Health research ethics in Africa.
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Africa↗
Biomedical subjects
S Jepsen
Publications and source records attributed to S Jepsen.
Naturally acquired antibodies to the glutamate-rich protein are associated with protection against Plasmodium falciparum malaria.
The development of effective malaria vaccines depends on the identification of targets of well-defined protective immune responses. Data and samples from a longitudinal study of a cohort of children from coastal Ghana were used to investigate the role of antibody responses to 3 regions of the Plasmodium falciparum glutamate-rich protein (GLURP). The data show that levels of the GLURP-specific IgG that occurs in the nonrepeat region of the antigen are significantly correlated with clinical protection from P. falciparum malaria, after correction for the confounding effect of age. Furthermore, levels of cytophilic antibodies were found to be of particular importance for protection, lending support to the hypothesis that antibody-dependent cellular inhibition is the important element in GLURP-specific protective immunity.
Adolescent↗
[Malaria prophylaxis one more time].
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Africa↗
European malaria vaccine initiative.
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Africa↗
Sinus floor augmentation with simultaneous placement of dental implants using a combination of deproteinized bone xenografts and recombinant human osteogenic protein-1. A histometric study in miniature pigs.
Maxillary sinus floor augmentation with autogenous bone has become a widely accepted procedure in implant dentistry. The use of osteoconductive bone substitutes in this indication is controversial, since their use can lead to a prolonged healing time, inhomogenous ossification, foreign body reaction, migration of particles and low bone-implant contact (BIC). The purpose of this study was to examine whether the combination of an osteoinductive protein (recombinant human osteogenic protein-1 (rhOP-1 = bone morphogenetic protein-7) with natural bovine bone mineral (BioOss) would improve ossification and the bone-implant contact (BIC) in a sinus floor augmentation with simultaneous placement of implants. In this study, the maxillary sinus floors in 5 miniature pigs were augmented with 3 ml BioOss containing 420 micrograms rhOP-1 on the test side and 3 ml BioOss alone on the control side. At the time of augmentation a titanium implant (ITI) was inserted from a laterocaudal direction. After 6 months of healing the sites of augmentation were removed and examined in non-decalcified sections by microradiography, fluorescence microscopy of sequentially labelled specimens and by histometry. On both sides, significant amounts of newly-formed bone were observed. However, on the test sites, the percentage of BIC in the augmented area was 80.0% versus 38.6% on control sites. It can be concluded that the application of bone morphogenetic proteins caused a more rapid and enhanced osseointegration of simultaneously placed implants when compared to the bone substitute alone. Therefore recombinant human osteogenic protein-1 delivered by natural bone mineral has the potential to become a clinical alternative for autogenous bone grafts in sinus floor augmentation.
Animals↗
Mandibular reconstruction in miniature pigs with prefabricated vascularized bone grafts using recombinant human osteogenic protein-1: a preliminary study.
A new technique of prefabrication of vascularized bone grafts in the latissimus dorsi muscle of miniature pigs, using recombinant human osteogenic protein-1 (rhOP-1) and xenogenic bone mineral as a carrier, is presented. The grafts were used to reconstruct a mandible using microsurgical anastomosis of the thoracodorsal vessels of the flap with a branch of the external carotid artery and the external jugular vein. The technique provided enough bone to reconstruct a mandible. The bone marrow stayed viable after transplantation, demonstrated by fluorescence microscopy and scintigraphy. Compared with identical defects of the contralateral side, which were treated with directly applied rhOP-1/bone mineral, a significantly better result was obtained with the prefabrication technique. The prefabrication technique may provide a means to treat irradiated patients with bone grafts produced by osteoinductive proteins and has a potential to become a clinical alternative to conventional vascularized bone grafts.
Animals↗
The glutamate-rich protein (GLURP) of Plasmodium falciparum is a target for antibody-dependent monocyte-mediated inhibition of parasite growth in vitro.
Monocyte-dependent as well as direct inhibitory effects of antimalarial antibodies point toward antigens accessible at the time of merozoite release as targets for biologically active antibodies capable of mediating protection against Plasmodium falciparum. The glutamate-rich protein (GLURP), being an antigen associated with mature schizont-infected erythrocytes, was therefore the object of the present investigation, in which we analyzed whether anti-GLURP antibodies can either interfere directly with merozoite invasion or act indirectly by promoting a monocyte-dependent growth inhibition, antibody-dependent cellular inhibition. GLURP-specific human immunoglobulin G (IgG) antibodies, from pooled IgG of healthy Liberian adults who were clinically immune to malaria, were purified by affinity chromatography on columns containing R0 (N-terminal nonrepetitive region of GLURP) or R2 (C-terminal repetitive region of GLURP) recombinant protein or synthetic peptides as ligands. Analysis of the pattern of reactivity of highly purified anti-GLURP antibodies led to the definition of at least four B-cell epitopes. One epitope was specific for R0, two were specific for R2, and the fourth displayed cross-reactivity between R0 and R2. None of the purified IgG antibodies had direct invasion-inhibitory effects, even at high concentrations. In contrast, when allowed to cooperate with monocytes, all anti-GLURP IgG preparations mediated a strong monocyte-dependent parasite growth inhibition in a dose-dependent manner.
Animals↗
Treatment of gingival recession with titanium reinforced barrier membranes versus connective tissue grafts.
It was the aim of this study to compare barrier membrane therapy with connective tissue grafts in the treatment of recession defects. Fifteen patients with 2 paired vestibular recession defects participated in the study. After thorough scaling and root surface conditioning with tetracycline-HCl, defects were randomly assigned to 1 of 2 treatment modalities. In one of the defects, a trapezoidal mucoperiosteal flap was prepared, and a titanium reinforced expanded polytetrafluoroethylene membrane was adapted to the defect and secured by a sling suture. The membrane was subsequently covered by a coronally positioned flap secured with crown attached sutures. The other defect was treated with a connective tissue graft employing the "envelope technique." Twelve months after therapy, both treatment modalities showed significant root coverage and probing attachment gain. Gingival recession decreased from 3.6+/-0.7 mm to 0.5+/-0.5 mm for membrane treated defects and from 3.6+/-1.0 mm to 0.5+/-0.5 mm following use of grafts, corresponding to mean root coverages of 87.1% and 86.9%, respectively. Mean gains of keratinized tissue of 1.5 mm (membrane) and 2.5 mm (graft) could be observed. Thus, the results of this study demonstrate that both titanium reinforced barrier membranes and connective tissue grafts can be successfully used to treat periodontal recession defects.
Adult↗
Recombinant human osteogenic protein 1 in the rat mandibular augmentation model: differences in morphology of the newly formed bone are dependent on the type of carrier.
Recombinant human osteogenic protein 1 (rhOP1), also known as bone morphogenetic protein 7, was investigated in a newly developed experimental model, the rat lateral mandibular augmentation model. Algipore and Bio-Oss Block were applied as carrier materials. Extensive induction of newly formed bone was demonstrated on the test side containing rhOP1 and did not occur on the control side without rhOP1. The interstitial bone formation was limited to the augmented area and was not observed in the surrounding masseter muscle. The morphology of the newly formed bone differed in both carrier systems, which may be an important characteristic for the clinical indication of carrier systems in combination with bone morphogenetic proteins.
Animals↗
Recombinant human osteogenic protein-1 induces dentin formation: an experimental study in miniature swine.
It was the aim of the present study to investigate the induction of dentin formation by recombinant human osteogenic protein-1 (hOP-1). In 4 adult miniature pigs a total of 16 teeth with artificially exposed dental pulps were capped with 3 mg of a complex of recombinant hOP-1 in collagen matrix (2.5 micrograms/mg), collagen matrix alone, or calcium hydroxide paste. Teeth were removed in block section after a healing period of 5 weeks. Decalcified sections were processed for light microscopy and histomorphometric analysis. In hOP-1 treated teeth substantial amounts of hard tissue formation (osteodentin and tubular dentin) had consistently led to a complete bridging of the defects. Less dentin formation was seen after calcium hydroxide application. In control defects collagen matrix alone failed to form complete dentin bridges. Recombinant human osteogenic protein-1 in a collagen carrier matrix appeared to be suitable as a bio-active capping agent for surgically exposed dental pulps.
Animals↗
European Commission COST/STD Initiative. Report of the expert panel I. Models for scientific and economic interaction in vaccines R & D.
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Chemistry, Pharmaceutical↗
Progressive peri-implantitis. Incidence and prediction of peri-implant attachment loss.
The aim of this prospective study was to characterize an implant patient population exhibiting clinical signs of peri-implantitis and to determine subsequently the incidence of progressive attachment loss. The predictive values of diagnostic parameters were evaluated. 25 patients with 54 endosseous implants that had been loaded for 41 +/- 15 months were included in the study. Clinical parameters included the assessment of plaque, bleeding on probing, probing depth, attachment levels, and Periotest values. Probing measurements were performed in duplicate by means of a controlled force electronic probe (Periprobe). Peri-implant crevicular fluid samples were collected and assayed for neutral proteolytic enzyme (NPE) activity (Periocheck). Analysis of duplicate baseline probing data revealed a high degree of reproducibility (mean difference: 0.1 +/- 0.3 mm). A minimum threshold of 1.0 mm (> 3 x S.D.) loss of probing attachment was chosen to classify a site as positive for breakdown. Alternatively, the tolerance method was employed to identify sites with progressive attachment loss. After 6 months, irrespective of the analytical method, 6 percent of all sites (in 19% of the implants) and 28% of the patients had experienced further peri-implant attachment loss. There were significant differences (p < 0.05) in mean plaque (73% vs. 45%) and NPE (36% vs. 12%) scores between patients with progressive peri-implantitis and those with stable peri-implant conditions. Both bleeding on probing and the NPE-test were characterized by high negative predictive values, and thus negative scores can serve as indicators for stable peri-implant conditions. For monitoring peri-implant health during recall visits, attachment level recordings with a controlled force electronic probe in conjunction with enzymatic diagnostic tests of the host response can be recommended.
Aged↗
Inhalation of nitric oxide as a treatment of pulmonary hypertension in congenital diaphragmatic hernia.
Congenital diaphragmatic hernia (CDH) still has a mortality risk of around 40%. The concomitant pulmonary hypoplasia and the persistent pulmonary hypertension are of major prognostic importance. The use of a selective pulmonary vasodilator may revert this vicious circle that is fatal to many children. Inhalation of nitric oxide (NO) has been suggested as a rational treatment of this condition. The authors report three cases of high-risk infants with CDH where NO was used successfully. It is concluded that hypoxemia in CDH can be treated successfully with NO inhalation when conventional treatment fails, and it may in some cases prove to be an alternative to ECMO.
Administration, Inhalation↗
Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli.
A recombinant Plasmodium falciparum glutamate-rich protein (GLURP) was produced in Escherichia coli as a nearly full-length protein. In order to map immunodominant regions on GLURP, the nonrepetitive amino-terminal region (R0) as well as the central repeat region (R1) and the carboxy-terminal repeat region (R2) were also produced as separate products. All four purified gene products reacted specifically with serum samples from adults living in an area of Liberia where malaria is holoendemic. It appears that the human immune response against GLURP is primarily directed against the R2 region because 94% of the serum samples reacted with this region in an immunoassay. Antibody reactivity against the R0 region was also observed in 75% of the serum samples, while the R1 region showed only weak antibody-binding activity. When the nearly full-length GLURP molecule was adsorbed to Al(OH)3 it was found to be immunogenic in mice. In these experiments, the antibody response was almost exclusively directed against the R2 region. When anti-GLURP sera were obtained from rabbits immunized with the three regions, R0, R1, and R2, respectively, they recognized in immunoprecipitation experiments authentic GLURP from P. falciparum grown in vitro. These results demonstrate that GLURP produced in E. coli can induce a humoral immune response against GLURP derived from blood-stage parasites.
Amino Acid Sequence↗
Immunogenicity of the Plasmodium falciparum glutamate-rich protein expressed by vaccinia virus.
The glurp gene of Plasmodium falciparum F32 has been inserted into a vaccinia virus, and the recombinant virus was designated VVG4. Expression of glurp in VVG4-infected Vero cells was analyzed by immunoprecipitation and revealed a primary GLURP product of approximately 220,000 Da; GLURP was detected both intracellularly and in culture supernatants. To study the immunogenicity of vaccinia virus-expressed GLURP, mice were immunized with VVG4 and serum samples were analyzed for antibody reactivity with three polypeptides, covering almost the entire GLURP molecule; these three polypeptides were produced in recombinant form in Escherichia coli. The immune response was primarily directed against a carboxy-terminal repeat region. The mouse anti-GLURP serum recognized authentic GLURP by immunoprecipitation analysis from P. falciparum grown in vitro. These results demonstrate that vaccinia virus-expressed glurp product can induce a humoral immune response against GLURP derived from blood-stage parasites.
Animals↗
The influence of N-acetylcysteine on the measurement of prothrombin time and activated partial thromboplastin time in healthy subjects.
The purpose of the study was to evaluate whether the infusion of N-acetylcysteine decreased the measurement of prothrombin time and activated partial thromboplastin time (APTT) in healthy persons. N-acetylcysteine was administered intraveneously 10 mg kg-1 as a loading dose and then at a rate of 10 mg kg-1 h-1 for 32 h in six male subjects. The intrinsic, extrinsic and common pathway of coagulation were monitored with activated partial thromboplastin time (APTT), and prothrombin time, respectively. In addition, the extrinsic coagulation pathway was monitored with the clotting activity of single factors II, VII, and X. No effect on the intrinsic coagulation pathway was observed. There was a significant and rapid decrease in prothrombin time. Coagulation factors II, VII and X, the three components of prothrombin time, decreased significantly to different degrees. We conclude that infusion of N-acetylcysteine intraveneously decreases the prothrombin time in healthy subjects. Thus, one should not make conclusions which are too far-reaching based on prothrombin time alone in patients who have been treated recently with N-acetylcysteine intraveneously.
Acetylcysteine↗
Capture ELISA for IgM antibodies against Plasmodium falciparum glutamate rich protein.
This report describes a novel mu chain capture ELISA for the detection of IgM antibodies against a Plasmodium falciparum antigen. A fragment of the 220 kDa P. falciparum glutamate rich protein containing amino acid residues 489-1271 was expressed in E. coli as a recombinant chimeric beta-galactosidase fusion protein and used as antigen after purification and biotinylation. Specific IgM antibodies were found in 51% (39/77) of sera from adult Liberians immune to malaria. The binding of IgM antibodies was specific for the malaria portion of the fusion protein and no cross-reactivity was found in sera from patients with IgM antibodies due to other diseases. Inhibition studies with a fusion protein containing amino acid residues 816-1134 (GLURP816-1134) representing the carboxy-terminal repeat region suggested a different use of epitopes for IgM antibodies in different individuals.
Animals↗