The haemotoxicity of mitomycin in a repeat dose study in the female CD-1 mouse

Mitomycin (MMC), like many antineoplastic drugs, induces a predictable, dose-related, bone marrow depression in man and laboratory animals; this change is generally reversible. However, there is evidence that MMC may also cause a late-stage or residual bone marrow injury. The present study in female CD-1 mice investigated the haematological and bone marrow changes induced by MMC in a repeat dose study lasting 50 days. Control and MMC-treated mice were dosed intraperitoneally on eight occasions over 18 days with vehicle, or MMC at 2.5 mg/kg, autopsied (n = 6-12) at 1, 7, 14, 28, 42 and 50 days after the final dose and haematological changes investigated. Femoral nucleated bone marrow cell counts and levels of apoptosis were also evaluated and clonogenic assays carried out; serum levels of FLT3 ligand (FL) were assessed. At day 1 post-dosing, MMC induced significant reductions in RBC, Hb and haematocrit (HCT) values, and there were decreases in reticulocyte, platelet, and femoral nucleated cell counts (FNCC); neutrophil, lymphocyte and monocyte values were also significantly reduced. On days 7 and 14 post-dosing, all haematological parameters showed evidence of a return towards normal values, but at these times, and at day 28, values for RBC and FNCC remained significantly reduced in comparison with controls. At days 42 and 50 post-dosing, many haematological parameters in MMC-treated mice had returned to control levels; however, there remained evidence of late-stage effects on RBC, Hb and HCT values, and FNCC also continued to be significantly decreased. Results for granulocyte-macrophage colony-forming units and erythroid colonies showed a profound decrease immediately post-dosing, but a return to normal values was evident at day 50. Serum FL concentrations demonstrated very significant increases in the immediate post-dosing period, but a return to normal was seen at day 50 post-dosing; a relatively similar pattern was seen in the number of apoptotic femoral marrow nucleated cells. The histopathological examination of kidney tissues from MMC animals at day 42 and 50 post-dosing showed evidence of hydronephrosis with cortical glomerular/tubular atrophy and degeneration. It is therefore concluded that MMC administered on eight occasions over 18 days to female CD-1 mice at 2.5 mg/kg induced profound changes in haematological and bone marrow parameters in the immediate post-dosing period with a return to normal levels at day 50 post-dosing; however, there was evidence of mild but significant late-stage/residual effects on RBC and FNCC, and on cells of the erythroid lineage in the bone marrow.     

Photochemistry and desorption induced by X-rays in water rich astrophysical ice analogs: implications for the moon Enceladus and other frozen space environments

Soft X-rays are an important agent for chemical processing in the Solar System and in the interstellar medium. The photolysis and photodesorption processes of H₂O-rich ices triggered by soft X-rays was, experimentally, addressed in this paper. The experiments were performed at the Brazilian synchrotron facility LNLS/CNPEN employing broadband radiation (from 6 to 2000 eV; mainly soft X-rays and a small fraction of VUV) in solid samples at temperatures of 20 and 80 K. The icy samples were monitored by infrared spectroscopy. We determined the effective destruction cross section (in the order 10⁻¹⁸ cm²) as well as the formation cross section for the new species produced after the irradiation. Among them, we list OCN⁻, CO, CO₃, CH₃OH, H₂O₂, HCOO⁻, NH₄⁺, HCONH₂ and CH₃HCO, mostly formed in the experiment at 80 K. The chemical equilibrium stage was characterized and molecular abundances were quantified. In addition, we discuss a methodology to estimate the amount of unknown species in the ice produced by photolysis. The samples reach chemical equilibrium at fluences around 2–3 × 10¹⁸ cm⁻². Timescales for reaching chemical equilibrium in space environments illuminated by X-rays were given, as well as the desorption yields induced by X-rays. The astrophysical implication on the surface chemistry and desorption processes at the moon Enceladus are provided.

Soft X-rays are an important agent for chemical processing in the Solar System and in the interstellar medium.     

Alcohol-related affordances and group subjectivities: A Q-Methodology study

Aims: An Ecological approach to alcohol behaviour focuses on understanding individual–environment transactions, rather than on cognitive antecedents of behaviour. Meaning exists in the interdependence of individuals and their environments, in terms of affordances. Through subjective experience, this study focussed on group viewpoints related to alcohol-related affordances, or opportunities to consume alcohol in shared drinking environments. Methods: Forty students with a range of self-reported drinking behaviours participated in a Q-Methodology study, ranking 60 statements along a symmetrical grid. This varied concourse of alcohol-related affordances was obtained from a previous observation study within licenced premises and a photo-elicitation interview study with drinkers. Findings: Factor analysis and post-sort interviews revealed four subjective perspectives held by groups about their drinking behaviour: 13 participants were aware of contextual influences, but autonomous in their drinking choices; 12 participants were conscious of influences and compliant to their effects; six participants were unaware of influences, but unanimous with their peers; two participants were concerned about acting appropriately in a context by taking up canonical affordances. Conclusions: Grouping subjectivities from a varied concourse of affordances can reveal subjective experience in relation to drinking environments and alcohol behaviour. This conceptual approach for understanding drinking behaviour should be studied further.     

“Everything is telling you to drink”: understanding the functional significance of alcogenic environments for young adult drinkers

Background: Dominant approaches to understanding alcohol consumption and preventing misuse focus on cognitive antecedents of drinking behaviour. However, these approaches are not only limited, but ignore wider contextual factors. Adopting an ecological approach, this paper considers the functional significance of alcogenic environments from the perspectives of individual drinkers, based on the availability of alcohol-related affordances.

Method: Twelve undergraduate students aged 18-30, with a range of self-reported drinking behaviours virtually navigated a range of drinking environments during photo-elicitation interviews. Participants individually described drinking contexts in terms of the form and function-based characteristics that they believed promoted and/or inhibited their alcohol consumption.

Results: Interpretative phenomenological analysis revealed the meaning drinking environments had for drinkers, based on their experiences. For participants, alcohol consumption was related to accessibility, communicating with others, consuming food, grasping items, furniture availability, watching or listening to entertainment, advertisement placement, premise décor and alternative action opportunities.

Conclusions: Focusing on the functional significance of drinking contexts may be more conducive to understanding contextual factors which may promote or prohibit alcohol consumption. The extent that alcohol-related affordances are linked with excessive consumption and alcohol-related problems merits further study.     

Outcome of congenital lung abnormalities detected antenatally

To determine the outcome of congenital lung abnormalities, data were collected retrospectively between January 1991 and December 1996 on any foetus found to have a lung lesion on antenatal ultrasound. A total of 23 foetuses had lung lesions on antenatal ultrasound. In two foetuses the antenatal ultrasound showed bilateral enlarged "bright" echogenic lungs with evidence of hydrops. Both pregnancies were terminated and tracheal atresia was confirmed. In 15 foetuses the antenatal ultrasound appearance was of a unilateral "bright" echogenic lung. There was one case of bronchial atresia and two cases of congenital lobar emphysema, which all had surgery. In nine cases there was a reduction in the size of the lesion on serial antenatal ultrasounds and no lesion was detected after birth. In three cases a small lesion was present after birth on chest radiography. In six foetuses the antenatal ultrasound appearance was of unilateral cystic or mixed cystic and echogenic lung lesions. Two pregnancies were terminated; both had congenital cystic adenomatoid malformation. Four pregnancies were continued and three infants had surgery soon after birth and were confirmed to have had congenital cystic adenomatoid malformation. One infant has been managed conservatively. In conclusion, a definitive diagnosis cannot usually be made antenatally. A large lesion on initial scan does not necessarily predict a poor outcome. The natural history of small asymptomatic postnatal lesions is unknown and a long-term prospective study is needed to determine the outcome of these lesions.