Minipool Caprylic Acid Fractionation of Plasma Using Disposable Equipment: A Practical Method to Enhance Immunoglobulin Supply in Developing Countries

Plasma-derived immunoglobulin G (IgG) is on WHO’s Essential Medicines List, yet developing countries face severe shortages of this critical treatment. Infusion of IgG prepared from locally-collected plasma provides an advantageous mix of antibodies to viral and bacterial pathogens found in the living environment, and this can reduce recurrent infections in immune-deficient patients. We developed a simple manufacturing process using disposable equipment (blood bags, hemodialyzer, and filters) to isolate immunoglobulins from minipools of 20 plasma donations. This process yields a ca. 90% pure virally-inactivated immunoglobulin fraction at 50–60% recovery. Anti-hepatitis B and anti-rubella immunoglobulins were enriched fourfold to sixfold. The product was free of in-vitro thrombogenic and proteolytic activity, confirming its expected clinical safety profile. Virus validations showed caprylic acid treatment robustly inactivated or removed infectivity of lipid-enveloped viruses, including human immunodeficiency virus (HIV) and hepatitis C virus model. This simple and cost-effective process is implemented in Egypt to prepare experimental batches for clinical evaluation. It can enhance immunoglobulin supplies to treat immunodeficient patients through passive transmission of antibodies directed against local pathogens. The method requires minimal training and reasonable infrastructure, and is a practical means to prepare convalescent hyperimmune IgG during infectious outbreaks such as the current Ebola episode.UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)UCR::Vicerrectoría de Docencia::Salud::Facultad de Microbiologí

Polybrominated diphenyl ethers in biosolids-amended soils

Polybrominated diphenyl ethers (PBDEs) are added to many consumer products as flame retardants. Their hydrophobic characteristics and high n-octanol-water coefficients make them partition in organic media such us sludge and biosolids, by-products of wastewater treatment which are commonly applied to agricultural soils to promote crop growth or discarded in landfills. Biosolids-amended soils have been found to contain up to 7x10⁶ pg PBDEs/g dry weight, whereas leachates from biosolids and flame-retarded products in landfills, contained up to 4,000 pg PBDEs/litre. PBDEs in the environment could potentially cause serious health effects. Research was conducted to determine the concentration and mobility of PBDEs in biosolids, biosolids-amended soil, and clay liners used to retain PBDEs. A field study investigated the degree of PBDE contamination due to the application of biosolids at an agricultural site near Kamloops and an agricultural field in Totem Field at the University of British Columbia in Vancouver. PBDEs were found to migrate downwards to depths of at least 0.85 m. Laboratory experiments determined leachability of PBDEs from biosolids. PBDEs sorbed on fine particles suspended in the leachate, allowing PBDEs to exceed their aqueous phase solubilities. Concentrations were much higher on ultra-fine than on fine particles. Leaching column tests demonstrated that PBDEs leached from biosolids-amended soils and migrated through the soils. PBDEs in soils upgradient and downgradient of solid waste facilities in Northern Canada varied widely from location to location. There was evidence that PBDE contamination in Iqaluit is due to long-range atmospheric transport, whereas that found at Yellowknife is mainly from the solid waste facility. Laboratory experiments showed that sand-bentonite partially retained PBDEs. The hydraulic conductivity decreased with leaching, and then gradually increased. The decrease is attributed to swelling, whereas the increase is due to shrinkage of the clay interlayer, owing to the hydrophobicity of the permeant. The research may be helpful in establishing regulations on land application of biosolids, regulating waste disposal and landfill design requirements.Applied Science, Faculty ofCivil Engineering, Department ofGraduat

Permeability improvements of electropolymerized polypyrrole films using dissolvable nano-CaCO3 particle templates

International audienc

Evaluation of Intra-articular Fracture Extension After Gunshot Wounds to the Lower Extremity: Plain Radiographs Versus Computer Tomography.

OBJECTIVE: This study was to compare the use of computer tomography with plain radiographs for the evaluation of intra-articular extension of long bone fractures in the lower extremity after low-energy gunshot wounds. DESIGN: Retrospective chart and radiographic review. SETTING: Level 1 Trauma Center. PATIENTS/PARTICIPANTS: Data were collected from a single institution from 2000 to 2014. Inclusion criteria consisted of patients greater than 17 years of age, low-velocity gunshot injuries causing fracture of the femur or tibia, plain radiographs with adequate films, and computed tomography (CT) imaging of the fracture. This consisted of 133 patients with 140 fractures. INTERVENTION: Intra-articular fracture extension was evaluated on initial plain radiographs and CTs. MAIN OUTCOME MEASURES: Comparison of gold standard CT with all reviewers\u27 evaluation of plain radiographs. RESULTS: There were 140 total fractures; 108 were femoral fractures and 32 were tibial fractures. By comparing plain radiographs with the gold standard CT, the reviewers demonstrated correct diagnosis in 85% of intra-articular fractures and 96% of non-intra-articular fractures. In addition, the reviewers accurately diagnosed 70.8% of intra-articular extensions in the diaphysis and 70.5% in the metaphysis. The sensitivity and specificity for plain radiographs were 85.3% and 96.0%, respectively, for all locations. Metaphyseal and diaphyseal fractures demonstrated the poorest sensitivity at 80.7% and 82.1%, respectively. CONCLUSIONS: Low-energy gunshot wounds with fractures in the diaphyseal of the distal femur and all metaphyseal fractures warrant CT evaluation to better examine for intra-articular fracture extension. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence

Properties and specifications (or range) of the IgG-enriched plasma fraction.

<p>* N = 10;</p><p>** N = 5 (consecutive batches)</p><p>Properties and specifications (or range) of the IgG-enriched plasma fraction.</p

Zone electrophoresis.

<p>A: Patterns of 5 consecutive batches of minipool IgG-enriched plasma fractions (Minipool IgG batches B1 to B5) and control IgG (C) showing the separation between albumin (Alb) and alpha-1 (α-1), alpha-2 (α-2), bêta- (β) and gamma- (γ) proteins. B: densitographic analysis showing the percentage (%) of albumin, alpha-1, alpha-2, bêta, and gamma proteins in 5 batches (B1–B5) of minipool IgG. Control: control IgG.</p

Percent increase in body weight of rats (3 groups of 7 rats) treated with saline, commercial IgG, or minipool IgG.

<p>Percent increase in body weight of rats (3 groups of 7 rats) treated with saline, commercial IgG, or minipool IgG.</p

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

<p>Patterns of 10 consecutive batches of minipool IgG-enriched plasma fractions (Minipool IgG batches B1 to B10) and control IgG (C) under non-reducing (A) or reducing (B) conditions. Control: control IgG; IgG: immunoglobulin G; Alb: albumin. MW: molecular weight markers (kDa).</p

Log removal factors of HIV-1, BVDV, and PRV during caprylic acid treatment (duplicate experiments).

<p>*Viral titers are expressed as TCID₅₀/mL.</p><p>**Infectious titers at the non-interfering dilution after large volume titration.</p><p>Log removal factors of HIV-1, BVDV, and PRV during caprylic acid treatment (duplicate experiments).</p