Neurotoxic nitric oxide rapidly depolarizes and permeabilizes mitochondria by dynamically opening the mitochondrial transition pore

Exposure of SH-SY5Y neuroblastoma or rat cortical neurons to diethylenetriamine-NO (DETA-NO) rapidly depolarized mitochondria. In SH-SY5Y DETA-NO activated caspase 3 and produced cell death. Mitochondrial depolarization in SH-SY5Y was visualized both with JC-1 accumulation and as dequenching of calcein fluorescence in mitochondria initially loaded with calcein-AM and tetramethylrhodamine methyl ester (TMRM). Calcein/TMRM-visualized mitochondrial depolarization was prevented by cyclosporin A (CsA) or approximately two-fold increased levels of BclXL protein. Dynamic imaging of mitochondrial potential (Deltapsi M) with TMRM showed that DETA-NO induced cycles of mitochondrial depolarization/repolarization ("flickering"). Fifteen-30 min of DETA-NO exposure caused high-frequency flickering with small peak size; 2 h of DETA-NO produced large peaks with prolonged depolarization. NO-induced flickering but not that from Bax was blocked by the calcium uniporter antagonist Ru360. Our findings show rapid-onset, dynamic regulation of Deltapsi M by NO, implying that neuroprotective therapies for brain ischemia target cell death processes downstream of effects of NO on mitochondria.     

A4T mutation in the SOD1 gene causing familial amyotrophic lateral sclerosis

We report the clinical and laboratory findings in the largest kindred so far recorded with familial amyotrophic lateral sclerosis due to an A4T mutation in the SOD1 gene. The age of onset ranged from 32 to 60 years, with a mean of 46 years. Weakness in the legs was the most frequent early symptom and there was a predominance of lower motor neuron signs. The mean time from onset of symptoms to death was 14 months. One man with onset at the age of 37 has shown a slowly developing form and is currently alive 76 months after diagnosis (October 2002), although severely affected. The A4T mutation, with one exception, was of similar severity to the A4V mutation.     

Periodontal disease is associated with lower antioxidant capacity in whole saliva and evidence of increased protein oxidation

The aim of this cohort study was to determine whether periodontitis and gingivitis are associated with impaired salivary antioxidant status and increased oxidative injury. One hundred and twenty-nine patients attending a routine dental check-up were recruited for the study. Periodontal disease status was characterized using the Community Periodontal Index of Treatment Needs (CPITN) system. Total salivary antioxidant capacity and salivary ascorbate, urate and albumin were determined in a sample of whole unstimulated saliva. Protein carbonyl concentrations were determined as an index of oxidative injury. Patients in the lowest tertile of CPITN score exhibited decreased salivary delivery of antioxidants and specifically urate than patients in the upper tertile. Poor periodontal health was associated with increased concentrations of protein carbonyls in saliva. Women had significantly lower total antioxidant status than men, regardless of periodontal health. Periodontal disease is associated with reduced salivary antioxidant status and increased oxidative damage within the oral cavity.     

The health-promoting nurse as a health policy career expert and entrepreneur

A plethora of literature suggests that many nurses struggle in their attempts to develop a political role that allows them to directly influence and implement health policy activity. Nursing curricula are an integral part of ensuring that nurses are capable of taking on a more active role in initiating and developing health policy processes, through a broadening of the health promotion curriculum that focuses on socio-political approaches to health care provision. Despite this, the available literature suggests that the majority of nursing curricula are yet to fulfil this role. Such a role could be supported by attempts to define and promote a specific career route that develops nurses as health policy experts and entrepreneurs early on in their careers. This article aims to put forward a rationale for developing such a position in nursing education.     

Lexicalization of idioms in urban fifth graders: a reaction time study

Idioms are an important aspect of language that comprises a sizeable portion of our vocabulary. However, lexical access research has largely been limited to understanding how literal words are accessed and processed in the mental lexicon. Adult data show that idioms are quickly accessed from the lexicon and are likely processed as long words [J. Verbal Learn. Verbal Behav. 18 (1979) 523]. The purpose of this study was to examine lexicalization of idioms in a group of school-aged children. Using a phrase classification design, this research tested the Lexical Representation Hypothesis [J. Verbal Learn. Verbal Behav. 18 (1979) 523] in 19 urban fifth graders (5 boys, 14 girls; M age=10.16 years). On a computer, the students classified 54 phrases, including 24 idioms (high, moderate, and low familiarity [J. Speech Hear. Res. 36 (1993) 728]), 24 grammatical control word strings and 6 unrelated foils as either idioms or nonidioms. The idioms were identified with 62% accuracy. Unexpectedly, the boys tended to show higher rates of accuracy than the girls. Response latencies were shorter on the idioms compared to the controls and high familiarity idioms were processed faster than moderate and low familiarity idioms. These findings provide developmental data for lexicalization of idioms and the relationship between lexicalization and familiarity. At the cocnlusion of this articel, the reader will be able to: (1). discuss the various theories of idiom access and processing, (2). discuss how lexical access relates to idiom knowledge in school-aged children, and (3). consider the association between lexical access and familiarity relative to idiom comprehension in school-aged children.     

G-CSF-induced spleen size changes in peripheral blood progenitor cell donors

BACKGROUND: PBPC donors given G-CSF experience splenic enlargement and, rarely, spontaneous rupture of the spleen. This study evaluated the incidence and time course of splenic enlargement in PBPC concentrate donors and assessed factors affecting size changes. STUDY DESIGN AND METHODS: Twenty healthy adults were given G-CSF (10 microg/kg/day) for 5 days and a PBPC concentrate was collected by apheresis. Ultrasound was used to assess craniocaudal spleen length before giving G-CSF, on the day of apheresis and 3 or 4 days after apheresis. The effects of donor age, gender, race, and changes in blood chemistries, blood counts, and CD34+ cell counts on spleen length change were assessed. RESULTS: Spleen length increased in 19 of 20 donors. Mean length changed from 10.9 +/- 2.0 cm before G-CSF to 12.3 +/- 2.1 cm on the day of apheresis (p < 0.001). The mean increase in length was 1.5 +/- 0.9 cm or 13.8 +/- 9.1 percent. Spleen length increased 20 percent or more in six subjects. The spleen length fell to 11.3 +/- 1.8 cm (p < 0.001) 3 or 4 days after apheresis, but it remained greater than baseline levels (p = 0.03). Spleen length change was not affected by donor gender, race, or age. There was no relationship between changes in spleen length and 1) baseline and apheresis-day blood counts and chemistries, or 2) changes in blood counts and chemistries. CONCLUSIONS: Spleen size increases in almost all PBPC donors. Enlargement is transient but may be marked in some donors and may place them at risk for splenic rupture.     

Health-related quality of life tools for venous-ulcerated patients

Healthcare manufacturing companies have developed many new and novel materials for wound care. They claim that the dressing materials will improve the healing progress of the wound or have a therapeutic value and have sought to assess their efficacy and effectiveness in clinical trials. These claims should be clearly supported by the perspectives of those who actually use the devices. Compression therapy, which is regarded as an effective treatment for venous leg ulcers, is far from ideal owing to a number of limitations that it possesses, such as patient discomfort, difficulty experienced in applying correct compression on the limbs, choosing a correct dressing for the wound or finding differences between the performance of various devices. It is necessary to investigate the patient's views and perspectives while randomized controlled clinical trials are conducted. In this review the concept of quality of life (QoL) and the tools used to measure QoL and studies that were conducted with patients suffering from chronic venous leg ulcers and undergoing therapy are considered, along with contributory factors to the healing process. In addition, a questionnaire modified from the original format is recommended as the suitable tool for assessing the QoL of patients suffering from venous leg ulcers while participating in clinical trials.