NanoImpactNet - Stakeholders' knowledge needs for research on the health and environmental impact of nanomaterials

NanoImpactNet (NIN) is a multidisciplinary European Commission funded network on the environmental, health and safety (EHS) impact of nanomaterials. The 24 founding scientific institutes are leading European research groups active in the fields of nanosafety, nanorisk assessment and nanotoxicology. This 4−year project is the new focal point for information exchange within the research community. Contact with other stakeholders is vital and their needs are being surveyed. NIN is communicating with 100s of stakeholders: businesses; internet platforms; industry associations; regulators; policy makers; national ministries; international agencies; standard−setting bodies and NGOs concerned by labour rights, EHS or animal welfare. To improve this communication, internet research, a questionnaire distributed via partners and targeted phone calls were used to identify stakeholders' interests and needs. Knowledge gaps and the necessity for further data mentioned by representatives of all stakeholder groups in the targeted phone calls concerned: potential toxic and safety hazards of nanomaterials throughout their lifecycles; fate and persistence of nanoparticles in humans, animals and the environment; risks associated to nanoparticle exposure; participation in the preparation of nomenclature, standards, methodologies, protocols and benchmarks; development of best practice guidelines; voluntary schemes on responsibility; databases of materials, research topics and themes. Findings show that stakeholders and NIN researchers share very similar knowledge needs, and that open communication and free movement of knowledge will benefit both researchers and industry. Consequently NIN will encourage stakeholders to be active members. These survey findings will be used to improve NIN's communication tools to further build on interdisciplinary relationships towards a healthy future with nanotechnology.

Undernutrition in children with profound intellectual and multiple disabilities (PIMD): its prevalence and influence on quality of life.

BACKGROUND: To estimate the prevalence of undernutrition among children with profound intellectual and multiple disabilities (PIMD) and to explore its influence on quality of life. METHODS: Seventy-two children with PIMD (47 male; 25 female; age range 2 to 15 years 4 months; mean age 8.6, SD 3.6) underwent an anthropometric assessment, including body weight, triceps skinfold thickness, segmental measures and recumbent length. Undernutrition was determined using tricipital skinfold percentile and z-scores of weight-for-height and height-for-age. The quality of life of each child was evaluated using the QUALIN questionnaire adapted for profoundly disabled children. RESULTS: Twenty-five children (34.7%) were undernourished and seven (9.7%) were obese. Among undernourished children only eight (32 %) were receiving food supplements and two (8%) had a gastrostomy, of which one was still on a refeeding programme. On multivariate analysis, undernutrition was one of the independent predictors of lower quality of life. CONCLUSION: Undernutrition remains a matter of concern in children with PIMD. There is a need to better train professionals in systematically assessing the nutritional status of profoundly disabled children in order to start nutritional management when necessary.

Sequential histological changes in Biomphalaria glabrata during the course of Schistosoma mansoni infection

Biomphalaria glabrata, highly susceptible to Schistosoma mansoni, were seen to shed less and less cercariae along the time of infection. Histological examination kept a close correlation with this changing pattern of cercarial shedding, turning an initial picture of no-reaction (tolerance) gradually into one of hemocyte proliferation with formation of focal encapsulating lesions around disintegrating sporocysts and cercariae, a change that became disseminated toward the 142nd day post miracidial exposure. Findings were suggestive of a gradual installation of acquired immunity in snails infected with S. mansoni.

Worm load and septal fibrosis of the liver in Capillaria hepatica-infected rats

Inocula, varying from 15 to 1,000 embryonated Capillaria hepatica eggs, were administered to young adult rats by gastric tube, in an attempt to investigate the influence of worm load in the production of septal fibrosis of the liver. Low doses of 15, 30 or 50 eggs were sufficient to produce septal fibrosis, but it appeared with variable degrees of intensity and always with focal distribution. Septal fibrosis became diffuse, progressive with time, and already well developed 40 days after infection, when 100 eggs or more were administered. However, higher inocula (200, 500 and 1,000 eggs) did not intensify septal fibrosis, although the number of parasitic focal lesions proportionally augmented.

Detection of Hepatitis B Virus Antigens in Paraffin-embedded Liver Specimens from the Amazon Region, Brazil

Hepatic viscerotomy of paraffin-preserved old specimens, collected in the period from 1934 to 1967, were analyzed by immunohistochemical assays to detect hepatitis B, hepatitis D, dengue and yellow fever virus antigens. The material belongs to the Yellow Fever Collection, Department of Pathology, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil and the cases were diagnosed at that time according to clinical aspects and histopathological findings reporting viral hepatitis, yellow fever, focal necrosis and hepatic atrophy. From the 79 specimens, 69 were collected at the Labrea Region and the other 10 in different other localities in the Amazon Region. The five micra thick histological slices were analyzed for the presence of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) by immunoperoxidase technique. An immunofluorescence assay was applied to the detection of hepatitis D, yellow fever and dengue virus antigens. Nine (11.4%) histological samples were HBsAg reactive and 5 (6.3%) were HBcAg reactive. The oldest reactive sample was from 1934. Viral antigens related to the other pathologies were not detected in this study. Our results confirm that the methodology described may be used to elucidate the aetiology of hepatitis diseases even after a long time of conservation of the specimens.

Preliminary Experience in Treatment of Papillary and Macular Retinoblastoma: Evaluation of Local Control and Local Complications After Treatment with Linear Accelerator-Based Stereotactic Radiotherapy with Micromultileaf Collimator as Second-Line or Salvage Treatment after chemotherapy.

PURPOSE: To determine the local control and complication rates for children with papillary and/or macular retinoblastoma progressing after chemotherapy and undergoing stereotactic radiotherapy (SRT) with a micromultileaf collimator. METHODS AND MATERIALS: Between 2004 and 2008, 11 children (15 eyes) with macular and/or papillary retinoblastoma were treated with SRT. The mean age was 19 months (range, 2-111). Of the 15 eyes, 7, 6, and 2 were classified as International Classification of Intraocular Retinoblastoma Group B, C, and E, respectively. The delivered dose of SRT was 50.4 Gy in 28 fractions using a dedicated micromultileaf collimator linear accelerator. RESULTS: The median follow-up was 20 months (range, 13-39). Local control was achieved in 13 eyes (87%). The actuarial 1- and 2-year local control rates were both 82%. SRT was well tolerated. Late adverse events were reported in 4 patients. Of the 4 patients, 2 had developed focal microangiopathy 20 months after SRT; 1 had developed a transient recurrence of retinal detachment; and 1 had developed bilateral cataracts. No optic neuropathy was observed. CONCLUSIONS: Linear accelerator-based SRT for papillary and/or macular retinoblastoma in children resulted in excellent tumor control rates with acceptable toxicity. Additional research regarding SRT and its intrinsic organ-at-risk sparing capability is justified in the framework of prospective trials.

Modulation of the gap junction protein Connexin36 in neurons in a mouse model of transient focalcerebral ischemia

Intercellular communication is achieved at specialized regions of the plasma membrane by¦gap junctions. Gap junctions are transmembrane channels allowing direct contacts between¦the cytoplasms of neighboring cells. Each cell participates with one hemichannel, or¦connexon, made of six protein subunits named connexins. Thanks to these junctions, cells¦potentially share a pool of small molecules and metabolites, such as nucleotides, amino acids¦and second messengers.¦In an ischemic (i.e. non-perfused) territory of the brain, irreversible damage progresses over¦time from the centre of the most severe flow reduction to the periphery with less disturbed¦perfusion. Functionally impaired tissue can survive and recover if sufficient reperfusion is reestablished¦within a limited time period, which depends on various factors and mechanisms¦modulating the signaling pathways leading to cell death.¦Observations were made indicating the presence of electrical coupling between neurons which¦resist better to an ischemic insult. This electrical coupling is likely to be mediated by¦Connexin36 (Cx36), a neuron specific connexin isoform. It was demonstrated in the past that¦global ischemia induces a selective upregulation of Cx36 expression in regions with neurons¦that survive the insult whereas others undergo apoptosis and die. These observations raise the¦possibility that the neuronal gap junction Cx36 might play a role in the destiny of neurons¦after cerebral ischemia.¦The aim of this work was to characterize the regulation of Connexin36 in a mouse model of¦transient focal cerebral ischemia by immunofluorescence and Western blot analysis. Our¦immunofluorescence results suggest a specific increase in Cx36 in the penumbral region of¦the ischemic hemisphere.

Neuroimagen en epilepsia

El objetivo de este estudio es describir las alteraciones interictales de perfusión en RM por técnica de arterial spin labelled (ASL) y difusión, en pacientes con epilepsia focal y analizar su posible valor lateralizador/localizador del foco epileptógeno. Se trata de un estudio transversal de 53 pacientes adultos con epilepsia focal diagnosticados por semiología, RM y EEG. En todos ellos se realizó una RM de 3 TESLA con protocolo de epilepsia, que incluía secuencias de ASL. Las imágenes fueron sometidas a un análisis visual por un neurorradiólogo, clasificándolas en alteraciones de perfusión hemisféricas o focales. La muestra tenía un 51% de hombres y una edad media de 42.9 años (±16.5). El 60% tenían epilepsias sintomáticas. El 64% eran fármacorresistentes. Las etiologías más frecuentes fueron vascular (15%), malformaciones del desarrollo cortical (15%) y tumoral (13%). Un 45% se clasificaron como epilepsia temporal, 32% frontal y 13% temporal posterior, 8% occipital y 2% parietal. El 45% presentaban crisis parciales complejas, entre las que la semiología automotora era la más frecuente (36%). El ASL mostró, en un 74% de los pacientes, alteraciones de la perfusión interhemisféricas, observándose un valor lateralizador de éstas, especialmente cuando se observa hiperperfusión en la localización del foco y cuando se trata de epilepsia sintomática. Se observaron alteraciones focales en ASL que a pesar de encontrarse en un bajo porcentaje podrían tener valor localizador del área epileptógena.

Primer fármaco antiepiléptico: patrón de uso y efectividad

Estudiem el primer fàrmac antiepileptic utlitzat en 430 pacients amb epilèpsia, per valorar la seva taxa de retenció, efectivitat i tolerabilitat en el primer any de tractament. El 81% van rebre àcid valproic, carbamazepina o feintoina com primer tractament, tot i que l’ús de la fenitoina ha disminuit significativamen en els últims anys. La taxa de retenció annual és del 87%, sent més altes amb levetiracetam i lamotrigina. Un 40% van presentar recurrències en el primer any, sent major el risc en epilèpsia focal (48%). Els pacients tractats amb fenobarbital o fenitoina presentaven major freqüència d’efectes adversos (57 y 48%).

Lupus eritematoso túmido. Estudio clínico, microscópico y fotobiológico

Hem realitzat un estudi retrospectiu de les característiques de 25 pacients amb lupus eritematós túmid (LET) i hem dut a terme un estudi fotobiológic en 9 pacients. Resultats: tots els pacients presentaren les lesions característiques de LET. Només un 20% associaren ANA positius i tan sols un pacient anti Ro positius. Cap pacient presentà complicacions sistèmiques. El 40% de les biòpsies mostraren alteracions epidérmiques lleus, sent el més freqüent la vaquolització de la basal. Estudi fotobiológic: fou positiu en el 55’5% dels pacients, amb un 80% de lesions provocades per UVB. Conclusions: El LET és una variant de LEC amb unes característiques clíniques i evolutives particulars. Microscòpicament, la presència d’alteracions epidérmiques lleus és molt més habitual del que alguns treballs reflecteixen. La fotoprovocació fou positiva en un percentatge significatiu de casos, predominantment dins de l’espectre UVB.

Ultrastructural alterations in adult Schistosoma mansoni caused by artemether

Progress has been made over the last decade with the development and clinical use of artemether as an agent against major human schistosome parasites. The tegument has been identified as a key target of artemether, implying detailed studies on ultrastructural damage induced by this compound. We performed a temporal examination, employing a transmission electron microscope to assess the pattern and extent of ultrastructural alterations in adult Schistosoma mansoni harboured in mice treated with a single dose of 400 mg/kg artemether. Eight hours post-treatment, damage to the tegument and subtegumental structures was seen. Tegumental alterations reached a peak 3 days after treatment and were characterized by swelling, fusion of distal cytoplasma, focal lysis of the tegumental matrix and vacuolisation. Tubercles and sensory organelles frequently degenerated or collapsed. Typical features of subtegumental alterations, including muscle fibres, syncytium and parenchyma tissues, were focal or extensive lysis, vacuolisation and degeneration of mitochondria. Severe alterations were also observed in gut epithelial cells and vitelline cells of female worms. Our findings of artemether-induced ultrastructural alterations in adult S. mansoni confirm previous results obtained with juvenile S. mansoni and S. japonicum of different ages.

High-resolution selective three-dimensional magnetic resonance coronary angiography with navigator-echo technique: segment-by-segment evaluation of coronary artery stenosis.

PURPOSE: To investigate the feasibility of high-resolution selective three-dimensional (3D) magnetic resonance coronary angiography (MRCA) in the evaluation of coronary artery stenoses. MATERIALS AND METHODS: In 12 patients with coronary artery stenoses, MRCA of the coronary artery groups, including the coronary segments with stenoses of 50% or greater based on conventional x-ray coronary angiography (CAG), was performed with double-oblique imaging planes by orienting the 3D slab along the major axis of each right coronary artery-left circumflex artery (RCA-LCX) group and each left main trunk-left anterior descending artery (LMT-LAD) group. Ten RCA-LCX and five LMT-LAD MR angiograms were obtained, and the results were compared with those of conventional x-ray angiography. RESULTS: Among 70 coronary artery segments expected to be covered, a total of 49 (70%) segments were fully demonstrated in diagnostic quality. The identification of segmental location of stenoses showed as high an accuracy as 96%. The retrospective analysis for stenosis of 50% or greater yielded the sensitivity, specificity, and accuracy of 80%, 85%, and 84%, respectively. CONCLUSION: Selective 3D MRCA has the potential for segment-by-segment evaluation of major portions of the right and left coronary arteries with high accuracy.

Extra-cellular matrix changes in Schistosoma mansoni-infected Biomphalaria glabrata

Reactivity of snails against parasites exhibits a primitive focal reaction, with encapsulation, phagocytosis and destruction of parasite larvae by macrophage-like cells - the hemocytes. This reaction mimics granulomatous inflammation seen in higher animals. However, different from the latter, little is known about the participation of extra-cellular matrix in such snail defense reactions. Normal and Schistosoma mansoni-infected Biomphalaria glabrata of different strains were submitted to cytological, histological, ultrastructural and biochemical methods in order to investigate the behavior of extra-cellular tissues at the site of anti-parasite reactions. In spite of the presence of two cell-types in peripheral hemolymph, only one cell-type was present at the sites of tissue reactions. Although pre-existent collagen and elastic fibers and microfibrils sometimes appeared slightly compressed around focal reactions, no evidences of duplication, synthesis or deposition of connective-tissue extra-cellular components were observed within or around the zones of reactive cell accumulations. Thus, tissue reactions against S. mansoni in the snail B. glabrata appeared exclusively dependent on one specific population of hemocytes.

Reduction in the expression of glucose transporter protein GLUT 2 in preneoplastic and neoplastic hepatic lesions and reexpression of GLUT 1 in late stages of hepatocarcinogenesis.

Expression of two important glucose transporter proteins, GLUT 2 (which is the typical glucose transporter in hepatocytes of adult liver) and the erythroid/brain type glucose transporter GLUT 1 (representing the typical glucose transporter in fetal liver parenchyma), was studied immunocytochemically during hepatocarcinogenesis in rats at different time points between 7 and 65 wk after cessation of 7-wk administration of 12 mg/kg of body weight of N-nitrosomorpholine p.o. (stop model). Foci of altered hepatocytes excessively storing glycogen (GSF) and mixed cell foci (MCF) composed of both glycogenotic and glycogen-poor cells were present at all time points studied. Seven wk after withdrawal of the carcinogen, GSF were the predominant type of focus of altered hepatocytes. Morphometrical evaluation of the focal lesions revealed that the number and volume fraction of GSF increased steadily until Wk 65. MCF were rare at 7 wk, increased slightly in number and size until Wk 37, but showed a pronounced elevation in their number and volume fraction from Wk 37 to Wk 65. In both GSF and MCF, GLUT 2 was generally decreased or partially absent at all time points. Consequently, foci of decreased GLUT 2 expression showed a steady increase in number and volume fraction from Wk 7 to Wk 65. GLUT 1 was lacking in GSF but occurred in some MCF from Wk 50 onward. The liver type glucose transporter GLUT 2 was decreased in all adenomas and hepatocellular carcinomas (HCC). In three of seven adenomas and 10 of 12 carcinomas, expression of GLUT 1 was increased compared with normal liver parenchyma. In two cases of adenoid HCC, cells of ductular formations coexpressed GLUT 2 and GLUT 1. In contrast, normal bile ducts, bile duct proliferations, and cystic cholangiomas expressed only GLUT 1. Seven of 12 HCC contained many microvessels intensely stained for GLUT 1, a phenomenon never observed in normal liver. Whenever adenoid tumor formations occurred, GLUT 1-positive microvessels were located in the immediate vicinity of these formations. Only in one HCC were such microvessels found in the absence of adenoid formations. Our studies indicate that a reduction of GLUT 2 expression occurs already in early preneoplastic hepatic foci and is maintained throughout hepatocarcinogenesis, including benign and malignant neoplasms. Reexpression of GLUT 1, however, appears in a few MCF and in the majority of adenomas and carcinomas.