Evaluation of endotoxin retention by adsorptive-based filtration media

Control of endotoxin contamination is an important issue in pharmaceutical and bioprocess manufacturing. Endotoxins can contaminate process intermediates used in pharmaceutical formulations, aqueous- and non-aqueous-based CIP fluids used in equipment and vial cleaning, and process fluids such as buffers used for chromatographic elution, diafiltration, and suspension of therapeutic protein-based drugs. A study was undertaken to evaluate the effectiveness of adsorptive-based depth and membrane filtration media in removing suspended endotoxin. The following variables were examined in order to determine their effects on endotoxin reduction: absorptive media type, residence time (flux), challenge solution pH, and interferences in endotoxin reduction as the result of challenge solution composition-water for injection, process buffer, and the presence of protein. The endotoxin removal capacities of the various media studied were also determined. The results of the study demonstrated differences in the effect on endotoxin removal of the variables evaluated. In addition, the results provide a strategy for conducting studies to select and validate an appropriate adsorptive filter media for control of endotoxin contamination.     

The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials

The effect of increasing strut porosity on the osteoinductive ability of silicate substituted calcium phosphate (SiCaP) biomaterials was investigated in an ectopic ovine model. Implants with strut porosities of 22.5%, 32.0% and 46.0% were inserted into the parapsinalis muscle. At 8, 12 and 24 weeks histological sections were prepared. Sections were examined using backscattered scanning electron microscopy and un-decalcified histology. Bone area, implant area and bone-implant contact were quantified. At 8 weeks there was no significant difference between the groups in terms of bone area and implant area. However at 12 weeks, the amount of bone formation observed was significantly greater in SiCaP-46 (6.17 ± 1.51%) when compared with SiCaP-22.5 (1.33 ± 0.84%) p=0.035. Results also showed significantly increased amounts of bone-implant contact to the SiCaP-46 scaffold (3.30 ± 1.17%) compared with SiCaP-22.5 (0.67 ± 0.52%, p=0.043) at 8 weeks and 12 weeks; (SiCaP-46 (21.82 ± 5.59%) vs SiCaP-22.5 (3.06 ± 1.89%), p=0.012). At 24 weeks, bone formation and graft resorption had significantly increased in all groups so that the level of bone formation in the SiCaP-46 group had increased 75-fold to 30.05 ± 8.38%. Bone formation was observed in pores <10 μm. Results suggest that bone graft substitute materials with greater strut porosity are more osteoinductive.     

Identification of a new variant, HLA-Cw*1507, differing from Cw*1502 only at the KIR-related dimorphism of codons 77 and 80

We describe here a novel allele, HLA-Cw*1507, identified by polymerase chain reaction using sequence-specific primers (PCR-SSP) and sequence-based typing (SBT). Cw*1507 is similar to Cw*1502 with differences at nucleotide positions 302 (A to G) and 312 (A to C) in exon 2. The substitutions observed in Cw*1507, change codon 77 from AAC (asparagine) to AGC (serine) and codon 80 from AAA (lysine) to AAC (asparagine), compared to Cw*1502. Residues 77 and 80 of HLA-C alleles are located in the alpha 1 domain, where they can influence interaction between antigenic peptides and the T-cell receptor. Also, the dimorphism at these residues from asparagine and lysine to serine and asparagine, respectively, are known to modulate interaction with the natural killer (NK) cell killer inhibitory receptor (KIR). The new HLA-Cw*1507, together with Cw*1502, represents the fourth pair of HLA-C alleles differing only at the KIR-related dimorphic codons 77 and 80.     

Disgust and eating disorders

Two studies are described which investigated the relationship between disgust sensitivity and eating disorders. In a normal sample, Study 1 found a significant correlation between measures of eating disorder and measures of disgust sensitivity, but only in female subjects. This relationship was not mediated by existing levels of anxiety or depression. Study 2 found that subjects who had clinically-diagnosed eating disorders exhibited significantly higher levels of disgust than matched normal control subjects. Both studies indicated that elevated disgust in relation to eating disorders appeared to be confined primarily to disgust of food, the body and body products, and did not extend to disgusting stimuli which are not associated with food or the body. © 1998 John Wiley & Sons, Ltd and Eating Disorders Association.     

Changes in dopa decarboxylase mRNA but not tyrosine hydroxylase mRNA levels in rat brain following antipsychotic treatment

The effects of antipsychotic administration (1–32 days, twice per day) on the levels of mRNA coding for dopa decarboxylase (DDC) and tyrosine hydroxylase (TH) in rat brain has been assessed by a procedure utilising solution hybridisation with oligonucleotides. Saline and sulpiride (20 mg/kg/day) had no apparent effect on DDC mRNA levels. Haloperidol (3 mg/kg/day) elicited increases in DDC mRNA levels of 240% after 32 days and loxapine (4 mg/kg/day) elicited increases of 180% in DDC mRNA levels. None of the drugs affected TH mRNA levels. These results indicate that DDC may be more important than TH in the long term regulation of dopamine production.     

Therapeutic strategies in common variable immunodeficiency

The treatment of common variable immunodeficiency (CVID) is currently based on the early recognition of the condition and replacement immunoglobulin combined with prompt treatment of infections and complications. The route of administration, dose and frequency of administration of immunoglobulin still vary between centres and countries. Other interventions aimed at overcoming the immunological defects in CVID such as interleukin-2 therapy are being studied but there is as yet insufficient evidence to support their routine use. The treatment of complications such as suppurative lung disease uses principles broadly similar to those used for cystic fibrosis, whereas the granulomatous complications involving the lungs and other organ systems are in need of much more research to define optimum therapies.