Surrogate Serum Research Articles

Biopsy assessment of drug efficacy in the gastrointestinal tract

When using biopsy pathology in clinical pharmacology to assess drug efficacy in the gastrointestinal tract, a number of questions must be answered: Is the biopsy necessary or more effective than macroscopic views by endoscopy? Can we extract maximal information from the specimen? Are there surrogate serum or other markers that give an overall measure of disease and/or improvement? Indeed, clinicopathological correlation is of paramount importance. If biopsy is to be used, it is important to utilize appropriate scoring systems. Many grading systems use continuous spectra, which are ordinal categorical variables and therefore a grading system of assigned 'numbers' which cannot be used in processes that require continuous variables such as linear regression. The use of grading vs a 'true' score with real numbers must be carefully considered, the site and number of biopsies must be precisely chosen and interobserver reproducibility of results evaluated before undertaking drug trials. Immunocytochemistry and in situ hybridization, however, can provide quantifiable molecular information related to mechanisms of drug action. The biopsy is of significant value as it is a true in vivo assessment if the above caveats are taken into account. However, further work is needed to determine sound histological criteria to assess the efficacy of drugs for use in gastrointestinal disease.

Development of a photolytic artificial lung: preliminary concept validation.

There is an established need for pulmonary technology capable of facilitated gas exchange in the blood, thereby bypassing the alveolar-capillary interface. To address this need, we emulated one of the best-known photolytic reactions in nature, photosynthesis, in which green plants use sunlight to drive the exchange of oxygen for carbon dioxide. Our goal in the current study was to demonstrate the feasibility of direct photolytic conversion of water to liquid phase oxygen (dissolved oxygen [DO]) in synthetic serum. To this end, we constructed a test flow cell consisting of a conductive coating of vacuum-deposited titanium (Ti) metal, adherent TiO2 (anatase), and MnO2, applied as a laminate to a glass substrate, and then immersed the device in Locke's-Ringer solution (synthetic blood serum). Long wavelength (low energy) ultraviolet A laser light, directed to the transparent glass slide, reproducibly resulted in the generation of an active form of oxygen (AO), which was subsequently converted directly by the catalytic action of MnO2 to DO. The absence of light activation provided an entirely null response. We conclude that the photolytic production of DO from water in a blood serum surrogate, with commensurate CO2 clearance, is feasible. A prototype photolytic module is proposed, which uses multiple parallel photolytic surfaces to improve system production capacity and CO2 clearance through selective gas-liquid separation from the oxygen-enriched fluid.

Genome-wide analysis of hepatic fibrosis in inbred mice identifies the susceptibility locus Hfib1 on chromosome 15

Background & Aims: Host genetic factors are likely to contribute to the variable course of hepatic fibrosis in response to chronic liver injury. Similarly, the fibrotic response differs among inbred mouse strains after challenge with CCl4. Our aim was to identify unknown susceptibility loci for hepatic fibrosis in a cross between fibrosis-susceptible and -resistant inbred mice. Methods: Seven inbred mouse strains were treated with CCl4, and hepatic fibrosis was phenotypically characterized by histology, hepatic hydroxyproline levels, and serum surrogate markers. F1 hybrids of susceptible BALB/cJ and resistant A/J inbred strains were intercrossed to obtain 358 F2 progeny. Quantitative trait loci (QTL) that determine hepatic fibrosis were identified by genome-wide interval mapping and haplotype analysis. Results: In this model, marked strain differences in fibrosis susceptibility exist, with BALB/c inbred mice being most susceptible. The hydroxyproline levels of F1 mice resemble the resistant parental strains, indicating that fibrosis susceptibility is a recessive trait. QTL analysis identifies a susceptibility locus on chromosome 15 that significantly affects the stage of fibrosis and hydroxyproline levels. According to standard nomenclature, this locus is called Hfib1 (hepatic fibrogenic gene 1). Hfib1 is defined by genetic markers D15Mit26 and D15Mit122. A suggestive QTL on chromosome 2 colocalizes with the complement factor 5 gene, known to be mutated in the resistant strain A. Conclusions: The set of inbred strains provides a framework for systematic analysis of fibrogenic genes. QTL mapping is useful to identify genetic susceptibility loci for hepatic fibrosis that might harbor new molecular targets for antifibrotic drug design.GASTROENTEROLOGY 2002;123:2041-2051

Correlation of hepatic matrix gene expression in diagnostic biopsies with surrogate serum markers of fibrogenesis and fibrolysis

Correlation of hepatic matrix gene expression in diagnostic biopsies with surrogate serum markers of fibrogenesis and fibrolysis

Correlation of hepatic matrix gene expression in diagnostic biopsies with surrogate serum markers of fibrogenesis and fibrolysis

Correlation of hepatic matrix gene expression in diagnostic biopsies with surrogate serum markers of fibrogenesis and fibrolysis

Antibodies to human myeloperoxidase in glomerular immune deposits of systemic lupus erythematosus.

Antibodies to human myeloperoxidase and cathepsin G have been detected in the serum of some patients with systemic lupus erythematosus. Therefore, the presence of antibodies to human myeloperoxidase and cathepsin G was examined in glomerular immune deposits. Glomerular basement membrane fragments were prepared from renal tissues obtained at autopsy from 19 patients with systemic lupus erythematosus. IgG was extracted from the glomerular basement membrane fragments and tested with sensitive immunoassays for antibodies to myeloperoxidase and cathepsin G. Antibodies to cathepsin G were not detected in the extracts but antibodies to human myeloperoxidase were found in extracts of one specimen. In the extract with 6M guanidine hydrochloride these antibodies were enriched 103-fold, compared to the initial supernatant of glomeruli, which served as a serum surrogate. The recovered antibodies to myeloperoxidase accounted for 12% of the recovered IgG. These findings add autoantibodies to human myeloperoxidase to the list of antibodies that have been shown to be present in glomerular immune deposits of patients with lupus glomerulonephritis.

The Connective Tissue Reaction to Acute Lung Injury in Children: Emerging Surrogate Serum Markers for the Pulmonary Matrix

The Connective Tissue Reaction to Acute Lung Injury in Children: Emerging Surrogate Serum Markers for the Pulmonary Matrix

Permeability of latex and thermoplastic elastomer gloves to the bacteriophage φX174

Background: Most studies challenging the integrity of the glove barrier have compared the permeability of vinyl and latex gloves. However, no studies of a new nonlatex, nonvinyl thermoplastic elastomer have been reported. This pilot study therefore compared the protective barriers provided by latex and thermoplastic elastomer surgical gloves against penetration of the bacteriophage φX174. Methods: Twenty thermoplastic elastomer gloves and 25 commercially available latex gloves (20. brand 1, 5 brand 2) were filled with a sterile serum surrogate and exposed to the φX174 virus in a flask, with shaking for 180 minutes at 37° C. Aliquots of 5 ml were withdrawn at baseline, 30, 60, 120, and 180 minutes and assayed by a standard plaque assay. The remaining contents of the gloves were then tested by an extremely sensitive qualitative assay (plaque assay without dilution of the sample). Results: With the standard plaque assay, virus was detected in 30% of the brand 1 latex gloves, in 80% of the brand 2 latex gloves, but in none of the thermoplastic elastomer gloves. The qualitative assay, which can detect even a single virus in the entire glove contents, had positive results for 30% of the thermoplastic elastomer gloves, 70% of the brand 1 gloves, and 100% of the brand 2 gloves. Conclusions: Despite the small sample, the results of this stringent assay suggest that the mechanical barrier offered by thermoplastic elastomer gloves is equal to or better than that provided by the latex gloves tested. Clinical studies are needed to evaluate thermoplastic elastomer gloves, which may withstand mechanical stress better than latex or vinyl. Thermoplastic elastomer gloves may therefore be a desirable alternative for health care workers in high-risk settings or for individuals with latex allergies.