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A Prince

Publications and source records attributed to A Prince.

70 records · Page 4Linked to original sources
PubMed1987

Inhibitors of cyclic AMP phosphodiesterase. 1. Analogues of cilostamide and anagrelide.

Evaluation of a series of lactam heterocyclic analogues of cilostamide (2) as inhibitors of cyclic AMP phosphodiesterase derived from both human platelets and rat heart in comparison with their corresponding methoxy-substituted heterocycles has revealed that the N-cyclohexyl-N-methyl-4-oxybutyramide side chain of 2 is an important lipophilic and/or steric pharmacophore. Attachment of this side chain to the parent heterocycle of the potent cyclic AMP phosphodiesterase inhibitor anagrelide (3) afforded the hybrid structure RS-82856 (1), shown to be more potent than either of its progenitors as an inhibitor of cyclic AMP phosphodiesterase or of ADP-induced platelet aggregation. The available in vitro data suggest that 1 possesses potentially useful antithrombotic and cardiotonic properties.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

Antibiotic resistance of Pseudomonas species.

Pseudomonas species are highly versatile organisms with genetic and physiologic capabilities that allow them to flourish in environments hostile to most pathogenic bacteria. Within the lung of the patient with cystic fibrosis, exposed to a number of antimicrobial agents, highly resistant clones of Pseudomonas are selected. These may have acquired plasmid-mediated genes encoding a variety of beta-lactamases or aminoglycoside modifying enzymes. Frequently these resistance determinants are on transposable elements, facilitating their dissemination among the population of bacteria. Mutations in chromosomal genes can also occur, resulting in constitutive expression of normally repressed enzymes, such as the chromosomal cephalosporinase of Pseudomonas aeruginosa or Pseudomonas cepacia. These enzymes may confer resistance to the expanded-spectrum beta-lactam drugs. Decreased cellular permeability to the beta-lactams and the aminoglycosides also results in clinically significant antibiotic resistance. The development of new drugs with anti-Pseudomonas activity, beta-lactam agents and the quinolones, has improved the potential for effective chemotherapy but has not surpassed the potential of the organisms to develop resistance.

Aminoglycosides↗
PubMed1984

Development of markers for cholinergic neurones in re-aggregate cultures of foetal rat whole brain in serum-containing and serum-free media: effects of triiodothyronine (T3).

Development has been studied in re-aggregate cultures derived from the 16 day foetal rat brain and the effects of triiodothyronine (T3) investigated. Cultures were maintained in either a medium containing 10% serum (S+), or in serum-free culture medium (S-) or in serum-free medium containing 30nM T3. The muscarinic cholinoceptor, measured by specific binding of [3H]-quinuclidinyl benzitate ([3H]-QNB) at 9 and 14 days in vitro, was at a lower level in the serum-free cultured cells compared with those in serum-containing culture medium (S+). In cultures in the latter medium, receptor concentration at day 14 was of a similar magnitude to that in rat brain at an equivalent postnatal age. Binding increased with development from 9 to 14 days in vitro in the S+ medium but not in the S- medium. T3 treatment caused an 85% increase in [3H]-QNB binding compared with the cultures in S- medium at day 14 to a level equivalent to that found in the cells grown in S+ medium. This increase was reflected in the Bmax but not in the KD (approx. 0.1nM). Choline acetyltransferase (ChAT) activity developed more slowly in the S- medium than in the S+ medium where the specific activity approximated values obtained in vivo. T3 treatment of cultures grow in S- medium significantly enhanced the developmental rate of increase of ChAT activity. The characteristics of [3H]-choline uptake and metabolism in the cultures was examined. Uptake was strictly Na+-independent but was energy-dependent, and inhibited by 2, 4'-dinitrophenol (2, 4'-DNP) and cooling (0-4 degrees C). Neither iodoacetate nor ouabain had any effect on the amount of uptake. Hemicholinium (HC3) was a potent inhibitor of uptake (70% inhibition at 10 microM HC3). Metabolism studies showed virtually no conversion to [3H]-acetylcholine ([3H]-ACH) in reaggregates grown in either the S+, S- or T3 containing media. However, a small amount of [3H]-choline was incorporated into phosphorylcholine. T3 treatment had no effect on this metabolic profile. The kinetics of [3H]-choline uptake by the re-aggregates was also studied in the re-aggregate cultures (after 12 and 22 days in vitro) using [3H]-choline at 0.05-100 microM. Both Eadie-Hofstee transformation and least-squares analysis of the data showed that the uptake comprised only a single low-affinity component with an apparent Kt = approx. 50 microM. Unlike ChAT and [3H]-QNB binding, there appeared to be no difference between the uptake in the different culture conditions. 6 It is concluded that the differentiation of cholinergic neurones and muscarinic receptors in serum-free cultured re-aggregates from foetal rat brain is enhanced by thyroid hormone treatment. The development of [3H]-choline uptake does not seem to be associated with cholinergic cells under these culture conditions, and is unaffected by thyroid hormone treatment.

Animals↗
PubMed1980

Speed of change in pancreatic mass and in intestinal bacteriology of parenterally fed rats.

1. Indices of pancreatic mass and bacterial counts for jejunal and ileal mucosa were studied in rats after 3, 6, 10 and 15 days of total parenteral nutrition and compared with the results from orally fed and sham intravenously fed control rats. 2. Pancreatic wet weight corrected for body weight decreased significantly by 31--42% after 3, 6, 10 and 15 days of total parenteral nutrition. The most striking decrease occurred within 3 days. Other indices of pancreatic mass (protein and DNA) showed a similar pattern suggesting pancreatic hypoplasia. There was more DNA per g of pancreas, indicating that unless there were changes in tissue water cellular hypotrophy must have accompanied the hypoplasia. 3. Pancreatic RNA also decreased significantly after 3--10 days of total parenteral nutrition, suggesting reduced protein synthesis. 4. Bacterial counts (log number) whether expressed as number/unit length of intestine or number/g wet weight of mucosa were decreased for anaerobic bacteria in the jejunum after 3--15 days of total parenteral nutrition. In the ileum both aerobic and anaerobic bacteria increased after 6 days of parenteral nutrition and then decreased significantly. 5. The changes in bacterial flora are unlikely to account for the adaptive hypoplasia seen in the intestine of intravenously fed rats.

Animals↗
PubMed1977

Incidence of diarrhea and colitis associated with clindamycin therapy.

A retrospective and prospective study was made of side effects in 200 patients who received clindamycin over a 15-month period. The incidence of gastrointestinal symptoms in this group of patients was 21.5%; of diarrhea, 13.5%; and of colitis, 2.5%. Factors associated with an increased incidence of diarrhea were older age and parenteral route of administration. Simultaneous use of other antibiotics, particularly aminoglycosides, and increased total dosage of clindamycin did not increase the incidence of diarrhea. The gastrointestinal side effects were usually self-limited if the drug was promptly discontinued and fluid support was provided.

Administration, Oral↗
PubMed1976

Beta-lactamase activity in Shigella sonnei.

The basis of ampicillin resistance in Shigella sonnei was analyzed for a number of isolates. Most isolates that were resistant to ampicillin and cephalothin failed to transfer resistance. Isolates resistant to cephalothin and ampicillin were inhibited by mecillinam, cefamandole, and cefoxitin. Six strains were selected for study. These differed on the basis of inhibition by 10 beta-lactam antibiotics and on differences in beta-lactamase activity. There was no correlation between the inhibitory concentration of antibiotic and the amount of antibiotic hydrolyzed. Use of sodium chloride and cloxacillin inhibition and acrylamide electrophoresis demonstrated that ampicillin resistance in Shigella is mediated by a number of different beta-lactamases. Organisms can contain more than one type of beta-lactamase.

Amidohydrolases↗
PubMedDate not supplied

Management of fever in patients with central vein catheters.

We have evaluated a standardized prospective system for managing episodes of fever in pediatric patients with indwelling central vein catheters being used primarily for delivery of parenteral nutrients. Over an 18-month period 72 such patients, accounting for 4347 "catheter days," were followed. Thirty-two patients experienced a total of 88 episodes of fever. An infection unrelated to the presence of the catheter (e.g. otitis media, pneumonia, urinary tract infection) was found to be the cause of fever in 27 episodes (31.7%); in all the infection responded to appropriate antibiotic therapy. Ten of the episodes of fever (11.4%) lasted for less than 2 hours and were not evaluated further. Two episodes occurred in patients who no longer required the catheter; these resolved with elective catheter removal. The cause of the remaining 49 episodes of fever was assumed to be catheter-related sepsis; these were treated empirically with an intravenous antibiotic regimen of vancomycin (40 mg/kg/day) and gentamicin (7.5 mg/kg/day). In 16 of these cases blood cultures were negative and the antibiotic regimen was either stopped or continued for other indications. The remaining 33 episodes of fever were associated with positive blood cultures, i.e. documented episodes of catheter-related sepsis. In 10 of these the catheters were removed. The remaining 23 episodes of catheter-related sepsis were treated for 14 days with antibiotics given through the central vein catheter. In 5 of these episodes blood cultures remained positive after 48 hours of specific antibiotic therapy at which time the catheter was removed.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗