Induction of apoptosis in human cancer cell lines by the novel anthracenyl-amino acid topoisomerase I inhibitor NU/ICRF 505.

Anthracenyl-amino acid conjugates represent a novel chemical class of topoisomerase (topo) inhibitor. NU/ICRF 505 is a lead compound that stabilises topo I cleavable complexes and is actively cytotoxic at low microM concentrations. In this study, endonucleolytic DNA cleavage was used as a marker of apoptosis to investigate mechanisms of cell death produced by this compound. NU/ICRF 505 (5 microM) induced a substantial increase in the level of DNA fragmentation in HL60 cells (up to 30% of total extracted DNA) but only after a 48 and 72 h drug exposure (compared with 6 h after treatment with camptothecin), as determined qualitatively by conventional gel electrophoresis and quantitatively by spectrofluorimetry. This effect was substantially reversed by co-treatment with zinc (1 mM). Subsequent studies with the human lung (NX002), ovarian (A2780) and colon (HT29) cancer cell lines yielded evidence of formation of higher molecular weight DNA fragments in NX002 and A2780 cells in response to NU/ICRF 505 (5 microM). Co-treatment with zinc (1 mM) caused a small decrease in DNA fragmentation. These data suggest that the induction of apoptosis may play an important role in the mechanism of cytotoxicity of NU/ICRF 505 in HL60 cells and that other pathways of cell death may also be operative in NX002 and A2780 in conjunction with apoptosis.     

Effect of Propofol Anesthesia and Continuous Positive Airway Pressure on Upper Airway Size and Configuration in Infants

Background: Infants are prone to obstruction of the upper airway during general anesthesia. Continuous positive airway pressure (CPAP) is often used to prevent or treat anesthesia-induced airway obstruction. The authors studied the interaction of propofol anesthesia and CPAP on airway caliber in infants using magnetic resonance imaging.

Methods: Nine infants undergoing elective magnetic resonance imaging of the brain were studied. Head position was standardized. Spin echo magnetic resonance images of the airway were acquired at the level of the soft palate, base of the tongue, and tip of the epiglottis. Four sets of images were acquired in sequence: (1) during light propofol anesthesia at an infusion rate of 80 [mu]g [middle dot] kg-1 [middle dot] min-1, (2) after increasing the depth of propofol anesthesia by administering a bolus dose (2.0 mg/kg) and increasing the infusion rate to 240 [mu]g [middle dot] kg-1 [middle dot] min-1, (3) during continued infusion of 240 [mu]g [middle dot] kg-1 [middle dot] min-1 propofol and application of 10 cm H2O CPAP, and (4) after removal of CPAP and continued infusion of 240 [mu]g [middle dot] kg-1 [middle dot] min-1 propofol.

Results: Increasing depth of propofol anesthesia decreased airway caliber at each anatomical level, predominantly due to anteroposterior narrowing. Application of CPAP completely reversed the propofol-induced decrease in airway caliber, primarily by increasing the transverse dimension.     

Assessment of the cariogenic potential of Streptococcus mutans strains and its relationship to in vivo caries experience

Strains of Streptococcus mutans isolated from the plaque of 6 subjects were studied using an in vitro model to determine whether differences in their cariogenic potential could be detected, and if so, whether the results correlated with the caries experience of the individuals. Each strain was incubated with a bovine enamel slab and 5% (w/v) sucrose for 24-h periods. The acidogenic potential was assessed by pH measurement and analysis of acid anion production. Microradiographic and microdensitometric assessment of the enamel, together with measurement of the change in calcium concentration of the reaction mixture were used to determine the demineralizing potential of each strain. Significant differences in cariogenic potential were found between some of the strains tested, and correlations were found between 3 of the test parameters and the decayed-missing-filled-surface score of the individuals. The results suggest that the caries experience of individuals may be related, to some extent, to the cariogenic potential of their S. mutans strains.     

Non-invasive radiological investigation for oculomotor palsy.

An application of computed tomography (CT) is described in which multiplanar high resolution images of the terminal carotid and basilar arteries are obtained. This has been applied in a series of 32 patients with IIIrd nerve palsy in whom the underlying pathology was thought to be a posterior communicating artery aneurysm. The results of the CT were compared with conventional angiography. Seventeen aneurysms were detected in 13 patients by CT and all were confirmed by angiography. Vessels considered to be normal on CT were confirmed to be normal by angiography. This CT technique is a simple non invasive first line investigation for IIIrd nerve palsy with the ability to exclude or predict an aneurysm.