Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration. Involvement in response to hypoxia/reoxygenation

BACKGROUND: Nitric oxide (NO); superoxide anion (O2.d-); the reaction product of NO with O2.d-, peroxynitrite (ONOO-); and ischemia/reperfusion have all been reported to inhibit respiration in isolated mitochondria. However, the specific species involved in the inhibition of respiration in intact tissues are poorly understood. METHODS AND RESULTS: O2 consumption in isolated cardiac muscle from bovine calf hearts was quantified by use of a Clark-type electrode. Exogenous and endogenous sources of NO, from S-nitroso-N-acetylpenicillamine (SNAP) and bradykinin or carbachol, reversibly inhibited respiration, whereas the O2.- releasing agent, pyrogallol (PG), inhibited respiration in a manner that was only partially reversed when examined 15 minutes after the removal of PG. The generation of ONOO- with SNAP + PG caused a potentiation of the O2(-)-elicited inhibition of respiration when examined 15 minutes after the removal of the ONOO- generating system. Tiron (a scavenger of O2.-) did not alter the actions of SNAP, but it attenuated the direct inhibitory effects of PG +/- SNAP and essentially eliminated the suppression of respiration observed 15 minutes after removal of the O2.- or ONOO- generating system. Urate (a scavenger of ONOO-) antagonized only the actions of PG + SNAP. After exposure of muscle slices to a model of hypoxia (15 minutes) and reoxygenation (10 minutes), respiratory inhibition was observed. This reoxygenation-induced inhibition was potentiated by L-arginine, the substrate for NO biosynthesis, and was markedly blocked by nitro-L-arginine (an NO synthase inhibitor), Tiron, or urate. CONCLUSIONS: The potentially physiological reversible regulation of respiration in cardiac muscle by NO is converted to an effect that does not show rapid reversibility under conditions in which ONOO- forms, and this could contribute to cardiac dysfunction in situations such as hypoxia/reoxygenation.     

Molecular characterization of erythrocyte glucose-6-phosphate dehydrogenase deficiency in Al-Ain District, United Arab Emirates

Operational skills involved in controlling a motor vehicle were measured in two groups of very healthy elderly drivers and a young control group to test the hypothesis that there are age-related declines in operational performance that may influence driver safety. An actual behind-the-wheel, standardized road test was employed using a motor vehicle equipped with sensors to record speed, braking activity, and lane position, as well as direction and magnitude of front-wheel and eye-movement excursions. The data from these sensors were used as dependent measures of operational performance. Older drivers made fewer steering and eye-movement excursions and drifted across the center line more frequently than the young control group. Younger drivers drove significantly faster and executed more braking applications than did their older counterparts. The motor-vehicle operational performance of older healthy drivers was related to visual-spatial attentional declines and the useful field of vision associated with the normal aging process.     

Radiographic appearances of esophageal stents

Among patients with esophageal carcinoma and associated dysphagia, more than 60% have unresectable disease at presentation. In such cases, the goal of treatment is primarily palliation of the dysphagia; treatment options include surgery, radiation therapy, laser ablation, and placement of stents. Beginning with the first stent-made of boxwood and silver in 1885-evolution in design led to the creation of large-diameter, rigid plastic stents placed at laparotomy and eventually placed by means of endoscopy. However, complications such as perforation, hemorrhage, dislodgment, pressure necrosis, and occlusion were frequently encountered with these stents. The development of small-diameter, expandable metal stents eliminated some of these complications. Metal stents have greatly reduced procedure-related morbidity and mortality, but complications such as perforation, malposition, migration, tumor ingrowth and overgrowth, food obstruction, and tracheoesophageal fistula persist. An efficacious and increasingly used method of treating malignant dysphagia, esophageal stent placement must undergo further improvements to reduce the frequency of complications, particularly migration and tumor ingrowth.     

Assessment of the efficacy of a low temperature hydrogen peroxide gas plasma sterilization system

The STERRAD 100 sterilization system (Johnson & Johnson Medical Ltd) uses low temperature hydrogen peroxide gas plasma for sterilization of heat labile equipment. The efficacy of the machine was tested by contaminating a standard set of instruments with different organisms and using a filtration method to assess recovery of organisms from the wash fluids of instruments post-sterilization. Experiments were performed under clean (the organism only) and dirty (organism mixed with egg protein) conditions. A parallel study conducted using a 3M STERIVAC ethylene oxide sterilizer could not be completed owing to closure of the ethylene oxide plant. For sterilization of instruments with long and narrow lumens, hydrogen peroxide adaptors are necessary. The STERRAD 100 sterilizer can achieve effective sterilization of heat labile instruments with a reduction of 6 log10 cfu/mL of organisms tested. This method has the advantages over ethylene oxide sterilization of safety, ease of maintenance and no requirement for aeration time.     

Exceptionally high seizure threshold: ECT device limitations

Numerous studies have confirmed the distinct biological behavior of two subsets of prostate cancer diagnosed incidentally after either transurethral resection (TURP) or open prostatectomy for presumed benign prostatic hyperplasia (BPH). Focal, low-grade lesions are associated with a low risk for clinical progression and are designated as stage T1a or A1. These cases have traditionally been managed conservatively with close clinical observation. In contrast, multifocal, high-volume, or high-grade tumors are associated with a more aggressive clinical course and are designated as stage T1b or A2. Early definitive intervention is usually advocated for these latter patients. Therefore, accurate pathological assignment to either stage T1a or T1b is crucial for selection of appropriate management options. A variety of methods for staging patients with incidentally detected prostate cancer have been proposed, including detailed histological analysis, repeat TURP or transurethral biopsy, serial prostate-specific antigen (PSA) analysis, and imaging with either transrectal ultrasound (TRUS) or magnetic resonance (MRI) techniques. This article critically examines the clinical utility of these staging modalities for patients with incidentally detected prostate cancer.     

Comparison of voice analysis systems for perturbation measurement

Dysphonic voices are often analyzed using automated voice analysis software. However, the reliability of acoustic measures obtained from these programs remains unknown, particularly when they are applied to pathological voices. This study compared perturbation measures from CSpeech, Computerized Speech Laboratory, SoundScope, and a hand marking voice analysis system. Sustained vowels from 29 male and 21 female speakers with mild to severe dysphonia were digitized, and fundamental frequency (F0), jitter, shimmer, and harmonics- or signal-to-noise ratios were computed. Commercially available acoustical analysis programs agreed well, but not perfectly, in their measures of F0. Measures of perturbation in the various analysis packages use different algorithms, provide results in different units, and often yield values for voices that violate the assumption of quasi-periodicity. As a result, poor rank order correlations between programs using similar measures of perturbation were noted. Because measures of aperiodicity apparently cannot be reliably applied to voices that are even mildly aperiodic, we question their utility in quantifying vocal quality, especially in pathological voices.