Various gastric irritants induce cell death of gastric mucosal cells, resulting in gastric ulcers in vivo. We recently reproduced gastric irritant-induced cell death in vitro, using primary cultures of guinea pig gastric mucosal cells. We found that the short-term treatment of cells with relatively high concentrations of irritants or the long-term treatment of cells with relatively low concentrations of irritants induce necrosis or apoptosis, respectively. We also reproduced the spontaneous apoptosis of matured gastric mucosal cells at gastric surface and found that the apoptosis-inducing pathway of this spontaneous apoptosis is different from that of the irritant-induced apoptosis. Heat shock proteins (HSPs) are known to make cells non-specifically resistant to various irritants. We found that preinduction of HSPs by geranylgeranylacetone or a low concentration of ethanol protects gastric mucosal cells from both apoptosis and necrosis induced by various gastric irritants. Therefore, non-toxic HSP-inducers, such as geranylgeranylacetone, seem to be clinically beneficial for gastric irritant-induced gastric ulcers.

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Dextran magnetite complex (DM) is a colloidal suspension of subdomain particles which efficiently generate heat under an alternating current (AC) magnetic field. Inductive heating using DM has attracted attention as a new method to overcome various problems in existing local hyperthermia. To make the system more convenient for clinical application, we developed a new portable device.
The device can use an alternating current (AC) of 200V (maximum output 3kW), and it is extremely small, about 0.4×0.4×0.4 meters long. The frequency can be adjusted continuously within the range of 100-500kHz. DM suspension containing 14mg Fe/ml (0.25M), 28mg Fe/ml (0.5M) or 56mg Fe/ml (1.0M) was used in an in vitro study, referring to our previous studies. The results obtained were as follows. 1) The temperature of DM rose in proportion to the iron concentration of DM. 2) The temperature of DM rose in proportion to the square of the magnetic field intensity. The temperature elevations were about 8°C/min and 14°C/min at frequencies of 299kHz and 418kHz, respectively, using a DM of 28mg Fe/ml and a magnetic flux density of 5.2mT. These results were identical to the results of the heating characteristics in the previous device. Moreover, this device was evaluated for its anti-tumor effect in VX-2 tumor-bearing rabbits. By using hyperthermia treatment with this device, the inhibition of the tumor growth in the treated group (n=8) was significantly greater than in the control group (n=3), and the frequency of lung metastasis was decreased, too. Thus, this study confirmed the usefulness of this portable hyperthermic device for local cancer therapy.

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How heat shock protein (HSP) mitigate liver damage after extensive hepatectomy after ischemic preconditioning or administration of HSP inducer, geranylgeranylacetone (GGA) may be of clinical significance. The purpose of the present study was to evaluate the cytoprotective effect of preconditioning and administration of GGA, and to elucidate the cytoprotective mechanism of HSP70 from the standpoint of the activation of transcription factor NF-_kB. Materials and methods. Male Wistar rats were subjected to 90% extensive hepatectomy. The animals were divided into 3 groups. Group N were subjected to 90% hepatectomy. Group P were subjected to 30-minute liver ischemia as preconditioning 48 hours prior to 90% hepatectomy. Group G were given oral GGA in a dose of 200mg/ kg body weight for 7 days prior to 90% hepatectomy. Examined were survival rate, expression of HSP70 and NF-_kB (Western blot analysis), and apoptosis of remnant liver cells (DNA fragmentation assay). Results. The 7-day survival rate in group N, group P, and group G was 0%, 40%, and 62.5%, respectively. HSP70 expression in group P and group G was increased 5 fold and 7 fold, respectively, after 90% hepatectomy. Expression of NF-_kB p65 was significantly lower in groups P and G than in group N. The percentage DNA fragmentation was significantly higher in group N than in groups P and G. In conclusion, ischemic preconditioning and administration of GGA prior to extensive hepatectomy may alleviate liver cell damage by maintaining cell viability and regulation of apoptosis. The HSP70 may inhibit the expression of NF-_kB at the transcriptional level and overexpression of the inflammatory response.

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