which is characterized by small-airway obstruction and destruction of pulmonary parenchyma: emphysema. We studied two groups of subjects: one exposed and the other one not-exposed to respiratory irritants, to investigate the relationship, if any, between occupational exposure and COPD. Subjects underwent high-resolution computed tomography-density mask of the chest to quantify pulmonary emphysema, pulmonary function tests, sputum induction and analysis for cell counts and measurements of metalloproteinase (MMP)-9 and its tissue inhibitor TIMP-1. Subjects with occupational exposure to respiratory irritants had higher residual volume and functional residual capacity, higher total inflammatory cells and neutrophils in induced sputum. By contrast, sputum levels of MMP-9, TIMP-1 and MMP-91TIMP-1 ratio did not differ between the 2 groups. We conclude that sputum induction and analysis could be a useful and non-invasive tool to study and follow subjects with occupational exposure to respiratory irritants.

Muscarinic cholinergic neuromodulation reduces proactive interference between stored odor memories during associative learning in rats.

Previous electrophysiological studies and computational modeling suggest the hypothesis that cholinergic neuromodulation may reduce olfactory associative interference during learning (M. E. Hasselmo, B. P. Anderson, & J. M. Bower, 1992; M. E. Hasselmo & J. M. Bower, 1993). These results provide behavioral evidence supporting this hypothesis. A simultaneous discrimination task required learning a baseline odor pair (A+B-) and then, under the influence of scopolamine, a novel odor pair (A-C+) with an overlapping component (A) versus a novel odor pair (D+E-) with no overlapping component. As predicted by the model, rats that received scopolamine (0.50 and 0.25 mg/kg) were more impaired at acquiring overlapping than nonoverlapping odor pairs relative to their performance under normal saline or methylscopolamine. These results support the prediction that the physiological effects of acetylcholine can reduce interference between stored odor memories during associative learning.

Contribution of the cholinergic basal forebrain to proactive interference from stored odor memories during associative learning in rats.

E. De Rosa and M. E. Hasselmo (2000) demonstrated that 0.25 mg/kg scopolamine (SCOP) selectively increased proactive interference (PI) from stored odor memories during learning. In the present study, rats with bilateral cholinergic lesions limited to the horizontal limb of the diagonal band of Broca, made with 192 IgG-saporin, were not impaired in acquiring the same olfactory discrimination task relative to control rats. Rats with bilateral 192 IgG-saporin lesions to all basal forebrain cholinergic nuclei (BF) also showed no impairment in acquisition of this task. However, the BF-saporin rats were hypersensitive to oxotremorine-induced hypothermia and demonstrated an increased sensitivity to PI following a low dose of SCOP (0.125 mg/kg) relative to control rats. The results suggest that weaker cholinergic modulation after cholinergic BF lesions makes the system more sensitive to PI during blockade of the remaining cholinergic elements.

Evaluation of the current risk of lead poisoning in the ceramics industry.

Evaluation of the current risk of lead poisoning in the ceramics industry. Scand j work environ health 9 (1983) 463-469. The authors evaluate the current possibility of lead poisoning in the production of ceramic tiles, an industrial sector which has always been considered dangerous due to the use of lead-rich glazes. The study was conducted in nine plants, four of which were repeatedly monitored (five checks on 94 exposed subjects). The other five plants (for a total of 221 exposed subjects) were only checked once. An analysis of all the results showed a clear reduction in mean blood lead levels, which the authors believe was due to the use of glazes with less lead. The results obtained were generally satisfactory; they indicated a definite improvement in the situation with respect to the authors' previous investigations, even for jobs in which workers were more frequently exposed. The data overlap those observed in the production of artistic pottery, which has always been considered less dangerous.

The ceramics industry and lead poisoning. Long-term testing.

The investigation evaluates the efficiency attributed to some measures (improvements in environment, individual health habits) in reducing the risk of lead poisoning in the ceramics industry. The evaluation of the average levels of lead in the blood of 154 exposed workers was carried out in four plants at a time interval of six to eight months. The study considers the variations in relation to possible measures brought about during the interval. A reduction of environmental risk was in effect shown by a clear improvement in the blood lead levels, which still, however, exceeded the internationally recommended limits in many of the subjects. It was concluded that further improvements can only be made by reducing the lead content of the glazes used.

The ceramics industry and lead poisoning. Lead poisoning in relation to technology and jobs.

The investigation evaluates the risk of lead absorption for 288 ceramics industry workers. Cases were studied in relation to sex, type and length of exposure, production plant characteristics, and jobs performed. The difference linked with sex was amplified by the fact that men usually performed the decidedly higher risk jobs, such as those connected with the direct use of ceramic glazes, in which--although to a variable extent--high percentages of lead are used. In fact, decreasing amounts of lead absorption were found for workers engaged in the operations of glazing, kiln work, maintenance and decoration, selection coming last. It was concluded that, in the Italian ceramics industry, lead exposure is linked to the use of lead-rich glazes and that this exposure may thus vary according to the different jobs or different technological cycles. Although female workers primarily carry out decoration and selection jobs, they nonetheless show high levels of lead in their blood, exceeding 1.9 mu mol/l--the limit currently recommended for women.

In vivo monitoring of bone-Pb and retrospective exposure: an assessment in occupationally exposed subjects.

In this work we present the preliminary results of an investigation in to the bone burden of lead in occupationally exposed subjects. The assessment of bone lead levels normalised to the mineral content (mg/kg bone mineral) were carried out by means of an in vivo X ray fluorescence techniques (Pb-XRF). The measurements were performed on the second phalanx of the right index finger and the minimum detectable limits of the XRF techniques was estimated around 25-30 mg/kg. Although the blood lead level monitoring over long time seems to indicate working activities in environments with low sources of lead contamination, high Pb-XRF levels, and not well correlated with the exposure time, were found. These anomalous values could be explained in term of the dependence of zinc protoporphyrin assessment against the measurement time.

[Chronic renal insufficiency and growth retardation: not an inseparable binomial]. / Insufficienza renale cronica e ritardo di crescita: oggi binomio non più inscindibile.

BACKGROUND: The aim of the study was to evaluate, in children with chronic renal failure and in conservative treatment, the degree to which their growth was compromised, in relation with bone age and with GRF. METHODS: The growth of children (12 F, 14 M) with CRI has been evaluated retrospectively in relation to bone age and GFR. Their mean age at diagnosis was 5.8 years. The pathologies-causing CRI were, in particular, congenital anomalies and hereditary nephropathies. The mean follow-up was 6.1 years. RESULTS: No significant difference was found between bone age (BA) and chronologic age (CA) (4.7 +/- 3.4 vs 5.7 +/- 3.5 years, p < 0.3) at diagnosis, while it was lightly delayed (8.6 +/- 5.2 vs 11 +/- 5.6 years, p < 0.07) at the end of the study. At diagnosis the mean height SDS for CA was 0.64 +/- 1.12, at the end of observation was -1.2 +/- 1. Only in 3 patients height was < -2DS: two of them underwent rhGH treatment; the third patient had a growth potential exhausted. The mean height velocity (HV) was 6 +/- 4.2 cm/y at diagnosis and 4.8 +/- 3 at last observation (p < 0.3). No significant difference at diagnosis was found between the HV cm/y and GRF stratified for range, at follow-up there was light significant difference between HV and light CRF vs severe (p < 0.02). Likewise no significant relationship between HV and CA was observed. Actually 20 patients are in conservative treatment, 6 received renal transplantation: for them the growth has been proportional to reached renal function and age of receiver. CONCLUSIONS: The conservative therapeutic regimens and good compliance allowed to limit growth deficiency.

Bilateral Legg-Calvé-Perthes disease: different from unilateral disease?

Twenty-five patients or 50 hips with bilateral Legg-Calvé-Perthes disease were reviewed at skeletal maturity in the orthopaedic departments of Leuven, Belgium, and Montpellier, France. The two groups were very similar as to age at onset of the disease, severity of involvement, and classification at skeletal maturity. The results seem to indicate that bilateral disease runs a more severe course as compared with unilateral Legg-Calvé-Perthes disease. Eighty percent presented with a Catterall group III and IV and Herring classification B and C. Forty-eight percent rated as Stulberg 4 and 5 at skeletal maturity.

[Industrial pollution by solvents with special reference to limited values for mixtures]. / Inquinamento industriale da solventi con particolare riferimento ai valori limite per miscele.

The report concerns the AA. experience in the field of pollution due to solvents, particularly in the following industries: shoe manufacturing, graphics and the production and application of paints. The exposure risk in these 3 indutries is quantitatively and qualitatively defined based on data obtained from the gas--chromatographic analysis of 238 work environment samples. The data are evaluated with reference to limit values established by the ACGIH, the Italian Society of Occupational Medicine and the Italian Society of Industrial Hygiene. In additon to the evaluation with respect to the TLV and VLP, the hygiene parameter of TLVs for mixtures is evaluated in the field of industrial hygiene.

[Risk of absorption of fluoride in electrode arc welding]. / Rischio di assorbimento di fluoro nella saldatura ad elettrodo.

The AA. in order to investigate the risk of fluoride absorption examined two factories in which arc-welding electrodes were used. They measured: a) fluoride content in two most used electrodes; b) airborne fluoride concentrations and dustness in the presumed respiratory area of welders with or without fume and dust capture devices; d) airborne fluoride concentrations and dustness three meters away from the welding place during unprotected work with basic electrodes; e) concentrations of fluoride in urine during a workweek in welders (n = 63) and in a control group (n. = 25). The AA. conclude that, in spite of the high teoretical risk of breathing fluoride, the intake of this compound is very low if welders are protected by easy devices.