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Biomedical subjects

K C Lowe

Publications and source records attributed to K C Lowe.

At least 73 records · Page 4Linked to original sources

Effects of emulsified perfluorochemicals on liver aryl esterase in rats.

1. The effects of intravenous (i.v.) injection of various perfluorochemical (PFC) emulsions have been studied separately in male and female rats. 2. Injection of 10 ml/kg body weight of either Fluosol-DA 20% (F-DA) or a novel perfluorodecalin emulsion containing a C-16 oil additive in male rats increased liver weight up to 7 days later; no corresponding change occurred in response to injection of Oxypherol (FC-43). 3. Liver weight was also increased in female rats at 72 hr after injection of the novel emulsion but this was less pronounced than in males; liver weight in female rats was unchanged in response to injection of either F-DA or FC-43. 4. Mean liver aryl esterase activity in male rats was increased 2- to 3-fold (P less than 0.05) at 7 days after injection of the novel emulsion. No significant alterations in aryl esterase activity occurred in response to injection of either F-DA or FC-43, although in both cases there was a trend towards increased activity. 5. Liver aryl esterase activity in female rats was significantly (P less than 0.05) decreased at 72 hr following FC-43 injection with similar, but much less pronounced, changes occurring in response to injection of F-DA and the novel emulsion. 6. These results show that injection of a single low dose of emulsified PFCs into rats can alter hepatic microsomal aryl esterase activity but the response is highly variable, depending on composition of emulsion injected and sex of recipient.

Animals↗

Synthetic oxygen transport fluids based on perfluorochemicals: applications in medicine and biology.

Recent advances in the development and assessment of synthetic oxygen transport fluids based on perfluorochemicals (PFCs) are reviewed. The basic properties of PFCs are outlined, together with the selection criteria for biomedical applications. PFCs must be emulsified for intravascular use and attention is focussed on the formulation and biocompatibility testing of both first- and second-generation emulsions and their components in man and other species. The multidisciplinary applications for PFCs in medicine and basic biomedical research are described, including the clinical use of Fluosol-DA 20% as an oxygen-carrying perfusate in percutaneous transluminal coronary angioplasty.

Biological Transport↗

Effects of Pluronic F-68 on 2-deoxyglucose uptake and amino acid incorporation into chick embryonic fibroblasts in vitro.

The effects of the nonionic surfactant Pluronic F-68 on 2-deoxyglucose uptake and amino acid incorporation in vitro into chick embryonic fibroblasts prepared from day 7 embryos have been studied. During early culture growth (3-10 days), Pluronic supplementation at 0.05% (w/v), but not at 0.1%, stimulated 2-deoxyglucose uptake by 20%-30% above control levels. Pluronic also markedly increased amino acid incorporation, maximally at 3 days of culture (200%-300% above control levels with 0.1% and 0.05% Pluronic, respectively), but to a lesser extent thereafter. These effects of Pluronic were seen only when freshly-prepared solutions were used; 'aged' solutions produced no comparable stimulation of 2-deoxy-glucose uptake or amino acid incorporation.

Amino Acids↗

Perfluorochemical oxygen carriers and ischaemic tissues.

This paper has outlined the potential beneficial effects of emulsified PFCs for ischaemic tissue rescue. There are very strong indications that PFC emulsions will come to play an important part in the management of the ischaemic tissues. However, the immediate goal of future studies should be to assess the value of improved formulations in this context together with analysis of their mechanism(s) of action, both alone and in combination with other therapeutic agents.

Angioplasty, Balloon, Coronary↗

Oxygen-transport fluid based on perfluorochemicals: effects on liver biochemistry.

The effects of (1) i.v. injection of various perfluorochemical (PFC) emulsions, (2) different fractions of the non-ionic poloxamer surfactant, Pluronic F-68, or (3) i.p. injection of component PFC oils have been studied separately in male and female rats. Injection of 10 ml/kg body wt of either Fluosol-DA 20% (F-DA) or a novel perfluorodecalin emulsion containing a C-16 oil additive in male rats increased liver weight up to 7 days later; no corresponding effect occurred in response to injection of Oxypherol (FC-43). Liver weight was also increased in female rats at 72 hr after injection of the novel emulsion but this was less pronounced than in males; liver weight in female rats was unchanged in response to injection of either F-DA or FC-43 but was 12% greater at 72 hr after injection of FDC oil. Mean liver microsomal cytochromes P-450 concentrations in male rats were increased 2-3 fold at 72 hr after injection of either FDC, F-DA or the novel emulsion; a less pronounced increase was also seen at 7 days in animals receiving the novel emulsion. No significant alterations in cytochromes activity occurred in response to injection of FTPA, FTBA, the C-16 oil, FC-43 or either commercial grade or purified pluronic solution. Liver cytochromes P-450 concentrations in female rats were unaffected by any of the experimental treatments.

Animals↗

Perfluorochemicals and photodynamic therapy in mice.

The effects of pre-treatment with a novel PFC emulsion on PDT-induced tumor necrosis have been studied in mice. Injection of emulsion either 2.5 hr or 24 hr before PDT did not affect the depth of tumour necrosis. However, pre-treatment with the emulsion appeared to protect skin against photodynamic damage although the mechanism(s) and active principle(s) involved were not identified. These results suggest that there may be specific advantages in using emulsified PFCs in conjunction with PDT which may be independent of changes in tumour oxygenation.

Animals↗

Perfluorochemicals for gas transport and improvement of cell cultures.

This paper has considered the effects and potential application of PFCs, their emulsions and emulsion components for regulating growth and metabolic functions of microbial, animal and plant cells in culture. PFCs will help to overcome problems encountered in conventional culture systems (e.g. limited gas supply, mechanical damage), especially where cells are grown to high density. While the commercial potential of PFCs for in vitro systems has not yet been fully exploited, the most exciting areas for future developments are in the culture of animal and plant cell lines of importance in biotechnology and medicine.

Animals↗

Effects of emulsified perfluorochemicals on liver cytochromes P-450 in rats.

1. The effects of intravenous (i.v.) injection of various perfluorochemical (PFC) emulsions or different fractions of the non-ionic poloxamer surfactant, Pluronic F-68, have been studied separately in male and female rats. 2. Injection of 10 ml/kg body wt of either Fluosol-DA 20% (F-DA) or a novel perfluorodecalin emulsion containing a C-16 oil additive in male rats increased liver weight up to 7 days later; no corresponding effect occurred in response to injection of Oxypherol (FC-43). 3. Liver weight was also increased in female rats at 72 hr after injection of the novel emulsion but this was less pronounced than in males; liver weight in female rats was unchanged in response to injection of either F-DA or FC-43. 4. Mean liver microsomal cytochromes P-450 concentrations in male rats were increased 2-3 fold at 72 hr after injection of either F-DA or the novel emulsion with a less pronounced increase also seen at 7 days in animals receiving the novel emulsion. No significant alterations in cytochrome concentration occurred in response to injection of FC-43 or either commercial grade or purified pluronic solution. 5. Liver cytochromes P-450 concentrations in female rats were unaffected by any of the experimental treatments. 6. These results show that injection of a single low dose of emulsified PFCs into male rats can increase hepatic microsomal cytochromes P-450 concentration but the response is highly variable, depending on composition of emulsion injected.

Animals↗

Effects of a novel perfluorochemical emulsion on lymphoid tissues and immunocompetence in rats: time course effects relative to immunological challenge.

1. The effects of intravenous (i.v.) injection of low doses of a novel perfluorochemical (PFC) emulsion on lymphoid tissues and antibody production against i.v.-injected sheep red blood cells (SRBC) have been studied relative to the timing of immunization in rats. 2. Spleen and, to a lesser extent, liver weights were significantly increased in response to injection of emulsion but no consistent pattern was observed. 3. Thymus weight was consistently decreased following injection of emulsion; in contrast, mesenteric lymph node (MLN) weights were unchanged throughout except for a significant increase in animals injected with emulsion 24 hr prior to immunization. 4. The mean plasma antibody titre to SRBC showed a variable response in animals receiving the emulsion: titres were significantly increased in rats injected with emulsion 1 hr prior to immunization whereas they were significantly reduced in animals injected with emulsion 7 days before SRBC. 5. These results show that lymphoid tissue weights and plasma antibody titres to SRBC vary according to the time of a previous or subsequent injection of PFC emulsion.

Animals↗

Purification of pluronic F-68 for perfluorochemical emulsification.

A novel technique for purification of Pluronic F-68 has been developed involving passage through a silica-Amberlite resin column. Impurities present in commercial grade Pluronic could be readily removed, as confirmed by analysis of absorption and fluorescence emission bands. Intravenous injection of a 4% (w/v) unpurified Pluronic solution in male rats increased mean liver weight by 14% (P less than 0.05) after 24 h and increased spleen weight in female rats by 29% (P less than 0.01) after 7 days. No corresponding tissue weight changes occurred following injection of purified Pluronic solution. Haematocrit and red cell counts were also unchanged throughout. We propose that the use of purified Pluronic for perfluorochemical emulsification may reduce previously reported side-effects.

Animals↗

Emulsified perfluorochemicals for oxygenation of microbial cell cultures?

PFCs and their emulsions may have value for increasing the efficiency of O2-transport to microbial cultures. Therefore, the effects of emulsion components on growth of S. cerevisiae and E. coli have been examined. Viable cell counts revealed that perfluorodecalin or the commercial emulsion, Fluosol-DA 20%, produced no obvious growth-inhibition over 6h. However, incubation of cells with up to 10% of the Pluronic F-68 surfactant reduced absorbance at 600nm. Further experiments to assess the effects of PFC emulsion components on growth and structure of microbial cells are in progress.

Culture Media↗

Emulsified perfluorochemicals for oxygen-transport to tissues: effects on lymphoid system and immunological competence.

Data from both in vivo and in vitro studies to assess lymphoid tissue and immune system responses to emulsified PFCs and their components have been discussed. It may be concluded that the extent to which PFC emulsions are retained in lymphoid tissues and their effects on the manifestation of humoral immune responses to immunological "challenges" is variable and depends upon: (1) Emulsion composition; (2) Dose administered; (3) Route of administration; (4) Tissue examined; (5) Timing of emulsion administration relative to immune challenge; and (6) Species studied. Such variability in the responses to emulsified PFCs has inevitably introduced difficulties in assessing their effects upon immunological competence. Further work is needed determine the extent to which lymphoid tissue functions may be altered by PFC emulsions and identify the active component(s) and mechanism(s) involved.

Fluorocarbons↗

Lymphoid tissue responses to perfluorocarbon emulsion in rats: time course effects relative to immune challenge.

1. The effects of either intraperitoneal (i.p.) or intravenous (i.v.) injection of low doses (10 ml/kg) of the commercial emulsion, Fluosol-DA 20% (F-DA), on lymphoid tissues and antibody production against sheep red blood cells (SRBC) have been studied relative to the timing of immunization in rats. 2. Spleen and liver weights were significantly increased in response to injection of F-DA although no consistent pattern was observed. 3. Thymus weight was decreased following F-DA injection in some experimental groups whereas mesenteric lymph node (MLN) weights were unchanged throughout. 4. The mean plasma antibody titre to SRBC was significantly increased in some groups of animals injected with F-DA both before or after immunization; maximum titres were observed following injection of emulsion simultaneously with SRBC. 5. These results show that lymphoid tissue weights and plasma antibody titres in rats immunized with SRBC vary according to the timing and route of a previous or subsequent injection of F-DA.

Animals↗

Novel compositions of emulsified perfluorochemicals for biological uses.

Physico-chemical characteristics of novel perfluorodecalin emulsions stabilized against Ostwald ripening by the addition of polycyclic, perfluorinated oil additives are described. The effects of varying both oil additive and emulsifier concentrations have been examined. Stabilizing effects of additives were found to be related to molecular weight and hence, boiling point and vapour pressure.

Blood Substitutes↗

Biocompatibility studies with a novel perfluorochemical emulsion.

Biocompatibility studies with a novel perfluorochemical (PFC) emulsion have been performed in rats. Injection of the emulsion was followed by changes in lymphoid tissue weights, comparable but not identical to those produced by the commercial formulation, Fluosol-DA 20% (F-DA). Peritoneal injection of either the novel emulsion or F-DA enhanced the humoral immune response to intraperitoneally-injected sheep red blood cells (SRBC) suggesting immunopotentiating properties of emulsion components.

Animals↗

Lymphoid tissue responses to emulsified perfluorochemicals: comparative aspects.

The effects of a single, low dose (10 ml/kg) injection of the perfluorochemical (PFC) emulsion, Fluosol-DA 20%, on lymphoid tissues and antibody production against sheep red blood cells (SRBC) have been studied relative to the timing of immunization in rats and mice. Intravenous (i.v.) or intraperitoneal (i.p.) injection of emulsion in both species produced alterations in lymphoid tissue weights and the magnitude of these responses was highly tissue- and species-specific. Injection of Fluosol-DA tended to potentiate the humoral immune response to SRBC but this depended on timing and route of emulsion administration relative to immunization. We conclude that lymphoid tissue responses to emulsified PFCs are highly variable and depend upon a number of factors including: emulsion composition and dose; route and timing of administration relative to immunological "challenge"; tissue and species examined.

Animals↗

Perfluorocarbons as oxygen-transport fluids.

1. An overview of the proposed biological applications of perfluorocarbons and their emulsions as oxygen-transport fluids is presented. 2. Aspects of the properties, preparation, composition and physiological assessment of perfluorocarbon emulsions are discussed. 3. The experimental basis for some of the potential therapeutic uses of PFCs in liquid ventilation, treatment of decompression sickness, organ perfusion, oxygenation of ischaemic and malignant tissues, and as contrast media for NMR imaging is described. 4. The extent to which emulsified perfluorocarbons may have value as substitutes for red blood cells is discussed in detail. Data from both animal and human studies with such emulsions is reviewed. Brief consideration is also given to the possible use of native and modified haemoglobin in blood replacement together with recent work on the preparation of so-called "synthetic red cells".

Animals↗