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Biomedical subjects

C Town

Publications and source records attributed to C Town.

At least 19 recordsLinked to original sources
PubMed1999

In vitro-in vivo evaluation of a controlled release buccal bioadhesive device for oral drug delivery.

PURPOSE: To investigate the use of buccal bioadhesive device in targeting controlled drug delivery to the gastrointestinal tract. METHODS: A three-leg crossover study was designed to evaluate the application of buccal bioadhesive device for providing controlled drug delivery to the gastrointestinal tract of a model drug cyanocobalamin in four healthy adult male beagle dogs. RESULTS: In vitro dissolution studies using deionized water as the medium indicated that 100% of the drug was released within 15 min from a immediate release oral capsule formulation, whereas 90% of the drug was released within a period of 18 hrs from a buccal bioadhesive device formulation. Drug release from the buccal bioadhesive devices appeared to follow Higuchi's square root of time dependent model. The terminal half-life of the drug following I.V. administration in four dogs was found to be 16.4+/-2.4 hrs. Following immediate release oral capsule administration of the drug Cmax, tmax and bioavailability were 2333+/-1469 ng/L, 2.5+/-1.0 hrs and 14.1+/-7.9%, respectively. Following buccal bioadhesive device administration of the drug Cmax, t(max) and bioavailability were 4154+/-1096 ng/L, 11+/-1.2 hrs and 35.8+/-4.1%, respectively. Significantly higher bioavailability of the drug was observed with the buccal bioadhesive device administration when compared to the immediate release oral capsule. CONCLUSIONS: The buccal bioadhesive device appears to improve the oral bioavailability of cyanocobalamin by providing controlled delivery of the drug to the gastrointestinal tract.

Adhesives↗
PubMed1995

Expression and characterization of the ponA (ORF I) gene of Haemophilus influenzae: functional complementation in a heterologous system.

The coding sequence of the Haemophilus influenzae ORF I gene was amplified by PCR and cloned into different Escherichia coli expression vectors. The ORF I-encoded protein was approximately 90 kDa and bound 3H-benzyl-penicillin and 125I-cephradine. This high-molecular-weight penicillin-binding protein (PBP) was also shown to possess transglycosylase activity, indicating that the ORF I product is a bifunctional PBP. The ORF I protein was capable of maintaining the viability of E. coli delta ponA ponB::spcr cells in transcomplementation experiments, establishing the functional relevance of the significant amino acid homology seen between E. coli PBP 1A and 1B and the H. influenzae ORF I product. In addition, the physiological functioning of the H. influenzae ORF I (PBP 1A) product in a heterologous species established the ability of the enzyme not only to recognize the E. coli substrate but also to interact with heterologous cell division proteins. The affinity of the ORF I product for 3H-benzylpenicillin and 125I-cephradine, the MIC of beta-lactams for E. coli delta ponA ponB::spcr expressing the ORF I gene, and the amino acid alignment of the PBP 1 family of high-molecular-weight PBPs group the ORF I protein into the PBP 1A family of high-molecular-weight PBPs.

Bacterial Proteins↗
PubMed1993

Deletion analysis of the essentiality of penicillin-binding proteins 1A, 2B and 2X of Streptococcus pneumoniae.

An internal fragment from each of the penicillin-binding protein (PBP) 1A, 2B and 2X genes of Streptococcus pneumoniae, which included the region encoding the active-site serine residue, was replaced by a fragment encoding spectinomycin resistance. The resulting constructs were tested for their ability to transform S. pneumoniae strain R6 to spectinomycin resistance. Spectinomycin-resistant transformants could not be obtained using either the inactivated PBP 2X or 2B genes, suggesting that deletion of either of these genes was a lethal event, but they were readily obtained using the inactivated PBP 1A gene. Analysis using the polymerase chain reaction confirmed that the latter transformants had replaced their chromosomal copy of the PBP 1A gene with the inactivated copy of the gene. Deletion of the PBP 1A gene was therefore tolerated under laboratory conditions and appeared to have little effect on growth or susceptibility to benzylpenicillin.

Bacterial Proteins↗
PubMed1993

Distribution of 1-aminobenzotriazole in male rats after administration of an oral dose.

1. 14C-labelled 1-aminobenzotriazole (ABT), a suicide inactivator of cytochrome P450, was synthesized and administered orally to male rats. The rats were killed at 1, 6, 24, 48 or 72 h after dosing and the concentration of total radioactivity in various tissues and organs measured. 2. The compound appears to be absorbed slowly with 50% of the radioactivity remaining in the stomach at 6 h after dosing and maximum plasma and tissue concentrations were observed at 24 h. 3. Approximately 71% of the dose of 14C was excreted in the urine and 12% in the faeces over 72 h, indicating oral absorption of at least 71%. Tissue-to-plasma ratios of 14C were highest in the liver, adrenals and kidneys, which all contain significant amounts of cytochrome P450; the half-lives of elimination for total 14C in liver, adrenals and kidneys were approximately 24, 16 and 12 h, respectively, while the half-life in plasma was approximately 9 h. 4. ABT was metabolized by N-acetylation, with the acetylated product attaining concentrations equal to ABT in the plasma; two other major metabolites were also excreted in the urine namely, the N-glucuronide of 1-aminobenzotriazole and the N-glucuronide of benzotriazole.

Administration, Oral↗
PubMed1992

The metabolism of acitretin and isoacitretin in the in situ isolated perfused rat liver.

1. The metabolism of acitretin and its 13-cis isomer, isoacitretin, has been investigated in the in situ isolated perfused rat liver in order to differentiate the action of the liver from that of the gut on the metabolism of these isomers. 2. Acitretin undergoes alpha-oxidation, chain shortening O-demethylation, and glucuronidation in the perfused rat liver. 3. Isoacitretin undergoes glucuronidation as the major, almost exclusive, route of metabolism in the perfused rat liver. 4. The difference in the hepatic metabolism of the cis and trans isomers of this retinoid may explain the differences in their pharmacokinetics, and may help in understanding the pharmacokinetics of related retinoids.

Acitretin↗
PubMed1992

Management.

Driving across the North Yorkshire moors in the course of a working day has its attractions, but the size of the largest FHSA in England and Wales can make for communication problems that need careful handling. For Chris Town, General Manager, North Yorkshire FHSA, management is about the art of diplomacy.

Administrative Personnel↗
PubMed1991

Discipline strategies and parental perceptions of preschool children with asthma.

Parents of 37 children with asthma (aged between three and five years) and of 37 healthy controls were interviewed about their involvement in everyday care, discipline practices, perceptions of their child and situations which were particularly stressful. There was little correlation between mothers' and fathers' preferences for different discipline practices. There was, however, greater agreement in their perceptions. Parents of children with asthma did not differ from those of healthy controls in discipline practices. However, children with asthma were perceived to be generally less healthy. Parents of those with asthma also reported a greater number of everyday situations to be stressful. These data do not support traditional assumptions that parents of children with asthma are more permissive or overindulgent. At least in this preschool sample, there was only limited indication of adverse effects of chronic disease on parenting practices.

Asthma↗
PubMed1987

Quantitation of ceftetrame in human plasma and urine by high-performance liquid chromatography.

A method is described for quantifying ceftetrame, the acid metabolite of methylene (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(methoxyimino)acetamido]-3- [(5-methyl-2H-tetrazol-2-yl)-methyl]-8-oxo-5-thia-1-azabicyclo[4.2 .0]oct-2-ene-2-carboxylate pivalate, an orally active cephalosporin. Sodium benzylpenicillin is added to the plasma as the reference standard. The compounds are extracted from plasma or urine using a Bond Elut phenyl column. An aliquot of the methanol eluate is analyzed by high-performance liquid chromatography using a Waters Nova-Pak phenyl column and a UV detector set to 225 nm. The ratios of the peak heights for ceftetrame and sodium benzylpenicillin are calculated and converted to concentrations of analyte with calibration curves that are generated from the analysis of analyte-free plasma or urine fortified with various amounts of ceftetrame and a fixed amount of sodium benzylpenicillin. For plasma, the limit of quantitation for the assay is 0.48 microgram/ml and the inter-assay precision (relative standard deviation) is 9.3%. For urine, the limit of quantitation for the assay is 19.1 micrograms/ml, and the inter-assay precision is 4.9%.

Adult↗
PubMed1987

Teachers' concerns about chronically sick children: implications for paediatricians.

147 experienced teachers completed a questionnaire concerning their knowledge of and attitudes toward chronic childhood disease. On the whole, their knowledge of the causes and treatments involved was rudimentary. Teachers were especially concerned that they did not know how to deal with medical emergencies in the classroom, and about the repercussions for other children. The results identify the type of information teachers feel they most need in order to teach sick children, and should increase awareness among paediatricians of how difficulties in school can arise.

Absenteeism↗
PubMed1985

Dress and care of infants in health and illness.

The mothers of 199 infants (mean age 36.7 days) were interviewed to determine how the infant was dressed and wrapped, and how the mother would deal with illness. These data were related to measures of the infant's toe and underarm temperatures and demographic information about the family. The data did not support the hypothesis that infants with particular types of clothing or bedding were at risk of overheating and shows that most mothers dress their infants appropriately. Mothers' ideas about management of illness were often inappropriate particularly in lower socioeducational groups.

Adolescent↗
PubMed1979

An oligosaccharide-containing factor that induces cell differentiation in Dictyostelium discoideum.

When Dictyostelium discoideum amoebae (strain V12 M2) are spread at high density on agar containing 1 mM cyclic AMP, essentially all the cells differentiate into stalk cells after 2-3 days. We showed previously that isolated amoebae plated at low density on agar containing cyclic AMP do not differentiate, but can be induced to do so by a layer of high density helper cells from which they are separated by a thin cellophane membrane. We now show that the high density cell population releases a dialyzable factor that, in the presence of cyclic AMP, is capable of inducing isolated amoebae to differentiate into stalk cells. Sugar inhibition, sensitivity to glycosidases, and lectin affinity suggest that the differentiation-inducing activity requires the integrity of an oligosaccharide group containing sialic acid, L-fucose, and N-acetylgalactosamine. In addition, a phosphate group appears to be necessary for biological activity.

Biological Assay↗
PubMed1973

Deoxyribonucleic acid synthesis in recA and recB derivatives of an Escherichia coli K-12 strain with a temperature-sensitive deoxyribonucleic acid polymerase I.

recA and recB derivatives of a strain of Escherichia coli with a temperature-sensitive deoxyribonucleic acid (DNA) polymerase I (polA12) are inviable at high temperature, but continue to incorporate (3)H-thymine into DNA for extended periods. The DNA made in pulse-chase experiments at high temperature in the polA12 parent and its double-mutant derivatives has been examined by alkaline sucrose gradient sedimentation analysis. The low-molecular-weight DNA fragments made during short pulses were joined at the same rate in each strain. Furthermore, the resulting high-molecular-weight DNA was of the same size in each case and was stable for at least 50 min. It is concluded that the inviability of the double mutants is due neither to a defect in converting low-molecular-weight DNA intermediates to high molecular weight nor to the presence of unrepaired random breaks in their DNA.

Carbon Isotopes↗
PubMedDate not supplied

Illness experience and related knowledge amongst children with asthma.

Forty-nine children with asthma (aged 7-16 years) completed a questionnaire concerned with (1) general knowledge about the body and how it works, and (2) specific knowledge about the cause and prognosis of asthma, knowledge of allergens and self-care behaviours. Compared with a matched group of healthy children, they were less well-informed about general knowledge of the body. Knowledge of asthma was also poor. Few children made any specific attempts to avoid situations known to precipitate attacks. There was no significant increase with age in knowledge of allergens or awareness of how to control attacks. The results indicate a need to make asthmatic children more aware of their illness, particularly with regard to self-care.

Adolescent↗
PubMedDate not supplied

The effect of the cytochrome P-450 suicide inactivator, 1-aminobenzotriazole, on the in vivo metabolism and pharmacologic activity of flurazepam.

Flurazepam (F) is an extensively prescribed hypnotic (Dalmane) whose in vivo activity has been suggested to be due to its primary metabolites, hydroxyethyl flurazepam (HEF) and N-desalkylflurazepam (DAF). In order to determine the intrinsic pharmacologic activity of F, mice were administered various doses of the cytochrome P-450 suicide inactivator, 1-aminobenzotriazole (ABT), 1 hr before the ip administration of 1 mg/kg 14C-F. One hr after 14C-F, 70 mg/kg pentylenetetrazole was administered iv and the mice were observed for convulsions. F alone offered no protection from convulsion (mean brain concentrations were 3.9, 32, and 11 ng/g for F, DAF, and HEF, respectively). F with 25 mg/kg ABT also offered no protection despite a 6-fold increase in brain concentrations of F. F with 100 mg/kg ABT offered a 57% protection from convulsions (mean brain concentrations were 99, 62, and 41 ng/g for F, DAF, and HEF, respectively). One mg/kg F with 400 mg/kg ABT offered 100% protection from convulsions (brain concentrations were 190, 47, and 18 ng/g for F, DAF, and HEF, respectively). These data indicate that F has intrinsic pharmacologic activity which must be considered when evaluating the pharmacodynamics of F.

Animals↗