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Biomedical subjects

C Stirling

Publications and source records attributed to C Stirling.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of particle-based DNA delivery for vaccination of sheep against FMDV.

As an alternative strategy to classical inactivated viral vaccine against FMDV, naked DNA vaccine is attractive because of safety, flexibility and low cost. However DNA vaccination is usually poorly efficient in target species. Indeed we found that naked DNA plasmids encoding for P1-2A3C3D and GM-CSF proteins did not induce any detectable immunity against FMDV in sheep. Interestingly, we demonstrate herein that formulations of DNA on poly(D,L-lactide-co-glycolide) (PLG) or in lipofectin triggered divergent types of immune responses: PLG stimulated a T cell response and could elicit significant neutralising antibody titers, whereas lipofectin generated even higher antibody titers but no significant T cell response. The DNA/PLG regimen used in five sheep protected against clinical symptoms and viraemia and prevented the carrier state in four of them. Thus formulated DNA can be remarkably efficient against FMDV in a ruminant species that is usually refractory to DNA vaccination.

Animals↗
PubMed2006

Porcine gammadelta T cells: possible roles on the innate and adaptive immune responses following virus infection.

gammadelta T cells recognise different types of antigen in alternative ways to alphabeta T cells, and thus appear to play a complementary role in the immune response. However, unlike alphabeta T cells, the role or function of gammadelta T cells is still unclear. As pigs possess a high proportion of circulating gammadelta T cells, they are suitable large animal model to study gammadelta T cell functions. This as yet has not been fully exploited, leaving porcine gammadelta T cell biology and its role in immunity in its infancy. Foot-and-mouth disease (FMD) high potency "emergency" vaccines are able to induce early protection from challenge and it has been suggested that, in part, there is some involvement of innate immune responses. The antigen component of the vaccine is able to stimulate purified naive pig gammadelta T cells and induce the mRNA of various cytokines and chemokines. This observation suggests that gammadelta T cells probably contribute to the early phase of the immune responses to FMD vaccination, and perhaps infection. A subset of these circulating gammadelta T cells display a phenotype similar to professional antigen presenting cells and are able to take up and present soluble antigen to CD4(+) T cells in a direct cell-cell interaction via MHC class II. This direct interaction between gammadelta T cells and CD4(+) T cells is likely to have a significant influence on the out come of the adaptive immune response.

Adaptation, Physiological↗
PubMed2004

The effect of high dose atorvastatin therapy on lipids and lipoprotein subfractions in overweight patients with type 2 diabetes.

Few data are available on the effects of high dose statin therapy on lipoprotein subfractions in type 2 diabetes. In a double blind randomised placebo-controlled trial we have studied the effects of 80 mg atorvastatin over 8 weeks on LDL, VLDL and HDL subfractions in 40 overweight type 2 diabetes patients. VLDL and LDL subfractions were prepared by density gradient ultracentrifugation. Triglycerides, cholesterol, total protein and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. Atorvastatin 80 mg produced significant falls in LDL subfractions (LDL(1) 66.2 mg/dl:36.6 mg/dl, LDL(2) 118:56.6 mg/dl, LDL(3) 36.9:19.9 mg/dl all P < 0.01 relative to placebo) and VLDL subfractions (VLDL(1) 55:22.1 mg/dl, VLDL(2) 40.1:19.1 mg/dl, VLDL(3) 52.6:30 mg/dl all P < 0.01 relative to placebo). There was no change in the proportion of LDL present as LDL(3). There was a reduction in the proportion of VLDL as VLDL(1) and a reciprocal increase in the proportion as VLDL(3). Changes in VLDL subfractions were associated with changes in lipid composition, particularly a reduction in cholesterol ester and a reduction in the cholesterol ester/triglyceride ratio. Effects on HDL subfractions were largely neutral. High dose atorvastatin produces favourable effects on lipoprotein subfractions in type 2 diabetes which may enhance antiatherogenic potential.

Aged↗
PubMed2003

Diarrhoea, vomiting and ACE inhibitors:--an important cause of acute renal failure.

The occurrence of severe acute renal failure in 3 patients who developed diarrhoea while taking angiotensin converting enzyme (ACE) inhibitors led us to undertake a retrospective cohort survey to determine the frequency with which diarrhoea and vomiting are associated with acute renal failure in patients taking this class of drug. Serum creatinine was measured as part of the diagnostic workup of 2398 consecutive admissions to an acute medical receiving unit in a district general hospital. Outcome measures were the presence of diarrhoea and/or vomiting, and whether taking an ACE inhibitor, NSAID or diuretic at the time of admission, also previous, initial and follow up serum creatinine concentrations. Peak serum creatinine in the 3 cases was 1159, 989 and 765 micromol/l. None of the 3 required dialysis and all recovered renal function completely after receiving large volumes of intravenous fluid. In the cohort study, 89 of 2398(3.7%) admissions had serum creatinine >/=200 micromol/l. Nine were regular dialysis patients. Of the remaining patients, 30 (37.5%) were taking an ACE inhibitor. Six of 30 (20%) gave a history of diarrhoea and/or vomiting. Median creatinine concentration in this group was 135 (range 111-209) micromol/l before admission, 292 (216-724) micromol/l when first seen in hospital, and 134 (94-219) micromol/l following the withdrawal of drug therapy and fluid replacement. In conclusion, volume depletion causing acute renal failure in patients taking ACE inhibitors is not uncommon. Such patients and their general practitioners should be aware that reversible renal impairment may occur during intercurrent illnesses, particularly if characterised by diarrhoea and/or vomiting.

Acute Kidney Injury↗
PubMed2001

Reactions in the oral mucous membrane after exposure to Carisolv--combined results from a clinical screening test in humans and an experimental study in rats.

OBJECTIVE: To evaluate reactions in the oral mucosa after direct contact with Carisolv. SETTING: The Faculty of Odontology in Göteborg, Sweden. SUBJECTS: 34 healthy persons for a clinical screening test and 35 Sprague Dawley rats for a histological study. DESIGN: Mixed Carisolv or 0.5 % NaOCl were soaked in paper and applied to either side of the medial frenula of the lower lip of 34 persons. The solutions were left on the oral mucosa for three minutes. Inspection was made and photographs were taken immediately after exposure and also after 1 hour, 24 hours, and 72 hours. Mixed Carisolv was applied in a similar manner as described above to 35 adult Sprague Dawley rats. The animals were killed and biopsies were taken immediately after Carisolv exposure and also after 1 hour, 24 hours, and 48 hours. The biopsies were sectioned and prepared for histomorphometrical evaluation in light microscopy where cells were counted on regions from the epithelium layer deeper into the mucous membrane. RESULTS: Some adverse reactions were detected on the oral mucosa of humans up to 24 hours after Carisolv exposure for 3 minutes. The detected inflammatory reactions were slight and no patient felt any discomfort. The results of the histological study on rat did not show any statistically significant increase of the number of cells at any time after Carisolv exposure. CONCLUSIONS: If the oral mucosa gets in direct contact with Carisolv for 3 minutes no or only a weak inflammatory response may be expected.

Adult↗
PubMed1998

Developing a non-aversive intervention strategy in the management of aggression and violence for people with learning disabilities using natural therapeutic holding.

This paper builds upon a previous piece of research regarding the development of 'natural therapeutic holding' as a non-aversive alternative to control and restraint (C and R) in managing aggression and violence in people with learning disabilities. This paper represents aspects of an ongoing programme of research and explains the aims and values which underpin natural therapeutic holding by describing the theory, aims, values and practical application. The concepts of individual risk management and pro-active intervention strategies are discussed with illustrations of practical application given by means of a case study. The case study shows that over a relatively short period of time, an individual with severe learning disabilities who is aggressive and violent, learns alternative coping strategies to aggression and violence through the application of natural therapeutic holding. The article concludes that natural therapeutic holding is a very effective intervention strategy in the management of violence in people with learning disabilities from two perspectives: (a) it provides staff with safe, professional and ethical skills with which they can manage aggressive and violent clients and (b) as a therapy, natural therapeutic holding gives clients the opportunity to learn coping strategies which are more effective than violence.

Adaptation, Psychological↗
PubMed1997

Natural therapeutic holding: a non-aversive alternative to the use of control and restraint in the management of violence for people with learning disabilities.

For at least the last 10 years, control and restraint (C&R) has gained increased popularity amongst nurses as a safe, professional and legal means to manage violence in health care settings. However, during this period there has been an increased momentum to find non-aversive management strategies for people with learning disabilities and there has been frequent debate on the abolition of practices which do not achieve this. More recently, the main criticisms of C&R have been the professional and ethical objections that the techniques used inflict some degree of pain or discomfort to the client, and the fact that it remains a reactive strategy with no theoretical framework for professional practice. On this basis, alternatives should be sought which seek to address these issues. This paper outlines the development of natural therapeutic holding, an approach which is non-aversive and which provides a theoretical structure for professionals to base their practice on in order to develop clear therapeutic goals for the client. Initial findings within a small community residential service for people with learning disabilities indicate that natural therapeutic holding was a preferred method of intervention strategy by staff, proving as effective as C&R in the management of violent incidents, with interventions being much shorter in duration and non-aversive in nature.

Ethics, Nursing↗
PubMed1992

Transport of particles of colloidal gold within and from rat lung after local deposition by alveolar microinjection.

Because inhalation and intratracheal instillation deposit particles throughout the respiratory tract, these methods of administration give little information on the movement of particles within the lung and no direct information on the clearance kinetics from locally defined sites within alveolar tissue. Approximately 0.05 microL of 195Au-labeled gold colloid was administered to 32 rats by microinjection into a small volume of subpleural alveoli. Its fate was studied by whole-body counting and serial sacrifice over 15 months. The kinetics of clearance from the subpleural deposition site showed that there was no rapid removal of particles, and the main clearance process was defined by an exponential term with a half-time averaging 583 days. There was a wide variation between individual animals. The distribution of 195Au at sacrifice showed that the gold colloid was nearly all retained within the respiratory tract. The particles were not appreciably redistributed throughout the lung volume, so most of the material not cleared from the lung remained close to the deposition site. At the later times after microinjection, much of the gold colloid was associated with thickened pleura and adjoining septae.

Animals↗
PubMed1991

Effects of pravastatin and cholestyramine on gonadal and adrenal steroid production in familial hypercholesterolaemia.

1. Adrenal and gonadal steroids are derived from cholesterol, which may be derived from plasma lipoproteins or de novo synthesis. 2. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate limiting enzyme in cholesterol synthesis, may therefore affect steroidogenesis when used as lipid-lowering agents in hypercholesterolaemia. 3. We have assessed gonadal and adrenal function in subjects with heterozygous familial hypercholesterolaemia (FH) before and after 12 weeks treatment with pravastatin, an HMG CoA reductase inhibitor, or cholestyramine as a control in maximal recommended doses. 4. No changes in measured plasma cortisol responses to tetracosactrin injection were seen in 11 patients on cholestyramine or 12 on pravastatin. 5. No changes were seen in testosterone, sex hormone binding globulin, androstenedione, dehydroepiandrosterone sulphate, oestradiol or 17 alpha-hydroxyprogesterone. 6. Gonadotrophin levels were unaffected in 10 male subjects on cholestyramine and 7 on pravastatin. 7. Measurements on a subset of subjects continuing to 24 weeks treatment also showed no changes. 8. No adverse effect on adrenal or gonadal function could be demonstrated in patients with familial hypercholesterolaemia on maximal recommended doses of pravastatin.

Adrenal Glands↗
PubMed1990

Genetic and biochemical evaluation of eucaryotic membrane protein topology: multiple transmembrane domains of Saccharomyces cerevisiae 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Both 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase isozymes of the yeast Saccharomyces cerevisiae are predicted to contain seven membrane-spanning domains. Previous work had established the utility of the histidinol dehydrogenase protein domain, encoded by HIS4C, as a topologically sensitive monitor that can be used to distinguish between the lumen of the endoplasmic reticulum and the cytoplasm. This study directly tested the structural predictions for HMG-CoA reductase by fusing the HIS4C domain to specific sites in the HMG-CoA reductase isozymes. Yeast cells containing the HMG-CoA reductase-histidinol dehydrogenase fusion proteins grew on histidinol-containing medium if the HIS4C domain was present on the cytoplasmic side of the endoplasmic reticulum membrane but not if the HIS4C domain was targeted to the endoplasmic reticulum lumen. Systematic exchanges of transmembrane domains between the isozymes confirmed that both isozymes had equivalent membrane topologies. In general, deletion of an even number of putative transmembrane domains did not interfere with the topology of the protein, but deletion or duplication of an odd number of transmembrane domains inverted the orientation of the protein. The data confirmed the earlier proposed topology for yeast HMG-CoA reductase, demonstrated that the yeast enzymes are core glycosylated, and provided in vivo evidence that the properties of transmembrane domains were, in part, dependent upon their context within the protein.

Amino Acids↗
PubMed1986

Acipimox in the treatment of patients with hyperlipidaemia: a double blind trial.

Fifty-two patients with Fredrickson Type IIb or Type IV hyperlipidaemia, in whom diet had not achieved satisfactory lipid levels, completed a double blind randomised study of acipimox versus placebo. The patients were given acipimox, 250 mg three times daily or placebo for a three month period, and plasma lipids and glucose were monitored. The patients receiving acipimox showed a fall in the mean concentration of plasma triglyceride compared to placebo (0.74 mmol/l) and this was most marked in patients whose initial plasma triglyceride levels were greater than 3 mmol/l (1.0 mmol/l, confidence limits 0.18, 1.82). Acipimox was well tolerated, and could be a useful addition to the drugs available for the treatment of patients with hypertriglyceridaemia.

Adult↗
PubMed1986

Paradoxical platelet behaviour in diabetic ketoacidosis.

Thrombotic events may occur in patients who present with severe uncontrolled diabetes or with diabetic coma. As a possible explanation for this, platelet function was investigated at presentation with diabetic ketoacidosis and during treatment in 10 patients. Concentrations of the platelet-specific proteins, platelet factor 4 (PF4) and beta-thromboglobulin (beta TG) were elevated and fell towards normal with treatment. Despite evidence of increased aggregation in vivo, platelets from subjects with ketoacidosis were insensitive to adenosine 5'-diphosphate (ADP), sensitivity increasing with correction of ketoacidosis. Platelets from ketoacidotic diabetics were initially insensitive to the anti-aggregatory action of prostacyclin (PGI2) and became normal with treatment. Initial blood glucose concentrations correlated with log10 ADP concentrations (r = 0.72, p less than 0.01) and with log10 PGI2 ID50 (the PGI2 concentration required to half-inhibit ADP-induced aggregation) (r = 0.66, p less than 0.025). Glucose concentrations throughout the 2-week study period correlated with all log10 ADP concentrations (r = 0.32, p less than 0.005) and all log10 PGI2 ID50 concentrations (r = 0.51, p less than 0.001). The decrease in ADP sensitivity in ketoacidosis, paradoxical in view of the evidence of increased in vivo platelet aggregation, may result from an acquired platelet storage pool deficiency.

Adenosine Diphosphate↗
PubMed1986

A method for microinjection into subpleural alveoli of rat lung in situ.

A new technique is described for the micropuncture of rat lung in the intact thorax. Under pentobarbital sodium anesthesia a glass micropipette is passed through a small area of the parietal pleura, which has been cleared of overlying intercostal muscle. The micropipette is passed into the lung parenchyma and withdrawn again without collapsing the lung. The current application of this technique is in the microinjection of fluid into subpleural alveoli, which is illustrated using a suspension of colloidal gold. The gold particles are immediately dispersed over the surface of many alveoli, a small proportion spreading laterally as far as 4-6 mm. There is no evidence of alveolar flooding.

Animals↗
PubMed1985

Effects of acipimox, a nicotinic acid derivative, on lipolysis in human adipose tissue and on cholesterol synthesis in human jejunal mucosa.

The mode of action of acipimox (5-methyl-pyrazine carboxylic acid 4-oxide), an hypotriglyceridaemic agent, was examined in human adipose tissue and intestinal mucosa. The rates of release of fatty acids and glycerol from human adipose tissue were measured in vitro. The release of fatty acids and glycerol from adipose tissue maximally stimulated by isoprenaline (10(-5) mol/l) fell by 40 and 25% respectively (P less than 0.025 and P less than 0.025) in the presence of acipimox (10(-5) mol/l). In submaximally stimulated adipose tissue (isoprenaline 10(-7) mol/l) acipimox (10(-4) mol/l) fully inhibited release of fatty acids (P less than 0.05) and glycerol (P less than 0.025) to basal rates. In unstimulated adipose tissue acipimox (10(-3) mol/l) reduced the rate of glycerol release (P less than 0.05), but not the rate of fatty acid release. Cholesterol synthesis in jejunal mucosa was measured in vitro by the incorporation of [2-14C]-acetate into sterols. Addition of cholesterol to the incubation reduced [2-14C]acetate incorporation into sterols from 8.7 +/- 2.1 (mean +/- standard error) to 3.7 +/- 1.0 pmol h-1 mg-1 of tissue (P less than 0.01). Acipimox at 10(-4)-10(-2) mmol/l had no consistent effect on cholesterol synthesis. Acipimox appears to exert its main hypolipidaemic effect by reducing lipolysis and free fatty acid flux to the liver, thereby reducing the precursor pool size of very low density lipoprotein (VLDL)-triglyceride and VLDL synthesis.

Adipose Tissue↗
PubMed1980

The localisation of particles retained in the trachea of the rat.

Particles of 133BaSO4 were deposited on the surface of rat trachea by intra-tracheal injection. Aggregates of particles were located in the trachea by autoradiography and electron microscopy. Following deposition, particles not rapidly removed by muco-ciliary clearance remained on the epithelium for some time. After 2 hr most had been ingested by macrophages on the surface, though some were still free in the mucus. By 24 hr, 74 per cent. of the aggregates remaining were beneath the epithelium in the lamina propria, and after 7 days almost all of them were in or beneath the epithelium. All the buried particles identified by EM were within macrophages. After 24 hr the particles in the tracheal wall were beneath epithelium which was not ciliated columnar, but cuboidal or flatter, with fewer or no ciliated cells and infiltrated with lymphocytes. It is suggested that particle retention in airways is accomplished by ingestion by macrophages which then migrate through this type of epithelium.

Animals↗