Generation of Escherichia coli nitroreductase mutants conferring improved cell sensitization to the prodrug CB1954.

Escherichia coli nitroreductase (NTR) activates the prodrug CB1954 to a cytotoxic derivative, allowing selective sensitization of NTR-expressing cells or tumors to the prodrug. This is one of several enzyme-prodrug combinations that are under development for cancer gene therapy, and the system has now entered clinical trials. Enhancing the catalytic efficiency of NTR for CB1954 could improve its therapeutic potential.

Determination by HPLC of chlortetracycline in pig faeces.

An HPLC assay used to determine chlortetracycline (CTC) in pig faeces is reported. Prodigy ODS3 (4.6 x 150 mm) was used for the stationary phase, whereas the mobile phase comprised oxalic acid, sodium oxalate and sodium decane sulfonate (66%)--each of 4 mM, and 34% acetonitrile.

Topical vancomycin applied on closure of the sternotomy wound does not prevent high levels of systemic vancomycin.

Objective: Vancomycin is effective in reducing the risk of mediastinits and topical vancomycin has been hypothesised to give high local dose concentrations while avoiding high systemic levels, thus avoiding the risk of bacterial resistance to this second-line antibiotic. However, this theory has never been tested and the degree to which vancomycin is absorbed systemically is unknown.

Methods: Fourteen patients undergoing elective coronary artery bypass grafts (CABG) received 500mg of topical vancomycin prior to sternotomy closure.

Ventilatory response of the cat to hypoxia in sleep and wakefulness.

This study characterized ventilation, the airflow waveform, and diaphragmatic activity in response to hypoxia in the intact adult cat during sleep and wakefulness. Exposure to hypoxia for up to 3 h caused sustained hyperventilation during both wakefulness and sleep. Hyperventilation resulted from significant increases in minute ventilation due to increases in both tidal volume and frequency.

Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement.

Twelve patients undergoing total hip replacement were given 600 mg of linezolid as a 20 min iv infusion along with conventional prophylaxis of 1 g of cefamandole immediately before surgery. Routine total hip arthroplasty was carried out, and at timed intervals during surgery samples of bone, fat, muscle and blood were collected for assay by high-performance liquid chromatography analysis. Samples of the haematoma fluid that formed around the operation site and further blood samples for assay were also collected at timed intervals following the operation.

Epidemiology and resource utilization for patients hospitalized for lower respiratory tract infection.

Objectives: To determine referral rates, patient characteristics, and resource utilization for patients admitted to hospital with community-acquired lower respiratory tract infections (LRTI).

Methods: Six hundred and thirteen patients, accounting for 704 LRTI episodes, were included in the study, if the referral diagnosis was LRTI and if both signs and symptoms on admission and patient management were consistent with this diagnosis. Patient records were abstracted to collect information on co-morbidities, patient demographics, resource utilization, episode outcome, pharmacy prescribing and diagnostic service utilization.

Antibiotic elution from bone cement: A study of common cement-antibiotic combinations.

The in vitro antibiotic elution characteristics (including the effects of cement fracture) of the following cements were studied: 1) CMW 1 with gentamicin, 2) Palacos R with gentamicin, 3) Palacos LV with gentamicin, 4) CMW 1 with gentamicin and vancomycin, 5) Palacos R with gentamicin and vancomycin, 6) CMW 1 with gentamicin and flucloxacillin, and 7) Palacos R with gentamicin and flucloxacillin. Elution of both gentamicin and vancomycin was satisfactory in all cases. There tended to be a peak of antibiotic release on cement fracture, suggesting sequestration of active antibiotic within deeper layers of the cement.

The excess cost of acute exacerbations of chronic bronchitis in patients aged 45 and older in England and Wales.

Introduction: Chronic Bronchitis is a serious and costly health problem. Prevalence is estimated at 45 per 10,000 persons in the United Kingdom. Approximately 120,000 Pounds would be saved for every 100 hospital admissions avoided.

The structure of Escherichia coli nitroreductase complexed with nicotinic acid: three crystal forms at 1.7 A, 1.8 A and 2.4 A resolution.

Escherichia coli nitroreductase is a flavoprotein that reduces a variety of quinone and nitroaromatic substrates. Its ability to convert relatively non-toxic prodrugs such as CB1954 (5-[aziridin-1-yl]-2,4-dinitrobenzamide) into highly cytotoxic derivatives has led to interest in its potential for cancer gene therapy. We have determined the structure of the enzyme bound to a substrate analogue, nicotinic acid, from three crystal forms at resolutions of 1.

The penetration of ceftriaxone and cefamandole into bone, fat and haematoma and relevance of serum protein binding to their penetration into bone.

Thirteen patients undergoing total hip replacement were given ceftriaxone 1 g and cefamandole 1 g simultaneously, either immediately or 8 h before surgery. For both agents the concentrations seen in the bone and fat during the operation, and for haematoma fluid View Article and Find Full Text PDF

Endogenous excitatory drive to the respiratory system in rapid eye movement sleep in cats.

A putative endogenous excitatory drive to the respiratory system in rapid eye movement (REM) sleep may explain many characteristics of breathing in that state, e.g. its irregularity and variable ventilatory responses to chemical stimuli.

Mu and delta opioid receptor regulation of pro-opiomelanocortin peptide secretion from the rat neurointermediate pituitary in vitro.

We investigated the ability of selective opioid agonists and antagonists to influence pro-opiomelanocortin peptide secretion from the rat neurointermediate lobe in vitro. The mu-opioid agonist DAMGO ([D-Ala(2), N-Me-Phe(4), Gly(5)-ol]enkephalin) significantly stimulated beta-endorphin and alpha-melanocyte-stimulating hormone release relative to controls early (30 min) in the incubation period. Similar effects on beta-endorphin secretion were observed with the selective mu-opioid agonist dermorphin.

Use of meropenem 3 g once daily for outpatient treatment of infective exacerbations of bronchiectasis.

Meropenem administered as a single iv 3 g dose once every 24 h was used to treat nine ambulatory patients with infective exacerbations of bronchiectasis. Serum meropenem concentrations were measured before dosing and at 30 min after each 30 min infusion. Mean pre-dose concentrations were <0.

alpha-melanocyte-stimulating hormone and habituation of prey-catching behavior in the Texas toad, Bufo speciosus.

We investigated dose-dependent effects of alpha-melanocyte-stimulating hormone (alpha-MSH) on habituation in the Texas toad, Bufo speciosus. Additionally, we determined changes in plasma and brain levels of alpha-MSH following peripheral administration of the peptide or following exposure to an ether stressor. The ability of alpha-MSH to facilitate acquisition of habituation was dose dependent.

Difficulties in the assay of liposomal amikacin (MiKasome) in serum.

Antibiotic-free human serum was spiked with known concentrations of liposomal amikacin and assayed on the Abbott TDx System, using polarization fluoroimmuno assay (PFIA) kits from Abbott Laboratories, Oxis and Sigma. Although all three kits gave a linear response, the Abbott and Oxis kits showed very low recovery (<21%) with only the Sigma kit giving near 100% recovery. Heating samples at 56 degrees C for 30 min improved recovery with the Abbott and Oxis kits (75-80% of target value), but decreased recovery with the Sigma kit (85% of target value).

A comparative study of the rifampicin binding and elution characteristics for collagen- and albumin-sealed vascular grafts.

Objectives: To assess the rifampicin binding and elution characteristics for three protein-sealed vascular grafts.

Design: In vitro study.

Materials: Cardial and Hemashield collagen-sealed and the DeBakey/Vasculour albumin-sealed vascular grafts.

Kinetics and toxicity of liposomal and conventional amikacin in a patient with multidrug-resistant tuberculosis.

The pharmacokinetics and toxicity of liposomal amikacin in a patient treated for advanced pulmonary multidrug-resistant tuberculosis are described. A dose of 20 mg/kg of liposomal amikacin was given on alternate days for 14 days and weekly thereafter for 9 weeks, for a total dose of 20.1 g in 17 divided doses.

Alterations in brain and pituitary beta-endorphin content in genetically epilepsy-prone rats.

We measured beta-endorphin concentrations in the anterior and neurointermediate lobes of the pituitary gland and in microdissected brain regions of moderate-seizure genetically epilepsy-prone rats (GEPR-3), severe-seizure GEPR-9s and Sprague-Dawley non-epileptic control rats. Plasma concentrations of beta-endorphin and beta-melanocyte-stimulating hormone (alpha-MSH) were also measured as indicators of pituitary POMC-peptide secretion. Concentrations of beta-endorphin in the anterior lobe of GEPR-3s were 53% higher compared to controls and 57% higher compared to GEPR-9s.