Are non-indigenous species hitchhiking offshore farmed mussels? A biogeographic and functional approach.

The epifauna associated to farmed mussels in southern Portugal coast was analysed, aiming at identifying the species with spreading potential through commercial transport. The presence of a relevant number of the species here found is not reported to at least one of the common mussel export/transposition countries. Indeed, important species biogeographic dissimilarities between the mussel farm area and the Greater North Sea and Western Mediterranean Sea sub-regions were detected, suggesting the potential transport of non-indigenous species (NIS) into other countries. Among them, fouling species such as the anemones Paractinia striata and Urticina felina, the acorn barnacles Balanus glandula and Balanus trigonus or the bryozoans Bugulina stolonifera and Schizoporella errata exhibit functional attributes that allow them to colonise and spread in new areas. This combined biogeographic and functional approach may contribute to clarify the role of aquaculture on the transport of NIS and to predict and prevent their spreading worldwide.

Unilateral accumbal dopamine depletion affects decision-making in a side-specific manner.

Mechanisms underlying affective and cognitive deficits in Parkinson's disease (PD) remain less studied than motor symptoms. Nucleus accumbens (NAc) is affected in PD and due to its well-known involvement in motivation is an interesting target in this context. Furthermore, PD is frequently asymmetrical, with side-specific deficits aligning with evidences of accumbal laterality. We therefore used a 6-hydroxydopamine (6-OHDA) model to study the role of left and right NAc dopamine depletion in a battery of behavioral tasks. 2 months old male rats were used in all experiments. Habitual-based and goal-directed decision-making, impulsivity, anxiety- and depressive-like behavior and motor performance were tested 3 weeks after left (6-OHDA L) or right (6-OHDA R) NAc lesion was induced. Upon contingency degradation, 6-OHDA R decrease their lever press rate less than Sham and 6-OHDA L, indicating an impairment in the shift from habit-based to goal-directed strategies. On the other hand, 6-OHDA L lesions lead to increased rates of premature responding when delays where increased in the variable delay-to-signal test. Importantly, in both paradigms task acquisition was similar between groups. In the same line we found no differences in the amount of sugared pellets eaten when freely available as well as in both general and fine motor behaviors. In conclusion, left and right NAc play distinct roles in the contingency degradation and impulsivity. More studies are needed to understand the mechanisms behind this functional lateralization and its implications for PD patients.

Hypoglycemic activity of dried extracts of Bauhinia forficata Link.

Leaves of the pantropical genus Bauhinia (Fabaceae) are known popularly as cow's foot, due to their unique characteristic bilobed aspect. The species Bauhinia forficata (Brazilian Orchid-tree) is widely used in folk medicine as an antidiabetic. The present work investigates the hypoglycemic activity of the dried extracts of Bauhinia forficata leaves in vivo, as well as the influence of the drying and granulation processes on this activity. The fluid extract was dried to generate oven-dried (ODE), spray-dried (SDE) and wet granulation (WGE) extracts, with the aid of colloidal silicon dioxide and/or cellulose:lactose mixture. The dried extracts were characterized by spectrophotometric, chromatographic and photo microscopy image analysis. 200 mg/kg body wt., p.o. of each dried product were administered orally to male Wistar rats over 7 days old, for biomonitoring of the hypoglycemic activity profile. The effect of the extracts was studied in STZ-induced diabetic rats. After 7 days of treatment, fasting glucose was determined, and the livers were removed, dried on tissue paper, weighed, and stored at -20 degrees C to estimate hepatic glycogen. Our results show that spray-drying or oven-drying processes applied to B. forficata extracts did not significantly alter its flavonoid profile or its hypoglycemic activity. Indeed, the dried extracts of B. forficata act differently from glibenclamide. Despite the lower active content in WGE, because of the higher concentration of adjuvants, the use of the granulation process improved the manufacturing properties of the ODE, making this material more appropriate for use in tablets or capsules.

Effects of lopinavir-ritonavir combined therapy during the rat pregnancy. Morphological and biochemical aspects.

OBJECTIVE: To evaluate the biochemical and morphological effects in rats subjected to three different dose associations of the protease inhibitors lopinavir and ritonavir administered throughout the entire period of pregnancy. STUDY DESIGN: The animals were treated throughout pregnancy with daily oral doses of lopinavir+ritonavir starting at the day one of pregnancy, and were divided into four groups: E1, 13.3+3.3 mg/kg; E2, 39.9+9.9 mg/kg; E3, 119.7+29.9 mg/kg and C, control (drug vehicle, propyleneglycol). The animals were then sacrificed and maternal blood and fetal and maternal organ samples were taken for morphological and biochemical analysis. RESULTS: No major changes were identified in the group treated with the lowest dose as compared with the control. In the group E2, we found hepatocytes with signs of atrophy, eosinophilic cytoplasm, picnotic nuclei and vasodilatation. The proximal convoluted tubules of maternal kidneys showed eosinophilic areas and hyperchromatic nuclei, as well as signs of vasodilation. In the group treated with the highest dose (group E3), in the maternal kidneys and livers, the morphological changes were similar to those found in E2, although more prominent. Regarding the fetal organs, the single abnormality observed was some liver vasodilation in the group E3 (highest dose). The treatment with lopinavir+ritonavir caused discrete, yet significant, alterations of aspartate aminotransferase activity, blood urea nitrogen and creatinine plasma levels. CONCLUSIONS: Our results showed that the administration of a combination of lopinavir plus ritonavir to pregnant rats can cause morphological as well as functional changes in maternal and fetal liver and kidneys and, in higher than therapeutic doses, might be toxic to those animals.

Perfil de isolamento microbiano em cães com otite média e externa associadas / Profile of microorganisms isolated from dogs with associated media and extern otitis

Comparou-se o perfil de isolamento microbiano de amostras coletadas de cães com otite média (OM) e externa (OE) associadas. Sessenta e quatro cães com otite média e externa foram avaliados durante 10 meses. Amostras dos condutos auditivos externos foram coletadas com auxílio de swabs estéreis e aquelas do ouvido médio pela técnica cirúrgica da osteotomia da bula timpânica. Os microrganismos foram cultivados e identificados de acordo com os métodos previamente descritos, e a susceptibilidade a antimicrobianos avaliada pelo método de difusão em ágar estabelecido pelo National Committee for Clinical Laboratory Standards. Bactérias anaeróbias estritas não foram isoladas em qualquer amostra. Todas as amostras de OE mostraram crescimento bacteriano e/ou fúngico. Na OM, a positividade nas culturas foi de 48 por cento. Os microrganismos mais isolados na OE foram: Bacillus sp. (26,9 por cento), M. pachydermatis (22,2 por cento) e S. intermedius (21,7 por cento); na OM foram: S. intermedius (32,5 por cento), S. aureus subsp. aureus (22,5 por cento) e bacilos Gram-negativos não fermentadores (10,0 por cento). Observou-se alguma diferença no perfil de isolamento entre os quadros de OM e OE em 96,7 por cento dos animais. Verificou-se elevada resistência de cepas de S. intermedius à penicilina G, ampicilina, eritromicina, tetraciclina e clindamicina.

The isolation pattern of samples collected from dogs with both media (OM) and extern otitis (OE) was compared. Sixty-four dogs suffering from those conditions were studied over a 10-month period. Samples from the external ear were collected with sterile swabs while those from the middle ear were collected by osteotomy of the tympanic bulla. The microorganisms were cultured and identified according to methods previously described and to the susceptibility of antimicrobials according to the National Committee for Clinical Laboratory Standards agar diffusion test. Anaerobic bacteria were not isolated in any sample. All samples from OE showed bacterial and/or fungal growth. Concerning media otitis, this percentage was 48 percent. The most common microorganisms isolated from OE were Bacillus sp. (26.9 percent), M. pachydermatis (22.2 percent) and S. intermedius (21.7 percent) and those from OM were S. intermedius (32.5 percent), S. aureus subsp. aureus (22.5 percent) and non-fermentative Gram-negative rods (10.0 percent). Some difference was observed in the isolation pattern between media and extern otitis in 96.7 percent of the animals. High resistance rates of S. intermedius strains to penicillin G, ampicillin, erythromycin, tetracycline and clindamycin were found.

Increasing seroprevalence of human herpesvirus 8 (HHV-8) with age confirms HHV-8 endemicity in Amazon Amerindians from Brazil.

Human herpesvirus 8 (HHV-8) seroprevalences were determined in two isolated Amazon Amerindian tribes, according to age, gender and familial aggregation. Plasma and serum samples obtained from 982 Amazon Amerindians (664 Tiriyó and 318 Waiampi) were tested for antibodies against lytic and latent HHV-8 antigens by using 'in-house' immunofluorescence assays. Overall, HHV-8 seroprevalence was 56.8 % (57.4 % in the Tiriyó tribe and 55.7 % in the Waiampi tribe). Seroprevalence was independent of gender and increased linearly with age: it was 35.0 % among children aged 2-9 years, 51.4 % in adolescents (10-19 years), 72.9 % in adults and 82.3 % in adults aged >50 years. Interestingly, 44.4 % of children under 2 years of age were HHV-8-seropositive. No significant differences in seroprevalence between tribes and age groups were detected. It is concluded that HHV-8 is hyperendemic in Brazilian Amazon Amerindians, with vertical and horizontal transmission during childhood, familial transmission and sexual contact in adulthood contributing to this high prevalence in these isolated populations.

Casein and soybean protein-based thermoplastics and composites as alternative biodegradable polymers for biomedical applications.

This work reports on the development and characterization of novel meltable polymers and composites based on casein and soybean proteins. The effects of inert (Al(2)O(3)) and bioactive (tricalcium phosphate) ceramic reinforcements over the mechanical performance, water absorption, and bioactivity behavior of the injection-molded thermoplastics were examined. It was possible to obtain materials and composites with a range of mechanical properties, which might allow for their application in the biomedical field. The incorporation of tricalcium phosphate into the soybean thermoplastic decreased its mechanical properties but lead to the nucleation of a bioactive calcium-phosphate film on their surface when immersed in a simulated body fluid solution. When compounded with 1% of a zirconate coupling agent, the nucleation and growth of the bioactive films on the surface of the referred to composites was accelerated. The materials degradation was studied for ageing periods up to 60 days in an isotonic saline solution. Both water uptake and weight loss were monitored as a function of the immersion time. After 1 month of immersion, the materials showed signal of chemical degradation, presenting weight losses up to 30%. However, further improvement on the mechanical performance and the enhancement of the hydrolytic stability of those materials will be highly necessary for applications in the biomedical field.

Coupling of HDPE/hydroxyapatite composites by silane-based methodologies.

Several coupling treatments based on silane chemicals were investigated for the development of high density (HDPE)/hydroxyapatite (HA) composites. Two HA powders, sintered HA (HAs) and non sintered HA (HAns), were studied in combination with five silanes, namely y-methacryloxy propyltrimethoxy silane (MEMO), 3-(2-aminoethyl)aminopropyltrimethoxy silane (DAMO), vinyltrimethoxy silane (VTMO), 3-aminopropyltriethoxy silane (AMEO) and trimethoxypropyl silane (PTMO). The HA particles were treated by a dipping in method or by spraying with silane solutions. After drying, the treated powders were compounded with HDPE or HDPE with acrylic acid and/or organic peroxide and subsequently compression molded. The tensile test specimens obtained from the molded plates were tensile tested and their fracture surfaces were observed by scanning electron microscopy (SEM). For the sintered HA (HAs) composites, the most effective coupling treatments concerning stiffness are those based on MEMO and AMEO. The low influence of these coupling procedures on strength is believed to be associated to the low volume fraction and the relatively smooth surface of the used HA particles. For the non-sintered HA (HAns) composites, it was possible to improve significantly both the stiffness and the strength. Amino silanes demonstrated to be highly efficient concerning strength enhancement. The higher effectiveness of the coupling treatments for HAns filled composites is attributed to their higher particle surface area, smaller particle size distribution and expected higher chemical reactivity. For both cases, the improvement in mechanical performance after the coupling treatment is consistent with the enhancement in interfacial adhesion observed by SEM.

Bi-composite sandwich moldings: processing, mechanical performance and bioactive behavior.

Two composite systems composed of high-density polyethylene (HDPE) filled with hydroxyapatite (HA) and carbon fiber (C fiber) were compounded in a co-rotating twin screw extruder and subsequently molded in a two component injection molding machine in order to produce test bars with a sandwich-like morphology. These moldings are based on a HDPE/HA composite outer layer and a HDPE/C fiber composite core. The mechanical performance of the obtained specimens was assessed by tensile and impact testing. The fracture surfaces were observed by scanning electron microscopy (SEM) and optical reflectance microscopy was used to characterize the morphology within the moldings. In order to study the bioactivity of the molded specimens, the samples were immersed for different periods of time up to 30 days in a simulated-body fluid (SBF) with an ion composition similar to human blood plasma. After each immersion period, the surfaces of the specimens were characterized by SEM. The chemical composition and the structure of the deposited films were studied by electron dispersive spectroscopy (EDS) and thin-film X-ray diffraction (TF-XRD). The evolution of the elemental concentrations in the SBF solution was determined by induced coupled plasma emission (ICP) spectroscopy. Bi-composite moldings featuring a sandwich-like morphology were successfully produced. These moldings present a high stiffness as a result of the C fiber reinforcement present in the molding core. Furthermore, as a result of the HA loading, the sandwich moldings exhibit a clear in vitro bioactive behavior under simulated physiological conditions, which indicates that an in vivo bone-bonding behavior can be expected for these materials.

In vitro degradation and cytocompatibility evaluation of novel soy and sodium caseinate-based membrane biomaterials.

Soy- and casein-based membranes are newly proposed materials disclosing a combination of properties that might allow for their use in a range of biomedical applications. Two of the most promising applications are drug delivery carrier systems and wound dressing membranes. As for all newly proposed biomaterials, a cytotoxic scanning must be performed as a preliminary step in the process of the determination of the compatibility with biological systems (biocompatibility). In this study, the cytotoxicity of both soy- and casein-based protein biomaterials has been evaluated and correlated with the materials degradation behavior. It was possible to show, through morphological and biochemical tests that these natural origin materials do not exert any cytotoxic effect over cells, and in some cases can in fact enhance cell proliferation. The different treatments to which the membranes were subjected during their processing (that include crosslinking with glyoxal and tannic acid, and physical modification by thermal treatment) seemed to have a clear effect both on the materials mechanical properties and on their in vitro biological behavior.

Use of coupling agents to enhance the interfacial interactions in starch-EVOH/hydroxylapatite composites.

Different zirconate, titanate and silane coupling agents were selected in an effort to improve the mechanical properties of starch and ethylene-vinyl alcohol copolymer (EVOH) hydroxylapatite (HA) composites, through the enhancement of the filler particles-polymer matrix interactions and the promotion of the interfacial adhesion between these two phases. The mechanical performance was assessed by tensile tests and discussed on the basis of the respective interfacial morphology (evaluated by scanning electron microscopy). The main relevant parameters were found to be the surface properties and reactivity of the filler (non-sintered HA) and the chemical nature (pH and type of metallic centre) of the added coupling agent. Significant improvements in the stiffness were achieved (about 30% increase in the modulus) when using the acidic zirconate coupling agents. The acidic zirconate combined the capability of crosslinking the polymer matrix with the establishment of donor-acceptor interactions and hydrogen bonding between it and the ceramic particles, leading to very good interfacial adhesion. The optimization of these coupling processes associated with the introduction of higher amounts of filler, may be an effective way to produce composites with mechanical properties analogous to those of the human cortical bone.

Novel starch thermoplastic/Bioglass composites: mechanical properties, degradation behavior and in-vitro bioactivity.

The present research aims to evaluate the possibility of creating new degradable, stiff and highly bioactive composites based on a biodegradable thermoplastic starch-based polymeric blend and a Bioglass filler. Such combination should allow for the development of bioactive and degradable composites with a great potential for a range of temporary applications. A blend of starch with ethylene-vinyl alcohol copolymer (SEVA-C) was reinforced with a 45S5 Bioglass powder presenting a granulometric distribution between 38 and 53 microm. Composites with 10 and 40 wt % of 45S5 Bioglass were compounded by twin-screw extrusion (TSE) and subsequently injection molded under optimized conditions. The mechanical properties of the composites were evaluated by tensile testing, and their bioactivity assessed by immersion in a simulated body fluid (SBF) for different periods of time. The biodegradability of these composites was also monitored after several immersion periods in an isotonic saline solution. The tensile tests results obtained indicated that SEVA-C/Bioglass composites present a slightly higher stiffness and strength (a modulus of 3.8 GPa and UTS of 38.6 MPa) than previously developed SEVA-C/Hydroxylapatite (HA) composites. The bioactivity of SEVA-C composites becomes relevant for 45S5 amounts of only 10 wt %. This was observed by scanning electron microscopy (SEM) and confirmed for immersion periods up to 30 days by both thin-film X-ray diffraction (TF-XRD) (where HA typical peaks are clearly observed) and induced coupled plasma emission (ICP) spectroscopy used to follow the elemental composition of the SBF as function of time. Additionally, it was observed that the composites are biodegradable being the results correlated with the correspondent materials composition.

Biocompatibility testing of novel starch-based materials with potential application in orthopaedic surgery: a preliminary study.

This paper describes an extensive biocompatibility evaluation of biodegradable starch-based materials aimed at orthopaedic applications as temporary bone replacement/fixation implants. For that purpose, a polymer (starch/ethylene vinyl alcohol blend, SEVA-C) and a composite of SEVA-C reinforced with hydroxyapatite (HA) particles, were evaluated in both in vitro and in vivo assays. For the in vitro analysis cell culture methods were used. The in vivo tissue reactions were evaluated in an intramuscular and intracortical bone implantation model on goats, using light and scanning electron microscopy. A computerized image analysis system was used to obtain histomorphometric data regarding bone contact and remodelling after 6 and 12 weeks of implantation. In both in vitro and in vivo models, the SEVA-C-based materials did not induce adverse reactions, which in addition to their bone-matching mechanical properties makes them promising materials for bone replacement fixation.

Cytocompatibility and response of osteoblastic-like cells to starch-based polymers: effect of several additives and processing conditions.

This work reports on the biocompatibility evaluation of new biodegradable starch-based polymers that are under consideration for use in orthopaedic temporary applications and as tissue engineering scaffolds. It has been shown in previous works that by using these polymers it is both possible to produce polymer/hydroxyapatite (HA) composites (with or without the use of coupling agents) with mechanical properties matching those of the human bone, and to obtain 3D structures generated by solid blowing agents, that are suitable for tissue engineering applications. This study was focused on establishing the influence of several additives (ceramic fillers, blowing agents and coupling agents) and processing methods/conditions on the biocompatibility of the materials described above. The cytotoxicity of the materials was evaluated using cell culture methods, according to ISO/EN 109935 guidelines. A cell suspension of human osteosarcoma cells (HOS) was also seeded on a blend of corn starch with ethylene vinyl alcohol (SEVA-C) and on SEVA-C/HA composites, in order to have a preliminary indication on cell adhesion and proliferation on the materials surface. In general, the obtained results show that all the different materials based on SEVA-C, (which are being investigated for use in several biomedical applications), as well as all the additives (including the novel coupling agents) and different processing methods required to obtain the different properties/products, can be used without inducing a cytotoxic behaviour to the developed biomaterials.

A new approach based on injection moulding to produce biodegradable starch-based polymeric scaffolds: morphology, mechanical and degradation behaviour.

One of the present challenges in polymer scaffold processing is the fabrication of three-dimensional (3D) architectures with an adequate mechanical performance to be used in the tissue engineering of hard tissues. This paper describes a preliminary study on the development of a new method to produce biodegradable scaffolds from a range of corn-starch-based polymers. In some cases, hydroxlapatite was also used as a reinforcement of the biodegradable polymers. The developed methodology consists of a standard conventional injection moulding process, on which a solid blowing agent based on carboxylic acids is used to generate the foaming of the bulk of the moulded part. The proposed route allows for the production of scaffolds with a compact skin and a porous core, with promising mechanical properties. By using the developed method it is possible to manufacture biodegradable polymer scaffolds in an easy (melt-based processing) and reproducible manner. The scaffolds can be moulded into complex shapes, and the blowing additives do not affect the non-cytotoxic behaviour of the starch-based materials. The materials produced using this method were evaluated with respect to the morphology of the porous structure, and the respective mechanical properties and degradation behaviour. It was demonstrated that it is possible to obtain, by a standard melt based processing route, 3D scaffolds with complex shapes that exhibit an appropriate morphology, without decreasing significantly the mechanical properties of the materials. It is believed that the optimisation of the proposed processing methodology may lead to the production of scaffolds that might be used on the regeneration of load-bearing tissues.

Dynamic mechanical properties of hydroxyapatite-reinforced and porous starch-based degradable biomaterials.

It has been shown that blends of starch with a poly(ethylene-vinyl-alcohol) copolymer, EVOH, designated as SEVA-C, present an interesting combination of mechanical, degradation and biocompatible properties, specially when filled with hydroxyapatite (HA). Consequently, they may find a range of applications in the biomaterials field. This work evaluated the influence of HA fillers and of blowing agents (used to produce porous architectures) over the viscoelastic properties of SEVA-C polymers, as seen by dynamic mechanical analysis (DMA), in order to speculate on their performances when withstanding cyclic loading in the body. The composite materials presented a promising performance under dynamic mechanical solicitation conditions. Two relaxations were found being attributed to the starch and EVOH phases. The EVOH relaxation process may be very useful in vivo improving the implants performance under cyclic loading. DMA results also showed that it is possible to produce SEVA-C compact surface/porous core architectures with a mechanical performance similar to that of SEVA-C dense materials. This may allow for the use of these materials as bone replacements or scaffolds that must withstand loads when implanted.

New starch-based thermoplastic hydrogels for use as bone cements or drug-delivery carriers.

The development of new biodegradable hydrogels, based on corn starch/cellulose acetate blends, produced by free-radical polymerization with methyl methacrylate monomer (MMA) and/or an acrylic acid monomer (AA), is reported. The polymerization was initiated by a redox system consisting of a benzoyl peroxide and 4-dimethlyaminobenzyl alcohol at low temperature. These hydrogels may constitute an alternative to the materials currently used as bone cements or drug-delivery carriers. Swelling studies were carried out, as a function of pH and temperature, in buffered solutions. The xerogels were further characterized by Fourier transform-infrared spectroscopy. Tensile and compression tests, and dynamic mechanical thermal analysis were used to assess the mechanical performance of the developed materials. The fracture surfaces were observed by scanning electron microscopy. The developed materials are sensitive to the pH, showing a clear reversible transition in a relatively narrow interval of pH, which is just in the range of physiological conditions. These properties make the materials developed in this study very promising for biomedical applications. Fickian-type diffusion is the mechanism predominant in these systems, except for the composition with a higher concentration of AA, that corresponds to the most desirable kinetical behavior for controlled release (case II-transport mechanism). Furthermore, the results obtained in the mechanical tests are in the range of those reported for typical PMMA bone cements, showing that it is possible to develop partially degradable cements with an adequate mechanical behavior.

Bone marrow transplantation in patients with Fanconi anemia: experience with cyclophosphamide and total body irradiation conditioning regimen.

Eleven patients with Fanconi anemia (FA) underwent bone marrow transplantation (BMT) between March 1985 and May 1990 in a single institution. Ten patients received bone marrow from healthy full human leukocyte antigen (HLA) matched siblings and one patient from her father (one antigen mismatch). Ten patients were conditioned with cyclophosphamide (Cy) at a dose of 5 mg/kg per day for 4 days followed by total body irradiation (TBI) for a total of 600 cGy over 3 days. Six of the 11 patients are alive and have normal reconstitution of their bone marrow. Median follow-up was 72 months (range 42-84). Three of the 10 patients who received Cy and TBI (two HLA compatible, one antigen mismatch) had graft failure. Five patients developed at least grade III acute graft-versus-host disease (GVHD). The rates of graft failure and GVHD are, however, still significantly high. Modification of the conditioning regimen and GVHD prophylaxis is needed to improve the outcome.

Treatments to induce the nucleation and growth of apatite-like layers on polymeric surfaces and foams.

In this work, a bioactive glass is used as a percusor of calcium-phosphate (Ca-P) film deposition onto several polymer-based materials. Both bioinert (high molecular weight polyethylene, HMWPE), and biodegradable (corn starch-based blends, SEVA-C) polymers, unreinforced or reinforced with hydroxylapatite (HA), were coated by the very simple proposed route. Also polyurethane (PU) foams, with an open-cell structure, were mineralized by the proposed method. In fact, it was possible to induce the growth of the Ca-P films not only at the surface, but also in the bulk of the PU foam. These cellular materials are intended for cancellous bone replacement applications. The morphology of the formed films was strongly dependent on the used substrate, its polar character, and on the presence of HA in its composition, as observed by SEM. Nevertheless, a well defined needly like structure was observed in all samples at high magnifications. The Ca:P ratios of the films were between 1.5 and 1.7, i.e. in the range of tricalcium phosphate-hydroxylapatite. Raman spectroscopy and thin-film x-ray diffraction (XRD) evidenced the formation of mostly amorphous calcium-phosphate films. After scraping the coating from the polymer surface and heat-treating the resulting powder at 1000 degrees C for 1 h, HA and beta-tricalcium phosphate (TCP) typical peaks were found on XRD patterns.

Bone marrow transplantation for infantile malignant osteopetrosis.

PURPOSE: Most patients diagnosed with malignant osteopetrosis die during infancy or early childhood from hemorrhage and infection due to bone marrow failure. Allogeneic bone marrow transplantation (BMT) has been reported to provide curative therapy for this disorder. We report our experience with eight patients with malignant osteopetrosis who underwent BMT. PATIENTS AND METHODS: Between May 1987 and August 1992, eight children with malignant osteopetrosis underwent allogeneic BMT. Median age at BMT was 9 months (range, 2-36 months). Six patients received marrow from HLA-identical sibling donors, one from phenotypically matched father, and one from a one antigen mismatched father. BMT conditioning for all patients was busulfan 16 mg/kg and cyclophosphamide 200 mg/kg each administered over 4 days. Graft versus host disease (GVHD) prophylaxis included cyclosporin A in six patients or cyclosporin A and methotrexate in two patients. RESULTS: Six patients, including those who received bone marrow from their father's, engrafted as documented by bone marrow biopsy showing an increase in osteoclasts in all cases and by chromosomal analysis in four patients. Two patients died without engraftment. Three out of six patients engrafted are alive and well at the follow-up of 48, 63, and 81 months. Serum calcium, alkaline, and acid phosphatase levels normalized within 2 months. These patients have full bone marrow reconstitution. Serial radiologic studies revealed bone marrow remodelling and a new nonsclerotic bone formation. Vision improved dramatically in the youngest patient. CONCLUSION: BMT offers cure to patients with malignant osteopetrosis with reconstitution of bone marrow and correction of metabolic disturbances. In our experience, reversibility in neurosensory deficit is possible when BMT is done at an early age.