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.     

Cell signaling by the type IV pili of pathogenic Neisseria

Neisseria gonorrhoeae and Neisseria meningitidis are Gram-negative bacterial pathogens that infect human mucosal epithelia. Type IV pilus-mediated adherence of these bacteria is a crucial early event for establishment of infection. In this work, we show that the type IV pili transduce a signal into the eucaryotic host cell. Purified adherent pili, but not pili from a low binding mutant, trigger an increase in the cytosolic free calcium ([Ca2+]i) in target epithelial cells, a signal known to control many cellular responses. The [Ca2+]i increase was blocked by antibodies against CD46, a putative pilus receptor, suggesting a role for this protein in signal transduction. Pilus-mediated attachment was inhibited by depletion of host cell intracellular Ca2+ stores but not by removal of extracellular Ca2+. Further, kinase inhibition studies showed that pilus-mediated adherence is dependent on casein kinase II. In summary, these data reveal a novel function of the type IV pili, namely induction of signal transduction pathways in host cells.     

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.