Experimental verification of synchronization in pulse-coupled oscillators with a refractory period and frequency distribution.

We propose herein globally pulse-coupled electronic-circuit oscillators with a refractory period and frequency distribution. The synchronization of such oscillators, which was analyzed by Konishi and Kokame [Chaos 18, 033132 (2008)], is verified by circuit experiments. Furthermore, we investigate a cluster state in the oscillators and analytically derive a simple condition to estimate the maximum possible number of clusters, which is confirmed by the circuit experiments.

Multiple mechanisms underlying troglitazone-induced mitochondrial permeability transition.

Troglitazone, a thiazolidinedione class antidiabetic drug, was withdrawn from the market because of its severe idiosyncratic hepatotoxicity. It causes a mitochondrial permeability transition (MPT), which may in part contribute to its hepatotoxicity. In the present study, the mechanism of troglitazone mitochondrial toxicity was investigated in isolated rat liver mitochondria. Mitochondrial swelling induced by 10 µM troglitazone was attenuated by bromoenol lactone (BEL), an inhibitor of Ca²+-independent phospholipase A2 (iPLA2). In contrast, that induced by 50 µM troglitazone was exacerbated by BEL. This exacerbation was diminished by addition of 2mM glutathione, an antioxidant. Oxygen consumption by state 3 respiration in isolated mitochondria was also decreased by troglitazone, but it was not affected by BEL. Mitochondrial swelling induced by 10 µM troglitazone was completely attenuated in the absence of Ca²+ while that induced by 50 µM troglitazone was not affected. Addition of 1 µM cyclosporin A (CsA), an inhibitor of MPT pores, completely attenuated swelling induced by 10 µM troglitazone while it only partly diminished that induced by 50 µM troglitazone. Thus, the MPT induced by 10 and 50 µM troglitazone are regulated by different mechanism; the MPT induced by 10 µM troglitazone is regulated by the activation of iPLA2 and caused by the opening of CsA-regulating MPT pores followed by accumulation of Ca²+ in mitochondria, while that induced by 50 µM troglitazone is partly regulated by reactive oxygen species and mainly caused by the opening of CsA-insensitive MPT pores.

Differential effects of physical and psychological stressors on immune functions of rats.

To study the effects of different types or durations of stressors on immune functions, male Fischer rats were exposed to chronic physical (electric foot shock) or psychological (non-foot shock) stress induced in the communication box. Superoxide production by alveolar macrophages (AMs), mitogen-induced splenic lymphocyte proliferation, and splenic natural killer (NK) cell cytolysis were examined in vitro. Repeated exposure to physical stress suppressed superoxide production by AMs (-58%, p<0.05 for opsonized zymosan (OZ) and -51%, p<0.05 for phorbol 12-myristate 13-acetate (PMA)), although psychological stress suppressed superoxide production after 24 h of repeated exposures (-40%, p<0.05 for OZ and -47%, p<0.05 for PMA). Acute suppression of the blastic response of splenic lymphocytes was only found in the physical stress group (p<0.05), although the chronic effects were only found in the psychological stress group (p<0.05). NK cell activity was suppressed immediately after the acute physical stress (-30%, p<0.05), but no effects were found in the psychological stress group. These results underline the importance of distinguishing between physical versus psychological stressors when examining the effects of stress on immune functions.