Vitamin D inhibits captopril-induced cell detachment and apoptosis in keratinocytes.

BACKGROUND: Captopril, an angiotensin I-converting enzyme inhibitor, is a commonly prescribed antihypertensive drug. Its cutaneous side-effects include pemphigus vulgaris acantholysis and bullous pemphigoid-like cell-matrix detachment. This medication also triggers apoptosis in human keratinocytes. Calcitriol, the hormonally active vitamin D metabolite, protects keratinocytes from programmed cell death induced by various noxious stimuli. OBJECTIVES: To examine if calcitriol protects proliferating keratinocytes from the damage inflicted by captopril. METHODS: Autonomously proliferating HaCaT keratinocytes, used as a model for basal layer keratinocytes, were exposed to captopril. Cell detachment was examined visually by light microscopy. Cytotoxicity was assessed by Hoechst 33342 staining and lactate dehydrogenase release. Apoptotic death was assessed by monitoring caspase 3-like activity. RESULTS: Cells exposed to captopril detached and became round. This process was accompanied by programmed cell death. From time-dependent monitoring of cell detachment and apoptosis, and examination of pan-caspase inhibitor effects on cell detachment we concluded that cell death is the consequence of cell detachment from the culture plate and not vice versa. Pretreatment with calcitriol significantly attenuated these events. The effects of calcitriol were already evident at 1 nmol L(-1) concentration of the hormone. CONCLUSIONS: The results of this study show that calcitriol protects keratinocytes from captopril-induced cell detachment and apoptosis.

Vitamin D protects keratinocytes from deleterious effects of ionizing radiation.

BACKGROUND: Radiotherapy can induce severe skin responses that may limit the clinically acceptable radiation dose. The responses include erythema, dry and moist desquamation, erosions and dermal-epidermal blister formation. These effects reflect injury to, and reproductive failure of, epidermal cells and may also be due to dysregulation of the tissue remodelling process caused by excessive proteolytic activity. Calcitriol, the hormonally active vitamin D metabolite, protects keratinocytes from programmed cell death induced by various noxious stimuli. OBJECTIVE: To examine whether calcitriol protects proliferating keratinocytes from the damage inflicted by ionizing radiation under conditions similar to those employed during radiotherapy. METHODS: Autonomously proliferating HaCaT keratinocytes, used as a model for basal layer keratinocytes, were irradiated using a linear accelerator. Cell death was monitored by vital staining, executioner caspase activation, lactic dehydrogenase release and colony formation assay. Induction of matrix metalloproteinase-9 was assessed by gelatinase activity assay and mRNA determination. Levels of specific proteins were determined by immunoblotting. RESULTS: Treatment with calcitriol inhibited both caspase-dependent and -independent programmed cell death occurring within 48 h of irradiation and increased the colony formation capacity of irradiated cells. These effects may be attributable to inhibition of the c-Jun NH(2)-terminal kinase cascade and to upregulation of the truncated antiapoptotic isoform of p63. Treatment with the hormone also attenuated radiation-induced increase in matrix metalloproteinase-9 protein and mRNA levels. CONCLUSIONS: The results of this study suggest that active vitamin D derivatives may attenuate cell death and excessive proteolytic activity in the epidermis due to exposure to ionizing radiation in the course of radiotherapy.

Technology architecture guidelines for a health care system.

Although the demand for use of information technology within the healthcare industry is intensifying, relatively little has been written about guidelines to optimize IT investments. A technology architecture is a set of guidelines for technology integration within an enterprise. The architecture is a critical tool in the effort to control information technology (IT) operating costs by constraining the number of technologies supported. A well-designed architecture is also an important aid to integrating disparate applications, data stores and networks. The authors led the development of a thorough, carefully designed technology architecture for a large and rapidly growing health care system. The purpose and design criteria are described, as well as the process for gaining consensus and disseminating the architecture. In addition, the processes for using, maintaining, and handling exceptions are described. The technology architecture is extremely valuable to health care organizations both in controlling costs and promoting integration.

A novel governance system for enterprise information services.

The authors created a novel system for governing the enterprise information services (IS) of a large health care system. The governance organization is comprised of key members of the attending medical staff, hospital and health system administration, and the IS department. A method for defining the requirements and business case for proposed new systems was developed for use by departments requesting new or expanded information services. A Technology Architecture Guideline document was developed and approved to provide a framework for supported hardware and software technologies. IS policies are approved by the main governance council. All project proposals are reviewed by specialized governance committees and, if approved, are launched for further development. Fully developed proposals are reviewed, approved and prioritized for funding by the governance council. This novel organization provides the methodology and structure for enlightened peer review and funding for well developed IS project proposals.