Background/Aim: Sonodynamic cancer therapy is based on the preferential uptake and/or retention of a sonosensitizing drug (sonosensitizer) in tumor tissues and the subsequent activation of the drug by ultrasound irradiation. In the present study, we investigated the sonodynamically-induced antitumoral effect with functionalized carbon nanotubes, such as poly-ethylene glycol-modified carbon nanotubes (PEGmodified CNTs). Materials and Methods: Antitumor effects were evaluated using histological observation and assessing tumor growth following sonodynamic exposure to PEGmodified CNTs. Results: The combined treatment of 100 μM PEG-modified CNT and ultrasound induced a 2-fold cytotoxicity. Sodium azide, which quenches singlet oxygen, significantly inhibited ultrasonication induced cell damage in the presence of PEG-modified CNTs. This suggests that singlet oxygen produced by the combined use of PEG-modified CNTs and ultrasound is involved in the induction of antitumoral effects. The destruction of tumor tissue was observed with the ultrasonic treatment in combination with PEG-modified CNTs, while neither the treatment with PEG-modified CNTs alone nor ultrasound alone caused any necrosis. Conclusion: These results indicate that PEG-modified CNT functions as a sonosensitizer and is effective for sonochemical treatment of solid tumors.There is a new promising strategy for cancer treatment using the synergistic effect of ultrasound and chemicals, which can efficiently cause crushing (cavitation), as a result of repeated expansion and contraction of microbubbles by ultrasound irradiation. In this way the biological effects of some chemicals can be enhanced. Substances activated via this non-thermal action are called ultrasound sensitizers (1-5). However, compared to the thermal effects of an ultrasoundabsorbing tumor treatment, there are only few research reports on non-thermal effects, such as sonochemical effects based on cavitation (2, 6-7).We have previously reported that photochemically active compounds, such as hematoporpyrin, ATX-70, pheophorbide A, rose bengal, adriamycin FAD104, THP-adriamycin, ATX-S10, and porfimer sodium, may be sonosensitizers that can be activated by ultrasound irradiation (2-4, 6, 8-16). Porphyrins have been observed to accumulate in tumor tissues following intravenous administration (5,7,(17)(18). The administration of such compounds followed by ultrasound to treat implanted murine tumors has been shown to significantly suppress tumor growth, whereas the application of ultrasound alone only slightly inhibits growth (5,7,(19)(20)(21)(22)(23)(24)(25)(26). This suggests that combinational use of sonodynamically active porphyrins and ultrasound may have antitumoral effects. We have proposed that this potential modality be called sonodynamic therapy (2,26).Nanomedicine is a medical application of nanotechnology for the diagnosis and treatment of human illnesses, using precisely designed materials (nanoparticles) with a diameter of typically 1-100 nm (27). Nanomaterials, such as functionalized car...

The present study aims to investigate sonodynamically-induced apoptosis using the phthalocyanine, chloroaluminum phthalocyanine tetrasulfonate (AlPcTS). HL-60 cells were exposed to ultrasound for up to 3 min in the absence and presence of AlPcTS. Apoptosis was analyzed by cell morphology, DNA fragmentation, and caspase-3 activity. Electron spin resonance was used to measure reactive oxygen species. The number of apoptotic cells showing membrane blebbing and cell shrinkage after combined treatment (ultrasound and AlPcTS) was significantly higher than following other treatments, including ultrasound alone and AlPcTS alone. Furthermore, DNA ladder formation, caspase-3 activation and enhanced nitroxide generation were observed in cells treated with ultrasound and AlPcTS. Sonodynamically induced apoptosis, caspase-3 activation, and nitroxide generation were significantly suppressed by histidine. The significant reduction by histidine indicated that ultrasonically generated reactive oxygen species, such as singlet oxygen, is an important mediator of sonodynamically-induced apoptosis.

Effects of propofol on contractile response, action potential, resting membrane potential and L-type voltagedependent calcium channel current were examined in guinea-pig single cardiac myocyte. Propofol ( M) inhibited contractile response induced by electrical stimulation (83.6% of control, n=5), but did not change the resting membrane potential. On the other hand, propofol reduced the overshoot of action potential M), and shortened the duration of action potential M). Whole-cell voltage clamp experiment showed inhibition of L-type calcium channel current (Ica, M: 83.4+-1.53%~ of control, n=5). In addition, propofol showed use-dependent block of Ica. It is concluded that negative inotropic effect of propofol is caused by suppression of action potential, and that inhibition of Ic, plays a role in shortening of the duration of action potential. and M: 90321.39, Propofol is a clinically available general anaesthetic, which has been used in surgical operations in recent years. The clinical use of propofol is associated in some reports with adverse cardiovascular effects, including decreases in cardiac output, heart rates, and arterial blood pressure Monk et al. 1987; Mozrzymas et al. 1996). This depression in the cardiovascular system seems to result in part from a decrease in sympathetic nerve activity and reduction in baroreceptor control (Sellgren et al. 1994). However, a recent paper shows that propofol inhibits L-type calcium channels directly (Zhou et al. 1997). Because L-type calcium channel plays a critical role in excitation-contraction coupling in cardiac muscles, it is reasonable to assume that L-type calcium channels play an important role for the depression in the cardiovascular system on the point that propofol increased the apparent dissociation constant for [3H] nitrendipine binding (Zhou et al. 1997). The present study was designed to examine the effects of propofol on the contraction in guinea-pig single myocyte. Furthermore, action potential, resting membrane potential and L-type calcium channel current (Ica) were examined to clarify the mechanisms of negative inotropic effect induced by propofol. Materials and MethodsPrepurrrrion q/ cardiac myocytes. After approval was obtained from the local animal committee, the hearts were excised from guineaAuthor for correspondence: Noboru Hatakeyama, Department of Anesthesiology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama-shi, Toyama 930-0194, Japan (fax +81 76 434 5040, e-mail nobo@ms.toyama-mpu.ac.jp).pigs antesthetized with sodium pentobarbital. The aortae of isolated hearts were cannulated and perfused with minimum essential medium (S-MEM, Joklik-modified, Life Technologies, U.S.A.) including 1 mM CaCI2, 20 mM Taurine, 0.6 mM MgS04, and 24 mM NaHC03. S-MEM solution was saturated with 95% O2 and 5% C02, warmed to 37". After the blood was washed out, S-MEM including 10 pM CaClz with 0.2 mg/ml collagenase (Type 11, Sigma, U.S.A.) and 0.03 mg/pl trypsine (Sigma, U.S.A.) was perfused for 10 min. Then the enzymes were washed...

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Hyperactivation of glutamatergic N-methyl-D-aspartate (NMDA) receptors has been implicated in the excitotoxicity and pathophysiology of Parkinson's disease (PD). NMDA receptor blockers have been used clinically to treat dementia, but their efficacy is controversial. Modulation of NMDA receptors might improve neuroinflammation and cognitive deficits in PD. D-cycloserine (DCS), a partial agonist binding to the glycine binding site of NMDA receptors, has been demonstrated to improve cognitive function in primates and rodents. Our previous study showed that DCS can reduce motor, emotional, and cognitive dysfunctions, as well as neuroinflammation and neurodegeneration in a PD animal model and may therefore have potential for the treatment of neuroinflammation and cognitive dysfunction in patients with PD. In addition, increased expression of cyclooxygenase type-2 (COX-2) has been observed in dopaminergic neurons and activated microglia in the brain of both PD patients and PD animal models. COX-2 inhibitors can suppress activation of microglia and protect dopaminergic neurons from degeneration. Thus, a combination of DCS and COX-2 inhibitors might prove useful in suppressing neuroinflammation and cognitive deficits in PD.