Biomedical subjects

C W Ford

Publications and source records attributed to C W Ford.

At least 37 records · Page 2Linked to original sources

PubMed1994

Effect of tumor necrosis factor-alpha, interleukin-1 beta, and antibiotics on the killing of intracellular Staphylococcus aureus.

A bovine blood polymorphonuclear neutrophil system was used to determine the ability of cytokines, alone or in combination with various antibiotics, to enhance the intracellular killing of Staphylococcus aureus sequestered within these phagocytes. Pretreatment of blood polymorphonuclear neutrophils with human recombinant tumor necrosis factor-alpha, bovine macrophage supernatant tumor necrosis factor-alpha, or human recombinant interleukin-1 beta enhanced the killing of S. aureus by the phagocytes compared with that of untreated polymorphonuclear neutrophils. This enhancement was dose-dependent and required 30 min of contact between the cytokine and the blood polymorphonuclear neutrophils. However, mammary gland polymorphonuclear neutrophils, macrophages, and blood monocytes showed no enhanced killing activity following pretreatment with tumor necrosis factor. Pretreatment of polymorphonuclear neutrophils with tumor necrosis factor and subsequent exposure to various antibiotics after infection with S. aureus enhanced intracellular bacterial killing by certain antibiotics, including paldimycin, rifampin, and ciprofloxacin (antibiotics that normally kill intracellular S. aureus). However, no enhancement occurred with antibiotics that do not normally kill intracellular S. aureus. Cytokine therapy may be a useful adjunct to antibiotic therapy in the treatment of bovine staphylococcal infection and mastitis.

Animals↗

PubMed1994

Efficacy of tumor necrosis factor-alpha and antibiotics in therapy of experimental murine staphylococcal mastitis.

The mouse model was used to determine the efficacy of the cytokine, tumor necrosis factor-alpha, and antibiotic in treatment of experimentally induced staphylococcal mastitis. Recombinant human tumor necrosis factor-alpha alone administered to the mammary glands of lactating mice recruited significantly more polymorphonuclear neutrophils into the gland by 4 h posttreatment than did the untreated control. One hundred times less recombinant mouse tumor necrosis factor-alpha than human tumor necrosis factor-alpha was required to enhance the killing of Staphylococcus aureus within the gland. Human tumor necrosis factor-alpha effectively enhanced the killing of the bacteria when it was administered 4 to 0 h prior to infection, but not 4 h after infection. When mice were first pretreated with tumor necrosis factor-alpha, infected, and then treated with antibiotics (ciprofloxacin and pirlimycin, but not cloxacillin), the combination of antibiotic and cytokine significantly reduced the number of bacteria within the gland compared with that for mice treated with antibiotic alone, cytokine alone, or placebo. Recombinant tumor necrosis factor-alpha may be an effective adjunct to antimicrobial therapy in treatment of staphylococcal mastitis in the bovine.

Animals↗

PubMed1993

Light and electron microscopic analysis of two divisions of the suprachiasmatic nucleus in the young and aged rat.

The suprachiasmatic nucleus (SCN) is a principal controller of mammalian circadian rhythms. However, in spite of documented disturbance of biological rhythms in old animals, few significant age-related changes have been observed in this nucleus. This study examined age-related differences in SCN volume, neuronal number, density, and ultrastructural features in the entire rat SCN and in its two divisions, the denser ventromedial (compacta) and less dense dorsolateral (dissipata). Light and electron microscopic morphometric techniques were utilized in weanlings (21-28 days), young adults (3-6 mo), and aged (30-36 mo) animals. The total SCN volume, as well as volumes of the compacta region, were significantly greater in young adult and aged rats than in weanlings. Thus, as the rat ages the SCN increases in total size. However, the dissipata region appears to decrease in volume while the compacta increases. Even though the total number of SCN neurons was quite constant in the three age groups, the number of neurons in the dissipata region was decreased significantly in the young adult and aged groups as compared to the weanling. Neurons in the compacta region were usually spindled-shaped with two dendritic processes, while oval to spheroidal cells with 3-4 processes predominated in the dissipata. Nuclei of SCN cells were often invaginated. In weanlings, more SCN neuronal nuclei had invaginated nuclei in the dissipata region (66%) compared to the compacta (37%). In the two older age groups of rats, a higher percentage of invaginated neuronal nuclei were found in both regions. However, more were still found in the dissipata (90%) compared to the compacta (72%), even though the number of these cells in the compacta doubled. Thus, there was a large increase in the number of invaginated nuclei, as well as the number of invaginations, in the young adult rats compared to the weanling group, and this increase persisted in aged rats. SCN neurons usually had nuclei surrounded by a thin perimeter of cytoplasm containing sparse mitochondria and granular endoplasmic reticulum, multiple Golgi regions, and a moderate number of free ribosomes. In weanlings, mitochondria contained dense cristae and the granular endoplasmic reticulum was relatively prominent. Degenerative ultrastructural changes which included mitochondrial enlargement/vacuolation, Golgi vacuolation, lysosome, and lipofuscin development occurred in less than 10% of young adult SCN cells, and were more frequently found in the dissipata. In aged, rats 30% of the neurons showed degenerative changes in the dissipata compared with 18% in the compacta. Degenerative changes appeared highly correlated with the degree of membrane folding.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗

PubMed1991

Activity of antibiotics against Staphylococcus aureus within polymorphonuclear neutrophils.

The intracellular location of certain strains of Staphylococcus aureus serves as a reservoir of bacteria which is thought to be important in therapy of recurrent infections in humans and in chronic staphylococcal mastitis in dairy cows. This overview summarizes data pertaining to the intracellular survival of Staphylococcus aureus within polymorphonuclear neutrophils (PMNs) both in vitro and in vivo in the face of antibiotic treatment. While compounds such as rifampin, clindamycin, erythromycin, and ciprofloxacin have been shown to be rapidly taken up by PMNs, the ability of antibiotics to concentrate within PMNs did not strictly correlate with their ability to kill intracellular Staphylococcus aureus. Rifampin and ciprofloxacin have been shown to be the most effective intraphagocytic killing agents, while clindamycin and erythromycin were inactive in these in vitro assays. In vivo, in therapy of Staphylococcus aureus arthritis and peritonitis in humans and in certain mouse models rifampin has generally been shown to be more effective than comparator antibiotics. In a staphylococcal subcutaneous abscess model, however, clindamycin was very effective in curing the Staphylococcus aureus abscesses in this system where PMNs were the primary inflammatory cells involved. The intracellular bacterial counts decreased as rapidly as the extracellular bacteria. Rifampin was also effective in the abscess model but ciprofloxacin was ineffective at the highest doses tested. The relevance of in vitro and in vivo models and the importance of PMNs as a reservoir of infection in staphylococcal diseases in humans and the dairy cow are discussed.

Anti-Bacterial Agents↗

PubMed1989

Establishment of an experimental model of a Staphylococcus aureus abscess in mice by use of dextran and gelatin microcarriers.

Staphylococcus aureus UC 9271 mixed with dextran or gelatin microcarrier beads and injected subcutaneously into mice resulted in the formation of reproducible, sustained abscesses with as few as 2 x 10(3) cfu. Without microcarrier beads, 4 x 10(7) cfu were required to produce an abscess. The abscesses that developed with microcarriers attained a diameter of up to 1.5 cm and persisted for several days before discharging through the skin. The pH of the abscesses fell from 7.1 to 6.6 within 24 h. Histological and microscopic examination of the abscesses revealed an influx of phagocytic cells, mostly polymorphonuclear leucocytes, within 1-2 h after injection. Cell debris accumulated and the abscess became encapsulated 24-48 h after infection. Enzymatic digestion of the abscess contents allowed analysis of the host and bacterial cell populations and treatment with lysostaphin permitted differentiation between phagocytosed and free bacterial populations of S. aureus. Phagocytosed but viable S. aureus comprised c. 50% of the total bacterial population after 24 h; however, by 96 h the phagocytosed population was only 1-5% of the total population, primarily because of an increase in extracellular bacterial numbers. Prevention of abscess formation by antibiotic treatment based upon the minimal inhibitory concentration (MIC) of an antibiotic for S. aureus was not always predictable. Tetracycline did not prevent abscess formation even though it possessed a low MIC for S. aureus; methicillin had a borderline MIC value but was quite active. However, the MIC values were quite predictive of antibiotic cures in a systemic-lethal S. aureus infection in mice.

Abscess↗

PubMed1988

Evaluation of antibiotic effectiveness against Staphylococcus aureus surviving within the bovine mammary gland macrophage.

Bovine mastitis due to Staphylococcus aureus may become chronic and refractory to antibiotic therapy because of the organism's ability to survive within the mammary gland macrophages and/or polymorphonuclear neutrophils (PMNs). Therefore, phagocytosis and killing of S. aureus by bovine udder macrophages, udder and blood neutrophils and blood monocytes were studied. Gland and blood PMNs were about equally effective at phagocytosing (2.5 log reduction in supernatant) and killing the bacteria (92% reduction of viable bacteria by two hours). Gland macrophages phagocytosed at a lower rate (1.5 log reduction) and were less effective at killing the bacteria (73% reduction by two hours). Blood monocytes phagocytosed and killed S. aureus at the lowest rate. An udder macrophage monolayer system was developed and used to evaluate the ability of antibiotics to kill surviving intracellular S. aureus. This assay was similar to our previously described system with blood PMNs. Several classes of antibiotics were investigated. These included naphthalenic ansamycin, lincosaminide, tetracycline, coumarin, peptide, paulomycin, quinolone, macrolide, cephalosporin, and penicillin-class antibiotics. The activity of these compounds was compared to positive (rifampicin), negative (cloxacillin), and nonantibiotic treated controls. Only naphthalenic ansamycin class antibiotics, paulomycin, paldimycin and ciprofloxacin caused significant reduction in viable intracellular bacteria in the macrophage system. These results were similar to those obtained in the blood PMN monolayer system. Because a low intraphagolysosomal pH could affect an antibiotic's ability to kill intracellular bacteria by affecting the drug itself or inhibiting bacterial growth, the effect of low pH on the minimum inhibitory concentration and the minimum lethal concentration of clindamycin and rifampicin against three strains of S. aureus was also tested. While the activity of clindamycin at pH 5.0 compared to pH 7.0 was not affected greatly, the activity of rifampicin was greatly enhanced at acidic pH. These results suggest that at least some of the excellent activity of rifampicin for intracellular S. aureus is due to potentiation of its activity in the intracellular acidic compartment of the phagolysosome.

Animals↗

PubMed1988

Trospectomycin, a novel spectinomycin analogue: antibacterial activity and preliminary human pharmacokinetics.

Trospectomycin (TSP; U-63366F) is a novel spectinomycin (SP) analogue with broad-spectrum antibacterial activity. The in vitro activity of the analogue was compared to that of SP against approximately 400 bacterial isolates. The in vivo activity of the compound was assessed using experimental infection models for both Gram-positive and Gram-negative facultative bacteria. The preliminary human pharmacokinetics of TSP were evaluated following single-dose i.v. or i.m. administration. TSP was more active in vitro than SP (2 to 32-fold) against strains of numerous bacterial species, including staphylococci, streptococci, Haemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Proteus spp., Bacteroides spp., Gardnerella vaginalis and Chlamydia trachomatis. The activity of TSP for most species of the family Enterobacteriaceae was comparable to that of SP. TSP was more active than SP (2 to 32-fold) in curing experimental infections due to streptococci, Salmonella typhi, Serratia marcescens, Klebsiella pneumoniae and Haemophilus influenzae. TSP was well-absorbed following both i.v. and i.m. administration. Pharmacokinetic analysis of microbiological assay data for the 1000 mg dose yielded the following mean values for the i.v. and i.m. routes, respectively: Cmax = 81.2, 28.7 micrograms/ml; serum half-life = 2.2, 2.2 h; Tmax = 25, 75 min; and AUC = 156.6, 116.2 h micrograms/ml. Pharmacokinetic analysis of assay data derived using the more sensitive HPLC assay revealed the biphasic nature of trospectomycin elimination, highlighted by a short apparent serum half-life (2.2 h) and a prolonged tissue half-life (approximately 36 h). TSP inhibits a variety of clinically important organisms, including agents of sexually transmitted diseases and pelvic inflammatory disease, and demonstrates favourable pharmacokinetic properties.(ABSTRACT TRUNCATED AT 250 WORDS)

Chromatography, High Pressure Liquid↗

PubMed1987

Ceftiofur sodium, a broad-spectrum cephalosporin: evaluation in vitro and in vivo in mice.

Ceftiofur sodium, a broad-spectrum beta-lactamase-resistant cephalosporin, was evaluated in vitro and in vivo in mice. Ceftiofur is the sodium salt of (6R, 7R)-7[( 2-amino-4-thiazolyl)-Z- (methoxyimino)acetyl]amino)-3-[( (2-furanylcarbonyl)thio]methyl)-8-oxo-5- thia-1-azabicyclo-[4.2.0]oct-2-ene-2-carboxylate. Minimal inhibitory concentration values were obtained with 264 strains representing 9 genera and 17 species of bacterial pathogens from cattle, swine, sheep, horses, poultry, dogs, cats, and human beings. Ceftiofur was more active than was ampicillin against all strains tested including beta-lactamase-producing organisms. In mice with systemic infections, ceftiofur was more active than or equivalent to ampicillin, cephalothin, cefamandole, cloxacillin, cefoperazone, or pirlimycin. These protection tests included infections with Escherichia coli, Haemophilus pleuropneumoniae, H somnus, Pasteurella haemolytica, P multocida, Salmonella typhimurium, or Staphylococcus aureus. In infant mice with E coli-induced lethal diarrhea and in mice with S aureus and E coli-induced mastitis, ceftiofur was comparable or more active than was ampicillin.

Ampicillin↗

PubMed1986

Evaluation of antibacterial agents in a high-volume bovine polymorphonuclear neutrophil Staphylococcus aureus intracellular killing assay.

A bovine polymorphonuclear leukocyte (PMN) monolayer system was used to determine the ability of different antibiotics to kill surviving intracellular Staphylococcus aureus. The following classes of antimicrobial agents were tested in this high-volume assay procedure: aminocyclitol, beta-lactam, coumarin, lincosaminide, macrolide, naphthalenic ansamycin, paulomycin, peptide, quinolone, and tetracycline. The activities of these compounds were compared with those of positive (rifampin), negative (cloxacillin), and non-antibiotic-treated controls. Only oxytetracycline, the ansamycins (rifampin, rifamycin SV, streptovaricin A, C, and D), paulomycin, and paldimycin caused a significant reduction in the viable count of intracellular S. aureus. Of these, however, the intracellular killing by the streptovaricins was directly related to the cytotoxicity (as determined by trypan blue exclusion) of these compounds for the PMNs. Although the paulomycins were cytotoxic for the PMNs, the cytotoxic and the intracellular killing activity of these new compounds could be distinguished. The relevance of these results to the therapeutic effectiveness of these antibiotics in the treatment of bovine staphylococcal mastitis is discussed.

Animals↗

PubMed1985

Efficacy of lincosaminide antibiotics in the treatment of experimental staphylococcal mastitis in lactating mice.

Staphylococcus aureus is a frequent cause of bovine mastitis worldwide. A model that may predict the efficacy of antimicrobial agents in the treatment of bovine mastitis induced by Staph. aureus was developed in lactating mice. Infection was established by the inoculation of lactating CF1 mice with Staph. aureus into the mammary gland via the teat duct. At the dose of bacteria used, 85-90% of the inoculated, untreated animals developed a nonlethal, acute mastitis within 48 h. Antibiotic treatment was administered subcutaneously or by the intramammary route. Lincosaminide antibiotics including lincomycin, clindamycin, and pirlimycin were evaluated in this system. Other compounds which have been used in therapy of bovine mastitis including novobiocin, penicillin G, ampicillin, cloxacillin and rifamycin-SV were used as reference antibiotics. Pirlimycin was the most effective of the antibiotics tested in this standardized system. Depending upon the route of administration, this novel lincosaminide was 15 to 95-fold more effective than clindamycin, three- to six-fold better than lincomycin, two- to ten-fold more effective than novobiocin, 13- to 17-times more effective than cloxacillin and 8- to 22-times better than rifamycin-SV on a weight-dose comparison. Penicillin G and ampicillin were the least effective drugs tested against mastitis induced by the beta-lactamase producing strain of Staph. aureus used in these assays. Pharmacokinetic experiments suggested that the greater effectiveness of pirlimycin compared to clindamycin and lincomycin was due to increased affinity for and prolonged retention in the mammary gland.

Animals↗

PubMed1984

A simple system for studying antibiotic binding to leukocytes.

Studies on the interaction between antibiotics and polymorphonuclear leukocytes (PMLs) usually require the availability of radiolabeled antibiotic, that the antibiotic kill intraleukocyte pathogens, or that the antibiotic affect some function of the leukocyte. The system described here does not have the requirements above but depends instead upon anti-staphylococci activity. The key features of the system are that, following incubation, extracellular antibiotic was removed from PMLs by centrifugation, contact between Staphylococcus aureus 502A and the phagocyte-antibiotic complex was assured by centrifugation at 4 degrees C in 96 well tissue culture dishes, phagocytosis was induced by incubation at 37 degrees C, and assessment of surviving bacteria was accomplished by collecting [3H]thymidine labeled bacteria using a cell harvester. Antibiotics that were active in this system included naphthalenic ansamycins (rifamycins and streptovaricins ), lincosaminides ( clindamycins and pirlimycins ), coumarins (novobiocin), erythromycin, tetracycline, tyrocidine and paulomycin .

Anti-Bacterial Agents↗

PubMed1982

A coordinated self-study/site survey in medical technology, occupational therapy, and physical therapy.

Accreditation is a major issue in allied health education, because it is a time-consuming and expensive process. Program accreditation needs to be streamlined to avoid costly duplication. Joint coordination of the accreditation process is one approach that needs to be tested. This article is a summary of a coordinated accreditation for the departments of medical technology, occupational therapy, and physical therapy at the State University of New York at Buffalo. It focuses on the rationale for such an approach, the protocol established to avoid duplication, the procedures and methods followed in preparing and implementing a joint self-study/site survey, and the results of the experiment. Specific recommendations include common areas of effort among the programs and methods of saving time. Some general observations about the process are made, and it is concluded that a coordinated model is one viable alternative to individual program accreditation.

Accreditation↗

PubMed1980

Improved protection against cholera in adult rabbits with a combined flagellar-toxoid vaccine.

Ligated ileal loops of adult rabbits were used to evaluate the prophylactic potential against cholera of a combined vaccine consisting of toxin-free crude flagella (CF) and glutaraldehyde-derived cholera toxoid (TV). The resulting fluid accumulation ratios were compared with those in rabbits immunized with saline (controls) and with CF and TV alone. Data for single vaccines confirmed the superior protection effect of CF over TV. In rabbits vaccinated with both CF and TV, maximal fluid accumulation ratios were not obtained with a challenge dose as high as 5 X 10(9) colony-forming units (CFU). Two rabbits similarly immunized failed to produce positive loops with challenges of 6.3 X 10(8) and 5 X 10(9) CFU, respectively. The vibriocidal titer of serum from rabbits immunized with a killed commercial vaccine in addition to those listed above was determined at intervals for a period of 164 days. No vibriocidal activity was detected in serum of control rabbits and of rabbits vaccinated with TV. Serum from animals given CF or commercial vaccine had similar vibriocidal titers even when the test bacteria were nonflagellated. Protection against challenge as evaluated by ileal loops did not, however, correlate with vibriocidal titer.

Animals↗

PubMed1979