Oxidative stress and genotoxicity in Rhinella arenarum (Anura: Bufonidae) tadpoles after acute exposure to Ni-Al nanoceramics.

The employ of nanomaterials (NMs) has exponentially grown due to the large number of technological advances in industrial, pharmaceutical and medical areas. That is the case of alumina (Al) nanoparticles which are extensively employed as support in heterogeneous catalysis processes. However, these NMs can cause great toxicity because of their ubiquitous properties, such as extremely small size and high specific surface area. So, it is required to assess the potential deleterious effects of these NMs on living organisms. In the present study, we analyze the oxidative stress and genotoxic potential of a nanoceramic catalyst Ni/-Al2O3 (NC) and the NMs involved in their synthesis, -Al2O3 support (SPC) and NiO/-Al2O3 precursor (PC) on Rhinella arenarum larvae. Biomarkers of oxidative stress and genotoxic damage were measured in tadpoles exposed to 5 and 25 mg/L of each NMs for 96 h. The results indicated an inhibition of catalase activity in tadpoles exposed to both concentrations of PC and to 25 mg/L of SPC and NC. Moreover, both exposure concentrations of PC and NC significantly inhibited superoxide dismutase activity. Exposure to the three NMs caused inhibition of glutathione S-transferase activity, but there were no significant variations in reduced glutathione levels. Oxidative stress damage (lipid peroxidation) was observed in tadpoles treated with 25 mg/L PC, while the other treatments did not produce alterations. The MNs frequency significantly increased in larvae exposed to 25 mg/L PC indicating irreversible genotoxic damage. The results show that these NMs exert genotoxic effects and antioxidant defense system disruption in R. arenarum larvae.

Lethality, neurotoxicity, morphological, histological and cellular alterations of Ni-Al nanoceramics on the embryo-larval development of Rhinella arenarum.

Alumina nanoparticles (NP-Al2O3) are widely used but their environmental effects are unknown, so they can become potentially dangerous. The aim of this study was to evaluate the toxicity of a nanoceramic catalyst Ni/γ-Al2O3 (NC) and NPs involved in their synthesis, γ-Al2O3 support (SPC) and NiO/γ-Al2O3 precursor (PC) on Rhinella arenarum embryo-larval development. The NPs toxicity significantly increased over time obtaining a similar sensitivity to PC and NC (336 h-LC50 = 4.03 and 5.11 mg/L respectively) and very low sensitivity to SPC (336 h-LC50 = 90.83 mg/L). Embryos exposed to SPC and PC exhibited general underdevelopment, axial flexures and behavioral alterations. Pharyngeal and intestinal epithelia alterations at the level of cell surface as dissociation, apoptosis and numerous lysosomes were observed at light and transmission electronic microscopy. Images of scanning electron microscope with backscattered electron detector revealed the presence of nickel in the intestinal epithelium. The increased toxicity of PC could be due to the presence of Ni as oxide which could interfere with vital functions such as breathing and feeding. Taking into account the exponential production and use of these NPs it is expected that their pollution levels will considerably increase and amphibians will be more exposed and at higher risk.

In vitro study of antimicrobial and cell viability on newly synthesized bioglass-based bone grafts: Effects of selenium and silver additions.

Selenium (Se)- and Silver (Ag)-doped Bioglass®-based biografts were synthesized using the sol-gel method. Fourier-transform infrared spectroscopy, inductively coupled plasma mass spectrometry, scanning electron microscopy and energy-dispersive X-ray analyses were carried out in order to examine mechanostructure of synthesized bioglass-based bioceramics. The effects of Se and Ag additions on cell viability were investigated via cytotoxicity and antibacterial activity analysis, respectively. The bacteria of Escherichia coli ( E. coli, JM103) and Gram-positive Staphylococcus aureus ( S. aureus, ATCC29293) were used to perform the antibacterial tests. Moreover, cell viability studies were conducted using the Saos-2 osteoblast cells by performing dimethylthiazol diphenyltetrazolium bromide assay. It was observed that while (PO4)3- and (CO3)2- peaks were observed in Fourier-transform infrared spectroscopy analyses, crystallinity also increased with increasing amount of AgNO3 addition into the Bioglass®. In addition, it was determined from scanning electron microscopy images that small irregular thin lamellar grain distribution was formed in synthesized B45Ag5Se20 and B30Ag10Se15 biografts. From antibacterial activity tests, it was determined that while some grafts was affected by E. coli, which is a Gram-negative, however, some did not affect the Gram-positive S. aureus and had antimicrobial activity on E. coli and S. aureus. According to the cell viability tests, it was found that the synthesized grafts did not have toxic effect on living cells. While the cell growth was greater for some grafts, however, some others had lower growth.

Engulfment of ceramic particles by fibroblasts does not alter cell behavior.

Despite many studies, the impact of ceramic particles on cell behavior remains unclear. The aim of the present study was to investigate the effects of nano-sized ceramic particles on fibroblastic cells. Fibroblasts (dermal fibroblasts freshly isolated from skin samples and WI26 fibroblastic cells) were cultured in a monolayer in the presence of alumina or cerium-zirconia particles (≈50 nm diameter) at two concentrations (100 or 500 µg ml-1). Fluorescent alumina particles were also used. The following properties were analyzed: cell morphology, cytoplasmic ceramic incorporation (using confocal and transmission electron microscopy) and migration (using a silicon insert). Sedimentation field-flow fractionation (SdFFF) was also used to evaluate the rate of incorporation of ceramic particles into the cells. Finally, after treatment with various concentrations of ceramic particles, fibroblasts were also included in a collagen type I lattice constituting a dermal equivalent (DE), and the collagen lattice retraction and cell proliferation were evaluated. In monolayer conditions, the presence of both alumina and cerium-zirconia ceramic particles did not cause any deleterious effects on cultured cells (dermal fibroblast and WI26 cells) and cell fate was not affected in any way by the presence of ceramic particles in the cytoplasm. Confocal (using fluorescent alumina particles) and electron microscopy (using both alumina and cerium-zirconia particles) showed that ceramic particles were internalized in the WI26 cells. Using fluorescent membrane labeling and fluorescent alumina particles, a membrane was observed around the particle-containing vesicles present in the cytoplasm. Electron microscopy on WI26 cells showed the presence of a classical bilayer membrane around the ceramic particles. Interestingly, SdFFF confirmed that some dermal fibroblasts contained many alumina ceramic particles while others contained very few; in WI26 cells, the uptake of alumina ceramic was more homogeneous. In DE, collagen lattice retraction and cell proliferation were unchanged when WI26 fibroblastic cells contained alumina or cerium-zirconia ceramic particles. Our data suggest that ceramic particles are internalized in the cells by endocytosis. The presence of ceramic particles in the cytoplasm has no affect on cell behavior, confirming the excellent biocompatibility of this material and anticipating a minimal harmful effect of potential wear debris.

"False" cytotoxicity of ions-adsorbing hydroxyapatite - Corrected method of cytotoxicity evaluation for ceramics of high specific surface area.

An assessment of biomaterial cytotoxicity is a prerequisite for evaluation of its clinical potential. A material is considered toxic while the cell viability decreases under 70% of the control. However, extracts of certain materials are likely to reduce the cell viability due to the intense ions adsorption from culture medium (e.g. highly bioactive ceramics of high surface area). Thus, the standard ISO 10993-5 procedure is inappropriate for cytotoxicity evaluation of ceramics of high specific surface area because biomaterial extract obtained in this method (ions-depleted medium) is not optimal for cell cultures per se. Therefore, a simple test was designed as an alternative to ISO 10993-5 standard for cytotoxicity evaluation of the biomaterials of high surface area and high ions absorption capacity. The method, presented in this paper, included the evaluation of ceramics extract prepared according to corrected procedure. The corrected extract was found not cytotoxic (cell viability above 70%), suggesting that modified method for cytotoxicity evaluation of ions-adsorbing ceramics is more appropriate than ISO 10993-5 standard. For such biomaterials, the term "false" cytotoxicity is more suitable. Moreover, it was noted that NRU assay and microscopic observations should be recommended for cytotoxicity evaluation of ceramics of high surface area.

Evaluation of Soft Tissue Reaction to Corundum Ceramic Implants Infiltrated with Colloidal Silver.

BACKGROUND: Corundum ceramic is a biomaterial used as a bone graft substitute. Silver is a well known antiseptic substance with many practical, clinical applications. OBJECTIVES: The aim of this study was to estimate soft tissue (in vivo) reaction to a new kind of ceramic implants. In our experiment, we examined the soft tissue reaction after implantation of corundum ceramic infiltrated with colloidal silver in the back muscles of 18 Wistar rats. The use of colloidal silver as a coating for the implant was designed to protect it against colonization by bacteria and the formation of bacterial biofilm. MATERIAL AND METHODS: In our study, based on the experimental method, we performed implantation operations on 18 Wistar rats. We implanted 18 modified ceramic implants and, as a control group, 18 unmodified implants. As a follow up, we observed the animals operated upon, and did postoperative, autopsy and histopathological examinations 14, 30, 90 and 180 days after implantation. RESULTS: We didn't observe any pathological reactions and significant differences between the soft tissue reaction to the modified implants and the control group. CONCLUSIONS: Lack of pathological reaction to the modified implants in the living organism is the proof of their biocompatibility. This is, of course, the first step on the long path to introduce a new kind of biocompatible ceramic implant with antiseptic cottage. Our experiment has an only introductory character and we plan to perform other, more specific, tests of this new kind of implant.

Ceramic nanoparticles: Recompense, cellular uptake and toxicity concerns.

Over the past few years, nanoparticles and their role in drug delivery have been the centre of attraction as new drug delivery systems. Various forms of nanosystems have been designed, such as nanoclays, scaffolds and nanotubes, having numerous applications in areas such as drug loading, target cell uptake, bioassay and imaging. The present study discusses various types of nanoparticles, with special emphasis on ceramic nanocarriers. Ceramic materials have high mechanical strength, good body response and low or non-existing biodegradability. In this article, the various aspects concerning ceramic nanoparticles, such as their advantages over other systems, their cellular uptake and toxicity concerns are discussed in detail.

Cytotoxicity of 45S5 bioglass paste used for dentine hypersensitivity treatment.

OBJECTIVES: 45S5 bioglass mixed with 50% phosphoric acid has been suggested to treat dentine hypersensitivity and incipient enamel caries. This study is going to evaluate the biocompatibility of using the aforementioned technique with the rat pulpal cells. METHODS: The relative cytotoxicity of 45S5 bioglass on rat dental pulp cells was compared to the cytotoxicity of a temporary filling material (Caviton; GC, Japan), Type 1 glass ionomer cement (Fuji I; GC, Tokyo, Japan) and commercial desensitising agent (SuperSeal; Phoenix Dental, Fenton, MI, USA) using a transwell insert model. Cell viability was measured by means of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The number of viable cell counts were compared using one way ANOVA (p<0.05). The morphological alterations of the pulp cells were observed directly by phase contrast microscope. RESULTS: The results of this study indicated that cell viability recorded by the 45S5 bioglass paste group did not differ significantly from those of the Caviton, glass ionomer or superseal, moreover pulpal cells microscopic analysis revealed that 45S5 bioglass elicited minimal toxic effect. CONCLUSIONS: 45S5 bioglass paste can serve as a biocompatible material that can potentially be used safely on dentine.

In-vitro study of cellular viability and nitric oxide production by J774 macrophages stimulated by interferon gamma with ceramic, polycarbonate, and polyoxymethylene brackets.

INTRODUCTION: Ceramic brackets are chemically inert in the oral cavity, whereas polycarbonate and polyoxymethylene brackets can degrade and release bisphenol-A and formaldehyde, respectively. More reliable tests are needed to assess the potential toxicity of these materials. In addition to traditional cytotoxicity tests, the study of nitric oxide (NO) cellular production stimulated by a specific material has been shown to be a reliable tool for evaluating cytotoxic potential. The purpose of this study was to assess, with esthetic brackets, cellular viability by 3,(4,5-dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide assay (Sigma, St. Louis, Mo) in the macrophage cell line J774 stimulated with interferon gamma. Interferon gamma is a key cytokine in the activation of macrophages, plays an important role in immunologic processes, and also quantifies NO production by these macrophages. METHODS: Well plates were seeded with 2 x 104 J774 cells per well, in a volume of 100 microL, resuspended in Roswell Park Memorial Institute Supplemented Medium 1640. The macrophage cell line J774 was stimulated with interferon gamma. Ceramic, polycarbonate, and polyoxymethylene brackets were added and kept in the culture for 24, 48, or 72 hours in 5% carbon dioxide at 37 degrees C; the control samples did not include brackets. At the end of each incubation period, the supernatant was collected for posterior NO quantification, and the cells were evaluated for cytotoxicity. RESULTS: Cellular viability in all groups was higher at 72 hours than at 24 hours. The final means in the bracket groups did not show significant differences compared with the control group. NO production was significantly greater in all groups at the final time than at the initial time. However, the brackets with the interferon gamma stimulation did not result in greater NO production than did the cells in the control group.

Biosilicate ototoxicity and vestibulotoxicity evaluation in guinea-pigs.

UNLABELLED: Changes, destructions and interruptions in middle ear ossicular chain architecture may be caused by infection, trauma, tumors, congenital alterations or prior surgeries. Nonetheless, infectious and inflammatory processes, focal or generalized which affect the middle ear are the most prevalent, causing a great demand for ossiculoplasty. Biosilicato is a new material which can be used in the middle ear with the goal of reconstructing the ossicular chain. It is a bioactive type A vitroceramic, in other words, it binds to bone or soft tissue in a matter of a few hours, thanks to the formation of hydroxy-carbonateapatatie in its contact surface when in contact with body fluids. AIMS: The goal of the present paper is to assess biosilicate ototoxicity and vestibular toxicity in experimental animals, for later use in humans. MATERIALS AND METHODS: This a clinical and experimental study in which otoacoustic emissions were performed before and after the placement of Biosilicate in the middle ear of experimental animals and a scanning electron microscopy was carried out in the cochlea, saccule, utriculus and macula of the semicircular canals after 30 and 90 days to assess oto and vestibular toxicity. RESULTS: There were no signs of oto or vestibular toxicity in any of the groups associated with biosilicate. CONCLUSION: Biosilicate is a safe material to be used in ossiculoplasties.

Development of a new zirconia-toughened alumina: promising mechanical properties and absence of in vitro carcinogenicity.

High purity alumina as well as zirconia ceramics have been widely used as orthopaedic implant biomaterials and dental devices displaying optimal, but sometimes exclusive, mechanical properties. In order to combine the advantages of alumina and zirconia ceramic materials different types of composites have been developed in which either zirconia is dispersed in an alumina matrix or vice versa. Orthopaedic and dental implant biomaterials are expected to be in contact with living tissues for a long period of time and their long term toxicity must be carefully evaluated. In this study we report the development of a high performance chromia-doped zirconia toughened alumina (ZTA) material which displays promising mechanical properties in terms of hardness, strength and fracture toughness that make it suitable for prosthesis even for small joints. The long-term biocompatibility of this material was also evaluated, mainly in terms of DNA damage, mutagenicity and cancerogenetic potential in mammalian cells. The results obtained suggest that this new ZTA material does not display any longterm carcinogenic effect and it is suitable for biomedical applications from a cancerogenetic point of view. In conclusion, we report the development of a new chromia-doped ZTA material with interesting properties, both from a mechanical and a biocompatibility point of view which warrant further studies on its suitability as a candidate biomaterial for orthopaedic implants and dental devices.

Biosilicate® Ototoxicity and Vestibulotoxicity evaluation in guinea-pigs / Avaliação da ototoxicidade e vestibulotoxicidade do biosilicato® em orelhas de cobaias

Changes, destructions and interruptions in middle ear ossicular chain architecture may be caused by infection, trauma, tumors, congenital alterations or prior surgeries. Nonetheless, infectious and inflammatory processes, focal or generalized which affect the middle ear are the most prevalent, causing a great demand for ossiculoplasty. Biosilicato® is a new material which can be used in the middle ear with the goal of reconstructing the ossicular chain. It is a bioactive type A vitroceramic, in other words, it binds to bone or soft tissue in a matter of a few hours, thanks to the formation of hydroxy-carbonateapatatie in its contact surface when in contact with body fluids. AIMS: The goal of the present paper is to assess biosilicate ototoxicity and vestibular toxicity in experimental animals, for later use in humans. MATERIALS AND METHODS: This a clinical and experimental study in which otoacoustic emissions were performed before and after the placement of Biosilicate in the middle ear of experimental animals and a scanning electron microscopy was carried out in the cochlea, saccule, utriculus and macula of the semicircular canals after 30 and 90 days to assess oto and vestibular toxicity. RESULTS: There were no signs of oto or vestibular toxicity in any of the groups associated with biosilicate. CONCLUSION: Biosilicate is a safe material to be used in ossiculoplasties

As alterações, destruições e interrupções da arquitetura da cadeia ossicular da orelha média podem ser causadas por infecções, trauma, tumores, alterações congênitas ou cirurgias prévias. Entretanto os processos inflamatórios e infecciosos, focais ou generalizados que acometem a orelha média são os mais prevalentes, gerando uma enorme demanda de ossiculoplastias. O Biosilicato® é um novo material que pode ser usado em orelhas médias com o objetivo de reconstruir a cadeia ossicular. Constitui-se de uma vitrocerâmica bioativa do tipo A, ou seja, que se liga a tecido ósseo ou a tecido mole em algumas horas, devido à formação de hidroxicarbonatoapatita em sua superfície de contato quando em contato com fluidos corpóreos. OBJETIVO: O objetivo deste trabalho é avaliar a ototoxicidade e vestibulotoxicidade do Biosilicato em cobaias, para posterior utilização em humanos. MATERIAL E MÉTODO: Trata-se de um estudo clínico e experimental, onde foram realizadas emissões otoacústicas antes e após a colocação de Biosilicato na orelha média de cobaias e realizada microscopia eletrônica de varredura da cóclea, sáculo, utrículo e máculas dos canais semicirculares após 30 e 90 dias para avaliar a oto e vestibulotoxicidade. RESULTADOS: Não houve sinais de oto ou vestibulotoxicidade em nenhum dos grupos relacionados ao Biosilicato. CONCLUSÃO: O Biosilicato é um material seguro para ser usado em ossiculoplastias.

Clinico-pathological features and somatic gene alterations in refractory ceramic fibre-induced murine mesothelioma reveal mineral fibre-induced mesothelioma identities.

Although human malignant mesothelioma (HMM) is mainly caused by asbestos exposure, refractory ceramic fibres (RCFs) have been classified as possibly carcinogenic to humans on the basis of their biological effects in rodents' lung and pleura and in cultured cells. Hence, further investigations are needed to clarify the mechanism of fibre-induced carcinogenicity and to prevent use of harmful particles. In a previous study, mesotheliomas were found in hemizygous Nf2 (Nf2(+/-)) mice exposed to asbestos fibres, and showed similar alterations in genes at the Ink4 locus and in Trp53 as described in HMM. Here we found that Nf2(+/-) mice developed mesotheliomas after intra-peritoneal inoculation of a RCF sample (RCF1). Clinical features in exposed mice were similar to those observed in HMM, showing association between ascite and mesothelioma. Early passages of 12 mesothelioma cell cultures from ascites developed in RCF1-exposed Nf2(+/-) mice demonstrated frequent inactivation by deletion of genes at the Ink4 locus, and low rate of Trp53 point and insertion mutations. Nf2 gene was inactivated in all cultures. In most cases, co-inactivation of genes at the Ink4 locus and Nf2 was found and, at a lower rate, of Trp53 and Nf2. These results are the first to identify mutations in RCF-induced mesothelioma. They suggest that nf2 mutation is complementary of p15(Ink4b), p16(Ink4a) and p19(Arf) or p53 mutations and show similar profile of gene alterations resulting from exposure to ceramic or asbestos fibres in Nf2(+/-) mice, also consistent with the one found in HMM. These somatic genetic changes define different pathways of mesothelial cell transformation.

Exposure to carcinogens for defined job categories in Norway's offshore petroleum industry, 1970 to 2005.

OBJECTIVES: To identify and describe the exposure to selected known and suspected carcinogenic agents, mixtures and exposure circumstances for defined job categories in Norway's offshore petroleum industry from 1970 to 2005, in order to provide exposure information for a planned cohort study on cancer. METHODS: Background information on possible exposure was obtained through company visits, including interviewing key personnel (n = 83) and collecting monitoring reports (n = 118) and other relevant documents (n = 329). On the basis of a previous questionnaire administered to present and former offshore employees in 1998, 27 job categories were defined. RESULTS: This study indicated possible exposure to 18 known and suspected carcinogenic agents, mixtures or exposure circumstances. Monitoring reports were obtained on seven agents (benzene, mineral oil mist and vapour, respirable and total dust, asbestos fibres, refractory ceramic fibres, formaldehyde and tetrachloroethylene). The mean exposure level of 367 personal samples of benzene was 0.037 ppm (range: less than the limit of detection to 2.6 ppm). Asbestos fibres were detected (0.03 fibres/cm3) when asbestos-containing brake bands were used in drilling draw work in 1988. Personal samples of formaldehyde in the process area ranged from 0.06 to 0.29 mg/m3. Descriptions of products containing known and suspected carcinogens, exposure sources and processes were extracted from the collected documentation and the interviews of key personnel. CONCLUSIONS: This study described exposure to 18 known and suspected carcinogenic agents, mixtures and exposure circumstances for 27 job categories in Norway's offshore petroleum industry. For a planned cohort study on cancer, quantitative estimates of exposure to benzene, and mineral oil mist and vapour might be developed. For the other agents, information in the present study can be used for further assessment of exposure, for instance, by expert judgement. More systematic exposure surveillance is needed in this industry. For future studies, new monitoring programmes need to be implemented.

Horizontal diffusion elutriation: a new size-separation technique for preparation of rodent-respirable fibers for animal testing.

Short-and long-term animal experiments are used to examine the toxicology and biopersistence of various types of fibers. In order to ensure an adequate exposure dose for testing, modern experimental protocols specify that the exposure aerosol (in an inhalation test) or the fibers (in an intratracheal instillation [IT] test) must contain at least a minimum concentration of long (> 20 mum) rodent-respirable fibers. As produced and handled, most fibers contain a distribution of diameters and lengths, only some of which are both long and rodent-respirable. Therefore, it is necessary to size-separate the fibers to enrich the proportion of long, rodent-respirable fibers in the material to be tested. This article presents a new and relatively simple method for size separation that avoids some of the difficulties associated with other methods. The method, termed horizontal diffusion elutriation (HDE), is illustrated by size-separating refractory ceramic fiber (RCF) and four polycrystalline alumina (PCA) fibers.

[Biomaterial studies in cultures of human stapedial bone-like cells]. / Untersuchung unterschiedlicher Biomaterialien in einer Knochenzellkultur des menschlichen Steigbügels.

BACKGROUND: Cell culture studies may provide information on the behavior of biomaterials in the intended implant environment. Cell cultures from such an environment could be used for the development of middle ear implants. MATERIAL AND METHODS: Secondary bone-like cell cultures derived from human stapes were exposed to different materials [Al(2)O(3) ceramic, glass ceramic (Ceravital), gold and titanium]. Proliferation was studied for up to 40 days. RESULTS: The proliferation of cultured stapes bone-like cells did not differ significantly between the four tested biomaterials. The well known cytotoxic effect of copper, which was used as a control, was evident. CONCLUSIONS: Four biomaterials [Al(2)O(3) ceramic, glass ceramic (Ceravital), gold and titanium] have similar biocompatibility and no toxicity when tested in human stapes cell cultures. This in vitro model may be of considerable value for the further development of middle ear implants, e.g., when coated with bone morphogenetic proteins.

Combined exchange transfusion and chelation therapy for neonatal lead poisoning.

OBJECTIVE: To describe the results of combined exchange transfusion and chelation therapy in a neonate with an elevated blood lead level (BLL). CASE SUMMARY: A 34-year-old Latina woman with a long history of pica (eating glazed pottery) gave birth to a healthy-appearing girl at 40 weeks of gestation. The mother's preconception BLL was 117 microg/dL and remained elevated throughout pregnancy. At parturition, the mother's BLL was 87 microg/dL and the infant's cord BLL was 100 microg/dL. The infant underwent single-volume exchange transfusion within 12 hours of birth. BLL was 28 microg/dL following the exchange, and a 5-day course of chelation with dimercaprol and CaNa2 ethylenediamine tetraacetic acid was initiated at 36 hours of life. The infant's BLL was 37 microg/dL at the end of inpatient chelation. DISCUSSION: Long-term neurologic disability from in utero lead exposure is well described, but the optimal treatment of elevated neonatal BLLs in healthy-appearing infants at the time of birth is not established. This strategy of combined chelation and exchange transfusion therapy was well tolerated and resulted in decreased lead levels, but the long-term neurologic efficacy of our combination strategy remains to be seen. CONCLUSIONS: Combined exchange transfusion and chelation therapy resulted in rapidly decreased lead levels in a neonate with chronic in utero lead exposure.

Subcutaneous inflammatory reaction to a synthetic auditory ossicle (Bioceram) in rats.

Cellular response and inflammatory reaction to synthetic auditory ossicle (Bioceram) made from aluminium oxide are investigated. Local inflammatory effects are important in wound healing and in determining biocompatibility of an implant, necessitating the study of biologic effects of implants, especially inflammation and fibrous capsule formation. Bioceram discs were implanted subcutaneously in the interscapular region of rats for various periods of time, ranging from 1 day to 300 days. Histological sections 6 microns thick were stained with haematoxylin and eosin. Cell types around the implants were examined quantitatively by light microscopy. Inflammatory cell reaction to Bioceram decreased rapidly within 14 days, similar to the reaction in control groups. From 30 days to 300 days after implantation, there was continuous reduction to very low levels for macrophages and lymphocytes, but fibrous connective tissue capsule around implants matured. Preliminary results suggest that Bioceram is a satisfactory biocompatible material for reconstructive surgery from the viewpoint of cellular response. We also briefly discuss the different tissue responses in light of our previous study on hydroxyapatite (Apaceram).

Comparison of biocompatibility of gel-derived bioactive ceramics in macrophage culture conditions.

The behaviour of rat alveolar macrophages cultured in the presence of three new gel-derived ceramic biomaterials (CaO-P2O5-SiO2 system) with slightly different chemical compositions was examined. The abilities of these three materials to stimulate alveolar macrophages were compared. Non-treated and lipopolysaccharide-treated macrophages were used as control. The level of macrophage activation was determined by nitrite and prostaglandin E2 assay and respiratory burst measurement by chemiluminescence. The results of these studies showed different macrophage responses to these three relatively similar stimuli. Two of the studied materials were shown to be potent activators of respiratory burst and prostaglandin E2 secretion without any significant release of nitric oxide. On the contrary, the material characterized as the most surface reactive strongly affected only nitric oxide generation by the cells.

Biological activity of respirable industrial fibres treated to mimic residence in the lung.

The durability of fibres in the lung environment after deposition could be a key factor in determining whether they accumulate to a sufficient tissue dose to cause pathological change. There is a shortage of information on the relative durabilities of respirable industrial fibres of various types. We describe a strategy for assessing the ability of different fibre types to persist in the lung milieu and to retain their biological activity. This is particularly important for the development of mesothelioma, where the long latent time that characterises this disease would be expected to exclude, from culpability, fibres that are not durable. We have combined a pre-treatment step in pH 5.0 or 7.0 with an assay that relies on the ability of fibres to damage the mesothelium. The long-term aim is to assess the impact that treatment in various pH solutions has on (a) fibre size/number, (b) loss of key elements, (c) the ability to damage the mesothelium. Such information should enable us to better predict the potential of fibres to cause mesothelioma.