Effects of perineural capsaicin treatment on cardiopulmonary reflexes elicited by laryngeal instillations of capsaicin and distilled water in sevoflurane-anesthetized dogs.

The aim of this study was to determine the effect of perineural capsaicin (CAPS) treatment on cardiopulmonary reflexes elicited by topical laryngeal instillation of CAPS and distilled water (DW) in sevoflurane-anesthetized dogs. Cardiopulmonary reflexes elicited by CAPS (10 microg/ml, 10 ml) were attenuated by perineural CAPS treatment to the superior laryngeal nerves (SLNs) (P<0.05), whereas those by DW (10 ml) remained unaffected (P>0.05). The reflex responses to DW that remained even after the perineural CAPS treatment were eliminated by laryngeal anesthesia with lidocaine. These results suggest that cardiopulmonary reflexes from the laryngeal mucosa elicited by CAPS instillation can be blocked by perineural CAPS treatment to the SLNs, which may result from inhibition of the laryngeal CAPS-sensitive C-fiber afferents.

Effects of perineural capsaicin treatment on compound action potentials of superior laryngeal nerve afferents in sevoflurane-anesthetized dogs.

Effects of perineural capsaicin (CAPS) treatment on compound action potentials of the superior laryngeal nerve (SLN) afferents were studied in 6 sevoflurane-anesthetized dogs. Perineural CAPS (100 microg/ml) to the bilateral SLNs reduced (P<0.01) the peak and integral amplitudes of the C-wave of the compound action potential. By contrast, the perineural CAPS had no effect on the A-wave component (P>0.05). Removal of the perineural CAPS recovered the C-wave to pretreatment level. The perineural CAPS treatment selectively blocks C-wave compound action potentials of the SLN afferents, providing a useful tool for studies of laryngeal C-fibers in respiratory physiology.

Differential signaling cascade of MAP kinase and S6 kinase depends on 3',5'-monophosphate concentration in schwann cells: correlation to cellular differentiation and proliferation.

Schwann cells produce myelin in the peripheral nervous system (PNS) and play an important role in the maintenance of the normal function of PNS. Our previous studies have shown that derivatives of adenosine 3',5'-monophosphate (cAMP) can regulate the cell-fate (i.e., proliferation and differentiation into cell surface galactocerebroside-positive cells) depending on its concentration in vitro. Higher concentration of cAMP can induce the expression of cell surface galactocerebroside, while proliferation can be induced by lower concentration of cAMP. However, the detailed molecular mechanism of how the same second messenger yields different phenotypes of Schwann cells depending on its concentration remains to be elucidated. Here we show that low concentration of 8-bromo cAMP, a cell-permeable derivative of cAMP, activates S6 kinase activity with a short-lived activation of mitogen-activated protein kinase (MAPK), whereas high dose of the reagent activates S6 kinase much less than that of low dose with a small and prolonged activation of MAPK in Schwann cells. These data clearly demonstrated that a rise in the intracellular cAMP uses the MAPK-S6 kinase pathway as an intracellular sinaling cascade and different magnitude and duration of the activation of this pathway might underlie the different cellular fate depending on the intensity of the stimulation.

Cytohistologic assessment of antitumor effects of intraperitoneal hyperthermic perfusion with mitomycin C for patients with gastric cancer with peritoneal metastasis.

For 15 patients with refractory gastric cancer and peritoneal metastasis, intraperitoneal hyperthermic perfusion (IPHP) using mitomycin C combined with extensive surgery was prescribed. The antitumor effects were assessed cytohistologically in pre-IPHP and post-IPHP specimens of the abdominal effusion and peritoneal tissue. Gastric cancer cells in the abdominal effusion and/or lavage vanished from post-IPHP peritoneal exudate obtained from the pouch of Douglas. Peritoneal tissues from nine patients were harvested just after the IPHP treatment. All the nuclei of cancer cells were pyknotic in three of nine patients, and two of these three patients are alive with no local recurrence; one patient died of hepatic metastasis. In the remaining six patients, four with preoperative ascitic effusion and positive post-IPHP histologic findings died of peritoneal, intraabdominal, and pericardial metastases. The other two had some residual microscopic foci in the subperitoneal deep layer; one patient died of pleural recurrence, and the other is alive with no evidence of recurrence 42 months after the IPHP. Among the other six patients, whose post-IPHP peritoneal tissues were not available because of disappearance of disseminating foci as a result of the IPHP, two are living with no recurrence and, of the remaining four patients, three died of hepatic and intraabdominal metastases and the other one died of other causes. The histologic findings are suggestive of the following: (1) uniform heat and drug distribution in the abdominal cavity with IPHP treatment, except for an area adjacent to the inflow point of the perfusate; and (2) limited penetration of heat and drug through the subperitoneal layer. Thus, IPHP treatment results in complete destruction of cancer cells in the abdominal effusion and on and just beneath the peritoneum.