Cytotoxic effects of topotecan combined with various anticancer agents in human cancer cell lines

BACKGROUND: Topotecan (TPT) is a topoisomerase I poison that exhibits antineoplastic activity. Analysis of the cytotoxic effects of combinations of TPT and other anticancer agents has been limited. PURPOSE: We assessed the cytotoxic effects produced by combinations of TPT and other antineoplastic agents in experiments involving multiple human cancer cell lines of diverse histologic origins. METHODS: The cytotoxic effects of various antimetabolites (fluorouracil, methotrexate, or cytarabine), antimicrotubule agents (vincristine or paclitaxel [Taxol]), DNA alkylating agents (melphalan, bis[chloroethyl]nitrosourea [BCNU], or 4-hydroperoxycyclophosphamide [4HC]), and a DNA-platinating agent (cisplatin), alone and in combination with TPT, were measured in clonogenic (i.e., colony-forming) assays. HCT8 ileocecal adenocarcinoma, A549 non-small-cell lung carcinoma, NCI-H82ras(H) lung cancer, T98G glioblastoma, and MCF-7 breast cancer cell lines were used in these assays. The data were analyzed by the median effect method, primarily under the assumption that drug mechanisms of action were mutually nonexclusive (i.e., completely independent of one another). For each level of cytotoxicity (ranging from 5% to 95%), a drug combination index (CI) was calculated. A CI less than 1 indicated synergy (i.e., the effect of the combination was greater than that expected from the additive effects of the component agents), a CI equal to 1 indicated additivity, and a CI greater than 1 indicated antagonism (the effect of the combination was less than that expected from the additive effects of the component agents). RESULTS: When the mechanisms of drug action were assumed to be mutually nonexclusive, virtually all CIs for combinations of TPT and either antimetabolites or antimicrotubule agents revealed cytotoxic effects that were less than additive. The CIs calculated at low-to-intermediate levels of cytotoxicity for combinations of TPT and the DNA alkylating agents melphalan, BCNU, and 4HC also showed drug effects that were less than additive; in most cases, however, nearly additive or even synergistic effects were observed with these same drug combinations at high levels of cytotoxicity (i.e., at > or = 90% inhibition of colony formation). Results obtained with combinations of TPT and cisplatin varied according to the cell line examined. With A549 cells, less than additive effects were seen at low-to-intermediate levels of cytotoxicity, and more than additive effects were seen at high levels of cytotoxicity. With NCI-H82ras(H) cells, synergy was observed over most of the cytotoxicity range. CONCLUSIONS AND IMPLICATIONS: TPT cytotoxicity appears to be enhanced more by combination with certain DNA-damaging agents than by combination with antimetabolites or antimicrotubule agents. Interactions between TPT and other drugs can vary depending on the cell type examined. Further investigation is required to determine the basis of the observed effects and to determine whether these in vitro findings are predictive of results obtained in vivo.     

Recurrent Epstein-Barr virus-associated lesions in organ transplant recipients

This paper discusses the problem of violence and its expression upon mortality due to external causes. A few indicators are offered, which have been worked upon it to emphasise the importance of the theme. In a general way, the study demonstrates violent death has had its magnitude increased along the years, not only throughout Latin America but also in Brazil and in Santa Catarina.     

The effect of topical corticosteroids on refractive outcome and corneal haze after photorefractive keratectomy

BACKGROUND: The effect of topical corticosteroids after excimer laser photorefractive keratectomy (PRK) remains a matter of some controversy. Refractive effects may be different according to the amount of myopia and timing of instillation. METHODS: Two groups of patients were studied: Study A consisted of 215 eyes (128 patients) with PRK (mean baseline myopia, -6.53 +/- 2.22 D) that received no corticosteroids (No Corticosteroid Group) unless significant regression or corneal haze appeared (Delayed Corticosteroid Group), and in Study B, we randomly assigned eyes to the Initial Corticosteroid Group (mean baseline myopia, -6.39 +/- 1.84 D) or the No/delayed Corticosteroid Group (mean baseline myopia -5.78 +/- 2.02 D). Clinical results after PRK for low-to-moderate and high myopia were compared. RESULTS: In the first group, 70.9% (73 eyes) of moderately myopic eyes (mean, -4.56 +/- 1.10 D) belonged to the No Corticosteroid Group that had a mean refraction of -5.39 +/- 1.77 D. Delayed Corticosteroid Group eyes were more myopic (mean, -7.52 +/- 2.10 D), and showed more severe haze than those in the No Corticosteroid Group. In study B, only in high myopes with more than -6.00 D (mean, -7.76 +/- 1.15 D) did refraction and corneal haze outcomes show significant difference between the Initial Corticosteroid Group and the No/delayed Corticosteroid Group. CONCLUSIONS: The effects of topical corticosteroids after PRK were less in moderate myopes compared to high myopes. Delayed instillation of corticosteroids did not reverse the regression or haze whereas initial instillation showed a beneficial effect on high myopes but not on moderate myopes.     

In vivo studies of an implantable energy convertor for skeletal muscle powered cardiac assist

A device that harnesses the mechanical energy of skeletal muscle contracting in a linear configuration has been implanted in goats. This energy convertor transforms muscle work to hydraulic energy that could drive a variety of cardiac assist devices. The device is mounted with a rib clamp and plate affixed to the sternum by cortical bone screws. A transcutaneous hydraulic line carries a silicon based working fluid to an external system that controls the muscle load. In 60 to 70 kg goats, the latissimus dorsi insertion was reattached to the energy convertor. A Telectronics myostimulator with intramuscular electrodes stimulated the latissimus dorsi. In acute implants, hydraulic pressures in excess of 150 psi were obtained. Chronic implantation of the device allowed system evaluation in the conscious unanesthetized animal. Two weeks after implant, hydraulic pressures in excess of 200 psi were obtained and energy transferred to the external loading system exceeded 1 J per contraction. Six weeks after implant, the device continued to cycle freely. These initial results are very promising and suggest an implantable energy convertor is feasible. Development of an energy convertor is an important step toward tether-free skeletal muscle powered cardiac assist devices.     

Coplanar waveguide-fed uniplanar bow-tie antenna

The design of coplanar waveguide (CPW)-fed bow-tie antenna for the 2.4-GHz ISM band is described. A coplanar waveguide-to-coplanar strips (CPW-to-CPS) balun is used to obtain the balanced feed line for the printed bow-tie. An analysis method based on the mixed potential integral equation method is used to characterize the input characteristics of the bow-tie antenna. The numerical results obtained are in good agreement with the experimental data. Through experiments with bow-tie antennas of various extended angles, the bow-tie antenna with a 90° extended angle exhibits the widest bandwidth in the desired frequency band which has a bandwidth of 17% for a VSWR <1.5:1     

Revised cutoff values of serum aminotransferase in detecting viral hepatitis among CAPD patients: experience from Taiwan, an endemic area for hepatitis B

BACKGROUND: To determine the best cutoff values of aspartate aminotransferase (AST) and alanine amino-transferase (ALT) in detecting viral hepatitis C infection among patients of continuous ambulatory peritoneal dialysis (CAPD). METHODS: 90 (44 male and 46 female) CAPD patients and 526 adult controls (266 male, 260 female) were enrolled. Serum AST and ALT were measured by an auto-analyser monthly. Serum HBsAg was examined using a RIA method and anti-HCV by an second-generation EIA method. The best cutoff values of AST and ALT for detecting viral hepatitis were obtained from the ROC (receiver-operating characteristic) curve. RESULTS: The prevalence of anti-HCV(+) was significantly higher in CAPD patients (16.7%) than in normal controls (4.9%), while that of HBsAg(+) was similar in both groups. CAPD patients had significantly lower levels of serum aminotransferases compared to normal controls. Mean AST were 23.8 IU/l in normal control and 18.8 IU/l in the CAPD patients (P < 0.001). Mean ALT were 21.9 IU/l in normal controls and 15.3 IU/l in the CAPD patients (P < 0.001). CAPD patients with HCV infection had higher serum AST and ALT levels than those without. However, HBV infection did not cause significant serum aminotransferase elevation in patients. The conventional cutoff values of AST (40 IU/l) and ALT (40 IU/l) for detecting viral hepatitis yielded only a sensitivity of 27.3 and 18.2% respectively; on the contrary, our revised cutoff values of AST (24 IU/l) and ALT (17 IU/l) had better sensitivities (AST, 72.7%; ALT, 63.6%). For serial aminotransferase values, the sensitivity of AST and ALT for detecting HCV were 36.4 and 27.3% by conventional criteria, and were both 81.8%, by our newly revised criteria. CONCLUSIONS: Serum aminotransferase cutoff values should be modified for screening viral hepatitis in a CAPD population. Our new cutoff criteria had important clinical implications in providing benefits of earlier detection and possible prevention from chronic hepatic deteriorations.     

The band areas of proteins determined by fluorescent scanning in the commercial automated gel electrophoresis apparatus

An automated gel electrophoresis apparatus, recently available commercially, allows one to follow the band during electrophoresis in real time, and lends itself therefore to an evaluation of bandwidth as a function of migration time (the dispersion coefficient), resolution and band shape. These determinations assume the constancy of band area with migration time and at various gel concentrations. The purpose of the present study was to verify these assumptions. Representative proteins and sodium dodecyl sulfate (SDS)-proteins, either natively fluorescent or fluorescein carboxylate labeled, were found to exhibit band areas which approach constancy as a function of migration time in both agarose and polyacrylamide gel electrophoresis, provided that (i) the protein concentration under the band was low enough to obviate self-quenching of fluorescence; (ii) the separation of the protein of interest from contaminants had progressed sufficiently during the time at which band areas were measured; (iii) the baseline under the peak was sufficiently well defined. However, band areas decrease with increasing gel concentration. Protein peaks exhibited leading and trailing tails. The ratio of the combined tail area to total area appeared to be near-constant at varying migration times. However, that ratio increases with increasing gel concentration. The tail area does not appear to be an artifact of fluorometric detection since it is reproduced upon fluorimetric analysis of the protein eluted from gel slices after electrophoresis. However, it may be due to photochemical destruction under the conditions of repetitive fluorometric peak detection.     

The Synthesis of Sulfated Titanium Oxide Nanotubes

TiO₂ nanotubes can be prepared in gram quantities by treating anatase TiO₂ powder with concentrated NaOH solution. These TiO₂ nanotubes acquired strong acidity after being impregnated with sulfuric acid solution and calcined at 300 °C. The anatase TiO₂ powder used to prepare the nanotube did not catalyze the esterification between cyclohexanol and acetic acid, while sulfated TiO₂ nanotubes were very reactive toward the esterification reaction.     

Broad-band MMICs based on modified loss-compensation method using 0.35-/spl mu/m SiGe BiCMOS technology

Using the concept of loss compensation, novel broad-band monolithic microwave integrated circuits (MMICs), including an amplifier and an analog multiplier/mixer, with LC ladder matching networks in a commercial 0.35-mum SiGe BiCMOS technology are demonstrated for the first time. An HBT two-stage cascade single-stage distributed amplifier (2-CSSDA) using the modified loss-compensation technique is presented. It demonstrates a small-signal gain of better than 15 dB from dc to 28 GHz (gain-bandwidth product=157 GHz) with a low power consumption of 48 mW and a miniature chip size of 0.63 mm² including testing pads. The gain-bandwidth product of the modified loss-compensated CSSDA is improved approximately 68% compared with the conventional attenuation-compensation technique. The wide-band amplifier achieves a high gain-bandwidth product with the lowest power consumption and smallest chip size. The broad-band mixer designed using a Gilbert cell with the modified loss-compensation technique achieves a measured power conversion gain of 19 dB with a 3-dB bandwidth from 0.1 to 23 GHz, which is the highest gain-bandwidth product of operation among previously reported MMIC mixers. As an analog multiplier, the measured sensitivity is better than 3000 V/W from 0.1 to 25 GHz, and the measured low-frequency noise floor and corner frequency can be estimated to be 20 nV/sqrt(Hz) and 1.2 kHz, respectively. The mixer performance represents state-of-the-art result of the MMIC broad-band mixers using commercial silicon-based technologies