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Biomedical subjects

R Fuller

Publications and source records attributed to R Fuller.

At least 19 recordsLinked to original sources

Fluticasone propionate--an update on preclinical and clinical experience.

Fluticasone propionate (FP) is a novel androstane glucocorticoid with potent anti-inflammatory activity which has been effectively used, intranasally, as therapy for seasonal and allergic perennial rhinitis. When taken by the inhaled route, FP has shown significant therapeutic efficacy in the management of asthma. Fluticasone propionate is a highly lipophilic molecule with good uptake, binding and retention characteristics in human lung tissue. Fluticasone propionate has high glucocorticoid receptor selectivity and affinity, demonstrating rapid receptor association and slow receptor dissociation. In vitro, FP has been shown to potently inhibit T lymphocyte proliferation, cytokine generation, tumour necrosis factor alpha (TNF-alpha)-induced adhesion molecule expression, interleukin-5-induced eosinophilia, mucosal oedema and toluene 2,4-diisocyanate-induced mast cell proliferation, while promoting secretory leucocyte protease inhibitor production and eosinophil apoptosis. In human studies, FP has demonstrated marked vasoconstrictor potency in normal subjects and inhibited antigen-induced mucosal platelet activating factor/eicosanoid production, T lymphocytes and CD25+ cells in patients with rhinitis. Biopsy data from mild asthmatics demonstrate FP-associated reduction in CD3, CD4, CD8 and CD25 cells, with an accompanying reduction in eosinophil and mast cell markers. Clinical studies have evaluated lung function, bronchial reactivity, exacerbation rates and oral corticosteroid-sparing effect. Results show that FP has at least twice the clinical potency of beclomethasone dipropionate and budesonide. This appears to be achieved without an accompanying increase in systemic effects, suggesting a therapeutic index which may be higher than other currently available inhaled corticosteroids.

Androstadienes

Endothelin-1 induces a histamine-dependent flare in vivo, but does not activate human skin mast cells in vitro.

The role of the mast cell in endothelin-1 induced flare has been investigated by in vivo and in vitro experiments. The intradermal injection of endothelin-1 (10 pmol) into human skin induced a pallor with surrounding axon-reflex flare which is similar to the flare response to histamine (1 nmol). At these doses, chosen to give identical flare areas, blood flow was increased in the area of the endothelin-induced flare over a longer period. A systemic H1-receptor antagonist significantly inhibited the area of both flares, although blood flow in the remaining portion of the endothelin-induced flare remained raised. Endothelin-1 at concentrations up to 3 x 10(-5) M failed to release histamine from human dispersed skin mast cells. We suggest from these results that a major component of endothelin-1 induced flare results from mast cell activation that is secondary to direct stimulation of sensory nerves by the peptide.

Adult

A note on the use of a plasmid as a DNA probe in the detection of a Lactobacillus fermentum strain in porcine stomach contents.

A plasmid (about 50 kb) was used as a DNA probe to enumerate, by colony hybridization, a strain of Lactobacillus fermentum in the stomach contents of eight piglets. The population sizes obtained by colony hybridization were in agreement with estimated levels calculated on the basis of plasmid profiling of colonies isolated at random from the total lactobacillus population.

Animals

Lactobacillus succession in the piglet digestive tract demonstrated by plasmid profiling.

Plasmid profiling was used to distinguish strains of lactobacilli inhabiting the digestive tract of piglets and the feces of sows. Fifteen plasmid profile types were detected among 328 isolates of lactobacilli. Plasmid profiling of lactobacilli permitted the following conclusions to be made: the maternal feces were a major source of lactobacilli colonizing the piglet digestive tract; the lactobacillus population of the gastric region of the piglet digestive tract was composed of lactobacillus strains different from those present in the rectal population; and a lactobacillus succession was observed in the digestive tract of piglets drawn from a single litter, and one plasmid profile type became dominant in the gastric region of these animals.

Animals

Plasmid profiling of members of the family Enterobacteriaceae, lactobacilli, and bifidobacteria to study the transmission of bacteria from mother to infant.

Plasmid profiles of isolates of the family Enterobacteriaceae, lactobacilli, and bifidobacteria cultured from vaginal, oral, and rectal swabs collected from women soon after admission to a maternity hospital were compared with those of strains detected in the feces of their infants. Lactobacilli inhabiting the vaginas of the mothers did not appear to colonize the infant digestive tract, but evidence for the transmission of fecal isolates of the Enterobacteriaceae and bifidobacteria from mother to infant was obtained in four out of five cases. Many of the bifidobacteria isolated were plasmid-free but could be distinguished with biochemical profiles.

Bifidobacterium

Factors influencing the presence of faecal lactobacilli in early infancy.

The faecal flora of 46 preterm infants and 52 born at full term was studied at 10 days of age; 46 born at full term and 37 preterm infants were also studied at 30 days. Viable counts of coliforms, lactobacilli, and bifidobacteria were made; gas liquid chromatography was used to identify the anaerobes. Lactobacilli, but not bifidobacteria, were found in high counts in the stools of most of the infants born at full term by 30 days of age. The mode of delivery, but not the method of feeding, had a significant influence on early colonisation. A selective deficiency of lactobacilli compared with coliform organisms was found in preterm infants. Previous treatment with antibiotics and being nursed in an incubator were also significantly associated with a lower rate of early colonisation with lactobacilli. Our findings indicate that lactobacilli may be an important part of the normal stool flora in early infancy, and that modern methods of neonatal care are associated with delayed or deficient colonisation.

Anti-Bacterial Agents

Postoperative jejunal feedings following complicated pancreatitis.

Some surgeons avoid placing a jejunostomy in patients with complications, fearing either exacerbation of the disease during enteral feedings or complications from the jejunostomies. Eleven patients with hemorrhagic pancreatitis (four), pancreatic abscess (five), or infected pseudocyst (two) underwent placements of needle (five) or Red Robinson (six) jejunal catheters during laparotomy. Five patients had been given 30.8 +/- 16 liters of TPN over 25 +/- 12 days preoperatively. Only two patients received TPN postoperatively because of progressive sepsis with enteral intolerance to feedings. One of these patients developed a jejunal leak near the placement of the Red Robinson catheter. Both patients died of complications from their pancreatic disease. The remaining nine patients received 35.6 +/- 8.6 liters of enteral feedings over 31 +/- 6.8 days before resuming oral intake. Glucosuria and hyperglycemia were common, but easily managed. No catheters were lost, and diarrhea necessitating slowing and diluting the diet was unusual after the first week. Enteral feeding did not elevate amylase values. Therefore, jejunal feedings can be given safely in patients with severe acute pancreatic disease to provide prolonged nutrition without aggravating the disease.

Adult

Probiotics in man and animals.

There is good evidence that the complex microbial flora present in the gastrointestinal tract of all warm-blooded animals is effective in providing resistance to disease. However, the composition of this protective flora can be altered by dietary and environmental influences, making the host animal susceptible to disease and/or reducing its efficiency of food utilization. What we are doing with the probiotic treatments is re-establishing the natural condition which exists in the wild animal but which has been disrupted by modern trends in conditions used for rearing young animals, including human babies, and in modern approaches to nutrition and disease therapy. These are all areas where the gut flora can be altered for the worse and where, by the administration of probiotics, the natural balance of the gut microflora can be restored and the animal returned to its normal nutrition, growth and health status.

Animals

Yeast KEX2 endopeptidase correctly cleaves a neuroendocrine prohormone in mammalian cells.

Mammalian cell lines (BSC-40, NG108-15, and GH4C1) that cannot process the murine neuroendocrine peptide precursor prepro-opiomelanocortin (mPOMC) when its synthesis is directed by a vaccinia virus vector were coinfected with a second recombinant vaccinia virus carrying the yeast KEX2 gene, which encodes an endopeptidase that cleaves at pairs of basic amino acid residues. mPOMC was cleaved intracellularly to a set of product peptides normally found in vivo, including mature gamma-lipotropin and beta-endorphin1-31. In GH4C1 cells (a rat pituitary line), product peptides were incorporated into stored secretory granules. These results suggest that the inability of any particular cell line to process a prohormone precursor is due to the absence of a suitable endogenous processing enzyme.

Cell Line