S-nitrosothiols signal the ventilatory response to hypoxia

Increased ventilation in response to hypoxia has been appreciated for over a century, but the biochemistry underlying this response remains poorly understood. Here we define a pathway in which increased minute ventilation (&Vdot;E ) is signalled by deoxyhaemoglobin-derived S-nitrosothiols (SNOs). Specifically, we demonstrate that S-nitrosocysteinyl glycine (CGSNO) and S-nitroso-l-cysteine (l-CSNO)-but not S-nitroso-d-cysteine (d-CSNO)-reproduce the ventilatory effects of hypoxia at the level of the nucleus tractus solitarius (NTS). We show that plasma from deoxygenated, but not from oxygenated, blood produces the ventilatory effect of both SNOs and hypoxia. Further, this activity is mediated by S-nitrosoglutathione (GSNO), and GSNO activation by gamma-glutamyl transpeptidase (gamma-GT) is required. The normal response to hypoxia is impaired in a knockout mouse lacking gamma-GT. These observations suggest that S-nitrosothiol biochemistry is of central importance to the regulation of breathing.     

Model systems demonstrating the volatile mutagenicity and carcinogenicity of sodium nitrite in rats

Summary Volatile mutagens derived from sodium nitrite buffered at various pH values or in the presence of human feces were detected using AmesSalmonella tester strain TA 1535 on petrie plates inverted over samples. Volatile mutagenicity increased as the pH decreased and was primarily a function of the nitrous acid produced from sodium nitrite and hydrogen ions. Sodium nitrite administered intracecally to 3 Wistar rats through surgically implanted cannula caused tumors (fibrosarcoma: 1/3 and squamous cell, 2/3). The possible role of nitrite-derived mutagens in GI cancer is discussed.The authors are grateful to Dr A. Carl MacDonald of the Dept. of Surgery, Dalhousie University for his advice and encouragement in this project.This work was supported by the National Cancer Institute of Canada.     

Exchange of tritium from randomly tritiated taurocholate by microbial bile salt oxidoreductases

Summary Tritium distribution on randomly labelled taurocholate (TC) was estimated at 28%, 4%, 1% and <0.5% on the hydrogens opposite the 3-, 7- and 12-OH groups and taurine moiety respectively. Anomalously,C. perfringens 3-hydroxysteroid dehydrogenase (3-HSDH) catalyzed tritium loss of 36% on formation of 7-, 12-dihydroxy-3-keto-5-cholanoate, implying additional losses of tritium at other sites by this enzyme.This work is supported by the National Cancer Institute.     

Book Reviews

Systemic Practice and Action Research -     

Low-coverage vaccination strategies for the conservation of endangered species

The conventional objective of vaccination programmes is to eliminate infection by reducing the reproduction number of an infectious agent to less than one, which generally requires vaccination of the majority of individuals. In populations of endangered wildlife, the intervention required to deliver such coverage can be undesirable and impractical; however, endangered populations are increasingly threatened by outbreaks of infectious disease for which effective vaccines exist. As an alternative, wildlife epidemiologists could adopt a vaccination strategy that protects a population from the consequences of only the largest outbreaks of disease. Here we provide a successful example of this strategy in the Ethiopian wolf, the world's rarest canid, which persists in small subpopulations threatened by repeated outbreaks of rabies introduced by domestic dogs. On the basis of data from past outbreaks, we propose an approach that controls the spread of disease through habitat corridors between subpopulations and that requires only low vaccination coverage. This approach reduces the extent of rabies outbreaks and should significantly enhance the long-term persistence of the population. Our study shows that vaccination used to enhance metapopulation persistence through elimination of the largest outbreaks of disease requires lower coverage than the conventional objective of reducing the reproduction number of an infectious agent to less than one.     

Simultaneous monitoring by optical techniques of respiratory chain and intracellular pH in toad ventricle strip.

Intracellular pH and oxidative metabolism can be measured in toad ventricle strips simultaneously by the use of the pH indicator dye, neutral red, and a rapid scanning spectrophotometer. The effects of hypoxia and acidification on mechanical function are approximately additive. The decrease in tension due to slight acidification is probably through an effect on the portion of the twitch tension supported by anaerobic metabolism.