Inhibition of caspases but not of calpains temporarily protect against C2-ceramide-induced death of CAD cells

Evidence has implicated apoptosis as a mechanism underlying cell death in diverse neurodegenerative diseases including Parkinson's disease (PD). Endogenous agents such as TNF-alpha, INF-gamma, IL-1beta and others stress signals activate the sphingomyelin pathway increasing ceramide levels. Ceramide triggers apoptotic pathways while inhibiting survival signalling, and is involved in the regulation of intracellular Ca(2+) homeostasis and compartmentalisation. The contribution of caspases in neuronal apoptosis has been highlighted by the increased survival exerted by caspase inhibition, but the involvement of calpains during neuronal apoptosis and the potential benefit of their inhibition is still controversial. In the present paper, we have analysed the contribution of caspases and calpains to cell death of CAD cells, a catecholaminergic cell line of mesencephalic origin, following C2-ceramide exposure. Ceramide caused CAD cell death by a dose and time dependant mechanism. 25microM of C2-ceramide caused apoptosis. Analysis of activation of caspases and calpains by differential cleavage of alpha-fodrin showed that although calpains are activated before caspases following C2-ceramide exposure, only caspase inhibition increased cell survival. These results demonstrate the activation of caspases and calpains in C2-ceramide-induced cell death, and support the role of caspase inhibition as a neuroprotective strategy and a plausible therapeutic approach to decrease catecholaminergic cell death.     

Unique system of photoreceptors in sea urchin tube feet

Different sea urchin species show a vast variety of responses to variations in light intensity; however, despite this behavioral evidence for photosensitivity, light sensing in these animals has remained an enigma. Genome information of the recently sequenced purple sea urchin (Strongylocentrotus purpuratus) allowed us to address this question from a previously unexplored molecular perspective by localizing expression of the rhabdomeric opsin Sp-opsin4 and Sp-pax6, two genes essential for photoreceptor function and development, respectively. Using a specifically designed antibody against Sp-Opsin4 and in situ hybridization for both genes, we detected expression in two distinct groups of photoreceptor cells (PRCs) located in the animal's numerous tube feet. Specific reactivity of the Sp-Opsin4 antibody with sea star optic cushions, which regulate phototaxis, suggests a similar visual function in sea urchins. Ultrastructural characterization of the sea urchin PRCs revealed them to be of a microvillar receptor type. Our data suggest that echinoderms, in contrast to chordates, deploy a microvillar, r-opsin-expressing PRC type for vision, a feature that has been so far documented only in protostome animals. Surprisingly, sea urchin PRCs lack any associated screening pigment. Indeed, one of the tube foot PRC clusters may account for directional vision by being shaded through the opaque calcite skeleton. The PRC axons connect to the animal internal nervous system, suggesting an integrative function beyond local short circuits. Because juveniles display no phototaxis until skeleton completion, we suggest a model in which the entire sea urchin, deploying its skeleton as PRC screening device, functions as a huge compound eye.     

The relationship between posttraumatic stress disorder and smoking outcome expectancies among U.S. military veterans who served since September 11, 2001

Posttraumatic stress disorder (PTSD) is associated with increased rates of smoking although little is known regarding the mechanisms underlying this relationship. The current study examined expectations about smoking outcomes among smokers with and without PTSD. The sample included 96 veterans (mean age of 34 years) and included 17% women and 50% racial minorities. Smoking expectancies were measured with the Smoking Consequences Questionnaire-Adult (Copeland, Brandon, & Quinn, 1995). Consistent with previous work suggesting that smokers with PTSD smoke in an effort to reduce negative affect, unadjusted analyses indicated that smokers with PTSD (n = 38) had higher expectations that smoking reduces negative affect than smokers without PTSD (d = 0.61). Smokers with PTSD also had increased expectancies associated with boredom reduction (d = 0.48), stimulation (d = 0.61), taste/sensorimotor manipulation aspects of smoking (d = 0.73), and social facilitation (d = 0.61). Results of hierarchical linear regression analyses indicated that PTSD symptom severity was uniquely associated with these expectancies beyond the effects of gender and nicotine dependence. More positive beliefs about the consequences of smoking may increase risk of continued smoking among those with PTSD who smoke. Further understanding of smoking expectancies in this group may help in developing interventions tailored for this vulnerable population.     

Oral Cancer Screening at Workplace in India��One-year Follow-up

Background:

Oral cancer remains the commonest form of cancer and cancer-related deaths among Indian males due to popularity of avoidable risk factors such as tobacco and alcohol use. A workplace oral cancer screening and tobacco cessation study was commenced on World No Tobacco Day 2007 at a chemical industry in rural Maharashtra.

Aims:

The objectives were to screen the employees for oral neoplasia and to correlate it with their tobacco consumption pattern. In addition, the objective was to provide tobacco cessation services at the workplace.

Materials and Methods:

This is an interventional cohort study among 104 employees of a chemical industrial unit in rural Maharashtra. Naked eye examination of the oral cavity was performed for all employees by a doctor irrespective of the tobacco habits at the beginning and at the end of 1 year. In between, the tobacco users were regularly examined during each follow-up.

Statistical analysis used:

Through personal interviews of the participants, data were manually recorded and were transferred to electronic data base. Data analysis was conducted in STATA™ 8.2 on intention to treat basis.

Results and Conclusions:

Among the 104 employees, 50 (48.08%) were current tobacco users at the beginning of the program. Oral precancers were seen exclusively among 20 (40%) tobacco users. After 1 year of workplace tobacco cessation intervention, 80% of oral precancers regressed. This shows that screening of the oral cavity at the workplace is effective when combined with tobacco cessation.