Lung vitamin E transport processes are affected by both age and environmental oxidants in mice

Despite the physiological importance of alpha-tocopherol (AT), the molecular mechanisms involved in maintaining cellular and tissue tocopherol levels remain to be fully characterized. Scavenger receptor B1 (SRB1), one of a large family of scavenger receptors, has been shown to facilitate AT transfer from HDL to peripheral tissues via apo A-1-mediated processes and to be important in the delivery of AT to the lung cells. In the present studies the effects of age and two environmental oxidants ozone (O(3)) (0.25 ppm 6 h/day) and cigarette smoke (CS) (60 mg/m(3) 6 h/day) for 4 days on selected aspects of AT transport in murine lung tissues were assessed. While AT levels were 25% higher (p<0.05) and 15% lower (p<0.05) in plasma and lung tissue, respectively, in aged versus young mice, acute environmental exposure to O(3) or CS at the doses used had no effect. Gene expression levels, determined by RT-PCR of AT transport protein (ATTP), SRB1, CD36, ATP binding cassette 3 (ABCA3) and ABCA1 and protein levels, determined by Western blots for SRB1, ATTP and ABCA1 were assessed. Aged mouse lung showed a lower levels of ATTP, ABCA3 and SRB1 and a higher level CD36 and ABCA1. Acute exposure to either O(3) or CS induced declines in ATTP and SRB1 in both aged and young mice lung. CD36 increased in both young and aged mice lung upon exposure to O(3) and CS. These findings suggest that both age and environmental oxidant exposure affect pathways related to lung AT homeostasis and do so in a way that favors declines in lung AT. However, given the approach taken, the effects cannot be traced to changes in these pathways or AT content in any specific lung associated cell type and thus highlight the need for further follow-up studies looking at specific lung associated cell types.     

Inhibition and recovery of maternal and foetal cholinesterase enzymes following fenitrothion administration in CD rats

The purpose of this study was to characterize tissue esterase activity and blood fenitrothion concentrations in the rat dam and foetus following in-utero exposure to the organophosphate insecticide fenitrothion. Time-mated, 8-week-old rats were gavaged on gestation day 19 with 0, 5, or 25 mg fenitrothion kg-1. Fenitrothion was absorbed rapidly from the gastrointestinal tract, with peak maternal and foetal blood levels observed 0.5-1.0 h after dosing. Fenitrothion concentrations in maternal and foetal blood were virtually identical and demonstrated a non-linear dose-response relationship. Acetylcholinesterase and carboxylesterase activities in maternal liver and blood and in foetal liver and brain decreased within 30-60 min of fenitrothion exposure. Esterase inhibition occurred at a fenitrothion dose (5 mg kg-1) that has not been previously associated with reproductive toxicity, suggesting that esterase inhibition should be considered as the critical effect in risk assessments for this pesticide.     

Enhanced identification of smoking-related words during the attentional blink in smokers

The attentional blink (AB) occurs when ongoing processing of one target (T1) in a series of rapidly presented stimuli impairs processing of a subsequently presented second target (T2), such that T2 cannot be consciously perceived or reported. There is evidence that the AB can be influenced by the emotional or motivational salience of T2. We examined whether the AB could be attenuated by smoking-related stimuli in smokers. Heavy smokers (N=55) performed an AB task on two occasions, once following 12-h of abstinence and once following ad libitum smoking. T2s were either smoking-related or neutral (household-related) words, and lagged T1 by 0 to 7 distracter words. T1s were all neutral words. Each word was presented for 130 ms. Subjects were required to recall T1 and T2 immediately after each trial. There was a significant word type by lag interaction, whereby smoking-related T2s were recalled better than neutral T2s at early, but not late, lags. The word type effect at early lags was significantly associated with attentional bias assessed on the smoking Stroop task, but was not significantly moderated by abstinence. These data indicate that, in heavy smokers, smoking-related stimuli are more likely to engage conscious awareness than neutral words under conditions of limited attentional resources.     

Decline in βhCG levels between days 0 and 4 after a single dose of methotrexate for ectopic pregnancy predicts treatment success: a retrospective cohort study

In current protocols for the medical management of ectopic pregnancies, the first indication of treatment response is obtained no sooner than day 7. We examined whether human chorionic gonadotrophin (βhCG) trends between days 0 and 4 after methotrexate provide an earlier indication of the likely outcome. Of 33 patients where serum βhCG dropped between days 0 and 4 after methotrexate, the ectopic pregnancy was resolved in 88% of cases without further treatment. Of 12 women where serum βhCG rose between days 0 and 4, only 42% had treatment success. A fall in βhCG between days 0 and 4 after treatment with methotrexate for ectopic pregnancy predicts a high likelihood of treatment success.     

Significance of abnormal sonographic findings in postmenopausal women with and without bleeding

ObjectiveWe sought to determine the incidence of cancer and to compare pathologic outcomes in bleeding and non-bleeding postmenopausal patients who underwent hysteroscopy.MethodsWe conducted a retrospective chart review of 294 postmenopausal women with abnormal uterine bleeding and 142 postmenopausal women without symptoms who underwent hysteroscopy. An 11 mm cut-off for asymptomatic women was applied to determine whether this endometrial thickness threshold would differentiate women with and without endometrial cancer in the asymptomatic group.ResultsIn symptomatic patients, 14 were found to have endometrial cancer and 10 were found to have endometrial hyperplasia. In the asymptomatic group, two women (1. 4%) were found to have endometrial cancer with average thickness 17 . 5 mm, and one (0 . 71%) was found to have endometrial hyperplasia . Logistic regression models showed the risk of a bleeding patient developing endometrial cancer at an endometrial thickness of 4 mm was the same as the risk in a non-bleeding patient at a thickness of 15 mm.ConclusionAsymptomatic postmenopausal women have a low risk of having significant endometrial pathology . Cancer was approximately four times more prevalent in women with bleeding than in women with no bleeding     

Symptomatic HIV seroconverting illness is associated with more rapid neurological impairment

OBJECTIVES: To establish whether symptomatic seroconverting illness in HIV infected people is associated with more rapid development of neurological impairment. METHODS: 166 HIV infected subjects with a known date of HIV infection enrolled in a longitudinal study of neurocognitive function were stratified by whether or not they had experienced a symptomatic serconverting illness. RESULTS: 29 of 166 (17.5%) dated HIV seroconverters had a history of symptomatic seroconverting illness. Though baseline neurocognitive function was similar, subjects with a symptomatic seroconverting illness developed clinical neurocognitive impairment significantly more rapidly than their asymptomatic counterparts in a survival analysis model (636 v 1075 days till impaired). CONCLUSION: Symptomatic seroconverting illness predisposes to more rapid neurocognitive impairment.     

Human myoblast engraftment is improved in laminin-enriched microenvironment

BACKGROUND: One major challenge in developing cell therapy for muscle diseases is to define the best condition for the recipient's muscle to niche donor cells. We have examined the efficiency of human myoblast transplantation in an immunodeficient animal model, after local irradiation, as well as the potential impact of laminin on myoblast behavior. METHODS: Human myoblasts were injected into preirradiated tibialis anterior muscles from immunodeficient mice. The donor cell engraftment, proliferation, and laminin content within the transplanted muscles were evaluated by immunocytochemistry. Additionally, the effect of laminin upon myoblast proliferation, migration, and survival was ascertained in vitro. RESULTS: Engraftment of human myoblasts into the skeletal muscle of immunodeficient Rag2-/gammac-/C5- mice presubjected to local irradiation provided the best niche for myoblast engraftment, as demonstrated by the number of viable and proliferating donor cells found in the host muscle. Local irradiation significantly enhanced laminin deposition within the recipient's muscle and donor cells were preferentially located in laminin-enriched areas. The same batch of myoblasts used for in vivo injections also responded to laminin in vitro with increased proliferation and cell survival, as well as an improved migratory response. CONCLUSIONS: We show that local irradiation enhances the laminin content in the host muscle microenvironment and provides a better engraftment of human myoblasts. In addition, laminin increases myoblast proliferation, survival, and migration in vitro. These data provide combined in vivo and in vitro evidence that laminin status should be taken into account when designing experimental and clinical cell therapy strategies for muscle disease.     

Enhanced activity of a hydrogen sulphide-releasing derivative of mesalamine (ATB-429) in a mouse model of colitis

Background and Purpose: