REACTIVATION OF NEUTRALIZED VIRUS BY FLUOROCARBON: MECHANISM OF ACTION AND DEMONSTRATION OF REDUCED REACTIVABILITY WITH TIME OF VIRUS-ANTIBODY INTERACTION.
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Antibodies↗
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BIOPHYSICAL AND BIOCHEMICAL CHARACTERIZATION OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS. 2. PARTIAL PURIFICATION BY DIFFERENTIAL CENTRIFUGATION AND FLUOROCARBON TECHNIQUES.
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Animals↗
Polymer-fume fever associated with smoking and use of a mold-release spray containing polytetrafluoroethylene.
An ephemeral and debilitating flu-like illness experienced by stamp-makers prompted them to solicit assistance from the National Institute for Occupational Safety and Health. It was determined that a combination of the use of a mold-release spray containing a fluorocarbon polymer (polytetrafluoroethylene), poor general hygiene, and smoking during and after use of the spray was responsible for the workers' symptoms, commonly referred to as "polymer-fume fever." Recommendations made, and which resulted in the abatement of illness included: ventilating the vulcanizing furnace, cessation of smoking in the workplace, or using a mold-release spray that does not contain fluorocarbon.
Adult↗
Perfluorochemicals and cell biotechnology.
Perfluorochemical (PFC) liquids have properties, especially high gas solubility, which make these compounds useful in medicine and biotechnology. PFCs are being employed to facilitate respiratory gas supply to both prokaryotic and eukaryotic cells and, in some systems, to improve biomass production and yields of commercially-important cellular products. Animal (including human) and plant cells have also been cultured at the interface between PFC liquids and aqueous culture medium, while fluorocarbon polymers have been employed as gaspermeable membranes in eukaryotic cell cultures. This paper presents an overview of the applications and beneficial effects of PFCs in microbial, animal and plant culture systems. PFCs have been compared with other physical and chemical options for manipulating respiratory gas supply to cultured cells. PFC-facilitated improvements in cell culture technology will have increasingly important biotechnological implications.
Animals↗
Alloplastic implants of the larynx.
Biocompatible Teflon fluorocarbon polymer (Proplast) and porous polyethylene (Plasti-Pore) are porous alloplastic implant materials that are widely used in reconstructive head and neck surgery. These two materials were used in our study as replacement grafts for defects in three groups of 12 canines. For the first time, Plasti-Pore was found equal and perhaps superior to Proplast in deep implantation, this in the anterior cricoid cartilage when the internal and external perichondrium were preserved. Rejection of both substances occurred when the implant was exposed to air and aerodigestive tract contaminants after the removal of the perichondrium, subglottic, and upper tracheal mucosa. Airway exposure to the alloplasts, even when lined with buccal mucosa, resulted in infection and extrusion, but at a much slower rate.
Animals↗
Pharmacolinetics of fluorocarbon 11 and 12 in dogs and humans.
Blood levels and exhalation bag contents of FC-11 and FC-12 from dogs and humans were used to elucidate the pharmacokinetic model describing the time-course of these agents. The derived pharmacokinetic parameters were in good agreement with the physicochemical properties of these substances. The model was used to estimate the percentage of dose absorbed, which averaged 77 per cent for FC-11 and 55 per cent for FC-12, and to predict the level of FC-11 and FC-12 under a variety of conditions simulating both short- and long-term exposure to the maximum allowable concentrations of these agents. With similar doses, an 8-hour continuous exposure was estimated to produce levels of FC-11 and FC-12 that are much lower than the corresponding levels reported to induce cardiac sensitization in dogs.
Animals↗
Determination of fluorocarbon in blood.
Because fluorocarbons can dissolve relatively large quantities of oxygen and carbon dioxide, there is considerable interest in utilizing them to develop new methods of extracorporael circulation, artificial red blood cells, and liquid breathing techniques. A method for the assay of fluorocarbon in blood is presented. The fluorocarbon is extracted from the blood with toluene, and fluoride is released from the fluorocarbon in the toluene extract by reaction with sodium biphenyl. The inorganic fluoride is then extracted with aqueous sodium acetate, the pH of the extract is adjusted, and the activity of the fluoride ion is read with a fluoride-specific ion electrode. The assay was effective for fluorocarbon concentrations in the range of 1 to 30 ppm.
Biphenyl Compounds↗
Surface spectroscopic studies of Avcothane.
Avcothane is a commercially available copolymer of polyether, polyurethane, and polydimethylsiloxane; it is used primarily in aortic balloon pumps. The pumps consist of three segments which are cemented or fused together to form the balloon. The objective of this work is to characterize the surfaces, inside and outside, of the three balloon pump sections. By using x-ray photoelectron spectroscopy (ESCA), ion scattering spectroscopy (ISS), and secondary ion mass spectrometry (SIMS) a detailed analysis of the Avcothane surfaces can be performed and comparisons between various surfaces made. Previous workers have reported ESCA and Auger electron spectroscopy (AES) measurements of Avcothane and comparisons with their results will be presented. SIMS and ISS are useful analytical tools for studying polymeric biomaterials because these techniques are usually more surface sensitive than either ESCA or AES. SIMS and ISS data indicate that a thin fluorine-rich film (probably a fluorocarbon polymer) is present on the Avcothane surface. Signals from the fluorine-rich layer are more intense from the inside of the balloon pump and the intensity generally decreases from top to bottom. The outside sections of the aortic balloon pump also show the presence of fluorine, but the signals are far less intense than from the inside. One possible explanation for the fluorine-rich layer is that a fluorine-containing compound is deposited on the balloon pump during molding and preparation. Another possibility is that the layer is deposited during preparation of the Avcothane itself, but is essentially removed from the outside during sterilization.
Assisted Circulation↗
Use of perfluorocarbon (fluorinert) to enhance reporter gene expression following intratracheal instillation into the lungs of Balb/c mice: implications for nebulized delivery of plasmids.
Perfluorocarbons combine high respiratory gas dissolving capabilities with extreme chemical and biological inertness and therefore offer an attractive option as an excipient in the area of pulmonary therapeutics. Perfluorocarbons have also been shown to "float" mucus, because of their high densities (1.9-2.5 g/mL), which may hold potential in gene delivery for cystic fibrosis patients, in terms of enhancing penetration through highly viscous mucus and thereby providing access to target epithelial cells to correct the gene defect. Additionally, their low surface tension allows for better dispersion. A commonly available perflurocarbon, heptacosafluorotributylamine (Fluorinert), was used to deliver either plasmid DNA (pDNA) alone or cationic-lipid-complexed plasmid DNA to the lungs of Balb/c mice by direct intratracheal instillation. The complexes consisted of supercoiled (SC) plasmid DNA (4.7 Kb, 0.625 mg/mL) and lipid (ethyldimyristoyl phosphatidylcholine [EDMPC]/cholesterol [1:1 mole ratio], with pDNA (3:1 mg pDNA/mM EDMPC in 20 mM Tris-HCl pH 8.0) expressing chloramphenicol acetyl transferase (CAT) or beta-galactosidase (beta-Gal). pDNA alone was supplemented with 14% w/v Fluorinert. Cationic lipid/pDNA complexes were supplemented with 3, 8, and 14% w/v Fluorinert. Results showed that the CAT expression from pDNA alone was enhanced 24 x using 14% w/v Fluorinert, whereas that from the cationic-lipid-formulated pDNA was enhanced 7 x using 14% w/v Fluorinert. Immunohistochemistry showed that beta-Gal expression was primarily from epithelial cells and not from F4/80 or MAC3 antigen-stained cells (predominantly macrophages), indicating efficient delivery.
Animals↗
Fluorocarbon aerosol propellants V: binding interaction with human albumin.
Binding of trichloromonofluoromethane, dichlorodifluoromethane, and dichlorotetrafluoroethane was studied in aqueous 5% human albumin solution, using the partition coefficient method in sealed serum bottles. The partition coefficient and the fraction of fluorocarbons bound were highly dependent on fluorocarbon concentrations. The average binding sites per molecule of albumin were 2.17, 0.30, and 0.42 and the binding association constants were 1.11 X10-3, 1.73 X10-3, and 5.06X10-3 M-minus 1, respectively. At the lowest concentration studied, 62.3, 25.5, and 65.6% were found bound to albumin, respectively. This appears to represent the first extensive study on any gas-albumin interaction.
Aerosol Propellants↗
Use of perfluorochemical liquid allows earlier detection of gene expression and use of less vector in normal lung and enhances gene expression in acutely injured lung.
One of the obstacles to successful lung gene transfer is effective delivery of vector to lung, particularly injured or diseased lung. We have previously demonstrated that intratracheal instillation of perfluorochemical (PFC) liquids along with instillation of recombinant adenovirus and adeno-associated virus vectors, or with cationic liposome vectors, increased total lung gene expression and enhanced distribution of gene expression throughout the lung. To further explore the potential benefits of PFC liquid use, we evaluated the effect of PFC liquid instillation on several other aspects of adenovirus-mediated gene expression in lung. Use of PFC liquid resulted in earlier detection of gene expression and allowed the use of less vector to achieve expression comparable to that observed with the use of higher amounts of vector alone. Using PFC liquid also enhanced gene expression in a rodent model of acute lung injury. PFC liquid did cause a transient inflammation when instilled into normal lungs but did not cause any additional inflammation when instilled alone or with adenovirus vector into acutely injured lungs. Thus, PFC liquid may be a useful adjunct for clinical lung gene transfer, particularly for injured or diseased lungs.
Adenoviridae↗
Comparison of surfactant and perfluorochemical liquid enhanced adenovirus-mediated gene transfer in normal rat lung.
Both surfactant- and perfluorochemical (PFC)-based vehicles enhance adenovirus-mediated gene transfer in the lung. To compare the relative effects of surfactant and PFC liquid, we infected orotracheally intubated Sprague-Dawley rats with 4 x 10(9) pfu of an E1a(-)/E3(-) adenovirus expressing either an Escherichia coli lacZ (AdlacZ) mini-gene or no cDNA (Adnull). Surfactant-mediated delivery was achieved via instillation of four, 200-microl aliquots of virus suspended in a 50% surfactant (Survanta) vehicle over a 15-minute period. PFC rats received virus in 100 microl of saline followed by instillation of the PFC liquid FC-75 (10 cc/kg body weight) over a 2- to 3- minute period. Lungs were collected 3 days later for measurement of beta-galactosidase (beta-gal) expression and indices of inflammation. Both PFC liquid and surfactant-based vehicles produced widespread beta-gal expression and increased total beta-gal activity over that observed with instillation of vector alone. Both vehicles comparably increased bronchoalveolar lavage fluid (BALF), total cell counts, neutrophils, total protein, and IFN(gamma). FC-75 was also associated with increased BALF IL1beta. In conclusion, surfactant and FC-75 are similarly effective vehicles for adenovirus-mediated gene transfer to the lung.
Adenoviridae↗
Large-scale perfusion culture process for suspended mammalian cells that uses a centrifuge with multiple settling zones.
A high-cell-density perfusion culture process, using a novel centrifuge, was developed. The centrifuge has spiral multiple settling zones to separate cells from culture medium. Because of the multiple zones, the separation area can be efficiently increased without enlarging the diameter of the centrifuge. The centrifuge used in this study had a separation capacity of 2600 ml culture medium min -1 at 100 g of the centrifugal force. A new cell separation and withdrawal method was also developed. The cells separated in the centrifuge can be withdrawn easily from the centrifuge with no cell clogging by feeding a liquid carrier such as a perfluorocarbon into the centrifuge and pushing the cells out with the liquid carrier. By this culture process, monoclonal antibodies were produced with mouse-human hybridoma X87X at a cell density of about 8 x 10(6) cells ml -1 for 25 days. This centrifuge culture shows promise as a large-scale perfusion culture process. (Himmelfarb et al. 1969; Feder and Tolbert 1983) usually have the problem of filter clogging, and perfusion culture processes with gravitational cell settling (Tokashiki and Arai 1989) are limited in scale-up because of low separation efficiency. Recently centrifugal separation of cells from culture medium has been used for perfusion culture processes (Hamamoto et al. 1989; Tokashiki et al. 1990; Apelman 1992; Jäger 1992). This process essentially has a high separation efficiency and can avoid further operational problems, such as filter clogging, by the type of filtration. To investigate the scale-up feasibility of the centrifuge culture system, we have developed a new type of centrifuge with four layers of spiral cell-settling zones to increase the separation area, and a novel cell separation and withdrawal method using a perfluorocarbon.
Animals↗
Clinical findings on the use of long-term heavy tamponades (semifluorinated alkanes and their oligomers) in complicated retinal detachment surgery.
BACKGROUND: Heavy tamponades for pathologies in the lower part of the retina are a new development, and different tamponades have recently come into clinical use: semifluorinated alkanes (F(6)H(6), F(6)H(8)) and their oligomers (OL62HV). METHOD: Nine patients had been operated on using F(6)H(8) (n=5) and by OL62HV (n=4). In all cases the reasons for using the tamponades were complicated retinal detachments in the lower part. In three cases the use was primary and in six cases tamponades were used after reoperations. In all cases the endotamponade was removed within 6 weeks. Fluorescein angiography (FLA) was performed in the F(6)H(8) group. RESULTS: In the F(6)H(8)group dispersion developed in two of the three aphacic patients. In two out of five cases soft epiretinal membranes and cellular material could be found between the substance and the lower periphery. In two membranes examined by light microscopy, cystic cells and amorphous material could be found. In one case (PDRP, aphacic) cyclophotocoagulation had to be performed because of persistent elevated IOP. FLA was unremarkable. In the OL62HV group, severe recurrent PVR reaction occurred in the lower periphery (2/4) and unusual precipitates were observed (4/4). In one case, after a normal postoperative period (VA 0.05 after 5 days) an extensive cellular reaction on the complete surface of the tamponade occurred. After 5 weeks VA was no light perception. During removal of the oligomer unusual adherent cellular components were found on the surface of the retina. The retina appeared necrotic, showed constricted retinal vessels and there was optic atrophy. Histologically, fluffy epiretinal material and a lens capsule obtained from one eye filled with OL62HV resembled the appearance with F(6)H(8). CONCLUSION: Heavy endotamponades on the basis of semifluorinated alkanes can lead to an unusual biological reaction and need further investigation before clinical use.
Adult↗
Fluorocarbon air pollutants II.
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Air Pollutants↗
Vertical gradients of pleural and transpulmonary pressure with liquid-filled lungs.
In supine dogs with saline-filled lungs the vertical gradient of pleural surface pressure (VGPpl) was not significantly different from -1 cm H2O/cm and that of transpulmonary pressure (VGPtp) was not significantly different from zero. Hence the hydrostatic gradient of the liquid was entirely taken up by the chest wall, the ribs being rigid in the direction of gravity and the diaphragm facing an equal hydrostatic gradient on both sides. In head-up dogs VGPpl was -0.8 cm H2O/cm when the level of the liquid in the filling system was 19.5 cm below the lung top and -0.5 cm H2O/cm when this level corresponded to the top. The hydrostatic gradient of the liquid was not entirely taken up by the rib cage because of its uneven regional compliance and VGPtp was reversed with respect to that of the air-filled lung. With fluorocarbon (specific gravity 1.75) filled lungs in the supine posture VGPpl was about -1.28 cm H2O/cm and VGPtp was reversed. In the head-up posture VGPpl was about -1.2 cm H2O/cm and VGPtp was reversed.
Airway Resistance↗
High-performance liquid chromatography with conductimetric detection of perfluorocarboxylic acids and perfluorosulfonates.
A rapid and simple method for separating and determining various environmentally harmful perfluorocarboxylic acids and perfluorosulfonates was successfully developed using high- performance liquid chromatography with conductimetric detection, for product and waste management of these compounds at manufacturing and processing sites. Compounds having C(3)-C(8) perfluoroalkyl groups were separated using a Tosoh TSKgel Super-ODS column and a mobile phase consisting of a mixture of methanol and aqueous NaH(2)PO(4) at several mixing ratios. The best detection limits for the compounds ranged from 0.12 to 0.66 mg l(-1) (ppm), and linear calibration graphs were obtained up to 87-109 mg l(-1). The combination of this method with concentration of the sample by solid-phase extraction with cartridges based on styrene-divinylbenzene-copolymer enabled the determination of approximately 50 microg l(-1) (ppb) for compounds with C(4)-C(8) perfluoroalkyl groups. This method was successfully used to monitor the artificial decomposition of the perfluorocarboxylic acid n-C(4)F(9)COOH induced by a photocatalyst.
Carboxylic Acids↗
Preservation of rainbow trout (Oncorhynchus mykiss) eyed eggs using a perfluorochemical as an oxygen carrier.
The objective of this study was to maintain the viability of chilled rainbow trout (Oncorhynchus mykiss) eyed eggs during storage using oxygenated perfluorochemical (PFC). Three trials were conducted using eggs at 161, 180 or 217 degree days (days from fertilization x incubation temperature in degrees C). A separate trial was conducted for 147 degree day eggs that were not at the eyed stage. For each trial, eggs were stored in a moisture-saturated atmosphere at 1 degrees C in PFC, water, and 1:1 combinations of PFC and PBS, PFC and 0.3 M glucose, PFC and mineral oil, or PFC and water. The PFC was oxygenated before each trial and all media were oxygenated at weekly intervals during the storage period. Eggs from each trial were also incubated without storage to provide Day 0 results. After 3 and 5 weeks of storage, eggs from each medium were incubated at 10 degrees C until hatch. Hatching percentage was expressed as a percentage of Day 0 results. The percentage of normal alevins that hatched was also determined. There were interactions (P < 0.01) between stage of development and treatment for hatching percentage after 3 and 5 weeks of storage. After 3 weeks of storage, eggs stored at 161, 180, or 217 degree days without PFC had hatching rates of 0-14.3% but eggs stored in any medium with PFC had hatching percentages from 75.1 to 106.4% of Day 0 values. After 5 weeks of storage, eggs stored at 161 degree days in PFC plus PBS or PFC plus water, and eggs stored at 217 degree days in PFC or PFC plus water, had higher (P < 0.05) hatching percentages than eggs stored in any of the other media. Eggs stored at 161 degree days for 5 weeks in PFC and water had a higher (P < 0.05) percentage of normal alevins hatching than eggs stored in PFC and PBS. Because of their early developmental stage, eggs stored at 147 degree days had low hatching percentages, except eggs stored for 3 weeks in PFC or PFC plus PBS. Chilling eyed eggs of rainbow trout to 1 degrees C and storing them in water with PFC as an oxygen carrier can preserve their viability for 5 weeks.
Animals↗