Reactive oxygen species: a breath of life or death?

New insights into cancer cell-specific biological pathways are urgently needed to promote development of rationally targeted therapeutics. Reactive oxygen species (ROS) and their role in cancer cell response to growth factor signaling and hypoxia are emerging as verdant areas of exploration on the road to discovering cancer's Achilles heel. One of the distinguishing and near-universal hallmarks of cancer growth is hypoxia. Unregulated cellular proliferation leads to formation of cellular masses that extend beyond the resting vasculature, resulting in oxygen and nutrient deprivation. The resulting hypoxia triggers a number of critical adaptations that enable cancer cell survival, including apoptosis suppression, altered glucose metabolism, and an angiogenic phenotype. Ironically, recent investigations suggest that oxygen depletion stimulates mitochondria to elaborate increased ROS, with subsequent activation of signaling pathways, such as hypoxia inducible factor 1alpha, that promote cancer cell survival and tumor growth. Because mitochondria are key organelles involved in chemotherapy-induced apoptosis induction, the relationship between mitochondria, ROS signaling, and activation of survival pathways under hypoxic conditions has been the subject of increased study. Insights into mechanisms involved in ROS signaling may offer novel avenues to facilitate discovery of cancer-specific therapies. Preclinical and clinical evaluation of agents that modify ROS signaling in cancer offers a novel avenue for intervention. This review will cover recent work in ROS-mediated signaling in cancer cells and its potential as a target for developmental therapeutics.     

The eye care profile and outcomes of multi-handicapped adults residing in Wayne County, Michigan group homes.

BACKGROUND: Patients with multi-handicaps present clinical challenges and are underserved. Central nervous system dysfunction and ocular disorders with this population are prevalent and well-documented. However, vision care outcomes data are limited and specific visual function recommendations to caregivers are rarely cited. METHODS: The charts of 110 multiply handicapped adults residing in 22 group homes in Wayne County. Michigan were retrospectively studied to identify ocular profiles and predictors of visual function. RESULTS: Sixty-five percent of the subjects were male and 80% were ages 26 to 55 years. There was no expressive language in 41%, and 37% were non-ambulatory. The median visual impairment level was moderate in both eyes (based on WHO). Significant associations between visual impairment level and subpopulations (such as seizure disorder, mental retardation without specific etiology, cerebral palsy, and Down syndrome) were identified. Successful spectacle wear statistically increased with higher refractive errors. Associations between cataract, nystagmus, and strabismus with particular subpopulations were significant (all P values < 0.0182). CONCLUSIONS: Clinicians who evaluate patients with multi-handicaps have few known predictors of treatment success. This study indicates that useful predictors of visual function can be made from refractive error, systemic conditions, and ocular diagnoses. No significant relationship was found with cognitive level and either vision impairment or spectacle use. The authors attribute successful implementation of recommendations to communication with group home caregivers.     

In Vitro and in Vivo Evaluation of Whole and Half Tablets of Sustained-Release Adinazolam Mesylate

The mechanism of release from sustained-release adinazolam mesylate tablets was assessed by the Higuchi equation and by analysis of drug release profiles through 60% released using the Peppas equation. Computed values of the diffusional exponent, n, ranged from 0.59 to 0.66. Values of n in this range are consistent with a mixed mechanism of release, with diffusion of drug through the hydrated polymer matrix and relaxation of this matrix being the principal processes controlling release. The rate of in vitro drug release was increased for half tablets relative to whole tablets and is attributed to an increase in the surface to volume ratio of half tablets of about 16%. This increase in surface-to-volume ratio of half tablets was reflected by an increase in the constant, k, from the Peppas equation of 20–23% and by an increase in the slope of Higuchi plots of 12–18% for four lots of tablets. In vivo/in vitro relationships from two bioavailability studies were thoroughly evaluated. Using either a linear or a quadratic relationship, an in vivo/in vitro correlation exists for sustained-release adinazolam mesylate tablets.     

Time for sport and health to be formally linked in a positive way

Preventing sports injury has rarely been cited as an appropriate action to respond to the obesity epidemic, and in fact a recent letter has suggested that those playing sport are as responsible for their predicament as those who are obese. This opinion piece argues that it is time for better prevention and management of sports injury to be seen as part of the complex solution to preventing obesity, rather than being a self-inflicted problem that governments should continue to ignore.     

A randomized multicenter study to determine the efficacy of activity restriction for preterm labor management in patients testing negative for fetal fibronectin.

OBJECTIVE: To assess the impact of activity restriction (AR) on the incidence of preterm birth in women treated for preterm labor testing negative for fetal fibronectin (fFN). STUDY DESIGN: Women who were diagnosed with preterm labor and tocolyzed with magnesium sulfate were concurrently screened with fFN for the purpose of subsequent management. Included were consenting patients with negative fFN, gestational age 23 0/7-33 6/7 weeks, cervical dilation < or =3 cm, and minimal vaginal bleeding. Patients were randomized to AR or no AR. Primary study outcome was incidence of preterm delivery and interval from randomization to delivery. RESULTS: A total of 73 women with negative fFN were randomized (36 with AR, 37 without AR). The overall preterm birth rate was 40%, with 44.4% of patients with AR and 35.1% of patients without AR delivering preterm, p=0.478. CONCLUSION: Maternal AR did not impact pregnancy outcome. The incidence of preterm birth in symptomatic women testing fFN negative was higher than previously reported.