Calpain and PARP Activation during Photoreceptor Cell Death in P23H and S334ter Rhodopsin Mutant Rats

Retinitis pigmentosa (RP) is a heterogeneous group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness. Many human cases are caused by mutations in the rhodopsin gene. An important question regarding RP pathology is whether different genetic defects trigger the same or different cell death mechanisms. To answer this question, we analysed photoreceptor degeneration in P23H and S334ter transgenic rats carrying rhodopsin mutations that affect protein folding and sorting respectively. We found strong activation of calpain and poly(ADP-ribose) polymerase (PARP) in both mutants, concomitant with calpastatin down-regulation, increased oxidative DNA damage and accumulation of PAR polymers. These parameters were strictly correlated with the temporal progression of photoreceptor degeneration, mirroring earlier findings in the phosphodiesterase-6 mutant rd1 mouse, and suggesting execution of non-apoptotic cell death mechanisms. Interestingly, activation of caspases-3 and -9 and cytochrome c leakage—key events in apoptotic cell death—were observed only in the S334ter mutant, which also showed increased expression of PARP-1. The identification of the same metabolic markers triggered by different mutations in two different species suggests the existence of common cell death mechanisms, which is a major consideration for any mutation independent treatment

Emergency department patient characteristics: Potential impact on emergency medicine residency programs in the Netherlands.

Contains fulltext : 49407.pdf (publisher's version ) (Closed access)OBJECTIVES: We set out to study emergency department patient characteristics at a busy level-2 trauma center, to gain insight into the practise of emergency medicine, which is not yet recognized as a specialty in the Netherlands. METHODS: From May 27 to July 4 2001, the following data were recorded from the charts of all patients presenting to the emergency department: age, time and form of presentation, diagnostics, treatment, disposition and the single best diagnosis (International Classification of Disease-10 classification). RESULTS: The majority (84%) of the 5234 patients (134/day) patients seen were self-referred and treated by the emergency department physician. The remaining 16% were referred, usually by their general practitioner, directly to a specialty service, which saw them in the emergency department. Self-referred patients tended to be younger (average 33 years), with minor trauma, and infrequently required diagnostics (37%), treatment (49%) or admission (4%). The referred patients were older (average 50 years), with 41% needing admission. Only 16% of all patients were under 16 years of age. In all, there were five deaths (referred patients), 12 resuscitations, seven intubations, seven chest tube insertions and no lumbar punctures performed during the study period. CONCLUSION: The acuity of self-referred patients seen by the emergency physicians is low, with little diagnostic testing and few interventions and resuscitations, even in a busy center. This has both training and practise implications and it may be inappropriate to take an emergency medicine practise model or curriculum from another country based on its emergency department population