Rodents of Senegal and their role as intermediate hosts of Hydatigera spp. (Cestoda: Taeniidae).

Hydatigera (Cestoda: Taeniidae) is a recently resurrected genus including species seldom investigated in sub-Saharan Africa. We surveyed wild small mammal populations in the areas of Richard Toll and Lake Guiers, Senegal, with the objective to evaluate their potential role as intermediate hosts of larval taeniid stages (i.e. metacestodes). Based on genetic sequences of a segment of the mitochondrial DNA gene cytochrome c oxidase subunit 1 (COI), we identified Hydatigera parva metacestodes in 19 out of 172 (11.0%) Hubert's multimammate mice (Mastomys huberti) and one out of six (16.7%) gerbils (Taterillus sp.) and Hydatigera taeniaeformis sensu stricto metacestodes in one out of 215 (0.5%) Nile rats (Arvicanthis niloticus). This study reports epidemiological and molecular information on H. parva and H. taeniaeformis in West African rodents, further supporting the phylogeographic hypothesis on the African origin of H. parva. Our findings may indicate significant trophic interactions contributing to the local transmission of Hydatigera spp. and other parasites with similar life-cycle mechanisms. We therefore propose that further field investigations of rodent population dynamics and rodent-borne infectious organisms are necessary to improve our understanding of host-parasite associations driving the transmission risks of rodent parasites in West Africa.

Cytochrome c oxidase dysfunction in sepsis.

Sepsis, the principal cause of death in critically ill patients, is associated with impaired oxygen extraction by tissues. One possible explanation is the development of mitochondrial dysfunction and ineffective oxygen utilization. This abnormality has been termed cytopathic hypoxia. This may be caused by an abnormality in the transport of electrons down the cytochrome chain on the mitochondrial inner membrane. In this article we review our studies on abnormalities in the function of complex IV (cytochrome oxidase), the final electron acceptor in this chain. In addition, we provide evidence that administration of cytochrome c may overcome these abnormalities and provide a novel therapeutic alternative.

Effect of leader peptides on the permeability of mitochondria.

Peptides with sequences based on the leader sequence of yeast cytochrome c oxidase subunit IV (pCOX IV-(1-25)) activate the electrophoretic uptake of K+ and other cations such as tetraethylammonium and lysine by rat liver mitochondria with EC50 = 11-15 microM. Uptake of these cations is dependent on respiration and is prevented by uncoupling agents, and the Vmax for K+ is 1.2-1.5 micromol/min/mg. Albeit more slowly, the non-electrolytes mannitol and sucrose are also transported by this pathway. Treatment of the peptides with proteinase K eliminates the stimulatory effect. Since the stimulated rate is not inhibited by ATP or by cyclosporin, we conclude that this pathway is not related to the mitochondrial KATP channel or the Ca2+-dependent permeability transition pore. Transport is stimulated by pCOX IV-(1-23), pCOX IV-(1-22), and pCOX IV-(1-12)Y, but not by a 13-amino acid peptide representing the nuclear location sequence of the SV40 large T antigen, which is responsible for directing that protein to the nucleus. Spermine, which has four positive charges, also has no stimulatory effect, and an amphiphilic 22-residue peptide derived from antithrombin III with seven net charges is only one-twentieth as effective as pCOX IV-(1-22). Thus, these data indicate that the sequence/structure is important for activation of transport. We also demonstrate that mitochondrial uncoupling, previously reported to be induced by these peptides, actually reflects coupled accumulation of salt. In view of our findings, it is also likely that the lytic effects attributed to these peptides are secondary to swelling and are not due to membrane damage per se. Finally, we show that, in non-ionic media, the peptide is an inhibitor of cytochrome c oxidase.

[Structural and functional characterization of cytochrome oxidase encapsulated in liposomes in sodium chloride solutions]. / Strukturno-funktsional'nye kharakteristiki tsitokhromoksidazy, vstroennoi v liposomy v rastvorakh khlorida natriia.

The effect of NaCl concentration (0-2 M) on the absorption spectrum and enzymic activity of cytochrome oxidase built in lecithin liposome has been studied at 24 and 8 degrees C. It is shown that at 0,8 M NaCl concentration a conformational transition occurs that leads to the enzyme inactivation. The relationship between protein conformation and liposome state has been established.