Cochlear blood flow (CoBF) and cerebral blood flow (CBF) were measured using laser Doppler flowmetry and the microsphere method during CO2 and O2 gas mixture inhalation in rabbits. Both methods revealed that CBF was increased by CO2 inhalation. CoBF measured by laser Doppler measurement decreased during CO2 inhalation while that measured by the microsphere method showed a slight increase, but lateral wall blood flow in the cochlea measured by the microsphere method showed no significant change. Our results obtained with laser Doppler flowmetry were not inconsistent with those reported in humans. It is considered that the rabbit, in which thick bone surrounds the cochlea, is a good model for the experimental evaluation of the laser Doppler technique used in the clinical measurement of CoBF.

Administration, Inhalation↗

PubMedDate not supplied

Nodular glomerulosclerosis (Kimmelstiel-Wilson) after total pancreatectomy.

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Diabetic Nephropathies↗

PubMedDate not supplied

Cycloprodigiosin hydrochloride, a H+/Cl- symporter, induces apoptosis in human colon cancer cell lines in vitro.

Recently, we reported that cycloprodigiosin hydrochloride (cPrG.HCl), a novel H+/Cl- symporter, induces acidification of the cytosol and leads to apoptosis on rat and human liver cancer cells. In the present study, the effects of cPrG.HCl, a H+/Cl- symporter, were examined in colon cancer cell lines in vitro. In the MTT assay, cPrG.HCl inhibited the growth of two colon cancer cell lines (WiDr and SW480) in a dose- and time-dependent manner. The cPrG.HCl treatment of both types of cells induced apoptosis as confirmed by the appearance of a sub-G1 population and intranucleosomal DNA fragmentation. In addition, cPrG.HCl lowered pHi (below pH 6.8) respectively. Therefore, these results suggest that cPrG.HCl may be useful for the treatment of colon cancer cells.

Antiporters↗

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A phase II multi-institutional study of estra-1,3,5(10)-triene-3,17 beta-diol, 3-benzoate, 17[[4-[4-[bis(2-chloroethyl)amino]phenyl]-1- oxobutoxy]acetate] (KM2210), a novel antitumor agent, for advanced and recurrent breast carcinoma.

In order to evaluate the efficacy of Estra-1,3,5(10)-Triene-3,17 beta-Diol, 3-Benzoate, 17[[4-[4-[Bis(2-Chloroethyl) Amino]Phenyl]-1-Oxobutoxy] Acetate] (KM2210), a multi-institutional cooperative Phase II study was performed in patients with measurable advanced and recurrent breast cancer. Two hundred miligrams of KM2210, a conjugate of chlorambucil and 17 beta-estradiol, were administered orally daily for more than 4 weeks to each patient. According to the WHO criteria of response, 103 evaluable cases were assessed. Complete response was obtained in 9 cases, partial response in 19, no change in 39 and progressive disease was observed in 36. The overall response rate was 27.2% (28/103). The response rate was higher in patients without prior treatment than in those with prior treatment. However, KM2210 was also effective against breast cancers treated previously with tamoxifen, anthracyclines and their combinations, showing response rates of 25.5%, 22.0% and 29.6% respectively, suggesting that this agent is also effective on breast carcinomas which were insensitive to tamoxifen and anthracyclines. For efficacy classified in terms of metastatic lesions, the response rate was significantly higher in soft tissues than in other involved organs, and the response rate of bone metastasis was limited. Bone marrow suppression, including leukopenia and thrombocytopenia, was thought to be the dose-limiting toxicity of KM2210. Genital bleeding due to the released estrogen was observed as a characteristic side effect. KM2210 is considered to be useful for the treatment of advanced and recurrent breast cancer when administered at a dose level of 200 mg per day for more than 4 weeks.

Adult↗