Clinical pharmacokinetics of carboplatin and MCNU in malignant brain tumor and normal brain tissues

We measured the concentrations of MCNU and CBDCA in the serum, brain tumor and normal brain tissue. Six patients with malignant glioma were treated with intravenous chemotherapy using 80mg/m2 MCNU and 300mg/m2 CBDCA during surgery. After drug administration, specimens of serum, tumor and normal brain tissue were collected every 30 min and then the drug concentration in each sample was measured. The highest MCNU levels in all samples were obtained immediately after administration which followed by gradual decrease. On the contrary, the mean CBDCA levels in the tumor and normal tissue remained almost at a constant level, although serum CBDCA level declined rapidly as MCNU. As expected, MCNU seemed to have advantages in the treatment of brain tumors as it distributed with higher concentration in the tumor tissue than in the serum and normal brain tissue. On the contrary, CBDCA in the tumor tissue did not exceed the concentration in the serum. Nevertheless, it remained longer in the tumor tissue with a constant level, suggesting that CBDCA can achieve an effective area under the concentration versus time curve (AUC) in the brain tumor tissue to kill tumor cells.     

The effect of 4,4'-diisothiocyanato-stilbene-2,2'-disulfonate on CO2 permeability of the red blood cell membrane

It has long been assumed that the red cell membrane is highly permeable to gases because the molecules of gases are small, uncharged, and soluble in lipids, such as those of a bilayer. The disappearance of 12C18O16O from a red cell suspension as the 18O exchanges between labeled CO2 + HCO3- and unlabeled HOH provides a measure of the carbonic anhydrase (CA) activity (acceleration, or A) inside the cell and of the membrane self-exchange permeability to HCO3- (Pm,HCO-3). To test this technique, we added sufficient 4, 4'-diisothiocyanato-stilbene-2,2'-disulfonate (DIDS) to inhibit all the HCO3-/Cl- transport protein (Band III or capnophorin) in a red cell suspension. We found that DIDS reduced Pm,HCO-3 as expected, but also appeared to reduce intracellular A, although separate experiments showed it has no effect on CA activity in homogenous solution. A decrease in Pm,CO2 would explain this finding. With a more advanced computational model, which solves for CA activity and membrane permeabilities to both CO2 and HCO3-, we found that DIDS inhibited both Pm,HCO-3 and Pm,CO2, whereas intracellular CA activity remained unchanged. The mechanism by which DIDS reduces CO2 permeability may not be through an action on the lipid bilayer itself, but rather on a membrane transport protein, implying that this is a normal route for at least part of red cell CO2 exchange.     

A high fill factor and progressive scan PtSi Schottky-barrier IR-CCD image sensor using new wiring technology

A back surface illuminated 130/spl times/130 pixel PtSi Schottky-barrier (SB) IR-CCD image sensor has been developed by using new wiring technology, referred to as CLOSE Wiring, CLOSE Wiring, designed to effectively utilize the space over the SB photodiodes, brings about flexibility in clock line designing, high fill factor, and large charge handling capability in a vertical CCD (VCCD). This image sensor uses a progressive scanned interline-scheme, and has a 64.4% fill factor in a 30 /spl mu/m/spl times/30 /spl mu/m pixel, a 3.9 mm/spl times/3.9 mm image area, and a 5.5 mm/spl times/5.5 mm chip size. The charge handling capability for the 3.3 /spl mu/m wide VCCD achieves 9.8/spl times/10/sup 5/ electrons, The noise equivalent temperature difference obtained was 0.099 K for operation at 120 frames/sec with a 50 mm f/1.3 lens.<>     

High-performance liquid chromatographic method for the determination of fenofibric acid and reduced fenofibric acid in human blood, plasma and urine

In this study, a very reliable HPLC method was developed for the determination of fenofibric acid and reduced fenofibric acid in the biological samples described as follows. After addition of the internal standard solution and 0.5 M HCl to the biological sample, fenofibric acid, reduced fenofibric acid and the internal standard were extracted with a mixed solvent of n-hexane and ethyl acetate (90:10) from the mixture. The acids were back-extracted from the organic phase with 0.1 M Na2HPO4 and then re-extracted from the aqueous phase with a mixed solution of n-hexane and ethyl acetate (95:5) after addition of 0.5 M HCl. The organic phase was evaporated to dryness under the vacuum. The residue was dissolved in MeOH and diluted with distilled water. An aliquot of the resulting solution was injected on the HPLC. High reproducibility was observed in this HPLC method (C.V.% less than 4%). Moreover it was confirmed that the conjugates in the urine could be hydrolyzed by incubation at 37 degrees C for 18 h after addition of 400 IU of beta-glucuronidase.     

Partial median sternotomy for pediatric cardiac surgery

There have been few reports on lymph node swelling in human parvovirus (HPV) B19 infection. A report of a 42-year-old female, who developed HPV B19-associated transient red cell aplasia with lymphadenopathy, is presented. The lymph node swelling began with the appearance of atypical lymphocytes in the peripheral blood and it disappeared as the patient recovered from the aplasia. Microscopically, the patient's bone marrow showed characteristic giant proerythroblasts with no maturation of the erythroid series. An excised inguinal lymph node showed florid, reactive follicular hyperplasia with paracortex expansion, and neutrophil infiltration and hemophagocytosis in the medullary sinus. These findings were compatible with the histology of a viral infection. A polymerase chain reaction study revealed HPV B19 in her serum and lymph node, but an immunohistochemical study failed to demonstrate HPV B19 capsid antigen in the lymph node or bone marrow. Although the present case suggests that reactive lymphadenopathy is associated with HPV B19 infection, the mechanism of the lymph node swelling still remains to be elucidated.     

Vascularized fibular graft for reconstruction of the wrist after excision of giant cell tumor

Seven patients with a giant-cell tumor involving the distal end of the radius were treated with en bloc resection and reconstruction with a free vascularized fibular graft. Two patients with stage 2 disease of Enneking's surgical staging and grade 2 of Campanacci's radiographic grading system were reconstructed with an articular fibular head graft. Five patients with stage 3 and grade 3 disease underwent wrist arthrodesis using fibular shaft transfer. There was radiographic evidence of bone union at the host-graft junctions in all cases. No local recurrence was seen in any of the patients at the most recent follow-up examinations. There were six good and one excellent functional results. Wrist arthroplasty using a vascularized fibula head graft is the best procedure for a stage 2 or grade 2 giant-cell tumor of the distal end of the radius. In cases of stage 3 or grade 3 disease, wrist arthrodesis using a vascularized fibular shaft graft is indicated.     

Use of Ozone to Prepare Silver Oxides

The possible use of ozone to produce higher oxides was analyzed thermodynamically. Because the activity of oxygen in ozone is ∼10¹⁸ at room temperature and ∼10⁸ at 773 K, ozone may react with metals to yield higher-oxidation-state products than does an ambient pressure of pure oxygen. In agreement with this thermodynamic prediction, silver oxides (AgO and Ag₂O) were synthesized experimentally by blowing a gas mixture of 6 vol% ozone and oxygen through a water-cooled lance. Neither Ag₃O₄ nor Ag₂O₃ was detected. Slow oxygen diffusion into a metal and/or reaction products and decomposition of unstable oxides that are formed successively are obstacles to practical applications of syntheses via ozone oxidation.     

DEVELOPMENT OF PLASMA SPRAYED LUBRICANT FREE SLIDE PLATES WITH CERAMIC COAT FOR RAILWAY USE

Ceramic coated slide plates were developed in order to ensure smooth sliding of the tongue rail and tight contact with stock rail. The 0·5 mm thickness thin metallic bonded layer was synthesized by spraying ceramic powders using conventional plasma spraying technique. Coated materials were mostly Al₂O₃ ceramic including metallic materials. It is concluded field tests that coated plates satisfied endurance specifications, corrosion, wear and load specifications without any maintenance of ceramic coated plates. Since field tests have been successfully performed, more than 10,000 slide plates are being used in Japan by Shin-kansen Rail Way and private railway companies.     

Brefeldin A protects ricin-induced cytotoxicity in human cancer KB cell line, but not in its resistant counterpart with altered Golgi structures

Brefeldin A (BFA), an isoprenoid fungal metabolite, dramatically disrupts intracellular protein transport and protein secretion. BFA protects cells from the cytotoxicity of a plant toxin, ricin or pseudomonas toxin, but not that of diphtheria toxin (Yoshida et al., 1991. Expt. Cell Res., 192: 389-395.). In this study, we examined whether BFA could differentially change the cytotoxicity of ricin between BFA-sensitive cells and BFA-resistant cells. As a BFA-resistant cell line, we used a resistant cell line, KB/BF2-2, derived from BFA-sensitive human cancer KB cells. BFA treatment caused the disappearance of typical Golgi cisternae and the concomitant appearance of dilated vesicles in the cytoplasm in KB cells. By contrast, KB/BF2-2 cells had already altered Golgi structures with poor development of cisternae and also many vesicles in the absence of BFA, and BFA treatment did not further induce the morphological changes. Although a plasma membrane-specific marker protein, alpha-adaptin, was localized similarly in KB/BF2-2 as KB, Golgi specific markers such as beta-cop and gamma-adaptin were distributed in the cytoplasmic small vesicles as well as Golgi compartments in KB/BF2-2 cells in the absence of BFA, and the mutant cells showed no apparent changes in the distribution even when exposed to BFA. Ricin inhibited protein synthesis in KB and KB/BF2-2 to similar levels while pretreatment of KB cells with BFA at 0.1 microgram/ml almost completely reversed the inhibitory effect of ricin. By contrast, the pre-exposure of KB/BF2-2 cells to 1.0 microgram/ml BFA only partially rescued the ricin-induced inhibition of protein synthesis. Exposure to BFA at 30 min before ricin addition or at 0 min with ricin rescued the protein synthesis inhibition, but no rescue occurred when BFA was added 30 min after ricin addition. BFA could not rescue the protein synthesis inhibition by another toxin, diphtheria toxin. Our results suggest that BFA-resistant mutation causes a specific change in the endocytic membrane traffic of ricin in human cells, and also that cytotoxicity of diphtheria toxin does not share a common pathway of the intracellular transport with that of ricin.