Effect of hydrogen sulfide on glycolysis-based energy production in mouse erythrocytes.

Hydrogen sulfide (H2 S) is a gasotransmitter that regulates both physiological and pathophysiological processes in mammalian cells. Recent studies have demonstrated that H2 S promotes aerobic energy production in the mitochondria in response to hypoxia, but its effect on anaerobic energy production has yet to be established. Glycolysis is the anaerobic process by which ATP is produced through the metabolism of glucose. Mammalian red blood cells (RBCs) extrude mitochondria and nucleus during erythropoiesis. These cells would serve as a unique model to observe the effect of H2 S on glycolysis-mediated energy production. The purpose of this study was to determine the effect of H2 S on glycolysis-mediated energy production in mitochondria-free mouse RBCs. Western blot analysis showed that the only H2 S-generating enzyme expressed in mouse RBCs is 3-mercaptopyruvate sulfurtransferase (MST). Supplement of the substrate for MST stimulated, but the inhibition of the same suppressed, the endogenous production of H2 S. Both exogenously administered H2 S salt and MST-derived endogenous H2 S stimulated glycolysis-mediated ATP production. The effect of NaHS on ATP levels was not affected by oxygenation status. On the contrary, hypoxia increased intracellular H2 S levels and MST activity in mouse RBCs. The mitochondria-targeted H2 S donor, AP39, did not affect ATP levels of mouse RBCs. NaHS at low concentrations (3-100 µM) increased ATP levels and decreased cell viability after 3 days of incubation in vitro. Higher NaHS concentrations (300-1000 µM) lowered ATP levels, but prolonged cell viability. H2 S may offer a cytoprotective effect in mammalian RBCs to maintain oxygen-independent energy production.

Examining tensions in the past and present uses of concepts.

Examining tensions between the past and present uses of scientific concepts can help clarify their contributions as tools in experimental practices. This point can be illustrated by considering the concepts of mental imagery and hallucinations: despite debates over their respective referential reliabilities remaining unresolved within their interdependent histories, both are used as independently stable concepts in neuroimaging experiments. Building on an account of how these concepts function as tools structured for pursuit of diverging goals in experiments, this paper explores this tension by re-examining the continued reliance of each concept on inverse characterisations inherited from the nominally-discarded 'mediator-view' of sensory-like mental phenomena (SLMP). In doing so, I seek to demonstrate how examining unresolved tensions can help highlight that entrenched associations can remain both integral to, and obscured by, the uses of concepts as goal-directed tools within experimental practices.

[Non-conventional therapies in childhood cancer: guidelines for distinguishing non-harmful from harmful therapies: a report of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology]. / Unkonventionelle Therapien bei Krebserkrankungen im Kindesalter: Richtlinien zur Abgrenzung unbedenklicher von schädlichen Behandlungsmethoden: Ein Bericht der SIOP-Arbeitsgruppe für Psychosoziale Fragen in der Pädiatrischen Onkologie.

This is the 11th official document of the SIOP Working Committee on Psychosocial Issues in Pediatric Oncology, instituted in 1991. There is a tendency for some physicians to make blanket statements against the use of non-proven, nonconventional therapies, even when these therapies are not harmful. There is an equal and opposite tendency on the part of many parents to do all that they possibly can for their children, including using any non-conventional therapy they feel might do some good. The health care team must open a healthy dialogue with parents that will lead to a clear distinction between those complementary therapies that are harmful and those that are not, indeed, might even be helpful psychologically if not therapeutically.

High-dose tobramycin combined with clindamycin or lincomycin in the treatment of septic peritonitis and intraabdominal sepsis.

Tobramycin in combination with clindamycin or lincomycin were used as systemic antibiotics in the treatment of 20 consecutive patients with septic peritonitis or intraabdominal sepsis, 10 of which were in septic shock. Doses were: tobramycin 1.5 mg/kg body weight every 8 hours, with prolonged dosage interval in patients with reduced renal function, clindamycin 0.9 g every 8 hours and lincomycin 1.2 g every 8 hours. Therapy was monitored by means of tobramycin serum concentration determinations and renal function tests. Eventual cure of the infection was obtained in 19 patients. In 2 of these, the effects of the antibiotics were doubtful. Side effects were observed on 8 occasions: One patient had a slight and temporary subjective hearing loss, coinciding with raised trough levels of tobramycin. Diarrhoea occurred in 3 cases and skin reactions in 3 cases. Superinfection with Candida albicans fungemia occurred in one patient. From the overall results it is concluded that the antibiotic regimen is of value in serious life-threatening infections. Although the tobramycin dose was higher than customarily used in Scandinavia at the time, 0 hour and 1 hour serum concentrations remained stable during therapy in patients whose renal function was normal at onset of therapy. Serum creatinine (S-Cr) levels in these patients were also essentially unchanged. Temporary reductions in osmolality (Osm) ratio Osm-urine/Osm-serum occurred in 11 patients despite normal S-Cr, but it was hard to attribute these impairments of renal function to tobramycin specifically. It was also doubtful whether tobramycin further aggravated renal function in those patients where it was impaired at onset of therapy. Thus, no conclusive evidence of clinically important tobramycin-induced nephrotoxicity were found. We suggest that the dosage schedule of tobramycin used in this study is applied when treating serious intraabdominal infections.